Electromechanical effects of bepridil on rabbit isolated hearts - PubMed (original) (raw)

Electromechanical effects of bepridil on rabbit isolated hearts

T Anno et al. Br J Pharmacol. 1984 Jan.

Abstract

Electromechanical effects of a new antianginal agent, bepridil, on Langendorff-perfused rabbit hearts were compared with those of verapamil and lidocaine. Bepridil at concentrations above 2 X 10(-7)M caused a dose-related decrease in heart rate (HR), a prolongation of the atrio-His bundle conduction time (A-H interval) and a prolongation of the functional refractory period (FRP) of the atrioventricular (A-V) node. Similar changes in HR, A-H interval and the FRP of the A-V node were observed with verapamil at concentrations above 2 X 10(-8)M. Lidocaine at above 4 X 10(-5)M prolonged slightly the A-H interval and the FRP of the A-V node but did not decrease the HR. Bepridil at concentrations above 10(-6)M prolonged both the His bundle-ventricular conduction time (H-V interval) and the effective refractory period (ERP) of ventricular muscles. Similar changes in the H-V interval and in the ERP of ventricular muscles were observed with lidocaine at above 10(-5)M. Verapamil ranging between 5 X 10(-8)M and 8 X 10(-7)M had no effect on the H-V interval and appreciably shortened the ERP of ventricular muscles. Bepridil at concentrations above 2 X 10(-6)M reduced the developed tension as did verapamil at above 10(-7)M. On a molar basis, the depressant effect of bepridil on HR and the A-V nodal conduction, which may reflect inhibitory action on the slow channels, was less than one tenth that of verapamil. Bepridil was more potent than lidocaine in prolonging the H-V interval and the ERP of ventricular muscles indicating a possible inhibition of the fast sodium channels. Both of these electrophysiological effects of bepridil may afford significant bases for the antiarrhythmic action of the drug.

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References

1. 1. Am Heart J. 1974 Mar;87(3):367-82 - PubMed
2. 1. J Pharmacol Exp Ther. 1974 May;189(2):414-22 - PubMed
3. 1. Circ Res. 1974 Sep;35(3):413-25 - PubMed
4. 1. Am Heart J. 1975 Apr;89(4):526-36 - PubMed
5. 1. Am Heart J. 1975 May;89(5):665-73 - PubMed

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