Referenced in: none

Automatically associated channels: Kv11.1

Title: Cellular basis for arrhythmogenesis in an experimental model of the SQT1 form of the short QT syndrome.

Authors: Chinmay Patel, Charles Antzelevitch

Journal, date & volume: Heart Rhythm, 2008 Apr , 5, 585-90

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18362027

Abstract
Short QT syndrome (SQTS) is a primary electrical disease of the heart associated with a high risk of sudden cardiac death. A gain-of-function in I(Kr), due to a mutation in KCNH2, underlies SQT1.This study sought to examine the cellular basis for arrhythmogenesis in an experimental model of SQT1 created using PD-118057, a novel I(Kr) agonist.Transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial regions of arterially perfused canine left ventricular (LV) wedge preparations, together with a pseudo-electrocardiogram.PD-118057 (10 micromol/l) abbreviated the QT interval from 267 +/- 4 to 232 +/- 4 ms and increased transmural dispersion of repolarization (TDR) from 33.7 +/- 2.0 to 49.1 +/- 3.1 ms (P <.001). T-wave amplitude increased from 18.0% +/- 1.4% to 23.1% +/- 1.7% of R-wave amplitude (P =.027). Reversing the direction of activation of the LV wall (epicardial pacing) resulted in an increase in QT interval from 269 +/- 5 to 282 +/- 5 ms and an increase in TDR from 34.1 +/- 2.0 to 57.6 +/- 3.3 ms (P <.001) under baseline conditions. PD-118057 abbreviated the QT interval from 282 +/- 5 to 258 +/- 5 ms and produced a proportional decrease in effective refractory period (ERP). TDR increased from 57.6 +/- 3.3 to 77.6 +/- 4.3 ms (P <.001). Polymorphic ventricular tachycardia (pVT) was induced in 10 of 20 preparations with a single S(2) applied to epicardium. Quinidine (10 micromol/l) increased the ERP and QT interval, did not significantly alter TDR, and prevented induction of pVT in 5 of 5 preparations.Our results suggest that a combination of ERP abbreviation and TDR amplification underlie the development of pVT in SQT1 and that quinidine prevents pVT principally by prolonging ERP.