Hypothermic Ex Vivo Perfusion of Donor Hearts can Safely Preserve Post‐transplant Cardiac Function in Sheep for 8 Hours

Abstract

IntroductionHeart transplantation (HTx) is the primary therapy for end‐stage heart failure. For HTx, donor hearts are typically preserved on ice in a cooler (devoid of oxygen), termed cold static storage (CSS). CSS beyond 4 hrs increases the risk of primary graft dysfunction (PGD), the leading cause of early death post‐HTx. Hypothermic ex vivo perfusion (HEVP) of donor hearts allows oxygen delivery during preservation, and we hypothesise, may safely extend donor heart preservation time without increasing PGD risk. We sought to compare post‐HTx recipient survival, cardiac contractility, mitochondrial function, and injury following donor heart preservation by CSS (2 hrs) or HEVP (2 and 8 hrs).MethodsBrain death was induced in donor sheep for 24 hrs, hearts were then preserved by a) CSS for 2 hrs (n=8), b) HEVP for 2 hrs (n=6), or c) HEVP for 8 hrs (n=7). Orthotopic HTx was performed in matched recipients, with progressive hemodynamic management and monitoring for 6 hrs post‐HTx. Recipient cardiac function was assessed by echocardiography, and troponin I levels were measured in plasma. Mitochondrial function, in vitro contractile responses to noradrenaline (trabeculae), and histopathological changes were determined in cardiac tissue collected at end‐study.ResultsAll HEVP recipients survived to 6 hrs post‐HTx, compared to 6/8 CSS recipients. HEVP (2 and 8 hrs) recipients required less vasoactive support for adequate hemodynamic function, and exhibited reduced blood lactate levels compared to CSS. Post‐HTx cardiac function and troponin I levels were comparable between groups over time, however improved contractile responses to noradrenaline were observed in isolated trabeculae from 2 and 8 hr HEVP hearts. Cardiac mitochondrial function was similar between all groups, except for the 2 hrs HEVP left ventricle, where greater improvements in mitochondrial membrane potential generation were observed. Regardless of preservation technique, histological scores revealed widespread cardiac injury (e.g. myocytolysis and neutrophil infiltration).ConclusionDonor heart preservation by HEVP shows promising post‐HTx outcomes in comparison to CSS in a sheep HTx model. HEVP can be safely extended up to 8 hrs, without compromising post‐HTx recipient survival, cardiac contractile or mitochondrial function. HEVP may assist in overcoming limitations in preservation time associated with HTx, without increasing PGD risk. The Australian Non‐Ischemic Heart Preservation (NIHP) trial is currently assessing extended HEVP in clinical HTx (ACTRN12620000595910p).