ABC | Volume 112, Nº2, February 2019

Original Article The Effects of Trimetazidine on QT-interval Prolongation and Cardiac Hypertrophy in Diabetic Rats Fatemeh Ramezani-Aliakbari, Mohammad Badavi, Mahin Dianat, Seyed Ali Mard, Akram Ahangarpour Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz – Iran Mailing Address: Mohammad Badavi • Persian Gulf Physiology Research Center, Dept. of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz – Iran E-mail: badavim@yahoo.com Manuscript received April 24, 2018, revised manuscript July 23, 2018, acepted July 23, 2018 DOI: 10.5935/abc.20180248 Abstract Background: Trimetazidine (TMZ) is an anti-ischemic drug. In spite of its protective effects on cardiovascular system, there is no scientific study on the usefulness of TMZ treatment for prolonged QT interval and cardiac hypertrophy induced by diabetes. Objectives: To evaluate the effects of TMZ on QT interval prolongation and cardiac hypertrophy in the diabetic rats. Methods: Twenty-four male Sprague-Dawley rats (200-250 g) were randomly assigned into three groups (n = 8) by simple random sampling method. Control (C), diabetic (D), and diabetic administrated with TMZ at 10 mg/kg (T10). TMZ was administrated for 8 weeks. The echocardiogram was recorded before isolating the hearts and transfer to a Langendorff apparatus. Hemodynamic parameters, QT and corrected QT interval (QTc) intervals, heart rate and antioxidant enzymes were measured. The hypertrophy index was calculated. The results were evaluated by one-way ANOVA and paired t-test using SPSS (version 16) and p < 0.05 was regarded as significant. Results: The diabetic rats significantly indicated increased hypertrophy, QT and QTc intervals and decreased Left ventricular systolic pressure (LVSP), Left ventricular diastolic pressure (LVDP), rate pressure product (RPP), Max dp/dt, and min dp/dt (±dp/dt max), heart rate, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase in the heart. Treatment with TMZ in the diabetic animals was significantly improved these parameters in comparison to the untreated diabetic group. Conclusions: TMZ improves QTc interval prolongation and cardiac hypertrophy in diabetes. (Arq Bras Cardiol. 2019; 112(2):173-178) Keywords: Diabetes Mellitus; Trimetadizine; Cardiomegaly; Electrocardiology; Oxidative Stress; Rats. Introduction Diabetes is associated with cardiovascular disorders and increased mortality rate in diabetic patients. 1 The statistic reveals that 30 million people were suffered from diabetes worldwide in 1985 and recently, it is predicted by WHO, there will be 300 million by the year 2025. 2 Diabetic cardiomyopathy is known as the structural and functional alterations in the heart induced by diabetes that are associated with cardiac hypertrophy, diastolic and/or systolic dysfunction in the absence of hypertension, valvular and ischemic heart diseases and other cardiac disorders. 3,4 QT and QTc intervals are electrocardiographic parameters that regarded as critical predictors of mortality and stroke in diabetic patients. 5,6 The pathological QT prolongation is known as a risk factor that increases ventricular arrhythmias and other heart diseases. Moreover, ventricular hypertrophy plays an important role in developing prolonged QT interval-related diabetes. 7 A previous study has confirmed the negative effects of hypertrophy and QT interval prolongation on the function of heart in diabetes. 8 The homeostasis of energy is effective in decreasing the hypertrophy in the heart. 9 Trimetazidine (TMZ) is an anti-angina agent that is known to improve metabolism of energy in the heart subjected to ischemia. 10,11 Previous studies have indicated reduced fatty acid oxidation via reducing mitochondrial 3-ketoacyl CoA thiolase (3-KAT) activity in beta-oxidation by TMZ treatment. 12 Others also indicated that TMZ has protective effects on cardiac fibrosis resulted from pressure overload. 13 In addition, there are some other investigations showing that the treatment with TMZ has positive effects on cardiac function in diabetic individuals with cardiovascular disorders. 14 Taken together, these results from related studies make evidence that TMZ has beneficial effects on cardiovascular system. However, the role of TMZ in QT interval prolongation and cardiac hypertrophy improvement in diabetes was still unknown. Therefore, the present study was undertaken to evaluate the effects of TMZ on QT interval prolongation and cardiac hypertrophy in the diabetic animals. 173