Acetylcholine-induced shortening of the epicardial action potential duration may increase repolarization gradients and LQT3 arrhythmic risk

Flaim, Sarah N. and McCulloch, Andrew D. (2007). Acetylcholine-induced shortening of the epicardial action potential duration may increase repolarization gradients and LQT3 arrhythmic risk. In: , Journal of Electrocardiology. Proceedings of: ISCE 32nd Annual Conference. ISCE 32nd Annual Conference, Mexico, (S66-S69). 21-26 April 2007.


Author Flaim, Sarah N.
McCulloch, Andrew D.
Title of paper Acetylcholine-induced shortening of the epicardial action potential duration may increase repolarization gradients and LQT3 arrhythmic risk
Conference name ISCE 32nd Annual Conference
Conference location Mexico
Conference dates 21-26 April 2007
Convener International Society for Computerized Electrocardiology
Proceedings title Journal of Electrocardiology. Proceedings of: ISCE 32nd Annual Conference   Check publisher's open access policy
Journal name Journal of Electrocardiology   Check publisher's open access policy
Place of Publication San Diego, Calif., U.S.A.
Publisher Churchill Livingstone
Publication Year 2007
Sub-type Fully published paper
DOI 10.1016/j.jelectrocard.2007.06.010
ISSN 0022-0736
1532-8430
Volume 40
Issue 6 Supp
Start page S66
End page S69
Total pages 4
Language eng
Formatted Abstract/Summary Unlike other variants of long QT syndrome, LQT3 patients are particularly susceptible to cardiac events during sleep. Changes in heart rate alone fail to fully account for this phenomenon. We hypothesize that the parasympathetic nervous system may play a role in increasing arrhythmic risk in the mammalian ventricular myocardium via acetylcholine (ACh)-mediated effects on repolarisation gradients and, furthermore, that the effects of ACh exhibit rate dependency. Here, we investigate this hypothesis in a mathematical model of action potential generation and excitation-contraction coupling in a canine left ventricular epicardial myocyte, using a previously developed formulation for the muscarinic K+ current IK,ACh. Our model was able to reproduce an experimentally observed dose-dependent reduction in canine epicardial action potential duration90 at 90% repolarization in response to application of ACh. Moreover, our model also predicts a rate-dependent reduction of epicardial APD90 with the greatest effects occurring at slower rates. This is likely to be due to decreased repolarisation reserve at these rates. Our results suggest that ACh-mediated effects on epicardial myocytes may amplify already steep repolarisation gradients in the mammalian left ventricular wall of LQT3 patients and consequently increase the risk of arrhythmia formation. 
Subjects 1102 Cardiovascular Medicine and Haematology
Keyword Acetylcholine
Arrhythmia mechanisms
Autonomic nervous system
Dispersion of repolarization
Epicardium
LQT3
Mutation
Parasympathetic nervous system
SCN5A
Ventricular heterogeneity
Q-Index Code EX

 
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