Transmembrane action potential heterogeneity in the canine isolated arterially perfused right atrium:: effect of IKr and IKur/Ito block

Transmembrane action potential heterogeneity in the canine isolated arterially perfused right atrium:: effect of IKr and IKur/Ito block
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DOI:
10.1152/ajpheart.01242.2003
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发表时间:
2004-06-01
影响因子:
4.8
通讯作者:
Antzelevitch, C
Antzelevitch, C
中科院分区:
医学2区
文献类型:
--
作者:
Burashnikov, A;Mannava, S;Antzelevitch, C

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电异质性在心律失常发生中的作用已得到公认。跨膜动作电位(TAP)异质性在多大程度上有助于氧合良好的心房的正常电生理尚不清楚。本研究的主要目的是确定在基线、快速激活延迟整流钾电流(I-Kr)阻滞和超速延迟整流和瞬时外向钾电流(I-Kur/I-to阻滞)联合阻滞下,犬离体灌注和动脉灌注右心房(RA)制备物中TAP特征的区域和透壁差异。存活的超灌注制剂通常显示三角形TAP。结果包括来自界嵴的细胞,其中可以记录具有正常平台的TAP。相比之下,大多数TAP记录从整个灌注RA显示尖峰和圆顶和/或平台形态。灌注RA显示复极化,V-最大值,和尖峰和圆顶形态沿着心外膜和内膜表面以及透壁,在上界嵴区域的不均匀分布。用E-4031阻断I-Kr可均匀地延长RA的复极化,而用低浓度4-氨基吡啶阻断I-Kur/I-to可不均匀地缩短90%复极化时的动作电位时程,导致复极化离散度降低。我们的数据表明,电异质性,先前描述的犬心室,也存在于心房内,I-Kr块不加重和I-Kur/I-to块减少RA复极分散。我们的研究还指出了使用灌注与动脉灌注心房准备记录的跨膜活动的主要差异。
The role of electrical heterogeneity in development of cardiac arrhythmias is well recognized. The extent to which transmembrane action potential (TAP) heterogeneity contributes to the normal electrophysiology of well-oxygenated atria is not well defined. The principal objective of the present study was to define regional and transmural differences in characteristics of the TAP in isolated superfused and arterially perfused canine right atrial (RA) preparations under baseline, rapidly activating delayed rectifier K+ current (I-Kr) block, and combined block of ultrarapid delayed rectifier and transient outward K+ current (I-Kur/I-to block). Superfused preparations that survived generally displayed a triangle-shaped TAP. Exceptions included cells from the crista terminalis, where TAPs with a normal plateau could be recorded. In contrast, most TAPs recorded from throughout the perfused RA displayed a spike-and-dome and/or plateau morphology. The perfused RA displayed a heterogeneous distribution of repolarization, V-max, and spike-and-dome morphology along the epicardial and endocardial surfaces as well as transmurally, in the region of the upper crista terminalis. I-Kr block with E-4031 prolonged repolarization homogeneously in the perfused RA, whereas I-Kur/I-to block using low concentrations of 4-aminopyridine abbreviated action potential duration at 90% repolarization heterogeneously, leading to a reduction in dispersion of repolarization. Our data indicate that the electrical heterogeneities, previously described for the canine ventricle, also exist within the atria and that I-Kr block does not accentuate and I-Kur/I-to block reduces RA dispersion of repolarization. Our study also points to major differences in the transmembrane activity recorded using superfused vs. arterially perfused atrial preparations.