Effects of Tirofiban on Random Skin Flap Survival in Rats

Abstract

Background Tirofiban is a glycoprotein IIb/IIIa receptor antagonist that is widely used clinically. In the present study, we investigated whether tirofiban promotes flap survival in rat random skin flap model.

Methods “McFarlane flaps” models were developed in 60 male rats. The rats were divided into a tirofiban-treated group (n = 30) and a saline-treated group (n = 30). The flap surviving rate was calculated 7 days after surgery. Tissue samples were collected and subjected to histopathological evaluation. Lead oxide–gelatin angiography and immunohistochemical staining analysis were taken to evaluate angiogenesis. Analysis of oxidative stress was performed by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA).

Results Compared with controls, the tirofiban-treated groups exhibited significantly larger mean areas of flap survival, significantly increased SOD activity, and vascular endothelial growth factor (VEGF) expression, and significantly reduced MDA level. Hematoxylin and eosin staining revealed that naringin promoted angiogenesis and inhibited inflammation.

Conclusion These findings demonstrate that tirofiban increases flap survival of random skin flaps in rats.

Keywords

tirofiban - random skin flap - flap survival

• References

• 1 Akhavani MA, Sivakumar B, Paleolog EM, Kang N. Angiogenesis and plastic surgery. J Plast Reconstr Aesthet Surg 2008; 61 (12) 1425-1437
• 2 Sloan GM, Reinisch JF. Flap physiology and the prediction of flap viability. Hand Clin 1985; 1 (04) 609-619
• 3 Wang WZ, Baynosa RC, Zamboni WA. Update on ischemia-reperfusion injury for the plastic surgeon: 2011. Plast Reconstr Surg 2011; 128 (06) 685e-692e
• 4 Yang M, Sheng L, Li H, Weng R, Li QF. Improvement of the skin flap survival with the bone marrow-derived mononuclear cells transplantation in a rat model. Microsurgery 2010; 30 (04) 275-281
• 5 Xiao-Xiao T, Sen-Min W, Ding-Sheng L. ; XiaoXiao T. Effects of vinpocetine on random skin flap survival in rats. J Reconstr Microsurg 2013; 29 (06) 393-398
• 6 Fang T, Lineaweaver WC, Chen MB, Kisner C, Zhang F. Effects of vascular endothelial growth factor on survival of surgical flaps: a review of experimental studies. J Reconstr Microsurg 2014; 30 (01) 1-13
• 7 Cai L, Huang W, Lin D. Effects of traditional Chinese medicine Shuxuetong injection on random skin flap survival in rats. Sci World J 2014; 2014 (01) 816545
• 8 Gilbert RE. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes. N Engl J Med 2001; 345 (21) 1574-1575 , author reply 1574–1575
• 9 Bolognese L, Falsini G, Liistro F. , et al. Randomized comparison of upstream tirofiban versus downstream high bolus dose tirofiban or abciximab on tissue-level perfusion and troponin release in high-risk acute coronary syndromes treated with percutaneous coronary interventions: the EVEREST trial. J Am Coll Cardiol 2006; 47 (03) 522-528
• 10 Lancet T. ; ESPRIT Investigators. Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet 2000; 356 (9247): 2037-2044
• 11 Investigators TR. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis. Circulation 1997; 96 (05) 1445-1453
• 12 Giordano A, Romano S, D'Angelillo A. , et al. Tirofiban counteracts endothelial cell apoptosis through the VEGF/VEGFR2/pAkt axis. Vascul Pharmacol 2016; 80: 67-74
• 13 Cai L, Cao B, Lin D. Effects of traditional Chinese medicine Huangqi Injection (Radix astragali) on random skin flap survival in rats. J Reconstr Microsurg 2015; 31 (08) 565-570
• 14 Kelly CP, Gupta A, Keskin M, Jackson IT. A new design of a dorsal flap in the rat to study skin necrosis and its prevention. J Plast Reconstr Aesthet Surg 2010; 63 (09) 1553-1556
• 15 Wang L, Zhou ZW, Yang LH. , et al. Vasculature characterization of a multiterritory perforator flap: an experimental study. J Reconstr Microsurg 2017; 33 (04) 292-297
• 16 Ozkan F, Şenayli Y, Ozyurt H, Erkorkmaz U, Bostan B. Antioxidant effects of propofol on tourniquet-induced ischemia-reperfusion injury: an experimental study. J Surg Res 2012; 176 (02) 601-607
• 17 Shi ZR, Itzkowitz SH, Kim YS. A comparison of three immunoperoxidase techniques for antigen detection in colorectal carcinoma tissues. J Histochem Cytochem 1988; 36 (03) 317-322
• 18 Yu YF, Xu HG, Wang H, Zhang W, Xiong SL, Zhang M. Change of autophagy in endplate chondrocytes of rats during aging process [in Chinese]. Zhonghua Yi Xue Za Zhi 2013; 93 (45) 3632-3635
• 19 Basu G, Downey H, Guo S. , et al. Prevention of distal flap necrosis in a rat random skin flap model by gene electro transfer delivering VEGF(165) plasmid. J Gene Med 2014; 16 (3-4): 55-65
• 20 Zhang F, Oswald T, Lin S. , et al. Vascular endothelial growth factor (VEGF) expression and the effect of exogenous VEGF on survival of a random flap in the rat. Br J Plast Surg 2003; 56 (07) 653-659
• 21 Giordano A, D'Angelillo A, Romano S. , et al. Tirofiban induces VEGF production and stimulates migration and proliferation of endothelial cells. Vascul Pharmacol 2014; 61 (2-3): 63-71
• 22 Azar RR, Badaoui G, Sarkis A. , et al. Effect of high bolus dose tirofiban on the inflammatory response following percutaneous coronary intervention. Clin Cardiol 2010; 33 (01) E14-E19
• 23 Cui J, Liu L, Zou J. , et al. Protective effect of endogenous hydrogen sulfide against oxidative stress in gastric ischemia-reperfusion injury. Exp Ther Med 2013; 5 (03) 689-694
• 24 Sirota TV, Zakharchenko MV, Kondrashova MN. Cytoplasmic superoxide dismutase activity is a sensitive indicator of the antioxidant status of the rat liver and brain [in Russian]. Biomed Khim 2014; 60 (01) 63-71