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Effect of botulinum toxin A on vasoconstriction and sympathetic neurotransmitters in a murine random pattern skin flap model

 Tai Suk Roh  ;  Bok Ki Jung  ;  Insik Yun  ;  Dae Hyun Lew  ;  Young Seok Kim 
 WOUND REPAIR AND REGENERATION, Vol.25(1) : 75-85, 2017 
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Animals ; Botulinum Toxins, Type A/administration & dosage* ; Cardiovascular Agents/administration & dosage* ; Disease Models, Animal ; Immunohistochemistry ; Injections ; Neuropeptide Y/analysis ; Neuropeptide Y/metabolism ; Neurotransmitter Agents/biosynthesis* ; Nitric Oxide/analysis ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/analysis ; Nitric Oxide Synthase Type III/metabolism ; Norepinephrine/analysis ; Norepinephrine/metabolism ; Rats ; Rats, Sprague-Dawley ; Skin/blood supply ; Skin/drug effects* ; Skin/physiopathology ; Surgical Flaps/blood supply* ; Sympathomimetics/metabolism ; Vasoconstriction/drug effects ; Vasoconstriction/physiology ; Wound Healing/drug effects* ; Wound Healing/physiology
Blood supply is the most important factor determining the survival of a skin flap. Botulinum toxin-A (Botox-A) is used as pharmacologic agent not only for aesthetic purposes, but also for its vasomotor actions. This study was conducted to establish whether local application of Botox-A increased survival of random pattern skin flaps in rats by changing the expression of neurotransmitters. Forty adult Sprague-Dawley rats with a caudally-based random pattern skin flap were divided into two groups: Botox-A group and saline group. Surviving flap area and cutaneous blood flow in the flap were evaluated on postoperative days 3 and 7. After injection of Botox-A, changes in vessels were analyzed using immunohistochemical staining. Levels of norepinephrine, neuropeptide-Y, nitric oxide, and endothelial nitric oxide synthase were analyzed quantitatively by high performance liquid chromatography, Western blot, and colorimetric assay. The survived area in the Botox-A group was significantly higher than that in the control group on postoperative days 3 and 7. Blood flow in the Botox-A group was significantly high in the proximal and middle areas immediately after the operation. The number of CD31-positive vessels in the Botox-A group was significant greater than that in the control group. Norepinephrine level in the Botox-A group decreased significantly immediately after flap elevation and at postoperative day 3. There were no significant differences in neuropeptide-Y level between the two groups. Nitric oxide level did not change significantly in either group despite the increase in endothelial nitric oxide synthase immediately after flap elevation and at 3 days postoperatively. In conclusion, Botox-A increased vascular blood flow and viable flap area in rats by reducing norepinephrine level. In contrast, neuropeptide-Y, another vasoconstrictor, was not affected by Botox-A. Nitric oxide, a vasodilator, was also not affected by Botox-A, despite the significant increase in endothelial nitric oxide synthase expression in the flaps.
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1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Young Seok(김영석) ORCID logo https://orcid.org/0000-0002-0981-2107
Roh, Tai Suk(노태석) ORCID logo https://orcid.org/0000-0001-8681-159X
Lew, Dae Hyun(유대현)
Yun, In Sik(윤인식) ORCID logo https://orcid.org/0000-0003-1103-7047
Jung, Bok Ki(정복기) ORCID logo https://orcid.org/0000-0002-4347-560X
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