Efficacy of the novel calcium antagonist R(+)-semotiadil in limiting the ventricular rate during atrial flutter in isolated guinea pig hearts

Ca2+ antagonists slow the ventricular rate by blocking conduction in the an terograde direction through the atrioventricular (AV) node. The aim of this study was to investigate the efficacy of the novel Ca2+ antagonist semotia dil compared with vepapamil and diltiazem on the filtering capacity of the AV node during simulated atrial flutter in isolated guinea-pig hearts perfu sed by the method of Langendorff. During sinus rhythm, semotiadil as well a s verapamil and diltiazem induced comparable depressant effects on AV-nodal conduction time and, during tachycardia, a comparable enhancement of this effect. The time constant (tau-on) for the drug-specific rate-dependent eff ect on AV-nodal conduction slowing was longest in the presence of verapamil compared with the long tau-on of semotiadil and the short tau-on of diltia zem. Verapamil and semotiadil exhibited a significantly greater effect than diltiazem on the mean ventricular cycle length (VCLmean), on the maximal v entricular cycle length (VCLmax) and on the standard deviation of the VCL ( SDVCL) during atrial flutter. Therefore the kinetics of the rate adaptation of AV-nodal conduction time in the presence of Ca2+ antagonists predicts t he filtering capacity of the AV node during atrial flutter. Semotiadil has a verapamil type of action on ventricular cycle length during atrial nutter , whereas the disadvantageous prolongation of maximal VCL as well as the di spersion of VCL with semotiadil was only about half those found with verapa mil.