<?xml version="1.0" encoding="UTF-8" standalone="no"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" "archivearticle.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="systematic-review">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Physiol.</journal-id>
<journal-title>Frontiers in Physiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Physiol.</abbrev-journal-title>
<issn pub-type="epub">1664-042X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fphys.2019.01239</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Physiology</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Acute and Chronic Responses of Aerobic Exercise With Blood Flow Restriction: A Systematic Review</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Silva</surname> <given-names>J&#x000FA;lio Cesar Gomes</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/723999/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Pereira Neto</surname> <given-names>El&#x000ED;sio Alves</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/811274/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Pfeiffer</surname> <given-names>Patrick Alan Souza</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/811105/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Neto</surname> <given-names>Gabriel Rodrigues</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/509578/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Rodrigues</surname> <given-names>Amanda Santos</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/811074/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Bemben</surname> <given-names>Michael G.</given-names></name>
<xref ref-type="aff" rid="aff6"><sup>6</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/168918/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Patterson</surname> <given-names>Stephen D.</given-names></name>
<xref ref-type="aff" rid="aff7"><sup>7</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/302493/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Batista</surname> <given-names>Gilm&#x000E1;rio Ricarte</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/806509/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Cirilo-Sousa</surname> <given-names>Maria S.</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Associate Graduate Program in Physical Education, Department of Physical Education, Federal University of Para&#x000ED;ba</institution>, <addr-line>Jo&#x000E3;o Pessoa</addr-line>, <country>Brazil</country></aff>
<aff id="aff2"><sup>2</sup><institution>Laboratory of Kinanthropometry and Human Performance, Department of Physical Education, Federal University of Para&#x000ED;ba</institution>, <addr-line>Jo&#x000E3;o Pessoa</addr-line>, <country>Brazil</country></aff>
<aff id="aff3"><sup>3</sup><institution>Faculty Nova Esperan&#x000E7;a (FAMENE/FACENE), Coordination of Physical Education, Nursing and Medical Schools</institution>, <addr-line>Jo&#x000E3;o Pessoa</addr-line>, <country>Brazil</country></aff>
<aff id="aff4"><sup>4</sup><institution>Coordination of Physical Education, University Center for Higher Education and Development (CESED/UNIFACISA/FCM/ESAC)</institution>, <addr-line>Campina Grande</addr-line>, <country>Brazil</country></aff>
<aff id="aff5"><sup>5</sup><institution>Alliance for Research in Exercise, Nutrition and Activity (ARENA), School of Health Sciences, University of South Australia</institution>, <addr-line>Adelaide, SA</addr-line>, <country>Australia</country></aff>
<aff id="aff6"><sup>6</sup><institution>Department of Health and Exercise Science</institution>, <addr-line>Norman, OK</addr-line>, <country>United States</country></aff>
<aff id="aff7"><sup>7</sup><institution>Faculty of Sport, Health and Applied Science, St Marys&#x00027; University</institution>, <addr-line>London</addr-line>, <country>United Kingdom</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Barbara Morgan, University of Wisconsin-Madison, United States</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Matthew J. Clarkson, Deakin University, Australia; James Grant Mouser, Troy University, United States</p></fn>
<corresp id="c001">&#x0002A;Correspondence: J&#x000FA;lio Cesar Gomes Silva <email>juliociesar123&#x00040;gmail.com</email></corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Exercise Physiology, a section of the journal Frontiers in Physiology</p></fn></author-notes>
<pub-date pub-type="epub">
<day>04</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<volume>10</volume>
<elocation-id>1239</elocation-id>
<history>
<date date-type="received">
<day>19</day>
<month>04</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>10</day>
<month>09</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2019 Silva, Pereira Neto, Pfeiffer, Neto, Rodrigues, Bemben, Patterson, Batista and Cirilo-Sousa.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Silva, Pereira Neto, Pfeiffer, Neto, Rodrigues, Bemben, Patterson, Batista and Cirilo-Sousa</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<abstract><p>This study systematically reviewed the available scientific evidence pertaining to the acute and chronic changes promoted by aerobic exercise (AE) combined with blood flow restriction (BFR) on neuromuscular, metabolic and hemodynamic variables. PubMed, Web of Science<sup>TM</sup> and Scopus databases were searched for the period from January 2000 to June 2019 and the analysis involved a critical content review. A total of 313 articles were identified, of which 271 were excluded and 35 satisfied the inclusion criteria. Twelve studies evaluated the acute effects and eight studies evaluated the chronic metabolic effects of AE &#x0002B; BFR. For the neuromuscular variables, three studies analyzed the acute effects of AE &#x0002B; BFR and nine studies analyzed the chronic effects. Only 15 studies were identified that evaluated the hemodynamic acute effects of AE &#x0002B; BFR. The analysis provided evidence that AE combined with BFR promotes positive acute and chronic changes in neuromuscular and metabolic variables, a greater elevation in hemodynamic variables than exercise alone, and a higher energy demand during and after exercise. Since these alterations were all well-tolerated, this method can be considered to be safe and feasible for populations of athletes, healthy young, obese, and elderly individuals.</p></abstract> <kwd-group>
<kwd>aerobic exercise</kwd>
<kwd>blood flow restriction</kwd>
<kwd>elderly</kwd>
<kwd>adults</kwd>
<kwd>hemodynamic</kwd>
</kwd-group>
<counts>
<fig-count count="1"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="54"/>
<page-count count="16"/>
<word-count count="12702"/>
</counts>
</article-meta> 
</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>The American College of Sports Medicine recommends adults to routinely perform moderate-intensity aerobic exercise 5&#x02013;7 days a week (40&#x02013;60% of VO<sub>2</sub> peak) or vigorous exercise 3 days a week (&#x02265;60% VO<sub>2</sub> peak) in order to improve cardiorespiratory fitness and reduce the risk of metabolic, cardiovascular and pulmonary diseases (Garber et al., <xref ref-type="bibr" rid="B15">2011</xref>). Aerobic exercise (AE) is considered a successful method for improving physical fitness in healthy individuals (Clemente Su&#x000E1;rez and Gonz&#x000E1;lez-Rav&#x000E9;, <xref ref-type="bibr" rid="B9">2014</xref>) as well as in individuals with special limitations (Kelley and Kelley, <xref ref-type="bibr" rid="B18">2008</xref>).</p>
<p>However, high-intensity AE, requires intense exertion and involves high mechanical stress, which makes it difficult to perform this exercise modality for elderly, those recovering from orthopedic injuries or individuals afflicted with chronic illness. Thus, a possible alternative to high-intensity aerobic training is a method that combines AE (walking or cycling) with blood flow restriction (BFR). BFR exercise involves the use of inflatable cuffs or elastic bands positioned at the proximal region of the exercising musculature (upper arms or upper legs) and is performed at low exercise intensities ranging between 20 and 40% of maximum oxygen consumption (VO<sub>2max</sub>) and for short durations. AE combined with BFR (AE &#x0002B; BFR) promotes significant changes in neuromotor and cardiorespiratory activities that are similar to those often observed with high intensity exercise (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>; Pope et al., <xref ref-type="bibr" rid="B42">2013</xref>).</p>
<p>AE &#x0002B; BFR has been shown to elicit neuromuscular (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>; Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Corvino et al., <xref ref-type="bibr" rid="B11">2014</xref>; Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>), metabolic (Abe et al., <xref ref-type="bibr" rid="B3">2010b</xref>; Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Park et al., <xref ref-type="bibr" rid="B39">2010</xref>; Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>; Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>; Taylor et al., <xref ref-type="bibr" rid="B52">2016</xref>; Silva et al., <xref ref-type="bibr" rid="B45">2019</xref>) and cardiovascular (Abe et al., <xref ref-type="bibr" rid="B1">2010a</xref>; Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref>; Silva et al., <xref ref-type="bibr" rid="B46">2018</xref>) adaptations in healthy adults, obese, elderly individuals, and athletes. However, a consensus on the protocols that are used to perform AE &#x0002B; BFR has not been attained. A consensus would establish the actual effectiveness of this type of intervention on the acute responses and chronic adaptations of AE &#x0002B; BFR on metabolic, neuromuscular and hemodynamic variables. Therefore, the objective of this review was to systematically analyse the available scientific evidence regarding the acute responses and chronic adaptations promoted by AE &#x0002B; BFR on metabolic, neuromuscular, hemodynamic variables in athletes, healthy adults, and obese, elderly individuals.</p>
</sec>
<sec sec-type="methods" id="s2">
<title>Methods</title>
<p>To conduct the searches, the following English descriptors were employed: (&#x0201C;aerobic exercise&#x0201D; OR &#x0201C;cycling&#x0201D; OR &#x0201C;walking&#x0201D;) AND (&#x0201C;kaatsu&#x0201D; OR &#x0201C;vascular occlusion&#x0201D; OR &#x0201C;blood flow restriction&#x0201D; OR &#x0201C;kaatsu training&#x0201D;). The following inclusion criteria were adopted: original research that was conducted human subjects, research published in journals indexed in the selected databases, and research that contained individuals in the age range from 18 to 80 years and evaluated the acute and chronic changes promoted by AE &#x0002B; BFR. Articles were excluded if they (a) had scores lower than six on the Physiotherapy Evidence Database (PEDro) scale; (b) review articles; (c) articles that used protocols with strength exercises; (d) articles of viewpoints/opinions, studies validation; (e) book chapters, theses or dissertations and (f) case study articles.</p>
<p>Two investigators (JC and EP) conducted the on-line search in an independent and blind manner; their findings were subsequently compared. In the case of disagreement, a third evaluator (GR) established a consensus. During screening, the title and abstract of the identified articles were read. Thus, studies in which the title and abstract provided sufficient information were obtained. All articles were then read in their entirety. The references of these articles were reviewed to identify other potentially relevant studies that had not been identified in the electronic search.</p>
<sec>
<title>Methodological Quality: PEDro Scale</title>
<p>Currently, the most used scale in the area of rehabilitation is the PEDro scale (<ext-link ext-link-type="uri" xlink:href="http://www.pedro.fhs.usyd.edu.au">http://www.pedro.fhs.usyd.edu.au</ext-link>), which was developed by the Physiotherapy Evidence Database for use with regard to experimental studies. This scale has a maximum total score of 10 points and includes criteria concerning the evaluation of internal validity and the presentation of the statistical analysis used. For each criterion defined in the scale, one point (1) are attributed to the presence of indicators regarding the quality of the evidence presented, and zero points (0&#x02013;0) are attributed to its absence. The PEDro scale is composed of the following elements: (a) the specification of inclusion criteria (item not scored); (b) random allocation; (c) concealment of allocation; (d) similarity of the groups at baseline or the initial phase; (e) blinding of all participants; (f) blinding of all therapists; (g) blinding of all assessors; (h) measures of at least one primary outcome obtained from more than 85% of participants allocated; (i) &#x0201C;intention to treat&#x0201D; analysis; (j) between-group comparisons of at least one primary outcome; and (k) reports of measures of variability and estimations of parameters concerning at least one primary variable (Maher et al., <xref ref-type="bibr" rid="B30">2003</xref>).</p>
<p>This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Liberati et al., <xref ref-type="bibr" rid="B25">2009</xref>). Data analysis was performed based on a critical review of the content using the following criteria: title, abstract, rationale, objectives, protocol, risk of bias across studies, study characteristics, individual study results, limitations, and conclusions.</p>
</sec>
</sec>
<sec sec-type="results" id="s3">
<title>Results</title>
<p>The synthesis of the studies&#x00027; results was presented based on a structured script that considered the following components: (a) author (year) of the study; (b) subjects; (c) variable; (d) exercise protocol; (e) intensity; (f) exercise volume; g) interval between sets; (h) BFR pressure used during exercise; (i) BFR time, and (j) cuff width and k) main results. Of the 313 articles that were identified, 271 (86.2%) articles were excluded based on their title and abstract. Thus, 42 articles were selected to be read in their entirety. Thirty five articles were selected after applying the eligibility criteria. This process was based on the analysis of the methodological quality of the studies. A systematic evaluation of the changes promoted by AE combined with BFR in metabolic, neuromuscular and hemodynamic variables was performed (<xref ref-type="fig" rid="F1">Figure 1</xref>).</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Flowchart of the study selection process.</p></caption>
<graphic xlink:href="fphys-10-01239-g0001.tif"/>
</fig>
</sec>
<sec id="s4">
<title>Effect of AE &#x0002B; BFR on Metabolic Variables</title>
<p>Based on the analysis of the studies that investigated AE &#x0002B; BFR, eleven studies evaluated the acute effect of this training method on metabolic variables (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>, <xref ref-type="bibr" rid="B28">2012</xref>; Mendonca et al., <xref ref-type="bibr" rid="B32">2014</xref>, <xref ref-type="bibr" rid="B31">2015</xref>; Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref>; Corvino et al., <xref ref-type="bibr" rid="B12">2016</xref>; Concei&#x000E7;&#x000E3;o et al., <xref ref-type="bibr" rid="B10">2018</xref>; Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref>; Pfeiffer et al., <xref ref-type="bibr" rid="B41">2019</xref>; Silva et al., <xref ref-type="bibr" rid="B45">2019</xref>) and nine studies evaluated the chronic effect of this training method on metabolic variables (Abe et al., <xref ref-type="bibr" rid="B1">2010a</xref>,<xref ref-type="bibr" rid="B3">b</xref>; Park et al., <xref ref-type="bibr" rid="B39">2010</xref>; Corvino et al., <xref ref-type="bibr" rid="B11">2014</xref>; de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref>; Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>; Taylor et al., <xref ref-type="bibr" rid="B52">2016</xref>; Paton et al., <xref ref-type="bibr" rid="B40">2017</xref>; Tanaka and Takarada, <xref ref-type="bibr" rid="B51">2018</xref>).</p>
<p>Studies that investigated the acute effect of AE &#x0002B; BFR assessed oxygen consumption (VO<sub>2</sub>) during exercise (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>; Corvino et al., <xref ref-type="bibr" rid="B12">2016</xref>; Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref>; Silva et al., <xref ref-type="bibr" rid="B45">2019</xref>), energy expenditure during exercise (Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>; Mendonca et al., <xref ref-type="bibr" rid="B32">2014</xref>; Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref>; Concei&#x000E7;&#x000E3;o et al., <xref ref-type="bibr" rid="B10">2018</xref>; Pfeiffer et al., <xref ref-type="bibr" rid="B41">2019</xref>) blood lactate concentration during exercise (Loenneke et al., <xref ref-type="bibr" rid="B28">2012</xref>; Corvino et al., <xref ref-type="bibr" rid="B12">2016</xref>; Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref>) and only one study investigated (Mendonca et al., <xref ref-type="bibr" rid="B31">2015</xref>) excessive post-exercise oxygen consumption (EPOC). Regarding the chronic effects of AE &#x0002B; BFR, some studies evaluated cardiorespiratory capacity (Abe et al., <xref ref-type="bibr" rid="B1">2010a</xref>,<xref ref-type="bibr" rid="B3">b</xref>; Park et al., <xref ref-type="bibr" rid="B39">2010</xref>; de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref>; Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>; Taylor et al., <xref ref-type="bibr" rid="B52">2016</xref>; Tanaka and Takarada, <xref ref-type="bibr" rid="B51">2018</xref>), time to exhaustion in severe exercise (Corvino et al., <xref ref-type="bibr" rid="B11">2014</xref>; Paton et al., <xref ref-type="bibr" rid="B40">2017</xref>), maximum power and onset blood lactate accumulation (de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref>).</p>
</sec>
<sec id="s5">
<title>Acute Effects of AE &#x0002B; BFR</title>
<sec>
