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．     

蝙蝠葛碱对豚鼠心室肌细胞L型钙电流阻断作用

目的：研究蝙蝠葛碱对豚鼠心室肌细胞Ｌ型钙电流的阻断作用及其特性。方法：利用全细胞记录方法，记录单个豚鼠心室肌细胞Ｌ型钙电流。结果：蝙蝠葛碱１，１０，１００μｍｏｌ·Ｌ＾－１可使钙电流分别减少１５．２％±２．２％，４１％±５％，８２％±８％。冲洗后，可使钙电流部分恢复，蝙蝠葛碱具有浓度依赖性阻断钙电流的作用。在刺激频率３Ｈｚ与１Ｈｚ，其阻断钙电流的程序相似。结论：蝙蝠葛碱具有阻断Ｌ型钙电流的作用。     

Electrophysiologic effect of enalapril on guinea pig papillary muscles in vitro

目的：研究依那普利（Ｅｎａ）对豚鼠乳头状肌电生理特性，哇巴因诱发的延迟后除极（ＤＡＤ）和触发电活动（ＴＡ）的直接作用．方法与结果：采用标准玻璃微电极技术记录豚鼠乳头状肌动作电位．Ｅｎａ呈浓度依赖性增加静息膜电位（ＲＰ）和动作电位幅度（ＡＰＡ），而对０期最大除极，超射，和动作电位时程无明显影响．Ｅｎａ１０μｍｏｌ·Ｌ－１则可明显抑制哇巴因０５μｍｏｌ·Ｌ－１诱发的ＤＡＤ和ＴＡ，ＤＡＤ幅度分别由５３±２３，５９±２８，７４±２１和８９±１３降至２６±０７，３１±１０，３７±１５和５３±１１（ｍＶ）（Ｐ均＜００１），刺激周长为２００ｍｓ时ＴＡ数目由３６±０７降至０８±０２（Ｐ＜００５）．结论：Ｅｎａ通过增加心肌细胞ＲＰ和ＡＰＡ抑制哇巴因诱发豚鼠乳头状肌ＤＡＤ和ＴＡ．     

Effects of dauricine on early afterdepolarizations and triggered activity induced by quinidine in guinea pig papillary muscle

用标准微电极技术观察了中药蝙蝠葛的有效成分蝙蝠葛碱对奎尼丁诱发的豚鼠乳头肌早后去极化及触发活动的影响．结果表明，奎尼丁２μｍｏｌ·Ｌ－１能诱发豚鼠乳头肌早后去极化及触发活动，早后去极化的发生率为８／２０，幅值为１３．４±２．６ｍＶ，起始电位为－４２±５ｍＶ，触发活动的发生率为２／２０．蝙蝠葛碱２０μｍｏｌ·Ｌ－１能明显抑制奎尼丁诱发的早后去极化及触发活动，早后去极化的发生率为４／２０，幅值为７．３±１．１ｍＶ，无触发活动．结果提示蝙蝠葛碱具有抗早后去极化所致心律失常．     

Dauricine in hibited L-type calcium current in single cardiomyocyte of guinea pig

目的：研究蝙蝠葛碱对豚鼠心室肌细胞Ｌ型钙电流的阻断作用及其特性．方法：利用全细胞记录方法，记录单个豚鼠心室肌细胞Ｌ型钙电流．结果：蝙蝠葛碱１，１０，１００μｍｏｌ·Ｌ－１可使钙电流分别减少１５２％±２２％，４１％±５％，８２％±８％．冲洗后，可使钙电流部分恢复，蝙蝠葛碱具有浓度依赖性阻断钙电流的作用．在刺激频率３Ｈｚ与１Ｈｚ，其阻断钙电流的程度相似．结论：蝙蝠葛碱具有阻断Ｌ型钙电流的作用     

