Twenty-Hour Hypothermic Oxygenated Perfusion Preserves Myocardial Viability and Bioenergetics with No Primary Graft Dysfunction After Porcine Heart Transplantation
Abstract
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.
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BibTeX
@misc{mitchell2026twentyhour,
title = {{Twenty-Hour Hypothermic Oxygenated Perfusion Preserves Myocardial Viability and Bioenergetics with No Primary Graft Dysfunction After Porcine Heart Transplantation}},
author = {W. Mitchell and C. Karcher and N. Ott and I. Mason and D. Albino and A. Adamo and F. Soliman and F. I. Schoettler and V. Zhang and E. Bektik and S. Orsini and K. Clerkin and C. Chan and E. Monsanto and M. Sekulic and S. K. Faruqi and C. J. Goergen and M. Tamini and M. Moroi and A. Elmously and K. Takeda and G. Ferrari},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.26366672},
url = {https://www.medrxiv.org/content/10.64898/2026.10.29.26366672v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Twenty-Hour Hypothermic Oxygenated Perfusion Preserves Myocardial Viability and Bioenergetics with No Primary Graft Dysfunction After Porcine Heart Transplantation
AU - W. Mitchell
AU - C. Karcher
AU - N. Ott
AU - I. Mason
AU - D. Albino
AU - A. Adamo
AU - F. Soliman
AU - F. I. Schoettler
AU - V. Zhang
AU - E. Bektik
AU - S. Orsini
AU - K. Clerkin
AU - C. Chan
AU - E. Monsanto
AU - M. Sekulic
AU - S. K. Faruqi
AU - C. J. Goergen
AU - M. Tamini
AU - M. Moroi
AU - A. Elmously
AU - K. Takeda
AU - G. Ferrari
PY - 2026
DA - 2026/10/29
PB - medRxiv
DO - 10.64898/2026.10.29.26366672
UR - https://www.medrxiv.org/content/10.64898/2026.10.29.26366672v1
AB - 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.
ER -