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Apamin induces early afterdepolarizations and torsades de pointes ventricular arrhythmia from failing rabbit ventricles exhibiting secondary rises in intracellular calcium.
Apamin induces early afterdepolarizations and torsades de pointes ventricular arrhythmia from failing rabbit ventricles exhibiting secondary rises in intracellular calcium.
- Source :
-
Heart rhythm [Heart Rhythm] 2013 Oct; Vol. 10 (10), pp. 1516-24. Date of Electronic Publication: 2013 Jul 05. - Publication Year :
- 2013
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Abstract
- 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.<br />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).<br />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.<br />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.<br />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.<br /> (© 2013 Heart Rhythm Society. All rights reserved.)
- Subjects :
- Action Potentials
Animals
Atrioventricular Block etiology
Atrioventricular Block physiopathology
Cardiac Pacing, Artificial
Disease Models, Animal
Heart Failure physiopathology
Rabbits
Torsades de Pointes physiopathology
Ventricular Dysfunction, Left metabolism
Ventricular Dysfunction, Left physiopathology
Apamin
Calcium physiology
Heart Failure chemically induced
Potassium Channel Blockers
Torsades de Pointes chemically induced
Ventricular Dysfunction, Left etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1556-3871
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Heart rhythm
- Publication Type :
- Academic Journal
- Accession number :
- 23835258
- Full Text :
- https://doi.org/10.1016/j.hrthm.2013.07.003