青滕碱对豚鼠心肌动作电位和收缩力的影响

青藤碱2.7μmol/L以上,呈浓度依赖性地降低豚鼠乳头肌收缩力,延长动作电位时程和有效不应期。小剂量时,青藤碱能降低动作电位0相上升最大速率;较大剂量时,动作电位幅度也降低。用TTX处理豚鼠乳头肌所致的慢反应电位,青藤碱能够抑制。此外,青藤碱能对抗乙酰胆碱缩短豚鼠左房肌动作电位时程的作用。结果提示:青藤碱对Na⁺,Ca²⁺和K⁺的跨膜转运均有抑制作用。     

低浓度非洛地平对豚鼠右心室乳头肌动作电位的影响

用细胞内微电板方法研究低浓度非洛地平对豚鼠右心室乳头肌动作电位的作用。非洛地平０．１，１ｎｍｏｌ·Ｌ－１对动作电位无作用。但在５ｎｍｏｌ·Ｌ－１时，非洛地平可明显延长动作电位时程。延长作用的起效时间为５ｍｉｎ，作用持续６０ｍｉｎ以上。用台氏液冲洗可使非洛地平的延长作用消失。非洛地平５ｎｍｏｌ·Ｌ－１和３μｍｏｌ·Ｌ－１对动作电位时程具有低浓度延长，高浓度缩短的双相作用。硝苯地平１ｎｍｏｌ·Ｌ－１可明显延长动作电位时程，但维拉帕米０．１．１和５ｎｍｏｌ·Ｌ－１对动作电位无明显作用。这表明低浓度激动心肌钙通遁可能是二氢吮嚏矣钙拮抗剂的共性，但不是所有钙拮抗剂的共性。     

对《新药与临床》刊登的“聚肌胞治疗婴幼儿秋季腹泻”一文的临床验证

目的：验证聚肌胞治疗婴幼儿秋季腹泻的疗效。方法：聚肌胞组３２例（男性１９例，女性１３例），在对照组的常规治疗基础上加用聚肌胞，年龄＜１ａ，１ｍｇ，ｉｍ，ｑｏｄ，年龄１ａ以上，２ｍｇ，ｉｍ，ｑｏｄ，共２～３次；对照组３０例，给口服补液盐，调整水、电解质平衡。２组年龄１２±ｓ５ｍｏ；病程２０±０．８ｄ；大便次数９．６±２．７次／ｄ。结果：治疗组和对照组退热时间和止泻时间分别为１．１±０．６ｄ，２．５±１．０ｄ和１．７±０．８ｄ，４．０±１．１ｄ，组间比较Ｐ＜０．０１。结论：聚肌胞治疗秋季腹泻有效。     

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(英文)

研究蝙蝠葛碱对氯化铯诱发家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１－２ ｍｍｏｌ·ｋｇ－１后 ＭＡＰＡ降低，ＭＡＰＤ９０， ＱＲＳ和Ｒ－Ｒ间期明显延长．给氯化铯后３０ｓ左右出现早后除极，并由此触发室性早搏和室性心动过速，蝙蝠葛碱降低早后除极幅度和心律失常发生率，早后除极幅度对照组为５２％±５％，蝙蝠葛碱组为２６％±９％（Ｐ＜０．０５），心律失常发生率对照组为８０％，蝙蝠葛碱组为２８％（Ｐ＜０．０５）、结论：蝙蝠葛碱具有抗氯化铯所致早后除极及触发性心律失常作用。     

生长抑素和胃粘膜血流量与应激性溃疡的关系

选用合格大鼠９６只，平均分为对照组、假手术组、隔下迷走神经切除组、胃窦切除组。分别测定应激前后各组大鼠损伤指数、胃粘膜血流量及生长抑紊的变化。结果：各组大鼠应激后６０ｍｉｎ时损伤指数分别为５．６７±１．５、５．７８±１．４、３．５５±０．７９、３．９８±０．８３，９０ｍｉｎ时分别为１７．８±２．５３、１９．６５±２．７、５．８３±０．８１、６．３５±１．２４。应激前各级大鼠胃粘膜血流量分别为１２４．８３±１３．０４、１２３±１３．２、１０２．３±１１．０８、１２０．７±１２．３。应激后３０ｍｉｎ各为９４．３±１１．５、９２。７±１１．３、８４．１±７．７６、００．３±１０．８，应激６０ｍｉｎ后行为７５．９±９．４、７３．７±１０．７、７１．３±６．８８、７１．１±８．３。应激９０ｍｉｎ后各为５５．８±８．３、５７．０±９．１、５２．３±９．４、５２．４±１０．４。应激前Ⅰ、Ⅱ、Ⅲ、Ⅳ组大鼠胃粘膜生长抑素含量各为５２．１７±８。０７、５０．８±９．３、７１．５±１０．０９、３５．９±８．５３。应激３０ｍｉｎ后各为１２．３±１０．７、０．９±９．２、８３．１６±８．１５、３０．８±７．５。应激６０ｍｉｎ后各为３?     

