NITRIC OXIDE IN EXPERIMENTAL SKIN FLAPS

The aim of the present study was (A) to investigate the effect of flap-surgery on nitric oxide synthase (NOS) activity and flap ultrastructure postoperatively and (B) to examine the effect of the NOS-inhibitor N^ω -nitro-L-arginine methyl ester (L-NAME) on skin blood-flow (preoperatively), NOS-activity and flap-survival in an ischemic dorsal flap-model in the rat. Methods： NOS-activity was measured by the conversion of L-arginine to L-citrulline and flap morphology was investigated using transmission electron microscopy. Skin blood-flow was measured using laser doppler technique. Results： (A) Intact skin showed Ca^2+ -dependent but no Ca^2+ -independent NOS-activity. A time-dependent decrease in Ca^2+ -dependent and increase in Ca^2+ -independent NOS-activity was seen in the flaps. Morphological analysis showed signs of endothelial damage and an increase in the number of leucocytes. (B) L-NAME increased the blood-pressure by 72%, decreased the skin blood-flow by 21% and abolished skin Ca^2+ -dependent NOS-activity preoperatively. Finally treatment with L-NAME resulted in a decreased survival of the skin flaps. Conclusion： These findings suggest that (A) ischemia caused by skin-flap surgery leads to (I) endothelial damage and a decrease in Ca^2+ -dependent, possibly endothelium-derived nitric oxide synthase (eNOS) activity and (II) to an induction of Ca^2+ -independent nitric oxide synthase (iNOS) activity. Furthermore (B) L-NAME given preoperatively decreases the blood-flow in skin destined for surgery probably by inhibiting Ca^2+ -dependent NOS in the endothelium. Our findings indicate that NO-production might be critically important for the postoperative survival of skin flaps.