Transgenic swine lungs expressing human cd59 are protected from injury in a pig-to-human model of xenotransplantation

AbstractBackground: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate xenotransplantation. Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation. Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections. Results: Mean lung survival for the experimental group was increased when compared with controls, 240 ± 0 minutes versus 35.3 ± 14.5 minutes, respectively, with a P value of less than .01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 ± 87 mm Hg · L–1 · min–1, in contrast to the control group (1579 ± 722 mm Hg · L–1 · min–1; P < .01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 ± 1.41 mL · cm–2 H2O and 4.11 ± 2.84 mL · cm–2 H2O, respectively; P < .01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group. Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation. (J Thorac Cardiovasc Surg 2000;119:690-9

Deep venous thrombosis and pulmonary embolism after lung transplantation

AbstractThe incidence of deep venous thrombosis or pulmonary embolism after lung or heart-lung transplantation has not been well defined. Pulmonary embolism may be of particular concern in the postoperative period owing to an inadequately developed or absent collateral bronchial circulation and potential risk of pulmonary infarction. Fourteen (12.1%) of 116 patients undergoing either lung (n = 87) or heart-lung (n = 29) transplantation developed thromboembolic complications 10 days to 36 months after operation. Deep vein thrombosis developed in nine patients, including three with upper body thrombosis related to indwelling central venous catheters. Seven patients (6%) had pulmonary embolism, and three of them died. Resolution of pulmonary embolism was successfully accomplished by selective pulmonary artery infusion of urokinase in three patients without complications. Our experience indicates that deep vein thrombosis and pulmonary embolism are significant problems after lung transplantation. Mortality is high in those patients in whom pulmonary embolism develops. Therefore, a comprehensive prevention protocol is warranted. (J THORAC CARDIOVASC SURG 1995;110:540-4