Background: Although interest in flap surgery has increased, a satisfactory research study on supportive drugs or methods for flap surgery has not been seen in the literature thus far. Despite several studies using botulinum toxin A for flap surgery being reported, their efforts to clarify the mechanisms are not sufficient. Therefore, the authors have studied the effect of botulinum toxin A on random cutaneous flap survival in a rat model under the hypothesis that it affects the microvascular system.
Method: Thirty 10-week-old Sprague-Dawley rats were divided into experimental (n=15) and control groups (n=15). The experimental group used 1.5 IU (International Units) of botulinum toxin A, and the control group used normal saline. A 2x8 cm random cutaneous flap was designed on the rats and then elevated. Normal saline (0.05 cc) and 1.5 IU of botulinum toxin A (0.05 cc) (Botox, Allergan, USA) were injected into the dermis layer of the central portion in the proximal one-third of the flap. Gross photographs were taken at days 1, 3, 5 and 7 after the operation. Laser-induced fluorescein fluoroscopy was performed on postoperative day 7 and tissues were retrieved for histological analysis. In addition, reverse transcriptase polymerase chain reaction (RT-PCR) was carried out for quantitative analysis.
Results: Gross photos and laser-induced fluorescein fluoroscopy reveal the survival rate of the Botox group was 8.3% higher than the control. In the histologic study, the diameter of vessels is larger and the number of immature vessels is more in the Botox group. The result of RT-PCR shows increased expression of VEGF (vascular endothelial growth factor), CD 31 (PECAM1, platelet/endothelial cell adhesion molecule) and iNOS (inducible nitric oxide synthase), which are considered to be related to vasodilation and endothelial proliferation.
Conclusion: Our results suggest that botulinum toxin A increases the survival rate of random cutaneous flaps by means of selective suppression of sympathetic neurons of the cutaneous microcirculation system.