PULMONARY INJURY IN RECIPIENTS OF DISCORDANT HEPATIC AND RENAL XENOGRAFTS IN THE DOG-TO-PIG MODEL

Work in our lab demonstrated that the early post-operative course of d iscordant hepatic and renal xenotransplantation is complicated by a pu lmonary injury. The aim of this study was to characterize the nature o f this injury, as well as to determine whether endothelin-1 (ET-1) and inducible-nitric oxide synthase (iNOS) are present in this form of pu lmonary injury. Dog-to-pig orthotopic liver and kidney xenografts were performed. Pulmonary artery pressures were monitored throughout ail p rocedures. The lungs were stained with monoclonal antibodies for ET-1, endothelin converting enzyme-1, and iNOS. The lungs from pig recipien ts of hepatic or renal xenografts were compared to lungs from untreate d pigs. Pulmonary artery pressures were elevated in recipients of live r xenografts when the suprahepatic caval cross clamp was placed and co ntinued to rise to systolic levels following unclamping. The mean pulm onary artery pressures in recipients of renal and hepatic xenografts r ose significantly following revascularization. Pathology in lungs from kidney and liver recipients was similar, showing congestion with peri bronchial and septal edema, with diffuse adhesion of PMN to alveolar e ndothelium. ET-1, endothelin converting enzyme-1 (ECE-1), and iNOS sta ining was widespread and intense in alveolar and pulmonary arterial en dothelium. Discordant xenotransplantation of livers and kidneys is ass ociated with a significant early pulmonary injury that is associated w ith early PMN infiltration and expression of ET-1 and iNOS.