Research Article| Volume 60, ISSUE 8, P861-863, August 2007

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Effects of clopidogrel on survival of rat skin flaps

Published:April 06, 2007DOI:


      Clopidogrel is a thienopyridine derivative that is chemically related to ticlopidine, which irreversibly inhibits platelet aggregation by selectively binding to adenylate cyclase-coupled adenosine diphosphate receptors on the platelet's surface. In animal models, clopidogrel has been shown to reduce the incidence of both arterial and venous thrombi. In the present study the effects of clopidogrel on the survival of rat epigastric island flaps was researched. Epigastric island flaps of 7×7 cm were raised from symphisis pubis to arcus costa with the panniculus carnosus. The experimental group received seven doses of 25 mg/kg clopidogrel postoperatively, the first dose given immediately after the suturing of the flaps. The rats were anaesthetised on postoperative day 7 to assess the survival of flaps.
      The difference between the clopidogrel and the control group was significant (P<0.005). The full-thickness skin samples obtained after the calculation of survival percentages revealed thinning of the epidermis layer and active chronic inflammation in both groups. However, diffuse dilated vessels, extravasated eritrocytes were seen in the clopidogrel group flaps. The results indicated a significant increase in flap survival in rats given clopidogrel. Further research is needed to assess the critical doses of clopidogrel to create optimal flap survival improvement.


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        • Bernat A.
        • Mares A.M.
        • Defreyn G.
        • et al.
        Effect of various antiplatelet agents on acute arterial thrombosis in the rat.
        Thromb Haemost. 1993; 70: 812-816
        • Herault J.P.
        • Dol F.
        • Gaich C.
        • et al.
        Effect of clopidogrel on thrombin generation in platelet-rich plasma in the rat.
        Thromb Haemost. 1999; 81: 957-960
        • Ghavami A.
        • Nutt M.P.
        • Hardy S.P.
        Heat shock protein and high-dose aspirin: effects on random skin flap survival in a rat model.
        Ann Plast Surg. 2002; 48: 60-67
        • Yoshida W.B.
        • Campos E.B.
        Ischemia and reperfusion in skin flaps: effects of mannitol and vitamin C in reducing necrosis area in a rat experimental model.
        Acta Cir Bras. 2005; 20: 358-363
        • Tyner T.R.
        • Russell D.
        • Yamaguchi K.T.
        Effects of lipoic acid and a reduced-calorie diet on skin flap survival in a rat model.
        Plast Reconstr Surg. 2004; 114: 1980-1982
        • Tyner T.R.
        • Shahbazian R.
        • Nakashima J.
        • et al.
        Propofol improves skin flap survival in a rat model: correlating reduction in flap-induced neutrophil activity.
        Ann Plast Surg. 2004; 53: 273-277
        • Akan M.
        • Cakir B.
        • Misirlioglu A.
        • et al.
        Effects of clopidogrel and high dose aspirin on survival of skin flaps in rats.
        Scand J Plast Reconstr Surg Hand Surg. 2005; 39: 7-10
        • Finseth F.
        • Cutting C.
        An experimental neurovascular island skin flap for the study of the delay phenomenon.
        Plast Reconstr Surg. 1978; 61: 412-420
        • Kerrigan C.L.
        • Daniel R.K.
        Pharmacologic treatment of the failing skin flap.
        Plast Reconstr Surg. 1982; 70: 541-548
        • Reinisch R.F.
        The pathophysiology of skin flap circulation.
        Plast Reconstr Surg. 1974; 54: 585-598
        • Kerrigan C.L.
        Skin flap failure: pathophysiology.
        Plast Reconstr Surg. 1983; 72: 766-777
        • Donavan W.E.
        Experimental model in skin flap research.
        in: Grabb W.C. Myers M.B. The Skin Flaps. Little, Brown, Boston1975: 11-20
        • Herbert J.M.
        • Bernat A.
        • Maffrand J.P.
        Importance of platelets in experimental venous thrombosis in the rat.
        Blood. 1992; 80: 2281-2286
        • Savi P.
        • Herbert J.M.
        • Pflieger A.M.
        • et al.
        Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel.
        Biochem Pharmacol. 1992; 44: 527-532
        • Matsagas M.
        • Jagroop I.A.
        • Geroulakos G.
        • et al.
        The effect a loading dose (300mg) of clopidogrel on platelet function in patients with peripheral arterial disease.
        Clin Appl Thromb Hemost. 2003; 9: 115-120