Intervention in ischaemia. Reperfusion syndrome. Rationale for trimetazidine.
Although early reperfusion of cardiac tissue is now considered to be the only intervention capable of restoring the various cellular functions altered by ischaemia and preventing progression towards necrosis of myocardial cells, reperfusion is frequently accompanied by various manifestations grouped under the heading of reperfusion syndrome or reperfusion injury. Functional recovery is therefore not immediate, but usually appears after a certain delay following a period of contractile dysfunction (myocardial stunning) lasting for several hours or even days after the start of reperfusion. Characteristics reperfusion-induced arrhythmias are also observed. The cellular mechanisms underlying the reperfusion syndrome may involve cellular calcium overload, over-production of oxygen-derived free radicals, acidosis and/or development of an inflammatory reaction. Numerous pharmacological studies have been conducted over several years designed to limit such reperfusion injury and, consequently, prevent stunning and/or reperfusion-induced arrhythmias. A number of experimental studies in this field have demonstrated that trimetazidine exerts direct anti-ischaemic effects, limiting calcium accumulation and acidosis, inflammation and oxygen-derived free radical production following reperfusion. This agent therefore appears to be particularly promising clinically in the treatment of reperfusion lesions, for example in combination with thrombolysis during the acute phase of myocardial infarction.
de Leiris
J
J
Groupe de Recherche sur la Physiopathologic Cellulaire Cardiaque Université Joseph Fourier, Grenoble, France.
Boucher
F
F
D000138:Acidosis / Q000209:etiology; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism; D005609:Free Radicals; D006801:Humans; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D009205:Myocarditis / Q000209:etiology; D017382:Reactive Oxygen Species; D014292:Trimetazidine / Q000627:therapeutic use*
D005609:Free Radicals; D017382:Reactive Oxygen Species; D014292:Trimetazidine; D002118:Calcium