Yamauchi Masaki, Watanabe Eiichi, Yasui Kenji, Takeuchi Hiroshi, Terasawa Toshiaki, Sawada Ken, Hishida Hitoshi, Kodama Itsuo
Department of Cardiology, Gifu Shakai Hoken Hospital, Kani, Japan.
Int J Cardiol. 2005 Aug 3;103(1):92-7. doi: 10.1016/j.ijcard.2004.09.016.
Antiarrhythmic potential of mexiletine in patients with congenital and acquired long-QT syndrome (LQTS) has been attributed to a reduction of transmural dispersion of repolarization (TDR). A similar mechanism could be involved in the antiarrhythmic activity of the drug in patients with normal QT intervals, but the issue remains to be investigated.
We analyzed 24-h Holter ECG recordings from 17 patients in sinus rhythm showing premature ventricular complexes (PVCs) with normal QT intervals (age, 62+/-10 years, mean+/-S.D.). Treatment of the patients with oral mexiletine (300 mg/day for 21-40 days) resulted in a significant reduction of PVCs (from 13899+/-18887 to 6949+/-12822 beats/24 h, p<0.01). Rate-dependent behavior of ventricular repolarization was analyzed by plotting QT intervals (QT(peak), QT(end)), and the interval from T-wave peak to T-wave end (TPE) against preceding respective RR intervals of sinus beats. Both the QT(peak) and QT(end) tended to be shortened by mexiletine at RR intervals from 600 ms to 1000 ms, although the changes did not reach statistical significances. TPE, which reflects TDR, was shortened significantly at relatively long RR intervals (by 14+/-9% at RR of 900 ms, p<0.05). There was a linear relationship between the percentage shortening of TPE and the percentage reduction of PVCs (r=0.86, p<0.04). TPE> or =70 ms was significantly associated with PVC suppression >75% with an odds ratio of 0.60 (95% confidence interval 0.36-0.98, per 1 ms increment).
Inhibitory effect of mexiletine against PVCs in patients with normal QT intervals is mediated at least in part by a reduction of TDR. Mexiletine may be effective in patients exhibiting longer baseline TPE.
美西律在先天性和获得性长QT综合征（LQTS）患者中的抗心律失常潜力归因于复极跨壁离散度（TDR）的降低。类似的机制可能参与了该药在QT间期正常患者中的抗心律失常活性，但这一问题仍有待研究。
我们分析了17例窦性心律患者的24小时动态心电图记录，这些患者表现为QT间期正常的室性早搏（PVCs）（年龄62±10岁，均值±标准差）。口服美西律治疗患者（300mg/天，持续21 - 40天）导致PVCs显著减少（从13899±18887次/24小时降至6949±12822次/24小时，p<0.01）。通过绘制QT间期（QT(peak)、QT(end)）以及T波峰到T波末的间期（TPE）与窦性心律搏动之前各自RR间期的关系，分析心室复极的频率依赖性行为。在RR间期从600ms到1000ms时，美西律使QT(peak)和QT(end)均有缩短趋势，尽管变化未达到统计学显著性。反映TDR的TPE在相对较长RR间期时显著缩短（RR为900ms时缩短14±9%，p<0.05）。TPE缩短百分比与PVCs减少百分比之间存在线性关系（r = 0.86，p<0.04）。TPE≥70ms与PVCs抑制>75%显著相关，优势比为0.60（95%置信区间0.36 - 0.98，每增加1ms）。
美西律对QT间期正常患者PVCs的抑制作用至少部分是通过降低TDR介导的。美西律可能对基线TPE较长的患者有效。
