Hypothermic Ex Vivo Perfusion of Donor Hearts can Safely Preserve Post‐transplant Cardiac Function in Sheep for 8 Hours
Authors: See Hoe Louise E. , Bouquet Mahe , Hyslop Kieran , Passmore Margaret R. , Wells Matthew A. , Sato Kei , Wilson Emily , Wildi Karin , Skeggs Kris , Palmeri Chiara , Reid Janice , O'Neill Hollier , Bartnikowski Nicole , Jung Jae‐Seung , Ainola Carmen , Abbate Gabriella , Colombo Sebastiano M. , Obonyo Nchafatso G. , McDonald Charles , Shuker Tristan , Heinsar Silver , Haymet Andrew , Pedersen Sanne , Molenaar Peter , Li Bassi Gianluigi , Suen Jacky Y. , McGiffin David C. , Fraser John F. ,   Dead Heart Project
Published: May 2022

Introduction

Heart 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).

Methods

Brain 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.

Results

All 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).

Conclusion

Donor 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).