Research Article: Synergistic Effect of Anemia and Red Blood Cells Transfusion on Inflammation and Lung Injury

Date Published: August 7, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Anping Dong, Manjula Sunkara, Manikandan Panchatcharam, Abdel Salous, Samy Selim, Andrew J. Morris, Susan S. Smyth.

http://doi.org/10.1155/2012/924042

Abstract

Anemia and resultant red blood cell transfusion may be associated with adverse long-term clinical outcomes. To investigate the mechanism(s) responsible, we profiled inflammatory biomarkers and circulating levels of the bioactive lysophospholipid mediator sphingosine-1-phosphate (S1P) in control and anemic mice with or without LPS-induced systemic inflammation. Acute anemia or lipopolysaccharide (LPS) challenge alone triggered an increase of circulating levels of the inflammatory markers IL-6 and keratinocyte-derived chemokine (CXCL1/KC). Moreover, administration of LPS to anemic mice reduced circulating S1P levels and augmented lung injury and pulmonary vascular permeability. Transfusion of aged, but not fresh, red blood cells (RBCs) worsened pulmonary vascular leak. S1P levels decline markedly during storage of mouse RBCs. Loading stored murine RBCs with S1P prior to transfusion partially attenuated anemia-associated acute pulmonary vascular leak. Taken together, our results indicate that anemia and systemic inflammation can alter the S1P buffering capacity of RBCs, suggesting possible strategies for alleviating transfusion-related lung injury in clinical practice.

Partial Text

Blood or packed erythrocytes are commonly administered to individuals with anemia, especially in settings of trauma and critical illness. While acutely lifesaving, transfusions may trigger events that contribute to, rather than prevent, long-term morbidity and mortality [1–4]. In patients with acute respiratory distress and multiorgan failure, red blood cell (RBC) transfusion can promote acute lung injury and may predict mortality. The adverse effects of transfusion are hypothesized to require two “hits”—one relating to inflammatory or additional predisposing condition(s) in the recipient and the second involving alterations in the transfused blood. For the later, the age of the transfused blood may be important, as alterations during storage may occur.

In this study, we investigated the consequences of RBC transfusion in the setting of anemia without or with a systemic inflammatory challenge in mice. Most previous preclinical models have not examined transfusion in the setting of anemia, nor have the consequences of transfusion in the background anemia and inflammation been described. In our model, blood transfusion was performed after blood loss alone, or in combination with an inflammatory challenge, to simulate the two “hits” thought to contribute to adverse effects observed in transfusion recipients. Acute, posthemorrhagic anemia was mimicked in mice by withdrawing ≈20% of the calculated blood volume [9], and systemic inflammation was elicited by injecting LPS (2 mg/kg). We observed that the combination of anemia and LPS administration resulted in higher plasma levels of the inflammatory markers IL-6 and CXCL1/KC than did either challenge alone. Hematocrit improved similarly in anemic mice transfused with fresh or aged RBCs, but plasma IL-6 and CXCL1/KC were higher after transfusion of aged RBCs.

In conclusion, loss of S1P associated with storage of RBCs may contribute to blood transfusion-related pulmonary vascular leak in the setting of acute anemia and systemic inflammation. Transfusion of exogenous S1P-loaded RBCs can partly attenuate acute pulmonary vascular leak. Our findings could have clinically important ramifications for novel therapeutic strategies to predict and prevent for transfusion-related injury.

 

Source:

http://doi.org/10.1155/2012/924042

 

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