肝细胞生长因子对大鼠心肌细胞动作电位的作用北大核心CSCD

目的研究肝细胞生长因子(HGF)对大鼠心肌细胞动作电位时程(APD)的影响。方法酶解法分离大鼠心肌细胞,随机分成对照组(HGF,0)和3个质量浓度实验组(HGF,5,10,50μg·m L^(-1)),以异丙肾上腺素(ISO)作为刺激因素,用膜片钳技术,分别记录各组心肌细胞在HGF作用下、当动作电位复极50%,90%所需时间(APD_(50)、APD_(90))。结果 ISO可明显延长对照组细胞的APD。与对照组相比,小、中、大3个质量浓度实验组细胞的APD_(50)的延长率分别下降1.2%,42.3%,49.2%,同时APD_(90)的延长率分别下降19%,41.1%,48.8%,HGF对抗ISO的作用成浓度依赖性增强趋势;而在不给予ISO刺激的情况下,与对照组相比,3个质量浓度实验组心肌细胞的APD_(90)分别缩短6.8%,13.3%,28.2%,HGF的作用同样呈浓度依赖性增强趋势。结论 HGF可缩短APD,促进细胞膜复极,具有对抗心肌肥大时的电重构潜力,有助于心肌肥厚的治疗。     

异紫堇啡碱对家兔窦房结及豚鼠心室肌动作电位的作用

用细胞内固定微电极技术观察了异紫堇啡碱(isocorydine)对家兔窦房结电活动、豚鼠心室肌动作电位及Ba~(2+)诱发的豚鼠心室肌自发电活动的作用。结果表明,异紫堇啡碱能使窦房结细胞APA,SP_0,SP_4减小、APD_(90)延长、自律性降低。3 μM异紫堇啡碱能使心室肌细胞的APD_(50),APD_(90)和ERP延长,300μM异紫堇啡碱则使心室肌细胞APD_(50)和APD_(90)缩短,但不缩短ERP,使ERP相对延长。300μM异紫茧啡碱亦能明显抑制Ba~(2+)诱发的心室肌自发电活动。     

呋喃二氢吡啶Ⅰ对豚鼠心肌收缩力及动作电位的影响

呋喃二氢吡啶I(FDP I)呈浓度依赖性地抑制豚鼠心肌收缩力,IC_(50)为1.62μmol·L~1,并能抑制心肌静息后增强效应.成对刺激及正阶梯现象的收缩幅度,离体心乳头状肌细胞跨膜电位实验表明:FDPI 1.0、4.0μmol·L~1能缩短动作电位之APD_(30)·APD_(50),APD_(90),硝苯碇(Nif)0.1.1.0,4.0μmol·L~1亦能缩短APD,但两药在所试浓度范围内,对APA和V_(max)均无明显影响。     

尼可地尔对体外培养乳鼠心肌细胞自发性搏动及动作电位的影响

目的:为了研究尼可地尔(nicorandil,Nic)抗心律失常的作用机制.方法:体外培养乳鼠心肌细胞并观察Nic对培养心肌细胞自发性搏动频率及动作电位的影响.结果:Nic能使体外培养乳鼠心肌细胞自发性搏动频率下降.Nic 60 μmol L~(-1)对CaCl_21 mmol L~(-1)及异丙肾上腺素2 μmol L~(-1)增加的细胞搏动率有抑制作用.Nic 32和160 μmol L~(-1)能使动作电位幅度(APA)及最大上升速率(V_(max))明显下降,使动作电位时程(APD_(50),APD_(90))缩短,搏动周期(SCL)显著延长.结论:Nic的抗心律失常机制与其对心肌细胞的直接作用有关.     

肉毒碱对兔在体缺血心室肌细胞动作电位的影响

本实验观察了人工合成肉毒碱d,1-carnitine盐酸盐(VBt)对在位兔心急性心肌缺血早期左室肌细胞动作电位的影响。阻断冠脉引起动作电位振幅(APA)和零期最大除极速度(dv/dt)明显降低以及复极50%时程(APD_(50))和复极90%时程(APD_(90))明显缩短。VBt有延长心室肌细胞动作电位时程的作用(P<0.01),并能显著减轻缺血心肌细胞的APD_(50)和APD_(90)的缩短程度,但对APA和dv/dt的缺血性变化则无明显改善。     