<title>Oxygen Consumption <italic>(l/min)</italic></title>
<p>Ozaki et al. (<xref ref-type="bibr" rid="B35">2010</xref>), conducted a study using a crossover model: ten young men performed two randomized cycling protocols on a cycle ergometer that was composed of four stages. Each protocol was performed with duration of 4 min, a constant speed of 70 revolutions per minute (rpm) and progressive intensities of 0, 20, 40, and 60% of VO<sub>2max</sub>. The results indicated that VO<sub>2</sub> during cycling with BFR at an intensity of 20% of VO<sub>2max</sub> exceeded the oxygen consumption for the cycling protocol without the use of BFR. Mendonca et al. (<xref ref-type="bibr" rid="B32">2014</xref>), found that exercise performed with BFR had a higher energy cost than the session performed at the same intensity without BFR. Similar results were observed by Silva et al. (<xref ref-type="bibr" rid="B45">2019</xref>), which indicated that the VO<sub>2</sub> during walking with BFR at an intensity of 40% of VO<sub>2peak</sub> exceeded the oxygen consumption for the walking protocol without BFR.</p>
</sec>
<sec>
<title>Energy Expenditure</title>
<p>Regarding the impact of BFR on energy expenditure (EE), two studies revealed that the performance of interval walking combined with BFR has a higher energy demand than walking without BFR. In both studies, energy expenditure (EE) was calculated using the caloric equivalents for the non-protein respiratory exchange ratio (RER) values for each liter of oxygen used. The unit of measure used was the kilocalorie (Kcal). Loenneke et al. (<xref ref-type="bibr" rid="B27">2011</xref>) found that exercise performed with BFR yielded higher VO<sub>2</sub> elevation and energy expenditure than the session with the same protocol without the use of elastic bands. A study by Karabulut and Garcia (<xref ref-type="bibr" rid="B17">2015</xref>) was performed using a crossover model: 34 obese people 18 men and 16 women performed three randomized cycling sessions with a speed of 50 rpm and a constant load of 50 Watts in two sets of 10 min and a 1-min interval between sets. An exercise protocol was performed without BFR, and two protocols were performed with BFR and inflatable cuffs in the thigh; demonstrating that exercise with BFR significantly increased energy demand during exercise.</p>
</sec>
<sec>
<title>Excessive Post-exercise Oxygen Consumption (EPOC)</title>
<p>Only one study investigated the impact of AE &#x0002B; BFR on excessive post-exercise oxygen consumption (Mendonca et al., <xref ref-type="bibr" rid="B31">2015</xref>). These authors observed that the exercise performed with BFR significantly increased the magnitude of EPOC compared to a session with the same intensity without the use of BFR.</p>
</sec>
<sec>
<title>Blood Lactate Concentration</title>
<p>In a study by Loenneke et al. (<xref ref-type="bibr" rid="B28">2012</xref>), the volunteers performed two random sessions of interval walking on a treadmill with five sets of 2 min and a 1-min interval between sets, with a constant speed of 75 meters per minute (m/min). The stimulus generated by walking with BFR was not sufficient for increasing post-exercise metabolic stress. However, separate studies by Corvino et al. (<xref ref-type="bibr" rid="B12">2016</xref>) and Thomas et al. (<xref ref-type="bibr" rid="B53">2018</xref>), both observed that AE &#x0002B; BFR increased the concentration blood lactate more than a AE session without BFR.</p>
</sec>
</sec>
<sec id="s6">
<title>Chronic Effects of AE &#x0002B; BFR</title>
<sec>
<title>Cardiorespiratory Capacity</title>
<p>Abe et al. (<xref ref-type="bibr" rid="B3">2010b</xref>) conducted a study with 19 active elderly individuals, including four men and 15 women (60&#x02013;78 years old) who were randomly divided into two groups: walking with BFR (W &#x0002B; BFR; <italic>n</italic> &#x0003D; 11) and walking without BFR (CONTROL; <italic>n</italic> &#x0003D; 8). Both groups performed 20 min of continuous walking 5 days per week for 6 weeks. W &#x0002B; BFR did not promote improvement in the cardiorespiratory capacity. In the study by Park et al. (<xref ref-type="bibr" rid="B39">2010</xref>), 12 college basketball players were randomly divided into two groups: (1) interval walking with BFR (IW &#x0002B; BFR; <italic>n</italic> &#x0003D; 7), and (2) interval walking without BFR (CONTROL, <italic>n</italic> &#x0003D; 5). Both groups performed five sets of 3 min with a 1-min interval between sets, speeds between 4 and 6 km/h and a 5% incline on the treadmill two times a day, six times a week for 2 weeks. A significant increase in the cardiorespiratory capacity of the basketball players was observed for the walking with BFR group.</p>
<p>The cycling protocol combined with BFR in the study by Abe et al. (<xref ref-type="bibr" rid="B1">2010a</xref>) promoted an increase in the cardiorespiratory capacity of young men after 8 weeks. Similarly, improvements in cardiorespiratory capacity of 20 trained men after 4 weeks of interval sprints with BFR were observed (Taylor et al., <xref ref-type="bibr" rid="B52">2016</xref>). However, that was not observed in 31 trained college students who performed 20 min of cycling with BFR at 30% of HR<sub>max</sub> three times a week for 6 weeks (Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>) (<xref ref-type="table" rid="T1">Table 1</xref>).</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Synthesis of the results of studies that evaluate the acute and chronic effects of combined aerobic exercise and blood flow restriction on metabolic variables in obese individuals, athletes and young adults.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left"><bold>References</bold></th>
<th valign="top" align="left"><bold>Subjects</bold></th>
<th valign="top" align="left"><bold>Variables</bold></th>
<th valign="top" align="center" colspan="3" style="border-bottom: thin solid #000000;"><bold>Exercise protocol</bold></th>
<th valign="top" align="left"><bold>Intensity or frequency of training/duration of study</bold></th>
<th valign="top" align="center" colspan="2" style="border-bottom: thin solid #000000;"><bold>Exercise volume</bold></th>
<th valign="top" align="center"><bold>Interval</bold></th>
<th valign="top" align="center"><bold>PADE</bold> <break/><bold>(mmHg)</bold></th>
<th valign="top" align="left"><bold>BFR between sets</bold></th>
<th valign="top" align="center"><bold>SW</bold> <break/><bold>(cm)</bold></th>
<th valign="top" align="left"><bold>Results</bold></th>
</tr>
<tr style="border-bottom: thin solid #000000;">
<th/>
<th/>
<th/>
<th valign="top" align="right"><bold>EX</bold></th>
<th valign="top" align="right"><bold>FE</bold></th>
<th valign="top" align="right"><bold>SE</bold></th>
<th/>
<th valign="top" align="left"><bold>Sets or continuous</bold></th>
<th valign="top" align="left"><bold>Repetitions or duration time</bold></th>
<th/>
<th/>
<th/>
<th/>
<th/>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Abe et al., <xref ref-type="bibr" rid="B3">2010b</xref></td>
<td valign="top" align="left">19 Elderly men and women</td>
<td valign="top" align="left">VO2<sub>max</sub></td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">67 m/min</td>
<td valign="top" align="left">5&#x000D7; week/6 weeks</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">20 min</td>
<td valign="top" align="center">-</td>
<td valign="top" align="center">200</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">No improvement in VO<sub>2Max</sub> in the groups</td>
</tr>
<tr>
<td valign="top" align="left">Abe et al., <xref ref-type="bibr" rid="B1">2010a</xref></td>
<td valign="top" align="left">19 Adult men</td>
<td valign="top" align="left">VO2<sub>max</sub></td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">40% VO<sub>2</sub> with and without BFR 1&#x000D7; day/3&#x000D7; week - 8 weeks</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">15 min with BFR <break/>45 min without BFR</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">160&#x02013;210</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191; VO<sub>2Max</sub> in cycling with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Park et al., <xref ref-type="bibr" rid="B39">2010</xref></td>
<td valign="top" align="left">12 Basketball players</td>
<td valign="top" align="left">VO2<sub>max</sub> <break/>VE<sub>Max</sub></td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">4&#x02013;6 km/h</td>
<td valign="top" align="left">2&#x000D7; day/6&#x000D7; week <break/>2 weeks</td>
<td valign="top" align="left">5 Series</td>
<td valign="top" align="left">3 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">160&#x02013;230</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="left">&#x02191;VE<sub>max</sub> and VO<sub>2max</sub> in training protocol with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Ozaki et al., <xref ref-type="bibr" rid="B38">2011</xref></td>
<td valign="top" align="left">10 Men</td>
<td valign="top" align="left">VO<sub>2</sub> (L/min)</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">70 rpm</td>
<td valign="top" align="left">20&#x02013;40&#x02013;60% VO<sub>2max</sub> with and without BFR</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">4 min each stage</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191;VO<sub>2</sub> between 20 and 60% in the session with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref></td>
<td valign="top" align="left">10 Men and women</td>
<td valign="top" align="left">EE and VO<sub>2</sub> (L/min)</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">75 m/min</td>
<td valign="top" align="left">AE &#x0002B; BFR <break/>AE</td>
<td valign="top" align="left">5 sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">Elastic</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">7.6</td>
<td valign="top" align="left">&#x02191;VO<sub>2</sub> and EE in the exercise session with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Loenneke et al., <xref ref-type="bibr" rid="B28">2012</xref></td>
<td valign="top" align="left">9 Men and women</td>
<td valign="top" align="left">[La<sup>&#x0002B;</sup>]</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">75 m/min</td>
<td valign="top" align="left">AE &#x0002B; BFR <break/>AE</td>
<td valign="top" align="left">5 sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">Elastic</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">7.6</td>
<td valign="top" align="left">WALKING&#x0002B;BFR does not change metabolic stress</td>
</tr>
<tr>
<td valign="top" align="left">Mendonca et al., <xref ref-type="bibr" rid="B32">2014</xref></td>
<td valign="top" align="left">18 Healthy men</td>
<td valign="top" align="left">Energy expenditure</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">&#x0003C;30%VO<sub>2max</sub></td>
<td valign="top" align="left">5 sets</td>
<td valign="top" align="left">3 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">6 &#x000D7; 83</td>
<td valign="top" align="left">Energy expenditure &#x0003E; for walking with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Corvino et al., <xref ref-type="bibr" rid="B11">2014</xref></td>
<td valign="top" align="left">13 Active subjects</td>
<td valign="top" align="left">TTE</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">30% P<sub>max</sub> &#x0002B; BFR <break/>30% P<sub>max</sub></td>
<td valign="top" align="left">2 Set</td>
<td valign="top" align="left">5&#x02013;8 Repetitions</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">140&#x02013;200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191; in TTE for walking with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Mendonca et al., <xref ref-type="bibr" rid="B31">2015</xref></td>
<td valign="top" align="left">17 Young men</td>
<td valign="top" align="left">EPOC</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">&#x0003C;30%VO<sub>2Max</sub></td>
<td valign="top" align="left">5 Sets</td>
<td valign="top" align="left">3 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">6 &#x000D7; 83</td>
<td valign="top" align="left">EPOC&#x0003E; in exercise session with BFR</td>
</tr>
<tr>
<td valign="top" align="left">de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref></td>
<td valign="top" align="left">37 Subjects</td>
<td valign="top" align="left">Pmax. PALS, VO<sub>2Max</sub></td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">30% P<sub>max</sub> &#x0002B; BFR110% P<sub>max</sub>30% P<sub>max</sub>110%-30% P<sub>max</sub> &#x0002B;BFR3x week/4 weeks</td>
<td valign="top" align="left">2 Sets</td>
<td valign="top" align="left">5&#x02013;8 Repetitions</td>
<td valign="top" align="center">5 min</td>
<td valign="top" align="center">140&#x02013;200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191;VO<sub>2Max</sub> and P<sub>max</sub> and improvement in PALS for the LI with BFR protocol</td>
</tr>
<tr>
<td valign="top" align="left">Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref></td>
<td valign="top" align="left">34 Obese men and women</td>
<td valign="top" align="left">EE, RER</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">50 rpm</td>
<td valign="top" align="left">40%&#x0002B;BFR <break/>60%&#x0002B;BFR <break/>Without BFR <break/>50 Watts</td>
<td valign="top" align="left">2 Sets</td>
<td valign="top" align="left">10 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">40% <break/>60%</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191; EE and RER &#x0003E; in the BFR protocol</td>
</tr>
<tr>
<td valign="top" align="left">Taylor et al., <xref ref-type="bibr" rid="B52">2016</xref></td>
<td valign="top" align="left">20 Trained men</td>
<td valign="top" align="left">VO<sub>2Max</sub></td>
<td valign="top" align="left">RUN</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">SIT &#x0002B; BFR <break/>SIT <break/>2&#x000D7; week/4 weeks</td>
<td valign="top" align="left">4, 5, 6. and 7 sprints</td>
<td valign="top" align="left">30 s</td>
<td valign="top" align="center">270 s</td>
<td valign="top" align="center">130 post-exercise</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">6 &#x000D7; 83</td>
<td valign="top" align="left">&#x02191;VO<sub>2Max</sub> for the protocol with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Kim et al., <xref ref-type="bibr" rid="B21">2016</xref></td>
<td valign="top" align="left">31 Trained <break/>young men</td>
<td valign="top" align="left">VO<sub>2Max</sub></td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">BICYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">3&#x000D7; week/6 weeks</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">20 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">160&#x02013;180</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">VO<sub>2</sub><sub>MAX</sub> did not increase in the LI group.</td>
</tr>
<tr>
<td valign="top" align="left">Corvino et al., <xref ref-type="bibr" rid="B12">2016</xref></td>
<td valign="top" align="left">12 Men</td>
<td valign="top" align="left">VO<sub>2</sub>, [La], VE</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">HI <break/>IBFR30 <break/>CBFR30 <break/>CON30 <break/>IBFR0</td>
<td valign="top" align="left">2 Sets with 5 reps <break/>Continuous</td>
<td valign="top" align="left">2 <break/>35 min</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">80%</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191; metabolic strain and muscle deoxigenation in protocol I-BFR30</td>
</tr>
<tr>
<td valign="top" align="left">Paton et al., <xref ref-type="bibr" rid="B40">2017</xref></td>
<td valign="top" align="left">10 men 6 women</td>
<td valign="top" align="left">RE, TTE and PRV</td>
<td valign="top" align="left">RUN</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">80%PRV</td>
<td valign="top" align="left">AE &#x0002B; BFRCON 2&#x000D7; week/4 weeks</td>
<td valign="top" align="left">2 Sets</td>
<td valign="top" align="left">5 repetitions</td>
<td valign="top" align="center">30 sec</td>
<td valign="top" align="center">Elastic</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">7&#x02013;10</td>
<td valign="top" align="left">&#x02191; RE, TTE and PRV in protocol with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Concei&#x000E7;&#x000E3;o et al., <xref ref-type="bibr" rid="B10">2018</xref></td>
<td valign="top" align="left">12 Men</td>
<td valign="top" align="left">TEE, ALM, AM, VE</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">60&#x02013;70 rpm</td>
<td valign="top" align="left">40% VO<sub>2Max</sub> &#x0002B; BFR <break/>40% VO<sub>2Max</sub></td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">30 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">80%</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191; metabolic anaerobic, aerobic, total energy expenditure and Ventilation in protocol AE &#x0002B; BFR</td>
</tr>
<tr>
<td valign="top" align="left">Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref></td>
<td valign="top" align="left">18 Men</td>
<td valign="top" align="left">VO<sub>2</sub> and [La]</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">HI 85%Pmax <break/>LI 40% <break/>LI &#x0002B; BFR</td>
<td valign="top" align="left">3 Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">2 min active</td>
<td valign="top" align="center">80%</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">10</td>
<td valign="top" align="left">&#x02191;VO<sub>2</sub>, [La] in protocol HI &#x0003E; LI&#x0002B;BFR and LI. <break/>VO<sub>2</sub>, [La] in protocol LI&#x0002B;BFR &#x0003E; LI</td>
</tr>
<tr>
<td valign="top" align="left">Tanaka and Takarada, <xref ref-type="bibr" rid="B51">2018</xref></td>
<td valign="top" align="left">30 Elderly men</td>
<td valign="top" align="left">VO<sub>2Max</sub></td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">40&#x02013;70%VO<sub>2Max</sub> &#x0002B; BFR <break/>3&#x000D7; week/6 months</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">15 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">40&#x02013;80 mmhg &#x02191; SBP</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">9 &#x000D7; 7</td>
