Document Detail

Dofetilide effects on the inhibition by trains of subthreshold conditioning stimuli.
MedLine Citation:
PMID:  15009858     Owner:  NLM     Status:  MEDLINE    
We investigated the electrophysiological actions of dofetilide upon the ventricular myocardium to determine whether the drug modifies the inhibitory effects of subthreshold stimuli trains upon ventricular refractoriness. In nine Langendorff perfused rabbit hearts, ventricular epicardial electrodes were used to determine the following parameters at baseline and during dofetilide perfusion (0.5 micromolar): effective (ERP) and functional (FRP) refractory periods, conduction velocity (CV), wavelength (WL), and ERP prolongation (inhibitory effect) induced by subthreshold stimuli trains (STr) at pulse frequencies of 100, 300, and 600 Hz. Dofetilide significantly prolongs ventricular refractoriness and WL: ERP increment (Dofetilide-baseline, 300 ms cycle length) = 33 +/- 20 ms (24 +/- 12%, P < 0.01); FRP increment = 37 +/- 19 ms (23%+/- 10%, P < 0.01); WL increment = 4.1 +/- 3.2 cm (27%+/- 20%, P < 0.01), without modifying CV. These effects are diminished upon increasing the stimulation frequency: ERP increment (Dofetilide-baseline, 150 ms cycle length) = 18 +/- 10 ms (18%+/- 12%, P < 0.05); FRP increment = 15 +/- 4 ms (14%+/- 5%, P < 0.01); WL increment = 1.9 +/- 1.7 cm (18%+/- 10%, P < 0.01). The STr significantly prolong ERP, and the increments obtained at baseline and during dofetilide perfusion are similar. In both cases the inhibitory effect is slight for STr of 100 Hz (baseline = 5 +/- 3 ms, dofetilide = 6 +/- 5 ms, with nonsignificant (ns) differences between them) and highly manifest for STr of 300 Hz (baseline = 76 +/- 33 ms, dofetilide = 87 +/- 32 ms, ns) and 600 Hz (baseline = 109 +/- 39 ms, dofetilide = 89 +/- 34 ms, ns). Dofetilide prolongs ventricular refractoriness and WL, exerting a reverse-frequency dependent effect without modifying CV. The inhibitory effect of STr is greater when their pulse frequency is increased, and its magnitude is similar under the influence of dofetilide. During dofetilide perfusion the inhibitory effect of STr adds to the ERP prolongation induced by the drug.
Francisco J Chorro; Juan Sanchis
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pacing and clinical electrophysiology : PACE     Volume:  27     ISSN:  0147-8389     ISO Abbreviation:  Pacing Clin Electrophysiol     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-10     Completed Date:  2004-07-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7803944     Medline TA:  Pacing Clin Electrophysiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  327-32     Citation Subset:  IM    
Service of Cardiology, Valencia University Clinic Hospital, Valencia, Spain.
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MeSH Terms
Anti-Arrhythmia Agents / pharmacology*
Cardiac Complexes, Premature / physiopathology
Cardiac Pacing, Artificial
Dose-Response Relationship, Drug
Electric Stimulation
Electrocardiography / drug effects*
Heart Conduction System / drug effects
Heart Ventricles / drug effects*
Models, Animal
Phenethylamines / pharmacology*
Potassium Channel Blockers / pharmacology*
Refractory Period, Electrophysiological / drug effects
Sulfonamides / pharmacology*
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Phenethylamines; 0/Potassium Channel Blockers; 0/Sulfonamides; 115256-11-6/dofetilide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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