A Standardized Pig to Macaque Heterotopic Heart Xenotransplantation Model

Although significant progress has been made in heart xenotransplantation, challenges such as donor-recipient matching, antibody-mediated rejection, primary graft dysfunction, and postoperative thrombosis remain unresolved. Compared to orthotopic transplantation, heterotopic abdominal heart transplantation offers a technically simpler procedure and allows the recipient to survive independently of graft function, making it particularly suitable for studying xenogeneic immune rejection. In countries where the use of baboons as experimental animals is prohibited, macaques represent the most appropriate alternative for studying immune rejection in heart xenotransplantation. However, the smaller body size of macaques presents greater challenges in donor selection and surgical techniques. This study established a heterotopic abdominal heart xenotransplantation model using α-Gal knockout (GTKO) pigs and macaques, incorporating systematic optimization of recipient selection, vascular anastomosis techniques, intraoperative procedures, and perioperative management. The present model enables repeated graft biopsies, providing a valuable platform for evaluating novel immunosuppressive strategies and investigating the mechanisms of xenogeneic rejection.