The protective effect of azelaic acid 5% and minoxidil 5% combination therapy in reducing skin flap necrosis of rats

Backgound and One important limitation of random pattern skin flap in plastic surgery is the necrosis of distant parts of the flap resulting from ischemia. This effect cause unwanted increase in the costs and hospitalization. Previously, large number of factors has been evaluated to decrease the flap necrosis. In present study we used two drugs. Main reason was their mechanism of action that seems to be similar to preconditioning pathways. Fifty-six male rats were divided into four groups. In two groups 5% minoxidil or 5% azelaic acid were applied topically to the flap area before flap elevation. In some rats of minoxidil treated group, a non selective ATP sensitive potassium channel (KATP) blocker, glibenclamide (0.3mg/kg) was injected i.p. to evaluate the role of this channel in action. In azelaic acid treated rats, some were selected for evaluation of the role of nitric oxide and therefore L-NAME (20 mg/kg), a non-selective iNOS inhibitor, was administered. Seven days after operation, the extent of flap necrosis was calculated. Topical minoxidil or azelaic acid significantly recused necrotic area of skin flap to 42% (P<0.05) and 34% (P<0.01), respectively. Combination of minoxidil and azelaic acid was the most effictive intervantion on reducing of necrotic area to 26%. Glibenclamide abolished protective effect of minoxidil (P<0.001) and L-NAME inhibited the effect of azelaic acid on skin flap survival (P<0.05). Both L-NAME and glibenclamide completely inhibited the effect of combination topical therapy. Present study suggested the role of KATP channels on minoxidil pathway and NO on L-NAME pathway of preserving skin flap survival. It seems that there is an overlap between the two pathways; however precise mechanism remained to be determined.