*Purpose: After successful prolongation of cardiac xenograft survival in a heterotopic position, the next step is to evaluate genetically engineered (GE) pig hearts for their ability to support life in the orthotopic position. Perioperative cardiac xenograft dysfunction (PCXD) was described by McGregor et al to be a major barrier to this translation and is characterized by graft dysfunction within 24-48 hours of transplantation. Here we describe the experience of PCXD in our program.

*Methods: Orthotopic transplantation of GE pig hearts was performed in 6 healthy baboons. The pigs were 1-3 galactosidase knockout and had the transgenic expression of human CD46, TBM, EPCR, TFPI and DAF, and CD47. Our established immunosuppression regimen included (Rituxan, CVF, ATG, antiCD40 mAb, MMF) and steroids. The standard technique of organ procurement with cold static preservation was used for all donor’s hearts, with no technical issues in preservation. In one animal ECMO was used to support the recipient. A full clinical transplant team was involved in these experiments and the procedure was performed by skilled transplant surgeons

*Results: A maximal survival of 36 hours was achieved in these experiments. All hearts were weaned from cardiopulmonary bypass with standard dose inotropic and vasopressor support. The cardiac xenografts maintained satisfactory hemodynamics for a few hours and then slowly failed with the increasing requirement of pharmocological support to maintain adequate blood pressure. All recipients’ within 4-6 hours started to develop metabolic acidosis, initially corrected with supplemental bicarbonate, but gradually worsened over a period of time. Supraventricular and ventricular dysrhythmias also occurred frequently and ultimately progressed to cardiac arrest. Histology of the explanted hearts was unremarkable and showed minimal evidence of antibody-mediated rejection.

*Conclusions: Despite excellent surgical technique, uneventful weaning from CPB, and adequate initial function, orthotopic cardiac xenografts slowly fail within 24-48 hours without significant evidence of rejection. Modification of preservation techniques, minimizing donor organ ischemic time and other measures to limit the use of inotropes after reperfusion may reduce the incidence and severity of PCXD.

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