[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.
D002463:Cell Membrane Permeability / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D005609:Free Radicals; D006801:Humans; D009206:Myocardium / Q000473:pathology; D010101:Oxygen Consumption; D010879:Piperazines / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014292:Trimetazidine / Q000494:pharmacology*
D005609:Free Radicals; D010879:Piperazines; D013481:Superoxides; D014292:Trimetazidine
Pertubations cellulaires induites par l'ischémie. L'action de la trimétazidine.