臺灣博碩士論文加值系統

背景：甲狀腺功能亢進患者的臨床表徵類似於交感神經興奮的狀態，這個觀察支持甲狀腺功能亢進併有自主神經系統異常的觀念。過去曾有很多的研究探討甲狀腺功能亢進與交感神經興奮狀態的關聯性，然而這些研究顯示互相矛盾的結論。心率變異度 (heart rate variability) 的分析是一種檢查心臟受自主神經調控的有效工具，而且可用來評估心率動力學的特徵。過去曾有研究，運用線性的心率變異度分析法，評估甲狀腺功能亢進患者的心血管自主神經系統，主要發現甲狀腺功能亢進患者的副交感神經系統對心跳速率的調控是被抑制的或是正常的。然而，心臟血管系統的生理學研究顯示，心跳速率訊號的產生，是受到非線性的混沌動力系統的調控。過去尚未有以非線性的心率變異度分析法，評估甲狀腺功能亢進患者的研究。

目標：本研究運用線性與非線性的心率變異度分析法，對甲狀腺功能亢進患者，評估甲狀腺功能亢進對自主神經系統所造成的影響。

方法：收集甲狀腺功能亢進的葛雷夫茲式病 (Graves’ disease) 的患者36人 (女性32與男性4；年齡30 ± 1歲，平均值 ± 標準誤)，與一批於性別、年齡與身體質量指數相當的正常對照組36人接受心電圖量測。從正常的R波與R波間隔序列 (R-R interval series)，計算時間域與頻率域的心率變異度參數，相關維度 [correlation dimension (CD)]，與去趨勢化變動分析 (detrended fluctuation analysis) 的參數。

結果：相較於正常對照組，甲狀腺功能亢進患者的平均R波與R波間隔 (mean R-R interval)，R波與R波間隔標準差 [standard deviation of R-R intervals (SDNN)]，總功率 [total power (TP)]，極低頻功率 [very low frequency power (VLF)]，低頻功率 [low frequency power (LF)]，高頻功率 [high frequency power (HF)]，標準化高頻功率 [high frequency power in normalized units (HF%)]，與相關維度均降低 (P < 0.001)；而其標準化低頻功率 [low frequency in normalized units (LF%)]，低頻功率相對高頻功率比值 [the ratio of low frequency power to high frequency power (LF/HF)]，短期比例指數 [short-term scaling exponent (α1)]，長期比例指數 [long-term scaling exponent (α2)]，與全體比例指數 [overall scaling exponent (α)] 是增加的 (P < 0.001)。

結論：運用線性與非線性的心率變異度分析法，我們證實甲狀腺功能亢進具有交感神經興奮與副交感神經被抑制的特徵。甲狀腺功能亢進的交感與副交感不平衡狀態，幫助解釋了甲狀腺功能亢進患者的高心房顫動盛行率與運動無法持久現象。而且，甲狀腺功能亢進患者的相關維度減低，表示甲狀腺功能亢進是處在一種系統複雜度降低與心臟血管受壓力之耐受度降低的狀態。此外，部分心率變異度的參數，能反映出甲狀腺功能亢進患者的疾病嚴重度。

Background: The observation that hyperthyroid patients manifest symptoms and signs similar to those of hyperadrenergic states suggests autonomic dysfunctions in hyperthyroidism. Despite many previous studies on the association between hyperthyroidism and the hyperadrenergic state, controversies still exist. The analysis of heart rate variability (HRV) is a useful tool to assess the modulation of cardiac autonomic nervous system and the characteristics of the heart rate dynamics. Among studies using linear analysis of HRV to investigate the autonomic nervous system functions in hyperthyroidism, some disclosed reduced vagal activity, whereas others showed no vagal activity impairment. However, studies on the physiology of the cardiovascular system suggested that the generation of the heart rate signal is governed by nonlinear chaotic dynamics. No study has investigated the nonlinear dynamics of heart rate in hyperthyroidism.

Objective: This study was designed to evaluate the impact of hyperthyroidism on the autonomic nervous system via linear and nonlinear analysis of heart rate dynamics in patients with hyperthyroidism.

Methods: Thirty-six hyperthyroid Graves’ disease patients (32 females and 4 males; age 30 ± 1 years, means ± SE) and 36 sex-, age-, and body mass index-matched normal control subjects were recruited to receive electrocardiogram (ECG) recording. Time and frequency domain HRV parameters, as well as correlation dimension (CD) and detrended fluctuation analysis (DFA) parameters were computed from the normal R-R interval series.

Results: The hyperthyroid patients revealed significant differences (P < 0.001) compared with the normal controls in the following HRV parameters: a decrease in the mean R-R intervals, the standard deviation of R-R intervals (SDNN), total power (TP), very low frequency power (VLF), low frequency power (LF), high frequency power (HF), HF in normalized units (HF%), and CD; and an increase in LF in normalized units (LF%), the ratio of LF to HF (LF/HF), short-term scaling exponent α1, long-term scaling exponent α2, and overall scaling exponent α.

Conclusions: Using linear and nonlinear analysis of HRV, we have shown that hyperthyroidism is characterized by concurrent sympathetic activation and vagal withdrawal. This sympathovagal imbalance state in hyperthyroidism helps to explain the higher prevalence of atrial fibrillation and exercise intolerance among hyperthyroid patients. In addition, the decreased CD in hyperthyroid patients implies reduced complexity and impaired tolerance to cardiovascular stresses in hyperthyroidism. Furthermore, some HRV parameters could reflect the disease severity in hyperthyroid patients.

Abstract(Chinese)..........................................1
Abstract...................................................3
1Introduction..............................................5
2Methods...................................................9
2.1Subjects................................................9
2.2Studyprotocol...........................................9
2.3 Measurement of the ECG................................10
2.4 Linear analysis of HRV................................10
2.5 Correlation dimension analysis of HRV.................10
2.6 Detrended fluctuation analysis of HRV.................12
2.7 Assays................................................14
2.8 Statistical analysis..................................14
3 Results.................................................15
3.1 Patient profile.......................................15
3.2 Linear analysis of HRV................................15
3.3 Correlation dimension analysis of HRV.................19
3.4 Detrended fluctuation analysis of HRV.................23
3.5 Correlation analysis..................................28
4 Discussion..............................................32
4.1 Linear analysis.......................................32
4.2 Correlation dimension analysis........................34
4.3 Detrended fluctuation analysis........................36
4.4 Correlation analysis..................................39
5 Conclusions.............................................41
6 References..............................................42

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