Effect of autonomic nervous system on the transmural dispersion of ventricular repolarization in intact canine

Therecentstudieshavefoundasub populationofcells ,namedmidmyocardiumcells(Mcell) ,withuniqueelectrophysiological propertiesinthedeepsubepicardiumoftheventricleofhuman ,canineandotheranimals .TheresearcherssuggestedthattheMcellsnotonlyformthecellularbasisof…     

Experimental Study of the Effect of Autonomic Nervous System on the Transmural Dispersion of Ventricular Repolarization under Acute Myocardial Ischemia in Vivo

The electrophysiologic heterogeneity of the ven-tricular myocardium is an important factor of devel-oping ventricular arrhythmia.Under the pathologiccondition,thedistribution and thefunction of the au-tonomic nerves,especially the sympathetic nerve,can produce the heterogeneity in the myocardium,which can accelerate the electrophysiologic hetero-geneity of the ventricular myocardium.Acute my-ocardial ischemia can induce the dysfunction of theautonomic nerve endings,resulting in the hetero-gene…     

Experimental study of the effect of autonomic nervous system on the transmural dispersion of ventricular repolarization under acute myocardial ischemiain vivo

Summary The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization (TDR) under acute myocardial ischemia in intact canine was investigated. Using the monophasic action potential (MAP) recording technique, MAPs of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs. MAPD₉₀ and TDR among three myocardial layers as well as the incidence of the early afterdepolarization (EAD) before autonomic nervous stimulation and during autonomic nervous stimulation were compared. It was found that 10 min after acute myocardial ischemia, TDR was increased from 55±8 ms to 86±15 ms during sympathetic stimulation (P<0.01). The TDR (53±9 ms) during parasympathetic stimulation was not significantly different from that of the control (55±8 ms) (P>0.05). The EAD was elicited in the Mid of 2 dogs (16%) 10 min after acute myocardial ischemia, but the EAD were elicited in the Mid of 7 dogs (58%) during sympathetic stimulation (P<0.01). It was concluded that: (1) Sympathetic stimulation can increase the transmural dispersion of repolarization and induce early afterdepolarizations in the Mid under acute myocardial ischemia, which provide the opportunity for the ventricular arrhythmia developing; (2) Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia. Zhang Cuntai, male, born in 1963, Associate Professor     

犬在体心肌跨室壁复极不均一性的实验研究

目的 :探讨犬在体心肌是否存在跨室壁复极不均一性。方法 :40 %的甲醛溶液 0 1～ 0 3ml注入房室结 ,制备完全性房室传导阻滞模型 ,心室起搏控制心室率。应用单相动作电位记录技术 ,同步记录犬在体心外膜 (epi cardium ,Epi)、中层 (midmyocardium ,Mid)及心内膜 (endocardium ,Endo)心肌单相动作电位 (MAP) ,测量单相动作电位时程 (MAPD)并比较其差异。结果 :在心动周期 (cyclelength ,CL) 30 0ms时 ,Epi、Mid、Endo的MAPD90 分别为 2 0 8 6 7± 44 37ms、2 0 9 17± 38 6 2ms、2 0 3 5 0± 33 84ms(n =10 ) ,在体三层心肌单相动作电位时程无明显差异 ,CL增加至2 0 0 0ms时 ,三层心肌MAPD呈慢频率依赖性延长 ,Epi、Mid、Endo的MAPD90 分别为 32 9 90± 31 90ms、36 9 90±35 0 9ms、317 2 0± 40 2 7ms ,其中Mid的MAPD90 延长最为显著 ,与Epi及Endo相比 ,差异有显著性意义 (P <0 0 5 )。结论 :犬在体心肌存在明显慢频率依赖性的跨室壁复极不均一性     

