Ischemic Postconditioning Transiently Improves Cardiac Mitochondrial Function during Resuscitation in a Porcine Model of Cardiac Arrest

Abstract

IntroductionIschemic postconditioning (IPC) is a technique of brief interruptions in blood flow at the onset of reperfusion to mitigate reperfusion injury after prolonged ischemia. When applied during cardiopulmonary resuscitation (CPR) following ventricular fibrillation (VF) cardiac arrest (CA) in a porcine model, IPC during CPR (IPC‐CPR) reduced adverse events and improved neurologically favorable survival 48 hours after return of spontaneous circulation (ROSC) compared to standard‐of‐care CPR (S‐CPR). IPC‐CPR also increased cardiac mitochondrial function prior to ROSC after 4 minutes of CPR compared to S‐CPR.ObjectiveWe investigated the effect of IPC‐CPR after prolonged VF CA on cardiac mitochondrial function 6 hours after ROSC.MethodsTwenty‐four female swine were intubated, anesthetized, and surgically prepared for continuous hemodynamic recording. Eight animals received no CA (Naïve, n=8) as a non‐ischemic control. The remaining animals received 15 minutes of untreated VF CA followed by CPR without (S‐CPR, n=8) or with IPC (IPC‐CPR, n=8). IPC was administered via three 20‐second pauses in chest compressions during the first 2 minutes of CPR. After 4 minutes of CPR, defibrillation was attempted. Six hours after ROSC, cardiac mitochondria were isolated via differential centrifugation for assessment of respiration, rate of ATP synthesis, and calcium retention capacity. ANOVA with Newman‐Keuls posthoc test was used for comparisons between treatments. The null‐hypothesis was rejected for p < 0.05.ResultsROSC was obtained in all animals that received a CA. Cardiac mitochondrial function did not differ between Naïve, S‐CPR, and IPC‐CPR treated animals.ConclusionsIn a porcine model of prolonged VF CA, cardiac mitochondrial function normalizes within 6 hours of ROSC. The previously documented reduction in adverse events and improvement in survival with IPC‐CPR treatment may be mediated by acute changes in cardiac mitochondrial function earlier than 6 hours post‐ROSC, or by mechanisms independent of cardiac mitochondrial functionSupport or Funding InformationStipend support was provided by the American Heart Association 16PRE27600038 (TRM). Project support was provided by NIH 1R01 OD016727‐01 (DY).