Interactions of Cardiopulmonary Bypass and Erythrocyte Transfusion in the Pathogenesis of Pulmonary Dysfunction in Swine

Abstract

Abstract Background: Allogeneic erythrocyte transfusion in cardiac surgical patients is associated with a fourfold increase in pulmonary complications. Our understanding of the processes underlying these observations is poor and there is no experimental model of transfusion-related acute lung injury that shows homology to cardiac surgical patients. Our objective was to develop a novel swine recovery model to determine how two clinical risk factors, allogenic erythrocyte transfusion and cardiopulmonary bypass, interact in the genesis of postcardiac surgery acute lung injury. Methods: Thirty-six pigs were infused with allogeneic 14- or 42-day-old erythrocytes or they underwent cardiopulmonary bypass with or without transfusion of 42-day erythrocyte. Controls received saline. All pigs were recovered and assessed for pulmonary dysfunction, inflammation, and endothelial activation at 24 h. Results: Transfusion of stored allogeneic erythrocytes in pigs compared with sham caused pulmonary dysfunction characterized by reduced lung compliance (mean difference −3.36 [95% CI, −5.31 to −1.42] ml/cm H2O), an increase in protein levels in bronchoalveolar lavage fluid, histological lung injury inflammation, and endothelial activation. Transfusion of blood stored for up to 42 days resulted in greater protein levels in bronchoalveolar lavage fluid, macrophage infiltration, platelet activation, and depletion of T-lymphocytes in recipient lungs versus 14-day-old blood. Transfusion interacted with cardiopulmonary bypass to increase lung injury in the absence of platelet activation. Conclusions: In this novel large animal model of allogeneic erythrocyte transfusion, pulmonary dysfunction occurs in the absence of any priming event, is increased when combined with other inflammatory stimuli, and is mediated by monocyte activation and T-lymphocyte depletion.