[Trimetazidine preservation of the energy potential of the myocardium during ischemia and reperfusion. Phosphorus NMR spectroscopy study of the isolated heart].

The effects of trimetazidine on ischaemia-induced metabolic damage were checked by 31 phosphore - nuclear magnetic resonance spectroscopy on the isolated rat heart. Isolated rat hearts, retrogradely perfused (37 degrees C, 9.81 kPa, pH 7.4 bicarbonate buffer) were submitted to partial global ischaemia (24 min, 0.2 ml.min-1 residual coronary flow) or total global ischaemia (12 min no flow). 31 phosphore-nuclear magnetic resonance spectra (132 i, 45 degrees, 101.3 MHz) were taken every 3 minutes. Changes in ATP, phosphocreatine and inorganic phosphore heart contents were followed, and intracellular pH was estimated from the chemical shift or inorganic phosphore. Trimetazidine was added to the perfusion fluid at the beginning of perfusion. The drug was used at two concentrations: 6.10(-7) M which has no effect on the contractility of the heart in normoxic conditions and 6.10(-4) which depresses significantly heart work. When trimetazidine was used at the concentration of 6.10(-7) M, the intracellular acidosis at the end of a 24 min low-flow ischaemia was less than in control hearts (6.6 versus 6). During reperfusion the restoration of the phosphorylation processes (as expressed by the ratio ATP/inorganic phosphore) was accelerated under the effect of the drug. Similar, but more pronounced, effects were observed in a 12 min total ischaemia when trimetazidine was given at a concentration (6.10(-4) M) which induces a reduction of cardiac work. In this case the myocardial ATP content was also protected during ischaemia. Under the effect of trimetazidine the phosphorylation processes are more rapidly restored during reperfusion than in control hearts. The protection of the mechanisms or structures involved in the energy transfers could be due to the reduction, under the effects of trimetazidine, of the intracellular acidosis induced by ischaemia.