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Effects of isoproterenol and propranolol on pharmacologically induced depression of intraventricular conduction
1Department of Medical Pharmacology, Claude Bernard University, Lyon, France.
Insights
Adrenergic drugs like isoproterenol and propranolol significantly impact depressed intraventricular conduction. Isoproterenol may prevent reentrant arrhythmias, while propranolol might trigger them by affecting conduction velocity.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- The cardiac adrenergic system typically has minimal impact on ventricular conduction velocity.
- Class IC antiarrhythmic drugs can depress intraventricular conduction.
Purpose of the Study:
- To investigate the effects of isoproterenol and propranolol on drug-induced intraventricular conduction delay.
- To determine the role of adrenergic modulation in preventing or triggering reentrant arrhythmias.
Main Methods:
- Anesthetized dogs were used to study intraventricular conduction time and effective refractory period (ERP).
- Conduction was slowed using cibenzoline, followed by administration of isoproterenol or propranolol.
- Electrocardiography and direct ventricular pacing were employed.
Main Results:
- Isoproterenol attenuated cibenzoline-induced conduction slowing, while propranolol aggravated it.
- The effect on effective refractory period (ERP) was not significantly different between drug groups.
- Adrenergic drugs significantly influence depressed intraventricular conduction.
Conclusions:
- Adrenergic modulation plays a crucial role in managing depressed intraventricular conduction.
- Isoproterenol may offer protection against reentrant arrhythmias, whereas propranolol could increase their risk.
- These findings highlight the sensitivity of impaired conduction to adrenergic influences, likely due to altered fiber polarization and sodium conductance.
Abstract:
The cardiac adrenergic system is known to have practically no influence on conduction velocity in the ventricles under normal conditions. The effects of isoproterenol and propranolol were investigated on depression of intraventricular conduction induced by a class IC antiarrhythmic drug, cibenzoline, in anaesthetized, closed-chest dogs. In addition to electrocardiogram for measurement of QRS duration in sinus rhythm, conduction time was measured in the ventricular contractile tissue between an electrode advanced to the apex and a pacing electrode near the base, at 400- and 200-ms pacing periods. Effective refractory period (ERP) was measured concurrently according to the extrastimulus method. After intraventricular conduction had been slowed down by cibenzoline IV administered (loading dose of 3 mg/kg plus infusion of 0.2 mg/kg/min over 15 min), isoproterenol was infused or propranolol injected by the intravenous route also (0.5 mn/micrograms/kg/min over 5 min and 0.4 mg/kg, respectively). When conduction time has been raised by 75/150% (depending on the pacing rate), isoproterenol appears to attenuate and propranolol to aggravate substantially the impairment of conduction, whereas the reduction undergone by ERP does not differ from usual. Thus, reentrant arrhythmias might be prevented by isoproterenol and triggered by propranolol. Intraventricular conduction, when depressed, therefore, is sensitive to adrenergic drugs, probably because of the enhanced influence of polarization of the fibres in the presence of a sodium conductance impairment.