<td valign="top" align="left">&#x02191; VO<sub>2Max</sub> in protocol AE &#x0002B; BFR</td>
</tr>
<tr>
<td valign="top" align="left">Silva et al., <xref ref-type="bibr" rid="B45">2019</xref></td>
<td valign="top" align="left">22 Men</td>
<td valign="top" align="left">VO<sub>2</sub></td>
<td valign="top" align="left">RUN <break/>WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">HIIE <break/>AE &#x0002B; BFR <break/>AE</td>
<td valign="top" align="left">6 Sets <break/>Continuous</td>
<td valign="top" align="left">90 s <break/>18 min</td>
<td valign="top" align="center">90 s active</td>
<td valign="top" align="center">50%</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191;VO<sub>2</sub> in protocol HIIE <break/>But, VO<sub>2</sub> in protocol AE &#x0002B; BFR &#x0003E; AE</td>
</tr>
<tr>
<td valign="top" align="left">Pfeiffer et al., <xref ref-type="bibr" rid="B41">2019</xref></td>
<td valign="top" align="left">24 Men</td>
<td valign="top" align="left">EE</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">40% Maximal Speed</td>
<td valign="top" align="left">5 Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">0 <break/>50% <break/>80% <break/>100%</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191;EE in protocol walk with 50% BFR</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><italic>BFR, blood flow restriction; VO<sub>2Max</sub>, maximum oxygen consumption; VE<sub>MAX</sub>, Maximum ventilation; P<sub>MAX</sub>, maximum power; EPOC, excessive post-exercise oxygen consumption; EE, energy expenditure; TEE, total energy expenditure; ALM, Anaerobic Lactic Metabolism; RE, running economy; TTE, time to exhaustion; AM, Aerobic Metabolism; VE, Ventilation; PRV, peak running velocity; RER, respiratory exchange ratio; OBLA, onset blood lactate accumulation; EX, exercise; FE, form of execution; SE, speed of execution; WALK, walking; CYC, cycling; RUN, running; CYCLE, cycle ergometer; min, minutes; s, seconds; CON, Control; PADE, pressure applied during the exercise; SW, sleeve width; &#x02013;, Not informed; &#x02191;, significant increase; LI &#x0002B; BFR, low intensity combined with blood flow restriction; LI, low intensity; HI, high intensity; HIIE, high intensity interval exercise; IBFR30, intermittent blood flow restriction; CBFR, continuous blood flow restriction</italic>.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<title>Time to Exhaustion</title>
<p>Four weeks of training with BFR increased the tolerance to severe exercise, but an increase was not observed in the exercise without BFR group in a study where Three men and ten women, physically active, were divided into two groups: interval training with BFR (<italic>n</italic> &#x0003D; 9) and interval training without BFR (<italic>n</italic> &#x0003D; 4). The training for both groups consisted of two sets of five to eight repetitions for 2 min at 30% of maximum power (P<sub>m&#x000E1;<italic>x</italic></sub>) with 1-min rest interval between the repetitions for 4 weeks Corvino et al. (<xref ref-type="bibr" rid="B11">2014</xref>) (<xref ref-type="table" rid="T1">Table 1</xref>).</p>
</sec>
<sec>
<title>Maximum Power and Onset Blood Lactate Accumulation</title>
<p>In a study by de Oliveira et al. (<xref ref-type="bibr" rid="B13">2015</xref>), 37 physically active subjects, including 22 men and 15 women (23.8 &#x000B1; 4 years), performed cycling training on a cycle ergometer three times a week for 4 weeks. The subjects were divided into four groups: (1) low-intensity interval training with BFR (LIIT &#x0002B; BFR; <italic>n</italic> &#x0003D; 10) performed at 30% of P<sub>max</sub>; (2) low-intensity interval training (LIIT; <italic>n</italic> &#x0003D; 7) performed at 30% of P<sub>max</sub>, (3) high-intensity interval training (HIIT; <italic>n</italic> &#x0003D; 10) performed at 110% of P<sub>max</sub> and (4) high-intensity interval training combined with BFR (HIIT &#x0002B; BFR; <italic>n</italic> &#x0003D; 10) performed 50% as HIIT and 50% as BFR. Both groups performed two sets of 5&#x02013;8 repetitions with 5-min intervals. The LIIT &#x0002B; BFR group improved the onset blood lactate accumulation by 16% and maximal power by 15% without a significant difference between the HIIT group and HIIT &#x0002B; BFR group (<xref ref-type="table" rid="T1">Table 1</xref>).</p>
</sec>
<sec>
<title>Exercises, Sample Size, Gender, and Standards in the Studies</title>
<p>The 20 training protocols of AE &#x0002B; BFR that were employed to investigate the metabolic variables are highlighted: (a) Seven studies (35%) involved walking; (b) ten studies (50%) involved cycling; (c) two studies (10%) involved running and (d) one study (5%) involved running and walking. It was observed that 10 studies (50%) used treadmill, nine studies (45%) used cycle ergometer and one study (5%) use bicycle. In addition, eight studies (60%) involved continuous aerobic exercise protocols and 12 studies involved interval aerobic exercise protocols. Given that sample size and gender may be important aspects of a study, the sample sizes in those studies were small and ranged from nine to 37 subjects, with a predominance of males. Thirteen studies (65%) consisted of only men and the samples of seven studies (35%) involved both men and women. Regarding the device used for BFR, seventeen studies (85%) used cuffs, with sizes that ranging from 5 to 18 cm, and three studies (15%) used elastic bands with a size of 7.6&#x02013;10 cm. Eleven studies were performed utilizing a fixed BFR pressure from 140 to 230 mmHg for all subjects, and six studies employed BFR pressure percentages that varied between 40 and 100% of arterial occlusion pressure. The studies that investigated the chronic effects of AE &#x0002B; BFR were conducted with 2&#x02013;8 weeks of training in basketball players, young adults and the elderly.</p>
</sec>
</sec>
<sec id="s7">
<title>Effect of ae &#x0002B; Bfr on Neuromuscular Variables</title>
<p>Based on the studies that investigated the impact of AE &#x0002B; BFR on neuromuscular variables, three studies analyzed the acute effects (Ozaki et al., <xref ref-type="bibr" rid="B36">2014</xref>, <xref ref-type="bibr" rid="B37">2015</xref>; Kim et al., <xref ref-type="bibr" rid="B20">2015</xref>) and 11 studies analyzed the chronic effects (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>,<xref ref-type="bibr" rid="B3">b</xref>; Ozaki et al., <xref ref-type="bibr" rid="B38">2011</xref>; Sakamaki et al., <xref ref-type="bibr" rid="B44">2011</xref>; Keramidas et al., <xref ref-type="bibr" rid="B19">2012</xref>; de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref>; Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>; Clarkson et al., <xref ref-type="bibr" rid="B8">2017</xref>). Studies that investigated the acute effects of AE &#x0002B; BFR assessed intracellular signaling associated with hypertrophy and muscular adaptations (Ozaki et al., <xref ref-type="bibr" rid="B36">2014</xref>; Kim et al., <xref ref-type="bibr" rid="B20">2015</xref>), and studies that investigated the chronic effects of AE &#x0002B; BFR evaluated muscle power (Keramidas et al., <xref ref-type="bibr" rid="B19">2012</xref>), muscle strength (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B3">2010b</xref>; Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref>; Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>), muscle hypertrophy (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>,<xref ref-type="bibr" rid="B3">b</xref>; Ozaki et al., <xref ref-type="bibr" rid="B38">2011</xref>, <xref ref-type="bibr" rid="B37">2015</xref>; Sakamaki et al., <xref ref-type="bibr" rid="B44">2011</xref>), and growth hormone (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>; Ozaki et al., <xref ref-type="bibr" rid="B37">2015</xref>) (<xref ref-type="table" rid="T2">Table 2</xref>).</p>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>Synthesis of the results of studies that evaluate the acute effect of combined aerobic exercise and blood flow restriction on neuromuscular variables in young adult and elderly subjects.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left"><bold>References</bold></th>
<th valign="top" align="left"><bold>Subjects</bold></th>
<th valign="top" align="left"><bold>Variable</bold></th>
<th valign="top" align="center" colspan="3" style="border-bottom: thin solid #000000;"><bold>Exercise protocol</bold></th>
<th valign="top" align="left"><bold>Intensity/requency of training/uration of study</bold></th>
<th valign="top" align="center" colspan="2" style="border-bottom: thin solid #000000;"><bold>Exercise volume</bold></th>
<th valign="top" align="center"><bold>Interval</bold></th>
<th valign="top" align="center"><bold>PADE</bold> <break/><bold>(mmHg)</bold></th>
<th valign="top" align="left"><bold>BFR between sets</bold></th>
<th valign="top" align="center"><bold>SW(cm)</bold></th>
<th valign="top" align="left"><bold>Results</bold></th>
</tr>
<tr style="border-bottom: thin solid #000000;">
<th/>
<th/>
<th/>
<th valign="top" align="right"><bold>EX</bold></th>
<th valign="top" align="right"><bold>FE</bold></th>
<th valign="top" align="right"><bold>VE</bold></th>
<th/>
<th valign="top" align="left"><bold>Sets or continuous</bold></th>
<th valign="top" align="left"><bold>Repetitions or duration time</bold></th>
<th/>
<th/>
<th/>
<th/>
<th/>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Abe et al., <xref ref-type="bibr" rid="B2">2006</xref></td>
<td valign="top" align="left">18 Men healthy <break/>adults</td>
<td valign="top" align="left">GH, MH, FM</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">50 m/min</td>
<td valign="top" align="left">2&#x000D7; day/6&#x000D7; week/weeks</td>
<td valign="top" align="left">5 Sets</td>
<td valign="top" align="left">2</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">120&#x02013;200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191;GH, MH and MS for the group with BFR compared to CG</td>
</tr>
<tr>
<td valign="top" align="left">Abe et al., <xref ref-type="bibr" rid="B3">2010b</xref></td>
<td valign="top" align="left">19 Elderly men and women</td>
<td valign="top" align="left">MS, MH, FC</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">67 m/min</td>
<td valign="top" align="left">5&#x000D7; weeks/6 weeks</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">20 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">160&#x02013;200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">-</td>
<td valign="top" align="left">&#x02191; MS, MH, HR in the group with BFR compared to CON</td>
</tr>
<tr>
<td valign="top" align="left">Abe et al., <xref ref-type="bibr" rid="B3">2010b</xref></td>
<td valign="top" align="left">19 Young men</td>
<td valign="top" align="left">HM</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">40% VO<sub>2max</sub> 3&#x000D7; week/8 weeks</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">15 min with BFR <break/>45 min CON</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">160&#x02013;210</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">-</td>
<td valign="top" align="left">&#x02191; TM in the group with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref></td>
<td valign="top" align="left">23 Sedentary men and women</td>
<td valign="top" align="left">MH, FM</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">40% HRmax /4&#x000D7; week/10 weeks</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">20 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">120&#x02013;200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191; Strength and muscular hypertrophy in the group with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Sakamaki et al., <xref ref-type="bibr" rid="B44">2011</xref></td>
<td valign="top" align="left">17 Healthy men</td>
<td valign="top" align="left">MH</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">50 m/min</td>
<td valign="top" align="left">2&#x000D7; day/6&#x000D7; week/3 weeks</td>
<td valign="top" align="left">5 Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">160&#x02013;230</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="left">&#x02191; in muscle area in the group with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Keramidas et al., <xref ref-type="bibr" rid="B19">2012</xref></td>
<td valign="top" align="left">20 Young men and women</td>
<td valign="top" align="left">Muscular Adaptation</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">3&#x000D7; week/6 weeks</td>
<td valign="top" align="left">3 Sets</td>
<td valign="top" align="left">2 min/2 min/6 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">90</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="left">BFR training induces peripheral muscle adaptation</td>
</tr>
<tr>
<td valign="top" align="left">Ozaki et al., <xref ref-type="bibr" rid="B36">2014</xref></td>
<td valign="top" align="left">6 Healthy men</td>
<td valign="top" align="left">ERK1/2, MTOR, P38. MAPK, AkT, S6K1</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">100 m/min</td>
<td valign="top" align="left">WALK &#x0002B; BFR <break/>WALK</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">20 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">240</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191; Activation of intracellular signaling pathways</td>
</tr>
<tr>
<td valign="top" align="left">Kim et al., <xref ref-type="bibr" rid="B20">2015</xref></td>
<td valign="top" align="left">10 Men</td>
<td valign="top" align="left">Muscular activation</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">50&#x02013;60 rpm</td>
<td valign="top" align="left">HI VO<sub>2max</sub> <break/>LI &#x0002B; 40%BFR <break/>LI &#x0002B; 60%BFR <break/>CON</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">HI&#x02212;14 minLI &#x0002B; 40%BFR&#x02212;28 minLI &#x0002B; 60%BFR- 30 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">50&#x02013;210</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191; muscle strees with high intensity exercise</td>
</tr>
<tr>
<td valign="top" align="left">de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref></td>
<td valign="top" align="left">37 young adults</td>
<td valign="top" align="left">MS</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">3&#x000D7; week/4 weeks</td>
<td valign="top" align="left">2 Sets of 5 to 8 reps</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min/reps and 5 min/sets</td>
<td valign="top" align="center">140&#x02013;200</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191; of MS in the group with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Ozaki et al., <xref ref-type="bibr" rid="B37">2015</xref></td>
<td valign="top" align="left">7 Elderly men</td>
<td valign="top" align="left">GH and MH</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">45% HRres with and without BFR</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="center">20 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">50&#x02013;200</td>
<td/>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">No correlation between GH and MH.</td>
</tr>
<tr>
<td valign="top" align="left">Kim et al., <xref ref-type="bibr" rid="B21">2016</xref></td>
<td valign="top" align="left">31 Healthy men</td>
<td valign="top" align="left">MS, MH</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">3&#x000D7; week/6 weeks</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">20 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">120&#x02013;180</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="left">No difference between groups</td>
</tr>
<tr>
<td valign="top" align="left">Clarkson et al., <xref ref-type="bibr" rid="B8">2017</xref></td>
<td valign="top" align="left">19 Men and women</td>
<td valign="top" align="left">FC</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">CIRCUIT</td>
<td valign="top" align="left">4 km/h</td>
<td valign="top" align="left">4&#x000D7; week/6 weeks</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">10 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">60% of BFR max</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">10.5</td>
<td valign="top" align="left">&#x02191; in FC in the group with BFR</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><italic>BFR, blood flow restriction; EX, exercise; FE, form of execution; VE, velocity of execution; WALK, walking; CYC, cycling; RUN, running; CYCLE, cycle ergometer; min, minutes; s, seconds; CON, Control; PADE, pressure applied during exercise; SW, sleeve width; &#x02013;, Not informed; &#x02191;, significant increase; LI &#x0002B; BFR, low intensity combined with blood flow restriction; LI, low intensity; HI, High intensity. GH, Growth Hormone; MDF, Maximum Dynamic Force; HR, Heart Rate; mTOR, mammalian target of rapamycin; MAPK, Mitogen-activated protein kinase; GH, Growth Hormone; MH, Muscle hypertrophy; FC, Functional Capacity; MS, muscle strength; HI, High Intensity; REPS, Repetitions</italic>.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s8">
<title>Acute Effects of AE &#x0002B; BFR</title>
<sec>
<title>Intracellular Signaling Associated With Hypertrophy</title>
<p>Ozaki et al. (<xref ref-type="bibr" rid="B36">2014</xref>) performed an analysis of muscle biopsies indicated that Erk 1/2 phosphorylation levels were significantly higher after exercise. However, only the leg that performed the exercise with BFR caused an increase in p38 phosphorylation. For the mTOR signaling pathway, no changes in the Akt, mTOR, or S6K1 phosphorylation levels were observed before or after walking. Thus, 3 h after exercise, the eEF2 phosphorylation level for the leg with BFR was significantly lower than the eEF2 phosphorylation level for the leg without BFR. Walking with BFR can activate the intracellular signaling pathways that are associated with muscle hypertrophy in young men.</p>
</sec>
<sec>
<title>Growth Hormone</title>
