Metabolic Choreography of Energy Substrates During DCD Heart Perfusion.

Background

The number of patients waiting for heart transplant far exceeds the number of hearts available. Donation after circulatory death (DCD) combined with machine perfusion can increase the number of transplantable hearts by as much as 48%. Emerging studies also suggest machine perfusion could enable allograft "reconditioning" to optimize outcomes. However, a detailed understanding of the energetic substrates and metabolic changes during perfusion is lacking.

Methods

Metabolites were analyzed using 1-dimensional

Results

Metabolite differences were observed comparing baseline perfusate to samples from hearts at time points 1-2, 3-4, and 5-6 h of perfusion and all pairwise combinations. Among the most significant changes observed were a steady decrease in fatty acids and succinate and an increase in amino acids, especially alanine, glutamine, and glycine. This core set of metabolites was also altered in a DCD porcine model perfused with a nonblood-based perfusate.

Conclusions

Temporal metabolic changes were identified during ex vivo perfusion of DCD hearts. Fatty acids, which are normally the predominant myocardial energy source, are rapidly depleted, while amino acids such as alanine, glutamine, and glycine increase. We also noted depletion of ketone, β-hydroxybutyric acid, which is known to have cardioprotective properties. Collectively, these results suggest a shift in energy substrates and provide a basis to design optimal preservation techniques during perfusion.

Informations de copyright

Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.

Déclaration de conflit d'intérêts

A.T., J.Z., and E.M.O. are employees of Olaris, Inc and have ownership and salary interest in the company. The other authors declare no conflicts of interest.