COMPARATIVE STUDIES ON THE CARDIOTONIC ACTION OF CORCHOROSIDE A, OUABAIN AND STROPHANTHIN K ON THE HEART-LUNG PREPARATION OF GUINEA PIG AND CAT

The cardiotonic potency and therapeutic range of corchoroside A were compared with the well-known cardiac glycosides in heart-lung preparations of guinea pigs and cats. Heart failure was produced by adding pentobarbital sodium to the blood in the venous reservoir of heart-lung preparations (HLP) at a uniform rate (1mg/minute) in most experiments. In some other experiments the preparations were allowed to deteriorate spontaneously.A Steady fall in the cardiac output and right atrial pressure rise was taken as an indication of failure. The cardiac Competence test was used to assess the cardiac function by raising the venous reservoir by 5～10 cm for 15 seconds.The reduction in atrial pressure and the increased cardiac output were taken as an indicator of "threapeutic dose". Following the appearance of therapeutic effects the continued infusion of a cardiac glycoside results in cardiac irregularities. These irregularities are accompanied by a progressive reduction in the cardiac output and a concomitant abrupt rise in atrial pressure with widened pulse waves. These phenomena mentioned above were taken as an indicator of "toxic dose". Further continuation of the infusion results in ventricular fibrillation and was taken as an indicator of "lethal dose".The ratios of the threapeutic dose and toxic dose to the lethal dose in three glycosides have been expressed in per cent of the dose respectively. In the HLP of cats corchoroside A usually yielded higher therapeutic effect than ouabain and strophanthin K. In the HLP of guinea pigs its therapeutic dose was similar with ouabain and higher than strophantin K. Corchoraside A not only improved cardiac function and increased cardiac competence but the manifestation of cardiotonic action was earlier.Under our experimental conditions in the HLP of guinea pigs the per centage ratio of therapeutic dose/lethal dose was 6.05 for corchoroside A, 17.45 for ouabain, 14.41 for strophanthin K and in the HLP of cats 10.86, 21.29, and 22.96 respectively. Hence, corchoroside A has a 2～3 fold greater "safety margin" than the other two glycosides studied. It is statistically significant, The utilization of the HLP of guinea pigs as a novel tool for the determination of the therapeutic range of cardiac glycosides is also discussed.