Preservation of Cardiac Xenografts in a Model of Infant Human Cardiac Transplantation

Xenotransplantation. 2025 Jan-Feb;32(1):e70009. doi: 10.1111/xen.70009.

Abstract

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.

Keywords: cardiac; infant; xenotransplantation.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Graft Survival
  • Heart Arrest, Induced / methods
  • Heart Transplantation* / methods
  • Heterografts*
  • Humans
  • Infant
  • Organ Preservation* / methods
  • Papio*
  • Swine
  • Transplantation, Heterologous* / methods