Abstract 136: Postresuscitation Cyclosporine Attenuates Myocardial Injury and Preserves Mitochondria in Newborn Piglets with Asphyxia-Reoxygenation
Introduction: Myocardial depression following asphyxia of the newborn is a significant cause of mortality. Cyclosporine reduces myocardial damage in adult patients undergoing percutaneous coronary intervention for myocardial infarction. However, the potential cardioprotective effects of cyclosporine in neonates have not yet been studied. We hypothesize that cyclosporine will attenuate myocardial injury and apoptosis, while improving mitochondrial energetics in asphyxiated newborn piglets.
Methods: Twenty piglets (1-4 days-old) were instrumented for continuous monitoring of cardiac output and systemic arterial pressure. After stabilization, normocapnic alveolar hypoxia (10-15% oxygen) was instituted for 2h followed by reoxygenation with 100% (0.5h), then 21% (3.5h) oxygen. Piglets were blindly, randomized to receive cyclosporine intravenous boluses (10-mg/kg) or normal saline (placebo, control) at 5 min of reoxygenation (n=8/group). Sham-operated piglets (n=4) had no asphyxia-reoxygenation. Blood gases and plasma troponin were intermittently determined as well as left ventricular lactate, aconitase, cytochrome-c and mitochondrial morphology. Statistical analyses were performed using ANOVA.
Results: At the end of 2h of hypoxia, all piglets demonstrated cardiogenic shock (cardiac output 45% of baseline), hypotension (systemic arterial pressure 30mmHg) and acidosis (pH=7.04). Following 4h of reoxygenation, plasma troponin and left ventricle lactate were significantly lower in the cyclosporine-treatment group, with preserved mitochondrial morphology. Mitochondrial aconitase activity improved and cytosol cytochrome-c was attenuated with cyclosporine treatment compared to controls (both P<0.05).
Conclusion: We first demonstrated that the post-resuscitation administration of cyclosporine attenuated myocardial and mitochondrial injury in newborn piglets following asphyxia-reoxygenation.
- © 2011 by American Heart Association, Inc.