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Further Insights into the Effect of Quinidine in Short QT Syndrome Caused by a Mutation in HERG
Author(s) -
WOLPERT CHRISTIAN,
SCHIMPF RAINER,
GIUSTETTO CARLA,
ANTZELEVITCH CHARLES,
CORDEIRO JONATHAN,
DUMAINE ROBERT,
BRUGADA RAMON,
HONG KUI,
BAUERSFELD URS,
GAITA FIORENZO,
BORGGREFE MARTIN
Publication year - 2005
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2005.04470.x
Subject(s) - quinidine , herg , qt interval , medicine , long qt syndrome , short qt syndrome , cardiology , heart rate , dofetilide , pharmacology , potassium channel , blood pressure
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 IC 50 of d‐sotalol but only a 5.8‐fold increase in IC 50 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.