血管感壓反射是維持血壓恆定的主要機制。它藉著調整心跳和周邊血管阻力，達到血壓的穩定。血管感壓反射敏感度是對於此反射功能的定量評估，定義為每單位的血壓變化（以毫米汞柱表示）所引起的心率變化（心電圖R-R間期，以毫秒表示）。血管感壓反射敏感度已被廣泛認為可做為評估各種心血管與腦血管疾病病患預後及危險分級的臨床指標。
頸動脈的硬化和狹窄，已被報告過會伴隨著血管感壓反射敏感度的降低。雖然頸動脈支架置放術已知可有效地治療嚴重的頸動脈狹窄，以避免中風的再發，但有報告指出，這項治療在實施當中或剛做完的短時間內，會引起血管感壓反射功能的異常。然而，這項治療對血管感壓反射功能及心血管自律神經功能的長期影響，目前並不清楚。
本論文分為三大部分。在第一部分，我們以非侵入性的方法，評估了22位接受過頸動脈支架置放術的病人的血管感壓反射敏感度，及其他的心血管自律神經功能，並將這些數據與另外二組受測者比較，其中一組，是性別與年齡適配的正常對照組；另一組，則是也有嚴重的頸動脈狹窄，卻未接受頸動脈支架置放術的危險條件對照組。我們發現，血管感壓反射敏感度在頸動脈支架置放病人組及危險條件對照組，均顯著的較正常對照組降低，但在頸動脈支架置放病人組及危險條件對照組之間，則無顯著差異。我們因此推論，造成血管感壓反射敏感度降低的原因，是病人的疾病本身，而非頸動脈支架置放術。
在第二部分，我們欲闡明在第一部分的研究中的一些意外發現。首先，我們發現在不同的血管感壓反射敏感度指標間，有些歧異性的結果。雖然以伐氏操作（Valsalva maneuver）所得的血管感壓反射敏感度指標，在病人組顯示出顯著的降低；但以序列方法（sequence method）分析心率及血壓自然起伏所得的血管感壓反射敏感度指標，在各組之間卻無顯著的差異。另外，這兩個指標之間的相關性，在病人組內被打斷了。我們推測，這二項結果都是因為呼吸的影響所致。因此，我們另外又找了3位頸動脈支架置放術後的病人，與原本的22位，總共25位病人，與相同數目的正常對照組，進行了如第一部分我們所做的檢查及分析。另外，我們將他們心率及血壓自然起伏的序列，以一個阻斷頻率為0.24至0.3赫茲（相當於每分鐘14到18下的呼吸頻率）的帶阻濾波器濾過，再以同樣的序列方法分析濾過後的心率及血壓起伏，得到一個新的血管感壓反射敏感度指標。這個新的指標，與用伐氏操作所得的血管感壓反射敏感度指標，重現了原本在病人組中失去的相關性。我們推論，在個體的血管感壓受器功能降低，可是中樞調控的心臟迷走神經反應卻相對保留的情況下，就如同這些頸動脈支架置放術後的病人，以序列方法分析所得的血管感壓反射敏感度指標，會受到呼吸的影響而產生誤差。
雖然上述帶阻濾波器的方法，在病人組重現了二個不同方式得到的血管感壓反射敏感度指標的相關性，但這顯然不是個去除呼吸影響的理想方案。因為呼吸的頻率（0.2至0.3赫茲），與高頻的心臟迷走神經調控頻率（0.15至0.4赫茲），大部分重疊。以濾波器濾掉呼吸頻率的同時，將許多該頻率範圍的有用資訊也濾掉了。所以，在最後一部分，我們用獨立成分分析（independent component analysis）的方法，分析了心率與血壓的變異性，試圖找到一個新指標，以用來分辨頸動脈支架置放術後的病人與正常對照組的自律神經狀態。假設心率與血壓的起伏振盪，可以分解為心臟交感神經活性及心臟副交感神經活性二個成分，由獨立成分分析所得的結果，我們便能得到一個表示交感、副交感平衡（sympathovagal balance）的新指標。這個新的指標，在頸動脈支架置放術後的病人與正常人的辨識上，有較佳的鑑別力，且比起傳統由心率變異頻譜分析所得的低高頻能量比所代表的交感、副交感平衡，它似乎是個更好的指標。
經由這一系列的研究，我們希望能對於頸動脈支架置放術後的病人，其血管感壓反射敏感度及心血管自律神經功能，有個整體的認識。我們並不去決定，這些方法之中哪一個較好，而是去發現這些方法所隱含的更多的生理意義，並評估其局限性。我們希望藉此能幫助臨床醫師，使其更了解這些自律神經功能指標與臨床及生理的關聯；也幫助研究者，使其在各種不同的實驗或臨床狀況下，能選擇更合理的方法來做研究。

Baroreflex is a key mechanism in blood pressure (BP) homeostasis that maintains stable BP by adjusting heart rate (HR) and total peripheral resistance. Baroreflex sensitivity (BRS) is a quantitative assessment of baroreflex function and thus defined as changes in HR (expressed as milliseconds of R-R interval) in response to changes in systolic BP (mmHg). BRS has been widely accepted as an important clinical indicator for prognosis prediction and risk stratification of patients with various cardiovascular and cerebrovascular diseases.
