Mitochondrial transplantation for myocardial protection in ex-situ‒perfused hearts donated after circulatory death

BACKGROUND: Donation after circulatory death (DCD) offers an additional source of cardiac allog-rafts, potentially allowing expansion of the donor pool, but is limited owing to the effects of ischemia. In this study, we investigated the efficacy of mitochondrial transplantation to enhance myocardial function of DCD hearts.METHODS: Circulatory death was induced in Yorkshire pigs (40-50 kg, n = 29) by a 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. After 15 minutes of reperfusion, hearts received either vehicle alone (vehicle [VEH], 10 ml; n = 8) or vehicle containing autologous mitochondria (vehicle with mitochondria as a single injection [MT], 5 x 10(9) in 10 ml, n = 8). Another group of hearts (serial injection of mitochondria [MTS]; n = 6) received a second injection of mitochondria (5 x 10(9) in 10 ml) after 2 hours of ex-situ heart perfusion and reperfused for an additional 2 hours. A Sham group (sham hearts; n = 6) did not undergo any warm ischemia.RESULTS: At the end of 4 hours of reperfusion, MT and MTS groups showed a significantly increased left ventricle/ventricular peak developed pressure (p = 0.002), maximal left ventricle/ventricular pressure rise (p < 0.001), fractional shortening (p < 0.001), and myocardial oxygen consumption (p = 0.004) compared with VEH. Infarct size was significantly decreased in MT and MTS groups compared with VEH (p < 0.001). No differences were found in arterial lactate levels among or within groups throughout reperfusion.CONCLUSIONS: Mitochondrial transplantation significantly preserves myocardial function and oxygen consumption in DCD hearts, thus providing a possible option for expanding the heart donor pool. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.