施泰可

名 称:盐酸索他洛尔片(Sotalol Hydrochloride Tablets) 商品名:施泰可~(TM)(Sotacor Tablets)。 特 点:施泰可兼有Ⅱ类(β-肾上腺素受体阻断药)和Ⅲ类(延长心肌动作电位复极时间)抗心律失常药特性。索他洛尔非选择性阻断β-肾上腺素受体,但无内在拟交感活性和膜稳定作用,小剂量时,表现出β-受体作用,可延长窦房周期和房室(AV)结不应期,减慢房室传导(延长AV时间);较大剂量时可延长心房、心室动作电位时间和有效不应期(ERP),在体表心电图上表现为QT间期及心率校正QT(QTc)间期延长,表现出Ⅲ类抗心律失常药特征。索他洛尔与胺磺酮不同.不抑制心肌动作电位O相去极化速率(Vmax),对QRS波和 HV间期无影响。     

新药橱窗

名称:盐酸索他洛尔片(Sotalol Hydrochloride Tablets) 商品名:施泰可~(TM)(Sotacor Tablets)。 特点:施泰可兼有Ⅱ类(β-肾上腺索受体阻断药)和Ⅲ类(延长心肌动作电位复极时间)抗心律失常药特性。索他洛尔非选择性阻断β-肾上腺素受体,但无内在拟交感活性和膜稳定作用,小剂量时,表现出β-受体作用,可延长窦房周期和房室(AV)结不应期,减慢房室传导(延长AV时间);较大剂量时可延长心房、心室动作电位时间和有效不应期(ERP),在体表心电图上表现为QT间期及心率校正QT(QTc)间期延长,表现出Ⅲ类抗心律失常药特征。索     

Effects of dauricine,quinidine,and sotalol on action potential duration of papillary muscles in vitro

目的：观察蝙蝠葛碱对豚鼠乳头状肌的动作电位是否具有使用依赖性特征，并与奎尼丁、索他洛尔作平行比较．方法：利用细胞内微电极技术记录豚鼠乳头状肌跨膜动作电位．结果：蝙蝠葛碱２０μｍｏｌ·Ｌ－１能明显延长乳头状肌跨膜动作电位时程，在刺激周长为２００，３００，４００，６００，８００，１０００，２０００ｍｓ时，其延长动作电位时程的百分率分别为２２±８，１１±６，９±５，７±５，６±３，４３±２８，４５±２８，蝙蝠葛碱延长动作电位时程作用于刺激周期较短时作用明显，呈使用依赖性特征．而奎尼丁１μｍｏｌ·Ｌ－１和索他洛尔１０μｍｏｌ·Ｌ－１延长动作电位时程作用随刺激周期延长而增强，呈现逆向使用依赖性特征．结论：蝙蝠葛碱使用依赖性延长豚鼠乳头状肌动作电位时程．     

抗心律失常新药索他洛尔

盐酸京他洛尔（sotalolbydrochloride）是一个强效非心脏选择性产肾上腺素能受体阻滞剂，无内在拟交感活性和膜稳定作用。与其他产阻滞剂不同的是，它延长心脏组织动作电位时程和不应期，延长体表心电图田问期，是一个有效的抗心律失常和抗颤动药。本品在欧美已被广泛用于口服治疗威胁生命的快速室性心律失常。且在肾上腺素能括抗作用市售的索他洛尔为＊一和人索他洛尔涓旋混合物。小异构体的尸阻滞活性不足人异构体的！／5oo索他洛尔对人和动物的产肾上腺素能阻滞劾酸类似普菲洛尔。8对膜电流的影响索他洛尔以浓度相关方式延长心脏动作电位…     

蝙蝠葛苏林碱对家兔在体心脏单相动作电位的影响(英文)

