Facial Plast Surg 2016; 32(04): 431-437
DOI: 10.1055/s-0036-1584948
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Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluation of the Effect of Bosentan-Mediated Endothelin Receptor Blockade on Flap Survival in Rats: An Experimental Study

Tahsin Görgülü
1   Department of Plastic, Reconstructive and Aesthetic Surgery, Bulent Ecevit University, Zonguldak, Turkey
,
Ramazan Guler
1   Department of Plastic, Reconstructive and Aesthetic Surgery, Bulent Ecevit University, Zonguldak, Turkey
,
Abdulkerim Olgun
1   Department of Plastic, Reconstructive and Aesthetic Surgery, Bulent Ecevit University, Zonguldak, Turkey
,
Merve Torun
1   Department of Plastic, Reconstructive and Aesthetic Surgery, Bulent Ecevit University, Zonguldak, Turkey
,
Eksal Kargi
1   Department of Plastic, Reconstructive and Aesthetic Surgery, Bulent Ecevit University, Zonguldak, Turkey
› Author Affiliations
Further Information

Publication History

Publication Date:
05 August 2016 (online)

Abstract

Local skin flaps are important tools for performing plastic surgery. Skin flaps are used for closure of defects after tumor excision or in tissue losses after trauma. However, problems associated with these flaps are commonly encountered, particularly in areas of marginal necrosis. Bosentan is a vasodilator that exerts its effect through endothelin receptor blockade, and has been shown to prevent ischemic tissue damage. However, no reports have addressed the effect of bosentan on skin flaps. The aim of the study was to investigate the effects of bosentan, which may be applied clinically to promote survival of ischemic skin flaps. A modified McFarlane flap was elevated in the dorsum of 20 Albino Wistar rats with a width-to-length ratio of 3 to 10 cm, respectively, with the caudal base. Perioperatively, 0.9% of physiologic NaCl and injectable distilled water of identical volume were injected into rats in Group 1 (n = 10), and 5 mg/kg bosentan was injected intraperitoneally into rats in Group 2 (n = 10). All of the rats were followed up for 7 days postoperatively. The surviving parts of the flaps were measured at the end of day 7. Acute and chronic inflammation, amount of granulation tissue, fibroblast maturation, amount of collagen, and amounts of reepithelialization and neovascularization present in the ischemic zones of the distal parts of the flaps were evaluated histopathologically, and results were compared statistically. The mean flap survivals were 61.1% in Group 1 and 91.1% in Group 2; the percentage of the surviving flap area in Group 2 was higher than that in Group 1 (p < 0.005). In both groups, there was significantly less acute inflammation in the ischemic zones in Group 2 than in Group 1 (p < 0.005). No significant difference was found in the amounts of chronic inflammation and granulation tissue between the two groups (p > 0.005). Fibroblast maturation, amount of collagen, and amounts of reepithelialization and neovascularization investigated in Group 2 were statistically significantly higher than those in Group 1 (p < 0.005). We believe that bosentan may be used prophylactically to increase survival in risky skin flaps because it decreases ischemic necrosis distal to skin flaps, thus exerting favorable effects on flap survival.