长期血浆内皮素-1水平升高对兔心室电生理特性及心律失常的影响

目的:探讨长期血浆内皮素-1(ET-1)水平升高对兔心室电生理特性及室性心律失常(VA)的影响。方法:雄性新西兰大耳兔30只,随机分为对照组(CTL组)和血浆ET-1升高组(ET-1组),每组15只。所有动物连续14d经耳缘静脉注射药物,其中ET-1组按10μg/(kg·d)剂量注射ET-1,而CTL组则给予注射0.9%生理盐水[1ml/(kg·d)]。所有动物完成药物注射7d后,在整体心脏Langendorff灌流条件下行离体电生理研究。同步记录起搏周长(PCL)为300ms时左室前游离壁心内膜(LAF-Endo)及心外膜(LAF-Epi)单相动作电位(MAP),并计算动作电位复极跨壁离散度(TDR);测量LAF-Epi的有效不应期(ERP),并构建标准动作电位恢复性质(AP-DR)曲线,计算标准APDR曲线最大斜率(Smax);于LAF-Epi行程控增频刺激,进行动作电位电交替(ALT)及室性心律失常(VA)诱发,记录诱发ALT及VA的最大PCL(PCLmax)。结果:与CTL组相比,ET-1组LAF-Epi及LAF-Endo的90%单相动作电位时程(MAPD90)、APDR曲线Smax、诱发ALT及VA的PCLmax中位数均增大(P均<0.05),而LAF-Epi的ERP/MAPD90(P<0.01)却明显减小;CTL组动物LAF-Epi的MAPD90短于LAF-Endo,而ET组动物LAF-Epi的MAPD90却较LAF-Endo延长(P均<0.05);TDR及LAF-Epi的ERP在两组间无明显差异(P均>0.05)。结论:长期血浆ET-1水平升高可引起心室正常复极顺序发生逆向改变、增大标准APDR曲线最大Smax及减小心室发生ALT的频率阈值,进而促进VA的发生。     

不同血钾水平时索他洛尔对在体跨室壁心肌复极不均一性的影响

为了观察正常血钾和低血钾时索他洛尔对在体跨室壁心肌复极不均一性的影响,探讨索他洛尔致室性心律失常的机制。24只兔随机分为两组,正常血钾组（12只）和低血钾组（12只）,分别静注索他洛尔1.0mg/kg,3.0mg/kg;同步记录兔左室心外膜心肌(Epi)、中层心肌(Mid)和心内膜心肌(Endo)的单相动作电位（MAP）,研究发现低钾时与血钾正常时相比,索他洛尔增加跨室壁心肌复极离散度（TDR）的作用更明显;更易引起Mid发生早期后除极（EAD）;低血钾组尖端扭转性室速（TdP）的发生率亦更高。     

Changes of Monophasic Action Potential Duration and Effective Refractory Period of Three Layers Myocardium of Canine during Acute Ischemia in Vivo

Ventricular tachyarrhythmias are readily gen-erated in acute ischemia/infarction.The majorityof serious ventricular arrhythmias during ischemiais caused by reentry and occurs withinthe first mi-nutes of onset[1].Moreover,a growing body of ev-idence suggests that heterogeneity of electrophysi-ological characteristics is an i mportant property ofthe ventricular myocardium[2,3].I mportantly,asubpopulation of cells,called midmyocardial cells(Mcells),have been described in the ventricularwall of th…     

药物致尖端扭转型室性心动过速的发生机制

目的探讨药物致尖端扭转型室性心动过速（Tdp）的发生机制。方法建立冠状动脉灌注的犬左室心肌楔形组织块模型,
同步记录左心室内膜、中层、外膜心肌细胞的动作电位及跨壁心电图,观察不同浓度D-Sotalol对动作电位时间（APD）、QT间期、
跨壁复极离散度（TDR）、早期后除极（EAD）及Tdp发生的影响。结果浓度为0~100 μmol/L的D-Sotalol呈剂量依赖性地延长
各层细胞APD,尤以中层细胞最为显著（P<0.05）,因而增加TDR;D-Sotalol在中层细胞可诱发EAD,触发室性早博并形成跨壁
折返导致Tdp。结论D-Sotalol在中层细胞诱发EAD、R on T室性早博是其致Tdp的始动因子,在TDR增加的基础上形成跨室
壁折返是Tdp得以维持的关键。
     

Changes of monophasic action potential duration and effective refractory period of three layers myocardium of canine during acute ischemia in Vivo

