Cardiac xenotransplantation

Abstract

Purpose of Review Cardiac xenotransplantation (CXTx) remains a promising approach to alleviate the chronic shortage of donor hearts. This review summarizes recent results of heterotopic and orthotopic CXTx, highlights the role of non-Gal antibody in xenograft rejection, and discusses challenges to clinical orthotopic CXTx. Recent Findings Pigs mutated in the α 1,3 galactosyltransferase gene (GTKO pigs) are devoid of the galactose α 1,3 galactose (αGal) carbohydrate antigen. This effectively eliminated any role for anti-Gal antibody in GTKO cardiac xenograft rejection. Survival of heterotopic GTKO cardiac xenografts in nonhuman primates continues to increase. GTKO graft rejection commonly involves vascular antibody deposition and variable complement deposition. Non-Gal antibody responses to porcine antigens associated with inflammation, complement, and hemostatic regulation and to new carbohydrate antigens have been identified. Their contribution to rejection remains under investigation. Orthotopic CXTx is limited by early perioperative cardiac xenograft dysfunction (PCXD). However, hearts affected by PCXD recover full cardiac function and orthotopic survival up to 2 months without rejection has been reported. Summary CXTx remains a promising technology for treating end-stage cardiac failure. Genetic modification of the donor and refinement of immunosuppressive regimens have extended heterotopic cardiac xenograft survival from minutes to in excess of 8 months.

The Coronary Microcirculation in Hamster-to-Rat Cardiac Xenografts

“…As xenogeneic transplantation could potentially solve the organ shortage in cardiac transplantation, special interest lies in overcoming the mechanisms of xenograft rejection [2,3]. Several innovations, like genetically modified donor animals [14], achieved increased long-term survival in preclinical xenotransplantation models [15,16,17]. Yet, cardiac xenotransplantation is still far from being established clinically [18].…”

Current status of pig heart xenotransplantation

“…A high level of perioperative mortality within the first 48 hours post transplant is reported in oCXTx studies [5]. This phenomenon, termed perioperative cardiac xenograft dysfunction (PCXD), has been seen at frequencies ranging from 40 to 60% by all research groups.…”

“…We refer the reader to previous reviews [3–5] for additional background related to these recent advances.…”

Plasma free triiodothyronine (fT3) levels in baboons undergoing pig organ transplantation: relevance to early recovery of organ function

“…There have been reports of a high early mortality after pig orthotopic heart Tx in baboons, particularly within the first 48 hours (12; Mohiuddin M, personal communication). If the baboon survives for 48 hours, then there is recovery of the myocardial function and longer-term survival is likely (12).…”

“…If the baboon survives for 48 hours, then there is recovery of the myocardial function and longer-term survival is likely (12). We suggest that the early high morbidity and mortality may be associated with a reduced level of plasma fT3, and that consideration should be given to T3 replacement therapy.…”