雷尼替丁对体外培养乳鼠心肌细胞自发性搏动及动作电位的影响

本实验以培养大白鼠乳鼠心肌细胞为模型,观察了雷尼替丁对培养心肌细胞自发性搏动频率及动作电位的影响.结果表明:雷尼替丁1～100μmol·L~(-1)对正常心肌细胞搏动频率影响不大,但100μmol·L~(-1)可以阻止组胺10μmol·L~(-1)引起的心肌细胞搏动频率的增快,而对异丙肾上腺素2μmol·L~(-1)引起的心肌细胞搏动频率无明显抑制作用.组胺10μmol·L~(-1)可以使心肌细胞动作电位的APA,V_(max)及OS明显增高,APD_(50)和APD_(90)明显延长,SCL明显缩短.雷尼替丁100μmol·L~(-1)可以抑制此反应.以上结果,说明雷尼替丁对组胺增高所致的心律失常可能有防治作用.     

卡托普利对培养大鼠心肌细胞缺氧和复氧损伤的保护作用

应用细胞内微电极技术观察列卡托普利(captopril, Cap)在40mg·L~(-1)浓度下能延长培养大鼠心肌细胞在缺氧环境中的搏动时间,减少搏动节律失常的发生。部分纠正由复氧所致异常心肌细胞电活动参数,缓解心肌细胞复极后再次停搏的发生,     

普鲁卡因对离体豚鼠右心室缺血再灌注心肌电活动的影响

目的　研究普鲁卡因对离体豚鼠心室肌心律失常及跨壁传导等电生理特性的影响。方法　模拟在体正常和缺血再灌注条件,用玻璃微电极同时记录离体豚鼠心室肌内、外膜下心肌细胞跨膜电位。结果　普鲁卡因可明显地降低心律失常发生率、增加缺血再灌过程的心内膜传导时间和跨壁传导时间、延长心肌动作电位时程和有效不应期,并可使心肌兴奋性降低。结论　降低心肌兴奋性、消除折返激动和触发活动可能是普鲁卡因拮抗缺血再灌注心律失常的重要途径     

甲基莲心碱对豚鼠心肌电—机械活动的影响

甲基莲心碱(Nef)0.1mM使豚鼠右心室乳头状肌的收缩力降低68. 3％,使动作电位APA和Vmax分别从112±5mV,240±37V/s降低到97±9 mV和86±25V/s;APD_(50),APD_(90)和ERP分别从173±23ms,205±17ms和201±16ms延长到201±26ms,239±28ms和249±23ms。Nef 1-200μM浓度依赖性地延长APD_(50),APD_(90)和ERP,降低Vmax和收缩力。30μM Nef能明显对抗10μM乙酰胆碱缩短豚鼠左心房APD的作用。结果提示,Nef对心肌Na~+,K~+,Ca~(2+)的跨膜转运均有抑制作用。     

磷酸羟基喹哌对豚鼠心室肌和家兔窦房结细胞慢反应电活动的影响

为进一步研究HPQP抗心律失常的机理,本实验采用细胞内固定微电极技术,观察到该药在30μmol/L可降低高钾除极化心肌动作电位APA和V_(max);对V_(max)呈频率依赖性抑制作用;抑制钡诱发的心室肌自发电活动;对家兔窦房结优势起搏细胞的V_(max)和APA均有抑制,延长APD_(50)和APD_(100),降低四相除极斜率。以上结果均表明该药对钙通道有阻滞作用。     

镉对豚鼠心脏乳头状肌动作电位及收缩力的影响

应用细胞内固定微电极技术,观察了不同浓度CdCl_2对豚鼠右心室乳头状肌快、慢反应AP及Fc的影响.结果表明20μmol/L CdCl_2对快反应APA及V_(max)无显著影响,但却抑制Fc;100和500μmol/L对上述各参数均呈抑制作用.各种剂量的CdCl_2对慢反应电位均可降低APA及V_(max),抑制Fc,缩短APD_(50)及APD_(90),对抗CaCl_2所致的正性频率作用.提示低剂量Cd使心肌细胞兴奋收缩脱耦联.可能有抗心肌Ca~(2+)流效应.     

