臺灣博碩士論文加值系統

目的：睡眠呼吸中止(Obstructive sleep apnea, OSA)及反覆睡眠覺醒(Arousal)將增強交感神經活性同時可能造成心室再極化之電干擾，心率變異度(Heart rate variability, HRV)之頻率指標以及校正心率後的校正QT區間(QTc)與T波波峰至終止之持續時間(Tp-e)、Tp-e/QT及Tp-e/QTc比分別作為目前極具代表性的自律神經活性及室性心律不整之心電圖指標，本研究旨在調查男性於睡眠週期中是否因睡眠呼吸中止或睡眠覺醒提高其QTc、Tp-e、Tp-e/QT或Tp-e/QTc之數值，且同時探討QTc、Tp-e、Tp-e/QT或Tp-e/QTc之數值是否隨心率變異度指標波動。
材料與方法：招募101位呼吸中止-淺呼吸指數(每小時17.7±18.3次)與覺醒指數(每小時33.0±17.6次)分佈較廣之健康男性受試者(年齡：43.5±7.9歲，BMI：26.7±3.3 kg/m2)，計算取自睡前清醒期(AWK)、非快速動眼期第二期(N2)、慢波睡眠期(N3)與快速動眼期(REM)之5分鐘未發生睡眠覺醒的心電圖數據，獲得經自然對數轉換之心率變異度指標、QTc、Tp-e、Tp-e/QT及Tp-e/QTc。
結果：所有受試者將分別以線性迴歸分析中與QTc或Tp-e呈顯著相關之呼吸中止-淺呼吸指數(正常控制組、輕-中度OSA與重度OSA)及覺醒指數分作三組，心率變異度指標隨睡眠週期之波動未因分組而呈現顯著差異，QTc於AWK、N2及N3發現重度OSA組大於正常控制組(分別為468±40 vs 431±39，p=0.01；469±46 vs 430±40，p=0.01；472±50 vs 434±41 ms，p=0.02)，然而Tp-e則是發現AWK、N2及N3呈現顯著性(p值分別為0.00、0.01與0.02)，但Tp-e/QT 與Tp-e/QTc則未呈現出顯著性，雖然與先前研究報告結果相同，心率變異度之頻率指標隨睡眠週期波動，但未發現QTc、Tp-e、Tp-e/QT及Tp-e/QTc出現如這些對應自律神經指標之震盪。
結論：根據本研究結果可能顯示了重度OSA或反覆發生覺醒似乎擁有較高的夜間心律不整風險，因其心室去極化/再極化時間延長且因長時間睡眠呼吸中止或睡眠覺醒負面影響之累積於心室再極化功能障礙上發揮了關鍵作用，而非即時的交感神經作用影響。

Objective: Obstructive sleep apnea and repetitive arousals enhance sympathetic activities, and potentially cause electrical disturbances during ventricular repolarization. Spectral parameters of heart rate variability (HRV) and heart rate corrected QT interval (QTc), the interval between peak and the end of T wave (Tp-e), Tp-e/QT ratio, and Tp-e/QTc ratio are promising surrogates for autonomic nervous activity and electrocardiographic indices of ventricular arrhythmogenesis, respectively. We aim to investigate that QTc, Tp-e, Tp-e/QT, and Tp-e/QTc are greater in male subjects with sleep apnea or hyperaousal over various night-sleep-stages and fluctuate with corresponding HRV parameters.
Material and method: Natural-logarithm-transformed power values of HRV, QTc, Tp-e, Tp-e/QT, and Tp-e/QTc from one 5-min arousal-free electrocardiography segment in each of pre-sleep-wakefulness (AWK), non-rapid-eye-movement stage 2 (N2), slow-wave (N3), and the latest rapid-eye-movement sleep (REM) were computed in 101 healthy males (43.5±7.9 yrs., 26.7±3.3 kg/m2) with wide-ranged apnea-hypopnea and arousal indices (17.7±18.3 and 33.0±17.6/hr., respectively).
Results: All participants were sub-grouped into normal, mild-moderate and severe OSA or low, moderate and high arousal in frequency by apnea-hypopnea index (AHI) or arousal index, which significantly correlated by QTc or Tp-e by linear regression analyses. No differences were found in fluctuation of each HRV parameter across various stages among three subgroups categorized by AHI values. QTc values at stages AWK, N2 and N3 are greater in severe OSA patient than normal control (468±40 vs 431±39; 469±46 vs 430±40; and 472±50 vs 434±41 ms; each p value is 0.01, 0.01 and 0.02 respectively), whereas Tp-e values sequentially decreased from high, middle and low arousal subjects at stages AWK, N2 and N3 (each p value is 0.00, 0.01 and 0.02) but with constant Tp-e/QT and Tp-e/QTc ratios. Though HRV spectral parameters fluctuating over various presleep wakefulness and three sleep stages as previous reports, QTc, Tp-e, Tp-e/QT ratio, and Tp-e/QTc ratio are not found oscillate with these corresponding automatic nervous indices.
Conclusions: It might suggest that severe OSA or repetitive arousals likely have a higher risk for nocturnal arrhythmia accounted for by prolonged repolarization and/or depolarization periods of ventricles and long-term accumulating adverse effect of OSA or arousals, rather than real-timed autonomic activities, play a major role in the dysfunction of ventricular repolarization.

誌謝 I
中文摘要 II
英文摘要 IV
目次 VI
圖次 IX
表次 XII
第一章緒論 1
1.1 前言 1
1.2 研究目的 4
1.3 研究假說 4
第二章文獻探討 5
2.1 QT區間延長症候群(Long QT syndrome, LQTS) 5
2.2 阻塞型睡眠呼吸中止症(Obstructive sleep apnea, OSA) 6
2.3 T波尖峰-終止區間(T peak to end interval, Tp-e interval) 7
第三章研究方法 8
3.1 研究流程 8
3.2 受試者族群 9
3.3 多導睡眠生理監測儀(Polysomnography, PSG) 11
3.4 血液生化分析(Blood biochemical analysis) 14
3.5 運動心肺功能(Cardiopulmonary exercise test) 14
3.6 心電圖訊號分析 15
3.6.1 心率變異度(Heart rate variability, HRV) 23
3.6.2 QT區間(QT interval)計算 24
3.6.3 T波尖峰-終止區間(T peak to end interval, Tp-e interval)計算 25
3.7 統計分析 26
第四章結果 27
第五章討論 47
第六章研究限制 53
第七章結論 54
第八章未來展望 55
附錄 56
附錄1 Q波波形示意 56
附錄2 S波-T波波形示意 57
附錄3 實際程式執行結果－心電圖7秒片段展示 58
參考文獻 61

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