Early Experience With Preclinical Perioperative Cardiac Xenograft Dysfunction in a Single Program

Area of Science:

• Transplantation immunology
• Xenotransplantation research
• Cardiovascular surgery

Background:

• Perioperative cardiac xenograft dysfunction (PCXD) is a significant hurdle for cardiac xenotransplantation.
• PCXD is defined as graft dysfunction within 24-48 hours post-transplant, independent of rejection.

Purpose of the Study:

• To describe the program's experience with PCXD in orthotopic cardiac xenotransplantation.
• To evaluate the feasibility and outcomes of genetically engineered pig heart transplantation in baboons.

Main Methods:

• Orthotopic transplantation of genetically engineered pig hearts into 6 baboons.
• Comprehensive immunosuppression regimen including induction and maintenance therapy.
• Graft function monitored via telemetry; extracorporeal membrane oxygenation used for support.

Main Results:

• Maximum survival of 40 hours achieved; surgical procedures were uneventful.
• Initial graft function was adequate, but support requirements increased within hours, leading to arrest.
• Histological examination revealed no signs of rejection in explanted hearts.

Conclusions:

• Orthotopic cardiac xenografts experience progressive dysfunction within 48 hours, despite successful surgery and immunosuppression.
• PCXD occurs without evidence of rejection, highlighting a critical challenge in xenotransplantation.
• Improved organ preservation and reduced ischemic time are potential strategies to mitigate PCXD.