<p>Two studies investigated the impact of AE &#x0002B; BFR on growth hormone concentrations. Abe et al. (<xref ref-type="bibr" rid="B2">2006</xref>) noted that after the training period there had been an increase in growth hormone was only observed in the group with BFR. On the other hand Ozaki et al. (<xref ref-type="bibr" rid="B37">2015</xref>), correlated hormonal responses and hypertrophy. They revealed that the change in growth hormone, insulin and noradrenaline levels did not significantly correlate with the hypertrophy caused by AE &#x0002B; BFR, which suggests that walking with BFR-induced elevation in these anabolic hormones, but may not impact muscle growth.</p>
</sec>
<sec>
<title>Muscle Torque and Muscle Activation</title>
<p>No significant changes in torque were observed for the protocols with BFR 1 min post exercise, but there was an increase in muscle thickness of the quadriceps (&#x0007E;2 mm) in the high intensity and low intensity protocols with 40% of BFR higher than other protocols of the study (Kim et al., <xref ref-type="bibr" rid="B20">2015</xref>). Muscle activation with high intensity cycling was significantly higher than muscle activation in the sessions combined with BFR (Kim et al., <xref ref-type="bibr" rid="B20">2015</xref>).</p>
</sec>
</sec>
<sec id="s9">
<title>Chronic Effects of AE &#x0002B; BFR</title>
<sec>
<title>Muscle Strength, Hypertrophy, and Physical Performance Tests</title>
<p>In the study of Abe et al. (<xref ref-type="bibr" rid="B2">2006</xref>), after the training period, an &#x0007E;4&#x02013;7% increase in the thigh muscle volume and cross-sectional area and an 8&#x02013;10% increase in the dynamic strength and maximum isometric force in the group that trained with BFR were observed. In another study (Abe et al., <xref ref-type="bibr" rid="B1">2010a</xref>), the authors discovered that the cycling combined with the BFR protocol promoted 3.4&#x02013;5.1% muscle hypertrophy and the isometric strength in knee extension tended to increase by 7.7%.</p>
<p>Walking with BFR improved the functional capacity, increased the isometric strength (11%) and isokinetic strength (7&#x02013;16%) in knee extension and flexion, and caused an increase in the cross-sectional area of the thigh (5.8%) and the leg (5.1%) (Abe et al., <xref ref-type="bibr" rid="B3">2010b</xref>). Improvements were also found in 23 sedentary subjects&#x02014;five men and 18 women&#x02014;that were randomized into two groups 1) continuous walking with BFR and 2) continuous walking without BFR. The training was performed for 20 min on the treadmill with 45% of HR<sub>max</sub> 4 days a week for 10 weeks. The group that trained with BFR used an inflatable cuff positioned in the region near the thighs with a severe pressure of 200 mmHg for all subjects. Increases in the maximal knee joint strength (&#x0007E;15%) and thigh muscle cross-sectional area (3%) were observed (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>).</p>
<p>Regarding muscle volume, a significant increase in the muscle volume of the proximal region of the thigh (3.8%) and leg (3.2%) was observed (Sakamaki et al., <xref ref-type="bibr" rid="B44">2011</xref>). Also, improvements in muscle strength by 11% were observed after a training program with BFR (de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref>). As for trained college students (<italic>n</italic> &#x0003D; 31) that performed 20 min of cycling, three times a week for 6 weeks no significant difference was found in muscle strength between the groups with or without BFR (Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>).</p>
<p>Elderly men and women (<italic>n</italic> &#x0003D; 19) that performed walking at a speed of 4 km/h for 10 min around a circuit in a field with a distance of 667 meters showed significant 2.5- to 4.5-fold improvement for the 30 s sit to stand, 6-min walk test, timed up and go, and a modified Queen&#x00027;s College step test was observed for the BFR group when compared with the control group after the 6-week training program (Clarkson et al., <xref ref-type="bibr" rid="B8">2017</xref>).</p>
</sec>
<sec>
<title>Local Aerobic Muscle Adaptations</title>
<p>In the study by Keramidas et al. (<xref ref-type="bibr" rid="B19">2012</xref>), twenty untrained subjects were randomized into a control group that trained without BFR and an experimental group that trained with BFR. Both groups trained 3 days per week for 6 weeks with the same relative intensity, and each training session consisted of 2 min at 90% of VO2<sub>max</sub> and 2 min of active interval training at 50% of VO2<sub>max</sub>. An incremental exercise test to exhaustion, a 6-min constant-power test at 80% of VO<sub>2max</sub> (Sub80) were performed pre- and post-training. It is notable that the AE &#x0002B; BFR group exhibited more pronounced muscle deoxygenation than the CON group, measured with near-infrared muscle spectroscopy. The higher post-training muscle deoxygenation shows up the capacity of the exercising muscles to work with a higher supply of oxygen.</p>
</sec>
<sec>
<title>Exercises, Sample Size, Gender, and Standards in the Studies</title>
<p>The 12 training protocols of AE &#x0002B; BFR that were employed to investigate the neuromuscular variables are highlighted: (a) seven studies (58.3%) involved walking and five studies (41.7%) involved cycling. It was observed that six studies (50%) used treadmill, five studies (41.7%) used cycle ergometer and one study (8.3%) use circuit exercise. Additionally, eight studies (66.7%) involved continuous aerobic exercise protocols and four studies (33.3%) involved interval aerobic exercise protocols. Given that the sample size and sex may be an important aspect in these studies, sample sizes were small and ranged from six to 31 subjects, with a predominance of males. Seven studies (58.3%) were conducted with only men, and five studies (41.7%) were conducted with men and women. Regarding the device used for BFR, all studies (100%) used the cuffs with sizes that ranging from 5 to 18 cm. The BFR pressure in the cuffs ranged from 50 to 230 mmHg during exercise sessions that were intermittently performed (without deflating the cuff between sets) or continuously performed, and only the study by Kim et al. (<xref ref-type="bibr" rid="B20">2015</xref>) determined the BFR pressure by estimating the thigh circumference. In the studies that investigated the chronic effects of AE &#x0002B; BFR, training was performed between 2 and 10 weeks by young and elderly adults.</p>
<sec>
<title>Effect of AE &#x0002B; BFR on Hemodynamic Variables</title>
<p>Based on the assessment of the articles that investigated AE &#x0002B; BFR, nine studies evaluated the acute effect of this training method on hemodynamic variables (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>; Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref>; Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref>; Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref>; Cirilo-Sousa et al., <xref ref-type="bibr" rid="B7">2017</xref>; Barilli et al., <xref ref-type="bibr" rid="B5">2018</xref>; Concei&#x000E7;&#x000E3;o et al., <xref ref-type="bibr" rid="B10">2018</xref>; Silva et al., <xref ref-type="bibr" rid="B46">2018</xref>, <xref ref-type="bibr" rid="B45">2019</xref>; Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref>). Studies that investigated the acute effect of AE &#x0002B; BFR assessed cardiac output (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref>; Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref>), heart rate variables (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>; Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref>; Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref>; Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref>; Cirilo-Sousa et al., <xref ref-type="bibr" rid="B7">2017</xref>; Barilli et al., <xref ref-type="bibr" rid="B5">2018</xref>; Silva et al., <xref ref-type="bibr" rid="B46">2018</xref>, <xref ref-type="bibr" rid="B45">2019</xref>; Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref>), stroke volume (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref>; Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref>), blood pressure (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref>; Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref>; Cirilo-Sousa et al., <xref ref-type="bibr" rid="B7">2017</xref>; Barilli et al., <xref ref-type="bibr" rid="B5">2018</xref>; Silva et al., <xref ref-type="bibr" rid="B46">2018</xref>; Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref>), total peripheral resistance (Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref>; Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref>), and double product (Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref>) (<xref ref-type="table" rid="T3">Table 3</xref>).</p>
<table-wrap position="float" id="T3">
<label>Table 3</label>
<caption><p>Synthesis of the results of studies that evaluate the acute effect of combined aerobic exercise and blood flow restriction on hemodynamic variables in athletes, young adults, and elderly individuals.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left"><bold>References</bold></th>
<th valign="top" align="left"><bold>Subjects</bold></th>
<th valign="top" align="left"><bold>Variable</bold></th>
<th valign="top" align="center" colspan="3" style="border-bottom: thin solid #000000;"><bold>Exercise protocol</bold></th>
<th valign="top" align="left"><bold>Intensity/frequency of training/study of duration</bold></th>
<th valign="top" align="center" colspan="2" style="border-bottom: thin solid #000000;"><bold>Exercise volume</bold></th>
<th valign="top" align="center"><bold>Interval</bold></th>
<th valign="top" align="center"><bold>PADE</bold> <break/><bold>(mmHg)</bold></th>
<th valign="top" align="left"><bold>BFR between sets</bold></th>
<th valign="top" align="center"><bold>SW(cm)</bold></th>
<th valign="top" align="left"><bold>Results</bold></th>
</tr>
<tr>
<th/>
<th/>
<th/>
<th valign="top" align="right"><bold>EX</bold></th>
<th valign="top" align="right"><bold>FE</bold></th>
<th valign="top" align="right"><bold>VE</bold></th>
<th/>
<th valign="top" align="left"><bold>Series or continuous</bold></th>
<th valign="top" align="left"><bold>Repetitions or duration time</bold></th>
<th/>
<th/>
<th/>
<th/>
<th/>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Abe et al., <xref ref-type="bibr" rid="B2">2006</xref></td>
<td valign="top" align="left">18 Healthy youth</td>
<td valign="top" align="left">HR</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">50 m/min</td>
<td/>
<td valign="top" align="left">5 Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">120&#x02013;220</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">-</td>
<td valign="top" align="left">&#x02191; HR during protocol with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Abe et al., <xref ref-type="bibr" rid="B1">2010a</xref></td>
<td valign="top" align="left">19 Young men</td>
<td valign="top" align="left">HR</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">50 m/min</td>
<td valign="top" align="left">40% VO<sub>2max</sub>BFR <break/>40% VO<sub>2Max</sub></td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">15 min with BFR <break/>45 min without BFR</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">160&#x02013;210</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191; HR in protocol with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref></td>
<td valign="top" align="left">17 men and women adults</td>
<td valign="top" align="left">HR, CO, DP and SBP</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">3.21 Km/h</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">5-Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">160</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="left">&#x02191; HR, BP and DP and &#x02193; SV during training with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref></td>
<td valign="top" align="left">10 Men</td>
<td valign="top" align="left">HR, CO, SBP, DBP, MAP, SV</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">0&#x02013;20&#x02013;40&#x02013;60% VO<sub>2max</sub> with and without BFR</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">4 min each stage</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191;HR, CO, SBP, DBP, MAP and &#x02193; VEJ in training with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref></td>
<td valign="top" align="left">10 Men and women</td>
<td valign="top" align="left">HR</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">75 m/min</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">5 Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">Elastic</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">7.6</td>
<td valign="top" align="left">&#x02191;HR in the exercise session with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref></td>
<td valign="top" align="left">8 Men</td>
<td valign="top" align="left">HR, SBP, DBP, SV, BP, CO, TPR</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">BICYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">40% VO<sub>2max</sub> with and without BFR</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">30 min</td>
<td valign="top" align="center">-</td>
<td valign="top" align="center">200</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191; HR BFR and CON <break/>&#x02191; SBP and DBP in training with BFR until 10 min</td>
</tr>
<tr>
<td valign="top" align="left">Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref></td>
<td valign="top" align="left">34 Obese men and women</td>
<td valign="top" align="left">HR, SBP, DBP</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">50 rpm</td>
<td valign="top" align="left">40% &#x0002B; BFR <break/>60% &#x0002B; BFR <break/>without BFR <break/>50 Watts</td>
<td valign="top" align="left">2 Sets</td>
<td valign="top" align="left">10 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">40%60%</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">5.0</td>
<td valign="top" align="left">&#x02191; &#x0003E; HR and SBP in BFR protocols</td>
</tr>
<tr>
<td valign="top" align="left">Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref></td>
<td valign="top" align="left">15 Adult men and women</td>
<td valign="top" align="left">HR, SBP, DBP, SV, CO, TPR</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">3.21 Km/h</td>
<td valign="top" align="left">WALK &#x0002B; BFR <break/>WALK</td>
<td valign="top" align="left">5 Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">160</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="left">&#x02191; &#x0003E; HR, SBP in protocol with BFR. SV and TPR is &#x0003E; for the control</td>
</tr>
<tr>
<td valign="top" align="left">Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref></td>
<td valign="top" align="left">21 Elderly men and women</td>
<td valign="top" align="left">HR, SBP, DBP, DP, SV, TPR, CO</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">40% VO<sub>2max</sub>BFR <break/>40% VO<sub>2max</sub> <break/>70% VO<sub>2Max</sub></td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">20 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">50%</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">17.5</td>
<td valign="top" align="left">&#x02191; HR and SBP in protocols BFR. DP in the protocol HI &#x0003E; LI and LI&#x0002B;BFR</td>
</tr>
<tr>
<td valign="top" align="left">Cirilo-Sousa et al., <xref ref-type="bibr" rid="B7">2017</xref></td>
<td valign="top" align="left">13 Men</td>
<td valign="top" align="left">HR, SBP, DBP</td>
<td valign="top" align="left">RUN</td>
<td valign="top" align="left">STATIONARY</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">50% HRM&#x000E1;x&#x0002B;BFR <break/>50% HRM&#x000E1;x</td>
<td valign="top" align="left">5 Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">1 min</td>
<td valign="top" align="center">80%</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191; HR, SBP and DBP in protocol with BFR</td>
</tr>
<tr>
<td valign="top" align="left">Concei&#x000E7;&#x000E3;o et al., <xref ref-type="bibr" rid="B10">2018</xref></td>
<td valign="top" align="left">12 Men</td>
<td valign="top" align="left">HR</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">60&#x02013;70 rpm</td>
<td valign="top" align="left">40% VO<sub>2Max</sub> &#x0002B; BFR <break/>40% VO<sub>2Max</sub></td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">30 min</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">80%</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191; HR in protocol AE&#x0002B;BFR</td>
</tr>
<tr>
<td valign="top" align="left">Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref></td>
<td valign="top" align="left">18 Men</td>
<td valign="top" align="left">BP, HR, CO</td>
<td valign="top" align="left">CYC</td>
<td valign="top" align="left">CYCLE</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="left">HI <break/>LI <break/>LI &#x0002B; BFR</td>
<td valign="top" align="left">3 Sets</td>
<td valign="top" align="left">2 min</td>
<td valign="top" align="center">2 min active</td>
<td valign="top" align="center">80%</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">10</td>
<td valign="top" align="left">&#x02191;BP, HR, CO in protocol HI &#x0003E; LI &#x0002B; BFR and LI <break/>BP, HR, CO in protocol LI &#x0002B; BFR &#x0003E; LI</td>
</tr>
<tr>
<td valign="top" align="left">Barilli et al., <xref ref-type="bibr" rid="B5">2018</xref></td>
<td valign="top" align="left">18 Elderly women</td>
<td valign="top" align="left">HR, SBP, DBP</td>
<td valign="top" align="left">WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td/>
<td valign="top" align="left">HIAE <break/>LI <break/>LI&#x0002B;BFR</td>
<td valign="top" align="left">Continuous</td>
<td valign="top" align="left">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">130% SBP rest</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">9.5</td>
<td valign="top" align="left">HR, SBP, and DPB in protocol HIAE &#x0003D; LI &#x0002B; BFR</td>
</tr>
<tr>
<td valign="top" align="left">Silva et al., <xref ref-type="bibr" rid="B46">2018</xref></td>
<td valign="top" align="left">23 Men</td>