Frequency-dependent effect of quinidine, mexiletine, and their combination on postrepolarization refractoriness in vivo

Combination therapy with mexiletine and quinidine has been shown to enhance antiarrhythmic efficacy. To assess further the underlying electrophysiological mechanism, the effect of therapeutic concentrations of mexiletine and quinidine, and of their combination, on action potential duration (at the level of 90% repolarization, APD90), effective refractory (ERP), and the relationship between these two parameters (ERP-APD90) was determined in 21 in vivo canine hearts. The frequency dependence of these effects was assessed over a range of paced steady-state cycle lengths from 250-600 ms. A modified contact electrode technique allowed measurements of both APD90 and ERP simultaneously and at the same ventricular site. In the drug-free state, both APD90 and ERP shortened linearly with shorter cycle lengths, maintaining a constant relationship (ERP-APD90) difference = -9 +/- 2 ms) at all cycle lengths. Quinidine prolonged APD90 by a near constant amount of 11 +/- 1 ms over the entire range of cycle lengths, while mexiletine tended to shorten it. Both mexiletine and quinidine increased ERP and ERP-APD90 in a rate-dependent fashion, the effect increasing with shorter cycle lengths. When used in combination, mexiletine attenuated the lengthening effect of quinidine on APD90 but augmented the rate-dependent increase in ERP, thereby producing greater postrepolarization refractoriness than either drug alone. This effect may explain the clinically favorable antiarrhythmic efficacy of mexiletine and quinidine combination therapy.     

醋毒毛花苷元对间离体浦肯野纤维动作电位时程的影响及与细胞外钾 …

AIM: To study the relation between the effect of acetylstrophanthidin on action potential duration (APD) and the extracellular potassium concentration. METHODS: Effect of acetylstrophanthidin (AS 0.15 mmol.L-1) on APD at different extracellular potassium concentrations was studied at the stimulation cycle lengths of 990 and 690 ms in sheep isolated cardiac Purkinje fibers using the standard microelectrode technique. RESULTS: At [K+]o 4.0 mmol.L-1, the biphasic effect of AS on APD appeared obviously. Both APD50 and APD90 were lengthened within the first 10 min of drug exposure. After 10 min, they were shortened at all pacing cycle lengths. On the other hand, at [K+]o 5.4 mmol.L-1, AS only shortened APD markedly without lengthening effect on it. The biphasic and monophasic effects of AS on APD were found at [K+]o 4.0 mmol.L-1 and 5.4 mmol.L-1, respectively. CONCLUSION: The effect of AS on APD was related to the concentration of [K+]o.     

The class III effect of azimilide is not associated with reverse use-dependence in open-chest dogs