 
  • References

  • 1 Vedder NB. Flap Physiology. In: Mathes SJ, ed. Mathes Plastic Surgery. 2nd ed. Philadelphia, PA: Saunders Elsevier; 2006: 483-506
  • 2 Vedder NB, Bucky LP, Richey NL, Winn RK, May Jr JW. Improved survival rates of random flaps in rabbits with a monoclonal antibody that blocks leukocyte adherence. Plast Reconstr Surg 1994; 93 (5) 1035-1040
  • 3 Angel MF, Ramasastry SS, Swartz WM, Basford RE, Futrell JW. Free radicals: basic concepts concerning their chemistry, pathophysiology, and relevance to plastic surgery. Plast Reconstr Surg 1987; 79 (6) 990-997
  • 4 Nathanson SE, Jackson RT. Blood flow measurements in skin flaps. Arch Otolaryngol 1975; 101 (6) 354-357
  • 5 Hosnuter M, Babucçu O, Kargi E, Altinyazar C. Dual preconditioning: effects of pharmacological plus ischemic preconditioning on skin flap survival. Ann Plast Surg 2003; 50 (4) 398-402
  • 6 Matsuzaki K. Effect of skin flap ischemia on plasma endothelin-1 levels. Ann Plast Surg 1993; 31 (6) 499-503
  • 7 Tane N, Inoue H, Aihara M, Ishida H. The effects of endothelin-1 on flap necrosis. Ann Plast Surg 1995; 35 (4) 389-395
  • 8 Kayaalp SO. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. 12th ed. Ankara: Pelikan Kitabevi; 2009
  • 9 Cetinkaya Z, Esen K, Ozercan IH, Ustundag B, Ayten R, Aygen E. The effect of Bosentan on healing of colonic anastomosis. World J Emerg Surg 2006; 1: 37
  • 10 Taniguchi T, Asano Y, Hatano M , et al. Effects of bosentan on nondigital ulcers in patients with systemic sclerosis. Br J Dermatol 2012; 166 (2) 417-421
  • 11 De Haro J, Acin F, Bleda S, Varela C, Esparza L. Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan. BMC Cardiovasc Disord 2012; 12: 5
  • 12 Botzoris V, Drosos AA. Management of Raynaud's phenomenon and digital ulcers in systemic sclerosis. Joint Bone Spine 2011; 78 (4) 341-346
  • 13 Fevang J, Ovrebø K, Myking O, Grong K, Svanes K. Role of endothelin in the circulatory changes associated with small bowel strangulation obstruction in pigs: effects of the endothelin receptor antagonist bosentan. J Surg Res 2001; 96 (2) 224-232
  • 14 Ellis H. The cause and prevention of postoperative intraperitoneal adhesions. Surg Gynecol Obstet 1971; 133 (3) 497-511
  • 15 Hammond DC, Brooksher RD, Mann RJ, Beernink JH. The dorsal skin-flap model in the rat: factors influencing survival. Plast Reconstr Surg 1993; 91 (2) 316-321
  • 16 Kryger Z, Zhang F, Dogan T, Cheng C, Lineaweaver WC, Buncke HJ. The effects of VEGF on survival of a random flap in the rat: examination of various routes of administration. Br J Plast Surg 2000; 53 (3) 234-239
  • 17 Abramov Y, Golden B, Sullivan M , et al. Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model. Wound Repair Regen 2007; 15 (1) 80-86
  • 18 Olivas TP, Saylor TF, Wong HP, Stephenson LL, Zamboni WA. Timing of microcirculatory injury from ischemia reperfusion. Plast Reconstr Surg 2001; 107 (3) 785-788
  • 19 Kargi E, Babuccu O, Hoşnuter M, Payasli C, Ayoğlu F. [The effect of combined use of vitamin C, vitamin E, and ibuprofen on flap viability: an experimental study]. Kulak Burun Bogaz Ihtis Derg 2005; 14 (5–6) 116-120
  • 20 Dvali LT, Dagum AB, Pang CY , et al. Effect of radiation on skin expansion and skin flap viability in pigs. Plast Reconstr Surg 2000; 106 (3) 624-629
  • 21 Khan A, Ashrafpour H, Huang N , et al. Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol 2004; 287 (5) R1219-R1229
  • 22 Alexandrou K, Hata Y, Matsuka K, Matsuda H. Effect of beraprost sodium (Procylin), a stable prostaglandin I2 analogue, on a dorsal skin flap model in rats. Scand J Plast Reconstr Surg Hand Surg 1996; 30 (1) 17-22
  • 23 Bailet JW, Hoffman LF, Trachy RE, Weymuller Jr EA. The effect of nifedipine on skin flap survival in rats. Laryngoscope 1994; 104 (3, Pt 1): 253-258
  • 24 Esclamado RM, Larrabee Jr WF, Zel GE. Efficacy of steroids and hyperbaric oxygen on survival of dorsal skin flaps in rats. Otolaryngol Head Neck Surg 1990; 102 (1) 41-44
  • 25 Pickens JP, Rodman SM, Wetmore SJ. The effects of extended perioperative pentoxifylline on random skin flap survival. Am J Otolaryngol 1994; 15 (5) 358-369
  • 26 Hart K, Baur D, Hodam J , et al. Short- and long-term effects of sildenafil on skin flap survival in rats. Laryngoscope 2006; 116 (4) 522-528
  • 27 Xiao-Xiao T, Sen-Min W, Ding-Sheng L. Effects of vinpocetine on random skin flap survival in rats. J Reconstr Microsurg 2013; 29 (6) 393-398
  • 28 Kim TK, Oh EJ, Chung JY, Park JW, Cho BC, Chung HY. The effects of botulinum toxin A on the survival of a random cutaneous flap. J Plast Reconstr Aesthet Surg 2009; 62 (7) 906-913
  • 29 Ergün H, Cilingir MG, Apaydin I, Erçöçen AR, Tulunay FC. The effect of dipyrone on survival of skin flaps. Scand J Plast Reconstr Surg Hand Surg 2001; 35 (1) 19-22
  • 30 Asai S, Fukuta K, Torii S. Topical administration of prostaglandin E1 with iontophoresis for skin flap viability. Ann Plast Surg 1997; 38 (5) 514-517
  • 31 Angel MF, Schieren G, Jorysz M, Knight KR, O'Brien BM. The beneficial effect of chlorpromazine on dorsal skin flap survival. Ann Plast Surg 1989; 23 (6) 492-497
  • 32 Matucci-Cerinic M, Denton CP, Furst DE , et al. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2011; 70 (1) 32-38
  • 33 Inoue H, Aihara M, Tomioka M, Ishida H. Changes in endothelin-1, 6-keto-PG-F1 alpha, and TX-B2 in random pattern flaps. J Cardiovasc Pharmacol 1998; 31 (Suppl. 01) S477-S479
  • 34 Wettstein R, Mörsdorf P, Bächle A , et al. Selective blockade of endothelin-B receptor improves survival of critically perfused musculocutaneous flaps. Langenbecks Arch Surg 2007; 392 (3) 331-338
  • 35 Pang CY, Zhang J, Xu H, Lipa JE, Forrest CR, Neligan PC. Role and mechanism of endothelin-B receptors in mediating ET-1-induced vasoconstriction in pig skin. Am J Physiol 1998; 275 (4, Pt 2): R1066-R1074
  • 36 Rücker M, Strobel O, Vollmar B, Spitzer WJ, Menger MD. Protective skeletal muscle arteriolar vasomotion during critical perfusion conditions of osteomyocutaneous flaps is not mediated by nitric oxide and endothelins. Langenbecks Arch Surg 2003; 388 (5) 339-343
  • 37 Eriksson C, Gustavsson A, Kronvall T, Tysk C. Hepatotoxicity by bosentan in a patient with portopulmonary hypertension: a case-report and review of the literature. J Gastrointestin Liver Dis 2011; 20 (1) 77-80