<td valign="top" align="left">HR, SBP, DBP</td>
<td valign="top" align="left">RUN <break/>WALK</td>
<td valign="top" align="left">TREADMILL</td>
<td/>
<td valign="top" align="left">HIIE <break/>AE &#x0002B; BFR <break/>AE</td>
<td valign="top" align="left">6 sets continuous</td>
<td valign="top" align="left">90 s <break/>18 min</td>
<td valign="top" align="center">90 s active-</td>
<td valign="top" align="center">50%</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02193; SBP, DPB in protocol HIIE and AE &#x0002B; BFR</td>
</tr>
<tr>
<td valign="top" align="left">Silva et al., <xref ref-type="bibr" rid="B45">2019</xref></td>
<td valign="top" align="left">22 Men</td>
<td valign="top" align="left">HR</td>
<td valign="top" align="left">RUNWALK</td>
<td valign="top" align="left">TREADMILL</td>
<td/>
<td valign="top" align="left">HIIE <break/>AE &#x0002B; BFR <break/>AE</td>
<td valign="top" align="left">6 set <break/>Continuous</td>
<td valign="top" align="left">90 s <break/>18 min</td>
<td valign="top" align="center">90 s active</td>
<td valign="top" align="center">50%</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">18</td>
<td valign="top" align="left">&#x02191;HR in protocol HIIE <break/>But, AE &#x0002B; BFR &#x0003E; AE</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><italic>BFR, blood flow restriction; HR, heart rate; BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; TPR, total peripheral resistance; CO, cardiac output; SV, stroke volume; DP, double product; EX, exercise; FE, form of exercise; VE, velocity of exercise; RPM, rotations per minute; WALK, walking; CYC, cycling; RUN, running; CYCLE, cycle ergometer; min, minutes; s, seconds; CON, Control; PADE, pressure applied during exercise; SW, sleeve width; &#x02013;, Not informed; &#x02191;, significant increase; LI &#x0002B; BFR, low intensity combined with blood flow restriction; LI, low intensity; HI, high intensity</italic>.</p>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
</sec>
<sec id="s10">
<title>Acute Effects of AE &#x0002B; BFR</title>
<sec>
<title>Cardiac Output</title>
<p>The studies that investigated cardiac output (CO) did not observe significant differences between a BFR exercise session and a control session performed without BFR (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref>). The study of Ozaki et al. (<xref ref-type="bibr" rid="B35">2010</xref>) did not identify a significant difference in AE of the same intensity with or without BFR but did reveal that the high intensity exercise yielded higher cardiac values than low intensity exercise and low intensity with BFR exercise.</p>
</sec>
<sec>
<title>Heart Rate</title>
<p>The study of Ferreira et al. (<xref ref-type="bibr" rid="B14">2016</xref>), which was performed with elderly individuals, demonstrated that heart rate (HR) in exercise performed with HI is higher than the heart rate in exercise performed with LI and LI &#x0002B; BFR. Some studies reported that during exercise, the increase in HR in LI &#x0002B; BFR exceeded the increase in HR in LI exercise (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>; Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>; Silva et al., <xref ref-type="bibr" rid="B46">2018</xref>, <xref ref-type="bibr" rid="B45">2019</xref>). The studies by Ozaki et al. (<xref ref-type="bibr" rid="B35">2010</xref>) and Karabulut and Garcia (<xref ref-type="bibr" rid="B17">2015</xref>) suggest a linear increase in HR with an increase in exercise intensity and suggest that the higher the BFR pressure, the higher the HR values during exercise.</p>
</sec>
<sec>
<title>Stroke Volume</title>
<p>Some studies reported that stroke volume in the exercise session performed with BFR was lower than the stroke volume in the control exercise session without BFR (Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref>). Ferreira et al. (<xref ref-type="bibr" rid="B14">2016</xref>) investigated hemodynamic variables up to 30 min after exercise and discovered that stroke volume only decreased in the exercise with BFR session.</p>
</sec>
<sec>
<title>Blood Pressure</title>
<p>Systolic blood pressure (SBP) and mean arterial pressure (MAP) increased immediately after the session AE &#x0002B; BFR (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>). However, it was observed that during the aerobic exercise with BFR, the SBP and MAP were significantly higher than in the control session without BFR (Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Karabulut and Garcia, <xref ref-type="bibr" rid="B17">2015</xref>; Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref>; Thomas et al., <xref ref-type="bibr" rid="B53">2018</xref>). Diastolic blood pressure (DBP) during in exercise with BFR was higher than the DBP in the control session without BFR (Sugawara et al., <xref ref-type="bibr" rid="B48">2015</xref>). The study by Ozaki et al. (<xref ref-type="bibr" rid="B35">2010</xref>) did not reveal any significant differences in MAP when the exercise was performed at 20% of VO2<sub>max</sub> between the exercise with BFR and the control session without BFR. However, when the exercise was performed at intensities of 40 and 60% of VO2<sub>max</sub>, the MAP values in the exercise combined with BFR was higher than the MAP values in the exercise without BFR. Barilli et al. (<xref ref-type="bibr" rid="B5">2018</xref>) showed that 30 min after aerobic exercise with and without blood flow restriction, SBP and DBP return to resting levels. In the studies by Cirilo-Sousa et al. (<xref ref-type="bibr" rid="B7">2017</xref>) and Silva et al. (<xref ref-type="bibr" rid="B46">2018</xref>) the hypotensive effect occurred after 50 min of aerobic exercise with BFR.</p>
</sec>
<sec>
<title>Total Peripheral Resistance</title>
<p>Kumagai et al. (<xref ref-type="bibr" rid="B23">2012</xref>) revealed that the total peripheral resistance (TPR) in the BFR exercise session was significantly greater than the TPR in the session with the same intensity without BFR. In the study by Ferreira et al. (<xref ref-type="bibr" rid="B14">2016</xref>), which was performed with elderly individuals, significant differences among the HI, LI, and LI &#x0002B; BFR protocols were not observed during and after the session. In the study by Ozaki et al. (<xref ref-type="bibr" rid="B35">2010</xref>), when exercise was performed with 20% of VO2<sub>max</sub>, significant differences were not observed between exercise with BFR and the control session. However, starting at 40% of VO2<sub>max</sub>, TPR in the BFR session was higher than the TPR in the control session.</p>
</sec>
<sec>
<title>Exercises, Sample Size, Gender, and Standards Used in the Studies</title>
<p>The 15 training protocols of AE &#x0002B; BFR that were employed to investigate the hemodynamic variables are highlighted: (a) eight studies (53.3%) involved walking; (b) six studies (40%) involved cycling, and one study (6.7%) involved running. It was observed that eight studies (53.3%) used treadmill, five studies (33.3%) used cycle ergometer, one study (6.73%) use bicycle and one study (6.7%) did not use any equipment. In addition, in eight studies (53.3%) continuous aerobic exercise protocols were performed and in seven studies (46.7%) interval forms of aerobic exercise protocols were performed. Given that sample size and sex may be important aspects, the sample size in these studies was small and ranged from eight to 34 subjects, with a predominance of males. Nine studies (60%) involved only men, five studies (33.3%) involved men and women and one study (6.7%) involved women. Regarding the device for BFR, fourteen studies (93.3%) used inflatable cuff sizes that range from 5 to 18 cm, and only one study (6.7%) was performed using 7.6-cm elastic bands. Six studies were performed utilizing a fixed BFR pressure from 120 to 220 mmHg for all subjects, and seven studies employed BFR pressure percentages that varied between 40 and 80% of arterial occlusion pressure, and one study used 130% of resting systolic blood pressure. The BFR pressure in the cuffs ranged from 50 to 230 mmHg during exercise sessions that were performed in intervals (without deflation between sets) or continuously performed.</p>
</sec>
</sec>
<sec sec-type="discussion" id="s11">
<title>Discussion</title>
<sec>
<title>Acute Effects of AE With BFR on Metabolic Variables</title>
<p>The studies that investigated the impact of AE with BFR on metabolic responses reported increases in VO<sub>2</sub> throughout the sessions and an increase in the magnitude of EPOC, which exceeds the VO<sub>2</sub> and EPOC in sessions with the same intensity without BFR; these findings may be related to an increase in exercise intensity (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>; Mendonca et al., <xref ref-type="bibr" rid="B31">2015</xref>; Silva et al., <xref ref-type="bibr" rid="B45">2019</xref>), cumulative oxygen deficit (Mendonca et al., <xref ref-type="bibr" rid="B31">2015</xref>), level of BFR pressure applied in the exercise (Pfeiffer et al., <xref ref-type="bibr" rid="B41">2019</xref>), and the increased activity of the leg muscles with restricted blood flow (Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>)</p>
<p>The increase in metabolic variables caused by BFR may be explained by the increase in ventilation, ratings of perceived exertion, heart rate, and lactate during exercise (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>; Concei&#x000E7;&#x000E3;o et al., <xref ref-type="bibr" rid="B10">2018</xref>; Silva et al., <xref ref-type="bibr" rid="B45">2019</xref>), which influences the replenishment of oxygen reserves in the blood and muscles, ATP and creatine phosphate resynthesis, lactate removal, and body temperature after exercise and contributes to an increase in the magnitude of EPOC (Mendonca et al., <xref ref-type="bibr" rid="B31">2015</xref>).</p>
<p>Another factor that seems to influence the increase in VO<sub>2</sub> throughout exercise sessions is the BFR pressure level applied during exercise with BFR (Pfeiffer et al., <xref ref-type="bibr" rid="B41">2019</xref>), as seen in the study by Karabulut and Garcia (<xref ref-type="bibr" rid="B17">2015</xref>). These authors evaluated obese subjects on the cycle ergometer and observed that the cycling session performed with 60% of arterial occlusion pressure increased the energy demand more than a session performed with 40% of arterial occlusion pressure and wich increased the energy demand more than a cycling session without BFR. Thus, the increase in the energy demand in sessions of AE with BFR may depend on the BFR pressures that are applied during exercise. This increased energy demand may help to explain other physiological changes, such as heart rate and ventilation during aerobic training sessions with BFR (Concei&#x000E7;&#x000E3;o et al., <xref ref-type="bibr" rid="B10">2018</xref>; Silva et al., <xref ref-type="bibr" rid="B45">2019</xref>).</p>
<p>AE with BFR may cause greater recruitment of the leg muscles (Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>; Kim et al., <xref ref-type="bibr" rid="B20">2015</xref>), which can be explained by the reduction in oxygen and subsequent metabolic accumulation. Thus, this accumulation of metabolites is believed to increase muscle fiber recruitment via stimulation of group III and IV afferent pathways, which may cause alpha motorneuron inhibition and an increase in the recruitment of muscle fibers to maintain force and protect against conduction failures (Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>). However, the lactate accumulation in AE with BFR is not a universal finding since Loenneke et al. (<xref ref-type="bibr" rid="B28">2012</xref>) discovered that low-intensity interval walking performed with a combination of elastic wraps did not promote metabolite accumulation due to the different amounts of BFR applied to the participants, which are influenced by the structure of the body segment, such as thigh circumference and limb composition.</p>
<p>Regarding the acute effects of AE with BFR, the study of Mendonca et al. (<xref ref-type="bibr" rid="B32">2014</xref>) reinforces the idea that an increase in the net VO<sub>2</sub> throughout the AE with BFR session may occur due to an increase in the recruitment of type II fibers. This hypothesis is supported by some studies of the low load resistance training literature utilizing BFR, which have reported increases EMG amplitude (Yasuda et al., <xref ref-type="bibr" rid="B54">2006</xref>; Karabulut et al., <xref ref-type="bibr" rid="B16">2010</xref>). Karabulut and Garcia (<xref ref-type="bibr" rid="B17">2015</xref>) determined that the increased dependence on carbohydrates during exercise with BFR may be explained by increased adrenaline and noradrenaline levels and a greater demand for type II muscle fibers.</p>
<p>Thus, recent studies suggest that walking with BFR increases the electromyographic activity of the vastus lateralis; these findings are compatible with an additional recruitment of type II muscle fibers (Mendonca et al., <xref ref-type="bibr" rid="B31">2015</xref>). Considering that type II muscle fibers require more O<sub>2</sub> than type I for the same amount of work (Mendonca et al., <xref ref-type="bibr" rid="B31">2015</xref>), fiber type recruitment has an important role in increasing VO<sub>2</sub> during AE with BFR. Although it has not been explored, increased activation of the gluteus maximus may also contribute to an increase in the net VO<sub>2</sub> during exercise with BFR.</p>
</sec>
<sec>
<title>Chronic Effect of AE With BFR on Metabolic Variables</title>
<p>Regarding the chronic effects of AE with BFR, the adaptive responses that are linked to prolonged severe exercise tolerance after cycling training with BFR seems to be attributed to the increase in physiological and metabolic stress induced by BFR (Corvino et al., <xref ref-type="bibr" rid="B11">2014</xref>; Concei&#x000E7;&#x000E3;o et al., <xref ref-type="bibr" rid="B10">2018</xref>). Thus, the determinants of the time of exhaustion also seem to be related to the exhaustion of finite anaerobic reserves and the accumulation of a variety of metabolic by products. Park et al. (<xref ref-type="bibr" rid="B39">2010</xref>) observed a 2.5% increase in the anaerobic capacity of the group that trained with AE combined with BFR; this improvement can be attributed to an increase in the glycogen content, as observed in other studies with BFR (Sundberg, <xref ref-type="bibr" rid="B49">1994</xref>; Burgomaster et al., <xref ref-type="bibr" rid="B6">2003</xref>).</p>
<p>In the same study, Park et al. (<xref ref-type="bibr" rid="B39">2010</xref>) discovered an increase in the cardiorespiratory capacity (9&#x02013;10% VO2<sub>max</sub>) in basketball players within 2 weeks; these results are similar to previous studies that used 7&#x02013;10 days of cycling at 60&#x02013;70% of VO2<sub>max</sub> (Spina et al., <xref ref-type="bibr" rid="B47">1996</xref>; Mier et al., <xref ref-type="bibr" rid="B33">1997</xref>). Thus, training with BFR induces similar improvements to exercise with greater intensity performed for the same period of time.</p>
<p>Abe et al. (<xref ref-type="bibr" rid="B1">2010a</xref>) observed an improvement in cardiorespiratory capacity after cycling training with BFR in young adults. This improvement may be attributed due to adaptations in muscle oxidation capacity (arterial and mixed venous blood oxygen (a-VO<sub>2</sub>) difference and systolic volume). In addition, increased muscle mass in the lower body, capillary density, and citrate synthesis activity may be associated with improvements in VO2<sub>max</sub> in the BFR training group. However, some studies that performed AE combined with BFR did not observe improvements in the cardiorespiratory capacity in elderly individuals (Abe et al., <xref ref-type="bibr" rid="B3">2010b</xref>) or young individuals (Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>).</p>
<p>In the study by Abe et al. (<xref ref-type="bibr" rid="B3">2010b</xref>), the exercise intensity and duration of the training program may have influenced the results. Although the elderly subjects walked 5 days a week, the speed used for the exercise was low (67 m/min) and insufficient for improving the cardiorespiratory capacity. The same outcome may have occurred in the study by Kim et al. (<xref ref-type="bibr" rid="B21">2016</xref>) due to the use of reserve HR for exercise prescription with BFR. Thus, reserve HR may not be appropriate due to the observed increase in HR with the application of BFR due to a decrease in venous return.</p>
<p>de Oliveira et al. (<xref ref-type="bibr" rid="B13">2015</xref>) observed that LIIT &#x0002B; BFR improved the onset of blood lactate accumulation by 16% and maximum power by 15% without a significant difference among the HIIT groups. Thus, it seems that this training method increases the respiratory capacity of the muscle and promotes angiogenesis due to ischemia and reperfusion because the cuffs were deflated during the interval periods during exercise and this intermittent hypoxia can cause additional effects in some responses. In the study by Taylor et al. (<xref ref-type="bibr" rid="B52">2016</xref>), BFR was employed after the sprints, and the running training with BFR post-exercise was efficient for increasing the cardiorespiratory capacity of trained youth. This finding may be attributed to increased skeletal muscle and capillary density via cell signaling induced by enhanced hypoxia given the increased expression of growth factor HIF-1&#x003B1;.</p>
</sec>
<sec>
<title>Effect of AE With BFR on Neuromuscular Variables</title>
<sec>
<title>Adaptation in the Muscle Strength</title>
