Effect’s of Danazol use on the viability of dorsal rat flap

Öz

Effect\'s of Danazol use on the viability of dorsal rat flap Repaire of large skin defects is one of the most challenging problem on reconstructive surgery. As known that, the most suitable functional and aesthetic way for flaps are preferrable for aesthetic and functional results. But flaps which used for large skin defects lenght are limited. When the flap\'s height lenghtens, flap surviving decreases. In this situation, necrosis and tissue lost is encorded. To prevent this problems, symphatolytic agents and anticoagulans which increases blood flow and changes reolytic property of blood are used. Moreover, cell membrane stabilization is attempted to be maintained. Danazol is antiinflammatory agent in the treatment of endometriosis and it has weak gonadotropic activity. In this study twenty female, adult Sprague-Dawley rat were included. Danazol can decrease random pattern skin flap necrosis due to the fact that danazol has anticoagulant and anti-inflammation property. Danazol may used for increasing survival of flap by decresing development of necrosis on distal part of random pattern skin flap. In this article, we mentioned antiinflammatory mechanism of danazol and influence viability of flap.

Anahtar Kelimeler

• Danazol, skin flap, necrosis

gı üzerine etkileri

Öz

Vücudun dıs örtü tabakası olan cildin büyük defektlerinin kapatılması, rekonstrüktif cerrahinin önemli sorunlarından biridir. Cilt defektlerinin kapatılmasında en uygun fonksiyonel ve estetik yaklasım, fleplerin kullanılmasıdır. Büyük defektlerin kapatılmasında kullanılan fleplerin boyutları da sınırlıdır. Planlanan flebin boyu uzadıkça flep yasayabilirliginde azalma gözlenmektedir. Bu durum kendisini özellikle flep distalinde nekroz ve doku kaybı olarak göstermektedir. Bu sorunları giderebilmek için kan akımını arttıran sempatolitik ajanlar ve antikoagülanlar, kanın reolitik özelligini degistiren ajanlar kullanılmıs, ayrıca iskemik hücrelerde hücre zarı stabilizasyonu saglanmaya çalısılmıstır. Danazol, antienflamatuar etkisi bulunan, endometriozis tedavisinde kullanılan zayıf etkili bir gonadotropik hormondur. Bu ajan, dokulara olan antienflamatuar etkisini çok degisik mekanizmalarla gösterir. Bu çalısmada deney hayvanı olarak disi, eriskin Sprague-Dawley sıçan kullanıldı. Deneysel dorsal rat flebi modelinde random paternli deri flebinin distal kısmında nekroz gelisimini azaltmak ve flebin yasayabilirligini arttırmak için antiinflamatuar ve antikoagülan etki mekanizmalarına sahip olabilen danazol kullanılmıstır. Bu yazıda danazolün antienflamatuar etki mekanizmasının yanında, flep canlılığına etkisi üzerine deginilmistir.

Anahtar Kelimeler

• Danazol, deri flebi, nekroz

Kaynakça

1. Yavuz M. Flepler. Acarturk S (ed). Plastik ve Rekonstrüktif Cerrahi Ders Notları, No:21. Adana, 2002: 17-22.
2. Smith JD, Pribaz JJ. Flaps. Achauer BM (ed). Plastic Surgery Indications, Operations and Outcomes, 2nd ed. California, 2000: 261290.
3. Fan QU, Zhou J, Baozhang MA. The effect of Chinese herbs on the cytokines of rats with endometriosis. J Altern Complement Med 2005; 11:627-630.
4. Carvalho EN, Ferreira LM, Carvalho NAS et al. Viability of random pattern dorsal skin flap in diabetic rats. Acta Cir Bras 2005; 20:225-229.
5. Gulmez SE, Serel S, Uluç A ve ark. Dipyrone increases the blood flow of arterial dorsal skin flaps. Aesthetic Plast Surg 2008; 32: 766-770.
6. Ghazinezami B, Rahimpour S, Gholipour T et al. Pharmacologic preconditioning of random-pattern skin flap in rats using local cyclosporine and FK-506 interaction with nitric oxide system. Ann Plast Surg 2007;59:435-440.
7. Kyama CM, Debrock S, Mwenda JM, et al. Potential involvement of the immune system in the development of endometriosis. Reprod Biol Endocrinol 2003;2:123-127.
8. Mori H, Nakagawa M, Itoh N et al. Danazol suppressed the production of interleukin-1 beta and tumor necrosis factor by human monocytes. Am J Reprod Immunol 1990; 24:45-50.

