Comparative study of MDL 17043 and MDL 19205, new positive inotropic agents, by use of isolated, blood-perfused dog-heart preparations

Summary

The cardiac and coronary vasodilator effects of MDL 17043 and MDL 19205 were compared in isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. In these preparations, MDL 17043 (0.01–3 µmol) and MDL 19205 (0.01–3 µmol) were injected intra-arterially. Both drugs increased the force of contraction of papillary muscles paced at a rate of 120 stimuli/min, and a ten-fold increase in dose produced about a 100% increase in the force. The two drugs increased the sinus rate in SA node preparations, and a tenfold increase in dose resulted in about a 12% increase in sinus rate with MDL 17043 and about a 17% increase with MDL 19205. These drugs increased the rate of automaticity of spontaneously beating papillary muscles and also the force of contraction. With a ten-fold increase in dose, the increase in the rate was about 16% for MDL 17043 and about 9% for MDL 19205. No ventricular arrhythmias were produced by either drug. The drugs equally decreased AV conduction time by accelerating AV nodal conduction in AV node preparations whose right atria were paced at a rate of 150 stimuli/min. However, the decrease remained about 5% with a ten-fold increase in dose of both drugs. No AV junctional tachycardia was produced. In all preparations, both drugs increased (coronary) blood flow. In paced papillary muscle preparations a tenfold increase in dose resulted in about a 37% increase in blood flow with MDL 17043 and about a 42% increase with MDL 19205. Thus, it can be concluded that both drugs possess an almost identical profile in cardiac and coronary vasodilator effects. If there is any difference between the two drugs, it may be in pharmacokinetics but not in pharmacodynamics.