采用单相动作电位记录技术研究蝙蝠葛苏林碱 (DS)对家兔在体心脏单相动作电位 (MAP)作用的使用依赖性特征 .结果显示DS在 2 4 0 ,2 10 ,180ms起搏周长 (CL)均能降低MAP振幅 (MAPA) ,延长MAP复极达 50 %和 90 %的时程 (MAPD50 ,MAPD90 ) ,有效不应期 (ERP)和ERP/MAPD90 .延长MAPD50 百分率分别为 12 .8± 2 .9,9.5± 2 .6 ,9.0± 1.6 ,延长MAPD90 百分率分别为 10 .9± 2 .6 ,7.5± 2 .4 ,6 .5±2 .7,延长ERP百分率分别为 2 5.7± 4 .3,18.5±4 .1,2 4 .2± 7.2 ,延长ERP/MAPD90 百分率分别为13.7± 4 .5,10 .2± 2 .2 ,16 .1± 5.1(P >0 .0 5) .其延长作用均呈非使用依赖性特征 .在所有起搏周长下 ,索他洛尔亦降低MAPA ,延长MAPD50 ,MAPD90 ,ERP ,ERP/MAPD90 ,但其延长MAPD90 ,ERP的作用均呈逆向使用依赖性特征 (P <0 .0 5) .结果表明 ,DS能明显降低家兔在体心脏MAPA ,延长MAPD50 ,MAPD90 ,ERP ,ERP/MAPD90 ,该作用呈非使用依赖性特征 .     

纯粹Ⅲ类抗心律失常药d-索他洛尔对症状性复杂室性早搏的疗效和安全性

消旋索他洛尔（d，l-sotalol）是能明显延长心脏组织动作电位时程（皿类抗心律失常活性）的强效产阻滞剂，是一种有效的抗心律失常药。它治疗的病例的存活率高于其他药物。它的主要缺点是有明显的q受体阻滞活性，有负性肌力作用，可引起窦性心动过缓、低血压或支气管痉挛。右旋索地洛尔（d－sotalol）无明显的产受体阻滞作用，对动作电位时程和不应期的作用类似消旋索他洛尔，具有明显的抗心律失常和抗颤动作用；。233例有症状的复杂室性早搏，随机口服求索他洛尔50mg每日2次（61例）、100mg每日2次（59例）、20Omg每日2次（58例）或安慰剂…     

新药橱窗

名称:盐酸索他洛尔片(Sotalol Hydrochloride Tablets) 商品名:施泰可~(TM)(Sotacor Tablets)。 特点:施粲可兼有Ⅱ类(β-肾上腺素受体阻断药)和Ⅲ类(延长心肌动作电位复极时间)抗心律失常药特性。索他洛尔非选择性阻断β-肾上腺素受体,但无内在拟交感活性和膜稳定作用,小剂量时,表现出β-受体作用,可延长窦房周期和房室(AV)结不应期,减慢房室传导(延长AV时间);较大剂量时可延长心房、心室动作电     

蝙蝠葛碱对多非利特诱发的早后除极的治疗作用

目的 研究蝙蝠葛碱（Dau）对多非利特(dof) 诱发的早后除极（EADs）的治疗作用和可能机制. 方法 用腹主动脉缩窄法制备家兔心肌肥厚模型; 标准微电极技术记录家兔右心室乳头肌动作电位, 观察1 μmol&#8226;L-1 dof对正常、肥厚、低钾及肥厚＋低钾状态下家兔乳头肌动作电位的影响;诱发出 EADs后, 给予终浓度30 μmol&#8226;L-1 的Dau, 观察Dau对以上不同病理状况下动作电位时程（APD）和EADs的影响. 结果 dof延长家兔乳头肌动作电位, 与正常组比较, 差异有显著性（P<0.05）;低钾和心肌肥厚时家兔乳头肌动作电位较正常家兔明显延长;dof在低钾和心肌肥厚状态下, EADs的发生率分别与正常组、低钾和心肌肥厚组相比均有显著升高;发生EADs后给予Dau, 可明显降低EADs的发生率. 结论 蝙蝠葛碱对EADs具有良好的治疗作用, 机制可能与其对多个离子通道的作用有关.     

