Cardiac versus coronary vasodilator actions of isobutylmethylxanthine in dogs: comparison with theophylline.

Cardiac and coronary vasodilator effects of isobutylmethylxanthine (IBMX) and theophylline were compared in isolated, blood-perfused papillary muscle, sino-atrial (SA) node and atrioventricular (AV) node preparations of dogs. IBMX (1 nmol-1 mumol) and theophylline (30 nmol-10 mumol) were injected intra-arterially. In paced papillary muscle preparations, both agents increased the force of contraction. In spontaneously beating papillary muscle preparations, both agents increased the rate of ventricular automaticity. In SA node preparations, both agents increased sinus rate. In AV node preparations, both agents decreased AV conduction time only when they were injected into the artery supplying the AV node. In all preparations, both agents increased coronary blood flow. However, both agents were not homogeneously effective on these cardiovascular variables, but showed selectivity in the following order: Ventricular muscle contraction not equal to coronary blood flow greater than SA nodal automaticity not equal to AV nodal conduction greater than ventricular automaticity. These results indicate that IBMX and theophylline have almost an identical profile in their cardiac and coronary vasodilator effects. The two agents were different in that IBMX was 40-50 times as potent as theophylline in producing these effects. Thus, both agents appeared to express their cardiovascular profiles mainly through inhibition of cyclic AMP phosphodiesterase, although theophylline has been claimed to have additional actions.