ISSN:
1435-1803
Keywords:
propafenone·HCl
;
enantiomers
;
cardiac conduction andrefractoriness
;
isolated guinea pig heart
;
Langendorff perfused
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The present study was focused on the stereoselective electrophysiological effects of (R)-and (S)-propafenone·HCl evaluated in isolated Langendorff perfused guinea pig hearts. Conduction intervals were measured using an ECG-recording method of high resolution. Refractory periods of the different parts of the myocardium were determined by stimulation with premature stimuli, as well as by stimulation with increasing pacing rate (rate-dependent/refractory periods). Drug concentrations of 0.1, 1 and 3 μM were tested. Both compounds induced a dose-dependent increase in AV-nodal, His-bundle, and intraventricular conduction time which reached significance (p〈0.01) following 3 μM of either compound. Sinus rate was also dose-dependently and significantly reduced. (R)- and (S)-propafenone·HCl induced a marked prolongation of the rate-dependent refractory period of sino-atrial (by 140±22%, p〈0.01 and by 141±14%, p〈0.01, respectively) and AV-nodal (by 34±22%, p〈0.01 and by 42±15%, p〈0.01, respectively) conduction and of the atrial (by 182±21%, p〈0.01 and by 195±15%, p〈0.01, respectively) and ventricular (by 93±16%, p〈0.01 and by 88±16%, p〈0.01, respectively) myocardium. The effective refractory periods evaluated by stimulation with premature stimuli were also significantly prolonged under the influence of (R)- and (S)-propafenone·HCl, except the ventricular myocardial refractoriness by (R)-propafenone·HCl (increase to 114±23%, n.s.). Both compounds showed a strong rate-dependence of their effects and, thus, the refractory periods evaluated by stimulation with increasing pacing rate were significantly more prolonged than the refractory periods evaluated by stimulation with premature stimuli. The main difference between the effects of (R)- and (S)-propafenone·HCl on the cardiac electrical activity is the lack of effect of (R)-propafenone·HCl on the ventricular myocardial refratoriness evaluated by stimulation with premature stimuli.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00795393
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