Genetically defined therapy of inherited long-QT syndrome - Correction of abnormal repolarization by potassium
Genetically defined therapy of inherited long-QT syndrome - Correction of abnormal repolarization by potassium
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DOI：
10.1161/01.cir.94.5.1018
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发表时间：
1996-09-01
期刊：
影响因子：
37.8
通讯作者：
Mason, JW
中科院分区：
文献类型：
--
作者：
Compton, SJ;Lux, RL;Mason, JW
遗传性长QT（LQT）综合征家族中的许多成员存在HERG突变，HERG是一种编码心脏钾通道的基因，受细胞外钾调节。我们假设，血清钾的增加将正常复极在这些patients.Methods和结果，我们研究了7例7-连锁LQT综合征和5个正常对照组。在窦性心律、运动和心房起搏期间，在血清钾升高之前和之后，通过ECG和体表电位标测测量复极。补钾可改善LQT综合征的复极。基线时，LQT受试者与对照受试者不同：静息校正QT间期QT（c），627+/-90 vs 425+/-25 ms，P=.0007），QT（c）离散度（133+/-62 vs 36+/-9 ms，P=.009），QT/RR斜率（0.35+/-0.08 vs 0.24+/-0.07，P= 0.04）和总体均方根QT间期（RMS-QT（c）; 525+/-68 vs 393+/-22，P= 0.002）。所有LQT受试者均为双相或切迹T波。在给予钾后，LQT组的静息QT（c）间期减少了24%（从617+/-92到469+/-23 ms，P= 0.004），而对照组减少了4%（从425+/-25到410+/-45 ms，P> 0.05）。LQT受试者的降低幅度显著更大（P= 0.018）。QT离散度在LQT受试者中变得正常，而在对照受试者中没有变化。QT间期和周期长度之间的关系的斜率（QT/RR斜率）向正常方向降低。7例LQT受试者中有6例T波形态改善。LQT组RMS-QT（c）较对照组有更大的降低（P= 0.04）。结论7号染色体连锁LQT患者血清钾的升高可纠正复极持续时间、T波形态、QT/ RR斜率和QT离散度的异常。
Background Many members of families with inherited long-QT (LQT) syndrome have mutations in HERG, a gene encoding a cardiac potassium channel that is modulated by extracellular potassium. We hypothesized that an increase in serum potassium would normalize repolarization in these patients.Methods and Results We studied seven subjects with chromosome 7-linked LQT syndrome and five normal control subjects. Repolarization was measured by ECG and body surface potential mapping during sinus rhythm, exercise, and atrial pacing, before and after serum potassium increase. Potassium administration improved repolarization in the LQT syndrome. At baseline, LQT subjects differed from control subjects: resting corrected QT interval QT(c), 627+/-90 versus 425+/-25 ms, P=.0007), QT(c) dispersion (133+/-62 versus 36+/-9 ms, P=.009), QT/RR slope (0.35+/-0.08 versus 0.24+/-0.07, P=.04), and global root-mean-square QT interval (RMS-QT(c); 525+/-68 versus 393+/-22, P=.002). All LQT subjects had biphasic or notched T waves. After administration of potassium, the LQT group had a 24% reduction in resting QT(c) interval (from 617+/-92 to 469+/-23 ms, P=.004) compared with a 4% reduction among control subjects (from 425+/-25 to 410+/-45 ms, P>.05). The reduction was significantly greater in LQT subjects (P=.018). QT dispersion became normal in LQT subjects and did not change in control subjects. The slope of the relation between QT interval and cycle length (QT/RR slope) decreased toward normal. T-wave morphology improved in six of seven LQT subjects. The LQT group had a greater reduction in RMS-QT(c) than control subjects (P=.04).Conclusions An increase in serum potassium corrects abnormalities of repolarization duration, T-wave morphology, QT/ RR slope, and QT dispersion in patients with chromosome 7-linked LQT.