Saving the zone of stasis in burns with activated protein C: An experimental study in rats

Salvage of the zone of stasis is a major subject of focus in burn research. Use of various antithrombotic, anti-inflammatory and antioxidant drugs have been studied experimentally, with reports of favourable results; however, none became popular in clinical practice. Activated protein C (APC) is a well-known physiologic anticoagulant. Recent studies revealed that APC contributes not only to systemic anticoagulant activities but also to anti-inflammatory activities by inhibiting leucocyte activation associated with TNF production. The likely favourable effects of APC on salvage of the zone of stasis were investigated on a well-described experimental rat burn model representing the zone of stasis according to the 'burn comb model'. Twenty Sprague-Dawley rats were used and randomly separated into experimental and control groups. Two hours after inducing injury, 100 mu g kg (1) APC (Sigma, Boehringer Ingelheim, Germany) was administered to the experimental group through the caudal vein while 0.9% saline was injected through the same route in the control group. Laser Doppler flowmetry measurements and autoradiography were used for evaluation of perfusion and viability in the zone of stasis. At day 3, the differences between the results obtained from the treatment and the control groups were found to be statistically significant (p < 0.05). Our experimental study revealed that APC improved tissue perfusion and decreased the area of skin necrosis in the zone of stasis in rats. The dual effect of APC, each of which has been shown to be favourable in saving the zone of stasis, may make this agent effective with a single effect in treatment of burn injury. (C) 2009 Elsevier Ltd and ISBI. All rights reserved.