Actions and interactions of theophylline and imidazole on cardiac contractility, phosphorylase activation and cyclic AMP.

Injection of 1.0 mg theophylline and 1.6 mg imidazole into guinea-pig hearts perfused by the Langendorff technique increased cardiac contractile force by 20.0 +/- 1.0% and 23.3 +/- 1.2% over control and activated phosphorylase without producing significant changes in cyclic AMP levels. When guinea-pig hearts were perfused with theophylline (10(-3) M) or imidazole (20 mM), injection of either imidazole or theophylline did not further increase cardiac contractility or phosphorylase a levels. In all cases there was no change in cycylic AMP levels. Data in the literature indicate that calcium plays a role in the cardiac biochemical and mechanical effects of theophylline and imidazole. Both drugs may thus produce their cardiac effects by a calcium rather than a cyclic AMP mediated mechanism.