臺灣博碩士論文加值系統

心房纖維顫動：心房電氣生理特性及經導管高頻幅射灼燒術治療
研究背景
心房纖維顫動(atrial fibrillation)會縮短心房有效不反應期(effective refractory period)，使心房纖維顫動更容易發生。此種心房有效不反應期的縮短是由於心房纖維顫動或是由於心房快速刺激所造成，目前尚不清楚。而且心房有效不反應期的縮短是否有區域性差異過去沒有相關報告。另一方面，鈣離子通道、鉀離子通道甚至抗心律不整的藥物對這現象的影響過去未被廣泛地研究。
對於藥物反應不佳的心房纖維顫動的病人，完全心房心室結合處灼燒再加上永久性人工心律調節器，或心房心室結合處修整二種方法都可以有效地控制病人心室的速度，然而這二種方法的長期效果仍未有研究進行比較。
研究目的
評估經快速心房刺激後心房電氣生理的改變並找出造成此現象的可能機轉。探究此種心房有效不反應期的縮短與心房刺激的速度的相關性，並評估抗心律不整藥物對此現象的影響。另一方面，針對藥物反應不佳的心房纖維顫動的病人，進行完全心房心室結合處灼燒或心房心室結合處修整，比較二種治療方式對於病人的生活品質和心臟功能的長期影響。
方法
在開胸的狗，三十分鐘快速心房刺激(800 bpm)之前與之後，測量右心耳90%再極化時動作電位週期(action potential duration at 90% repolarization)及七處心房部位的心房有效不反應期。快速心房刺激引起心房有效不反應期改變的強度及恢復時間如上述設計模式在8隻狗身上進行研究。為了尋找引起心房有效下反應期縮短的可能機制，32隻狗在快速心房刺激前以隨機方式接受verapamil，ryanodine，nicorandil或d-sotalol，之後再如上述設計進行研究。
5隻狗接受完全心房心室結合處灼燒及心室人工心律調節器(80 bpm)。15隻狗接受完全心房心室結合處灼燒、心房人工心律調節器(780 bpm)及心室人工心律調節器。在手術之前及手術8星期之後測量心房有效不反應期並評估心房纖維顫動發作情形。
利用五個刺激週長(450，400，350，300以及250毫秒)的十分鐘快速心房刺激前後，以500毫秒的基礎週長測量10個病患的右心房有效不反應期。另外入選60個病人來研究抗心律不整藥物對心房纖維顫動引起的心房有效不反應期改變的影響。在一次因刺激引起的心房纖維顫動前後，以一個500毫秒基本週長來測量心房有效不反應期，經由隨機方式服用6種抗心律不整藥物(procainamide, propafenone, propranolol, dl-sotalol, amiodarone與verapamil)的其中之一後，在另一次因刺激引起的心房纖維顫動前後，測量心房有效不反應期。
六十位患有藥物反應不佳的心房纖維顫動病人，被隨機分配進行完全心房心室結合處灼燒及植入永久性人工心律整律器或心房心室結合處修整，其手術前、手術後第一個月和第六個月的生活品質之主觀認定以調查表評估。另外在手術後24小時內(基準)、第一個月及第六個月，以心臟超音波和核醫放射檢查法評量心臟的收縮功能。
結果
心房有效不反應期及90%再極化單一動作電位週期二者在三十分鐘快速心房刺激後會明顯地縮短。Nicorandil及d-sotalol不影響刺激後心房有效不反應期及90%再極化單一動作電位週期縮短的程度及其恢復期，然而verapamil及ryanodine會使刺激後二者縮短的程度明顯地減弱很多。
植入心室人工心律調節器8星期之後的心房電氣生理特性和手術前並無差別，然而8星期心房快速刺激後心房電氣生理特性包括心房有效不反應期的縮短，有效不反應期非生理調節的增加，續發性心房纖維顫動引發率和持續時間的增加。這些變化會逐漸恢復至和手術前並無差異，然而心房有效不反應期的縮短及非生理調節和心房纖維顫動的引發率的恢復在左心房比右心房和Bachmann’s氏束來得緩慢。
經過十分鐘的快速心房刺激後，病人心房有效不反應期明顯縮短，而縮短的程度與刺激週長有關。在刺激之前注射verapamil，會減緩有效不反應期的縮短(-4.61.2%對-15.13.4%, P<0.001)，但是注射其他抗心律不整藥物後並無改變。
對於藥物反應不佳的心房纖維顫動病人，完全心房心室結合處灼燒及植入永久性人工心律調節器和心房心室結合處修整都可以改善病人的日常生活品質、嚴重症狀出現的頻率及發作症狀。兩組病人在治療後，住院、送急診室和使用抗心律不整藥物的頻率都降低，然而接受完全心房心室結合處灼燒的病人，其日常生活品質、嚴重症狀出現頻率及發作症狀等方面（包括心悸、暈眩、胸悶、視覺模糊和昏厥）有較大的改善。
結論
我們證實30分鐘快速心房刺激會引起心房有效不反應期縮短。ATP依存的鉀離子電流及遲發性內向整流鉀離子電流的快速部分並不會明顯影響這現象，L型鈣離子通道及肌漿網狀組織的鈣離子通道的阻斷會明顯影響此現象。八星期心博過速所引發心房電氣生理變化的恢復在左心房比較慢，左心房可能在心房纖維顫動的復發扮演重要的角色。心搏過快引起的心房有效不反應期縮短和刺激速度有關，verapamil不同於其他類的抗心律不整藥物，可明顯減緩心房有效不反應期的縮短。
完全心房心室結合處灼燒及植入永久性人工心律調節器，比心房心室結合處修整之治療方式，更能降低發作頻率並緩解心房纖維顫動症狀，接受前者治療方式的病人比較滿足治療後的健康狀況。

Atrial Fibrillation: Atrial Electrophysiological Properties and Radiofrequency Catheter Ablation Therapy
Background
Atrial fibrillation(AF) has been shown to shorten atrial effective refractory period(ERP) and make atrium more vulnerable to AF. Whether the atrial ERP shortening is a specific response to AF or a common response to rapid atrial rate is not clear. Whether there are regional differences in the change of atrial ERP after rapid atrial pacing is unknown. Furthermore, the effects of calcium channel, potassium channel and different classes of antiarrhythmic drugs on this phenomenon have not been extensively investigated.
