IngentaConnect Further Insights into the Effect of Quinidine in Short QT Syndrom...

Authors: CHRISTIAN WOLPERT¹; RAINER SCHIMPF¹; CARLA GIUSTETTO²; CHARLES ANTZELEVITCH³; JONATHAN CORDEIRO³; ROBERT DUMAINE³; RAMON BRUGADA³; KUI HONG³; URS BAUERSFELD⁴; FIORENZO GAITA²; MARTIN BORGGREFE¹

Source: Journal of Cardiovascular Electrophysiology, Volume 16, Number 1, January 2005 , pp. 54-58(5)

Publisher: Blackwell Publishing

Abstract:

Arrhythmia Prevention in Short QT Syndrome.

Introduction: The principal aim of this study was to assess the efficacy of quinidine in suppressing I_Kr in vitro and in modulating the rate dependence of the QT interval in the “SQT1” form of the short QT syndrome.

Methods and Results: Graded-intensity bicycle exercise testing was performed off drug in three patients and during oral quinidine in two patients with short QT syndrome and compared to a control group of healthy normal subjects. The in vitro effects of quinidine on currents in patch clamp technique were investigated. Off drugs QT_pV3/heart rate correlation is much weaker in patients with short QT syndrome, and QT_pV3 shortens less with heart rate increase compared to normal subjects. In addition to prolonging the QT interval into the normal range, quinidine restored the heart rate dependence of the QT interval toward a range of adaptation reported for normal subjects. Data from heterologous expression of wild-type and mutant HERG genes indicate the mutation causes a 20-fold increase in IC₅₀ of d-sotalol but only a 5.8-fold increase in IC₅₀ of quinidine.

Conclusion: Oral quinidine is effective in suppressing the gain of function in I_Kr responsible for some cases of short QT syndrome with a mutation in HERG and thus restoring normal rate dependence of the QT interval and rendering ventricular tachycardia/ventricular fibrillation noninducible.

(J Cardiovasc Electrophysiol, Vol. 16, pp. 54-58, January 2005)

Keywords: short QT syndrome; sudden death; quinidine

Document Type: Research article

DOI: 10.1046/j.1540-8167.2005.04470.x

Affiliations: 1: 1st Department of Medicine-Cardiology, University Hospital Mannheim, Mannheim, Germany 2: Division of Cardiology, Ospedale Civile di Asti, Asti, Italy 3: Masonic Medical Research Laboratory, Utica, NY, USA 4: University Children's Hospital Zurich, Switzerland

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Further Insights into the Effect of Quinidine in Short QT Syndrome Caused by a Mutation in HERG