Summary The effect of acute ischemia on the electrophysiological characteristics of the three layers myocardium of caninein vivo was investigated. Twelve canines were divided into two groups randomly: acute ischemia (AI) group and sham operation (SO) group. By using the monophasic action potential (MAP) technique, MAP and effective refractory period (ERP) of the three layers myocardium were measured by specially designed plunge needle electrodes and the transmural dispersion of repolarization (TDR) and transmural dispersion of ERP (TDE) were analyzed. The results showed that in the AI group, MAP duration (MAPD) was shortened from 201.67±21.42 ms to 169.50±13.81 ms (P<0.05), but ERP prolonged to varying degrees and TDE increased during ischemia. In the SO group, MAPD and ERP did not change almost. Among of the three layers myocardium of canine, MAPD was coincident in two groups. It was concluded that during acute ischemia, MAPD was shortened sharply, but there was no significant difference among of the three layers myocardium. The prolonged ERP was concomitant with increased TDE during acute ischemia, which may play an important role in the occurrence of arrhythmias induced by acute ischemia. These findings may have important implications in arrhythmogenesis. ZHANG Fanzhi, male, born in 1973, M. D., Ph. D.     

Electrical heterogeneity of canine right ventricular transient outward potassium currents

Background Some studies have confirmed that the right ventricular walls of most rodents, such as canines and humans, have evident transient outward potassium current (Ito1) heterogeneity, and this heterogeneity is closely related to J point elevation, J wave formation, and some ventricular tachycardias such as ventricular fibrillations caused by Brugada syndrome. This study is designed to investigate transmural electrical heterogeneity of the canine right ventricle during repolarization (phase 1) from the viewpoint of 4-aminopyridine sensitive and calcium-independent Ito1. Methods Adult canine single right ventricular epicardial (Epi) cells, mid-myocardial (M) cells, and endocardial (Endo) cells were enzymatically dissociated. Whole cell voltage-clamp recordings were made to compare the Ito1 values of the three cell types. Results At 37℃ and using 0.2 Hz and +70 mV depolarizing test potentials, the average peak Ito1 values of Epi cells and M cells averaged (4070±1720) pA and (3540±1840) pA, respectively. The activated and inactivated Epi and M cells kinetic processes were in accordance with the Boltzmann distribution. Compared with Ito1 in Epi cells and M cells, the average peak Ito1 in Endo cells was very low, averaged (470±130) pA. Conclusions These results suggest that there are evident differences and potent gradients in Ito1 between the three cardiac cell types, especially between Epi and Endo cells. These differences are among the prominent manifestations of right ventricular electrical heterogeneity, and may form an important ionic basis and prerequisite for some malignant arrhythmias in the right ventricle, including those arising from Brugada syndrome and other diseases.     

心肌缺血时复极和传导交替是T波电交替的电生理机制

目的:探讨缺血性T波电交替(TWA)的电生理学机制.方法:在体实验组家兔10只,开胸后结扎左冠状动脉前降支(LAD),造成心肌缺血模型,在结扎LAD前、结扎后60 min重复观测缺血区域心室壁内膜下层、中层和外膜下层的单相动作电位时程(MAPD)、有效不应期(ERP),快速心室刺激诱发TWA.离体实验组家兔10只,快速开胸取出心脏后作Langendorff灌流,先用正常Tyrode's液灌流30 min再用模拟缺血液灌流.在Tyrode's液灌流20 min后、模拟缺血液灌流60 min后重复观测模拟肢体导联心电图,以及左心室前壁、侧壁、右心室和心尖部心外膜的MAPD、ERP,快速心室刺激诱发TWA.结果:缺血后各位点MAPD的频率适应性降低,MAPD90和ERP缩短.与生理状态相比,心肌细胞复极梯度发生了明显重排.20个在体和离体心脏在缺血后全部可用快速心室刺激诱发TWA,诱发TWA的心动周期(CL)窗口在130-170ms之间,CL=140,150 ms时可稳定地诱发TWA.TWA时伴有单相动作电位复极和传导的交替.离体心外膜增频刺激时,CL=170 ms开始出现TWA,随后的减频刺激至CL=200 ms时TWA消失,即TWA的滞后现象.结论:心肌细胞复极不均一可能是引起心电图T波的原因之一.心肌缺血使心脏正常的复极梯度发生改变,在快速心室刺激时易于发生动作电位复极和传导的交替,在体表心电图上表现为TWA.     

