Ionic basis of ventricular arrhythmias in remodeled rat heart during long-term myocardial infarction
Ionic basis of ventricular arrhythmias in remodeled rat heart during long-term myocardial infarction
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DOI：
10.1016/s0008-6363(99)00070-x
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发表时间：
1999-05-01
影响因子：
10.8
通讯作者：
Vassort, G
中科院分区：
文献类型：
--
作者：
Aimond, F;Alvarez, JL;Vassort, G
目的：心肌梗死期间会出现有害的电异常。本研究的目的是分析冠状动脉结扎引起的心脏病晚期失代偿期的电流变化，并比较不同心脏区域的变化。方法：对年轻大鼠进行左冠状动脉结扎。 4-6个月后，用酶法从左心室上部基底区域以及隔膜、心尖和右心室分离并分离细胞，然后在全细胞膜片钳下进行研究。结果：基础 L 型 Ca2+ 电流，+10 mV 引发的 I-CaL 在对照中和心肌梗塞后 (PMI) 后均未表现出区域依赖性。 I-CaL 显示峰值振幅显着降低（7 个对照心脏和 7 个 PMI 心脏分别为 17.1+/-2.8 pA/pF 与 9.9+/-1.4 pA/pF，n=32 和 40），并且失活速度较慢，使得 700 ms 去极化脉冲期间的内向电荷量几乎没有变化。 β-肾上腺素能刺激在增加 PMI 细胞中的 I-CaL 方面效果较差，但它进一步减缓了失活。观察到 K+ 电流的显着差异。仅 I-to 出现区域分布，右心室振幅最大（pA/pF：右心室、心尖部、隔膜和左心室分别为 23.1+/-2.4、18.3+/-3.9、14.8+/-2.4、8.3+/-1.7，n=8、7、8 和 9）。尽管 I-to 在四个区域中的每一个区域减半（以 pA/pF 为单位：12.2+/-2.5、11.2+/-1.9、5.1+/-1.0 和 4.8+/-1.0，分别为 n=12、12、11 和 13），但在衰竭的心脏细胞中也是如此。 PMI 细胞中的 I-KI 也显着降低了 20%。双向方差分析表明，信号的地形起源与大鼠的生理状态之间不存在相互作用。 α(1)-肾上腺素能激动剂甲氧胺在假手术细胞和 PMI 细胞中显着降低 I-to 和 I-KI 至相同程度，分别降低约 35% 和 20%。结论：长期左冠状动脉闭塞会导致两个心室中 Ca2+ 和 K+ 电流发生显着变化，且幅度相似。它们包括 I-to 振幅的显着降低以及 I-CaL 失活的减慢。这两个因素都可能导致心肌梗塞后心脏细胞电行为的紊乱和心律失常的发生。 (C) 1999 Elsevier Science B.V. 保留所有权利。
Objective: Deleterious electrical abnormalities evolve during myocardial infarction. The goal of this study was to analyse current changes during the late decompensated phase of heart disease induced by coronary ligation and to compare them in various heart regions, Methods: Young rats were submitted to left coronary ligature. After 4-6 months, cells were enzymatically dissociated and isolated from the upper part basal region of the left ventricle, as well as from the septum, apex and the right ventricle before being studied under whole-cell patch-clamp. Results: Basal L-type Ca2+ current, I-CaL elicited at +10 mV did not exhibit regional dependence neither in control nor after post-myocardial infarction (PMI). I-CaL showed both a significantly reduced peak amplitude (17.1+/-2.8 pA/pF versus 9.9+/-1.4 pA/pF in seven control and seven PMI hearts, n=32 and 40, respectively) and a slower inactivation, such that the amount of inward charges during a 700 ms-depolarizing pulse was nearly unchanged. beta-Adrenergic stimulation was less effective in increasing I-CaL in PMI cells but it slowed inactivation further. Significant differences in the K+ currents were observed. A regional distribution was seen for I-to only, with the largest amplitude in the right ventricle (in pA/pF: 23.1+/-2.4, 18.3+/-3.9, 14.8+/-2.4, 8.3+/-1.7 in the right ventricle, apex, septum and left ventricle, respectively n=8, 7, 8 and 9). This was also true in failing heart cells despite I-to being halved in each of the four regions (in pA/pF: 12.2+/-2.5, 11.2+/-1.9, 5.1+/-1.0 and 4.8+/-1.0, respectively n=12, 12, 11 and 13). I-KI was also significantly reduced by 20% in the PMI cells. Two-way analyses of variance demonstrated the absence of interaction between the topographical origin of the tells and the physiological state of the rats. The alpha(1)-adrenergic agonist, methoxamine significantly reduced I-to and I-KI to the same extent in both sham and PMI cells, by about 35% and 20% respectively. Conclusions: Long-term left coronary occlusion induces significant alterations in both Ca2+ and K+ currents that occur with similar amplitude in both ventricles. They include a marked reduction in I-to amplitude as well as a slowing of I-CaL inactivation. Both factors could contribute to the disturbances in cellular electrical behaviour and the occurrence of arrhythmias in the post-myocardial infarcted heart. (C) 1999 Elsevier Science B.V. All rights reserved.