https://scholars.lib.ntu.edu.tw/handle/123456789/194580
標題: | 心臟衰竭之研究與藥物探索─心電生理特性,抗心律不整效力及不整脈誘發性之測定,包括CARVEDILOL及THALIDOPARHINE等新衍發物(2/3) | 作者: | 吳美環 | 公開日期: | 2000 | 出版社: | 臺北市:國立臺灣大學醫學院小兒科 | 摘要: | 1. 本實驗室工作群長期致力於由天然植 物萃取有效之化合物。經評估後,目 前有兩大類化合物, 一為 thalidiporphine , 一為 liriodenine,兩者皆具有適宜之心肌 收縮促進效果及抗心律不整效力。 2. 因此本群體計劃之目的在(1)將此兩大 類化合物予以改變部份結構,使具有 部份α與β拮抗作用(2)且能維持充份 之心臟收縮促進效果及抗心律不整效 力。 3. 本子計劃之主要工作在執行(1)第一 年:先界定carvedilol是否有直接抗 心律不整效力,或對心臟電生理特性 有直接影響,若有,其機轉為何?(2) 其次, 第二年: 將予界定 thalidoporplinie各類衍生物之抗心 律不整之效力及對心臟傳導系統之影 響(3)第三年:將予界定liriodenine 各類衍生物之抗心律不整之效力及對 心臟傳導系統之影響。 4. 方法:(1)心臟電生理特性之評估:以 Langendorff灌流之離體心臟作評估, 以自製特別之電極導線放入心房、心 室及希氏束處,記錄並刺激,以得到 各項組織之電生理特性資料。 實驗:(2) 動物:一般正常hamster及心 衰竭品種hamster。 5. 第二年計劃結果顯示:結果顯示心衰 竭hamster的心臟傳導系統有顯著房室 結之傳導延長現象,其AH間距由44±3 延長到56±4ms,而wenckrbach週期由 149±9延長到195±13ms。而若在實驗 前每天投予thalidoporphine 4.5mg/day 則可有效縮短這些延長現象。此外, thalidoporphine pretreatment能有效延長 心房的refroctory period。然而不論是 正常或心衰竭hamster的離體灌流心 臟,thalidoporphine皆能有效依劑量成 正比的延常房室結的傳導與 refractoriness。6. 推論:thalidoporphine能改善心衰竭心 臟電氣傳導性質,然而這些影響與 thalidoporphine的直接心臟效果並不盡 然相同,自主神經系之調節或抗氧化 的作用是必須考慮的機轉。 Background. We have identified the compound, thalidoporphine, to possess an antiarrhythmia potential and a low negative inotropy. Methods. The direct modification by various interventions on cardiac conduction system was performed by intracardiac recording and stimulation in isolated, Langendorff perfused hearts. The changes were measured in the hearts isolated from normal and cardiomyopathic hamster. Results. As compared to the normal hamster, the failing heart isolated from the cardiomyopathic hamster showed significantly prolongation of the conduction through the AV node as well as the refractoriness of the AV node (AH interval was 44±3 in normal and 56±4 ms in the failing hearts. The Wenckebach cycle length was 149±9 ms in normal and 195±13 ms in the failing hearts). Pretreatment by thalidophorphine (4.5 mg/day) improved the conduction. The AH interval was shortened to 48±2 ms and the Wenckebach cycle length was shortened to 176±6 ms. There was no significant differences in the conduction and refractory period of the atrial and ventricular tissue between the normal and heart failure hamster. However, pretreatment by thlidophorine would increase the atrial refractory period. (the atrial effective refractory period was 45±3 in normal, 41±4 in failing hearts and 54±7 ms in the thlaidophorine group). No arrhythmia could be induced by programmed pacing in any of the 3 groups. However, thlidoporphine still could prolong the conduction through the AV node, the refractory period of the atrial and ventricular tissue dose-dependently in both normal and failing hearts of cardiomyopathic hamsters. Conclusions. Failing heart of the cardiomyopathic hamster was characterized by a prolongation of conduction and refractory period of the AV node, which could be improved by pretreatment by thlidoporphine. Nonetheless, thalidoporphine could prolong the AV conduction and refractory period of the atrial and ventricular period of the cardiomyopathic hamster and normal hamster. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/29834 | 其他識別: | 892320B002019M48 | Rights: | 國立臺灣大學醫學院小兒科 |
顯示於: | 醫學系 |
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