Journal Article

Magnesium abolishes inadequate kinetics of frequency adaptation of the Q-aT interval in the presence of sotalol

Gerhard Stark, Ingrid Schwarzl, Ulrike Heiden, Ulrike Stark and Helmut A Tritthart

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 35, issue 1, pages 43-51
Published in print July 1997 | ISSN: 0008-6363
Published online July 1997 | e-ISSN: 1755-3245 | DOI:

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Objective: It has been well established that class III antiarrhythmic drugs can also induce ventricular arrhythmias. Marked changes in the QT interval are correlated with an increased dispersion of repolarization which is an important factor for the induction of ventricular arrhythmias. The aim of the present study was to investigate the effects of sotalol alone and in combination with MgSO4 on the Q-aT interval during abrupt changes in heart rate. Methods: The experiments were performed on isolated guinea-pig hearts perfused by the method of Langendorff. The rate adaptation of the Q-aT interval was estimated after abruptly changing the ventricular pacing rate from 220 to 180 ms and back to 220 ms. Results: In the presence of 10 μM sotalol, at a constant pacing cycle length of 220 ms, the QT interval was prolonged significantly (P<0.01) from 152±4 to 166±3 ms (mean±s.e.m., n = 8 in each group). The addition of 3.4 mM MgSO4 caused a slight further prolongation of the QT interval. After abruptly shortening the pacing cycle length from 220 to 180 ms, the Q-aT interval shortened within 2 min by 11.3±0.5 ms with a time constant (τ) of 77±9 beats under control conditions, by 15.4±0.9 ms (P<0.05 vs. control) with τ = 52±7 beats (P<0.05 vs. control) in the presence of sotalol, and by 13.1±1.2 ms with τ = 158±13 beats under the combination of sotalol (10 μM) and MgSO4 (3.4 mM). After abrupt shortening of the pacing cycle length the Q-aT interval of the first beat was shortened by 3.3±0.3 ms under control conditions, by 7.1±0.2 ms (P<0.01 vs. control) under sotalol, and by 4.2±0.2 ms with the combination of sotalol and MgSO4. If the pacing cycle length was abruptly increased from 180 to 220 ms, the effects were comparable to those described above. Conclusions: Sotalol led to inadequate kinetics of rate adaptation of the Q-aT interval indicated by a high amplitude of Q-aT interval change, especially within the first beat after abrupt change in the pacing rate. MgSO4 abolished this effect of sotalol. These findings suggest that MgSO4 could reduce sotalol-induced inadequate kinetics of rate adaptation and therefore also dispersion of repolarization, which may result in a reduction of sotalol- induced ventricular arrhythmias.

Keywords: Use dependence; Repolarization; QT interval; Sotalol; Magnesium; Guinea-pig, heart

Journal Article.  5188 words.  Illustrated.

Subjects: Cardiovascular Medicine