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

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 H 2 O), 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. What We Already Know about This Topic• Transfusion of allogeneic erythrocytes increases the risk of pulmonary morbidity postcardiac surgery.• Using a novel in vivo porcine model of pulmonary dysfunction, this study determined whether (1) the transfusion of older erythrocytes would cause greater pulmonary dysfunction compared with younger erythrocytes; and (2) erythrocyte transfusion would interact with cardiopulmonary bypass to increase the severity of pulmonary dysfunction. What This Article Tells Us That Is New• Allogeneic erythrocyte transfusion of older erythrocytes causes pulmonary dysfunction, which is characterized by marked neutrophil/macrophage infiltration. Moreover, transfusion interacted with cardiopulmonary bypass to increase lung injury.

How do you solve a problem like transfusion‐related acute lung injury?

“…Hence, the true risk of non‐antibody‐mediated TRALI may have been under‐appreciated. In contrast, data from various animal models have demonstrated a clear association between the transfusion of older PRBC and platelet products, with pulmonary dysfunction and the development of TRALI (Table ) .…”

“…Microparticles (MPs) have also been identified as potential BRMs which accumulate in both platelet and PRBC units during routine storage . The effect of BRMs from stored blood products has been demonstrated through in vitro models as well as small and large animal models, which have been summarized in Table .…”

Lessons from sheep models of transfusion

“…Comparison of animals commonly used to model transfusion against humans. (Adapted from Simonova et al[19])[2,[13][14][15][16][18][19][20][21][22][23] …”

Diagnostic and therapeutic medical devices for safer blood management in cardiac surgery: systematic reviews, observational studies and randomised controlled trials

“…33 Experimental studies have shown that these changes cause inflammatory organ injury through complex mechanisms including platelet and monocyte activation, endothelial injury and oxidative stress and the loss of microcirculatory autoregulation. [255][256][257][258] This results in paradoxical tissue hypoxia, despite apparently adequate oxygen delivery, tissue inflammation and organ dysfunction. The most important change that occurs in stored red cells over time is the depletion of high-energy phosphates.…”