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

Teke, Zafer; Sacar, Mustafa; Yenisey, Cigdem; Atalay, A. Ozgur; Bicakci, Tuncay; Erdem, Ergun

doi:10.1016/j.amjsurg.2007.06.025

« Previous Next »The American Journal of Surgery
Volume 195, Issue 6 , Pages 861-873, June 2008

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

Zafer Teke, M.D.
- Department of General Surgery, Pamukkale University, School of Medicine, Denizli, Turkey
- Corresponding author. Tel.: +90-542-2644046; fax: +90-258-2134922.
Mustafa Sacar, M.D.
- Department of Cardiovascular Surgery, Pamukkale University, School of Medicine, Denizli, Turkey
Cigdem Yenisey, Ph.D.
- Department of Biochemistry, Adnan Menderes University, School of Medicine, Aydin, Turkey
A. Ozgur Atalay, M.D.
- Department of General Surgery, Pamukkale University, School of Medicine, Denizli, Turkey
Tuncay Bicakci, M.D.
- Department of Cardiovascular Surgery, Pamukkale University, School of Medicine, Denizli, Turkey
Ergun Erdem, M.D.
- Department of General Surgery, Pamukkale University, School of Medicine, Denizli, Turkey

Received 26 April 2007; received in revised form 1 June 2007 published online 27 March 2008.

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.

Keywords: Activated protein C, Ischemia/reperfusion, Reperfusion injury, Mesenteric ischemia, Acute lung injury, Lung reperfusion injury