Previous reports have demonstrated that complete catheter ablation of the atrioventricular junction (AVJ) with permanent pacing and AVJ modification could effectively control the ventricula rate during AF in the patients with medically refractory AF. However, there were no previous studies to compare the long-term effects of complete AVJ ablation with those of AVJ modification in the patients with medically refractory AF.
Purpose
To assess the change and recovery course of atrial electrophysiological properties after rapid atrial pacing, and the possible mechanisms underlying this phenomenon, to define the rate-dependency of atrial ERP change, to evaluate the effects of different antiarrhythmic drugs on tachycardia-induced change of atrial ERP, and to prospectively compare the long-term effects on quality of life (QOL) and cardiac performance after complete AVJ ablation and permanent pacing with those after AVJ modification in patients who had medically refractory AF.
Methods
In opened-chest dogs, the endocardial monophasic action potential duration at 90% repolarization (APD90) from the right atrial appendage and ERP from seven atrial sites were measured before and after rapid atrial pacing at 800 bpm for 30 minutes. The magnitude and time course of pacing-induced change of atrial ERP were assessed in 8 dogs subjected to the rapid pacing protocol described above. Thirty-two dogs were randomly assigned to receive one of the four drugs before rapid atrial pacing: verapamil, ryanodine, nicorandil, or d-sotalol.
Atrial ERP and inducibility of AF were assessed in 5 dogs before and every 4 hours for 48 hours after complete AVJ ablation with 8-week VVI pacing (80 bpm). Atrial ERP and inducibility of AF were assessed in 15 dogs before and after complete AVJ ablation with 8-week rapid atrial pacing (780 bpm) and VVI pacing.
The right atrial ERP was measured with a drive cycle length of 500ms before and after 10 minutes of rapid atrial pacing using five pacing cycle lengths(450, 400, 350, 300 and 250 ms) in 10 patients. Sixty patients were included to study the effects of antiarrhythmic drugs on change of atrial ERP induced by AF. The atrial ERP was measured with a drive cycle of 500ms before and after an episode of pacing-induced AF. After randomized to receive one of the 6 antiarrhythmic drugs (procainamide, propafenone, propranolol, dl-sotalol, amiodarone and verapamil), the atrial ERP was measured before and after another episode of pacing-induced AF.
Sixty patients with medically refractory AF were randomly assigned to receive or complete AVJ ablation with permanent pacing or AVJ modification. Subjective perception of QOL was assessed by a semiquantative questionnaire before, 1 and 6 months after ablation. Cardiac performance was evaluated by echocardiography and radionuclide angiography within 24 hours (baseline), at first month and at sixth month after ablation.
Results
Both the atrial ERP and APD90 significantly shortened after 30-minute rapid atrial pacing. Pretreatment with nicorandil and d-sotalol had no effects on the magnitude or recovery course of atrial ERP shortening after pacing. However, the degree of ERP and APD90 shortening after pacing was significantly attenuated in the verapamil and ryanodine groups.
