Mitochondrial Transplantation for Myocardial Protection in Ex-Situ Perfused Hearts Donated after Cardio-Circulatory Death

Purpose Donation after circulatory death (DCD) offers an additional source of cardiac allografts, potentially allowing expansion of the donor pool. In this study, we investigated the efficacy of mitochondrial transplantation to improve myocardial function in DCD hearts. Methods Cardiocirculatory death was induced in Yorkshire pigs (40-50 kg, n=22) by cessation of mechanical ventilation. After 20 minutes of warm ischemia, cardioplegia was administered. The hearts were then reperfused on an ex-situ blood perfusion system for 240 minutes. Following 15 minutes of ex-situ perfusion, mitochondria (5 × 109 in respiration buffer, Mitochondria, n=8) or respiration buffer alone (Vehicle, n=8) were delivered as a single bolus to the coronary arteries. A control group (Sham, n=6) was not subjected to warm ischemia. Hearts were perfused in a resting mode for 120 minutes before converting the system to a continuous isovolumic loading mode. Left ventricular (LV) global function, myocardial oxygen consumption, and arterial lactates were compared by two-way repeated-measures analysis of variance (ANOVA) with Bonferroni adjustment. Results At the end of 240 minutes of reperfusion, LV peak developed pressure (LVdevP) and dP/dt max were significantly higher in the Sham group than in Vehicle (p 0.05), which was significantly lower in Vehicle (p=0.004). No differences were found in arterial lactate levels (Figure D) (p> 0.05). Conclusion Mitochondrial transplantation significantly preserves myocardial function and oxygen consumption in DCD hearts, thus providing an additional possible benefit for expanding heart donor pool.