Molecular and Cellular Adaptations to Extended Hypothermic Oxygenated Perfusion in Donation-After-Circulatory-Death Hearts in a Porcine Model

HOPE preservation maintained myocardial structure, cardiomyocyte viability, and sinus rhythm after 24 hours, sixfold beyond the conventional preservation window. Flow cytometry revealed measurable populations of troponin-positive viable cardiomyocytes after 24-hour HOPE, in contrast to complete loss after 24-hour SCS. RNA sequencing and metabolomics demonstrated minimal transcriptional or metabolic shift between 2-hour SCS and 24-hour HOPE hearts, with preservation of oxidative and glycolytic balance and limited inflammatory activation.

In contrast, omission of NRP during procurement resulted in marked loss of contractility and cardiomyocyte integrity, underscoring its potential role in pre-preservation harvest in a porcine model. Conclusions: In a swine model extended hypothermic oxygenated perfusion preservation sustains myocardial and metabolic integrity after circulatory death by minimizing transcriptional and metabolic injury signatures. These findings identify a biologically distinct preservation state that mitigates ischemia-reperfusion injury and may inform novel strategies for organ and tissue preservation.