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Frequency-dependent effects of amiodarone on atrioventricular nodal function and slow-channel action potentials: evidence for calcium channel-blocking activity
- Source :
- Scopus-Elsevier
- Publication Year :
- 1987
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1987.
-
Abstract
- The purpose of these experiments was to determine the frequency dependence of the effects of amiodarone and its active desethyl metabolite on slow-channel tissues. Intravenous amiodarone and desethylamiodarone (10 or 25 mg/kg) increased atrioventricular conduction time (AVCT) and refractory period (AVERP) in open-chest, chloralose-anesthetized dogs. Drug effects on AVCT and AVERP were greatly augmented by increasing atrial stimulation frequency. The frequency dependence of drug effects was quantified by studying the response of atrioventricular (AV) conduction to changes in coupling interval. Under control conditions, premature atrial stimulation increased AVCT with a time constant of 70 msec. In the presence of amiodarone and desethylamiodarone, a biexponential relationship between AVCT and coupling interval was observed. One component had a time constant similar to control, and a slower component with a time constant of about 1 sec appeared. Slow-channel action potentials produced in canine cardiac false tendons by elevated potassium (25 mM) and isoproterenol in vitro showed interval-dependent changes in Vmax with a time constant averaging 74 msec in the absence of amiodarone. In the presence of amiodarone, a slower recovery phase of Vmax with a time constant averaging 0.94 sec was observed. These results indicate that amiodarone and its metabolite produce heart rate-dependent changes in AV nodal function in vivo and suggest use-dependent calcium-channel blockade as a mechanism of this action. Amiodarone's rate-related effects on slow-channel properties should produce selective depression of supraventricular tachyarrhythmias involving rapid activation of the AV node.
- Subjects :
- Male
medicine.medical_specialty
Refractory period
Metabolite
Action Potentials
Amiodarone
chemistry.chemical_compound
Dogs
Heart Conduction System
In vivo
Physiology (medical)
Internal medicine
medicine
Animals
business.industry
Calcium channel
Time constant
Calcium Channel Blockers
Atrioventricular node
medicine.anatomical_structure
chemistry
Atrioventricular Node
Cardiology
Female
Electrical conduction system of the heart
Cardiology and Cardiovascular Medicine
business
medicine.drug
Subjects
Details
- ISSN :
- 15244539 and 00097322
- Volume :
- 76
- Database :
- OpenAIRE
- Journal :
- Circulation
- Accession number :
- edsair.doi.dedup.....761793e31db41e8b3a0cf5d61425b3ff