Pulmonary injury in recipients of discordant hepatic and renal xenografts in the dog‐to‐pig model

Abstract

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.

Thrombocytopenia after pig‐to‐baboon liver xenotransplantation: where do platelets go?

“…In studies by Tector et al. in a dog‐to‐pig liver xenotransplantation model [16–18], profound thrombocytopenia was observed within minutes following xenograft reperfusion. No sequestration of platelets was observed in the livers, but examination for phagocytes by the LSEC was not carried out, e.g.…”

Aberrations in hemostasis and coagulation in untreated discordant hepatic xenotransplantation: Studies in the dog-to-pig model

“…Lungs of untreated recipients of liver xenografts have areas of hemorrhage and thrombosis. 31 It is possible that platelets are sequestered in the lungs, rather than livers, of recipients. An alternative explanation to account for the lack of platelets in the liver is that the liver xenograft could liberate a substance that prevents platelet adherence or aggregation on the endothelial surface.…”

Prolonged Function of Macrophage, von Willebrand Factor-Deficient Porcine Pulmonary Xenografts

“…In acute lung injury and some xenotransplant models, evidence suggest PIMs may contribute significantly to the rapid development of pulmonary hypertension and edema (24,26,30).…”