Certain class III antiarrhythmic agents manifest loss of effect at short cycle lengths (CLs). This effect may limit their efficacy in the presence of tachycardia. We studied the frequency-dependent effect of azimilide (NE-10064), a new class III agent, on the right ventricular monophasic action potential (APD90) in 12 open-chest dogs. The monophasic action-potential duration at different pacing CLs (140-400 ms), during sinus rhythm, and ventricular fibrillation CL (VFCL) from left epicardial electrograms were recorded before and after increasing doses of intravenous azimilide. At pacing CL of 400 ms, APD90 was significantly prolonged after 7, 17, and 30 mg/kg of azimilide by 5.4, 7.7, and 10.7%, respectively. The extent of APD90 prolongation was independent of rate. Azimilide increased the APD90 by similar amounts at CL of 400 ms and at the fastest possible stimulation rate maintaining 1:1 capture (mean, 171 +/- 23 ms): by 2.6 +/- 8.6% and 5.6 +/- 5.9% at 2 mg/kg, 5.4 +/- 4.8% and 4.8 +/- 4.7% at 7 mg/kg, 7.7 +/- 5.6% and 9.9 +/-4.5% at 17 mg/kg, and 10.7 +/- 2.6% and 19.3 +/- 11.9% at 30 mg/kg, respectively. Azimilide caused no changes in arterial blood pressure or heart rate. Azimilide prolongs APD90 even at very short CLs. The absence of reverse use-dependence of effect on APD90 may have clinical importance.     

蝙蝠葛碱对在体家兔左心室单相动作电位和有效不应期的影响

目的:研究蝙蝠葛碱(Dau)和索他洛尔对在体家兔左心室单相动作电位和有效不应期的作用.方法:采用单相动作电位测定技术记录家兔在体心脏单相动作电位,用程序电刺激法测定左心室有效不应期.结果:Dau 0.5mg·kg~(-1)·min~(-1)恒速静脉灌注明显降低单相动作电位幅度,由用药前的(17±6)mV降至给药后24min的(7.1±1.5)mV.Dan显著延长单相动作电位复极50％和90％时程及有效不应期,给药前分别为(130±26),(167±25),(128±12)ms,给药后24min分别延长至(198±33),(235±34),(185±25)ms.但对有效不应期与单相动作电位时程(MAPD_(90))之比值无明显影响.索他洛尔对上述各指标的作用与Dau相似.结论:研究结果表明,Dau和索他洛尔降低单相动作电位幅度,延长单相动作电位时程和有效不应期.     

1—（2，6—二甲基苯氧基）—2—（3，4—二甲氧基苯乙氨基）丙烷盐酸盐抑制豚鼠心室肌细胞内向整流和延迟整流钾电流

目的:研究1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐(DDPH)对心室肌细胞动作电位(AP)、内向整流钾通道电流(I_(K1))及延迟整流钾通道电流(I_K)的影响。方法:全细胞膜片箝技术。结果:DDPH 10,100μmol·L~(-1)使豚鼠心室肌细胞AP时程APD_(50)明显缩短;但DDPH(>1μmol·L~(-1))延长APD_(90)。DDPH浓度依赖性地抑制I_K尾电流(I_(K·tail)),EC_(50)为13.3(11.6.6-16.7)μmol·L~(-1)。DDPH(>1.0μmol·L~(-1))明显抑制I_(Kl);同时,DDPH使I_(Kl)翻转电位向正电位方向移动。结论:DDPH对豚鼠心室肌细胞I_(Kl)和I_K具有明显的抑制作用。     

The cellular electrophysiologic effect of a new amiodarone like antiarrhythmic drug GYKI 16638 in undiseased human ventricular muscle: comparison with sotalol and mexiletine

The cellular electrophysiologic effect of GYKI 16638, a new antiarrhythmic compound was studied and compared with that of sotalol and mexiletine in undiseased human right ventricular muscle preparation by applying the conventional microelectrode technique. GYKI 16638 (5 microM), at stimulation cycle length of 1000 ms, lengthened action potential duration (APD(90)) from 338.9 +/- 28.6 ms to 385.4 +/- 24 ms (n = 9, p > 0.05). This APD lengthening effect, unlike that of sotalol (30 microM), was rate-independent. GYKI 16638, contrary to sotalol and like mexiletine (10 microM), exerted a use-dependent depression of the maximal rate of depolarization (V(max)) which amounted to 36.4 +/- 11.7% at cycle length of 400 ms (n = 5, p < 0.05) and was characterised with an offset kinetical time constant of 298.6 +/- 70.2 ms. It was concluded that GYKI 16638 in human ventricular muscle shows combined Class IB and Class III antiarrhythmic properties, resembling the electrophysiological manifestation seen after chronic amiodarone treatment.     

