Conduction and refractory disorders in the diabetic atrium.
Conduction and refractory disorders in the diabetic atrium.
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DOI：
10.1152/ajpheart.00010.2012
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发表时间：
2012-07
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通讯作者：
Masaya Watanabe;H. Yokoshiki;Hirofumi Mitsuyama;K. Mizukami;Taisuke Ono;H. Tsutsui
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作者：
Masaya Watanabe;H. Yokoshiki;Hirofumi Mitsuyama;K. Mizukami;Taisuke Ono;H. Tsutsui
糖尿病（DM）是房颤的独立风险。然而，它的致癌底物仍不清楚。本研究旨在研究糖尿病心房肌动作电位（AP）的精确传播和时空离散度。在8周龄雄性Wister大鼠中，用链脲佐菌素（65 mg/kg）诱导DM。16 wk后，对对照组（n = 26）和DM组（n = 27）大鼠的右心房（RA）进行光学标测和组织学分析。利用光学标测测量RA传导速度（CV）的频率依赖性改变及其异质性和AP的空间分布。快速心房刺激诱发的房性快速心律失常持续时间DM组较DM组长（2.4 ± 0.6vs.0.9 ± 0.3s，P < 0.05）。糖尿病组CV降低，其异质性大于对照组。在起搏周期长度（PCL）为200 ms时，RA内四个区域的平均80%复极动作电位时程（APD（80））延长APD（80）的变异系数DM组大于对照组（0.20 ± 0.02vs.0.15 ± 0.01%，P < 0.05）。后交叉韧带<200 ms时APD（80）与200 ms时APD（80）的比值明显小于对照组（P < 0.001），APD交替发生率明显高于对照组（100 vs. 0%，P < 0.001）。糖尿病组间质纤维化程度较对照组明显加重，连接蛋白40表达较对照组明显降低。糖尿病心房重构的特征如下：更易受AT的影响，传导减慢及其异质性增加，APD延长，APD的空间离散度增加和频率依赖性缩短，以及APD交替发生率增加。
Diabetes mellitus (DM) is an independent risk of atrial fibrillation. However, its arrhythmogenic substrates remain unclear. This study sought to examine the precise propagation and the spatiotemporal dispersion of the action potential (AP) in the diabetic atrium. DM was induced by streptozotocin (65 mg/kg) in 8-wk-old male Wister rats. Optical mapping and histological analysis were performed in the right atrium (RA) from control (n = 26) and DM (n = 27) rats after 16 wk. Rate-dependent alterations of conduction velocity (CV) and its heterogeneity and the spatial distribution of AP were measured in RA using optical mapping. The duration of atrial tachyarrhythmia (AT) induced by rapid atrial stimulation was longer in DM (2.4 ± 0.6 vs. 0.9 ± 0.3 s, P < 0.05). CV was decreased, and its heterogeneity was greater in DM than control. Average action potential duration of 80% repolarization (APD(80)) at pacing cycle length (PCL) of 200 ms from four areas within the RA was prolonged (53 ± 2 vs. 40 ± 3 ms, P < 0.01), and the coefficient of variation of APD(80) was greater in DM than control (0.20 ± 0.02 vs. 0.15 ± 0.01%, P < 0.05). The ratio of APD(80) at PCL shorter than 200 ms to that at 200 ms was smaller (P < 0.001), and the incidence of APD alternans was higher in DM than control (100 vs. 0%, P < 0.001). Interstitial fibrosis was greater and connexin 40 expression was lower in DM than control. The remodeling of the diabetic atrium was characterized as follows: greater vulnerability to AT, increased conduction slowing and its heterogeneity, the prolongation of APD, the increase in spatial dispersion and frequency-dependent shortening of APD, and increased incidence of APD alternans.