Abstract 2272: Mitochondrial Transplantation for Cardioprotection
Background: Previously, we have demonstrated that ischemia induces mitochondrial damage and dysfunction which persists throughout reperfusion and impacts negatively on post-ischemic functional recovery and cellular viability. We hypothesized that viable respiration competent, mitochondria, isolated from remote tissue unaffected by ischemia and then directly injected into the ischemic zone of myocardial tissue during early reperfusion would enhance post-ischemic functional recovery and limit infarct size.
Methods: To test this hypothesis, New Zealand rabbits (n=23) were subjected to Langendorff perfusion. Following 30 minutes equilibrium, the left anterior coronary artery was encircled with a silk suture to form a snare. Regional ischemia (RI) was induced for 30 minutes by tightening the snare. At 29 minutes of RI, mitochondria (5.6±1.2×106/mL ) isolated from a donor rabbit heart (RI-mito, n=7), or vehicle (RI-sham, n=7) were injected into the regional ischemic zone (8 × 0.1 mL). The snare was released and the hearts were reperfused for 120 minutes. Control hearts (n = 6) were perfused without regional ischemia at 37°C for 180 minutes. Global myocardial function, systolic shortening (SS) and infarct size were determined. A separate group of hearts (n=3) were injected with mitochondria pre-labeled with MitoTracker orange CMTMRos for confocal microscopy analysis.
Results: LVPDP and SS in RI-mito hearts retuned to 75% and 83% of equilibrium value, respectively at 120 minutes reperfusion as compared to 57% and 62% respectively in RI-sham (p<0.05). Area at risk and heart weight were not significantly different. Infarct size/area at risk in RI-sham was 30.7±7.3% and 11.43±3.1% in RI-Mito (p<0.05 vs. RI-sham). Confocal microscopy demonstrated that injected mitochondria were present following 120 minutes reperfusion and were distributed from the epi- to the sub-endocardium.
Conclusions: These results demonstrate that that the direct injection of viable respiration competent mitochondria, into the ischemic zone of myocardial tissue during early reperfusion significantly decreases infarct size and significantly enhances post-ischemic functional recovery and provides an alternative method for cardioprotection.