<p>A review of the selected studies reveals that the increased muscle strength via AE &#x0002B; BFR is not a universal finding. In four studies, an increase of 7.7&#x02013;15% in muscle strength was observed within a period of 3&#x02013;10 weeks of training with BFR (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>; Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; de Oliveira et al., <xref ref-type="bibr" rid="B13">2015</xref>). Thus, an increase in muscle strength via this training method is explained by neural adaptations during training-induced hypoxia (Abe et al., <xref ref-type="bibr" rid="B1">2010a</xref>) and also partly via factors that increase muscle hypertrophy such as myogenic factors during exercise (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>; Keramidas et al., <xref ref-type="bibr" rid="B19">2012</xref>), however, the physiological mechanisms that explain the increase of muscle strength through AE &#x0002B; BFR need to be better elucidated. In only one study, muscle strength was not increased after an aerobic training program with BFR (Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>), which may have been attributed to the influence of the volume, intensity, and duration of training being lower than those from other studies.</p>
</sec>
</sec>
<sec>
<title>Adaptations in the Muscle Hypertrophy</title>
<p>Regarding the chronic effects of AE with BFR in muscle hypertrophy, it is known that this training method promotes muscle hypertrophy, however, this finding is not always observed. One study, which involved cycling with BFR, did not identify an increase in hypertrophy (Kim et al., <xref ref-type="bibr" rid="B21">2016</xref>) after the training program. This can be explained by the use of very low training intensity (30% of HR<sub>max</sub>), lower than those from other studies. Thus, it has been demonstrated that performing 20 min of cycling, 3 times a week for 6 weeks using very low intensity training (30% of HR<sub>max</sub>) combined with BFR is not enough stimulus to promote adaptations in muscle strength and hypertrophy.</p>
<p>In addition, five studies investigating EA &#x0002B; RFS reported an increase between 3 and 7% of muscle hypertrophy in the thigh and leg (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>,<xref ref-type="bibr" rid="B3">b</xref>; Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>; Sakamaki et al., <xref ref-type="bibr" rid="B44">2011</xref>). However, the gains of muscle hypertrophy through AE &#x0002B; BFR are not the same as the ones achieved by resistance training with BFR (RT &#x0002B; BFR). Studies with resistance training &#x0002B; BFR reported gains of 5&#x02013;12.3% of muscle hypertrophy in the thigh (Takarada and Ishii, <xref ref-type="bibr" rid="B50">2002</xref>; Abe et al., <xref ref-type="bibr" rid="B4">2005</xref>; Kubo et al., <xref ref-type="bibr" rid="B22">2006</xref>; Laurentino et al., <xref ref-type="bibr" rid="B24">2008</xref>). Although gains in AE &#x0002B; BFR are lower than resistance training with BFR, the AE &#x0002B; BFR training method is still effective and can be used as a tool to maximize muscle strength and hypertrophy in young and old individuals.</p>
<p>In the study by Abe et al. (<xref ref-type="bibr" rid="B3">2010b</xref>), in which walking with a weekly frequency of 5 days was performed for 6 weeks, an increase in hypertrophy for thigh (5,8%) and lower leg (5,1%) muscles was observed in a group of elderly subjects who trained with BFR. Ozaki et al. (<xref ref-type="bibr" rid="B35">2010</xref>) found an increase in thigh hypertrophy (3%) in young individuals after 10 weeks an AE &#x0002B; BFR training program. In the study by Abe et al. (<xref ref-type="bibr" rid="B1">2010a</xref>), a cycling training program with BFR (40% of VO2max) with a duration of 8 weeks and a weekly frequency of three times a week promoted increase (3.4&#x02013;5.1%) in hypertrophy in 19 young men. In the studies by Abe et al. (<xref ref-type="bibr" rid="B2">2006</xref>) and Sakamaki et al. (<xref ref-type="bibr" rid="B44">2011</xref>) the subjects underwent a low-intensity walk combined with BFR twice a day at a weekly frequency of 6 days for 3 weeks. It was observed that in the study by Abe et al. (<xref ref-type="bibr" rid="B2">2006</xref>) there was an increase of 4&#x02013;7% in hypertrophy and in the study by Sakamaki et al. (<xref ref-type="bibr" rid="B44">2011</xref>) there was an increase of 3.2&#x02013;3.8% in hypertrophy.</p>
<p>This increase in the hypertrophy may be attributed to increased levels phosphorylation of Erk1/2 and p38 (Ozaki et al., <xref ref-type="bibr" rid="B36">2014</xref>), and increase in protein synthesis in the vastus lateralis muscle and the Akt/mTOR signaling pathway in young and elderly men, i.e., anabolic responses may significantly contribute to muscle hypertrophy induced by training with BFR. Still, in relation to the physiological mechanisms that explain the increase of hypertrophy through AE &#x0002B; BFR, it is worth noting that up until now the increase of hypertrophy cannot be explained by the elevation of growth hormone levels. In the study by Ozaki et al. (<xref ref-type="bibr" rid="B37">2015</xref>), there was no correlation between growth hormone and muscle hypertrophy, this reveals that elevations in growth hormone levels may not have a prominent role in muscle hypertrophy induced by walking with BFR.</p>
<p>Another important point that does not appear to influence the gains of hypertrophy through AE &#x0002B; BFR is muscle fatigue. Thus, regarding low intensity aerobic exercise in combination with BFR, Ogawa et al. (<xref ref-type="bibr" rid="B34">2012</xref>) observed no decrease in torque following slow or fast walking, suggesting that muscle fatigue may not be a prominent mechanism behind the skeletal muscle hypertrophy observed with low intensity aerobic exercise.</p>
<p>The results by Ogawa et al. (<xref ref-type="bibr" rid="B34">2012</xref>) corroborate the findings of Kim et al. (<xref ref-type="bibr" rid="B20">2015</xref>) that did not find significant changes in post-exercise torque, i.e., regardless of the intensity or pressure applied, the muscle was able to recover to a certain extent. Nevertheless, this is in contrast to the large decreases observed after exercise with resistance training (Loenneke et al., <xref ref-type="bibr" rid="B26">2013</xref>). This large acute decrease immediately after resistance exercise appears to be evidence of fatigue and is thought to provide at least part of the mechanistic rationale for BFR inducing skeletal muscle hypertrophy when it is combined with resistance exercise (Loenneke et al., <xref ref-type="bibr" rid="B29">2010</xref>).</p>
</sec>
<sec>
<title>Adaptations in the Physical Performance Tests</title>
<p>Regarding the chronic effects of AE &#x0002B; BFR in the physical performance tests, it is observed that this training method promotes improvement of physical performance tests in elderly. In the study by Abe et al. (<xref ref-type="bibr" rid="B3">2010b</xref>) occurred improvement of physical performance and an increase in the isometric and isokinetic strength of the lower limbs in elderly after 6 weeks of AE &#x0002B; BFR. Furthermore, the study by Clarkson et al. (<xref ref-type="bibr" rid="B8">2017</xref>) found a positive correlation between increased knee extension strength and physical performance tests (for the 30 s sit to stand, 6-min walk test, timed up and go, and a modified Queen&#x00027;s College step test) following an aerobic training program with BFR. Therefore, it seems that a possible explanation for this adaptation to the AE &#x0002B; BFR would be the increase of muscle strength in elderly.</p>
</sec>
<sec>
<title>Effect of AE With BFR on Hemodynamic Variables</title>
<p>Based on the evaluation of the studies that investigated the impact of aerobic exercise with BFR, the increase in HR, double product (DP) and SBP, DBP, and MAP during AE with BFR is greater than the increase observed in a session with the same intensity without BFR (Abe et al., <xref ref-type="bibr" rid="B2">2006</xref>, <xref ref-type="bibr" rid="B1">2010a</xref>; Ozaki et al., <xref ref-type="bibr" rid="B38">2011</xref>; Kumagai et al., <xref ref-type="bibr" rid="B23">2012</xref>; Loenneke et al., <xref ref-type="bibr" rid="B28">2012</xref>; Silva et al., <xref ref-type="bibr" rid="B45">2019</xref>). This finding can be partly explained by the level of BFR pressure during exercise, such that the pressure exerted by the cuff increases blood accumulation in the limbs and affects the strock volume due to a decreased venous return and elevation of noradrenaline concentration, which increases the peripheral vascular resistance (Ozaki et al., <xref ref-type="bibr" rid="B35">2010</xref>).</p>
<p>Karabulut and Garcia (<xref ref-type="bibr" rid="B17">2015</xref>) observed a significant increase in SBP during cycling with BFR compared with a session of the same intensity without BFR. The phenomenon was attributed to an increase in cardiac contractility, which was caused by sympathetic stimulation or an increase in peripheral resistance when using BFR during exercise. Ferreira et al. (<xref ref-type="bibr" rid="B14">2016</xref>), Cirilo-Sousa et al. (<xref ref-type="bibr" rid="B7">2017</xref>), and Silva et al. (<xref ref-type="bibr" rid="B45">2019</xref>) indicated that following the post-exercise recovery period, the reduction in HR, DP and BP in the walking protocol with BFR was greater than the reduction in HR, DP, and BP in a session with the same intensity without BFR, with the autonomic cardiac modulation followed the same pattern. This finding was probably attributed to the increase in parasympathetic reactivation that was observed after the training session with BFR (Ferreira et al., <xref ref-type="bibr" rid="B14">2016</xref>). These results have important clinical implications because the DP is well-correlated with the oxygen consumption in the myocardium, which demonstrates lower cardiovascular stress after the session with BFR.</p>
</sec>
<sec>
<title>Standardization in the Interventions</title>
<p>The results of this review indicate that AE &#x0002B; BFR is an effective method to improve cardiorespiratory capacity, muscle strength, and hypertrophy of young and old individuals, despite the use relatively low training intensities. Most studies were conducted with healthy young men and the samples varied from 6 to 37 subjects in the investigations. In addition, it is difficult to compare the studies because most of them used training sessions with different intensities and duration. Furthermore, the studies also used a variety of methods to apply BFR in exercise protocols. Some studies used elastic bands, other studies used fixed restriction pressures for all subjects, and present large differences in occlusion cuff width.</p>
<p>To illustrate this point, some studies submitted subjects to walk or cycling using elastic bands, also known as practical BFR (Loenneke et al., <xref ref-type="bibr" rid="B27">2011</xref>, <xref ref-type="bibr" rid="B28">2012</xref>). Although the use of elastic bands allows for the practical application of BFR outside the laboratory setting, it is impossible to determine the pressure that is being applied to each subject included in the study. Other studies have used the approach of applying a fixed (constant) restrictive pressure to all subjects (Abe et al., <xref ref-type="bibr" rid="B3">2010b</xref>; Renzi et al., <xref ref-type="bibr" rid="B43">2010</xref>; Mendonca et al., <xref ref-type="bibr" rid="B32">2014</xref>). Applying the same amount of pressure to all subjects without considering other factors such as limb size and composition may limit the interpretation of outcomes from these studies because a fixed pressure may elicit different degrees of occlusion across different individuals. A better approach was first proposed by Laurentino et al. (<xref ref-type="bibr" rid="B24">2008</xref>) who determined the BFR pressure individually for each subject based off the total auscultatory occlusion pressure for the limb as measured at rest through Doppler ultrasound.</p>
</sec>
<sec>
<title>Suggestions for Future Research</title>
<p>We suggest that future studies investigate the effects of AE &#x0002B; BFR, acute changes and effects of a longer training period, in other variables not necessarily related to the muscle, such as blood pressure, sympathetic activation and vascular function, especially in clinical populations (i.e., people with hypertension, COPD, diabetes). That will provide more information about the impact of BFR in other systems of the body and would add knowledge about the safety of this type of exercise.</p>
</sec>
</sec>
<sec sec-type="conclusions" id="s12">
<title>Conclusions</title>
<p>Evidence reveals that AE combined with BFR promotes positive acute and chronic changes in neuromuscular and metabolic variables, a greater elevation in hemodynamic variables and a higher energy demand during and after exercise when compared to sessions of AE with the same intensity without BFR. The BFR was reported as well-tolerated in the populations targeted by the studies used in this review (i.e., athletes, healthy young individuals, obese and elderly individuals) since the increases hemodynamic variables during AE &#x0002B; BFR were smaller than high intensity training. However, these results may not be same in populations other that the ones covered by this review. In addition, the characteristics of the exercises used (i.e., form of execution, exercise intensity, determination of BFR pressure, and width of cuff or elastic band) were not standard among the studies, which may have caused the different acute and chronic responses to the AE with BFRE.</p>
</sec>
<sec id="s13">
<title>Author Contributions</title>
<p>JS, GN, and EP participated in protocol design and data extraction. PP and AR in participated data analyses. MC-S, MB, SP, and GB participated in the preparation and review of the manuscript. All authors have read and approved the final manuscript.</p>
<sec>
<title>Conflict of Interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
</sec>
</body>
<back>
<ref-list>
<title>References</title>
<ref id="B1">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Abe</surname> <given-names>T.</given-names></name> <name><surname>Fujita</surname> <given-names>S.</given-names></name> <name><surname>Nakajima</surname> <given-names>T.</given-names></name> <name><surname>Sakamaki</surname> <given-names>M.</given-names></name> <name><surname>Ozaki</surname> <given-names>H.</given-names></name> <name><surname>Oga</surname> <given-names>R.</given-names></name> <etal/></person-group>. (<year>2010a</year>). <article-title>Effects of low-intensity cycle training with restricted leg blood flow on thigh muscle volume and VO2max in young men</article-title>. <source>J. Sports Sci. Med</source>. <volume>9</volume>, <fpage>452</fpage>&#x02013;<lpage>458</lpage>. <pub-id pub-id-type="pmid">24149640</pub-id></citation></ref>
<ref id="B2">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Abe</surname> <given-names>T.</given-names></name> <name><surname>Kearns</surname> <given-names>C. F.</given-names></name> <name><surname>Sato</surname> <given-names>Y.</given-names></name></person-group> (<year>2006</year>). <article-title>Muscle size and strength are increased following walk training with restricted venous blood flow from the leg muscle, Kaatsu-walk training</article-title>. <source>J. Appl. Physiol</source>. <volume>100</volume>, <fpage>1460</fpage>&#x02013;<lpage>1466</lpage>. <pub-id pub-id-type="doi">10.1152/japplphysiol.01267.2005</pub-id><pub-id pub-id-type="pmid">16339340</pub-id></citation></ref>
<ref id="B3">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Abe</surname> <given-names>T.</given-names></name> <name><surname>Sakamaki</surname> <given-names>M.</given-names></name> <name><surname>Fujita</surname> <given-names>S.</given-names></name> <name><surname>Ozaki</surname> <given-names>H.</given-names></name> <name><surname>Sugaya</surname> <given-names>M.</given-names></name> <name><surname>Sato</surname> <given-names>Y.</given-names></name> <etal/></person-group>. (<year>2010b</year>). <article-title>Effects of low-intensity walk training with restricted leg blood flow on muscle strength and aerobic capacity in older adults</article-title>. <source>J. Geriatr. Phys. Ther</source>. <volume>33</volume>, <fpage>34</fpage>&#x02013;<lpage>40</lpage>. <pub-id pub-id-type="pmid">20503732</pub-id></citation></ref>
<ref id="B4">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Abe</surname> <given-names>T.</given-names></name> <name><surname>Yasuda</surname> <given-names>T.</given-names></name> <name><surname>Midorikawa</surname> <given-names>T.</given-names></name> <name><surname>Sato</surname> <given-names>Y.</given-names></name> <name><surname>Kearns</surname> <given-names>C. F.</given-names></name> <name><surname>Inoue</surname> <given-names>K.</given-names></name> <etal/></person-group>. (<year>2005</year>). <article-title>Skeletal muscle size and circulating IGF-I are increased after two weeks of twice daily kaatsu resistance training</article-title>. <source>Int. J. Kaatsu Training Res</source>. <volume>1</volume>, <fpage>7</fpage>&#x02013;<lpage>14</lpage>. <pub-id pub-id-type="doi">10.3806/ijktr.1.65</pub-id></citation></ref>
<ref id="B5">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Barilli</surname> <given-names>A.</given-names></name> <name><surname>Corralo</surname> <given-names>V. D. S.</given-names></name> <name><surname>Cardoso</surname> <given-names>A. M.</given-names></name> <name><surname>M&#x000E2;nica</surname> <given-names>A.</given-names></name> <name><surname>Bonadiman</surname> <given-names>B. D. S. R.</given-names></name> <name><surname>Bagatini</surname> <given-names>M. D.</given-names></name> <etal/></person-group>. (<year>2018</year>). <article-title>Acute responses of hemodynamic and oxidative stress parameters to aerobic exercise with blood flow restriction in hypertensive elderly women</article-title>. <source>Mol. Biol. Rep.</source> <volume>45</volume>:<fpage>1099</fpage>&#x02013;<lpage>1109</lpage>. <pub-id pub-id-type="doi">10.1007/s11033-018-4261-1</pub-id></citation></ref>
