Cardiac effects of a new cardiotonic drug, AR-L 115 BS.

Abstract

In isolated blood-perfused dog-heart preparations, cardiac and coronary vasodilator effects of AR-L 115 BS were investigated in comparison with those of theophylline. Furthermore, the inhibitory effect of both drugs was examined on the crude cyclic AMP phosphodiesterase (PDE) prepared from the dog heart ventricle. When injected intra-arterially, AR-L 115 BS (3 μg - 1 mg) and theophylline (3 μg - 1 mg) increased force of contraction and rate of automaticity of the papillary muscle, sinus rate, decreased AV nodal conduction time in respective preparations, and increased blood flow in all of them. However, AR-L 115 BS was far more selective for inotropy than for chronotropy as compared with theophylline. AR-L 115 BS was also more selective for inotropy than for coronary blood flow as compared with theophylline, whereas it was opposite for the latter. Both drugs were less effective on ventricular automaticity. AR-L 115 BS (0.3 -10 mM) was less effective than theophylline (0.3 - 3 mM) in the PDE inhibitory activity, although the former was about 3 times more effective than the latter in producing a positive inotropic effect. The present results suggest that unknown mechanisms besides PDE-inhibition also contribute to the positive inotropic effect of AR-L 115 BS.