Stark G, Schwarzl I, Heiden U, Stark U, Tritthart H A
Department of Internal Medicine, Karl-Franzens-University, Graz, Austria.
Cardiovasc Res. 1997 Jul;35(1):43-51. doi: 10.1016/s0008-6363(97)00074-6.
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 and the Q-aT interval during abrupt changes in heart rate.
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.
In the presence of 10 microM 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 (tau) of 77 +/9 beats under control conditions, by 15.4 +/- 0.9 ms (P < 0.05 vs. control with tau = 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 combination of sotalol (10 microM) 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.
Sotalol led to inadequate kinetics of fate 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.
Ⅲ类抗心律失常药物也可诱发室性心律失常，这一点已得到充分证实。QT间期的显著变化与复极离散度增加相关，而复极离散度增加是诱发室性心律失常的一个重要因素。本研究的目的是探讨索他洛尔单独使用及与硫酸镁联合使用时对心率突然变化期间Q-aT间期的影响。
实验采用Langendorff灌流法在离体豚鼠心脏上进行。在将心室起搏频率从220ms突然改变为180ms然后再变回220ms后，评估Q-aT间期的频率适应性。
在存在10μM索他洛尔的情况下，在起搏周期长度恒定为220ms时，QT间期从152±4ms显著延长至166±3ms（均值±标准误，每组n = 8）（P < 0.01）。加入3.4mM硫酸镁后，QT间期进一步稍有延长。在将起搏周期长度从220ms突然缩短至180ms后，在对照条件下，Q-aT间期在2分钟内缩短了11.3±0.5ms，时间常数（τ）为77±9次搏动；在索他洛尔存在时，缩短了15.4±0.9ms（与对照相比P < 0.05，τ = 52±7次搏动，与对照相比P < 0.05）；在索他洛尔（10μM）和硫酸镁（3.4mM）联合使用时，缩短了13.1±1.2ms，τ = 158±13次搏动。在起搏周期长度突然缩短后，第一搏的Q-aT间期在对照条件下缩短了3.3±0.3ms，在索他洛尔作用下缩短了7.1±0.2ms（与对照相比P < 0.01），在索他洛尔和硫酸镁联合使用时缩短了4.2±0.2ms。如果将起搏周期长度从180ms突然增加至220ms，其效应与上述情况相当。
索他洛尔导致Q-aT间期频率适应性的动力学不足，表现为Q-aT间期变化幅度较大，尤其是在起搏频率突然改变后的第一搏内。硫酸镁消除了索他洛尔的这种效应。这些发现提示硫酸镁可减少索他洛尔诱发的频率适应性动力学不足，进而也减少复极离散度，这可能会减少索他洛尔诱发的室性心律失常。
