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Sumatriptan increase skin flap survival through activation of 5HT 1b/1d receptors in rats

the mediating role of nitric oxide pathway

Dehdashtian, Amir1,2,3; Afshari, Khashayar1,2,3; Jazaeri, Seyedeh Zarifeh1; Haddadi, Nazgol-Sadat1,2,3; Sheikhi, Mehdi1,2,3; Abbaszadeh-Kasbi, Ali1; Tavangar, Seyed Mohammad4,5; Jazaeri, Farahnaz7; Amirlak, Bardia6; Dehpour, Ahmad Reza2,6,*

Plastic and Reconstructive Surgery: April 11, 2019 - Volume PRS Online First - Issue - p
doi: 10.1097/PRS.0000000000005740
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Background: Random pattern skin flaps are applicable to reconstruct any defects in plastic surgery. However, they are limited to apply due to necrosis. Sumatriptan, a selective 5HT 1b/1d agonist, routinely use to subset acute migraine attack. Recent studies suggested Sumatriptan may induce vasodilation in lower concentration. Our aim is to investigate the effect of sumatriptan on skin flap survival and the role of nitric oxide in this phenomenon.

Methods: Seventy-two Sprague-Dawley male rats were divided into 8 groups. Increasing doses of Sumatriptan (0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg) was given intraperitoneally to three different groups after performing dorsal random pattern skin flap. To assess the exact role of 5HT 1b/1d receptors, GR127935 was administered solely and with sumatriptan. L-NAME (non-selective NOS inhibitor) has been used to evaluate any possible involvement of NO in this study. All the rats were examined 7 days later.

Results: Our results demonstrated that flap survival has been increased by lower doses of sumatriptan comparing to control group (P = 0.03, Mean Difference = 32, SE = 8 for 0.3 mg/kg, and P = 0.02, Mean Difference = 26, SE = 8 n; for 0.1 mg/kg). This protective effect was vanished by co-administration of GR127935 or L-NAME with sumatriptan. Histopathologic studies revealed, a significant increase in capillary count and collagen deposition, while the decreased amount of edema, inflammation, and degeneration.

Conclusion: Sumatriptan in lower concentration increases the skin flap survival via activation of 5HT 1b/1d receptors. This effect is mediated through nitric oxide synthase pathway.

1 School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

3 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

4 Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

5 Professor of Pathology, Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

6 Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center, Dallas, Texas

7 Professor of Pharmacology, Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran

©2019American Society of Plastic Surgeons