title: Effect of botulinum toxin A on vasoconstriction and sympathetic neurotransmitters in a murine random pattern skin flap model.
abstract: 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.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tai Suk
authors.initials: TS
authors.lastname: Roh
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Bok Ki
authors.identifier: 0000-0002-4347-560X
authors.initials: BK
authors.lastname: Jung
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Insik
authors.initials: I
authors.lastname: Yun
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lew
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007267:Injections; D009478:Neuropeptide Y / Q000032:analysis / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000032:analysis / Q000378:metabolism; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D013524:Surgical Flaps / Q000098:blood supply*; D013566:Sympathomimetics / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D002317:Cardiovascular Agents; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D013566:Sympathomimetics; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019274:Botulinum Toxins, Type A; D009638:Norepinephrine