Current status of pig heart xenotransplantation

Abstract

Significant progress in understanding and overcoming cardiac xenograft rejection using a clinically relevant large animal pig-to-baboon model has accelerated in recent years. This advancement is based on improved immune suppression, which attained more effective regulation of B lymphocytes and possibly newer donor genetics. These improvements have enhanced heterotopic cardiac xenograft survival from a few weeks to over 2 years, achieved intrathoracic heterotopic cardiac xenograft survival of 50 days and orthotopic survival of 57 days. This encouraging progress has rekindled interest in xenotransplantation research and refocused efforts on preclinical orthotopic cardiac xenotransplantation.

Keywords: Anti CD154 antibody; Anti CD20 antibody; Anti CD40 antibody; Cardiac xenotransplantation; Heterotopic; Intrathoracic heterotopic; Orthotopic.

Figure 1

Illustrations of cardiac xenotransplantation surgical techniques. A. Heterotopic abdominal transplantation. Only the coronary arteries are perfused (via the abdominal aorta), the coronary venous blood enters the right atrium, then the ventricle. It is ejected (via the pulmonary trunk) into the inferior cava. The heart is beating, but non-working. B. Orthotopic cardiac transplantation. The recipient heart is removed at the atrial level; ascending aorta and the pulmonary trunk are cut. The donor organ is then connected accordingly. C. Intrathoracic heterotopic cardiac transplantation. The donor organ is to the right of the recipient heart, within the right chest. There are two common atria, since they are end-to-end anastomosed. The blood volume is ejected by both hearts via two end-to-side connections at the levels of the ascending aortas, the pulmonary artery trunks (the latter needs a graft interposition). Both organs work non-synchronously. Their shares of the cardiac output depend on the respective preloads, which in turn are related to the parts of the cycles of the two hearts.(illustrations by Nina Bantschow)

Figure 1

Illustrations of cardiac xenotransplantation surgical techniques. A. Heterotopic abdominal transplantation. Only the coronary arteries are perfused (via the abdominal aorta), the coronary venous blood enters the right atrium, then the ventricle. It is ejected (via the pulmonary trunk) into the inferior cava. The heart is beating, but non-working. B. Orthotopic cardiac transplantation. The recipient heart is removed at the atrial level; ascending aorta and the pulmonary trunk are cut. The donor organ is then connected accordingly. C. Intrathoracic heterotopic cardiac transplantation. The donor organ is to the right of the recipient heart, within the right chest. There are two common atria, since they are end-to-end anastomosed. The blood volume is ejected by both hearts via two end-to-side connections at the levels of the ascending aortas, the pulmonary artery trunks (the latter needs a graft interposition). Both organs work non-synchronously. Their shares of the cardiac output depend on the respective preloads, which in turn are related to the parts of the cycles of the two hearts.(illustrations by Nina Bantschow)

Figure 1

Illustrations of cardiac xenotransplantation surgical techniques. A. Heterotopic abdominal transplantation. Only the coronary arteries are perfused (via the abdominal aorta), the coronary venous blood enters the right atrium, then the ventricle. It is ejected (via the pulmonary trunk) into the inferior cava. The heart is beating, but non-working. B. Orthotopic cardiac transplantation. The recipient heart is removed at the atrial level; ascending aorta and the pulmonary trunk are cut. The donor organ is then connected accordingly. C. Intrathoracic heterotopic cardiac transplantation. The donor organ is to the right of the recipient heart, within the right chest. There are two common atria, since they are end-to-end anastomosed. The blood volume is ejected by both hearts via two end-to-side connections at the levels of the ascending aortas, the pulmonary artery trunks (the latter needs a graft interposition). Both organs work non-synchronously. Their shares of the cardiac output depend on the respective preloads, which in turn are related to the parts of the cycles of the two hearts.(illustrations by Nina Bantschow)