Advances in clinical immunosuppression and characterization of optimal donor genetics continue to move the field of xenotransplantation toward a clinical reality with extremely long-term survival being achieved in heterotopic cardiac xenotransplants. Orthotopic life-supporting models for cardiac xenografts are being developed with the major barrier being significant peri-operative mortality. Here we describe the technical and practical aspects of the development of an orthotopic pig-to-baboon cardiac xenotransplant model.

Specific pathogen free baboons were transplanted with GTKO.CD46 donor pig hearts in the orthotopic position (n = 4) by cardiac transplant and congenital cardiac surgeons. The clinical team also included a perfusionist, cardiac anesthesiologist, cardiac critical care nurse, and surgical residents. These baboons were recovered from prior experiments and per institutional protocol were approved for non-survival studies; cases were performed with intended short term survival under anesthesia followed by elective euthanasia. All recipient baboons were transplanted and weaned off of cardiopulmonary bypass with life sustaining cardiac function. Low dose inotropic support was continued in all cases; vasopressor support was continued in two cases. Two cases were electively terminated after wean from bypass; one recipient suffered arrest three hours post wean from bypass; and one case was electively terminated after overnight (18 hour) survival for histology. Recipients were monitored using femoral arterial lines, transesophageal echocardiogram, external EKG, continuous pulse oximetry, and serial bloodwork including ABG, CBC, BMP, and ACT. Invasive hemodynamic monitoring, pretreatment with anti-arrhythmics, and availability of cardioversion for the donor pig allowed rapid reversal of fibrillation episodes during procurement. Atrial and ventricular pacing wires proved integral to the cardiopulmonary bypass weaning process for the recipient baboon. Ideal cold ischemia time was found to be close to one hour; shorter ischemia time resulted in poorer xenograft function (n = 1) as evidenced by difficult wean from bypass and persistent need for vasopressor support.

CITATION INFORMATION: DiChiacchio L., Singh A., Lewis B., Strauss E., Odonkor P., Williams B., Ayares D., Deatrick K., Kon Z., Mohiuddin M. Experience in the Development of a Life-Supporting Large Animal Orthotopic Cardiac Xenotransplant Model Am J Transplant. 2017;17 (suppl 3).

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