96 Cardioprotective effect of trimetazidine in rats induced to an experimental model of acute myocardial infarction after the use of isoproterenol

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Abstract

Introduction

Trimetazidine (TMZ) is an anti-ischaemic drug that is not commonly used during acute myocardial infarction (AMI) and its pharmacological properties suggest that it may help to repair this disease.

Objective

To evaluate the effect of TMZ on experimentally induced AMI rats regarding the following parameters: the proportion of hearts with AMI scars and their respective area in the trimetazidine (T) group when compared to placebo (P) and control (C) groups, as well as to evaluate the weight of the hearts of groups C, P and T.

Methods

The animals were split into two groups (T and P) of 30 mice each. Prior to induction of AMI the T group received TMZ at the dose of 2.5 mg/kg and the P group received 1 ml of distilled water per gavage every 12 hours respectively. A third group C with 12 rats did not receive any drug. After two weeks of treatment the T and P groups were submitted to the experimental infarction with subcutaneous isoproterenol infusion at a dose of 150 mg/kg/day for two consecutive days. After 60 days they were anaesthetised, electrocardiogram was performed and they were euthanized. The hearts were removed, weighed and submitted to histological analysis with Mason’s trichrome. Statistical analysis was performed using the Student t-test or ANOVA for quantitative variables with normal distribution and chi-square test for qualitative variables and the software Excel and SPSS 21.0.

Results

In the electrocardiographic evaluation, electrically inactive zones were found in 8.3%, 66.7% and 48% of the animals of groups C, P and T (p=0.005). Regarding the infarcted wall, the most common area of infarct was the inferior wall, occurring in 0%, 38.1% and 32% of the animals in the C, P and T groups (p=0.132).In the histological analysis were found areas of fibrosis corresponding to old AMI in 0%, 40% and 70% in the C, P and T groups (p<0.001).As for the intensity of ischemia, it was considered mild intensity at 0%, 60% and 40% and moderate at 0%, 10% and 0% in the C, P and T groups, respectively (p=0.001) In relation to the proportion of AMI scar area, were found the following values: 22.20 ± 13.04% in the T group and 57.28 ± 21.28% in the P group (p<0.001). As for the weight of the hearts were found the following values: 1.32 ± 0.11 g, 1.44 ± 0.12 g and 1.38 ± 0.14 g (p=0.026), for groups C, P and T respectively.

Conclusion

Were found a lower proportion of AMI scars in the T group when compared to the P group, both by electrocardiographic analysis and histological evaluation (p<0.005). It was also noticed a larger area with AMI in Group P when compared to T group (p<0.001) and greater heart‘s weight in group P when compared to group T and C (p=0.0026).

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