Sumatriptan Increases Skin Flap Survival through Activation of 5-Hydroxytryptamine 1b/1d Receptors in Rats: The Mediating Role of the Nitric Oxide Pathway

Amir Dehdashtian, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Khashayar Afshari, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Seyedeh Zarifeh Jazaeri, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Nazgol-Sadat Haddadi, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Mehdi Sheikhi, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Ali Abbaszadeh-Kasbi, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Seyed Mohammad Tavangar, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Farahnaz Jazaeri, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Bardia Amirlak, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.
Ahmad Reza Dehpour, From the School of Medicine, the Experimental Medicine Research Center, School of Public Health, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, the Department of Pathology, Dr. Shariati Hospital, and the Department of Pharmacology, Tehran University of Medical Sciences; and the Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center.

Document Type

Article

Publication Title

Plastic and reconstructive surgery

Abstract

BACKGROUND: Random pattern skin flaps are applicable for reconstructing any defect in plastic surgery. However, they are difficult to apply because of necrosis. Sumatriptan, a selective 5-hydroxytryptamine 1b/1d agonist, is routinely used to offset acute migraine attacks. Recent studies have suggested that sumatriptan may induce vasodilation at lower concentrations. The authors' aim is to investigate the effect of sumatriptan on skin flap survival and the role of nitric oxide in this phenomenon. METHODS: Seventy-two male Sprague-Dawley rats were divided into eight groups. Increasing doses of sumatriptan (0.1, 0.3, and 1 mg/kg) were given intraperitoneally to three different groups after dorsal random pattern skin flaps were performed. To assess the exact role of 5-hydroxytryptamine 1b/1d receptors, GR-127935 was administered solely and with sumatriptan. N-ω-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used to evaluate any possible involvement of nitric oxide in this study. All rats were examined 7 days later. RESULTS: The authors' results demonstrated that flap survival was increased by lower doses of sumatriptan compared to a control group for both 0.3 mg/kg (p = 0.03, mean difference = 32, SE = 8) and 0.1 mg/kg (p = 0.02, mean difference = 26, SE = 8). This protective effect was eliminated by coadministration of GR-127935 or N-ω-nitro-L-arginine methyl ester with sumatriptan. Histopathologic studies revealed a significant increase in capillary count and collagen deposition and a decreased amount of edema, inflammation, and degeneration. CONCLUSIONS: Sumatriptan in lower concentration increases skin flap survival by means of activation of 5-hydroxytryptamine 1b/1d receptors. This effect is mediated through the nitric oxide synthase pathway.

First Page

70e

Last Page

77e

DOI

10.1097/PRS.0000000000005740

Publication Date

7-1-2019

Identifier

31246821 (pubmed); 10.1097/PRS.0000000000005740 (doi); 00006534-201907000-00033 (pii)

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