Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis

Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis
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DOI:
10.1016/s0008-6363(02)00271-7
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发表时间:
2002-05-01
影响因子:
10.8
通讯作者:
Rosen, MR
Rosen, MR
中科院分区:
医学1区
文献类型:
--
作者:
Anyukhovsky, EP;Sosunov, EA;Rosen, MR

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目的:心房颤动的发病率随年龄增长而增加。我们假设,年龄相关的心房动作电位(AP)和传导速度的变化提供了一个基板的异常传导和mammogenesis。方法:应用微电极技术记录1-5岁(成年)和>8岁(成年)犬右心房壁内膜AP。在相距3-10 mm的两个微电极之间测量传导速度。进行组织学研究以评估纤维化。结果如下:而静息电位,AP振幅和V-最大值没有随着年龄的增长而变化,高原是更负和AP持续时间较长的旧组织。L-型钙电流(I-Ca,I-L)激动剂BayK 8644(10(-8)-10(-6)mol/l)使老年人的平台升高,APD缩短。使得老年心房AP轮廓接近成人。而I-Ca、I-L阻断剂尼索地平(10(-8)-10(-5)mol/l)则使成年人的平台降低,对老年人无影响。两组之间正常搏动的传导速度没有差异,而对于早期过早冲动,与成人组织相比,在老年人中检测到传导速度降低和更宽的时间窗,表现为传导缓慢。在老年心房中检测到纤维组织的量增加了两倍。结论:成人和老年人心房AP的轮廓有明显差异。对Bay K8644和尼索地平的反应表明老年心房组织的I-Ca、I-L降低。AP轮廓的改变和纤维化的增加可能是老年心房早期早搏传导减慢的原因。与年龄相关的早搏传导变化与阵发性房颤患者中观察到的变化一致,可能导致老年人更容易发生房颤。(C)2002 Elsevier Science B. V.保留所有权利。
Objective: The incidence of atrial fibrillation increases with age. We hypothesized that aging-associated changes in the atrial action potential (AP) and conduction velocity provide a substrate for abnormal conduction and arrhythmogenesis. Methods: We used microelectrode techniques to record AP from the endocardium of the right atrial wall of dogs aged 1-5 (adult) and >8 years (old). Conduction velocity was measured between two microelectrodes 3-10 mm apart. Histological study was carried out to assess fibrosis. Results: Whereas resting potential, AP amplitude and V-max did not differ with age, the plateau was more negative and AP duration was longer in old tissue. The L-type calcium current (I-Ca,I-L) agonist Bay K8644 ( 10(-8)-10(-6) mol/l) elevated the plateau and shortened APD more in old than in adult. such that AP contour in old atria approached that of adult. In contrast, the I-Ca,I-L blocker nisoldipine (10(-8)-10(-5) mol/l) depressed the plateau in adult and had no effect in old. There was no difference between the two groups in conduction velocity of normal beats, whereas for early premature impulses, reduced conduction velocity and a,wider time window manifesting slow conduction were detected in old in comparison to adult tissue. A twofold increase in the amount of fibrous tissue was detected in old atria. Conclusions: Our data show significant differences in contour of AP in adult and old atria. The responses to Bay K8644 and nisoldipine suggest a decreased I-Ca,I-L in old atrial tissue. The alterations in AP contour and increased fibrosis may be responsible for slower conduction of early premature heats in old atria. The age-related changes in conduction of premature beats are consistent with those observed in patients with paroxysmal atrial fibrillation and may contribute to the greater propensity to atrial fibrillation in the aged. (C) 2002 Elsevier Science B.V. All rights reserved.