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Modulation of procainamide's effect on conduction by cellular uncoupling in perfused rabbit hearts
J F Spear1, B G Hook, M E Josephson
1Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, USA.
Journal of Cardiovascular Electrophysiology
|February 1, 1997
Summary
The antiarrhythmic drug procainamide’s impact on heart electrical conduction is altered by cell-to-cell coupling. Reduced coupling, induced by heptanol, attenuated procainamide’s slowing effect on conduction velocity.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Biophysics
Background:
- The influence of cell-to-cell electrical coupling on antiarrhythmic drug efficacy remains poorly understood.
- Investigating this relationship is crucial for understanding drug mechanisms and optimizing antiarrhythmic therapies.
Purpose of the Study:
- To evaluate how varying degrees of cell-to-cell electrical coupling affect the action of procainamide on myocardial conduction.
- To determine if procainamide's effects on conduction velocity are modulated by altered electrical coupling.
Main Methods:
- Langendorff-perfused rabbit hearts were used to record electrograms at multiple ventricular epicardial sites.
- Conduction velocity was measured during pacing, both longitudinally and transversely to myocardial fibers.
- Graded doses of heptanol were administered to progressively reduce cell-to-cell electrical coupling, with and without procainamide (15 mg/L).
- Intracellular potentials were recorded using microelectrode techniques in isolated myocardium.
Main Results:
- Procainamide alone slowed myocardial conduction velocity.
- Increasing doses of heptanol attenuated procainamide's depressant effect on conduction velocity.
- At the highest heptanol dose, procainamide's effect was reversed, particularly for longitudinal conduction.
- Heptanol did not affect action potential amplitude or maximum rate of depolarization when procainamide was present.
Conclusions:
- The effect of procainamide on conduction velocity is significantly influenced by the degree of cell-to-cell electrical coupling.
- This study provides a model for assessing how pharmacologic agents modulate cardiac conduction under conditions of altered electrical coupling.