心房心律不整與心率變異性之研究

A research of atrial arrhythmia and heart rate variability

張建榮(Chien-Jung Chang)

指導教授 ： 楊騰芳

國立交通大學/生物科技學院/生物科技學系暨研究所/博士(2015年)

https://doi.org/10.6842/NCTU.2015.00845

摘要

摘要
1. 研究壹: sitagliptin對肺靜脈與心房之電生理與機械特性之調控
肺靜脈與心房是造成心房顫動之異位性病灶及心房顫動之所在。而高血壓與糖尿病是已知的心房顫動之危險因子。Dipeptidyl peptidase-IV抑制劑(DPP-4I)是一新型降血糖藥且具有心臟血管之生理作用，然而我們並不清楚DPP-4I是否對有高血壓之肺靜脈與心房組織具有電生理之調控。實驗分為Wistar-Kyoto大鼠(WKY)，自發性高血壓大鼠(spontaneously hypertensive rats, SHR) ，餵食sitagliptin (10 mg/kg)四週之WKY(WKYs)與SHR(SHRs)四組。從已麻醉之動物取得心臟後進行非存活實驗，藉由傳統微電極測定並比較肺靜脈自動節律及左右心房組織之動作電位(AP)。實驗結果發現sitagliptin治療明顯影響肺靜脈與心房組織之電生理與機械特性，此影響又受到高血壓之調控。
2. 研究貳: 選擇性與非選擇性非類固醇抗發炎藥物對肺靜脈與心房心律不整發生之控制差異
已知非類固醇抗發炎藥物(NSAIDs)會增加心房顫動(AF)之風險，本研究主要探討選擇性與非選擇性NSAIDs是否對肺靜脈與心房心律不整發生之調控有無差異。本實驗藉由傳統微電極分別於選擇性(celecoxib)與非選擇性(indomethacin) NSAIDs 治療前後測定並比較兔子竇房結與有自動節律之肺靜脈的自發性節律速率，也測定並比較左右心房組織細胞之動作電位(AP)。 並用全細胞膜片箝制(patch clamp)技術測定並記錄celecoxib治療前後之肺靜脈細胞的鈉鈣交換離子流(NCX)，L型鈣離子流(ICa-L)及晚期鈉離子流(INa-late) 。實驗結果發現選擇性與非選擇性NSAIDs對肺靜脈與心房之電生理特性的控制有明顯差異。Celecoxib可能透過增加NCX離子流而誘發觸發活動(triggered activity)進而導致心律不整產生。
3. 研究參:姿態與性別分別對二尖瓣脫垂患者及正常人的心率變異性之影響
心率變異性(HRV)對正常人及二尖瓣脫垂(MVP)患者的自律神經活性是一個有用的分析工具。但是在臺灣，姿態與性別分別對二尖瓣脫垂患者及正常人的HRV之影響則尚未確定。我們先經由心臟超音波確診二尖瓣脫垂。使用本土研發之心電圖機分別記錄三種穩定姿勢時MVP患者及正常人之HRV參數，再使用快速傅立葉轉換(FFT) 或自動迴歸方法(AR)分析HRV之時域及頻域參數。實驗結果發現女性於非站立狀態有較明顯之副交感神經活性，但患MVP的女性及患MVP男性皆有較高的之交感神經張力。MVP患者的頻域參數對於姿勢改變有較遲頓之反應則意味著其自律神經控制失調。

關鍵字

心房顫動 ； 肺靜脈 ； 心房 ； 心電生理 ； 心率變異性 ； 二尖瓣脫垂

並列摘要

Abstract
Research 1:
Sitagliptin Modulates the Electrical and Mechanical Characteristics of Pulmonary Vein and Atrium
The pulmonary veins (PVs) and atria are important foci during that period when atrial fibrillation (AF) is generated and maintained. It is well understood that hypertension and diabetes mellitus (DM) are important risk factors for AF. Dipeptidyl peptidase-IV (DPP-4) inhibitors are new agents in the fight against type 2 DM, though they have been found to have several cardiovascular effects. However, it is not clear whether DPP-4 may modulate the electrical and mechanical characteristics in hypertensive atrium or PVs. Conventional microelectrodes were used to record the action potentials (APs) in isolated PVs, right atrium (RA), and left atrium (LA) in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without sitagliptin (10 mg/kg) for 4 weeks. Out study found that the sitagliptin significantly affects the electromechanical characteristics of PVs and atria, which can be modulated by hypertension.
Research 2:
Selective and Non-selective Non-steroidal Anti-inflammatory Drugs Differentially Regulate Pulmonary Vein and Atrial Arrhythmogenesis
Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of atrial fibrillation (AF).This study investigated whether selective and non-selective NSAIDs differentially regulate the arrhythmogenesis of pulmonary veins and atria. Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial node (SAN), left atrium (LA), and right atrium (RA) preparations before and after celecoxib or indomethacin administration. A whole-cell patch clamp was used to record the sodium-calcium exchanger (NCX) current, L-type calcium current (ICa-L), and late sodium current (INa-late) before and after celecoxib administration in isolated PV cardiomyocytes. Out study found that the selective and non-selective NSAIDs differentially modulate PV and atrial electrophysiological characteristics. Celecoxib increased PV triggered activity through enhancement of the NCX current, which contributed to its arrhythmogenesis.
Research 3:
Posture and Gender Differentially Affect Heart Rate Variability of Symptomatic Mitral Valve Prolapse and Normal Adults
Heart rate variability (HRV) has been shown to be a useful measure of autonomic activity in healthy and mitral valve prolapsed (MVP) subjects. However, the effects of posture and gender on HRV in symptomatic MVP and normal adults had not been elucidated in Taiwan. The diagnosis of MVP was confirmed by cross-sectional echocardiography. A locally developed Taiwanese machine was used to record the HRV parameters for MVP and control groups in three stationary positions. The HRV time-domain parameters, and the frequency-domain parameters derived from fast Fourier transform (FFT) or autoregressive (AR) methods were analyzed. Our study found that the resting female dominated by higher parasympathetic activity, but MVP female and male had higher sympathetic outflow. The obtunded postural effects on frequency domain in MVP subjects demonstrated an autonomic dysregulation.

並列關鍵字

atrial fibrillation ； pulmonary vein ； atria ； cardiac electrophysiology ； heart rate variability ； mitral valve prolapse

參考文獻

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