RESUMO
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 (NO(2)(-)). 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 (NO(2)), 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 NO(2) 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.
Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Óxido Nítrico/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Retalhos Cirúrgicos/irrigação sanguínea , Administração Cutânea , Animais , Ácido Ascórbico/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fluxometria por Laser-Doppler , Masculino , Óxido Nítrico/administração & dosagem , Nitritos/metabolismo , Dióxido de Nitrogênio/metabolismo , Pomadas , Ratos , Ratos Sprague-Dawley , Pele/irrigação sanguíneaRESUMO
The aim of the present study was to examine the effect of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) on skin and flap blood flow, NOS activity and flap survival in an ischaemic dorsal flap model in the rat. Fifty-four rats were used in the study. l-NAME or the inactive enantiomere d-NAME was given intravenously either pre-, per- and postoperatively or only postoperatively. Controls received saline treatment. Blood pressure and skin and flap blood flow were monitored. NOS activity was measured in intact skin before and after l-NAME and d-NAME infusion and in flap tissue 48h postoperatively. Forty-eight hours postoperatively flap survival was determined in all rats. l-NAME treatment caused: (1) a marked attenuation of constitutive Ca(2+) dependent NOS activity in intact skin (p<0.001), (2) an increase in blood pressure (p<0.05), (3) a decrease in blood flow in intact skin and in skin flaps (p<0.05), and (4) a decrease in flap survival (p<0.05). In saline and d-NAME treated animals no change in blood pressure, blood flow or NOS activity in intact skin was noted. In conclusion this study shows that l-NAME attenuates constitutive Ca(2+) dependent NOS activity in intact skin, decreases skin and flap blood flow and decreases the survival of skin flaps. These results indicate that constitutive nitric oxide synthase is important for basal blood flow in skin and flap tissue and for the survival of skin flaps.