BACKGROUND: Ex situ heart perfusion (ESHP) decreases ischemic time and improves myocardial preservation for transplantation. However, the effects of machine perfusion on endothelial function has not yet been determined. We aimed to compare coronary vasomotor function and endothelial activation following transplantation between hearts donated after circulatory death (DCD) and controls (beating-heart donations) preserved in cold storage or ESHP.
METHODS AND RESULTS: DCD pigs underwent hypoxic circulatory arrest via asphyxiation followed by 15min of warm ischemia. Both DCD and control hearts were preserved with either 3h of cold storage or 4h of ESHP. Following transplantation, both groups were reperfused for 3h. We assessed coronary artery segments for endothelial-dependent (Edep) and -independent (Eind) relaxation, and sensitivity to vasospasm using a small vessel myograph. Expression of VCAM-1, and endothelin receptors A (ETa) and B (ETb) were measured with immunoblotting. Preservation with ESHP partially improved Edep (p=0.098) and significantly enhanced Eind (p=0.004) in controls. DCD hearts showed no differences in Edep (p=0.266), Eind (p=0.182) compared to controls when preserved in cold storage. Preservation of DCD hearts using ESHP significantly improved Edep (p < 0.001) and Eind (p < 0.001). No differences were seen in vasospasm between groups in any of the comparisons (Fig1 a, b, c). Likewise, ESHP decreased VCAM-1 expression in both controls and DCD hearts. No difference was seen in ETa/ETb ratio between groups.
CONCLUSION: ESHP strategies have enabled DCD heart transplantation and expansion of the donor heart pool. Limiting cold ischemia by machine perfusion with a normothermic, oxygenated, and blood-based perfusate seems to limit endothelial activation and dysfunction by decreasing ischemia-reperfusion injury. This may lead to a reduced rate of early graft dysfunction and late development of allograft vasculopathy.