THE EFFECTS OF CALCIUM DOBESILATE ON SKELETAL MUSCLE ISCHEMIA REPERFUSION INJURY

Özet Amaç: Kalsiyum dobesilatýn kapiller fonksiyon bozukluklarýný düzelttiði, lenfatik akýmý arttýrdýðý, trombosit agregasyonu ve trombogenezi inhibe ettiði bilinmektedir. Bu deneysel çalýþmada venotonik bir ajan olarak kullanýlan kalsiyum dobesilatýn, iskelet kasýnda iskemi reperfüzyon hasarýna etkileri araþtýrýlmýþtýr. Materyal ve Metod: Sprague Dawley cinsi 25 rat 5 gruba ayrýldý. Grup 1’de sadece anestezi, Grup’2 de turnike yöntemiyle sað arka ekstremiteye 4 saat iskemi uygulandý. Ýskemi lazer dopler ile gösterildi. Grup 3 ve Grup 4'de 5 gün süre ile oral kalsiyum dobesilat verildi. Grup 3'de 4 saat iskemi, Grup 4 ve Grup 5'de 4 saat iskemiyi takiben 2 saat reperfüzyon yapýldý. Tüm gruplarda soleus kasý, akciðer ve karaciðer dokusu lipit peroksidasyonunun son ürünü olan malondialdehit seviyelerinin ölçümü için çýkarýldý. Serum kreatin fosfokinaz düzeyleri çalýþýldý. Ayrýca histopatolojik inceleme amacýyla soleus kasýndan alýnan doku kesitleri nitroblue tetrazolium boyasý ile boyanarak oksidatif enzimlerde kullanýmý gösteren menekþe renkli hücrelerin sayýmý yapýldý. Bulgular: Ýlaçsýz iskemi grubu ile kalsiyum dobesilat alan iskemi grubu karþýlaþtýrýldýðýnda, kalsiyum dobesilatlý iskemik grupta adale ve karaciðer malondialdehit düzeylerinde ve kreatin fosfokinaz düzeylerinde istatistiksel anlamlý azalma vardý (p < 0.05). Kalsiyum dobesilatlý iskemi reperfüzyon ile ilaçsýz iskemi reperfüzyon gruplarý karþýlaþtýrýldýðýnda, kalsiyum dobesilatlý iskemi reperfüzyon grubunda serum kreatin fosfokinaz ve adale malondialdehit düzeylerinde anlamlý azalma görüldü ( p < 0.05 ). Sonuç: Þu anda klinik kullanýmda yalnýzca oral formu bulunan ve venöz hastalýklarýn tedavisinde kullanýlan bu ilacýn iskeminin etkilerini ayrýca kladikasyonun oluþturduðu iskemi reperfüzyon hasarýný azaltabileceði için kronik arteriyel iskemili hastalarýn tedavisinde kullanýlabileceði sonucuna varýldý. Anahtar kelimeler: Kalsiyum dobesilat, reperfüzyon, kladikasyo intermittant Summary Background: It’s known that calcium dobesilate improves capillary dysfunction and lymphatic flow, inhibits thrombogenesis and thrombocytic aggregation. In this experimental study the effects of calcium dobesilate, a venotonic agent, on skeletal muscle ischemia –reperfusion injury is investigated. Method: Sprague-Dawley type 25 rats were divided into 5 groups. In Group 1 only anesthesia was performed. Ischemia was obtained in right lower extremity using tourniquet method in Group 2. Ischemia was documented by laser doppler. In group 3 and 4 , oral calcium dobesilate was given for five days. In Group 3 four hours of ischemia, in Group 4 and 5 two hours of reperfusion following 4 hours of ischemia was performed. Soleus muscle, lung and liver tissues were extracted for measurement of malondialdehyde levels which is the last product of lipid peroxidation. Serum creatine phospokinase levels were also studied. In addition , tissue samples of soleus muscle were dyed with nitroblue tetrazolium and then purple colored cells were counted in order to show the usage of oxidative enzymes. Results: When ischemia groups without calcium dobesilate and with calcium dobesilate were compared, in latter group there was a decrease in malondialdehyde levels of soleus muscle and liver tissues and also in serum creatine phosphokinase levels, which was statistically significant (p < 0.05). When comparing ischemia-repefusion groups with and without calcium dobesilate, there was statistically significant decrease in serum creatine phosphokinase and muscular malondialdehyde levels in the former group (p < 0.05). Conclusion: Even though calcium dobesilate is available only in oral form and used in treatment of venous diseases, it can also be used in the treatment of patients with chronic arterial disease to prevent ischemia and ischemia-reperfusion injury induced by claudication.