Congenital Heart Surgeons' Society

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Perioperative Cardiac Xenograft Dysfunction After Orthotopic Transplantation
Kristopher B. Deatrick, MD, Sunjay Kaushal, MD PhD, Muhammad Mohiuddin, MD, Bartley Griffith, MD.
University of Maryland, Baltimore, MD, USA.

Objective(s): The shortage of donor hearts for infants remains critical. Prolonged graft survival following heterotopic transplant of genetically engineered (GE) porcine cardiac xenografts has been reported, but survival of orthotopic cardiac xenografts remains unproven. A major barrier to this advance is perioperative cardiac xenograft dysfunction (PCXD) characterized by graft dysfunction within 24-48 hours of transplantation.
Methods:
Orthotopic transplantation of GE pig hearts was performed in 7 healthy baboons. The genes modified included 1-3 galactosidase knockout with multiple combinations of transgenic expression of human CD46, TBM, EPCR, TFPI, DAF, and CD47. Our established immunosuppression (IS) regime (Rituxan, CVF, ATG, anti-CD40 antibody, MMF and steroids) was used. Cold static preservation was used for all donor hearts, with no technical issues in preservation.
Results:
Graft ischemic times were under 60 minutes. All recipients weaned from cardiopulmonary bypass but survived for fewer than 48 hours with standard inotropic and vasopressor support. Satisfactory hemodynamics were maintained for up to 36 hrs, but slowly failed with increasing inotropic and vasopressor support. Dysrhythmias were frequent and ultimately progressed to cardiac arrest. In three recipients, function was maintained for 24 hours without inotropic support. Histology of the explanted hearts was unremarkable and showed minimal evidence of antibody-mediated rejection.
Conclusions:
Despite excellent surgical technique, preservation, 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, avoiding allogeneic blood transfusion and other measures may be necessary to reduce the incidence and severity of PCXD.