Differential Responses to Beta-Adrenergic Stimulation in the Long-QT Syndrome Type 1: Characterization and Mechanisms

Sampedro-Puente, Adolfo () ; Fernández-Bes, Jesús () ; Pueyo, Esther ()

Abstract: Long QT syndrome type 1 (LQT1) is caused by muta- tions that impair the function of the slow delayed rectifier potassium (IK s ) channels. Most LQT1 patients experience arrhythmic events during beta-adrenergic stimulation (β- AS). A full description of the ionic mechanisms underlying arrhythmogenecity in LQT1 patients and their relation to β-AS is still lacking. In this study we constructed a set of stochastic human ventricular cell models reproducing ex- perimental AP properties at baseline and following ionic inhibitions. Using the constructed models, we showed that AP duration, morphology and beat-to-beat variability in LQT1 are highly specific of the underlying ionic character- istics. Likewise, the response of individual IK s -deficient cells to β-AS can range from negligible to as much as 200% increase in AP temporal variability, recognized as a marker of arrhythmogenesis in the setting of LQT1. By partial correlation analysis, major ionic factors driving AP changes associated with LQT1 and β-AS were ascer- tained.

Idioma: Inglés

Año: 2017

En: Computing in Cardiology (2017, Rennes, France)

Financiación: info:eu-repo/grant/Agreement/ES/MINECO TIN2013-41998-R
Financiación: info:eu-repo/grant/Agreement/ES/MINECO DPI2016-75458-R
Financiación: info:eu-repo/grant/Agreement/EU/ERC-2014-StG-638284