<ref id="B6">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Burgomaster</surname> <given-names>K. A.</given-names></name> <name><surname>Moore</surname> <given-names>D. R.</given-names></name> <name><surname>Schofield</surname> <given-names>L. M.</given-names></name> <name><surname>Phillips</surname> <given-names>S. M.</given-names></name> <name><surname>Sale</surname> <given-names>S. G.</given-names></name></person-group> (<year>2003</year>). <article-title>Resistance training with vascular occlusion: metabolic adaptations in human muscle</article-title>. <source>Med. Sci. Sports Exerc.</source> <volume>35</volume>, <fpage>1203</fpage>&#x02013;<lpage>1208</lpage>. <pub-id pub-id-type="doi">10.1249/01.MSS.0000074458.71025.71</pub-id><pub-id pub-id-type="pmid">12840643</pub-id></citation></ref>
<ref id="B7">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cirilo-Sousa</surname> <given-names>M. S.</given-names></name> <name><surname>Ara&#x000FA;jo</surname> <given-names>J. P.</given-names></name> <name><surname>Freitas</surname> <given-names>E. D.</given-names></name> <name><surname>Aniceto</surname> <given-names>R. R.</given-names></name> <name><surname>Ara&#x000FA;jo</surname> <given-names>V. C.</given-names></name> <name><surname>Pereira</surname> <given-names>P. M. G.</given-names></name> <etal/></person-group>. (<year>2017</year>). <article-title>Acute effect of aerobic exercise with blood flow restriction on blood pressure and heart rate in healthy young subjects</article-title>. <source>Motricidade</source> <volume>13</volume>, <fpage>17</fpage>&#x02013;<lpage>24</lpage>. <pub-id pub-id-type="doi">10.6063/motricidade.12874</pub-id></citation></ref>
<ref id="B8">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Clarkson</surname> <given-names>M. J.</given-names></name> <name><surname>Conway</surname> <given-names>L.</given-names></name> <name><surname>Warmington</surname> <given-names>S. A.</given-names></name></person-group> (<year>2017</year>). <article-title>Blood flow restriction walking and physical function in older adults: a randomized control trial</article-title>. <source>J. Sci. Med. Sport</source>. <volume>20</volume>, <fpage>1041</fpage>&#x02013;<lpage>1046</lpage>. <pub-id pub-id-type="doi">10.1016/j.jsams.2017.04.012</pub-id><pub-id pub-id-type="pmid">28483555</pub-id></citation></ref>
<ref id="B9">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Clemente Su&#x000E1;rez</surname> <given-names>V. J.</given-names></name> <name><surname>Gonz&#x000E1;lez-Rav&#x000E9;</surname> <given-names>J. M.</given-names></name></person-group> (<year>2014</year>). <article-title>Four weeks of training with different aerobic workload distributions &#x02013; Effect on aerobic performance</article-title>. <source>Eur. J. Sport Sci</source>. <volume>14</volume>, <fpage>1</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1080/17461391.2011.635708</pub-id><pub-id pub-id-type="pmid">24444193</pub-id></citation></ref>
<ref id="B10">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Concei&#x000E7;&#x000E3;o</surname> <given-names>M. S.</given-names></name> <name><surname>Gasparil</surname> <given-names>A. F.</given-names></name> <name><surname>Ramkrapes</surname> <given-names>A. P. B.</given-names></name> <name><surname>Junior</surname> <given-names>E. M. M.</given-names></name> <name><surname>Bertuzzi</surname> <given-names>R.</given-names></name> <name><surname>Cavaglieri</surname> <given-names>C. R.</given-names></name> <etal/></person-group>. (<year>2018</year>). <article-title>Anaerobic metabolism induces greater total energy expenditure during exercise with blood flow restriction</article-title>. <source>PLoS ONE</source> <volume>13</volume>:<fpage>e0194776</fpage>. <pub-id pub-id-type="doi">10.1371/journal.pone.0194776</pub-id><pub-id pub-id-type="pmid">29596452</pub-id></citation></ref>
<ref id="B11">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Corvino</surname> <given-names>R. B.</given-names></name> <name><surname>Oliveira</surname> <given-names>M. F. M.</given-names></name> <name><surname>Santos</surname> <given-names>R. P.</given-names></name> <name><surname>Denadai</surname> <given-names>B. S.</given-names></name> <name><surname>Caputo</surname> <given-names>F.</given-names></name></person-group> (<year>2014</year>). <article-title>Four weeks of blood flow restricted training increases time to exhaustion at severe intensity cycling exercise</article-title>. <source>Rev. Bras. Cineantropom. Desempenho Hum.</source> <volume>16</volume>, <fpage>570</fpage>&#x02013;<lpage>578</lpage>. <pub-id pub-id-type="doi">10.5007/1980-0037.2014v16n5p570</pub-id></citation></ref>
<ref id="B12">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Corvino</surname> <given-names>R. B.</given-names></name> <name><surname>Rossiter</surname> <given-names>H. B.</given-names></name> <name><surname>Loch</surname> <given-names>T.</given-names></name> <name><surname>Martins</surname> <given-names>J. C.</given-names></name> <name><surname>Caputo</surname> <given-names>F.</given-names></name></person-group> (<year>2016</year>). <article-title>Physiological responses to interval endurance exercise at different levels of blood flow restriction</article-title>. <source>Eur. J. Appl. Physiol</source>. <volume>117</volume>, <fpage>39</fpage>&#x02013;<lpage>52</lpage>. <pub-id pub-id-type="doi">10.1007/s00421-016-3497-5</pub-id><pub-id pub-id-type="pmid">27826654</pub-id></citation></ref>
<ref id="B13">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>de Oliveira</surname> <given-names>M. F. M.</given-names></name> <name><surname>Caputo</surname> <given-names>F.</given-names></name> <name><surname>Corvino</surname> <given-names>R. B.</given-names></name> <name><surname>Denadai</surname> <given-names>B. S.</given-names></name></person-group> (<year>2015</year>). <article-title>Short-term low-intensity blood flow restricted interval training improves both aerobic fitness and muscle strength</article-title>. <source>Scand. J. Med. Sci. Sports</source> <volume>26</volume>, <fpage>1017</fpage>&#x02013;<lpage>1025</lpage>. <pub-id pub-id-type="doi">10.1111/sms.12540</pub-id><pub-id pub-id-type="pmid">26369387</pub-id></citation></ref>
<ref id="B14">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ferreira</surname> <given-names>M. L. V.</given-names></name> <name><surname>Sardeli</surname> <given-names>A. V.</given-names></name> <name><surname>Souza</surname> <given-names>G. V.</given-names></name> <name><surname>Bonganha</surname> <given-names>V.</given-names></name> <name><surname>Santos</surname> <given-names>L. D. C.</given-names></name> <name><surname>Castro</surname> <given-names>A.</given-names></name> <etal/></person-group>. (<year>2016</year>). <article-title>Cardiac autonomic and haemodynamic recovery after a single session of aerobic exercise with and without blood flow restriction in older adults</article-title>. <source>J. Sports Sci</source>. <volume>35</volume>, <fpage>2412</fpage>&#x02013;<lpage>2420</lpage>. <pub-id pub-id-type="doi">10.1080/02640414.2016.1271139</pub-id><pub-id pub-id-type="pmid">28029066</pub-id></citation></ref>
<ref id="B15">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Garber</surname> <given-names>C. E.</given-names></name> <name><surname>Blissmer</surname> <given-names>B.</given-names></name> <name><surname>Dsechenes</surname> <given-names>M. R.</given-names></name> <name><surname>Franklin</surname> <given-names>B. A.</given-names></name> <name><surname>Lamonte</surname> <given-names>M. J.</given-names></name> <name><surname>Lee</surname> <given-names>I. M.</given-names></name> <etal/></person-group>. (<year>2011</year>). <article-title>American College of Sports Medicine position stand- quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults</article-title>. <source>Med. Sci. Sports Exerc</source>. <volume>43</volume>, <fpage>1334</fpage>&#x02013;<lpage>1359</lpage>. <pub-id pub-id-type="doi">10.1249/MSS.0b013e318213fefb</pub-id><pub-id pub-id-type="pmid">21694556</pub-id></citation></ref>
<ref id="B16">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Karabulut</surname> <given-names>M.</given-names></name> <name><surname>Cramer</surname> <given-names>J. T.</given-names></name> <name><surname>Abe</surname> <given-names>T.</given-names></name> <name><surname>Sato</surname> <given-names>Y.</given-names></name> <name><surname>Bemben</surname> <given-names>M. G.</given-names></name></person-group> (<year>2010</year>). <article-title>Neuromuscular fatigue following low-intensity dynamic exercise with externally applied vascular restriction</article-title>. <source>J. Electromyogr. Kinesiol.</source> <volume>20</volume>, <fpage>440</fpage>&#x02013;<lpage>447</lpage>. <pub-id pub-id-type="doi">10.1016/j.jelekin.2009.06.005</pub-id><pub-id pub-id-type="pmid">19640732</pub-id></citation></ref>
<ref id="B17">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Karabulut</surname> <given-names>M.</given-names></name> <name><surname>Garcia</surname> <given-names>S. D.</given-names></name></person-group> (<year>2015</year>). <article-title>Hemodynamic responses and energy expenditure during blood flow restriction exercise in obese population</article-title>. <source>Clin. Physiol. Funct. Imaging</source> <volume>37</volume>, <fpage>1</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1111/cpf.12258</pub-id><pub-id pub-id-type="pmid">26046808</pub-id></citation></ref>
<ref id="B18">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kelley</surname> <given-names>G. A.</given-names></name> <name><surname>Kelley</surname> <given-names>K. S.</given-names></name></person-group> (<year>2008</year>). <article-title>Efficacy of aerobic exercise on coronary heart disease risk factors</article-title>. <source>Prev. Cardiol.</source> <volume>11</volume>, <fpage>71</fpage>&#x02013;<lpage>75</lpage>. <pub-id pub-id-type="doi">10.1111/j.1751-7141.2008.08037.x</pub-id><pub-id pub-id-type="pmid">18401233</pub-id></citation></ref>
<ref id="B19">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Keramidas</surname> <given-names>M. E.</given-names></name> <name><surname>Kounalakis</surname> <given-names>S. N.</given-names></name> <name><surname>Geladas</surname> <given-names>N. D.</given-names></name></person-group> (<year>2012</year>). <article-title>The effect of interval training combined with thigh cuffs pressure on maximal and submaximal exercise performance</article-title>. <source>Clin. Physiol. Funct. Imaging</source> <volume>32</volume>, <fpage>205</fpage>&#x02013;<lpage>213</lpage>. <pub-id pub-id-type="doi">10.1111/j.1475-097X.2011.01078.x</pub-id><pub-id pub-id-type="pmid">22487155</pub-id></citation></ref>
<ref id="B20">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname> <given-names>D.</given-names></name> <name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Thiebaud</surname> <given-names>R. S.</given-names></name> <name><surname>Abe</surname> <given-names>T.</given-names></name> <name><surname>Bemben</surname> <given-names>M. G.</given-names></name></person-group> (<year>2015</year>). <article-title>The acute muscular effects of cycling with and without different degrees of blood flow restriction</article-title>. <source>Acta Physiol. Hung</source>. <volume>102</volume>, <fpage>428</fpage>&#x02013;<lpage>441</lpage>. <pub-id pub-id-type="doi">10.1556/036.102.2015.4.10</pub-id><pub-id pub-id-type="pmid">26690035</pub-id></citation></ref>
<ref id="B21">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname> <given-names>D.</given-names></name> <name><surname>Singh</surname> <given-names>H.</given-names></name> <name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Thiebaud</surname> <given-names>R. S.</given-names></name> <name><surname>Fahs</surname> <given-names>C. A.</given-names></name> <name><surname>Rossow</surname> <given-names>L. M.</given-names></name> <etal/></person-group>. (<year>2016</year>). <article-title>Comparative effects of vigorous-intensity and low-intensity blood flow restricted cycle training and detraining on muscle mass, strength, and aerobic capacity</article-title>. <source>J. Strength Cond. Res.</source> <volume>30</volume>, <fpage>1453</fpage>&#x02013;<lpage>1461</lpage>. <pub-id pub-id-type="doi">10.1519/JSC.0000000000001218</pub-id><pub-id pub-id-type="pmid">26439780</pub-id></citation></ref>
<ref id="B22">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kubo</surname> <given-names>K.</given-names></name> <name><surname>Komuro</surname> <given-names>T.</given-names></name> <name><surname>Ishiguro</surname> <given-names>N.</given-names></name> <name><surname>Sato</surname> <given-names>Y.</given-names></name> <name><surname>Ishii</surname> <given-names>N.</given-names></name> <name><surname>Kanehisa</surname> <given-names>H.</given-names></name> <etal/></person-group>. (<year>2006</year>). <article-title>Effects of low-load resistance training with vascular occlusion on the mechanical properties of muscle and tendon</article-title>. <source>J. Appl. Biomech.</source> <volume>22</volume>:<fpage>112</fpage>&#x02013;<lpage>119</lpage>. <pub-id pub-id-type="doi">10.1123/jab.22.2.112</pub-id><pub-id pub-id-type="pmid">16871002</pub-id></citation></ref>
<ref id="B23">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kumagai</surname> <given-names>K.</given-names></name> <name><surname>Kurobe</surname> <given-names>K.</given-names></name> <name><surname>Zhong</surname> <given-names>H.</given-names></name> <name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Thiebaud</surname> <given-names>R. S.</given-names></name> <name><surname>Ogita</surname> <given-names>F.</given-names></name> <etal/></person-group>. (<year>2012</year>). <article-title>Cardiovascular drift during low intensity exercise with leg blood flow restriction</article-title>. <source>Acta Physiol. Hung</source>. <volume>99</volume>, <fpage>392</fpage>&#x02013;<lpage>399</lpage>. <pub-id pub-id-type="doi">10.1556/APhysiol.99.2012.4.3</pub-id><pub-id pub-id-type="pmid">23238541</pub-id></citation></ref>
<ref id="B24">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Laurentino</surname> <given-names>G.</given-names></name> <name><surname>Ugrinowitsch</surname> <given-names>C.</given-names></name> <name><surname>Aihara</surname> <given-names>A. Y.</given-names></name> <name><surname>Fernandes</surname> <given-names>A. R.</given-names></name> <name><surname>Parcell</surname> <given-names>A. C.</given-names></name> <name><surname>Ricard</surname> <given-names>M.</given-names></name> <etal/></person-group>. (<year>2008</year>). <article-title>Effects of strength training and vascular occlusion</article-title>. <source>Int. J. Sports Med.</source> <volume>29</volume>, <fpage>664</fpage>&#x02013;<lpage>667</lpage>. <pub-id pub-id-type="doi">10.1055/s-2007-989405</pub-id><pub-id pub-id-type="pmid">18213536</pub-id></citation></ref>
<ref id="B25">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Liberati</surname> <given-names>A.</given-names></name> <name><surname>Altman</surname> <given-names>D. G.</given-names></name> <name><surname>Tetzlaff</surname> <given-names>J.</given-names></name> <name><surname>Mulrow</surname> <given-names>C.</given-names></name> <name><surname>G&#x000F8;tzsche</surname> <given-names>P. C.</given-names></name> <name><surname>Ioannidis</surname> <given-names>J.</given-names></name> <etal/></person-group>. (<year>2009</year>). <article-title>The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration</article-title>. <source>Ann. Intern. Med.</source> <volume>151</volume>, <fpage>165</fpage>&#x02013;<lpage>194</lpage>. <pub-id pub-id-type="doi">10.7326/0003-4819-151-4-200908180-00136</pub-id><pub-id pub-id-type="pmid">19622512</pub-id></citation></ref>
<ref id="B26">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Thiebaud</surname> <given-names>R. S.</given-names></name> <name><surname>Fahs</surname> <given-names>C. A.</given-names></name> <name><surname>Rossow</surname> <given-names>L. M.</given-names></name> <name><surname>Abe</surname> <given-names>T.</given-names></name> <name><surname>Bemben</surname> <given-names>M. G.</given-names></name></person-group> (<year>2013</year>). <article-title>Blood flow restriction does not result in prolonged decrements in torque</article-title>. <source>Eur. J. Appl. Physiol.</source> <volume>113</volume>, <fpage>923</fpage>&#x02013;<lpage>931</lpage>. <pub-id pub-id-type="doi">10.1007/s00421-012-2502-x</pub-id></citation></ref>
<ref id="B27">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Thrower</surname> <given-names>A. D.</given-names></name> <name><surname>Balapur</surname> <given-names>A.</given-names></name> <name><surname>Barnes</surname> <given-names>J. T.</given-names></name> <name><surname>Pujol</surname> <given-names>T. J.</given-names></name></person-group> (<year>2011</year>). <article-title>The energy requirement of walking with restricted blood flow</article-title>. <source>Sport Sci</source>. <volume>4</volume>, <fpage>7</fpage>&#x02013;<lpage>11</lpage>.</citation></ref>
<ref id="B28">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Thrower</surname> <given-names>A. D.</given-names></name> <name><surname>Balapur</surname> <given-names>A.</given-names></name> <name><surname>Barnes</surname> <given-names>J. T.</given-names></name> <name><surname>Pujol</surname> <given-names>T. J.</given-names></name></person-group> (<year>2012</year>). <article-title>Blood flow-restricted walking does not result in an accumulation of metabolites</article-title>. <source>Clin. Physiol. Funct. Imaging</source> <volume>32</volume>, <fpage>80</fpage>&#x02013;<lpage>82</lpage>. <pub-id pub-id-type="doi">10.1111/j.1475-097X.2011.01059.x</pub-id></citation></ref>
<ref id="B29">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Wilson</surname> <given-names>G. J.</given-names></name> <name><surname>Wilson</surname> <given-names>J. M.</given-names></name></person-group> (<year>2010</year>). <article-title>A mechanistic approach to blood flow occlusion</article-title>. <source>Int. J. Sports Med</source>. <volume>31</volume>, <fpage>1</fpage>&#x02013;<lpage>4</lpage>. <pub-id pub-id-type="doi">10.1055/s-0029-1239499</pub-id><pub-id pub-id-type="pmid">19885776</pub-id></citation></ref>