通心络胶囊对兔心肌梗死后心肌微循环、心功能及心电生理的影响

目的探讨通心络胶囊对兔心肌梗死后心脏微循环灌注、心功能及心电生理的影响。方法选取新西兰大耳白兔24只,随机分成假手术组、心肌梗死组及通心络组,每组8只。通过结扎左冠状动脉前降支建立心肌梗死模型,假手术组除不结扎动脉之外,其余均同心肌梗死组与通心络组。从术后第1天开始,通心络组给予通心络超微粉0.4 g·kg^(-1)·d(-1)·d^(-1)灌胃;假手术组与心肌梗死组给予等量的生理盐水灌胃,连续8周。分别在术后2、4周后,应用实时心肌超声造影检测梗死后心肌的微循环灌注情况。在术后8周,3组均利用超声心动图检测心功能,并进行在体电生理检测,测量梗死周边区的心肌内、中、外膜MAPD_(90)、跨室壁复极离散度(TDR)、有效不应期(ERP)和室颤阈值(VFT)。结果与心肌梗死组比较,通心络组显著改善梗死相关区域的微循环灌注,心肌血流量明显提高[2周后:(7.24±1.11)dB×s(-1)灌胃;假手术组与心肌梗死组给予等量的生理盐水灌胃,连续8周。分别在术后2、4周后,应用实时心肌超声造影检测梗死后心肌的微循环灌注情况。在术后8周,3组均利用超声心动图检测心功能,并进行在体电生理检测,测量梗死周边区的心肌内、中、外膜MAPD_(90)、跨室壁复极离散度(TDR)、有效不应期(ERP)和室颤阈值(VFT)。结果与心肌梗死组比较,通心络组显著改善梗死相关区域的微循环灌注,心肌血流量明显提高[2周后:(7.24±1.11)dB×s^(-1)vs.(10.66±1.23)dB×s(-1)vs.(10.66±1.23)dB×s^(-1),P<0.05;4周后:(7.23±0.81)dB×s(-1),P<0.05;4周后:(7.23±0.81)dB×s^(-1)vs.(11.12±1.73)dB×s(-1)vs.(11.12±1.73)dB×s^(-1),P<0.05)。术后8周与心肌梗死组比,通心络组明显改善心肌梗死后心功能、延缓心肌梗死后心力衰竭发展进程、增加左室射血分数(FS:0.25±0.02 vs.0.30±0.02;LVEF:0.51±0.04 vs.0.61±0.03,P<0.05);缩短梗死周边区心肌MAPD_(90)[内膜:(170.65±7.64)ms vs.(159.01±5.48)ms;中膜:(169.34±6.35)ms vs.(160.32±5.46)ms;外膜:(167.16±5.72)ms vs.(156.74±4.43)ms,P<0.05],缩小TDR[(7.72±2.83)ms vs.(4.95±2.26)ms,P<0.05];延长ERP[(126.56±5.87)ms vs.(135.25±5.63)ms,P<0.05],增加VFT[(28.63±6.21)V vs.(44.75±13.73)V,P<0.05]。结论通心络明显改善心肌梗死后梗死相关区微循环灌注,同时改善心肌梗死后心功能;对心肌梗死后心脏的电生理具有重要的影响,可能具有潜在的抗心律失常作用。     

Effects of Volsartan on Transmural Heterogeneous Changes of Transient Outward Potassium Currents in Hypertrophic Cardiomyocytes in Rabbits

Leftventricularhypertrophyisassociatedwithanincreasedriskofmalignantventriculararrhythmia .Thisappearstobetheresultsofactionpotentialpro longationandincreasedrepolarizationheterogene ity[1] .Theprolongationofactionpotentialduration(APD)canbeduetoalteratio…     

