Abstract 4369033: Prolonged Trans-Valvular Unloading with an Impella CP for 6 hours Protects Against Myocardial Damage in Preclinical Models of Acute Myocardial Infarction

Acute myocardial infarction (AMI) is a major cause of mortality and heart failure worldwide. Reducing left ventricular (LV) workload using a trans-valvular pump (TVP) and delaying reperfusion reduces infarct size in preclinical models and is currently under clinical investigation. Impaired mitochondrial function mediates reperfusion injury and heart failure after AMI. The impact of prolonged LV unloading on myocardial damage and salvage is unknown. We hypothesized that LV unloading limits myocardial injury by reducing ischemic burden and preserves mitochondrial function before and after coronary reperfusion. Method: Myocardial ischemia was induced by percutaneous balloon occlusion of the left anterior descending (LAD) artery for 90 minutes in adult male swine. In Groups A and B, an additional 360 minutes of LAD occlusion was performed (450 minutes of total LAD occlusion time) followed by 120 minutes of coronary reperfusion in the presence or absence of a TVP (Impella CP, Abiomed Inc; Figure A). Infarct size normalized to the area at risk (IS/AAR), hemodynamic parameters and mitochondrial function were assessed at the end of each study protocol. Result: In Group A, 450 minutes of LAD occlusion and 120 minutes of reperfusion infarct size was significantly higher compared to 360 minutes TVP activation before reperfusion group (66±4.5 vs 32±10, p<0.0009; Figure B). Seahorse analysis was performed on isolated mitochondria from the AAR in all groups. Without TVP activation, mitochondrial Complex I (CI) activity was significantly reduced after 450 minutes of LAD compared to 360 minutes TVP activation before reperfusion group (Figure C). Among all Groups, compared to no TVP, CI activity was significantly higher with TVP activation. Conclusion: We identified for the first time that prolonged trans-valvular unloading for up to 360 minutes before reperfusion reduces myocardial damage, preserves mitochondrial function before coronary reperfusion . Further investigation into the clinical utility of LV unloading and delayed reperfusion to limit infarct size after AMI is required.