DIAGNOSTIC VALUE OF ASYMMETRIC DI-METHYL ARGININE LEVEL FOR FLAP SURVIVAL IN EXPERIMENTAL ISCHEMIA REPERFUSION MODEL

Year 2016, Volume: 49 Issue: 3, 186 - 191, 01.12.2016

Melike Oruç Yüksel Kankaya Kadri Özer Veysel Murat Işık Özlem Çolak Koray Gürsoy Uğur Koçer

Abstract

OBJECTIVE: Nitric oxide is important for skin flap survival. Systemic production of endogenous nitric oxide synthase inhibitor molecule ‘asymmetric di-methyl arginine’ ADMA is greater in animals having ischemia reperfusion injury. Aim of this study was to evaluate possible correlation of elevated levels of ADMA with skin flap survival in an experimental model.MATERIAL AND METHODS: I26 adult Wistar rats were used in study. In group I abdominal flaps were elevated and sutured back. Abdominal axial flaps were elevated and subsequent 8 hours of warm ischemia period was created in group II. Plasma ADMA levels were calculated preoperatively and after 4 hours of reperfusion. RESULTS: Mean preoperative ADMA levels were calculated as 0,283 and 0,301 µmol/l in group 1 and group 2. Postoperative ADMA levels were 0,296 and 0,471 µmol/l respectively. At postoperative 10th day, mean area of flep necrosis were found to be as 2.6 %± 3.0 and 44.4% ± 10.7 in group 1 and group 2. Differences between preoperative ADMA levels were not statistically significant p>0.05 but postoperative ADMA levels were significantly higher in group II p

Keywords

Ischemia, reperfusion injury, surgical flap, asymmetric dimethyl arginine

DENEYSEL İSKEMİ REPERFÜZYON MODELİNDE ASİMETRİK DİMETİL ARJİNİN SEVİYESİNİN FLEP YAŞAMI ÜZERİNDE TANI KOYDURUCU DEĞERİ

Abstract

AMAÇ: Endojen bir nitrik oksit sentetaz inhibitor molekülü olan ‘asimetrik di-metil arjinin’ ADMA konsantrasyonu belli spesifik durumlarda artmaktadır. ADMA’nın sistemik üretimi iskemi reperfüzyon hasarına uğramış hayvanlarda daha fazladır. Bunun yanında nitrik oksit ve nitric oksit sentetaz, deri fleplerinin sağ kalımında oldukça önemlidir. Bu çalışmanın amacı da artmış ADMA seviyesi ve deri flep yaşayabilirliği arasındaki muhtemel ilişkinin deneysel olarak incelenmesidir. GEREÇ VE YÖNTEMLER: Çalışmada 26 adet erişkin Wistar sıçan kullanıldı. Grup 1’de abdominal flepler kaldırıldı ve tekrar yerine dikildi. Grup 2’de ise süperfisyal epigastrik damarlar bazlı abdominal aksiyel flepler eleve edildi ve sonrasında vasküler pedikül klemplenerek 8 saatlik sıcak iskemi periyodu oluşturuldu. Plazma ADMA seviyeleri preoperatif ve reperfüzyon sonrası 4. saatte ölçüldü. BULGULAR: Grup 1 ve grup 2’de ortalama preoperatif ADMA seviyeleri 0,283 ve 0,301 olarak hesaplandı. Postoperatif ADMA seviyeleri ise sırasıyla 0,296 ve 0,471 µmol/l olarak bulundu. Postoperatif 10.günde, ortalama flep nekroz alanı grup 1’de 2.6 %± 3.0 ve grup 2’de 44.4% ± 10.7 olarak hesaplandı. Preoperatif ADMA seviyeleri arasındaki fark istatistiksel olarak anlamlı değildi p>0.05 fakat postoperatif ADMA seviyeleri grup 2’de istatistiksel olarak anlamlı derecede yüksekti p

