Modulating intraventricular conduction through competition of two class 1 antiarrhythmic agents: Experience with ethacizin and lidocaine in canine heart*1
| Autor: | J. C. Makielski, E.M. Bugrij, T. Ivanovoch, C F Starmer, A.V. Mazaev, Vladislav V. Nesterenko, G.G. Beloshapko, L.V. Rosenshtraukh, E.P. Anyukhovsky |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
biology
Lidocaine Local anesthetic medicine.drug_class Chemistry Sodium channel Fissipedia Stimulation biology.organism_classification Nerve conduction velocity Electrophysiology medicine.anatomical_structure Ventricle Anesthesia medicine Cardiology and Cardiovascular Medicine Molecular Biology medicine.drug |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 23:115-124 |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/0022-2828(91)90030-p |
| Popis: | The frequency-dependent effects on the intraventricular conduction through the dog heart in situ produced by two class 1 antiarrhythmic drugs, ethacizin and lidocaine, with different kinetic properties were investigated. Conduction delay was measured using stimulation of the His-bundle after pharmacologically induced atrioventricular (AV) block. Electrical events were derived from local epicardial bipolar electrograms at the base of the right ventricle. The stimulation program consisted of several 50-pulse trains with progressively shorter interstimulus intervals (ISI) separated by a 1-s pause. Ethacizin (1.5 mg/kg) increased conduction delay by 30% at ISI of 1000 ms, and the effect was enhanced when ISI was shortened to 200 ms; 1-s pauses did not significantly increase conduction velocity. Addition of lidocaine (12 mg/kg) strongly potentiated the ethacizin effect at ISI shorter than 300 ms without any noticeable increase in conduction delay at longer intervals. The major result was dramatic acceleration of conduction during the 1-s pauses while both drugs were infused. With this combination, conduction delay after pause was shorter than with ethacizin alone, which is consistent with the competition of the drugs for the same binding site inside the sodium channel. Combination of two class 1 compounds in clinical practice may enhance their antiarrhythmic effects without adversely inhibiting normal impulse conduction in the heart. Computer-predicted data were in reasonable agreement with experimental results. The “guarded receptor” model, thus, can provide a simple method for predicting local anesthetic drug interactions in man. |
| Databáze: | OpenAIRE |
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