臺灣博碩士論文加值系統

心室性心律不整佔心臟突發性停止的80％。雖然心律不整可能發生在所有年齡段，但在老年人中更為常見。在過去的的研究中，心律失常與心臟的動態電性傳導有關。當竇房結發給心肌細胞電信號時，電傳導將導致心房和心室收縮以將血液泵送到整個身體。因此，紊亂動態電傳導可能會影響心肌功能並誘發心律不整。此外，過去的研究中表示，治療心衰竭的藥物： sacubitril / valsartan 有降低心律不整發生的跡象。因此，我們假設心律不整的抑制是通過穩定動作電位週期的恢復和動態電性傳導所代表的電動力學來實現的。因此我們利用正常及高血壓的大鼠進行實驗，我們將Optical mapping用於研究大鼠心律不整的保護，並與valsartan進行比較。此外，進行optical mapping的分析方法過去大多是手動分析的，為了提高分析效率，我們開發了整合性的分析軟體，其中包括心率變異性分析，動作電位持續時間（Action potential duration, APD），舒張間期（Diastolic interval, DI），二維的傳導速度(2-D Conduction velocity, 2-D CV)，傳導速度圖(Conduction velocity map)和主要頻率（Dominant frequency, DF）。在我們的結果中，SHR大鼠餵食sacubitril / valsartan後，APD恢復曲線的最大斜率明顯低於餵食纈沙坦和生理鹽水（SHR-CON：1.32±0.12 vs. SHR-DIO：0.29±0.04，p <0.001; SHR-CON：1.32±0.12 vs. SHR-ENT：0.10±0.03，p <0.001）。文獻指出當斜率大於1時，心律不整的風險會增加。在CV圖分析中，我們計算了等時線圖的傳導角度（STDAngle）的標準偏差。用valsartan和sacubitril / valsartan治療後，SHR組的STDAngle有明顯的降低（SHR-CON：0.599±0.017 vs. SHR-DIO：0.521±0.023弧度，p = 0.021; SHR-CON：0.599±0.017 vs. SHR -ENT：0.405±0.031弧度，p <0.001），但WKY有不同的情況，餵食sacubitril / valsartan或valsartan的大鼠的STDAngle反而會增加，其中死亡率也有顯著的增加（WKY-CON：0.507±0.032 vs. WKY-DIO：0.594±0.017弧度，p = 0.037）。因此，我們認為sacubitril / valsartan可以讓心臟電性傳導時更為平坦，也可以讓SHR大鼠的心室有效地收縮，從而將血液泵送到全身。但是，對於正常受試者而言，sacubitril/valsartan提供心律失常保護似乎不是一個好的選擇。

Ventricular arrhythmia accounts for 80% of sudden cardiac arrest. Although arrhythmia may occur in all ages, it is more common in the elderly. And the previous studies have shown that the arrhythmia was associated with the propagation of the electrodynamics. When the SA Node triggers the electrical signal to cardiomyocytes, the electrical conduction will cause the atrium and ventricle contraction to pump the blood to the whole body. Therefore, the disorder electrodynamics may affect the function of the myocardium and induce arrhythmia. Also, there were studies showed that the drugs (sacubitril/valsartan) to treat heart failure could also reduce the incidence rate of arrhythmia. So, we hypothesize that the inhibition of arrhythmogenesis is through the stabilization of electrical dynamics, as represented by electrical restitution and conduction. The animals are aged 8-week-old female spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) Rat are used in these experiments. We applied the optical mapping technique to investigate the protection of arrhythmia for rats and compare them with the valsartan. In addition, the analysis methods were manual in the past, in order to improve the efficiency of analyzing, we developed the integrated analysis software, which was included the heart rate variability analysis, action potential duration (APD), diastolic interval (DI), conduction velocity, conduction velocity map, and dominant frequency (DF). In our results, the SHR rats after feeding the sacubitril/valsartan which maximum slope of the APD restitution curve is significantly lower than feeding the valsartan and the saline (SHR-CON: 1.32±0.12 vs. SHR-DIO: 0.29±0.04, p<0.001; SHR-CON: 1.32±0.12 vs. SHR-ENT: 0.10±0.03, p<0.001). If the slope > 1, the risk of arrhythmia will increase. In the CV map analysis, we calculated the standard deviation of the conduction angles (STDAngle) of the isochrones map. The STDAngle of the SHR groups is decreased after the treatment with valsartan and sacubitril/valsartan (SHR-CON: 0.599±0.017 vs. SHR-DIO: 0.521±0.023 radian, p=0.021; SHR-CON: 0.599±0.017 vs. SHR-ENT: 0.405±0.031 radian, p<0.001), but the WKY had different changes, the STDAngle of rats that fed the sacubitril/valsartan or fed the valsartan was increased, so did the mortality rate (WKY-CON: 0.507±0.032 vs. WKY-DIO: 0.594±0.017 radian, p=0.037). Therefore, we considered that the sacubitril/valsartan could let the electrodynamics more flatten and it could also let the myocardium of SHR rats create effectively contraction to pump the blood to the whole body. But it seems not a good choice to provide the protection of the arrhythmia for normal subjects.

Contents I
List of Figures III
List of Tables V
Acknowledgment VI
中文摘要 VII
Abstract VIII
Chapter 1. Introduction 1
1.1 Background 1
1.2 The impact caused by arrhythmia 2
1.3 Relation of arrhythmia and dynamic electricity conduction 2
1.4 Sacubitril/valsartan treatment for heart failure 3
1.5 Review literature about the electrodynamics and arrhythmia 4
1.6 Hypothesis and Research Motivation 4
1.7 Optical mapping for isolated heart 5
Chapter 2. Methods 6
2.1 Graphical user interfaces in MATLAB 6
2.2 The animal experiment design of optical mapping 7
2.3 Optical mapping analysis software front end design 10
2.4 Analysis of heart rate variability 11
2.5 Analysis of action potential duration and diastolic interval 15
2.6 Analysis of 2D conduction velocity 18
2.7 Analysis of conduction velocity map for electrical conduction 20
2.8 Analysis of dominant frequency 24
2.9 The accuracy for the self-made software 26
2.10 Statistical analysis 26
Chapter 3. Results 27
3.1 The reliability of the self-made software 27
3.2 HRV analysis 29
3.3 Effects of valsartan and sacubitril/valsartan on VT/VF induction 32
3.4 Effects of valsartan and sacubitril/valsartan on cardiophysiology 34
Chapter 4. Discussion 41
4.1 High mortality rate for normotensive rats 41
4.2 The effect of sacubitril/Valsartan for anti-arrhythmia 42
4.3 Evaluation of cardiac physiology by Langendorff Isolated Heart Perfusion 42
4.4 The relation between dynamic electrical conduction and antiarrhythmic 43
4.5 Limitation of the analysis software 44
Reference 45
Publication 51
Conference 51

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