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Updated: Jun 3, 2025
A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft
Published on: February 14, 2022
Preservation of Cardiac Xenografts in a Model of Infant Human Cardiac Transplantation
Chace B Mitchell1, Joe Simmons2, Clementine Vo1,3
1Division of Cardiac Surgery, Department of Surgery, Children's Hospital of Los Angeles, Los Angeles, California, USA.
Insights
Modified Del Nido cardioplegia effectively preserved cardiac xenograft function in baboons, demonstrating its potential for life-sustaining orthotopic cardiac xenotransplantation and reducing the need for ex vivo perfusion systems.
Area of Science:
- Cardiovascular Surgery
- Xenotransplantation
- Organ Preservation
Background:
- Standard organ preservation protocols are insufficient for cardiac xenotransplantation, especially with pediatric donors.
- Existing human allotransplantation techniques are not viable for xenografts.
- Xenotransplantation offers reduced organ ischemic times through donor-recipient co-location.
Purpose of the Study:
- To evaluate a modified Del Nido cardioplegia solution for organ preservation in life-sustaining orthotopic cardiac xenotransplantation.
- To assess the efficacy of reduced ischemic times in xenograft management.
- To determine if a pediatric cardiac surgery solution is viable for xenotransplantation.
Main Methods:
- Orthotopic cardiac xenotransplantation performed from genetically engineered pigs to baboons.
- Modified Del Nido cardioplegia used for donor heart arrest and prior to implantation.
- Hemodynamics and cardiac function monitored invasively and non-invasively.
Main Results:
- Mean ischemic time was 54.1 ± 14.6 minutes.
- Ejection fraction remained >50% post-implantation and at 48 hours.
- Mean inotropic score at 24 hours was 9.7 ± 3.
Conclusions:
- Modified Del Nido cardioplegia with short ischemic times shows promise for preventing primary graft dysfunction in cardiac xenografts.
- This approach may eliminate the need for ex vivo perfusion systems in clinical xenotransplantation.
- Successful xenograft function was achieved in a small animal model.
Introduction:
There is no standard protocol for management of organ preservation for orthotopic, life-sustaining cardiac xenotransplantation, particularly for hearts from pediatric sized donors. Standard techniques and solutions successful in human allotransplantation are not viable. We theorized that a solution commonly used in reparative cardiac surgery in human children would suffice by exploiting the advantages inherent to xenotransplantation, namely the ability to reduce organ ischemic times by co-locating the donor and recipient.
Methods:
Orthotopic cardiac xenotransplantation was performed from genetically engineered pigs to size matched baboons. A dose of modified Del Nido cardioplegia initiated donor heart arrest and was followed by a second dose mixed with recipient blood prior to implant. Hemodynamics and cardiac function were tracked with a combination of invasive and non-invasive measures.
Results:
Mean ischemic time and cardiopulmonary bypass times were 54.1 ± 14.6 and 84.1 ± 14 min respectively. The ejection fraction following chest closure was preserved at >50% for all animals. This finding persisted at 48hours. Mean inotropic score at 24 h post-implant was 9.7 ± 3.
Conclusion:
Del Nido cardioplegia solution when combined with short graft ischemic times demonstrates promising outcomes to avoid primary graft dysfunction for cardiac xenografts in a small animal model of life-sustaining orthotopic cardiac xenotransplantation. Ex vivo perfusion systems may be unnecessary for successful clinical implementation of this evolving technology.
