Acute myocardial infarction (AMI) is a life-threatening condition caused by sudden coronary artery occlusion because of plaque rupture or thrombosis. Therefore, timely reopening of the infarct-related artery is necessary, for salvaging the jeopardized myocardium and restoring the blood flow (1). Percutaneous coronary intervention (PCI) is the primary treatment method for relieving the occluded coronary artery and is associated with minimal invasiveness and rapid recovery (2–4). Despite successful recanalization, 41% of the cases report insufficient blood flow that can lead to a severe complication called as slow flow/no reflow (SF-NR) (5, 6). Patients with SF-NR can develop severe complications, such as like ventricular arrhythmias, heart failure, and sudden death, all of which result in poor prognosis and negate the benefits of PCI in the AMI patients (7–9). SF-NR is associated with a five-fold increase in risk of myocardial infarction and a four-fold increase in the mortality rate (10).

The mechanisms causing SF-NR include microvascular embolization, in situ thrombosis, endothelial cell damage, microvascular spasms, and inflammation (11–15). Currently, there are no specific universal class I treatment strategies for alleviating SF-NR. Patients with SF-NR are treated with drugs such as vasodilators and glycoprotein IIb/IIIa antagonists, as well as mechanical treatments, including thrombus aspiration (16, 17). However, there is no definitive evidence that these treatments specifically target and alleviate SF-NR. These treatment methods often target only one causative factor and result in inconsistent and unstable effects. Moreover, most of the treatments are associated with significant adverse effects. For example, excessive use of tirofiban is associated with elevated bleeding risk (18), whereas improper thrombus aspiration causes complications such as thrombus dislocation (19). Therefore, there is an urgent need to discover safe and more effective treatment strategies for alleviating SF-NR.

Acupuncture demonstrates various biological effects, including autonomic nervous system regulation, anti-inflammatory properties, enhanced microcirculation, antioxidant activity, reduced lipid levels, and perioperative pain relief (20, 21). Therefore, it may be a promising strategy for addressing coronary microvascular dysfunction, injury, and obstruction following AMI, such as SF-NR. Firstly, it modulates sympathetic and parasympathetic balance, thereby attenuating sympathetic overactivity and enhancing parasympathetic tone, which may contribute to vasodilation and improved coronary microcirculation (22, 23). Secondly, acupuncture exhibits robust anti-inflammatory properties, as evidenced by its ability to downregulate pro-inflammatory cytokines and inhibit the activation of nuclear factor-kappa B (NF-κB), thus mitigating the inflammatory cascade implicated in microvascular injury post-MI (24). Thirdly, acupuncture exerts antioxidant effects by bolstering endogenous antioxidant defenses and scavenging reactive oxygen species, thereby mitigating oxidative stress-induced damage to endothelial cells and preserving microvascular integrity. Notably, EA has been shown to modulate endothelial function, promoting endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, pivotal mediators of vasodilation and endothelial homeostasis, thereby counteracting endothelial dysfunction associated with MI-induced microvascular impairment (25, 26). Therefore, acupuncture may potentially prevent SF-NR during PCI by reducing endothelial cell damage. Fourthly, acupuncture holds promise in mitigating microvascular spasm and obstruction by virtue of its vasodilatory effects and modulation of vascular smooth muscle tone (27). This is further corroborated by emerging evidence suggesting that acupuncture may regulate the renin-angiotensin-aldosterone system (RAAS), a key regulator of vascular tone and remodeling, thereby conferring vasoprotective effects and attenuating microvascular dysfunction post-MI (28). Furthermore, acupuncture has been shown to stimulate the release of endogenous opioids and neuropeptides, including β-endorphin and substance P, which contribute to pain relief and myocardial protection (29, 30). Additionally, PCI primarily targets large and medium-sized coronary vessels with stenosis but is not effective in treating thin or small-diameter vessels (31). Acupuncture addresses this limitation as an economical and non-invasive option for the treatment of blood flow issues in smaller blood vessels or complex or risky needle insertion situations. Acupuncture is also a viable option for patients seeking to avoid the side effects of drugs (32). Moreover, acupuncture is one of the earliest therapies for emergency treatment in traditional Chinese medicine (TCM) according to ancient classics. The clinical spectrum of acupuncture includes 16 categories with 461 types of human diseases, of which 26% were acute diseases (33). Acupuncture, particularly electroacupuncture (EA), shows significant clinical benefits. EA is a safe and effective intervention that is easier to standardize, more controllable than manual acupuncture, and provides prolonged stimulation, precise intensity control, and enhanced acupuncture sensation (34, 35). Therefore, combinatorial therapy with EA and PCI is a promising strategy for enhancing clinical outcomes, optimizing coronary blood flow, and improving patient prognosis.

Previous reports have suggested that acupuncture may be effective in preventing or alleviating SF-NR. However, it is not known whether electroacupuncture is effective in preventing or alleviating SF-NR in AMI patients undergo PCI, and high-quality randomized-controlled clinical trials (RCTs) are urgently necessary to investigate its efficacy and safety. Therefore, in this pilot RCT, we aim to investigate the potential benefits of intraoperative EA in reducing SF-NR during PCI in the AMI patients. The findings of this study are expected to lay the foundation for subsequent multicenter trials to establish the clinical safety and efficacy of intraoperative electroacupuncture as a novel strategy for managing SF-NR in AMI patients during PCI.

