Document Detail


Apamin induces early afterdepolarizations and torsades de pointes ventricular arrhythmia from failing rabbit ventricles exhibiting secondary rises in intracellular calcium.
MedLine Citation:
PMID:  23835258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: A secondary rise of intracellular Ca(2+) (Cai) and an upregulation of apamin-sensitive K(+) current (I(KAS)) are characteristic findings of failing ventricular myocytes. We hypothesize that apamin, a specific I(KAS) blocker, may induce torsades de pointes (TdP) ventricular arrhythmia from failing ventricles exhibiting secondary rises of Cai.
OBJECTIVE: To test the hypothesis that small conductance Ca(2+) activated IKAS maintains repolarization reserve and prevents ventricular arrhythmia in a rabbit model of heart failure (HF).
METHODS: We performed Langendorff perfusion and optical mapping studies in 7 hearts with pacing-induced HF and in 5 normal control rabbit hearts. Atrioventricular block was created by cryoablation to allow pacing at slow rates.
RESULTS: The left ventricular ejection fraction reduced from 69.1% [95% confidence interval 62.3%-76.0%] before pacing to 30.4% [26.8%-34.0%] (N = 7; P < .001) after pacing. The corrected QT interval in failing ventricles was 337 [313-360] ms at baseline and 410 [381-439] ms after applying 100 nmol/L of apamin (P = .01). Apamin induced early afterdepolarizations (EADs) in 6 ventricles, premature ventricular beats (PVBs) in 7 ventricles, and polymorphic ventricular tachycardia consistent with TdP in 4 ventricles. The earliest activation site of EADs and PVBs always occurred at the site with long action potential duration and large amplitude of the secondary rises of Ca(i). Apamin induced secondary rises of Ca(i) in 1 nonfailing ventricle, but no EAD or TdP were observed.
CONCLUSIONS: In HF ventricles, apamin induces EADs, PVBs, and TdP from areas with secondary rises of Ca(i). I(KAS) is important in maintaining repolarization reserve and preventing TdP in HF ventricles.
Authors:
Po-Cheng Chang; Yu-Cheng Hsieh; Chia-Hsiang Hsueh; James N Weiss; Shien-Fong Lin; Peng-Sheng Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-07-05
Journal Detail:
Title:  Heart rhythm : the official journal of the Heart Rhythm Society     Volume:  10     ISSN:  1556-3871     ISO Abbreviation:  Heart Rhythm     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-30     Completed Date:  2014-06-05     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  101200317     Medline TA:  Heart Rhythm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1516-24     Citation Subset:  IM    
Copyright Information:
© 2013 Heart Rhythm Society. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials
Animals
Apamin*
Atrioventricular Block / etiology,  physiopathology
Calcium / physiology*
Cardiac Pacing, Artificial
Disease Models, Animal
Heart Failure / chemically induced*,  physiopathology
Potassium Channel Blockers*
Rabbits
Torsades de Pointes / chemically induced*,  physiopathology
Ventricular Dysfunction, Left / etiology*,  metabolism,  physiopathology
Grant Support
ID/Acronym/Agency:
P01 HL078931/HL/NHLBI NIH HHS; P01HL78931/HL/NHLBI NIH HHS; R01 HL071140/HL/NHLBI NIH HHS; R01HL71140/HL/NHLBI NIH HHS; R21 HL106554/HL/NHLBI NIH HHS; R21HL106554/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Potassium Channel Blockers; 24345-16-2/Apamin; SY7Q814VUP/Calcium
Comments/Corrections

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


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