ABC | Volume 112, Nº2, February 2019

Original Article Badavi et al Trimetazidine effects on diabetic hearts Arq Bras Cardiol. 2019; 112(2):173-178 Figure 1 – QT interval (a), QTc interval (b) values in control (C), diabetic (D) and diabetic treated with TMZ (10 mg/kg, T10) groups eight weeks after treatment in the rats. The results were presented as mean ± SD. ## p < 0.01 compared to the control group, * p < 0.05 compared to the diabetic group. 120 A 100 80 60 40 20 0 QT (ms) 120 B 100 80 60 40 20 0 QTc (ms) ## ## * * C D T10 Animal groups C D T10 Animal groups Table 1, the diabetic rats indicated a decrease in the heart rate compared to the control rats (198 ± 41.21 vs. 268 ± 27.99, p = 0.002). Obviously, the administration of diabetic group with TMZ significantly increased the heart rate compared to the untreated diabetic rats (263 ± 35.02 vs. 198 ± 41.21, p = 0.006). Markers of cardiac function At the end of the experiment, LVSP, LVDP, ±dp/dt max and RPP were observed significantly lower in the diabetic group than control group. However, TMZ administration for 8 weeks was associated with a significant increase in these parameters in comparison with the untreated diabetic rats (Table 1). Effect of TMZ on myocardial hypertrophy As indicated, the hypertrophy index increased significantly in the diabetic rats on 8 weeks compared to the control group (56.62 ± 6.50 vs. 48.62 ± 7.90, p = 0.039). According to our findings, in the diabetic rats, administrationwith TMZ remarkably decreased the hypertrophy indexwhen compared to the diabetic rats (41.87 ± 7.50 vs. 56.62 ± 6.50, p < 0.001, Figure 2). Effect of TMZ on antioxidant enzymes As indicated in Table 2, antioxidant enzymes, GPx, CAT and SOD significantly decreased in the heart of diabetic animals as compared to the control group (p < 0.001, p = 0.002, respectively). However, oral administration with TMZ was significantly improved GPx, CAT and SOD (p < 0.001, p < 0.049, respectively). Discussion Our results indicated that alloxan injection significantly increased QT and QTc intervals and decreased heart rate, LVSP, LVDP, RPP, ±dp/dt max, and cardiac hypertrophy, SOD, GPx and CAT in the heart of the diabetic rats when compared with control group. However, treatment with TMZ was able to improve QT and QTc intervals, heart rate, hemodynamic parameters, SOD, CAT and hypertrophy significantly. Previous studies have demonstrated that diabetes is associated with the alterations of electromechanical and prolonged QTc interval in the heart. 23 Diastolic and systolic dysfunctions are the earliest manifestations in thedevelopment of diabetic cardiomyopathy. 24 The ±dp/dt max, LVSP, LVDP, RPP, cardiac diastolic and systolic indexes, are widely used to evaluate cardiac function. The alloxan-induced diabetic rats progressed cardiac dysfunction as demonstrated by a significant decrease in±dp/dt LVSP, LVDP, RPP. TMZ treatment in turn improved each of these parameters. In our model of type 1 diabetes, ECG indicated prolonged QTc, a finding that is consistent with previous studies. Treatment with TMZ significantly decreased these QT and QTc dispersions. This result is in agreement with previous reports which indicated that TMZ treatment improved QT prolongation in individuals with kidney disorders. 25,26 In the present study, we also observed that diabetes led to bradycardia in the diabetic animals. It is revealed that in the diabetic rats heart rate tends to decrease after eight weeks. 27 On the other hand, diabetes increases vagal tone and decreases sympathetic tone in diabetic rats. 28 In addition, treatment with TMZ improves autonomic tone in individuals with acute coronary syndrome. 29 Improved sympathetic and parasympathetic tone can partly explain the increased heart rate in the diabetic rats treated with TMZ. Diabetic cardiomyopathy is associated with cardiac hypertrophy and dysfunction. High blood glucose and oxidative stress maybe considered to be critical factors that involved in hypertrophy and dysfunction of the heart. 30 In the present study, the diabetic rats showed cardiac hypertrophy demonstrated by the increased heart wieght/body wieght ratio. Similar results have been indicated in previous studies. 31 It is well established that, increased VLDL-c and decreased HDL-c levels can result in reduction in anti-oxidant defense system. 27 In a previous study, it was indicated that the impairment of lipid profile levels in diabetic animals could be attributed to increased lipid breakdown and release of a large amount of free fatty acids. 17 The released free fatty acids are susceptible to oxidation 175