晚钠电流分布不均一性与频率依赖性复极离散关系的研究

发布时间：2019-04-19 04:37

【摘要】：(第一部分)背景:QT间期是心室复极的一个指数,具有频率依赖性,心室复极的频率依赖性异常增加具有致心律失常性,目前还不知道复极的频率依赖性是不是具有区域性的不同。所以,该研究的目的是研究复极是不是存在区域性的不同,如果有不同,晚钠电流是不是也存在区域性不同,而这种不同是不是会产生复极离散。方法:动作电位时程,具有频率依赖性,我们分别研究四个心腔心肌细胞的晚钠电流分布及在药物作用下的区域性反应。动作电位时程用标准微电极技术进行记录,晚钠电流用全细胞膜片钳技术进行记录。结果:四个心腔细胞之间动作电位时程及其频率依赖性具有明显的区域性不同。左室心肌细胞具有最长的动作电位时程,最明显的频率依赖性改变,而右房及左房心肌细胞具有最短的动作电位时程,最不明显的频率依赖性改变。有趣的是,晚钠电流密度分布具有不均一性,并且和区域性的动作电位时程改变和频率依赖性改变相一致,具体分布如下:左室右室左房/右房。多非利特(IKr阻断剂)和ATX-II(晚钠电流增强剂)均明显增加左室动作电位时程的频率依赖性,从而加重了复极的区域性离散。与此对比,心房对以上两种QT延长药物反应不明显。雷诺嗪(晚钠电流阻断剂)在30μM浓度作用下明显减少心室细胞动作电位时程的频率依赖性,且明显减少慢频率依赖的区域性复极离散。结论:研究结果表明:晚钠电流在四个心腔分布完全不同,即左室密度右室左房/右房,晚钠电流分布的不均一性对复极频率依赖性的区域性不一致性改变具有重要贡献,在延长动作电位药物的作用下,这种影响更加明显。(第二部分)背景:第一部分对晚钠电流的研究表明,晚钠电流在四个心腔分布不同,左室心肌细胞晚钠电流分布最多,右室分布少于左室,心房心肌细胞分布最少,晚钠电流的分布不均一性是复极频率依赖性离散的离子基础。第一部分的实验是电流水平的研究,并未在大体标本进行研究,因此,本实验的目的是验证晚钠电流在大体标本上对复极频率依赖性离散的影响。方法:用冠状动脉灌注的楔形组织块的方法,记录左室、右室、心房动作电位时程(APD)、QT间期,以及上述参数的频率依赖性。结果:和第一部分相同,不同心腔之间存在不同的复极时间,复极随着频率改变的改变幅度也不相同,具体如下:左室拥有最长的QT间期及动作电位时程,其频率依赖性改变最明显,右室次之,心房的变化最少。结论:通过增加及减少晚钠电流的研究表明:晚钠电流的分布不同导致了不同心腔之间复极时间的不同,以及复极频率依赖性改变的差异。
[Abstract]:(part I) background: QT interval is an index of ventricular repolarization, which is frequency-dependent. Abnormal increase in frequency-dependent ventricular repolarization has arrhythmogenicity. It is not known whether the frequency dependence of repolarization is regional. Therefore, the purpose of this study is to study whether there are regional differences in repolarization and, if there are differences, whether there are regional differences in late sodium currents, and whether this difference will result in repolarization dispersion. Methods: the time course of action potential was frequency dependent. We studied the distribution of late sodium current in four cardiac myocytes and the regional response under the action of drugs. The action potential duration was recorded by standard microelectrode technique, and the late sodium current was recorded by whole-cell patch clamp technique. Results: there were significant regional differences in the action potential duration and its frequency dependence among the four cardiac lumen cells. Left ventricular cardiomyocytes had the longest action potential duration and the most obvious frequency-dependent changes, while the right atrium and left atrium cardiomyocytes had the shortest action potential duration and the least obvious frequency-dependent change. Interestingly, the distribution of late sodium current density is heterogeneous and is consistent with regional changes of action potential duration and frequency dependence. The distribution is as follows: left ventricle, right ventricle, left atrium / right atrium. Both IKr blocker and ATX-II (late sodium current enhancer) significantly increased the frequency dependence of left ventricular action potential duration, thus aggravating the regional dispersion of repolarization. In contrast, atrial response to these two QT prolongation drugs was not significant. Ranolazine (late sodium current blocker) significantly reduced the frequency-dependent action potential duration of ventricular cells at the concentration of 30 渭 M, and decreased the slow frequency-dependent regional repolarization dispersion. Conclusion: the results show that the distribution of late sodium current is completely different in four cardiac cavities, that is, left atrium / right atrium of left ventricular density, and the heterogeneity of late sodium current distribution plays an important role in the regional inconsistencies of repolarization frequency dependence. Under the action of action potential drugs, this effect is more obvious. Background: in the first part, the distribution of late sodium current in four cardiac cavities is different, the distribution of late sodium current in left ventricular myocytes is the most, the distribution of right ventricle is less than that of left ventricle, and the distribution of atrial cardiomyocytes is the least. The uneven distribution of late sodium current is the ion basis of frequency-dependent dispersion of repolarization. The first part of the experiment is the study of the current level, not in the gross sample. Therefore, the purpose of this experiment is to verify the effect of late sodium current on the dispersion of repolarization frequency dependence on the gross sample. Methods: the left ventricular, right ventricular, atrial action potential duration (APD), QT intervals and the frequency dependence of these parameters were recorded by means of wedge-shaped tissue mass perfused by coronary artery. Results: as in the first part, there were different repolarization time between different cardiac cavities, and the extent of repolarization changed with the change of frequency. The results were as follows: left ventricular had the longest QT interval and action potential duration. The frequency-dependent changes were the most obvious, followed by the right ventricle, and the atrial changes were the least. Conclusion: the study of increasing and decreasing the late sodium current shows that the different distribution of the late sodium current leads to different repolarization time between different cardiac cavities and the difference of repolarization frequency dependent change.
【学位授予单位】：郑州大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.7

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