Mechanism of origin of conduction disturbances in aging human atrial bundles: Experimental and model study
Mechanism of origin of conduction disturbances in aging human atrial bundles: Experimental and model study
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DOI：
10.1016/j.hrthm.2006.10.023
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发表时间：
2007-02-01
期刊：
影响因子：
5.5
通讯作者：
Barr, Roger C.
中科院分区：
文献类型：
--
作者：
Spach, Madison S.;Heidlage, J. Francis;Barr, Roger C.
背景：衰老与心房性心动过速的显著增加有关，尤其是心房颤动。在另一个部位过早的刺激之前，由一个部位的刺激人为地产生宏观复极梯度，这被广泛认为是实验室中引发此类心律失常所必需的实验方案的一部分。这种梯度如何在老化的心房组织中自然发生尚不清楚。目的：本研究的目的是确定老化的人类心房束的细胞连接模式是否产生可变的早期反应机制。方法对老化的人心房束进行对照和过早刺激后，记录细胞外和细胞内电位。我们还测量了细胞的几何形状、连接素的分布和胶原间隔的分布。根据形态学结果建立心房束模型。在模型中分析了过早刺激后的动作电位传播和钠电流。结果早衰刺激后的细胞外电位波形与模型相似。心房结构老化单一模型解释了不同的早传导模式。模型结果的一个主要特征是，多个部位的传导事件和钠电流的大小对过早刺激的位置和时间的微小变化非常敏感。结论仅从单一部位刺激衰老的心房束，过早刺激可诱导可变的致心律失常传导反应。在衰老过程中，细胞连通性的重塑大大增强了这些反应的产生。结果提供了洞察钠电流结构相互作用作为心律失常性心房反应的一般机制过早刺激。
BACKGROUND Aging is associated with a significant increase in atrial tachyarrhythmias, especially atrial fibrillation. A macroscopic repolarization gradient created artificially by a stimulus at one site before a premature stimulus from a second site is widely considered to be part of the experimental protocol necessary for the initiation of such arrhythmias in the Laboratory. How such gradients occur naturally in aging atrial tissue is unknown.OBJECTIVE The objective of this study was to determine if the pattern of cellular connectivity in aging human atrial bundles produces a mechanism for variable early premature responses.METHODS Extracellular and intracellular potentials were recorded after control and premature stimuli at a single site in aging human atrial bundles. We also measured cellular geometry, the distribution of connexins, and the distribution of collagenous septa. A model of the atrial bundles was constructed based on the morphological results. Action potential propagation and the sodium current were analyzed after premature stimuli in the model.RESULTS Similar extracellular potential waveform responses occurred after early premature stimuli in the aging bundles and in the model. Variable premature conduction patterns were accounted for by the single model of aging atrial structure. A major feature of the model results was that the conduction events and the magnitude of the sodium current at multiple sites were very sensitive to small changes in the location and the timing of premature stimuli.CONCLUSION In aging human atrial bundles stimulated from only a single site, premature stimuli induce variable arrhythmogenic conduction responses. The generation of these responses is greatly enhanced by remodeling of cellular connectivity during aging. The results provide insight into sodium current structural interactions as a general mechanism of arrhythmogenic atrial responses to premature stimuli.