NDLI: Modelling effects of sotalol on T-wave morphology

Content Provider	IEEE Xplore Digital Library
Author	Brennan, T.P. Fink, M. Stokeley, D. Rodriguez, B. Tarassenko, L.
Copyright Year	2007
Description	Author affiliation: Dept. of Eng. Sci., Univ. of Oxford, Oxford (Brennan, T.P.; Tarassenko, L.) \|\| Dept. of Physiol., Univ. of Oxford, Oxford (Fink, M.) \|\| Comput. Lab., Univ. of Oxford, Oxford (Stokeley, D.; Rodriguez, B.)
Abstract	The QT interval has well-documented shortcomings as a predictor of Torsades de Pointes (TdP) and recent studies have shown that T-wave morphology might provide insight into drug effects on ventricular repolarisation. In this paper, we investigate the underlying mechanisms of the effects of sotalol, a known anti-arrhythmic drug, on T-wave morphology as seen in the surface electrocardiogram (ECG). Analysis of clinical ECG data from a controlled study shows that sotalol alters T-wave morphology, resulting in particular in a decrease in T-wave amplitude. Our multi-scale modelling approach uses a Markov formulation to represent sotalolpsilas interaction with the rapid delayed rectifier potassium channel current $(I_{Kr}),$ validated using experimental data. The ion channel model is then incorporated into a human ventricular cell model, which is then used in a 1D fibre model with transmural heterogeneities to simulate a pseudo-ECG. The simulation results show sotalol-induced changes in $I_{Kr}$ cause rate and dose-dependent increase in action potential duration (APD) and in transmural APD heterogeneities, which result in a decrease of T-wave amplitude and an increase in T-wave dispersion in the pseudo-ECG signal. Thus, our modelling study is able to explain the ionic mechanisms underlying the main sotalol-induced changes in clinical T-wave morphology.
Starting Page	249
Ending Page	252
File Size	1603020
Page Count	4
File Format	PDF
ISBN	9781424425334
ISSN	02766547
DOI	10.1109/CIC.2007.4745468
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2007-09-30
Publisher Place	USA
Access Restriction	Subscribed
Rights Holder	Computers in Cardiology(CinC)
Subject Keyword	Electrocardiography Drugs Heart rate interval Humans Surface morphology Hidden Markov models Predictive models Physiology Laboratories Delay
Content Type	Text
Resource Type	Article

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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