Early Results of an Infant Model of Orthotopic Cardiac Xenotransplantation

Genetically engineered porcine hearts may have an application for infants in need of a bridge to cardiac allotransplantation. The current animal model that resulted in 2 human applications has been validated in adult non-human primates only. We sought to create an infant animal model of life sustaining cardiac xenotransplantation to understand limitations specific to this age group.

We performed 11 orthotopic cardiac xenotransplants from genetically modified infantile pigs into size-matched baboons (Papio spp). Porcine grafts were preserved using a modified Del Nido solution. Protocolized post-operative care and outcomes were tracked with invasive monitoring, echocardiogram, and serial chemistries (including a 7-cytokine panel).

Mean ischemic time was 52.1 +/- 13.9 min. All porcine hearts separated from bypass in normal sinus rhythm with normal systolic function documented by echocardiogram at chest closure and again at 24 h. In the first 48 post-operative hours, mean vasoactive inotropic score for the recipients was 9.6 +/- 3.5. Survival >3months was achieved in 6 animals. Five animals succumbed early (<7days) either due to errors in care (n=2) or pulmonary complications (n=3) confirmed on chest radiograph and necropsy. Cytokine levels objectively increased following xenograft implant but were not significantly different between survivors and non-survivors.

In a non-human primate model of infant orthotopic cardiac xenotransplantation, cardiac function does not hinder early peri-operative survival. Instead, pulmonary edema and pleural effusions in the setting of systemic inflammation preclude clinical progression. Targeted therapies are necessary to encourage prolonged survival.