REVIEW article
Front. Cardiovasc. Med.
Sec. Heart Failure and Transplantation
This article is part of the Research TopicEmerging Techniques in Graft Preservation: Machine Perfusion and Therapeutic Interventions - Volume IIView all 7 articles
Improving metabolic support during normothermic ex-situ heart perfusion
Provisionally accepted
- University of Alberta, Edmonton, Canada
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Ex-situ heart perfusion (ESHP) is an innovative technology that has the power to greatly improve donor heart utilization and may eventually provide a platform for improvement of suboptimal hearts. However, its impact is limited by functional decline whilst on the platform, which is characterized by the development of oxidative stress and inflammation. Pathologic metabolism during normothermic ESHP may be an underlying factor in the development of such characteristics, however it is understudied within the context of machine perfusion. In the following review article, we discuss the limitations of the current metabolic substrate provision approach during ESHP (analogous to post-prandial glucose and insulin) from a mechanistic standpoint. We discuss alternative approaches and substrates that may be more conducive to physiologic preservation and recovery on the platform. We advocate for a support strategy mimicking fasting insulin and glucose, and alternative substrates such as free fatty acids and ketone bodies, which may be more adapted to the non-physiologic state encountered during ESHP. Throughout, we outline research gaps yet to be explored that would enable substrate provision approaches during machine perfusion of the donor heart to be further optimized.
Keywords: Ex-situ heart perfusion, Heart transplantation (HTx), cardiac metabolism, Machine perfusion, Organ Preservation
Received: 17 Aug 2025; Accepted: 08 Dec 2025.
Copyright: © 2025 Wagner, Hatami, Hassanzadeh, Sutendra, Conway and Freed. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mitchell Wagner
Darren Freed
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