AUTHOR=Lee Tze-Fun , Lu Min , Pasquin Matteo P. , Schmölzer Georg M. , Cheung Po-Yin 

TITLE=Attenuation of Acute Renal Injury After the Post-resuscitation Administration of Doxycycline in Surviving Newborn Piglets With Severe Hypoxia-Reoxygenation

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 7 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2019.00075

DOI=10.3389/fped.2019.00075

ISSN=2296-2360

ABSTRACT=Background: Asphyxiated neonates often have myocardial dysfunction and renal insufficiency. Previously we demonstrated that doxycycline improved cardio-renal function through matrix metalloproteinase (MMP)-2 inhibition in an acute swine model of neonatal hypoxia-reoxygenation. The prolonged cardio-renal protective effects of doxycycline in neonates still remained unknown. We therefore hypothesized that the protective effects of doxycycline persisted in surviving subjects. 
Methods: Newborn piglets were instrumented and subjected to 1 hour of hypoxia followed by reoxygenation with 21-25% oxygen and observed for 4 days. Intravenous doxycycline (30 mg/kg) or normal saline (1 mL, saline-control group) was given at 5 minutes of reoxygenation (n=8/group) in a randomized, blinded fashion. Sham-operated piglets (n=5) received no hypoxia-reoxygenation. At 96 hours after reoxygenation, the left ventricular function was assessed by Millar® catheter. Renal injury was investigated by measuring plasma creatinine, urinary N-acetyl-D-glucosaminidase activity, renal tissue lactate and MMP-2 activity. 
Results: Both hypoxia-reoxygenation groups had similar hypoxic stress with severe lactate acidosis, and hemodynamic recovery. Doxycycline-treated piglets had higher urine output with lower urine N-acetyl-D-glucosaminidase, plasma creatinine and renal MMP-2 activity (vs. saline-controls; all p<0.05). These markers were all negatively correlated with urine output. 
Conclusions: In newborn piglets surviving hypoxia-reoxygenation, we observed a weak but significant and persistent attenuation of renal injury and improved recovery with the post-resuscitation administration of doxycycline.