Multiagent pharmacotherapy to enhance skin flap survival: lack of additive effect of nitroglycerin and allopurinol.

Pathological vasospasm and free radical production contribute to skin flap necrosis. This study was undertaken to determine if postoperative combination therapy with the vasodilator nitroglycerin and the anti-free radical agent allopurinol would result in an additive enhancement of skin flap survival in the rat model. Thirty-one Sprague-Dawley rats were randomized into four groups and two cranially based dorsal skin flaps were raised on each rat. Both surgeon and data collector were blinded to treatments and all agents were given postoperatively. Control rats demonstrated 51 +/- 7.4% skin flap survival. Mean flap survival was significantly increased in groups receiving single agent therapy with either transdermal nitroglycerin (63 +/- 12% survival, mean +/- 2 SEM, p < 0.05) or intravenous allopurinol (62 +/- 10% survival, p < 0.01). No additional survival was seen in rats receiving both agents, which displayed 61 +/- 13% survival (p < 0.05, compared with controls). This study provides the first well-controlled demonstration that postoperatively applied transdermal nitroglycerin significantly enhances skin flap survival and includes a discussion of reasons for lack of additive effect of these agents.