Effects of procaine amide, quinidine and ethmozin on delayed afterdepolarizations

We studied the effects of three chemically different antiarrhythmic drugs on ouabain-induced delayed afterdepolarizations (DAD) in canine Purkinje fibers. The three drugs, ethmozin, 4.6 X 10(-6) M; procaine amide, 1.1 X 10(-4) M; and quinidine, 1.13 X 10(-6) M reduced DAD amplitude equivalently at drive cycle lengths less than 500 ms. Quinidine and procaine amide in these concentrations had no effect on the action potential characteristics except for a prolongation of action potential duration (APD) induced by procaine amide. Ethmozin reduced action potential amplitude, maximum upstroke velocity of phase 0 (Vmax), and APD measured to 50% and full repolarization (APD50 and APD100). Rate dependent changes in Vmax and maximum diastolic potential (MDP) were not exaggerated by quinidine in the ouabain intoxicated Purkinje fibers. The DAD coupling interval was increased as DAD amplitude decreased with all three drugs. Although ethmozin, procaine amide and quinidine similarly reduced DAD amplitude; procaine amide and quinidine exerted these effects in the absence of other transmembrane potential effects, whereas ethmozin did so only in concentrations that depressed the action potential as well.     

dl-四氢巴马汀对家兔窦房结和豚鼠心室肌慢反应电活动的影响

用细胞内固定微电极技术观察到dl-四氢巴马汀(THP)30～100μM使家兔窦房结细胞动作电位的振幅(APA)、零相去极化速率(SP_0)和舒张期4相去极化速率(SP_4)逐渐降低,小剂量使动作电位复极90％的时程(APD_(90))延长,大剂量使其缩短,并使心率(HR)减慢。THP 30～300μM使高K~+除极和河豚毒素(TTX)所致的豚鼠乳头状肌细胞慢反应动作电位的APA、零相最大上升速率(V_(max))逐渐降低,复极50％的时程(APD_(50))缩短。实验结果提示THP可能有钙拮抗作用。     

呋喃苯胺酸对蟾蜍心肌电与机械活动的影响

使用浮置式细胞内微电极方法,结合肌力换能器,观察了呋喃苯胺酸(Furosemide,Fur6×10~(-4)mol/L)对蟾蜍离体心肌电及机械活动的影响。结果显示:Fur作用20min时使右心房收缩力(FC)增加到147.50%;动作电位幅值(APA)、O相上升最大速率(V_(max))及动作电位时程(APD_(50))分别增加到108.69%、106.58%及103.45%。对APD_(25)、APD_(90)及窦性周长(SCL)无明显影响,Fur的正性肌力作用能被维拉帕米(Verapamil,Ver2.2×10~(-7)mol/L)所取消。实验结果提示Fur具有促进Ca~(2+)内向电流的作用。     

Role of action potential shortening in the prevention of arrhythmias in canine cardiac tissue

1. The effects of the K+ channel opener diazoxide and the oxime-containing Ca2+ and K+ channel blocker salicylaldoxime were tested in canine cardiac Purkinje tissue. 2. Both drugs shortened action potential duration (APD). For salicylaldoxime (0.1-1.0 mmol/L), the reductions in APD were statistically significant at the 25% level of repolarization (APD25) for 0.1 mmol/L (P < 0.05, n = 14) and 0.5 and 1.0 mmol/L (P < 0.01, n = 6), at the 50% level of repolarization (APD50) for 0.1 mmol/L (P < 0.05, n = 14) and 0.5 and 1.0 mmol/L (P < 0.01, n = 6) and at the 90% level of repolarization (APD90) for 0.5 and 1.0 mmol/L (P < 0.01, n = 6). In contrast, diazoxide (0.05-0.1 mmol/L) significantly shortened APD at all levels of repolarizations, with the APD50 and APD90 reduced most significantly (P < 0.01, n = 6) for higher concentrations of the drug (0.07-0.1 mmol/L). Both drugs significantly reduced the force of contraction. 3. Diazoxide (10 experiments) was more potent in suppressing strophanthidin-induced arrhythmias than salicylaldoxime (three of seven experiments). Salicylaldoxime reduced APD even further in the presence of diazoxide. 4. Although salicylaldoxime and diazoxide modulate different ion channels, it appears APD shortening may be a necessary, but insufficient, factor for the suppression of strophanthidin-induced arrhythmias.     

Electrophysiological effects of homocysteine in isolated rat right ventricular papillary muscles and left atria.

