Transdermally administered nitric oxide by application of acidified nitrite increases blood flow in rat epigastric island skin flaps

Surgical flaps are commonly used in the reconstruction of tissue defects after tumour surgery and trauma. Flap failure continues to be a clinical problem and the underlying causes are not fully understood. In the present study a system that generates nitric oxide (NO) in a non-enzymatic fashion was created through the acidification with vitamin C of a cream containing increasing concentrations (0.125%, 0.25%, 0.5%, 1.25% and 2.5%) of nitrite (NO₂^-). The cream was applied for 30 min to a modified epigastric island skin flap in the rat. Blood flow in the supplying artery was measured by transit-time ultrasound flowmetry throughout the experiment and superficial skin blood flow was measured by laser Doppler perfusion imaging before and after treatment. Mean arterial blood pressure was also monitored. NO and the gas nitrogen dioxide (NO₂), which is formed when NO reacts with atmospheric oxygen, were measured above the cream using chemiluminescence. In flaps treated with the NO generating cream, a concentration-dependent increase in blood flow in the supplying artery and flap skin of up to 130% was observed. Cream base alone or cream base acidified with vitamin C had no effect on blood flow. Also, concentration-dependent formation of both NO and NO₂ was seen. NO increases both supplying artery blood flow and superficial cutaneous blood flow in an epigastric island skin flap model in the rat indicating that NO is of importance in flap physiology and possibly also for flap survival.