Protective Effect of Antithrombin III Against Lung and Myocardial Injury in Lower-Limb Ischemia–Reperfusion Syndrome

Abstract

Restoration of blood flow to an acutely ischemic limb can trigger systemic inflammation. We investigated whether antithrombin III (AT-III) exerts a protective action against remote lung and myocardial injury in an experimental animal model of lower-limb ischemia-reperfusion. Ischemia was induced by lower-limb arterial occlusion for 6 hours in 60 male Wistar rats. Animals were divided into those receiving AT-III (dose, 250 mg/kg) 30 minutes before the reperfusion (group A, n = 30) and those receiving placebo (group B, n = 30). Animals were then sacrificed, and lung and myocardial tissue samples were taken at baseline, 30 minutes, and 4 hours after reperfusion. Levels of malondialdehyde (MDA), a compound used as indirect index of oxygen free radicals, were estimated in lung and myocardium, and the two groups were compared at different time points using the independent sample t test. Animals administered AT-III had significantly lower levels of lung MDA compared with the placebo group at baseline and at 30 minutes, but not at 4 hours (P = 0.001, P = 0.01, and P = 0.9, respectively), indicating a protective action of AT-III against remote lung injury early in the reperfusion phase. With regard to myocardial MDA levels, no statistically significant differences existed between the AT-III and placebo groups at baseline, at 30 minutes, and at 4 hours (P = 0.07, P = 0.07, and P = 0.2, respectively) after reperfusion. In this experimental animal model, AT-III appears to exert a protective effect against remote ischemia-reperfusion injury in the lung tissue, but not in the myocardium.