Carotid atherosclerosis and stenosis have been reported to be associated with reduced BRS. Although carotid stenting (CAS) have been proven as an effective treatment for severe carotid stenosis in prevention of further stroke, the intervention has been reported to cause baroreflex dysfunction during or shortly after this procedure. However, little is known about long-term outcomes of baroreceptor and cardiovascular autonomic function in patients with CAS.
There are 3 main parts in this thesis. In the first part, we assessed BRS and other cardiovascular autonomic functions by using non-invasive methods in 22 adult patients who had received CAS for 6 months or more and compared their data with 2 other groups, the one with sex and age matched normal volunteer subjects (normal control group) and the other with patients having severe carotid stenosis but without CAS (risk control group). We found that baroreceptor function is significantly reduced in groups of CAS patients and risk control patients compared to normal control subjects while there is no significant difference between groups of CAS patients and risk controls. Thus we suggest that reduced baroreceptor function in CAS patients may be due to underlying diseases rather than the CAS procedure.
In the second part, we aimed to elucidate some incidental findings in the first part of our study: 1) diverse results between the two BRS parameters by different methods, BRS_VM, which is obtained from valsalva maneuver, and BRS_seq, which is computed from sequence method by analysis of spontaneous oscillations of HR and BP; while BRS_VM shows significant decrement in patient groups compared to the normal subjects, BRS_seq dose not reveal significant difference between CAS patients and normal subjects; and 2) interruption of correlation between these 2 BRS parameters in patient groups. We suggested that these results are due to interference of respiration. Therefore, we enrolled 3 more CAS patients (25 totally) as well as the same number of normal subjects to receive the similar tests as we had done in the first part. We had their oscillations of HR and BP filtered by a band-stop filter with stop-band from 0.24 to 0.3 Hz, corresponding to respiration rate of 14-18 cycles per minute. Sequence method was done again on the filtered sequences to get a new BRS parameter, BRS_seq_r. The correlation between parameters of BRS_VM and BRS_seq_r in patient group is then restored. We conclude that there is a bias from respiratory effect in computing spontaneous BRS using sequence method when the subjects have impaired baroreflex function with relatively preserved centrally mediated cardiovagal function, such as patients with CAS.
Although the band-stop filter restored the correlation between two BRS parameter obtained from different methods, it is not an ideal solution to avoid respiratory effect. Because the respiratory frequency (0.2-0.3 Hz) and the high-frequency cardiovagal modulation (0.15-0.4 Hz) are mostly overlapped, we may loss too much information in the overlapping band using this filter. Thus in the last part, we analyzed variabilities of HR and BP using independent component analysis (ICA) and tried to find new parameters useful in discriminating CAS patients with normal subjects. Assuming that the oscillations of HR and BP can be decomposed to cardiac sympathetic and cardiac parasympathetic activities, we have a novel index of sympathovagal balance from the computation of ICA. The new index has higher discrimination power in distinguishing the autonomic status of CAS patients from that of the control subjects and seems to be a better index than the conventional one, the ratio of low-to-high frequency spectra power of HR variability.
Through these series of studies, we aim to have a global scope on BRS as well as cardiovascular autonomic functions of CAS patients. We never try to determine which is a “better” method, but, instead, to explore more physiological implication of these methods and to evaluate their limitations. We hope it will do some help for physicians to learn more clinical and physiological relevance of these autonomic parameters, and for researchers to have a rational choice of either method in any given experimental or clinical situation.

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