Aizawa Y, Uchiyama H, Yamaura M, Nakayama T, Arita M
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
J Electrocardiol. 1998 Apr;31(2):117-23. doi: 10.1016/s0022-0736(98)90042-5.
Congenital or idiopathic long QT syndrome is characterized by a frequently lethal ventricular arrhythmia called torsades de pointes (TdP) as well as a prolonged QT interval. The long QT interval related to an abnormal gene of the Na+ channel has been shown to be shortened by mexiletine. However, the action of K+ channel openers on the QT interval associated with abnormal genes of the K channel has yet to be studied. Seven patients of five families with long QT syndrome were included in this study, of whom six had syncope and six had documented TdP. Either long QT interval or sudden cardiac death had been observed in family members of all seven patients. At 1 to 3 weeks after admission, when TdP or frequent ventricular arrhythmia had subsided, nicorandil, an ATP-sensitive K channel opener, was administered orally at a dose of 15 mg/day in five patients and at 30 mg/day in the remaining two patients, and the effects were assessed on the third day after drug administration. In four patients, the effective refractory period was measured in the right ventricle before and after administration of K channel opener administration. The QT interval (QTc) prior to administration of the K channel opener was 0.60 +/- 0.09 ms (mean +/- SD) (0.61 +/- 0.10 second(1/2)), which was shortened to 0.54 +/- 0.05 ms (0.55 +/- 0.06 second(1/2)) on the third day of drug administration (P < .05 for both): 10.4 +/- 8.0% (8.6 +/- 5.5%). The QT interval at varying preceding R-R intervals on Holter electrocardiograms showed a shift toward the right as a result of the drug administration. The effective refractory period showed a significant prolongation, 256 +/- 26 ms versus 280 +/- 22 ms before and after drug administration, respectively (P <.05). Intravenous administration of nicorandil resulted in no significant change in heart rate or blood pressure, while QTc showed a tendency to shorten, but nonsignificantly (P = .08). However, a hump on the monophasic action potential was abolished, especially at the long preceding R-R interval induced by premature stimulation of the ventricle. It is concluded that nicorandil shortens the QT interval slightly when administered orally, whereas the effective refractory period shows a slight prolongation. The physiologic and clinical significance of these effects needs to be studied further.
先天性或特发性长QT综合征的特征是一种称为尖端扭转型室性心动过速（TdP）的常致命性室性心律失常以及QT间期延长。已证明与钠通道异常基因相关的长QT间期可被美西律缩短。然而，钾通道开放剂对与钾通道异常基因相关的QT间期的作用尚未得到研究。本研究纳入了5个长QT综合征家族的7名患者，其中6人有晕厥，6人有记录的TdP。所有7名患者的家庭成员均观察到长QT间期或心源性猝死。入院1至3周后，当TdP或频发室性心律失常消退时，5名患者口服剂量为15mg/天的ATP敏感性钾通道开放剂尼可地尔，其余2名患者口服剂量为30mg/天，并在给药后第三天评估效果。在4名患者中，在给予钾通道开放剂前后测量右心室的有效不应期。给予钾通道开放剂前的QT间期（QTc）为0.60±0.09ms（平均值±标准差）（即0.61±0.10秒的平方根），在给药后第三天缩短至0.54±0.05ms（0.55±0.06秒的平方根）（两者P均<0.05），缩短了10.4±8.0%（8.6±5.5%）。动态心电图上不同前R-R间期时的QT间期因给药而向右移位。有效不应期显著延长，给药前后分别为256±26ms和280±22ms（P<0.05）。静脉注射尼可地尔导致心率或血压无显著变化，而QTc有缩短趋势，但不显著（P=0.08）。然而，单相动作电位上的驼峰被消除，尤其是在心室过早刺激诱导的长前R-R间期时。得出的结论是，口服尼可地尔可使QT间期稍有缩短，而有效不应期稍有延长。这些效应的生理和临床意义需要进一步研究。
