| Differential effects of D-sotalol, quinidine, and amiodarone on dispersion of ventricular repolarization in the isolated rabbit heart. | |
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MedLine Citation:
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PMID: 9395166 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Increased dispersion of ventricular repolarization has been suggested as a cause of proarrhythmic effects of Class IA or III antiarrhythmic drugs, such as d-sotalol, quinidine, and amiodarone. METHODS AND RESULTS: The influence of d-sotalol, quinidine, and amiodarone on the dispersion of monophasic action potential (MAP) durations was studied in 55 isolated Langendorff-perfused rabbit hearts at different pacing cycle lengths (CLs). MAP duration measured at 90% repolarization (APD90) was determined from 6 to 8 endocardial and epicardial MAP recordings with dispersion of ventricular repolarization defined as the range of APD90. The protocol was repeated 60 minutes after initiation of a perfusate containing increasing concentrations of d-sotalol (n = 12, 10[-6] M, 10[-5] M, and 5 x 10[-5] M) and quinidine (n = 8, 10[-6] M and 10[-5] M). Seventeen rabbits were fed with an aqueous solution of amiodarone (50 mg/kg per day over 4 weeks). The data of these experiments (n = 17) were compared with a series of 18 untreated control rabbits. Dispersion of ventricular repolarization was unchanged with the low concentration of d-sotalol (10[-6] M) but was increased-particularly at long CLs-with higher d-sotalol concentrations. With both concentrations of quinidine, dispersion of ventricular repolarization was increased in a rate-independent manner. Amiodarone did not affect dispersion of ventricular repolarization. CONCLUSIONS: Rate-dependent and concentration-dependent increases in dispersion of ventricular repolarization by d-sotalol and quinidine in this isolated rabbit heart model may help explain their proarrhythmic effects while the absence of an increase in dispersion of ventricular repolarization with amiodarone correlates with its clinically observed lower incidence of proarrhythmia. |
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Authors:
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M Zabel; S H Hohnloser; S Behrens; R L Woosley; M R Franz |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of cardiovascular electrophysiology Volume: 8 ISSN: 1045-3873 ISO Abbreviation: J. Cardiovasc. Electrophysiol. Publication Date: 1997 Nov |
Date Detail:
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Created Date: 1997-12-29 Completed Date: 1997-12-29 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9010756 Medline TA: J Cardiovasc Electrophysiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1239-45 Citation Subset: IM |
Affiliation:
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Division of Clinical Pharmacology, Georgetown University and Veterans Administration Medical Center, Washington, DC 20422, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials
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drug effects Amiodarone / pharmacology* Animals Anti-Arrhythmia Agents / pharmacology* Heart Ventricles / drug effects* Quinidine / pharmacology* Rabbits Sotalol / pharmacology* Ventricular Function |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 1951-25-3/Amiodarone; 3930-20-9/Sotalol; 56-54-2/Quinidine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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