Atrial electrophysiological properties obtained immediately and during 48-hour measurements after pacing did not show any change after 8-week VVI pacing. Recovery of atrial electrophysiological properties after 8-week rapid atrial pacing included a progressive recovery of atrial ERP shortening, recovery of atrial ERP maladaptation, and decrease of duration and episode of reinduced AF. However, recovery of shortening and maladaptation of atrial ERP, and inducibility of AF was slower at left atrium (LA) than those at right atrium and Bachmann’s bundle.
In humans, atrial ERP shortened significantly after 10 minutes of rapid atrial pacing and the degree of shortening was correlated with the pacing cycle length. The atrial ERP shortening was attenuated after verapamil infusion(-4.61.2% vs. -15.13.4%, P<0.001) but not changed after infusion of other antiarrhythmic drugs.
Complete AVJ ablation with permanent pacing and AVJ modification were associated with significant improvements in the general QOL, frequency of significant symptoms and symptoms during attacks. The frequency of hospital admission and emergency room visits, and antiarrhythmic drug trials significantly decreased after ablation in both groups. However, patients after complete AVJ ablation had a significantly greater improvement in the general QOL, frequency of significant symptoms and symptoms during attacks (including palpitation, dizziness, chest oppression, blurred vision and syncope).
Conclusions
Shortening of atrial ERP could be induced by 30-minute rapid atrial pacing. Both the ATP-dependent potassium current and rapid component of the delayed rectifier did not significantly influence this phenomenon. Intracellular calcium from both the L-type calcium channel and sacroplasmic reticulum contributed significantly to this phenomenon. LA had a slower recovery of tachycardia-induced changes of atrial electrophysiological properties and this might play a critical role in the initiation of AF. The atrial ERP shortening induced by tachycardia was a rate-dependent response. Verapamil, but not other classes of antiarrhythmic drugs, could markedly attenuate this effect.
Atrioventricular junction ablation with permanent pacing, as compared with AVJ modification, had a significantly greater effect to decrease the attack frequency and symptom extent of AF, and the patients who received this procedure were more satisfied with their general well-being.

封面
中文摘要　
英文摘要　
第一章　前言
第二章　短期快速心房刺激造成心房不反應期的改變：區域性差異及可能的機轉　　
一. 前言
二. 方法　　　　　　
三. 結果　　　　　　
四. 討論　　　　　　
五. 表格　　　　　　
六. 圖形　　　　　　
第三章　心搏過速引起心房電生理變化的復原過程的局部差異　　　
一. 前言　　　　　　
二. 方法　　　　　　
三. 結果　　　　　　
四. 討論　　　　　　
五. 表格　　　　　　
六. 圖形　　　　　　
第四章　人體心房有效不反應期因心搏過速引起的變化：速度依賴性及抗心律不整藥物的影響
一. 前言　　　　　　
二. 方法　　　　　　
三. 結果　　　　　　
四. 討論　　　　　　
五. 表格　　　　　　
六. 圖形　　　　　　
第五章　比較患有藥物反應不佳的心房纖維顫動病人，完全心房心室結合處灼燒阻斷和心房心室結合處灼燒修整後，兩者的生活品質和心臟功能
一. 前言　　　　　　　
二. 方法　　　　　　　
三. 結果　　　　　　　
四. 討論　　　　　　
五. 表格　　　　　　
第六章　未來研究方向
參考文獻　　　　　　
論文相關著作　　　　

1. Lee SH, Chen SA, Yu WC, Cheng JJ, Kaun P, Hung, Chang MS, Lin FY. Change of Atrial Refractory Period After Short Duration of Rapid Atrial Pacing: Regional Differences and Possible Mechanisms. PACE (in press)
2. Lee SH, Lin FY, Yu WC, Cheng JJ, Kuan P, Hung CR, Chang MS, Chen SA. Regional Differences in the Recovery Course of Tachycardia-Induced Changes of Atrial Electrophysiological Properties. Circulation (in press)
3. Yu WC, Chen SA, Lee SH, Tai CT, Feng AN, Kuo BIT, Ding YA, Chang MS. Tachycardia-Induced Change of Atrial Refractory Period in Humans: Rate-Dependency and Effects of Antiarrhythmic Drugs. Circulation 1998;97:2331-2337
4. Lee SH, Chen SA, Tai CT, Chiang CE, Wen ZC, Cheng JJ, Ding YA, Chang MS. Comparisons of Quality of Life and Cardiac Performance After Complete Atrioventricular Junction Ablation and Atrioventricular Junction Modification in Patients With Medically Refractory Atrial Fibrillation. J Am Coll Cardiol 1998;31:637-644