Objective: Myocardial ischemia affects mitochondrial functions, leading to ionic imbalance and susceptibility to ventricular fibrillation. Trimetazidine, a metabolic agent, is clinically used in anti-anginal therapy.
Methods: In this study, the rats were orally treated by gavage with trimetazidine 10 mg/kg/d for 7 days, and the effects of trimetazidine on mitochondrial respiratory function, biosynthesis, and fission/fusion in rats with acute myocardial ischemia were evaluated.
Results: It has been suggested that acute myocardial ischemia leads to a damage to mitochondrial functions. However, compared with ischemia group without trimetazidine administration, a significant reduction in the infarct size was observed in trimetazidine-treated ischemia group (31.24±3.02% vs. 52.87±4.89%). Trimetazidine preserved the mitochondrial structure and improved respiratory control ratio and complex I activity. Furthermore, trimetazidine improved mitochondrial biosynthesis and fission/fusion, as demonstrated by the promotion of peroxisome proliferator-activated receptor gamma (PPARγ) co-activator 1α (PGC-1α), mitofusins 1 (Mfn1), dynamin-related protein 1 (Drp1), and optic atrophy 1 (Opa1) expressions in rats with acute myocardial ischemia.
Conclusion: Taken together, it was suggested that in this rat model of myocardial ischemia, trimetazidine demonstrated cardioprotective effects attributing to the preservation of mitochondrial respiratory function, biosynthesis, and fission/fusion and, thus, could be considered as an agent for cardioprotection.