【摘要】：(第一部分)背景:QT間期是心室復(fù)極的一個(gè)指數(shù),具有頻率依賴性,心室復(fù)極的頻率依賴性異常增加具有致心律失常性,目前還不知道復(fù)極的頻率依賴性是不是具有區(qū)域性的不同。所以,該研究的目的是研究復(fù)極是不是存在區(qū)域性的不同,如果有不同,晚鈉電流是不是也存在區(qū)域性不同,而這種不同是不是會產(chǎn)生復(fù)極離散。方法:動(dòng)作電位時(shí)程,具有頻率依賴性,我們分別研究四個(gè)心腔心肌細(xì)胞的晚鈉電流分布及在藥物作用下的區(qū)域性反應(yīng)。動(dòng)作電位時(shí)程用標(biāo)準(zhǔn)微電極技術(shù)進(jìn)行記錄,晚鈉電流用全細(xì)胞膜片鉗技術(shù)進(jìn)行記錄。結(jié)果:四個(gè)心腔細(xì)胞之間動(dòng)作電位時(shí)程及其頻率依賴性具有明顯的區(qū)域性不同。左室心肌細(xì)胞具有最長的動(dòng)作電位時(shí)程,最明顯的頻率依賴性改變,而右房及左房心肌細(xì)胞具有最短的動(dòng)作電位時(shí)程,最不明顯的頻率依賴性改變。有趣的是,晚鈉電流密度分布具有不均一性,并且和區(qū)域性的動(dòng)作電位時(shí)程改變和頻率依賴性改變相一致,具體分布如下:左室右室左房/右房。多非利特(IKr阻斷劑)和ATX-II(晚鈉電流增強(qiáng)劑)均明顯增加左室動(dòng)作電位時(shí)程的頻率依賴性,從而加重了復(fù)極的區(qū)域性離散。與此對比,心房對以上兩種QT延長藥物反應(yīng)不明顯。雷諾嗪(晚鈉電流阻斷劑)在30μM濃度作用下明顯減少心室細(xì)胞動(dòng)作電位時(shí)程的頻率依賴性,且明顯減少慢頻率依賴的區(qū)域性復(fù)極離散。結(jié)論:研究結(jié)果表明:晚鈉電流在四個(gè)心腔分布完全不同,即左室密度右室左房/右房,晚鈉電流分布的不均一性對復(fù)極頻率依賴性的區(qū)域性不一致性改變具有重要貢獻(xiàn),在延長動(dòng)作電位藥物的作用下,這種影響更加明顯。(第二部分)背景:第一部分對晚鈉電流的研究表明,晚鈉電流在四個(gè)心腔分布不同,左室心肌細(xì)胞晚鈉電流分布最多,右室分布少于左室,心房心肌細(xì)胞分布最少,晚鈉電流的分布不均一性是復(fù)極頻率依賴性離散的離子基礎(chǔ)。第一部分的實(shí)驗(yàn)是電流水平的研究,并未在大體標(biāo)本進(jìn)行研究,因此,本實(shí)驗(yàn)的目的是驗(yàn)證晚鈉電流在大體標(biāo)本上對復(fù)極頻率依賴性離散的影響。方法:用冠狀動(dòng)脈灌注的楔形組織塊的方法,記錄左室、右室、心房動(dòng)作電位時(shí)程(APD)、QT間期,以及上述參數(shù)的頻率依賴性。結(jié)果:和第一部分相同,不同心腔之間存在不同的復(fù)極時(shí)間,復(fù)極隨著頻率改變的改變幅度也不相同,具體如下:左室擁有最長的QT間期及動(dòng)作電位時(shí)程,其頻率依賴性改變最明顯,右室次之,心房的變化最少。結(jié)論:通過增加及減少晚鈉電流的研究表明:晚鈉電流的分布不同導(dǎo)致了不同心腔之間復(fù)極時(shí)間的不同,以及復(fù)極頻率依賴性改變的差異。
[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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R541.7

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