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The efficacy of class III anti-arrhythmic drugs in 3D canine atrial models: Is the blockade of ikca pro- or anti-arrhythmic?

Research output: Contribution to journalConference paper

Marta Varela, Purwa Dar, Jules C. Hancox, Oleg V. Aslanidi

Original languageEnglish
Pages (from-to)1-4
Number of pages4
JournalComputing in Cardiology
Volume44
Early online date24 Sep 2017
DOIs
StatePublished - 2017
EventComputing in Cardiology 2017: Conference - Rennes, France
Duration: 24 Sep 201727 Sep 2017

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  • 375-410 VoR CCBY

    375_410_VoR_CCBY.pdf, 552 KB, application/pdf

    23/04/2018

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King's Authors

Abstract

Small conductance calcium-activated potassium channel current, IKCa, has recently been characterized in atrial tissue and linked with atrial arrhythmogenesis. As IKCa does not contribute significantly to the ventricular action potential, there is great interest in developing pharmacological agents targeting these channels. However, experimental data so far have presented conflicting evidence as to whether IKCa inhibition is pro- or anti-arrhythmic. We have created a new formulation for IKCa, which we included in recently developed heterogeneous and anisotropic 3D canine atrial models. These were applied to investigate the effect of IKCa blockade compared to inhibition of other potassium currents: IKr and IKur. Blocking IKCa led to the termination of AF in the 3D atrial model, in contrast to blockades of IKur or IKr. Blocking IKCa prolonged action potential duration, APD, by at least 20 ms in all atrial cell types, whereas IKr or IKur blocks did not increase APD by more than 10 ms, thus explaining IKCa's effectiveness in terminating AF. Nevertheless, the blockade of IKCa also led to an increase in APD dispersion, which is expected to be proarrhythmic. In cases when the APD dispersion effects dominate over the APD prolongation, the blockade of IKCa is expected to be pro-arrhythmic, as seen in experimental models of non-remodelled canine atria.

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