Effects of Graft Preservation Conditions on Coronary Endothelium and Functional Recovery in a Rat Model of Donation after Circulatory Death

Purpose Donation after circulatory death (DCD) could significantly improve cardiac graft availability. However, DCD hearts are subjected to potentially damaging conditions prior to circulatory arrest and during warm ischemia and reperfusion. Although the feasibility of DCD heart transplantation has been demonstrated, protocols for graft preservation and storage require optimization to ensure graft quality. Therefore, we aimed to compare the current clinical conditions used for heart preservation (St. Thomas n°2) with a potentially more suitable solution for DCD hearts, evaluating endothelial and cardiac function to investigate differences in cardioprotective effects. Methods Following anaesthesia, diaphragm transection, and circulatory arrest in male Wistar rats to simulate DCD conditions, hearts were subjected to either 0 or 18 minutes of warm, in-situ ischemia. At end-ischemia, hearts were perfused with either: St. Thomas n°2 cardioplegia at 4°C as in current clinical practice, or normokalemic, adenosine-lidocaine cardioplegia (A-L) at 4°C or 22°C. Afterwards, hearts were stored for 15 min in their respective solutions, and then reperfused ex-situ for either 30 min (to assess endothelial function) or 60 min (to assess cardiac function and biochemical parameters). Results A-L cardioplegia at 22°C better preserves vascular function as compared to cold A-L or St. T cardioplegia, as demonstrated by greater eNOS coupling (p Conclusion Use of A-L and avoidance of profound hypothermia and hyperkalemic cardioplegia could improve endothelial and contractile function, potentially through the promotion of eNOS dimerization and activation of the RISK pathway; these approaches should help to optimize clinical protocols in DCD heart transplantation and facilitate its widespread adoption in clinical practice.