缝隙连接抑制剂庚醇在不影响复极性能和不应期的情况下，通过减慢传导速度，增加室性心律失常
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Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by reducing conduction velocity without affecting repolarization properties or myocardial refractoriness in Langendorff-perfused mouse hearts
背景与目的
本研究的目的是探讨在大鼠离体心脏灌注中缝隙连接抑制剂庚醇（0.05mM）的致心律失常效应。
方 法
右心室起搏时从左心室心外膜记录心肌单相动作电位。观察使用庚醇之前和之后12只心脏在8 Hz起搏期间的常规活动。
结 果
相比之下，庚醇处理后使用S1S2刺激方案（Fisher's精确检验; P <0.05）观察到有6只心脏诱发出室性心动过速（VT）。 庚醇的致心律失常作用与激活潜伏期从13.2±0.6增加到19.4±1.3ms（方差分析，P <0.001）和传导速度（CVs）从0.23±0.01降低到0.16±0.01ms（方差分析，P <0.001）相关，APDx = 90％（38.0±1.0 vs 38.3±1.8ms），70％（16.8±1.0 vs 19.5±0.9ms），50％（9.2±0.8 vs 10.1±0.6ms）或30％（4.8±0.5 vs 6.3±0.6ms）或有效不应期（ERPs）（39.6±1.9 vs 40.6±3.0ms）（P> 0.05）。 因此，兴奋波长（λ; CV x ERP）从9.1±0.6减少到6.5±0.6 mm（P <0.01），但再兴奋的临界间期（APD90 - ERP）差异无统计学意义（-1.1±2.4 vs -2.3±1.8ms; P> 0.05）。
结 论
据我们所知，该观察结果第一次证明使用低浓度庚醇（0.05mM）可单独抑制缝隙连接从而降低CV，其单独使用足以通过减少λ而提前刺激导致VT的发生，且这在发生心律失常的倾向中具有重要决定作用。
原始文献摘要
Tse G; Yeo JM; Tse V; Kwan J; Sun B；Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by reducing conduction velocity without affecting repolarization properties or myocardial refractoriness in Langendorff-perfused mouse hearts；Molecular Medicine Reports. 14(5):4069-4074, Nov，2016；
BCGROUND:
In the current study, arrhythmogenic effects of the gap junction inhibitor heptanol (0.05 mM) were examined in Langendorff-perfused mouse hearts.
METHODS:
1. Monophasic action potential recordings were obtained from the left ventricular epicardium during right ventricular pacing. Regular activity was observed both prior and subsequent to application of heptanol in all of the 12 hearts studied during 8 Hz pacing.
RESULTS:
1. By contrast, induced ventricular tachycardia (VT) was observed after heptanol treatment in 6/12 hearts using a S1S2 protocol (Fisher's exact test; P<0.05). The arrhythmogenic effects of heptanol were associated with increased activation latencies from 13.2±0.6 to 19.4±1.3 msec (analysis of variance; P<0.001) and reduced conduction velocities (CVs) from 0.23±0.01 to 0.16±0.01 msec (analysis of variance; P<0.001) in an absence of alterations in action potential durations (ADPs) at x=90% (38.0±1.0 vs. 38.3±1.8 msec), 70% (16.8±1.0 vs. 19.5±0.9 msec), 50% (9.2±0.8 vs. 10.1±0.6 msec) or 30% (4.8±0.5 vs. 6.3±0.6 msec) repolarization (APDx) or in effec-tive refractory period (ERPs) (39.6±1.9 vs. 40.6±3.0 msec) (all P>0.05). Consequently, excitation wavelengths (λ; CV x ERP) were reduced from 9.1±0.6 to 6.5±0.6 mm (P<0.01), however critical intervals for re-excitation (APD90 - ERP) were unal-tered (-1.1±2.4 vs. -2.3±1.8 msec; P>0.05).
CONCLUSIONS:
Together, these observations demonstrate for the first time, to the best of our knowledge, that inhibition of gap junctions alone using a low heptanol concentration (0.05 mM) was able to reduce CV,which alone was sufficient to permit the induction of VT using premature stimulation by reducing λ, which therefore appears central in the determination of arrhythmic tendency.
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