9. Harada T, Iwabe T, Tarakawa N. Role of cytokines in endometriosis. Fertil Steril 2001; 76:1-10.
10. Markowska J, Kowalska M, Gogacz M et al. Cytokines and endometriosis. Clin Exp Obstet Gynecol 2004; 31:269-270.
11. Wu MY, Ho HN. The role of cytokines in endometriosis. Am J Reprod Immunol 2003; 49:285-296.
12. Iwabe T, Harada T, Terakawa N. Role of cytokines in endometriosis-associated infertility. Gynecol Obstet Invest 2002; 53:1925.
13. Matalliotakis I, Neonaki M, Zolindaki A et al. Changes in immunologic variables (TNF-a, sCD8 and sCD4) during danazol treatment in patients with endometriosis. Int J Fert Women’s Med 1997; 42:211-214.
14. Clarkson TB, Herndan CN, Holleman IL, Flaps. Morehead RP (ed). Human Pathology: An Introduction to Medicine, 1st ed. UK, 1965: 97-127.
15. Ozmen N, Cebeci BS, Kardesoğlu E. Kalp yetersizliğinde inflamatuvar göstergeler. Anadolu Kardiyol Derg 2006; 6:51-54.
16. Lichtman AH, Jordan SP. Immunology. Abbas AK (ed). Cellular and Molecular Immunology, 5th. ed. UK, 2003: 243-275.
17. Kumar V, Cotran RS. Acute and Chronic Inflammation. Robbins SL (ed). Basic Pathology, 5th ed. Philadelphia, 1992: 25-46.
18. Vedder NB. Flaps. Mathes SJ (ed). Plastic Surgery. 2th ed. Philadelphia, 2006: 483506.
19. Fracs J, Byrd H. Surgical flaps. Kayser MR (ed). Selected Readings in Plastic Surgery, vol 9, number 2. Byler, 1999: 3-44.
20. Monaco JL, Lawrence TM. Acute wound healing; An overview. Clin Plast Surg 2003; 57-65.
21. Özbay G. Kan akımı bozuklukları ve şok. Cerrahpasa Tıp Fak Derg 1992;61-82.
22. Ruiz-Argulles GJ, Ruiz-Argulles A, Perez-Romano B et al. Protein S deficiency associated to anti-protein S antibodies in a patient with mixed connective-tissue disease and its reversal by danazol. Acta Haematol 1993; 89: 206-208.
23. Ledford MR, Horton A, Wang G et al. Efficacy of danazol in a patient with congenital protein s deficiency: Paradoxical evidence for decreased platelet activation with increased thrombin generation. Thromb Res 1997;87:473482.
24. Al- Momen AK, Gader AMA, Shamena AR et al. Significant elevation of Protein C and Protein S levels in thrombotic disorders by low dose danazol. Blood Coagul Fibrinolysis 1991; 2: 495-499.
25. White INH. Metabolic activation of acetylenic substituents to derivatives in the rat causing the loss of hepatic cytochrome p-450 and haem. Biochem J 1978;174: 853-861.
26. Tonks AM. Streptokinase salvage of a rectus abdominis free flap. Plast Reconstr Surg 1995; 95:933-936.
27. Senderoff DM, Zhang WX, Israeli D et al. The additive beneficial effect of UW solution and urokinase on experimental microvascular free-flap survival. J Reconstr Microsurg 1993;9:197-202.
28. Khouri RK, Koudsi B, Kaiding F et al. Prevention of thrombosis by topical application of tissue factor pathway inhibitor in a rabbit model of vascular trauma. Ann Plast Surg 1993; 30: 398-402.
29. Akoum A, Lemay A, Paradis I et al. Secretion of interleukin-6 by human endometriotic cells and regulation by proinflammatory cytokines and sex steroids. Hum Reprod 1996; 11:2269-2275.
30. Morley KD, Parke A, Hughes GRV. Systemic lupus erythematosus: two patients treated with danazol. BMJ 1982;1431-1432.