Twenty-Hour Hypothermic Oxygenated Perfusion Preserves Myocardial Viability and Bioenergetics with No Primary Graft Dysfunction After Porcine Heart Transplantation

Background: Hypothermic oxygenated perfusion (HOPE) may extend donor heart preservation beyond conventional storage durations. We evaluated early graft function and myocardial cellular and metabolic integrity following porcine heart transplantation after 20 hours of HOPE. Methods: Ten donor hearts underwent various preservation conditions: static cold storage (SCS) for 4 hours (n=2), HOPE for 4 hours (n=3), and HOPE for 20 hours (n=5), followed by heart transplantation (HT) in recipient pigs. Graft function was monitored over 3 hours by serial echocardiography, invasive hemodynamics, optical flow analysis, and vasoactive support scoring; myocardial tissue was analyzed by histopathology, flow cytometry, mitochondrial respirometry, transcriptomics, and proteomics. Results: Ejection fraction, right atrial pressure and systolic blood pressure did not differ between groups, and no graft met criteria for primary graft dysfunction. LV contractility was within normal range with comparable vasoactive support among all groups. Preservation-associated weight gain was greatest after HOPE 20h, and histopathology showed comparable findings with edema present in all cohorts, without fibrosis, thrombosis, or necrosis. Cardiomyocyte viability was preserved across all groups. Maximal oxygen consumption rate was elevated in HOPE 20h versus HOPE 4h and SCS 4h, while basal and non-mitochondrial respiration were similar. Transcriptomics and proteomics revealed limited differences in gene and pathway expression among groups. Conclusions: HOPE preserves donor heart viability, mitochondrial integrity, and ventricular function after 20 hours of preservation, without evidence of primary graft dysfunction, supporting extended preservation for heart transplantation. Edema, recovery of function, and metabolic responses warrant further investigation with longer-term monitoring.