Donor heart ischemic time can be extended beyond 9 hours using hypothermic machine perfusion in sheep

BACKGROUND: The global shortage of donor hearts available for transplantation is a major problem for the treatment of end-stage heart failure. The ischemic time for donor hearts using traditional preserva-tion by standard static cold storage (SCS) is limited to approximately 4 hours, beyond which the risk for primary graft dysfunction (PGD) significantly increases. Hypothermic machine perfusion (HMP) of donor hearts has been proposed to safely extend ischemic time without increasing the risk of PGD. METHODS: Using our sheep model of 24 hours brain death (BD) followed by orthotopic heart transplan-tation (HTx), we examined post-transplant outcomes in recipients following donor heart preservation by HMP for 8 hours, compared to donor heart preservation for 2 hours by either SCS or HMP. RESULTS: Following HTx, all HMP recipients (both 2 hours and 8 hours groups) survived to the end of the study (6 hours after transplantation and successful weaning from cardiopulmonary bypass), required less vasoactive support for hemodynamic stability, and exhibited superior metabolic, fluid sta-tus and inflammatory profiles compared to SCS recipients. Contractile function and cardiac damage (troponin I release and histological assessment) was comparable between groups. CONCLUSIONS: Overall, compared to current clinical SCS, recipient outcomes following transplanta-tion are not adversely impacted by extending HMP to 8 hours. These results have important implica-tions for clinical transplantation where longer ischemic times may be required (e.g., complex surgical cases, transport across long distances). Additionally, HMP may allow safe preservation of marginal donor hearts that are more susceptible to myocardial injury and facilitate increased utilization of these hearts for transplantation. J Heart Lung Transplant 2023;42:1015-1029 & COPY; 2023 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY-NC-ND license