Effects of trimetazidine on mitochondrial respiratory function, biosynthesis, and fission/fusion in rats with acute myocardial ischemia.

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.