The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025
Early Results of an Infant Model of Orthotopic Cardiac Xenotransplantation.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Mitchell Chace B, Simmons Joe, Hodo Carolyn L, Neal Sarah J, Chitta Sriram, Vo Clementine, Bakshi Kanwarpal, Juliani Julie, Fenske Julie, Cleveland David C, Cleveland John D
Аннотация
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.