Keywords

İskemi reperfüzyon, flep, sağ kalım, asimetrik dimetil arjinin

References

• 1)Martin-Sanz P, Olmedilla L, Dulin E. Presence of methylated arginine derivatives in orthotopic human liver transplantation: relevance for liver function. Liver transplantation : of ficial publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003; 9: 40-48.
• 2)Moncada S. Nitric oxide in the vasculature: physiology and pathophysiology. Annals of the New York Academy of Sciences. 1997; 811: 60-67.
• 3)Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994; 78: 915-918.
• 4)Serracino-Inglott F, Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. American Journal of Surgery. 2001; 181: 160-166.
• 5)Beltowski J, Kedra A. Asymmetric dimethylarginine (ADMA) as a target for pharmacotherapy. Pharmacological Reports. 2006; 58: 159-178.
• 6)Zhang Z, Zou YY, Li FJ. Asymmetric dimethylarginine: a novel biomarker of gastric mucosal injury? World Journal of Gastroenterology. 2011; 17: 2178-2180.
• 7)Stuhlinger MC, Conci E, Haubner BJ. Asymmetric dimethyl L-arginine (ADMA) is a critical regulator of myocardial reperfusion injury. Cardiovascular Research. 2007; 75: 417-425.
• 8)Sousse LE, Yamamoto Y, Enkhbaatar P ve ark. Acute lung injury-induced collagen deposition is associated with elevated asymmetric dimethylarginine and arginase activity. Shock. 2011; 35: 282-288.
• 9)Fliser D. Perspectives in renal disease progression: the endothelium as a treatment target in chronic kidney disease. Journal of Nephrology. 2010; 23: 369-376.
• 11)Prada FS, Arrunategui G, Alves MC. Effect of allopurinol, superoxide-dismutase, and hyperbaric oxygen on flap survival. Microsurgery. 2002; 22: 352-360.
• 12)Trocha M, Merwid-Lad A, Szuba A. Effect of simvastatin on nitric oxide synthases (eNOS, iNOS) and arginine and its derivatives (ADMA, SDMA) in ischemia/reperfusion injury in rat liver. Pharmacological Reports. 2010; 62: 343-351.
• 13)Um SC, Suzuki S, Toyokuni S. Involvement of nitric oxide in survival of random pattern skin flap. Plastic and Reconstructive Surgery. 1998; 101: 785-792.
• 14)Kuntscher MV, Kastell T, Altmann J, Menke H, Gebhard MM, Germann G. Acute remote ischemic preconditioning II: the role of nitric oxide. Microsurgery. 2002; 22: 227-231.
• 15)Azizzadeh B, Buga GM, Berke GS, Larian B, Ignarro LJ, Blackwell KE. Inhibitors of nitric oxide promote microvascular thrombosis. Archives of Facial Plastic Surgery. 2003; 5: 31-35.
• 16)Gribbe O, Samuelson UE, Wiklund NP. Effects of nitric oxide synthase inhibition on blood flow and survival in experimental skin flaps. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2007; 60: 287-293.
• 17)Gribbe O, Gustafsson LE, Wiklund NP. Transdermally administered nitric oxide by application of acidified nitrite increases blood flow in rat epigastric island skin flaps. European Journal of Pharmacology. 2008; 578: 51-56.
• 18)Dayoub H, Rodionov RN, Lynch C ve ark. Overexpression of dimethylarginine dimethylaminohydrolase inhibits asymmetric dimethylarginine-induced endothelial dysfunction in the cerebral circulation. Stroke. 2008; 39: 180-184.
• 19)Shibata R, Ueda S, Yamagishi S. Involvement of asymmetric dimethylarginine (ADMA) in tubulointerstitial ischaemia in the early phase of diabetic nephropathy. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2009; 24: 1162-1169.
• 20)Karaaslan O, Sonmez E, Kankaya Y ve ark. Monitorization of asymmetric dimethylarginine (ADMA) levels in an experimental ischemia-reperfusion flap model: a preliminary report. Journal of Reconstructive Microsurgery. 2013; 29: 417-4.