Brief hypothermic oxygenated perfusion provides cardioprotection in a pig model of donation after circulatory death

Objectives: Donation after circulatory death provides excellent patient outcomes in heart transplantation; however, warm ischaemic graft damage remains a concern. We have reported that a brief period of hypothermic oxygenated perfusion prior to normothermic reperfusion improves graft recovery in a rat model. Here, we investigated the cardioprotective benefits and mechanisms of this approach compared to the current clinical standard in a large animal model. Methods: Circulatory death was induced in anaesthetized male Schweizer Edelschwein pigs (55 kg). Hearts underwent 20 min of warm, in-situ ischaemia, followed by a cold coronary flush and explantation. After 15 min backtable preparation, hearts underwent either 15 min cold static storage (control) or 30 min hypothermic oxygenated perfusion. All hearts were perfused ex vivo under normothermic conditions; 3 h in an unloaded mode, followed by 1 h with left ventricular loading to assess cardiac recovery. Results: Compared to control conditions (n = 5), hypothermic oxygenated perfusion (n = 5) increased recovery of left ventricular function (cardiac output and maximum relaxation rate, P < 0.001 for both) and decreased cell death marker release (heart-type fatty acid binding protein, P = 0.009 and myoglobin, P < 0.001). In parallel, hypothermic oxygenated perfusion reduced the release of succinate and the oxidative stress marker 8-hydroxy-2'-deoxyguanosine. Conclusions: A brief period of hypothermic oxygenated perfusion, applied as a reperfusion therapy between graft procurement and normothermic machine perfusion, provides cardioprotection in a porcine model of donation after circulatory death. Hypothermic oxygenated perfusion is a promising, easily applicable, cardioprotective reperfusion strategy; this study provides key evidence to support clinical translation.