A Standardized Approach to Orthotopic (Life-Supporting) Porcine Cardiac Xenotransplantation in a Non-Human Primate Model

Abstract

Abstract There are 5.7 million people in the United States with heart failure, which is life-limiting in 20% of patients.1 While data is most robust in the United States for this cohort, it is known to be a global problem with over 23 million people carrying the diagnosis.1 For end-stage heart failure, many require a heart transplantation, however, there is a shortage in the supply of organ donors. Cardiac xenotransplantation has been proposed to “bridge the gap” in supply for these patients requiring transplantation. Recent pre-clinical success using genetically modified pig donors in baboon recipients has demonstrated survival greater than 6 months.2–5 First-in-human transplantation of a genetically modified pig kidney demonstrated 54 hour rejection-free function when perfused by a deceased human recipient, demonstrating the feasibility of cross-species transplantation and invigorating enthusiasm further to utilize this new organ source for a population that would otherwise die waiting for a human organ.6 While this human study demonstrated proof-of-principle of overcoming hyperacute rejection, further regulatory oversight by Food and Drug Administration (FDA) may be required with pre-clinical trials in large animal models of xenotransplantation with long-term survival. These studies not only require a multi-disciplinary team and expertise in orthotopic transplantation (cardiac surgery, anesthesia and cardiopulmonary bypass), immunology and genetic engineering; but also, specifically handling large animal recipients that cannot communicate their symptoms. Here we detail our approach to pig-to-primate large animal model of orthotopic cardiac xenotransplantation perioperatively and in the months thereafter in long-term surviving animals. We also detail xenograft surveillance methods and common issues that arise in the postoperative period specific to this model and ways to overcome them.