[Cellular disorders induced by ischemia. The effect of trimetazidine]

In contrast with the classical anti-anginal drugs, trimetazidine appears to be a very specific treatment, especially to the ischaemic cell. Whereas beta-blockers, nitrates and calcium antagonists all act outside the real ischaemic area (on peripheral veins or arteries, coronary vessels, whole heart muscle contractility, sinus node, endo-epicardial blood flow ratio, etc...) trimetazidine is only efficient on the ischaemia-induced loss of membrane functions and its consequences. The disturbance of tissue oxygen supply during ischaemia decreases mitochondrial ATP production and increases the generation of free radicals (O2-., OH-.). By diminishing the bioavailability of free radicals, trimetazidine lessens all their toxic effects: trimetazidine acts on the inactivation of enzymatic membrane proteins (which induces ATP over-reduction, creatine phosphokinase and lactate release outside the cell and electrolyte shifts); trimetazidine corrects the elevation of passive membrane permeability (increased by free radical-induced peroxidation of unsaturated membrane lipids); it antagonises free radical-induced stimulations of phospholipase A2 and thromboxane synthetase. In conclusion, trimetazidine restores energy-producing processes in the ischaemic heart cell by lessening the toxic effects of oxygenated free radicals.