The effect of cyclosporine A on cardiac arrhythmias and connexin 43 and nitric oxide synthase expression in ischemia-reperfusion injury model of diabetic rats

Abstract

Ischemic heart disease leads to many deaths worldwide and the role of diabetes risk factor in disease malignancy and the role of some intercellular communication structures in reducing ischemic-reperfusion injury during disease is clinically important. The aim of this study is to evaluation of the effect of cyclosporine A on cardiac arrhythmias and connexin 43 and nitric oxide Synthase expression in ischemia-reperfusion injury model of diabetic rats. Materials and Methods: This study was performed as experimental which was done at Tabriz Medical School in 2020-21. In this study, 36 male wistar rats in the weight range of 250-300 g (6 rats in each group) and 12 additional rats (due to the possibility of mortality in diabetic groups) were used. The animals were randomly divided into 6 groups and tested. 1. The group (Control) that did not experience any ischemia-reperfusion (IR). 2. The group (diabetic) that was created diabetes by intraperitoneal injection of 50 mg / kg of streptozotocin as a single dose and did not experience any ischemia-reperfusion. 3. Group (control-IR) that experienced regional ischemia for 30 minutes and then reperfusion for 60 minutes. 4. Group (diabetic-IR) who experienced regional ischemia for 30 minutes and then reperfusion for 60 minutes. 5. Group (control-IR-CyclospA) that after induction of IR damage, at the beginning of reperfusion for 15 minutes received Krebs containing mPTP inhibitor (cyclosporine A). 6. Group (diabetic-IR-CyclospA) that after induction of IR damage, at the beginning of reperfusion for 15 minutes received Krebs containing mPTP inhibitor (cyclosporine A). Cardiac arrhythmias were recorded by relevant recorder electrodes and transducer by powerlab device. At the end of reperfusion, the heart was isolated from the apparatus and Western blotting was used to measure the expression of connexin 43 and nitric oxide synthase. Results: In this study, the number and duration of premature ventricular complexes (PVC), number, duration and incidence of ventricular tachycardia (VT), number and duration of ventricular fibrillation (VF) and the severity of total arrhythmia in the group (control-IR-CyclospA) were significantly lower than the group (control-IR) (P <0.05). Also, the variable duration of ventricular fibrillation (VF) in the group (diabetic-IR-CyclospA) was significantly less than the group (diabetic-IR) (P <0.05). On the other hand, the expression of connexin 43 and eNOS proteins in the group (control-IR-CyclospA) was significantly higher than the group (control-IR) (P <0.05).