A Transient Inflammatory Reaction in the Lung After Experimental Hemorrhagic Shock and Resuscitation With a Hemoglobin-Vesicles Solution Compared With Rat RBC Transfusion

Abstract

Transfusion for hemorrhagic shock can improve oxygenation, but immunoreactions may induce inflammation. Artificial oxygen carriers have been developed to address clinical concerns of infection and stability, but whether an artificial oxygen carrier might induce inflammation is not well known. To address this question, we compared inflammatory reactions after resuscitation with hemoglobin vesicles (HbVs) or red blood cells (RBCs) in a hemorrhagic shock rat model. Both HbVs and the stored and irradiated rat RBCs deprived of buffy coat were suspended in recombinant human serum albumin [(Hb) = 8.6 g/dL]. Under anesthesia, hemorrhagic shock was induced for 30 min, followed by resuscitation by 20 min transfusion of HbVs or rat RBCs in a volume equivalent to the volume of withdrawn blood. Lungs were excised 2 or 24 h after resuscitation, and mRNA levels of tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), nitric oxide synthase 2 (iNOS), nitric oxide synthase 3, hypoxia-inducible factor 1 alpha, and heme oxygenase 1 (HO-1) were measured. In rats resuscitated with HbVs, mRNA levels of TNF-alpha and HO-1 2 h after resuscitation were significantly higher than those in the rat RBC group, but the levels at 24 h were similar in both groups. The expression of iNOS and ICAM-1, second messengers of inflammation, was not affected, and inflammatory levels after 24 h with HbVs are similar to rat RBC transfusion. The rat RBC group did not show an expected inflammatory reaction related to a transfusion-induced lung injury, and a clinical relevance concerning this level of transient inflammatory reaction induced by HbVs is not known; however, attention to the early stage of resuscitation in ongoing studies of HbV is required.