Dexamethasone increases survival and attenuates induction of inducible nitric oxide synthase in experimental skin flaps.

The molecule nitric oxide synthesized by the enzyme nitric oxide synthase (NOS) has been shown to be of major physiological and pathophysiological importance in the body. During ischemia and reperfusion, induction of free ionic calcium (Ca2+)-independent inducible NOS (iNOS) is thought to result in an overproduction of NO, leading to tissue damage. The glucocorticoid dexamethasone is known to inhibit the induction of iNOS, and the aim of the current study was to determine the effect of dexamethasone on viability and NOS activity in an ischemic flap model on the dorsum of the rat. Vehicle (N = 20) or dexamethasone (N = 20) was administered 3 hours prior to operation. The surviving area was measured and the flaps were removed after 24 hours for 10 rats in each group and after 48 hours for the remaining 10 rats in each group. Treatment with dexamethasone resulted in an improved flap viability at both 24 hours (p < 0.001) and 48 hours (p < 0.01), and a reduced induction of Ca2+-independent NOS activity in the proximal part of the flaps at 24 hours (p < 0.001). In the current study the authors show that dexamethasone attenuates the induction of Ca2+-independent NOS and increases survival in experimental skin flaps.