Activated protein C attenuates intestinal reperfusion-induced acute lung injury: an experimental study in a rat model

Abstract

Background: Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. APC has been shown to attenuate local deleterious effects of ischemia/reperfusion (I/R) injury in many organs. We aimed to investigate the effects of APC on lung reperfusion injury induced by superior mesenteric occlusion. Methods: Male Wistar-Albino rats were allocated into 4 groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to group 1 except for APC treatment (n = 12); (3) intestinal I/R group, 60 minutes of ischemia followed by 3 hours of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 µg/kg injection of APC intravenously, 15 minutes before reperfusion (n = 12). Evans blue dye was injected into half of the rats in all groups. We assessed the degree of pulmonary tissue injury by measuring activities of oxidative and antioxidative enzymes, as well as nitrate (NO3-)/nitrite (NO2-) levels, biochemically. We evaluated acute lung injury (ALI) by establishing pulmonary neutrophil sequestration and ALI scoring histopathologically. Pulmonary edema was estimated by using Evans blue dye extravasation and wet/dry ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. Results: APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the lung tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes (P < .05). Pulmonary neutrophil sequestration and ALI scores were decreased significantly with APC administration (P < .05). In addition, APC treatment significantly alleviated pulmonary edema (P < .05). Conclusions: This study clearly showed that APC treatment significantly attenuated the lung reperfusion injury. Further clinical studies are required to clarify whether APC has a useful role in the reperfusion injury during particular surgeries in which I/R-induced organ injury occurs. © 2008 Elsevier Inc. All rights reserved.