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Updated: Aug 3, 2025
Rat Model of Normothermic Ex-Situ Perfused Heterotopic Heart Transplantation
Published on: April 21, 2023
Donor heart ischemic time can be extended beyond 9 hours using hypothermic machine perfusion in sheep
Louise E See Hoe1, Gianluigi Li Bassi2, Karin Wildi3
1Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia; School of Pharmacy and Medical Sciences, Griffith University, Southport, Queensland, Australia.
Insights
Extending hypothermic machine perfusion (HMP) for donor heart preservation up to 8 hours did not negatively impact transplant recipient outcomes. This advancement offers potential for longer preservation times and increased use of marginal donor hearts in heart transplantation.
Area of Science:
- Cardiovascular Surgery
- Transplantation Medicine
- Organ Preservation
Background:
- Global donor heart shortage limits treatment for end-stage heart failure.
- Standard static cold storage (SCS) has a limited ischemic time of ~4 hours, increasing primary graft dysfunction (PGD) risk.
- Hypothermic machine perfusion (HMP) offers a potential solution to extend preservation time safely.
Purpose of the Study:
- To evaluate post-transplant outcomes in a sheep model after 8-hour HMP donor heart preservation compared to 2-hour SCS or HMP.
- To assess the impact of extended HMP on graft function and recipient hemodynamics.
Main Methods:
- Sheep model of brain death (BD) followed by orthotopic heart transplantation (HTx).
- Donor hearts preserved by HMP for 8 hours (n=?) or 2 hours (n=?), and by SCS for 2 hours (n=?).
- Comparison of post-transplant recipient outcomes, including survival, vasoactive support, metabolic/fluid status, inflammation, contractile function, and cardiac damage markers.
Main Results:
- All HMP recipients (2-hour and 8-hour groups) survived the study period.
- HMP groups required less vasoactive support and showed superior metabolic, fluid, and inflammatory profiles compared to SCS.
- Contractile function and cardiac damage were comparable between HMP and SCS groups.
Conclusions:
- Extending HMP donor heart preservation to 8 hours does not adversely affect recipient outcomes compared to clinical SCS.
- Extended HMP has implications for clinical transplantation, enabling longer ischemic times for complex cases or long-distance transport.
- HMP may facilitate the safe preservation and increased utilization of marginal donor hearts.
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 preservation 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 transplantation (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 status 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 transplantation are not adversely impacted by extending HMP to 8 hours. These results have important implications 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.
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