普萘洛尔治疗长QT综合征的电生理机制探讨

目的：观察普萘洛尔对家兔跨左室壁不同部位心肌细胞电生理特性的影响，探讨普萘罗尔治疗长QT综合征（LQTS）的电生理机制。方法：采用标准玻璃微电极记录技术，记录心外膜心肌（epicardium，Epi）、中层心肌（mid—myocardium，Mid）和心内膜心肌（endocardium,Endo）的跨膜动作电位（transmembrance action potential，TAP）。用基础周长（basic cycle length，BCL）为2000m刺激心肌标本，观察不同浓度的普萘洛尔对三种心肌TAP的影响。结果：1．普萘洛尔浓度依赖性缩短d—sotalol灌流的三层心肌的APD90，与Epi和Endo相比，Mid的APD90缩短更明显，使TDR降低，且随着剂量的增加这种作用更为显著。2．普萘洛尔浓度依赖性地抑制d—sotalol诱导的早期后除极（Early afterdepolarization，EAD）。结论：普萘洛尔降低三层心肌间的复极离散度和抑制早期后除极是普萘洛尔治疗LQTS的电生理机制。     

正常家兔左心室三层心肌Cx43表达的异质性研究

目的 观察正常家兔三层心肌间跨室壁缝隙连接蛋白43 (Cx43)分布的差异,探讨恶性室性心律失常(MVA)的发生机制.方法 检测并对比正常家兔左心室三层心肌间的单相动作电位复极90%时程(APD90)以及Cx43蛋白(Cx43-pro)和mRNA(Cx43-Cq)的表达差异.结果 (1)正常家兔三层心肌间APD90存在差别,中层心肌(233.80±19.37)组织APD90均长于心内膜(201.20±18.72)和心外膜下(202.70±19.91)心肌组织(P<0.05),说明家兔三层心肌间存在跨室壁复极的离散;(2)正常家兔三层心肌间的Cx43-pro [(0.58±0.08) vs (0.47±0.04) vs (0.57±0.07)]与Cx43-Cq [(24.61±2.82) vs (22.18±2.62) vs (24.43±3.31)]差异均有统计学意义(P<0.05),中层心肌较心内膜与心外膜下心肌组织表达减少,表明家兔三层心肌间存在跨室壁Cx43表达的异质性.结论 正常家兔中层心肌与心内外膜下心肌间存在Cx43蛋白表达不均一,这是左心室存在心肌横断面上复极离散的蛋白基础.     

胺碘酮对家兔正常和缺血心脏心室复极及复极离散度影响的研究

目的探讨胺碘酮对正常和缺血心脏心室复极及复极离散度的影响,给临床研究提供实验依据。方法采用同步记录心室外膜多个部位单相动作电位的方法,观察家兔正常心脏（正常组）和急性缺血心脏（缺血组）静注胺碘酮前后单相动作电位时程（ＭＡＰＤ９０）和单相动作电位离散度（ＭＡＰＤｄ）的变化。结果正常组用药后左室前壁、左室心尖部和左室侧壁ＭＡＰＤ９０均显著延长（Ｐ均＜０００１）,ＭＡＰＤｄ无显著变化（Ｐ＞００５）。缺血组用药后缺血区（左室前壁及左室心尖部）和非缺血区（左室侧壁）ＭＡＰＤ９０均显著延长（Ｐ均＜０００１）,但ＭＡＰＤｄ明显减小（Ｐ＜００１）。结论胺碘酮可延长正常和缺血心脏心室复极,对正常心脏复极离散度无影响,但对缺血心脏可使其复极离散度缩小。     

Effects of Amiodarone on Transmural Dispersion of Ventricular Effective Refractory Periods across Myocardial Layers in the Normal and Hypertrophic Canine Heart

Recently studies have been focused on the re-lationship between the ventricular arrhythmia andthe transmural dispersion of ventricular effectiverefractory periods (ERPs) aross the three myocar-dial layers (epi myocardium, midmyocardium andendomyocardium) . Amiodarone is one of the mostwidely used antiarrhythmia drugs in clinical prac-tice . This study examined the effect of amiodaroneon ERPs-dispersion across three myocardial layersof normal and hypertrophic hearts of dogs beforeand after ma…     

