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.