静脉注射伊布利特对中国健康受试者及房颤与房扑患者心电图QTc间期的影响

目的 静脉注射伊布利特(抗心律失常药物)对健康人及房颤与房扑患者用药后心电图QTc间期变化的比较研究.方法 40例健康男性随机分为6组(每组分别为4,10,6,6,6,8人),分别静脉注射伊布利特5,10,20μg·kg-1及单次给药0.5,0.75,1.0mg.房颤、房扑患者各100例应用伊布利特(1 mg iv;体质量小于60 kg者,按0.01 mg·kg-1)转复心律治疗,必要时重复给药1次.结果 健康受试者药后QTc间期明显延长,峰值出现于给药完成后.5,10,20μg·kg-1组R QTc均值最大值分别为(469±7),(592±35)及(678±14)ms;0.5,0.75,1.0 mg组的最大值分别为(605±39),(616±8)及(683±9)ms.100例房颤、房扑患者的药后QTc间期延长,峰值出现于静脉注射结束即刻;1次给药者QTc峰值为(476±9)ms;2次给药者QTc峰值为(510±8)ms,于4 h恢复基线水平.相同给药方式,健康受试者较患者的QTc间期延长更为显著(P<0.05).有43%接受2次给药的患者,QTc可延长至500～600 ms;9%可延长至600 ms以上.发生1例尖端扭转型室性心动过速(1%)、2例室性心动过速(2%).结论 静脉注射伊布利特后,中国健康受试者和房颤、房扑患者QTc间期均明显延长,最大可达600 ms以上;但健康人QTc延长较房颤、房扑患者更显著.要严密监测QTc间期至少应到药后4 h.     

索他洛尔对兔急性心肌梗死后再灌注性心律失常的影响

目的 :观察索他洛尔对兔急性心肌梗死再灌注心律失常的防治作用。方法 :30只兔随机分为对照组 (n =15 )和治疗组 (n =15 ) ,结扎冠状动脉左前降支 30min后松解 ,观察对照组和治疗组 (静注索他洛尔 )再灌注后ECG参数和心电生理刺激后快速性室性心律失常的变化。结果 :冠状动脉结扎前 2组HR、QT间期、QTd无显著性差异 (P >0 0 5 ) ;再灌注后治疗组较对照组HR明显减慢 [(182± 37 9)beats·min-1vs (2 2 9± 5 2 4 )beats·min-1],QT间期显著延长 [(172± 2 6 4 )msvs (15 2± 2 1 1)ms],QTd明显缩短 [(2 6 2± 2 6 )msvs (43.5± 3 9)ms];治疗组再灌注后快速性室性心律失常发生率明显减少 (13 3%vs33.3%,P <0 0 5 ) ;2组电生理刺激诱发快速性室性心律失常发生率也明显减少 (2 0 %vs 6 0 %,P <0 0 5 )。结论 :小剂量静注索他洛尔预防实验性再灌注性快速性室性心律失常是有效的。     

蝙蝠葛碱,硅尼丁和索他洛尔对离体乳头状肌动作电位时程的作用

目的：观察蝙蝠葛碱对豚鼠乳头状肌的动作电位是否具有使用依赖性特征，并与奎尼丁，索他洛尔作平行比较。方法；利用细胞内微电极技术记录豚鼠乳头状肌跨膜动作电位。结果：蝙蝠葛碱２０μｍｏｌ．Ｌ＾－１能明显延长乳头状肌跨膜动作电位时程，在刺激周长为２００，３００，４００，６００，８００，１０００，２０００ｍｓ时，其延长动作电位时程的百分率分别为２２±８，１１±６，９±５，７±５，６±３，４．３±２．８，４．     

Sotalol exhibits reverse use-dependent action on monophasic action potentials in normal but not in infarcted canine ventricular myocardium.