Effect of Calcium-Channel Antagonist on Repolarization Heterogeneity of Ventricular Myocardium in an in Vitro Rabbit Model of Long QT Syndrome

Intracellular Ca2＋ and Ca2＋-dependent signaling molecule play an essential role in the genesis of long-QT （LQT） syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential （MAP） recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts purfused by Langendorff method with standard Tyrode＇s solution. Bradycardia was induced by com- plete ablation of atrioventricular node. A catheter was introduced into the right ventricle to pace at the cycle lengths （CLs） of 1500, 1000, and 500 ms, successively. Quinidine （2 μmol/L） prolonged QT interval and ventricular MAP duration （MAPD）, and increased transmural dispersion of repolarization （TDR） in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil （0.01--0.05μmol/L） used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syndrome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.     

胺碘酮对左室肥厚家兔跨室壁Cx43异质性的影响

目的：观察胺碘酮片剂对左室肥厚(LVH)家兔三层心肌间Cx43表达的差异,探讨LVH恶性室性心律失常(MVA)的机制及处理措施。方法将20只家兔按随机数字法分成胺碘酮治疗组和LVH对照组,每组各10只。两组家兔均采用传统的腹主动脉缩窄术后继续喂养8周以制备LVH模型。治疗组手术后给予经口喂服盐酸胺碘酮片,每日50 mg/kg,连续4周,然后继续喂养4周并进行实验;对照组喂养生理盐水8周后进行实验。分别检测两组家兔心外膜下、中层心肌和心内膜下心肌细胞的单相动作电位复极90%时程(APD90)、跨室壁复极离散度(TDR)以及左心室三层心肌Cx43蛋白表达的差异。结果(1)治疗组家兔心内、外膜下、中层心肌的APD90分别为(275.30±11.42) ms、(251.50±10.98) ms和(295.40±12.41) ms,均较LVH对照组的(236.30±16.51) ms、(217.69±14.25) ms和(265.12±20.01) ms显著延长,差异具有显著统计学意义(P<0.01),但是治疗组的TDR为(38.96±10.91),明显小于对照组的(48.56±11.23),差异有统计学意义(P<0.05)。(2)治疗组家兔三层心肌的Cx43蛋白表达分别为(0.60±0.07)、(0.48±0.05)和(0.57±0.06),均较对照组的(0.53±0.04)、(0.31±0.06)和(0.48±0.04)明显提高(P<0.05),但以中层心肌的增加更为明显,从而缩小了三层心肌间Cx43蛋白表达的差异,△Cx43减少[(0.14±0.06) vs (0.23±0.08),P<0.01]。结论胺碘酮能改善左室肥厚的跨室壁Cx43表达异质性,缩小左心室心肌跨室壁复极不均一性,这可能是其减少MVA发作的生理机制。     

地昔帕明预处理对心肌缺血后心室肌单向动作电位和有效不应期的影响

目的探讨地昔帕明预处理对大鼠心肌缺血后心室肌单向动作电位和有效不应期的影响。方法SD大鼠随机分为3组：心肌缺血组夹闭左冠状动脉前降支30min;地昔帕明组（预处理组）先单次静脉给予地昔帕明0．8mg／kg,5min后夹闭左冠状动脉前降支30min;假手术组仅开胸但不夹闭左冠状动脉。喂养1周后开胸测定单向动作电位（MAP）和有效不应期（ERP）。结果心肌缺血组梗死周边区心室肌的MAPD50、MAPD90和ERP较假手术组显著延长（P〈0．05）;地昔帕明预处理后,其MADP90和ERP比心肌缺血组明显缩短（P〈0．05）。与非梗死区心室肌的MADP90和ERP相比,梗死周边区心室肌的MADP90和ERP显著延长（P〈0．05）,地昔帕明组的ERP离散度较心肌缺血组降低。结论心肌缺血后心室的复极化不均一性和ERP离散度增加,地昔帕明预处理能够增加缺血心肌的电稳定性,发挥抗心律失常作用。