Effects of MS-551, a new class III antiarrhythmic drug,on action potential and membrane currents in rabbit ventricular myocytes.

1. Electrophysiological effects of MS-551, a new class III antiarrhythmic drug, were examined and compared with those of (+)-sotalol in rabbit ventricular cells. 2. In rabbit ventricular muscles stimulated at 1.0 Hz, MS-551 (0.1-10 microM) and (+)-sotalol (3-100 microM) prolonged action potential duration (APD) and effective refractory period without affecting the maximum upstroke velocity of phase 0 depolarization (Vmax). The class III effect of MS-551 was approximately 30 times more potent than that of (+)-sotalol. 3. Class III effects of MS-551 and (+)-sotalol showed reverse use-dependence, i.e., a greater prolongation of APD at a longer cycle length. 4. In rabbit isolated ventricular cells, 3 microM MS-551 and 100 microM sotalol inhibited the delayed rectifier potassium current (IK) which was activated at more positive potentials than -50 mV and saturated around +20 mV. 5. MS-551 at a higher concentration of 10 microM decreased the transient outward current (Ito) and the inward rectifier potassium current (IK1) although 100 microM sotalol failed to inhibit these currents. 6. MS-551 is a non-specific class III drug which can inhibit three voltage-gated K+ channels in rabbit ventricular cells.     

雌二醇抑制豚鼠心室肌细胞内向整流和延迟整流钾通道电流

研究雌二醇对心室肌细胞动作电位,内向整流钾通道电流及延迟整流钾通道电流的影响。方法：全细胞膜片箝技术。结果：ＥＳＴ１０μｍｏｌ．Ｌ＾－１使豚鼠心室肌细胞ＡＰ时程明显缩短,ＡＰＤ５０由给药前（４７４±７１）ｍｓ缩短至（３３０±７５）ｍｓ（Ｐ〈０．０５）,Ｅｓｔ１００μｍｏｌ．Ｌ＾－１使ＡＰＤ５０缩短至（２２９±６７）ｍｓ,ＡＰＤ９０由（５８７±６０）ｍｓ缩短至（４１８±７９）ｍｓ,Ｅｓｔ浓度依赖性地     

依那普利对离体豚鼠乳头状肌的电生理作用

目的：研究依那普利（Ｅｎａ）对豚鼠乳头状肌电生理特性，哇巴因诱发的延迟后除极（ＤＡＤ）和触发电活动（ＴＡ）的直接作用方法与结果，采用标准玻璃微电极技术记录豚鼠乳头状肌动作电位，Ｅｎａ呈浓度依赖性增加静息膜电位（ＲＰ）和动作电位幅度（ＡＰＡ），而对０期最大除极，超射，和动作电位时程无明显影响Ｅｎａ１０μｍｏｌ．Ｌ＾－１则可明显抑制哇巴因０．５μｍｏｌ．Ｌ＾－１则可明显抑制哇巴因０．５μｍｏｌ．Ｌ＾－     

性激素对豚鼠心室乳头状肌动作电位和收缩的影响

AIM: To study the effects of sex hormones, estradiol (Est), progesterone (Pro) and testosterone (Tes) on the action potential (AP) and contraction of guinea pig papillary muscle. METHODS: Using conventional glass microelectrode and mechanical recording of myocardial contraction. RESULTS: Est slowed down the maximal rate of rise of phase 0 (Vmax) of AP at low concentration (1 mumol.L-1). At 10 mumol.L-1 and above, Est also prolonged AP duration (APD50 and APD90), effective refractory period (ERP) and decreased the maximal isometric tension (Pmax) and velocity of tension development (dT/dt) of contraction. Tes (100 mumol.L-1 - 1 mmol.L-1) prolonged APD90 and ERP with decreased Pmax and dT/dt. But Pro (1 mumol.L-1 - 1 mmol.L-1) had no effects on both AP and contraction. CONCLUSION: Est prolonged AP and depressed contraction of guinea pig papillary muscle.