Influence of Trimetazidine on Refractory Period of Isolated Rat Cardiac Muscle

Abstract

SummaryIsolated 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 O. 001% (w/v) , i. e. , O. 003 and O. 03 mIV11 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.