Protective effects of trimetazidine on ischaemic myocardial dysfunction

Experimental and clinical studies have shown that trimetazidine has a number of potentially useful cytoprotective features. The drug has been reported to limit intracellular acidosis, sodium and calcium accumulation, to preserve contractile function and to limit cytolysis and membrane damage caused by oxygen free radicals. All these effects contribute towards reducing the deleterious effects of ischaemic insult. Improved cellular function during ischaemia could explain the beneficial effects of trimetazidine on resting and dobutamine-induced myocardial ischaemic dysfunction. Preserving mitochondrial function and energy metabolism from chronic oxygen deprivation may reduce ischaemic left ventricular dysfunction. Experimental studies also suggest that trimetazidine acts by affecting myocardial substrate utilization because the drug inhibits oxidative phosphorylation and utilization of fatty acid substrates and shifts metabolism from fatty acid to glucose oxidation. As these effects occur in the absence of detectable changes in systemic and coronary haemodynamics, the in vivo effects of trimetazidine on ischaemic myocardium are likely to depend on direct cytoprotection.