Electrophysiological and antiarrhythmic properties of propafenon in isolated cardiac preparations
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Abstract:
Propafenon, a new antiarrhythmic drug, caused a 30% decrease in maximal driving frequency and a 65 ms net increase in functional refractory period of isolated guinea pig atria at a concentration as low as 0.5 microgram/ml. The spontaneous rate of isolated atria and the contractility of electrically driven ventricular strips were reduced after treatment with propafenon 1 microgram/ml. Propafenon 0.5 microgram/ml also altered action potentials of sheep Purkinje fiber. It reduced the action potential and overshoot amplitudes, decreased the maximum rate of depolarization of the action potential upstroke in a frequency-dependent fashion, shortened the action potential and effective refractory period, and depressed the membrane responsiveness. Moreover, propafenon antagonized the chronotropic and inotropic effects of isoprenaline in isolated guinea pig heart preparations; the pA2 value was about 6.4. Finally, propafenon possessed very weak calcium antagonist properties, being about 100 times less potent than verapamil in this respect. We conclude that propafenon is an antiarrhythmic drug with beta-adrenoceptor blocking and "membrane stabilizing" activities in the same range of concentrations and that it has a calcium antagonistic activity only at much higher concentrations.
Insights
Propafenone, an antiarrhythmic drug, effectively reduces heart rate and strengthens the refractory period in cardiac tissues. It exhibits beta-adrenoceptor blocking and membrane-stabilizing effects, with minimal calcium antagonism at therapeutic concentrations.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Electrophysiology
Background:
- Antiarrhythmic drugs are crucial for managing cardiac rhythm disorders.
- Understanding the electrophysiological effects of novel antiarrhythmics is essential for clinical application.
- Propafenone is a Class Ic antiarrhythmic agent with known efficacy.
Purpose of the Study:
- To investigate the electrophysiological and pharmacological effects of propafenone.
- To determine the concentration-dependent actions of propafenone on cardiac function.
- To elucidate the mechanisms underlying propafenone's antiarrhythmic properties.
Main Methods:
- Isolated guinea pig atria and sheep Purkinje fiber preparations were used.
- Electrophysiological parameters including action potential and refractory period were measured.
- Effects on isoprenaline and calcium channel activity were assessed.
Main Results:
- Propafenone decreased maximal driving frequency and increased atrial refractory period.
- It reduced spontaneous atrial rate, ventricular contractility, and altered Purkinje fiber action potentials.
- Propafenone antagonized isoprenaline's effects and showed weak calcium channel blocking activity.
Conclusions:
- Propafenone exhibits significant beta-adrenoceptor blocking and membrane-stabilizing activities at relevant concentrations.
- Its antiarrhythmic effects are mediated through these mechanisms.
- Calcium antagonism by propafenone is minimal and occurs at much higher concentrations.