Hearts from Donations after Circulatory Death (DCD) Donors - Ischaemic Post-Conditioning Significantly Improves Recovery of Cardiac Function Following Warm Ischaemia in A Porcine Model

Abstract

Introduction: Utilisation of hearts from Donations after circulatory death (DCD) donors has been limited by fear of warm ischaemic damage. We aim to investigate the impact of varying periods of warm ischaemia on cardiac function in DCD hearts, and evaluate ischaemic post-conditioning strategies to limit warm ischaemic injury. Methods: Utilising a porcine DCD model, 3 warm ischaemic time (WIT) periods were evaluated. All hearts were antegrade flushed with Celsior solution after the designated period of warm ischaemia. Ischaemic post-conditioning was affected with the supplementation of Celsior with glyceryl trinitrate (GTN), erythropoietin (EPO), and zoniporide - this approach has been studied extensively in our laboratory1. (table 1)Hearts were explanted onto an isolated working heart circuit. Left heart performance was assessed for 4 hours - functional assessment (Cardiac Output, Coronary Flow, Left Atrial Pressure (LAP) vs Aortic Flow (AF) challenge), metabolic recovery (pH, lactate, myocardial oxygen consumption), and biochemical parameters (troponin, LDH) were evaluated. Results: When compared with control hearts, Group 1 hearts showed complete functional recovery, Group 2 had partial recovery and Group 3 had no recovery. Cardiac Output was inferior with Group 2 hearts (graph 1). The increase in AF in response to increased LAP was significantly blunted for Group 2 (p=0.05), when compared with control and Group 1. Group 2 hearts also remained more acidotic (p=0.03), had higher lactate levels (p=0.03), greater troponin release (p=0.03) and had non-significant trends towards higher LDH levels than control or Group 1 hearts. Following the supplementation of the preservation flush for 30 minute warm ischaemia hearts (Group 4) there was a significantly improved functional and biochemical recovery when compared with group 2 hearts (unsupplemented 30 minute warm ischaemia hearts). Comparing group 2 and group 4, group 4 had superior Cardiac Output (p < 0.01, see graph 1), higher coronary flows (p < 0.01), superior performance in the AF vs LAP challenge (p = 0.03), and decreased troponin release (p=0.05).Figure: [Graph 1]Conclusion: Hearts with a WIT of less than 20 minutes demonstrate excellent recovery, supporting the potential for DCD hearts in transplantation. The detrimental effects of warm ischaemia become evident beyond 20 minutes - here, ischaemc post-conditioning strategies aimed at mitigating ischaemia-reperfusion injury significantly improve cardiac recovery. With the utilization of such strategies in preserving cardiac function following 30 minutes of warm ischaemia, the potential for translation to clinical DCD heart transplantation is greatly strengthened and warrants further investigation.