The link between repolarisation alternans and ventricular arrhythmia: Does the cellular phenomenon extend to the clinical problem?

Myles, R.C. , Burton, F.L., Cobbe, S.M. and Smith, G.L. (2008) The link between repolarisation alternans and ventricular arrhythmia: Does the cellular phenomenon extend to the clinical problem? Journal of Molecular and Cellular Cardiology, 45(1), pp. 1-10. (doi:10.1016/j.yjmcc.2008.03.024)

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Publisher's URL: http://dx.doi.org/10.1016/j.yjmcc.2008.03.024

Abstract

T-wave alternans is considered a potentially useful clinical marker for the risk of ventricular arrhythmia in patients with heart disease. Cellular repolarisation alternans is thought to underlie T-wave alternans, and moreover, to cause re-entrant ventricular arrhythmia. This review examines the experimental and clinical evidence linking repolarisation alternans and T-wave alternans with the occurrence of ventricular arrhythmia. Repolarisation alternans, manifest as alternating changes in action potential duration, is observed in isolated ventricular cardiomyocytes and in multicellular preparations. Its underlying causes are discussed particularly with respect to the role of intracellular Ca2+. The repolarisation alternans observed at the single cell level is compared to the alternating behaviour observed in isolated multicellular preparations including the perfused ventricular wedge and Langendorff perfused heart. The evidence concerning spatial differences in repolarisation alternans is considered, particularly the situation where adjacent regions of myocardium exhibit repolarisation alternans of different phases. This extreme behaviour, known as discordant alternans, is thought to produce marked gradients of repolarisation that can precipitate unidirectional block and re-entrant ventricular arrhythmias. Finally, the difficulties in extrapolating between experimental models of alternans and arrhythmias and the clinical manifestation are discussed. The areas where experimental evidence is weak are highlighted, and areas for future research are outlined.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Myles, Dr Rachel and Burton, Dr Francis and Cobbe, Professor Stuart
Authors: Myles, R.C., Burton, F.L., Cobbe, S.M., and Smith, G.L.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Molecular and Cellular Cardiology
Publisher:Elsevier
ISSN:0022-2828
ISSN (Online):1095-8584
Published Online:09 April 2008

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