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 discordant hepatic and renal xenotransplantation is complicated by a pulmonary injury. The aim of this study was to characterize the nature of this injury, as well as to determine whether endothelin-1 (ET-1) and inducible-nitric oxide synthase (iNOS) are present in this form of pulmonary injury. Dog-to-pig orthotopic liver and kidney xenografts were performed. Pulmonary artery pressures were monitored throughout all procedures. The lungs were stained with monoclonal antibodies for ET-1, endothelin converting enzyme-1, and iNOS. The lungs from pig recipients of hepatic or renal xenografts were compared to lungs from untreated pigs. Pulmonary artery pressures were elevated in recipients of liver xenografts when the suprahepatic caval cross clamp was placed and continued to rise to systolic levels following unclamping. The mean pulmonary artery pressures in recipients of renal and hepatic xenografts rose significantly following revascularization. Pathology in lungs from kidney and liver recipients was similar, showing congestion with peribronchial and septal edema, with diffuse adhesion of PMN to alveolar endothelium. ET-1, endothelin converting enzyme-1 (ECE-1), and iNOS staining was widespread and intense in alveolar and pulmonary arterial endothelium. Discordant xenotransplantation of livers and kidneys is associated with a significant early pulmonary injury that is associated with early PMN infiltration and expression of ET-1 and iNOS.