Topikal Atorvastatinin Random Paternli Cilt Fleplerinin Yaşayabilirliğine Etkisi ,Deneysel Çalışma

Yıl 2021, Cilt: 43 Sayı: 4, 396 - 402, 18.05.2021

Bilgen Can , Okan Özgür Özturan , Meltem Oral , Sadi Bener

https://doi.org/10.20515/otd.858659

Öz

Random fleplerin yaşayabilirliğinin arttırılması plastik cerrahide,süregelen araştırmalara konu olmuştur. Bir çok ajan denenmiş ancak çoğu klinik kullanıma girememiştir. Atorvastatinler lipid düşürücü olarak kullanılmaktadır. Ayrıca , sistemik uygulama ile flep yaşayabilirliğini , arttırdıkları deneysel olarak gösterilmiştir. Bu çalışmada atorvastatinin , topikal uygulama ile flep yaşayabilirliğine etkisi araştırılmıştır. 180-230 gram ağırlığında wibstor albino tipi , 20 erkek rat kontrol ve deney grubu olarak ayrılmıştır. Her bir grupta , Mc Farlane flebi eleve edilmiş , deney grubunda flep üzerine, hazırlanan atorvastatin krem uygulanırken;kontrol grubu herhangi bir tedavi almamıştır. İşlemden 7 gün sonra flep sağlıklı ve nekrotik doku geçiş zonundan 4 mm’ lik kesitler halinde doku örnekleri alınarak ,hematoksilen eozin ile boyanmış ve ışık mikroskobu altında lenfosit hücre yoğunluğu, notrofil hücre yoğunluğu , kapiller dansite ve granulasyon dokusu dansitesi açısından incelenmiştir. Fleplerdeki nekroz alanları sasaki kağıdı metodu ile işaretlenmiş, işaretleme AUTOCAT 2012 programına aktarılarak fleplerdeki nekroz oranları bulunmuştur. Histolojik parametlerin ve fleplerdeki nekroz oranlarının karşılaştırılması için Mann Whitney U testi kullanılmıştır (p<0,05) Çalışmaya göre deney grubunda notrofil hücre yoğunluğu ve kapiller dansite artmış, granulasyon dokusu dansitesi ve lenfosit hücre yoğunluğu ise değişmemiştir. Flep nekroz oranının atorvastatin uygulanan grupta azaldığı gösterilmiştir. Flep nekroz oranı kontrol grubunda 32,1% iken deney grubunda 14,17% olarak bulunmuştur .Ek çalışmalara ihtiyaç olmakla birlikte , atorvastatin topikal olarak kullanım ile flep yaşayabilirliğini arttırmaktadır.

Anahtar Kelimeler

flep, yaşayabilirlik, atorvastatin, topikal, anjiyogenez

Destekleyen Kurum

yok

Proje Numarası

2011-143

Teşekkür

istatitik çalışması konusunda yardımları için Salih Ergöçen e teşekkürler

The Effect of Topical Atorvastatin on Viability of Random Pattern Skin Flaps, Experimental Study

Öz

Augmentation of viability of random pattern flaps has long been an issue in plastic surgery. Up to date no agents were clinically introduced. Atorvastatins are used clinically for lipid lowering. They are also effective on flap survival with their angiogenic, anti-inflammatory, antioxidant effects with systeic administration. In this study, Atorvastatin is used topically for flap survival alleviation in Mc Farlane flap in rats. Wibstar albino type 20 male rats weighing about 180-230 grams were classified as experiment and control group. Results were evaluated by flap necrosis ratios, lymphocyte cells, neutrophile cells, capillary and granulation tissue density on the 7th postoperative day.. Flap necrosis areas were evaluated with Sasaki's paratemplate method. Tissue biopsies of 1x1 cm at the transition zone between necrotic and healthy tissue, were embedded in parafin blocks after fixation in 10% formalin. Biopsies were sliced by 4 micrometer thickness with a microtome. Cross sections were painted with hematoxylene eosin and evaluated with a light microscope. Whitneyy U test was performed for clinical and histopathological evaluation of groups (p<0,05). Flap viability was alleviated. Average necrosis ratios on flaps were 32.1% in the control group and 14.17% in experimental group. Capillary tissue and neutrophile cell density were found to be higher in atorvastatin group. . Granulation tissue and lymphocyte cell density were not found significantly higher.. Atorvastatins, when applied topically, are effective on flap survival. Further studies should be carried out for human clinical use.

