https://scholars.lib.ntu.edu.tw/handle/123456789/194581
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(3/3) | 作者: | 吳美環 | 公開日期: | 2001 | 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,有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(2)抗心律不整之效 力檢定:以Langendorff定壓灌流之模 式,經綁住再放鬆左冠狀動脈支以誘發 ischemia-reperfusion不整脈,比較 liriodeninetreatment與control之差異。 5. 本年度計劃結果顯示:較低濃度(0.3與1 μM)之liriodenine對於心臟傳導系統並 無顯著之影響,然而較高濃度之 liriodenine則可延緩心臟之傳導,包括經 過心房、心室結與希氏束之傳導。此 外,心臟組織包括房室結、希氏束及心 室組織的refractory period都會延長,這 些變化在心室組織最為明顯。然而在10 μM liriodenine的實驗有10次可誘發心室 頻脈。 Background. We have identified the compound, liriodenine, to possess an antiarrhythmia potential and a positive inotropic effect. 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 rats and rabbits. Results. The changes of the electrophysiological parameters after liriodenine were determined in 10 rats. At low concentrations, 0.3 to 1 mM, the cardiac conduction and the refractoriness of the cardiac conduction system were not significantly altered by liriodenine. At higher concentrations, 3 and 10 mM, liriodenine could significantly prolong the conduction over the heart, including the intratrial conduction (SA interval), atrioventricular conduction (AH interval), conduction over the His-Purkinje system (HV interval). The refractory period of the atrioventricular nodal, His-Purkinje system and ventricular tissue were also significantly prolonged. But, the sinus cycle length and the atrial refractory period were not changed. However, ventricular tachyarrhythmias could be induced by ventricular extrastimulation at 3 mM (one rat) and 10 mM (4 rats) liriodenine infusion. In the ischemia-reperfusion model, liriodenine could convert the reperfusion ventrciualr arrhythmia with an EC50 of 0.3 mM. Conclusions. After the delineation of the inhibitory effects of liriodenine on the ionic currents (INa, ICa, Ito, and IK1) in isolated rat ventricular myocytes, the electrophysiological study in Langendorff-perfused isolated rat hearts defined its electrophysiological modulation by drugs. Liriodenine at low concentrations could effectively convert the reperfuion arrhythmias, but at high concentration that 30 folds higher than the EC50 for conversion of the reperfusion arrhythmias might induce ventricular arrhythmia via extremely prolonged centrciualr refractoriness and QT intervals. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/29835 | 其他識別: | 892320B002253M48 | Rights: | 國立臺灣大學醫學院小兒科 |
顯示於: | 醫學系 |
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