# Improving metabolic support during normothermic ex-situ heart perfusion

## TL;DR

This paper reviews how to improve heart preservation during a new technology that keeps donor hearts alive outside the body by adjusting the nutrients they receive.

## Contribution

The paper proposes using fasting-like metabolic substrates, such as free fatty acids and ketone bodies, to better support donor hearts during ex-situ perfusion.

## Key findings

- Current metabolic support during ESHP resembles post-prandial conditions, which may not be optimal.
- Alternative substrates like free fatty acids and ketone bodies may better support heart function during ESHP.
- Research gaps exist in optimizing metabolic strategies for donor heart preservation.

## Abstract

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.