Acupuncture shows the potential for improving microvascular perfusion in clinical studies but its efficacy in alleviating the SF-NR phenomenon in the AMI patients during PCI has not been established. A previous study reported the beneficial therapeutic effects of acupuncture in patients with slow flow after PCI (51). However, currently, there are no published reports regarding the role of acupuncture in preventing the complications from SF-NR during the PCI procedure. Therefore, we designed this trial to determine whether intraoperative electroacupuncture was effective in alleviating SF-NR in AMI patients undergoing PCI. AMI patients undergoing PCI alone were considered as controls. To the best of our knowledge, this study represents the first randomized controlled trial aimed at investigating the feasibility and clinical efficacy of intraoperative electroacupuncture-assisted PCI in preventing SF-NR in a diverse population of AMI patients.

Acupoint selection is crucial for the success of acupuncture treatment, with the primary principle being that the acupoints linked through the meridians. The pericardium meridian is generally used for the treatment of cardiovascular diseases (52). Based on previous literature and clinical experience, there is consensus among researchers for using PC6 and PC4 acupoints to treat patients with cardiovascular diseases. PC6 is the Luo-connecting point of the pericardium meridian and is traditionally used to treat heart-related conditions for alleviating circulation problems by regulating qi and activating the meridians to relieve pain (53, 54). PC4 is the cleft point of the pericardium meridian that is commonly used in acute and critical cases to invigorate Qi and blood, calm the heart, and soothe the spirit (55, 56). Stimulating these acupoints with “De Qi” sensation can regulate Qi and blood flow, enhance cardiovascular function, promote anti-inflammatory and antioxidant effects, and relieve pain and anxiety (57–59). Furthermore, to avoid interfering with the coronary stent implantation route, acupuncture will be performed on the left side. The selection of acupuncture points in this trial are consistent with the principles of “treatment based on syndrome differentiation” in TCM.

SF-NR is a common and serious PCI complication associated with poor prognosis. In this study, we will evaluate several secondary outcomes in addition to assessing the incidence of SF-NR as the primary outcome. We will measure the cardiac biomarkers to monitor the status of AMI (60). We will assess inflammatory biomarkers such as leukocytes, neutrophils, lymphocytes, and Hs-CRP, which are linked with SF-NR and are predictors of adverse cardiac events in the patients that have undergone PCI (61–63). Patient pain levels will be quantified using the NRS Chest Pain Scale, an internationally recognized method. Since long-term pain has significant emotional impact (64, 65), we will also use the VAS-A scale to determine if acupuncture alleviates or decreases emotional disorders in patients with AMI (66). The TCM symptom score will be used to assess the therapeutic effects of acupoint selection based on syndrome differentiation. Electrocardiography will be used to investigate the potential treatment effects of acupuncture in the patients with AMI. A one-month follow-up will assess the lasting effects of the treatment and the cardiovascular events. These comprehensive measures will thoroughly evaluate the effects of intraoperative acupuncture on various aspects of SF-NR. At the completion of the trial, we will evaluate recruitment time, participant consent rates, adverse events, blinding success, and feasibility of the outcome measurement tools. Furthermore, we will use flexible approaches for the follow-up, including remote video questionnaires, to minimize the dropout rates.

This study aims to confirm the efficacy of acupuncture as an adjunct to standard AMI therapy with strict quality control. However, there are few limitations. Firstly, conducting a fully randomized placebo-controlled acupuncture trial is challenging because of the nature of electroacupuncture intervention. To overcome this, we will implement a series of measures to minimize the single-blind bias as much as possible. We have meticulously designed our trial and adhering to methodological standards for allocation concealment and blinding will enhance the generalizability of our findings. To avoid unwarranted interference or risk to AMI patients through sham needling and focus more closely on studying the effects of acupuncture, this pilot study will use a non-acupuncture control group and implement blinding for the outcome evaluators and statisticians to minimize bias. Secondly, cardiac magnetic resonance (CMR) is considered the preferred method for assessing microvascular damage and offers benefits in the assessment of myocardial perfusion and cardiac function (67). In future clinical trials, the potential utilization of CMR for evaluating the cardioprotective effects of acupuncture will be explored. Thirdly, because of the financial and workforce constraints, this trial is not a multi-center study. This would result in a small sample size and therefore, the results may be potentially influenced by the geographical factors. Therefore, larger multi-center RCTs will be necessary to validate the results of this pilot trial. Finally, the pathophysiological mechanisms involved in coronary microvascular dysfunction, injury, and obstruction include microembolization, edema/capillary obstruction, RBC stasis, capillary rupture, leukocyte adhesion, and impaired vasomotion (68–70). However, the precise myocardial protective mechanisms of acupuncture remain ambiguous. We will intend to seek approval from the ethics committee to retain blood samples from patients both pre- and post-treatment, with the goal of investigating relevant plasma biomarkers to elucidate the therapeutic mechanisms of EA.

In summary, this pilot trial will investigate the role of electroacupuncture in preventing SF-NR during PCI and address the current research gaps. If proven effective, it will provide a new therapeutic strategy against SF-NR and lay the foundation for subsequent multicenter clinical trials. Furthermore, this trial will offer a new alternative for the clinical management of AMI by synergizing traditional acupuncture techniques with modern cardiovascular interventions for optimal patient care, prevent PCI-related complications, and guide treatment strategies for other severe cardiovascular diseases. This approach is more valuable when the conventional therapies are limited or contraindicated. It also promotes the application of TCM in modern medicine, establishes scientific credibility for TCM in new clinical areas, and provides a more comprehensive and effective choice for societal healthcare services. Future research should investigate the acupuncture mechanisms and the optimal timing of acupuncture treatment to further elucidate its potential benefits as a complementary therapy for patients with cardiovascular diseases.

The trial recruitment is ongoing.

The studies involving humans were approved by the Ethics Committee of the Yueyang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine (approval number: 2023-090-01). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.