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Open Access Novel H-shunt Venovenous Bypass for Liver Transplantation in Cynomolgus Macaques

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Cynomolgus monkeys are often used in preclinical transplantation research. Performing liver transplantation in cynomolgus monkeys is challenging because they poorly tolerate portal vein clamping during the anhepatic phase. Finding an alternative to portal vein clamping is necessary before preclinical liver transplant models can be performed with reliable outcomes. We used 3 different techniques to perform 5 liver transplants in male cynomolgus macaques (weight, 7.4–10.8 kg; mismatched for MHC I and II; matched for ABO). In procedure A, we clamped the portal vein briefly, as in human transplants, as well as the superior mesentery artery to minimize congestion at the expense of temporary ischemia (n = 2). In procedure B, we performed a temporary portocaval shunt with extracorporeal venovenous bypass (n = 1). For procedure C, we developed an H-shunt system (modified portocaval shunt) with extracorporeal bypass (n = 2). Postoperative immunosuppression comprised cyclosporine A, mycophenolate mofetil, and steroids. Recipients in procedure A developed hemodynamic instability and were euthanized within 2 d. The recipient that underwent procedure B was euthanized within 11 d due to inferior vena caval thrombosis. The H-shunt in procedure C led to minimal PV congestion during the anhepatic phase, and both recipients reached the 21-d survival endpoint with good graft function. Our novel H-shunt bypass system resulted in successful liver transplantation in cynomolgus macaques, with long-term posttransplant survival possible. This technical innovation makes possible the use of cynomolgus monkeys for preclinical liver transplant tolerance models.
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Document Type: Research Article

Affiliations: 1: Departments of Surgery, Columbia Center for Translational Immunology, College of Physicians and Surgeons, Columbia University, New York, New York 2: Columbia Center for Translational Immunology, College of Physicians and Surgeons, Columbia University, New York, New York 3: Departments of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York 4: Institute of Comparative Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 5: Departments of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 6: Departments of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York;, Email: [email protected]

Publication date: October 1, 2017

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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