Abstract 14096: Ischemic Postconditioning During Cardiopulmonary Resuscitation Normalizes Mitochondrial Function in a Porcine Model of Prolonged Cardiac Arrest

Abstract

Introduction: Mitochondrial dysfunction is a hallmark of prolonged ischemia, however it’s onset during cardiac arrest (CA) and reperfusion with cardiopulmonary resuscitation (CPR) has yet to be elucidated. In a porcine model of CA, ischemic postconditioning (IPC) during CPR increased neurologically intact survival. We hypothesized that reperfusion injury, as evidenced by mitochondrial dysfunction, develops during CPR and is rescued with IPC. We investigated the effect of CA, CPR, and IPC on mitochondrial function and viability. Methods: After 15 min of ventricular fibrillation, 30 animals were randomized to no CPR (VF, n=10), active compression decompression + impedance threshold device (ACD-ITD) CPR (Control, n=9), or ACD-ITD CPR + IPC (IPC, n=11). Aortic blood pressure and ECG were continuously recorded. IPC consisted of 3 cycles of 20 sec compression / 20 sec pause for the first 2 min of CPR. Cardiac mitochondria were isolated via differential centrifugation 4 min after initiation of CPR. Additionally, mitochondria were isolated from 6 animals that did not suffer CA (non-ischemic controls). Respiration and calcium retention capacity (CRC) were measured for complex I (pyruvate+malate) and II (succinate+rotenone) substrates. Respiratory control index (RCI) was calculated as the ratio of states 3 to 4 respiration. Data were compared with ANOVA. A p value < 0.05 was considered significant. Results: Coronary perfusion pressure was similar between groups during CPR. Compared to the non-ischemic group, VF resulted in decreased complex I and II RCI and decreased complex I CRC. Control CPR increased complex I and II RCI compared to VF but did not affect complex I CRC. IPC increased complex I and II RCI and complex I CRC compared to VF and Control to a level comparable with the non-ischemic group. Complex II CRC was unchanged between groups. Conclusion: Complex I and complex II RCI and complex I CRC are diminished during VF. Respiration is partially restored with standard CPR. IPC improved mitochondrial function to non-ischemic values as early as 4 min after initiation of CPR. These improvements were independent of changes in blood pressure, suggesting that initiation of CPR is a source of mitochondrial reperfusion injury and a critical time for intervention.