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 right lower limb arterial occlusion for 4 hours in 60 male Wistar rats. Animals were divided into those receiving AT III (dose 250mg/kg, Kybernin P; Aventis Behring GmbH) 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. Malondialdehyde (MDA) levels, a compound used as indirect index of oxygen free radicals which play a significant role in the pathogenesis of ischemia-reperfusion syndrome, were estimated in lung and myocardium and the two groups were compared at different time points using the independent sample t-test.
Animals given AT III had significantly lower lung MDA levels comparing 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 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).
In this experimental animal model, AT III seems to exert a protective effect against remote ischemia-reperfusion injury in the lung tissue but not in the myocardium.
AT III may prove to be of clinical benefit in attenuating remote lung injury in ischemia-reperfusion syndrome. Further experimental and clinical studies are warranted.
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