[Current concepts in cellular ischemia: role of trimetazidine]

Comparative clinical trials have already enabled to appreciate the clinical efficacy of trimetazidine (TMZ) during chronic coronary angina. Two recent controlled studies have been done in patients with chronic stable angina, and conducted in double blind versus placebo, with randomized assignment of the treatments. They showed that TMZ administered either in a single dose (60 mg), or for one month at a daily dose of 60 mg, enabled on the one hand an improvement of the stress ability: increase of the total work (respectively 31 and 38 per cent), and of the duration of the stress (17 per cent in an average), and on the other hand, the recession of the myocardial ischemic threshold: increase in the time of appearance of a 1 mm sub-shift of ST (respectively 7 and 17 per cent). The absence of alteration, in each of the placebo and trimetazidine groups, of the cardiac frequency and systolic arterial blood pressure at rest and the double product on exertion, suggested a different mechanism of action from the usual anti-angina medications. Many experimental works have been able to show that trimetazidine has an intra-cellular "anti-ischemic" activity and a cardioprotective effect which would be present during ischemic phases. The anti-ischemic activity would counteract the harmful effects of hypoxia by maintaining cellular energetic reserves, and by decreasing the deadly membrane effects of the free radicals, particularly passive permeability to potassium. In the same experimental conditions of ischemia, the cardioprotective effect is demonstrated by the decrease of the creatine kinase leakage and the upholding or the rapid recovery of the myocardial electric activity.(ABSTRACT TRUNCATED AT 250 WORDS)