Superior cardiac protection in combined ex-situ perfusion of heart and liver

Sanaz Hatami; Joshua Hefler; Guilherme da Silva; Mitchell Wagner; Mobashir Khan; Sayed Himmat; Shubham Shan; Xiuhua Wang; Benjamin Adam; James Shapiro; Jayan Nagendran; Darren H Freed

doi:10.1016/j.healun.2025.09.012

Superior cardiac protection in combined ex-situ perfusion of heart and liver

J Heart Lung Transplant. 2026 Feb;45(2):289-299. doi: 10.1016/j.healun.2025.09.012. Epub 2025 Sep 24.

Authors

Affiliations

¹ Departments of Medicine, University of Alberta, Edmonton, Alberta, Canada; Canadian Transplant Research Program, Edmonton, Alberta, Canada.
² Departments of Surgery, University of Alberta, Edmonton, Alberta, Canada; Canadian Transplant Research Program, Edmonton, Alberta, Canada.
³ Departments of Surgery, University of Alberta, Edmonton, Alberta, Canada.
⁴ Departments of Surgery, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute, Edmonton, Alberta, Canada.
⁵ Departments of Pathology, University of Alberta, Edmonton, Alberta, Canada.
⁶ Departments of Surgery, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute, Edmonton, Alberta, Canada; Canadian Transplant Research Program, Edmonton, Alberta, Canada.
⁷ Departments of Surgery, University of Alberta, Edmonton, Alberta, Canada; Departments of Physiology, University of Alberta, Edmonton, Alberta, Canada; Departments of a Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute, Edmonton, Alberta, Canada; Canadian Transplant Research Program, Edmonton, Alberta, Canada. Electronic address: dhfreed@ualberta.ca.

PMID: 41005516
DOI: 10.1016/j.healun.2025.09.012

Abstract

Background: Normothermic ex-situ heart perfusion has helped expand the heart donor pool however, it is not optimized yet. Experimental ex-situ organ perfusion incorporating cross-circulation with a live animal has achieved significantly longer safe ex-situ preservation times; however, the underlying mechanisms are not clear.

Methods: In this study, combined ex-situ heart-liver perfusion of porcine hearts was compared to ex-situ isolated heart perfusion. Discarded human donor hearts were also perfused ex-situ and cardiac function and metabolism was studied.

Results: The hearts perfused together with liver were preserved significantly better, with lower edema, preserved key nutrients, and lower oxidative stress, (comparable to in vivo samples). Human donor hearts subjected to ex-situ perfusion had similar function and oxidative patterns compared to isolated porcine hearts, suggesting these hearts are vulnerable to the same phenomena as porcine hearts.

Conclusions: Our findings suggest that efficient antioxidant and energy metabolite support is necessary for improving the functional preservation of the donor heart during ex-situ perfusion.

Keywords: ex-situ perfusion; heart donation; heart preservation; porcine model; translational research.

MeSH terms

Animals
Female
Heart Transplantation* / methods
Heart* / physiology
Humans
Liver*
Male
Myocardium* / metabolism
Organ Preservation* / methods
Oxidative Stress
Perfusion* / methods
Swine
Tissue Donors