In 12 anesthetized mongrel dogs (30 mg/kg pentobarbital), a thoracotomy was performed, and the left anterior descending coronary artery was ligated proximally. Eight to 12 days later, monophasic action potentials were recorded endocardially from the apex of the noninfarcted right ventricle and infarcted areas of the left ventricle, and the effects of 1.5 mg/kg intravenous sotalol were evaluated. Monophasic action potentials from the infarcted zone of the left ventricle were obtained from areas where fractionated bipolar electrograms could be recorded; this was histologically confirmed. After sotalol, in sinus rhythm, the monophasic action potential duration at 90% repolarization of the infarcted zone increased from 186 +/- 31 to 226 +/- 45 ms (+ 22%, p less than 0.05), and monophasic action potential duration of the noninfarcted zone increased from 184 +/- 31 to 225 +/- 47 ms (+ 22%, p less than 0.05). Programmed ventricular stimulation was performed with single extrastimuli at a basic drive cycle length of 300 ms. With long coupling intervals (290 ms), monophasic action potential duration of the infarcted zone increased from 165 +/- 23 to 183 +/- 25 ms (+ 11%, p less than 0.05) after sotalol; and monophasic action potential duration of the noninfarcted zone increased from 159 +/- 20 to 180 +/- 25 ms (+ 13%, p less than 0.05). With short coupling intervals (200 ms), the monophasic action potential duration of the noninfarcted zone increased from 157 +/- 19 to 173 +/- 18 ms (+ 10%, p less than 0.05), and monophasic action potential duration of the noninfarcted zone increased from 150 +/- 18 to 157 +/- 18 ms (+ 5%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

蝙蝠葛碱抑制氯化铯诱发家兔在体心脏早后除极及心律失常

研究蝙蝠葛碱对氯化铯诱发有兔在体心脏早后除极及触发性心律失常的作用。方法;采用单向动作电位记录及触发性心律失常的作用。方法：采用单向动作电位技术记录家兔在体心脏单向动作电位,用氯化铯诱发家兔心脏早后除极及触发性心律失常。结果：静脉注射氯化铯１－２ｍｍｏｌ．ｋｇ＾－１后ＭＡＰＡ降低,ＭＡＰＤ９０,ＱＲＳ和Ｒ－Ｒ间期明显延长。     

Comparison of the in vitro electrophysiologic and proarrhythmic effects of amiodarone and sotalol in a rabbit model of acute atrioventricular block

The mechanisms for the different proarrhythmic potential of antiarrhythmic drugs in the presence of comparable QT prolongation are not completely understood. The reasons for the lower proarrhythmic potential of amiodarone as compared with other class-III antiarrhythmic drugs such as sotalol, a fact that has been well established for years, is insufficiently known. Therefore, the aim of our study was to assess the different electrophysiologic effects of amiodarone and sotalol in a previously developed experimental model of proarrhythmia. In eight male rabbits, amiodarone (280-340 mg/d) was fed over a period of six weeks. Hearts were excised and retrogradely perfused. Up to eight simultaneous epi- and endocardial monophasic action potentials (MAP) were recorded. Results were compared with sotalol-treated (10-50-100 microM) hearts (n = 13). Amiodarone and sotalol (50 microM and 100 microM) led to a significant increase in QT interval (mean increase: amiodarone: 31 +/- 6 ms; sotalol: 41 +/- 4 ms and 61 +/- 9 ms) and MAP-duration (mean increase-MAP90: amiodarone: 20 +/- 5 ms; sotalol: 17 +/- 5 ms and 25 +/- 8 ms) (P < 0.01). In bradycardic (AV-blocked) hearts, MAP-recordings demonstrated reverse-use dependence and a significant increase in dispersion of repolarization (MAP90) in the presence of sotalol (P < 0.01), but not in amiodarone-treated hearts (10%; p = ns). Sotalol led to early afterdepolarizations (EAD) and torsade de pointes (TdP) after lowering of potassium concentration (6 of 13 hearts). In amiodarone-treated, hypokalemic hearts, no EAD or TdP occurred. Sotalol changed the MAP configuration to a triangular pattern (ratio-MAP90/50: 1.52 as compared with 1.36 at baseline) whereas amiodarone caused a rectangular pattern of MAP prolongation (ratio-MAP90/50: 1.36). In conclusion, these results show no direct correlation between the occurrence of TdP and the degree of QT prolongation. Several factors including reverse-use dependence, dispersion of repolarization, and the propensity to induce early afterdepolarizations but also differences in the action potential configuration may help to understand proarrhythmic side effects of drugs.     