<ref id="B30">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Maher</surname> <given-names>C. G.</given-names></name> <name><surname>Sherrington</surname> <given-names>C.</given-names></name> <name><surname>Herbert</surname> <given-names>R. D.</given-names></name> <name><surname>Moseley</surname> <given-names>A. M.</given-names></name> <name><surname>Elkins</surname> <given-names>M.</given-names></name></person-group> (<year>2003</year>). <article-title>Reliability of the PEDro scale for rating quality of randomized controlled trials</article-title>. <source>Phys. Ther.</source> <volume>83</volume>, <fpage>713</fpage>&#x02013;<lpage>721</lpage>. <pub-id pub-id-type="doi">10.1093/ptj/83.8.713</pub-id><pub-id pub-id-type="pmid">12882612</pub-id></citation></ref>
<ref id="B31">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mendonca</surname> <given-names>G. V.</given-names></name> <name><surname>Vaz</surname> <given-names>J. R.</given-names></name> <name><surname>Pezarat-Correia</surname> <given-names>P.</given-names></name> <name><surname>Fernhall</surname> <given-names>B.</given-names></name></person-group> (<year>2015</year>). <article-title>Effects of walking with blood flow restriction on excess post-exercise oxygen consumption</article-title>. <source>Int. J. Sports Med.</source> <volume>36</volume>, <fpage>e11</fpage>&#x02013;<lpage>e18</lpage>. <pub-id pub-id-type="doi">10.1055/s-0034-1395508</pub-id><pub-id pub-id-type="pmid">25665001</pub-id></citation></ref>
<ref id="B32">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mendonca</surname> <given-names>G. V.</given-names></name> <name><surname>Vaz</surname> <given-names>J. R.</given-names></name> <name><surname>Teixeira</surname> <given-names>M. S.</given-names></name> <name><surname>Gr&#x000E1;cio</surname> <given-names>T.</given-names></name> <name><surname>Pezarat-Correia</surname> <given-names>P.</given-names></name></person-group> (<year>2014</year>). <article-title>Metabolic cost of locomotion during treadmill walking with blood flow restriction</article-title>. <source>Clin. Physiol. Funct. Imaging</source> <volume>34</volume>, <fpage>308</fpage>&#x02013;<lpage>316</lpage>. <pub-id pub-id-type="doi">10.1111/cpf.12098</pub-id><pub-id pub-id-type="pmid">24237757</pub-id></citation></ref>
<ref id="B33">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mier</surname> <given-names>C.</given-names></name> <name><surname>Turner</surname> <given-names>M.</given-names></name> <name><surname>Ehsani</surname> <given-names>A.</given-names></name> <name><surname>Spina</surname> <given-names>R.</given-names></name></person-group> (<year>1997</year>) <article-title>Cardiovascular adaptations to 10 days of cycle exercise</article-title>. <source>J. Appl. Physiol</source>. <volume>83</volume>, <fpage>1900</fpage>&#x02013;<lpage>1906</lpage>. <pub-id pub-id-type="doi">10.1152/jappl.1997.83.6.1900</pub-id><pub-id pub-id-type="pmid">9390961</pub-id></citation></ref>
<ref id="B34">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ogawa</surname> <given-names>M.</given-names></name> <name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Yasuda</surname> <given-names>T.</given-names></name> <name><surname>Fahs</surname> <given-names>C. A.</given-names></name> <name><surname>Rossow</surname> <given-names>L. M.</given-names></name> <name><surname>Thiebaud</surname> <given-names>R. S.</given-names></name> <etal/></person-group>. (<year>2012</year>). <article-title>Time course changes in muscle size and fatigue during walking with restricted leg blood flow in young men</article-title>. <source>J. Phys. Educ. Sport Manag</source>. <volume>3</volume>, <fpage>14</fpage>&#x02013;<lpage>19</lpage>. <pub-id pub-id-type="doi">10.5897/JPESM12.00</pub-id></citation></ref>
<ref id="B35">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ozaki</surname> <given-names>H.</given-names></name> <name><surname>Brechue</surname> <given-names>W. F.</given-names></name> <name><surname>Sakamaki</surname> <given-names>M.</given-names></name> <name><surname>Yasuda</surname> <given-names>T.</given-names></name> <name><surname>Nishikawa</surname> <given-names>M.</given-names></name> <name><surname>Aoki</surname> <given-names>N.</given-names></name> <etal/></person-group>. (<year>2010</year>). <article-title>Metabolic and cardiovascular responses to upright cycle exercise with leg blood flow reduction</article-title>. <source>J. Sports Sci. Med</source>. <volume>9</volume>, <fpage>224</fpage>&#x02013;<lpage>230</lpage>. <pub-id pub-id-type="pmid">24149689</pub-id></citation></ref>
<ref id="B36">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ozaki</surname> <given-names>H.</given-names></name> <name><surname>Kakigi</surname> <given-names>R.</given-names></name> <name><surname>Kobayashi</surname> <given-names>H.</given-names></name> <name><surname>Loenneke</surname> <given-names>J. P</given-names></name> <name><surname>Abe</surname> <given-names>T.</given-names></name> <name><surname>Naito</surname> <given-names>H.</given-names></name></person-group> (<year>2014</year>). <article-title>Effects of walking combined with restricted leg blood flow on mTOR and MAPK signalling in young men</article-title>. <source>Acta Physiol</source>. <volume>211</volume>, <fpage>97</fpage>&#x02013;<lpage>106</lpage>. <pub-id pub-id-type="doi">10.1111/apha.12243</pub-id><pub-id pub-id-type="pmid">24479982</pub-id></citation></ref>
<ref id="B37">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ozaki</surname> <given-names>H.</given-names></name> <name><surname>Loenneke</surname> <given-names>J. P.</given-names></name> <name><surname>Abe</surname> <given-names>T.</given-names></name></person-group> (<year>2015</year>). <article-title>Blood flow-restricted walking in older women: does the acute hormonal response associate with muscle hypertrophy?</article-title> <source>Clin. Physiol. Funct. Imaging</source> <volume>37</volume>, <fpage>379</fpage>&#x02013;<lpage>383</lpage>. <pub-id pub-id-type="doi">10.1111/cpf.12312</pub-id><pub-id pub-id-type="pmid">26517965</pub-id></citation></ref>
<ref id="B38">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ozaki</surname> <given-names>H.</given-names></name> <name><surname>Miyachi</surname> <given-names>M.</given-names></name> <name><surname>Nakajima</surname> <given-names>T.</given-names></name> <name><surname>Abe</surname> <given-names>T.</given-names></name></person-group> (<year>2011</year>). <article-title>Effects of 10 weeks walk training with leg blood flow reduction on carotid arterial compliance and muscle size in the elderly adults</article-title>. <source>Angiology</source> <volume>62</volume>, <fpage>81</fpage>&#x02013;<lpage>86</lpage>. <pub-id pub-id-type="doi">10.1177/0003319710375942</pub-id><pub-id pub-id-type="pmid">20682613</pub-id></citation></ref>
<ref id="B39">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Park</surname> <given-names>S.</given-names></name> <name><surname>Kim</surname> <given-names>J. K.</given-names></name> <name><surname>Choi</surname> <given-names>H. M.</given-names></name> <name><surname>Kim</surname> <given-names>H. G.</given-names></name> <name><surname>Beekley</surname> <given-names>M. D.</given-names></name> <name><surname>Nho</surname> <given-names>H.</given-names></name></person-group> (<year>2010</year>). <article-title>Increase in maximal oxygen uptake following 2-week walk training with blood flow occlusion in athletes</article-title>. <source>Eur. J. Appl. Physiol</source>. <volume>109</volume>, <fpage>591</fpage>&#x02013;<lpage>600</lpage>. <pub-id pub-id-type="doi">10.1007/s00421-010-1377-y</pub-id><pub-id pub-id-type="pmid">20544348</pub-id></citation></ref>
<ref id="B40">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Paton</surname> <given-names>C. D.</given-names></name> <name><surname>Addis</surname> <given-names>S. M.</given-names></name> <name><surname>Taylor</surname> <given-names>L.</given-names></name></person-group> (<year>2017</year>). <article-title>The effects of muscle blood flow restriction during running training on measures of aerobic capacity and run time to exhaustion</article-title>. <source>Eur. J. Appl. Physiol.</source> <volume>117</volume>, <fpage>2579</fpage>&#x02013;<lpage>2585</lpage>. <pub-id pub-id-type="doi">10.1007/s00421-017-3745-3</pub-id><pub-id pub-id-type="pmid">29058111</pub-id></citation></ref>
<ref id="B41">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Pfeiffer</surname> <given-names>P. S.</given-names></name> <name><surname>Cirilo-Sousa</surname> <given-names>M. S.</given-names></name> <name><surname>Santos</surname> <given-names>H. H. D.</given-names></name></person-group> (<year>2019</year>). <article-title>Effects of different percentages of blood flow restriction on energy expenditure</article-title>. <source>Int. J. Sport Med</source>. <volume>40</volume>, <fpage>186</fpage>&#x02013;<lpage>190</lpage>. <pub-id pub-id-type="doi">10.1055/a-0828-8295</pub-id><pub-id pub-id-type="pmid">30703847</pub-id></citation></ref>
<ref id="B42">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Pope</surname> <given-names>Z. K.</given-names></name> <name><surname>Willardson</surname> <given-names>J. M.</given-names></name> <name><surname>Schoenfeld</surname> <given-names>J.</given-names></name></person-group> (<year>2013</year>). <article-title>Exercise and blood flow restriction</article-title>. <source>J. Strength Cond. Res</source>. <volume>27</volume>, <fpage>2914</fpage>&#x02013;<lpage>2926</lpage>. <pub-id pub-id-type="doi">10.1519/JSC.0b013e3182874721</pub-id><pub-id pub-id-type="pmid">23364292</pub-id></citation></ref>
<ref id="B43">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Renzi</surname> <given-names>C. P.</given-names></name> <name><surname>Tanaka</surname> <given-names>H.</given-names></name> <name><surname>Sugawara</surname> <given-names>J.</given-names></name></person-group> (<year>2010</year>). <article-title>Effects of leg blood flow restriction during walking on cardiovascular function</article-title>. <source>Med. Sci. Sports Exerc.</source> <volume>42</volume>, <fpage>726</fpage>&#x02013;<lpage>732</lpage>. <pub-id pub-id-type="doi">10.1249/MSS.0b013e3181bdb454</pub-id><pub-id pub-id-type="pmid">19952840</pub-id></citation></ref>
<ref id="B44">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Sakamaki</surname> <given-names>M. G.</given-names></name> <name><surname>Bemben</surname> <given-names>M.</given-names></name> <name><surname>Abe</surname> <given-names>T.</given-names></name></person-group> (<year>2011</year>). <article-title>Legs and trunk muscle hypertrophy following walk training with restricted leg muscle blood flow</article-title>. <source>J. Sports Sci. Med.</source> <volume>10</volume>, <fpage>338</fpage>&#x02013;<lpage>340</lpage>. <pub-id pub-id-type="pmid">24149880</pub-id></citation></ref>
<ref id="B45">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Silva</surname> <given-names>J. C. G.</given-names></name> <name><surname>Domingos-Gomes</surname> <given-names>J. R.</given-names></name> <name><surname>Freitas</surname> <given-names>E. D.</given-names></name> <name><surname>Neto</surname> <given-names>G. R.</given-names></name> <name><surname>Aniceto</surname> <given-names>R. R.</given-names></name> <name><surname>Bemben</surname> <given-names>M. G.</given-names></name> <etal/></person-group>. (<year>2019</year>). <article-title>Physiological and perceptual responses to aerobic exercise with and withou blood flow restriction</article-title>. <source>J. Strength Cond. Res.</source> <pub-id pub-id-type="doi">10.1519/JSC.0000000000003178</pub-id>. [Epub ahead of print].</citation></ref>
<ref id="B46">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Silva</surname> <given-names>J. C. G.</given-names></name> <name><surname>Neto</surname> <given-names>E. P. A.</given-names></name> <name><surname>Bittar</surname> <given-names>S. T.</given-names></name> <name><surname>Domingos-Gomes</surname> <given-names>J. R.</given-names></name> <name><surname>Neto</surname> <given-names>G. R.</given-names></name> <name><surname>Cirilo-Sousa</surname> <given-names>M. S.</given-names></name></person-group> (<year>2018</year>). <article-title>Effect of interval and continuous aerpbic exercise with and without restriction of blood flow on post-exercise blood pressure</article-title>. <source>Motricidade</source> <volume>14</volume>, <fpage>89</fpage>&#x02013;<lpage>96</lpage>.</citation></ref>
<ref id="B47">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Spina</surname> <given-names>R. J.</given-names></name> <name><surname>Chi</surname> <given-names>M. M.</given-names></name> <name><surname>Hopkins</surname> <given-names>M. G.</given-names></name> <name><surname>Nemeth</surname> <given-names>P. M.</given-names></name> <name><surname>Lowry</surname> <given-names>O. H.</given-names></name> <name><surname>Holloszy</surname> <given-names>J. O.</given-names></name></person-group> (<year>1996</year>). <article-title>Mitochondrial enzymes increase in muscle in response to 7&#x02013;10 days of cycle exercise</article-title>. <source>J. Appl. Physiol</source>. <volume>80</volume>, <fpage>2250</fpage>&#x02013;<lpage>2254</lpage>. <pub-id pub-id-type="doi">10.1152/jappl.1996.80.6.2250</pub-id><pub-id pub-id-type="pmid">8806937</pub-id></citation></ref>
<ref id="B48">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Sugawara</surname> <given-names>J.</given-names></name> <name><surname>Tomoto</surname> <given-names>T.</given-names></name> <name><surname>Tanaka</surname> <given-names>H.</given-names></name></person-group> (<year>2015</year>). <article-title>Impact of leg blood flow restriction during walking on central arterial hemodynamics</article-title>. <source>Am. J. Physiol. Regul. Integr. Comp. Physiol</source>. <volume>309</volume>, <fpage>732</fpage>&#x02013;<lpage>739</lpage>. <pub-id pub-id-type="doi">10.1152/ajpregu.00095.2015</pub-id><pub-id pub-id-type="pmid">26246503</pub-id></citation></ref>
<ref id="B49">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Sundberg</surname> <given-names>C. J.</given-names></name></person-group> (<year>1994</year>). <article-title>Exercise and training during graded leg ischaemia in healthy man</article-title>. <source>Acta Physiol. Scand.</source> <volume>615</volume>, <fpage>1</fpage>&#x02013;<lpage>50</lpage>. <pub-id pub-id-type="pmid">8140900</pub-id></citation></ref>
<ref id="B50">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Takarada</surname> <given-names>Y.</given-names></name> <name><surname>Ishii</surname> <given-names>N.</given-names></name></person-group> (<year>2002</year>). <article-title>Effects of lowintensity resistance exercise with short interset rest period on muscular function in middle-aged women</article-title>. <source>J. Strength Cond. Res</source>. <volume>16</volume>, <fpage>123</fpage>&#x02013;<lpage>128</lpage>. <pub-id pub-id-type="doi">10.1519/00124278-200202000-00019</pub-id></citation></ref>
<ref id="B51">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tanaka</surname> <given-names>Y.</given-names></name> <name><surname>Takarada</surname> <given-names>Y.</given-names></name></person-group> (<year>2018</year>). <article-title>The impact of aerobic exercise training with vascular occlusion in patients with chronic heart failure</article-title>. <source>Esc. Heart Fail</source>. <volume>5</volume>, <fpage>586</fpage>&#x02013;<lpage>591</lpage> <pub-id pub-id-type="doi">10.1002/ehf2.12285</pub-id><pub-id pub-id-type="pmid">29575708</pub-id></citation></ref>
<ref id="B52">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Taylor</surname> <given-names>C. W.</given-names></name> <name><surname>Ingham</surname> <given-names>S. A.</given-names></name> <name><surname>Ferguson</surname> <given-names>R. A.</given-names></name></person-group> (<year>2016</year>). <article-title>Acute and chronic effect of sprint interval training combined with postexercise blood-flow restriction in trained individuals</article-title>. <source>Exper Physiol</source>. <volume>101</volume>, <fpage>143</fpage>&#x02013;<lpage>154</lpage>. <pub-id pub-id-type="doi">10.1113/EP085293</pub-id><pub-id pub-id-type="pmid">26391312</pub-id></citation></ref>
<ref id="B53">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Thomas</surname> <given-names>H. J.</given-names></name> <name><surname>Scott</surname> <given-names>B. R.</given-names></name> <name><surname>Peiffer</surname> <given-names>J. J.</given-names></name></person-group> (<year>2018</year>). <article-title>Acute physiological responses to low- intensity blood flow restriction cycling</article-title>. <source>J. Sci. Med. Sports</source> <volume>21</volume>, <fpage>969</fpage>&#x02013;<lpage>974</lpage> <pub-id pub-id-type="doi">10.1016/j.jsams.2018.01.013</pub-id><pub-id pub-id-type="pmid">29650336</pub-id></citation></ref>
<ref id="B54">
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yasuda</surname> <given-names>T.</given-names></name> <name><surname>Fujita</surname> <given-names>S.</given-names></name> <name><surname>Miyagi</surname> <given-names>Y.</given-names></name> <name><surname>Kubota</surname> <given-names>Y.</given-names></name> <name><surname>Sato</surname> <given-names>Y.</given-names></name> <name><surname>Abe</surname> <given-names>T.</given-names></name></person-group> (<year>2006</year>). <article-title>Electromyographic responses of arm and chest muscle during bench press exercise with and without KAATSU</article-title>. <source>Int. J. KAATSU Train Res.</source> <fpage>15</fpage>&#x02013;<lpage>18</lpage>. <pub-id pub-id-type="doi">10.3806/ijktr.2.15</pub-id></citation></ref>
</ref-list>
<fn-group>
<fn fn-type="financial-disclosure"><p><bold>Funding.</bold> This study was financed in part by the Coordena&#x000E7;&#x000E3;o de Aperfei&#x000E7;oamento de Pessoal de N&#x000ED;vel Superior - Brasil (CAPES).</p>
</fn>
</fn-group>
</back>
</article>