The effect of simvastatin on the survival of ischaemic skin flap: an experimental study in rats.

Thrombomodulin (TM) is down-regulated from the vascular endothelial surfaces and corresponds to disturbed dermal blood flow and microthrombus formation in the ischaemic skin flap. We examined the therapeutic potential of simvastatin which up-regulates endothelial cell TM expression and activity in the dorsal ischaemic skin flap model. The study was carried out on 30 rats, divided into three groups. Group 1 was treated with simvastatin at a dose of 5mgkg(-1) day(-1) by intraperitoneal injection. Group 2 was treated with 1mgkg(-1) day(-1) with a phosphate-buffered saline for 7 days. Group 3 was the control group. Tissue blood flow, vascularisation and the survival rate of the skin flaps from each group were compared. The mean surviving area of group 1 was higher than groups 2 and 3 (p<0.05). The blood flow change rate did not decrease in the treatment group in contrast to the control groups at 3cm and 5cm (p<0.05). Microangiography demonstrated decreased flap vascularity in groups 2 and 3. There was no evidence of necrosis or positive peroxidase staining for TM in group 1 at 3cm and 5cm., although it was negative in groups 2 and 3. In this study, it was demonstrated that simvastatin prevented shedding of endothelial TM and contributed to flap survival.