MAGNESIUM ABOLISHES INADEQUATE KINETICS OF FREQUENCY ADAPTATION OF THE Q-AT INTERVAL IN THE PRESENCE OF SOTALOL

Objective: It has been well established that class III antiarrhythmic drugs can also induce ventricular arrhythmias. Marked changes in the Q T interval are correlated with an increased dispersion of repolarizati on which is an important factor for the induction of ventricular arrhy thmias. The aim of the present study was to investigate the effects of sotalol alone and in combination with MgSO4 on the Q-aT interval duri ng abrupt changes in heart rate. Methods: The experiments were perform ed on isolated guinea-pig hearts perfused by the method of Langendorff . The rate adaptation of the Q-aT interval was estimated after abruptl y changing the ventricular pacing rate from 220 to 180 ms and back to 220 ms. Results: In the presence of 10 mu M sotalol, at a constant pac ing cycle length of 220 ms, the QT interval was prolonged significantl y (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 pro longation of the QT interval. After abruptly shortening the pacing cyc le length from 220 to 180 ms, the Q-aT interval shortened within 2 min by 11.3 +/- 0.5 ms with a time constant (tau) of 77 +/- 9 beats under control conditions, by 15.4 +/- 0.9 ms (P < 0.05 vs. control) with ta u = 52 +/- 7 beats (P < 0.05 vs. control) in the presence of sotalol, and by 13.1 +/- 1.2 ms with tau = 158 +/- 13 beats under the combinati on of sotalol (10 mu M) and MgSO, (3.4 mM). After abrupt shortening of the pacing cycle length the Q-aT interval of the first beat was short ened 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 comb ination of sotalol and MgSO4. If the pacing cycle length was abruptly increased from 180 to 220 ms, the effects were comparable to those des cribed 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 find ings suggest that MgSO4 could reduce sotalol-induced inadequate kineti cs of rate adaptation and therefore also dispersion of repolarization, which may result in a reduction of sotalol-induced ventricular arrhyt hmias.