Anahtar Kelimeler

Flap, survival, atorvastatin, topically, angiogenesis

Proje Numarası

2011-143

Kaynakça

• referans 1. Katzung BG. Basic and clinical pharmacology. Norwalk, Appleton and Lange; 1995
• referans2. Liao JK, Laufs U. Pleiotropic Effects of Statins. NIH Public Access. 2005;45:89‐118
• referans3. Dulak J, Loboda A, Jazwa A, et al. Atorvastatin Affects Several Angiogenic Mediators in Human Endothelial Cells. Endothelium. 2005 ; 12: 233–41
• referans4. Weis M, Heeschen C, Glassford AJ, et al. Statins have biphasic effects on angiogenesis. Circulation. 2002;105:739-45.
• referans5. Karamouzian S, Eskandary H, Saeed A, et al. Effect of atorvastatin on angiogenesis in degenerated intervertebral disc in rat. Spine (Phila Pa 1976).2011;36:1824-8.
• referans6. Macin SM, Perna ER, Farías EF, et al. Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome: results of a randomized, double-blind, placebo-controlled study. Am Heart J. 2005 ;149:451-7
• referans7. Liu M, Wang F, Wang Y, et al. Atorvastatin improves endothelial function and cardiac performance in patients with dilated cardiomyopathy: the role of inflammation. Cardiovasc Drugs Ther. 2009;23:369-76
• referans8. Barsante MM, Roffê E, Yokoro CM, et al. Anti-inflammatory and analgesic effects of atorvastatin in a rat model of adjuvant-induced arthritis. Eur J Pharmacol. 2005 15;516:282-9.
• referans9. Cangemi R, Loffredo L, Carnevale R, et al. Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E. Eur Heart J. 2008;29:54-62.
• referans10. Riad A, Du J, Stiehl S, et al. Low-dose treatment with atorvastatin leads to anti-oxidative and anti-inflammatory effects in diabetes mellitus. Eur J Pharmacol. 2007;569:204-11
• referans11. Hamilton PK, Hughes SM, Plumb RD, et al. Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia. Clin Sci (Lond). 2010;118:359-66.
• referans12. Hernández-Perera O, Pérez-Sala D, Navarro-Antolín J, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest. 1998;101:2711-9.
• referans13. Endres M, Laufs U, Huang Z, et al. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad .1998;95:8880-5
• referans14. S.-C. Yang Atorvastatin alleviated viability of rat ischemic flap dependent of VEGF m RNA expression Plastic & Reconstructive Surgery. 128 Supplement 2S, Third Annual European Plastic Surgery Research Council Abstract Supplement:620, August 2011
• referans15. Toker S, Gulcan E, Cayc MK, et al. Topical atorvastatin in the treatment of diabetic wounds. Am J Med Sci. 2009;338:201-4.
• referans16. Hart K, Baur D, Hodam J, et al. Short- and long-term effects of sildenafil on skin flap survival in rats. Laryngoscope. 2006;116:522-8.
• referans17. Emery FM, Kodey TR, Bomberger RA, et al. The effect of nifedipine on skin-flap survival. Plast Reconstr Surg. 1990;85:61-3.
• referans18. Green CJ, Dhami L, Prasad S, Healing G, Shurey C. The effect of desferrioxamine on lipid peroxidation and survival of ischaemic island skin flaps in rats. Br J Plast Surg. 1989;42:565-9.
• referans19. Kargi E, Babuccu O, Hoşnuter M, et al .The effect of combined use of vitamin C, vitamin E, and ibuprofen on flap viability: an experimental study]. Kulak Burun Bogaz Ihtis Derg. 2005;14:116-20
• referans20. Senderoff DM, Israeli D, Zhang WX, et al. Iloprost improves survival of ischemic experimental skin flaps. Ann Plast Surg. 1994;32:490-5
• referans21. Shalom A, Hadad E, Friedman T, et al. Effect of hyaluronic acid on random-pattern flaps in rats. Dermatol Surg. 2008;34:1212-5.
• referans22. Sahin C, Aysal BK, Ergun O. Is It Possible to Increase Flap Viability by Hydrostatic Dilation?: An Experimental Study in the Rat Abdominal Fasciocutaneous Flap Model. Ann Plast Surg. 2016;77:26-30
• referans23. Özyazgan İ, Baykan H. The effect of TENS on random pattern flap survival in nicotinized rats. Ann Plast Surg. 2015;74:365-70
• referans24. Baris R, Kankaya Y, Ozer K, et al. The effect of microneedling with a roller device on the viability of random skin flaps in rats. Plast Reconstr Surg. 2013;131:1024-34
• referans25. Hamamcıoğlu K, Vural O. Statins For The Treatment of Multiple Sclerosis. Journal of Neurological Sciences.2005;22:221-30
• referans26. Takeuchi H, Mano Y, Terasaka S, Sakurai T, Furuya A, et al. Usefulness of rat skin as a substitute for human skin in the in vitro skin permeation study. Exp Anim. 2011;60:373-84
• referans27. Jakasa I, Kezic S. Evaluation of in-vivo animal and in-vitro models for prediction of dermal absorption in man. Hum Exp Toxicol. 2008;27:281-8.