Intra-Abdominal Heterotopic Cardiac Xenotransplantation: Pearls and Pitfalls.

Joshua L Chan,Nicole M Shockcor,Philip Corcoran,Avneesh K Singh,Keith A Horvath,Tianshu Zhang,Muhammad M Mohiuddin,Billeta G Lewis,Laura Dichiacchio,David Ayares

doi:10.3389/fcvm.2019.00095

Abstract

Heterotopic cardiac xenotransplantation in the intra-abdominal position has been studied extensively in a pig-to-baboon model to define the optimal donor genetics and immunosuppressive regimen to prevent xenograft rejection. Extensive investigation using this model is a necessary stepping stone toward the development of a life-supporting animal model, with the ultimate goal of demonstrating suitability for clinical cardiac xenotransplantation trials. Aspects of surgical technique, pre- and post-operative care, graft monitoring, and minimization of infectious risk have all required refinement and optimization of heterotopic cardiac xenotransplantation over time. This review details non-immunologic obstacles relevant to this model described by our group and in the literature, as well as strategies that have been developed to address these specific challenges.

Highlights

Heterotopic cardiac xenotransplantation model is widely used to study the immunology of xenograft rejection and to test various immunosuppressive regimens
Multiple challenges affect the successful transplantation of a heterotopic cardiac xenograft
Viral pathogens, such as cytomegalovirus (CMV) herpes simplex virus (HSV) and simian T-cell leukemia virus (STLV) are common in baboons, this has been lessened with the implementation of specific-pathogen-free baboons, early weaning, and serologic screening [6, 7]

Summary

INTRODUCTION

Heterotopic cardiac xenotransplantation model is widely used to study the immunology of xenograft rejection and to test various immunosuppressive regimens. Cefazolin is routinely utilized for bacterial prophylaxis for 1 week following placement of a central venous catheter (Bard Medical, Covington, GA) This line is maintained until the xenograft is explanted to allow for delivery of medications over extended periods of time (e.g., continuous heparin, 2-h infusion of MMF, etc.), access for routine blood draws, or administration of therapies during emergent circumstances. A donor pig of ∼80% of the recipient baboon weight allows enough room for the heart to function without compression at abdominal closure. Xenografts greater than this size ratio frequently resulted in decreased systolic function, abdominal compartment syndrome, and lethal cardiac arrhythmias. Ventricular fibrillation is a potential etiology that could not be excluded on post-mortem exam

CONCLUSIONS

Findings

ETHICS STATEMENT