Influence of Trimetazidine on Refractory Period of Isolated Rat Cardiac Muscle

Abstract

Isolated rat atrial and papillary muscles were kept in a Locke's solution aerated with 100%oxygen at 30°C, of which refractory period was measured by using Govier's double stimulus method. Changes of the refractory period were examined when the temperature of the medium was changed from 30°C to 25 or 40°C and oxygen concentraton in the aeration gas from 100% to 60,40,20 or 10% by replacing the oxygen by nitrogen. In the case in which the medium was aerated with 100% oxygen gas, the refractory period of the atrial and papillary muscles was lengthened when the temperature was lowered from 30 to 25°C, and was shortened when it was raised from 30 to 40°C. Each refractory period generally shortened with reducing the oxygen concentration in aeration gas: it was most marked when the atrial muscle was kept at 25,30 or 40°C and when the papillary muscle was kept at 40°C; and not so marked when the papillary muscle was kept at 25 or 30°C. By the presence of trimetazidine [0.0001 and 0.001% (w/v), i. e., 0.003 and 0.03 mM] in the medium, the shortening of the refractory period induced by the reduction of oxygen concentration was prevented in atrial muscle kept at 25,30 or 40°C and in papillary muscle kept at 40°C; although the shortening of the refractory period was not so marked in papillary muscle kept at 25 or 30°C, the drug caused it longer than value obtained in the muscle aerated by 100%oxygen gas. The results suggest a new possible application of trimetazidine to the clinical field, as no serious side effect of the drug has been reported in spite of its wide clinical use as an anti-anginal drug in this country.