Thrombin Generation and Platelet Activation in a Xenogenic Lung Perfusion Model Determine Survival of GalTKO.hCD46 Lungs

Abstract

Purpose The development of GalTKO pigs with additional expression of hCD46 has contributed to significantly improved outcome of lungs in an ex vivo xenogenic perfusion setting. However, “survival” of those lungs varies from a very early failure to an elective termination after 4h of perfusion. Here we evaluate factors that correlate with early GalTKO.hCD46 lung failure. Methods and Materials 33 transgenic GalTKO.hCD46 pig lungs were perfused with heparinized fresh human blood until failure (by oxygenation or PA flow and pressure criteria) or elective termination at 4h. Based on the survival time, experiments were divided into 3 groups (group 1: survival Results Median survival time was 171’ with 11 lungs surviving Conclusions Results of this analysis demonstrate that intensity of initial coagulation cascade and platelet activation (but not complement activation or anti-non-Gal IgM level) correlates with the outcome of xenogenic lung perfusion. We conclude that targeting coagulation and platelet activation, rather than complement or antibody, are required to improve survival of xenogenic lungs.