Differential effects of ischemia/reperfusion on endothelial function and contractility in donation after circulatory death

BACKGROUND Donation after circulatory death (DCD) could significantly improve cardiac graft availability. However, DCD hearts undergo potentially deleterious warm ischemia/reperfusion (I/R). As endothelial damage is a key factor in cardiac I/R injury, we aimed to investigate the tolerance of cardiac and endothelial function after various durations of warm ischemia to improve the timing and choice of cardioprotective therapies. METHODS Isolated, working rat hearts were perfused for 20 minutes aerobically, then underwent various periods of warm global ischemia and either 30 or 60 minutes of reperfusion. RESULTS Compared with non-ischemic hearts, recovery of left ventricular work (heart rate–developed pressure product) was significantly reduced at 60 minutes of reperfusion with ≥27 minutes of ischemia ( p p p p CONCLUSIONS The first signs of endothelial dysfunction after cardiac ischemia occur with less ischemia than cardiac functional alterations, and may result from increased eNOS uncoupling. Strategies aimed at improving eNOS coupling may thus help to optimize both endothelial and myocardial recovery, ultimately facilitating DCD heart transplantation.