Effect of Botulinum Toxin A and Nitroglycerin on Random Skin Flap Survival in Rats

T he random skin flap (RSF) is a type of flap that has no discrete blood vessels.Consequently, RSFs are dependent on different microvascular plexuses for their metabolic needs; thus, RSFs are prone to ischemic injury (1).In normal conditions, skin blood flow is mainly regulated by the neural input; however, in the case of a skin flap, humoral vasoactive substances, such as nitric oxide (NO), also play an important role (2).In the immediate aftermath of flap elevation, local loss of sympathetic input, coupled with the unchallenged activity of humoral vasoconstrictors, leads to an ischemic state in RSFs, which is most pronounced during the first 6 h to 12 h postoperatively (3).This ischemic state is normally reversed after day 3.However, if necrosis follows the ischemic insult, the process would be irreversible and flap failure ensues.Such a scenario is encountered especially when the length-to-width ratio of the RSF is increased (2-4).Based on the donor site, RSFs with length-to-width ratios >2:1 to 3:1 will usually fail to some extent due to ischemia in the absence of additional interventions such as delay procedures (5).Delay techniques are devised to facilitate the adaptation of the RSFs to the ischemic environment.Surgical delay procedures are currently the gold standard for such techniques; however, they have some drawbacks.Notably, ≥1 surgical stage(s) are needed before the main procedure can be performed (6).Many pharmacological and physical therapies have been investigated to mimic the effects of surgical delay.Some agents have shown promising results in RSFs and other types of skin flaps, as well as in ischemic conditions such as chronic anal fissure.Experiments using botulinum toxin type A (BTX-A) and NO donors, such as nitroglycerin, resulted in interesting outcomes in a variety of ischemic conditions such as RSFs and chronic anal fissures (2,7,8).Furthermore, one study reported a synergistic effect between BTX-A and nitroglycerin in chronic anal fissure, which is a well established ischemic condition (9).Although ischemia is also considered to be the pathophysiological process in the failure of RSFs, no study has investigated a possible synergistic or additive effect between BTX-A and nitroglycerin in this regard.Therefore, the purpose of the present study was to investigate the effects of nitroglycerin, BTX-A and their combination on the survival of RSFs.