Dose-dependent effects of a nitric oxide donor in a rat flap model

Previous studies have proven the effectiveness of nitric oxide (NO) donors to enhance flap survival in experimental models. The purpose of this study was to determine the ideal dose of the NO donor spermine/nitric oxide complex (Sper/NO) with respect to flap survival and hemodynamic side effects. Additionally, the influence of the type of application (systemically versus intra-arterial into the flap artery) was observed.Seventy-two male Wistar rats were divided into 9 experimental groups. An extended epigastric adipocutaneous flap (6 x 10 cm) based on the left superficial epigastric artery and vein was raised in each animal. The average percentage of flap necrosis was 69.8% in the control group with ischemia and 29.8% in the non ischemic controls. The average necrosis areas in the 3 groups after preischemic intravenous (i.v.) application of Sper/NO (250, 500, and 750 nmol/kg body weight) were 63.5%, 33.8%, and 38.4%, respectively. The application of similar doses into the flap artery resulted in 63.5%, 72.3%, and 64.3% flap necrosis; 52.7% average flap loss was observed in an additional group receiving Sper/NO adjusted to flap weight (500 nmol/kg flap weight). Only the intravenous application of 500 and 750 nmol/kg resulted in a significant reduction of flap necrosis compared with the ischemic controls (P < 0.01). The drop in mean arterial pressure was less after i.v. application of 500 nmol/kg Sper/NO compared with 750 nmol. Our data show that the preischemic intravenous application of 500 nmol/kg Sper/NO achieved the best results with acceptable side effects. A dose of 250 nmol/kg i.v., as well as the application of Sper/NO into the flap artery, was demonstrated to be ineffective.