November 24, 1998Circulation
Cellular Basis for the ECG Features of the LQT1 Form of the Long-QT Syndrome
Population
Arterially perfused wedge of canine left ventricle
Comparison
Chromanol 293B alone, and in combination with… vs Baseline conditions or chromanol 293B alone
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Provides mechanistic support for beta-blockers in LQT1; leaves open clinical translation and mexiletine utility.
Structured PICO
P
Population
Arterially perfused wedge of canine left ventricle
I
Intervention
Chromanol 293B (1 to 100 micromol/L) alone, and in combination with isoproterenol (10 to 100 nmol/L), propranolol (0.5 to 1 micromol/L), or mexiletine (2 to 20 micromol/L)
C
Comparator
Baseline conditions or chromanol 293B alone
O
Outcome
Transmural dispersion of repolarization (TDR), T wave widening, and induction of torsade de pointes (TdP)surrogate
This preclinical model demonstrates that beta-adrenergic stimulation in the setting of IKs deficiency increases transmural dispersion of repolarization and induces TdP, providing a mechanistic basis for the efficacy of beta-blockers and potentially class IB antiarrhythmics in LQT1.
Cite This Study
Shimizu et al. (1998) studied this question.