Work

Molecular and cellular adaptations to extended hypothermic oxygenated perfusion in donation-after-circulatory-death hearts in a porcine model

Year: 2026

Type: article

Abstract: Introduction: Donation after circulatory death (DCD) criteria serves as a potential strategy to expand the organ pool for heart transplantation. However, DCD procurement introduces prolonged warm ischemic times that accelerate endothelial and cardiomyocyte injury. Hypothermic oxygenated perfusion (HOPE) has emerged as a novel metabolic preservation strategy, yet its biological mechanisms remain undefined. We investigated how extended HOPE preservation modulates cardiomyocyte viability and metabolic stability after DCD in a porcine model. Methods and results: normothermic regional perfusion (NRP), porcine hearts were preserved either by static cold storage (SCS) for 2 h or by HOPE for 24 h. A third experimental group included hearts that were directly procured without NRP and preserved by HOPE for 2 h. All hearts were subsequently reperfused and reanimated using an extracorporeal circuit under normothermic conditions. Flow cytometry revealed measurable populations of troponin-positive viable cardiomyocytes even 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. Furthermore, 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.

Source: Frontiers in Cardiovascular Medicine

DOI: 10.3389/fcvm.2026.1800470