There is clinical and epidemiological evidence that elevated plasma homocysteine (Hcy) levels are associated with increased myocardial infarction mortality; however, very little is known about Hcy's direct cardiac effects. Thus, we aimed to characterize the cellular electrophysiologic effects of Hcy, a sulfur-containing amino acid in isolated rat hearts. A conventional microelectrode technique was used in left atria and right ventricular papillary muscles. At concentrations higher than 10(6) M, Hcy significantly decreased the maximum rate of rise of the depolarization phase (Vmax) in both cardiac preparations in a dose-dependent manner. Hcy at 10(-4)-5 x 10(-4) M concentrations increased the action potential duration (APD) at late stages of repolarization (at 75% and 90% of APD) both in atria and in ventricles. There was a slight decrease in action potential amplitude in ventricular papillary muscles and atria at concentrations higher that 10(-5) M. The resting membrane potential and the early repolarization phase (APD25 and APD50) remained unchanged in every preparation studied at all concentrations of Hcy administered. The present data suggest that homocysteine may decrease the Na+ channel activity in in vitro cardiac preparations. reserved.     

DIFFERENTIAL EFFECTS ON ACTION POTENTIAL DURATION OF CLASS IA, B AND C ANTIARRHYTHMIC DRUGS: MODULATION BY STIMULATION RATE AND EXTRACELLULAR K+ CONCENTRATION

1. Standard microelectrode techniques were used to study the effects on the action potential duration (APD) of canine Purkinje fibres of a therapeutic concentration of nine Class I antiarrhythmic drugs. At an extracellular K+ concentration of 5.6 mmol/L all nine agents reduced APD at all drive rates studied (range of interstimulus intervals = 200-1000 ms). At lower levels of K+, quinidine (5 mumol/L) and disopyramide (10 mumol/L) (Class Ia agents) revealed dual effects on APD. At the lowest levels of K+ (2 mmol/L) and the longest interstimulus interval used (2000 ms), both agents significantly prolonged APD. Under all other conditions, APD was either unchanged or reduced. Lignocaine, 15 mumol/L (Class Ib agent) reduced APD at all rates and all K+ concentrations and this effect was greatest at the slowest rates. 2. Flecainide (1 mumol/L) (Class Ic) shortened APD at K+ = 5.6 and 4 mmol/L but had no effect at K+ = 2 mmol/L. 3. We conclude that these data result from opposing drug actions on inward sodium and outward potassium currents flowing during the plateau of the action potential. 4. Class Ia drugs exhibit significant depression of both currents, with the resultant effect on APD being modulated by external K+ concentration and drive rate. 5. Class Ib agents predominantly depress the sodium current and hence shorten APD, and Ic compounds have intermediate actions. 6. These differential effects on APD must be considered when planning antiarrhythmic therapy, and are directly relevant to the proarrhythmic propensities of these agents.     

Effects of long-term oral administration of amiodarone on the electromechanical performance of rabbit ventricular muscle.

1. The effects of long-term administration of oral amiodarone on transmembrane action potential and contraction of ventricular muscle were investigated in rabbits. 2. ECGs of rabbits that received oral amiodarone 50 mg or 100 mg kg-1 daily for 4 weeks, showed a significant prolongation of RR, QT and corrected QT (QTc) intervals, whereas PQ and QRS were unaffected. Serum and myocardial tissue amiodarone concentrations were 0.14-0.18 micrograms ml-1 and 1.47-3.63 micrograms g-1 wet wt. respectively. 3. Right ventricular papillary muscles isolated from treated rabbits were characterized by a moderate prolongation of action potential duration (APD) compared with controls. A slight decrease of the maximum upstroke velocity (Vmax) was also observed at the higher dose. The APD prolongation by chronic amiodarone, unlike acute effects of sotalol, E-4031, Cs+ and 4-aminopyridine, did not show marked reverse use-dependence. 4. APD and Vmax restitution following slow basic stimuli (0.03 Hz) were unaffected by chronic treatment with amiodarone. 5. Acute application of amiodarone (10 microM) caused a significant decrease in APD and developed tension, as well as a marked use-dependent Vmax inhibition with fast recovery kinetics. 6. These findings suggest that a major and consistent electro-physiological effect of chronic amiodarone is repolarization delay (Class-III action) showing minimal frequency-dependence. However, when amiodarone above a certain concentration is present in the extracellular space, a fast kinetic Class-I action would be added as an acute effect.