Effect of sotalol and acute ventricular dilatation on action potential duration and dispersion of repolarization after defibrillation shocks

Ventricular dilatation shortens action potential duration and increases the defibrillation threshold, whereas sotalol prolongs action potential duration and may decrease the defibrillation threshold. Whether these action potential changes remain after defibrillation shocks, and how they relate to defibrillation success, is not known. In this study, eight monophasic action potentials were recorded simultaneously during electrical defibrillation (shock strength: 20%-200% of the defibrillation threshold) in 16 normal and acutely dilated isolated rabbit hearts at baseline and after addition of sotalol (2 x 10-5 M). Post-shock action potential duration (PS-APD) and dispersion of PS-APD [Disp(PS-APD)] of monophasic action potentials were analyzed after 322 defibrillation shocks at different repolarization levels and related to defibrillation success. Acute ventricular dilatation shortened PS-APD, whereas sotalol prolonged PS-APD. Successful defibrillation was associated with lower Disp(PS-APD) at all repolarization levels in the normal and dilated heart at baseline and with sotalol (mean difference: 33%-46%, all P < 0.005). Minimal PS-APD was longer (mean difference: 5%-11%), while maximal PS-APD was shorter (mean difference: 2%-16%) after successful defibrillation shocks than after failing defibrillation shocks. Therefore, sotalol prolongs action potential duration after defibrillation shocks. Synchronization of repolarization, caused by both prolongation of short PS-APD and shortening of long PS-APD, is associated with successful defibrillation in the normal, acutely dilated, and sotalol-treated heart.     

Effects of propranolol on ventricular repolarization in man

Summary The acute effects on monophasic action potentials (MAP), QT interval, and right ventricle effective refractory period (V-ERP) of propranolol 0.2 mg · kg^–1 body weight have been studied in 10 patients with coronary artery disease.The median duration of MAP at 90% repolarization (MAP₉₀) was shortened from 238 to 228 ms at a constant paced heart rate of 100 beats · min^–1, while V-ERP remained unchanged.The median ratio V-ERP/MAP₉₀ increased from 1.00 to 1.03.The electrical restitution curves of the duration of premature action potentials, normalized to those paced at constant heart rate, were more horizontal after propranolol.Isometric handgrip shortened MAP₉₀ from 217 to 211 ms and after propranolol similar shortening was found (215 to 209 ms), although both values were slightly lower than before beta-blockade.     

蝙蝠葛碱对猫冠脉结扎和复灌性心律失常的影响及电生理作用

本文报道蝙蝠葛碱(Dau)对猫缺血和非缺血心脏MAP和FRP的影响及其抗心律失常作用。剂量依赖性延长猫左心室MAPD_(50)和MAPD_(90)及FRP,累积剂量9mg/kg时,分别由给药前的170±19ms,216±16ms和177±15ms延长至197±20ms,249±18ms和238±20ms。Dau5mg/kg iv,然后以0.1mg/kg·min~(-1)恒速灌注30min,可防止缺血边缘区MAPD_(50)缩短,使缺血边缘区,中心区和非缺血区FRP延长,并降低3个区域间FRP离散程度和LAD结扎和复灌引起的VF发生率和死亡率。     

蝙蝠葛碱对麻醉兔体内希氏束电图的影响及与几种药物的相互作用

蝙蝠葛碱(Dau)剂量依赖性延长麻醉家兔希氏束电图(HBE)的A-H,H-V间期,使V波增宽,并延长心房和房室结不应期。利多卡因(Lid)、对HBE各间期无明显影响,但有减弱Dau延长H-V间期的作用。异丙肾上腺素(Iso)可对抗Dau延长A-H,H-V间期及增宽V波的作用。阿托品(Atr)可缩短Dau已延长的A-H间期。提示Atr和Lid可分别改善Dau抑制的房室及希—浦系统的传导,而Iso对房室传导和室内传导均有改善作用。