Cardioprotective Actions of a Glucagon-like Peptide-1 Receptor Agonist on Hearts Donated After Circulatory Death.

Abstract

Background Heart transplantation with a donation after circulatory death (DCD) heart is complicated by substantial organ ischemia and ischemia-reperfusion injury. Exenatide, a glucagon-like peptide-1 receptor agonist, manifests protection against cardiac ischemia-reperfusion injury in other settings. Here we evaluate the effects of exenatide on DCD hearts in juvenile pigs. Methods and Results DCD hearts with 15-minutes of global warm ischemia after circulatory arrest were reperfused ex vivo and switched to working mode. Treatment with concentration 5-nmol exenatide was given during reperfusion. DCD hearts treated with exenatide showed higher myocardial oxygen consumption (exenatide [n=7] versus controls [n=7], over 60-120 minutes of reperfusion, P<0.001) and lower cardiac troponin-I release (27.94±11.17 versus 42.25±11.80 mmol/L, P=0.04) during reperfusion compared with controls. In working mode, exenatide-treated hearts showed better diastolic function (dp/dt min: -3644±620 versus -2193±610 mm Hg/s, P<0.001; Tau: 15.62±1.78 versus 24.59±7.35 milliseconds, P=0.02; lateral e' velocity: 11.27± 1.46 versus 7.19±2.96, P=0.01), as well as lower venous lactate levels (3.17±0.75 versus 5.17±1.44 mmol/L, P=0.01) compared with controls. Higher levels of activated endothelial nitric oxide synthase (phosphorylated to total endothelial nitric oxide synthase levels: 2.71±1.16 versus 1.37±0.35, P=0.02) with less histological evidence of endothelial damage (von Willebrand factor expression: 0.024±0.007 versus 0.331±0.302, pixel/μm, P=0.04) was also observed with exenatide treatment versus controls. Conclusions Acute treatment of DCD hearts with exenatide limits myocardial and endothelial injury and improves donor cardiac function.