Antithrombin III attenuates pulmonary tissue injury caused by mesenteric. ischemia-reperfusion

Background: Mesenteric ischemia-reperfusion (I/R) is a well-known event causing both local and remote organ injuries, including the lungs. Recently, several studies indicated that activated leukocyte-endothelial cell interactions play an important role in the mechanisms of these injuries. As a natural inhibitor of serine proteases, antithrombin was shown previously to attenuate the tissue damage after local I/R in several organ systems. Here, we examined the effects of antithrombin on pulmonary injury after mesenteric I/R. Methods: Wistar albino rats underwent median laparotomy and were randomized into 3. groups: (1) sham-operated control (n = 12), (2) 60 minutes of mesenteric ischemia and 3 hours of reperfusion (n = 12), and (3) antithrombin-pretreated (250 U/kg) group before the I/R (n = 12). At the end of reperfusion, animals were killed and neutrophil sequestration, myeloperoxidase (MPO) activity, and Evans blue dye extravasation in the lung parenchyma were assessed and compared. Results: There was a statistically significant increase in the quantity of Evans blue dye concentration, leukocyte sequestration, and MPO activity in the I/R group when compared with the control group. The pretreatment of animals with antithrombin significantly decreased the pulmonary injury characterized by increased Evans blue dye extravasation, leukocyte sequestration, and MPO activity. Conclusion: The data of the present study suggest that mesenteric ischemia and reperfusion induces pulmonary injury characterized by activated neutrophil sequestration and increased microvascular leakage in the lungs. A-significant attenuation of intestinal I/R-related lung injury with the use of antithrombin concentrate warrants further studies to elucidate the potential role of this natural serine protease inhibitor in clinical settings. (C) 2005 Excerpta Medica Inc. All rights reserved.