溫度及鈣動力學對離體心臟心率之影響

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姓名

涂筱雯(Hsiao-wen Tu) 查詢紙本館藏

畢業系所

生物物理研究所

論文名稱

溫度及鈣動力學對離體心臟心率之影響
(The effects of temperature and calcium dynamics on cardiac interbeat intervals)

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摘要(中)

心臟心率是靠竇房節(SA node)控制,竇房節藉由細胞及細胞間的偶合產生同步之跳動。在離體老鼠全心臟的灌流系統中，我們利用藥物調控鈣離子濃度以研究鈣動力對竇房節心率之影響，我們亦探討溫度的影響。心臟細胞培養系統可用來模擬竇房節，在此系統下我們討論溫度及纖維母細胞濃度的效應。
心率的長條統計圖可以顯示平均的心率及心率變異性隨著溫度增加而上升。並且他們之間呈現冪次定理關係(power low relation)。心率之Poincare map和angle map也顯示在高溫時心率是相對規律的。溫度也許會影響細胞間偶合的強度導致 AV delay隨著溫度下降而變長。
我們在心臟細胞培養系統觀察到和離體心臟相似的結果，心率和傳導速度隨著溫上升而上升。在不同溫度下心率和傳導速率呈現線性關係，由此可看出波長是固定的。纖維母細胞會隨著培養天數而增生進而降低心率及傳導速度。

摘要(英)

Cardiac interbeat interval (IBI) is regulated by sinoatrial (SA) node. The information of contraction provided by SA node propagates through inter-cell coupling; leading to synchronous contrac-
tion. To investigate the effect of calcium dynamics on the beat rate of SA node, the heart of rat in a Langendorff system is cannulated and perfused with different chemicals which tune the calcium dynamics. As for the temperature effect, we tune the temperature in both the whole heart system and the primary cardiac co-culture of rat. Temperature is used as a parameter to change system properties (intrinsic frequency and coupling strength) on heart rate. Co-cultures of cardiac myocytes and fibroblasts are used to model the SA node. In the whole heart system, the histogram of IBI shows that both the average IBI and the IBI variability decrease
with increasing temperature. The IBI variability and average IBI exhibit power law relation. The Poincare map of IBIs and the angle map also show more regular IBI at higher temperature. The longer atrioventricular (AV) delay with decreasing temperature may be caused by the temperature-dependent coupling. In the culture system, the beat frequency (BF) and conduction velocity (CV) increase with temperature; similar to the results of whole heart experiment. The linear relation between BF and CV suggests indicates a constant wavelength. The higher fibroblast density in cultures with longer culture time decreases both the BF and CV.

關鍵字(中)

★ 變異性
★ 心率
★ 鈣
★ 溫度
★ 心臟

關鍵字(英)

★ Interbeat interval
★ Calcium
★ Temperature
★ Heart
★ variability

論文目次

Contents
List of Figures vi
List of Tables xv
1 Introduction 1
1.1 Basic cardiac structure and function . . . . . . . . . . . . . . 1
1.2 Conduction system . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2.1 The structure of SA node . . . . . . . . . . . . . . . . 3
1.2.2 Conduction . . . . . . . . . . . . . . . . . . . . . . . . 5
1.3 Basic electrocardiogram (ECG) theory . . . . . . . . . . . . . 6
1.3.1 The ECG waveform of cardiac activation . . . . . . . 7
1.4 Cells in the heart . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.4.1 The action potential of cardiomyocyte cell . . . . . . . 7
1.4.2 Excitation-contraction (EC) coupling . . . . . . . . . . 10
1.4.3 The membrane potential of fibroblast . . . . . . . . . 12
1.4.4 Gap junction . . . . . . . . . . . . . . . . . . . . . . . 13
1.5 Cardiomyocyte . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.6 Model of cardiac dynamics . . . . . . . . . . . . . . . . . . . 15
1.6.1 Excitable and unexcitable systems [17] . . . . . . . . . 15
1.6.2 Cell-Cell coupling . . . . . . . . . . . . . . . . . . . . 17
iiiContents
1.7 The motivation . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.7.1 The effect of calcium . . . . . . . . . . . . . . . . . . . 18
1.7.2 The effect of temperature . . . . . . . . . . . . . . . . 19
1.7.3 The effect of fibroblast on co-culture [30] . . . . . . . . 21
1.8 The purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2 Methods and Experimental setup 23
2.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.2 Isolated whole heart system . . . . . . . . . . . . . . . . . . . 24
2.2.1 Langendorff system . . . . . . . . . . . . . . . . . . . 24
2.2.2 Measurement system . . . . . . . . . . . . . . . . . . . 26
2.2.3 Sample preparation . . . . . . . . . . . . . . . . . . . 33
2.2.4 Noise reduction . . . . . . . . . . . . . . . . . . . . . . 35
2.3 Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.3.1 Microscope system with a small incubator . . . . . . . 36
2.3.2 Phase contrast optics system . . . . . . . . . . . . . . 37
2.3.3 Primary cultures of dissociated cardiac cells . . . . . . 41
2.4 Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3 Results 45
3.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
3.2 Result of isolated whole heart . . . . . . . . . . . . . . . . . . 46
3.2.1 The pseudo-ECG data . . . . . . . . . . . . . . . . . . 46
3.2.2 Statistic properties of IBI . . . . . . . . . . . . . . . . 47
3.2.3 The Q 10 Temperature coefficient . . . . . . . . . . . . 49
3.2.4 The properties of Pressure . . . . . . . . . . . . . . . . 50
3.2.5 Delay time of signal propagation from SA node to ven-
tricular . . . . . . . . . . . . . . . . . . . . . . . . . . 51
ivContents
3.2.6 Poincare map and angle map . . . . . . . . . . . . . . 52
3.2.7 The temperature effect . . . . . . . . . . . . . . . . . 54
3.2.8 The effect of different drugs on isolated heart . . . . . 55
3.3 Cardiac culture . . . . . . . . . . . . . . . . . . . . . . . . . . 57
3.3.1 Microscopy of cardiac contraction . . . . . . . . . . . 57
3.3.2 Contraction wave . . . . . . . . . . . . . . . . . . . . . 59
4 Discussions 62
4.1 The temperature effect . . . . . . . . . . . . . . . . . . . . . . 62
4.2 Effects of Ca handling on pacing making in isolated heart . . 63
4.3 The number of fibroblasts in cardiac culture . . . . . . . . . . 64
Bibliography 65
Appendix 70

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指導教授

陳志強、黎璧賢
(Chi-keung Chan、Pik-yin Lai)

審核日期

2010-7-30

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