title: Efficacy of the novel calcium antagonist R(+)-semotiadil in limiting the ventricular rate during atrial flutter in isolated guinea pig hearts.
abstract: Ca2+ antagonists slow the ventricular rate by blocking conduction in the anterograde direction through the atrioventricular (AV) node. The aim of this study was to investigate the efficacy of the novel Ca2+ antagonist semotiadil compared with verapamil and diltiazem on the filtering capacity of the AV node during simulated atrial flutter in isolated guinea-pig hearts perfused by the method of Langendorff. During sinus rhythm, semotiadil as well as 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 effect 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 diltiazem. Verapamil and semotiadil exhibited a significantly greater effect than diltiazem on the mean ventricular cycle length (VCLmeun), on the maximal ventricular cycle length (VCLmax) and on the standard deviation of the VCL (SD(VCL)) during atrial flutter. Therefore the kinetics of the rate adaptation of AV-nodal conduction time in the presence of Ca2+ antagonists predicts the filtering capacity of the AV node during atrial flutter. Semotiadil has a verapamil type of action on ventricular cycle length during atrial flutter, whereas the disadvantageous prolongation of maximal VCL as well as the dispersion of VCL with semotiadil was only about half those found with verapamil.
authors.affiliation: Department of Internal Medicine, Karl-Franzens-University, Graz, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Schwarzl
authors.forename: U
authors.initials: U
authors.lastname: Stark
authors.forename: M
authors.initials: M
authors.lastname: Brodmann
authors.forename: U
authors.initials: U
authors.lastname: Haiden
authors.forename: H A
authors.initials: HA
authors.lastname: Tritthart
authors.forename: G
authors.initials: G
authors.lastname: Stark
mesh_terms: D000818:Animals; D001282:Atrial Flutter / Q000188:drug therapy*; D001283:Atrioventricular Node / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004110:Diltiazem / Q000627:therapeutic use; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D013844:Thiazoles / Q000627:therapeutic use*; D013997:Time Factors; D016276:Ventricular Function / Q000187:drug effects*; D014700:Verapamil / Q000627:therapeutic use
chemical_list: D002121:Calcium Channel Blockers; D013844:Thiazoles; D014700:Verapamil; C064356:sesamodil; D004110:Diltiazem