Effect of Autonomic Nervous System on the Transmurai Dispersion of Ventricular Repolarization in Intact Canine

Summary: The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization in intact canine was investigated. By using the monophasic action potential (MAP) recording technique, monophasic action potentials (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 in 12 open-chest dogs. MAPD90 and transmural dispersion of repolarization among three myocardial layers as well as the incidence of the EAD before autonomic nervous stimulation and during autonomic nervous stimulation were compared. The results showed that the MAPD90 of Epi, Mid and Endo before autonomic nervous stimulation were 278±11 ms,316± 16 ms and 270± 12 ms respectively, the MAPD90of Mid was significantly longer than that of Epi or Endo (P＜0.01). MAPD90 of Epi, Mid and Endo were shortened by 19±4 ms, 45±6 ms,18± 3 ms respectively during sympathetic stimulation. Compared with that of the control, the transmural dispersion of repolarization during sympathetic stimulation was shortened from 44 ± 4 ms to 15±3 ms (P＜0. 01), but early afterdepolarizations were elicited in the Mid of 5 dogs (41 0%)during sympathetic stimulation. Parasympathetic stimulation did not significantly affect the MAPD90 in the three layers. It is concluded that there is the transmural dispersion of ventricular repolarization in intact canine. Sympathetic stimulation can reduce transmural dispersion of repolarization, but it can produce early afterdepolarizations in the Mid. Parasympathetic stimulation does not significantly affect the transmural dispersion of ventricular repolarization.     

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     

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…     

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     

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…     

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。     

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。
     

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。     

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。     

Effect of Lidocaine and Amiodarone on Transmural Heterogeneity of Ventricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia

Someresultsofmeta analysesofrandomizedcontroltrialsonmyocardialinfarctionfoundthatlidocaineandamiodaronecanbeusedforthetreat mentofventriculartachyarrhythmias,butlido cainedonotreducemortalityinpatientswithven triculararrhythmiasaftermyocardialinfarctionwhileamiodaronecan[1,2].Themechanismisnotfullyunderstood.Inrecentyears,discoveryoftheMcells,andthreelayersmyocardiumtheorybeendrawed,thatmostelectrophysiologicalphenomenahadgotnewexplains[3,4].Thisexperimentthemonophasicactionpotentials(MAPs)…     

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…     

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.     

Na+/Ca2+交换体电流在兔左心室壁分布的异质性

目的探讨Na+/Ca2+交换体电流(INa+/Ca2+)在左室肌不同部位的分布特征及其与跨壁复极异质性的关系.方法采用全细胞膜片钳技术,分别记录兔左心室肌内膜下、中层及外膜下细胞的动作电位(AP)、INa+/Ca2+及IK.结果中层细胞AP时程明显长于外膜下细胞(P<0.01);在+40 mV时,外向INa+/Ca2+密度在中层细胞明显大于外膜下及内膜下细胞(P分别＜0.01,0.05);在-100 mV时,内向INa+/Ca2+密度在中层细胞明显大于外膜下(P<0.05);在测试电压为+50mV时,中层细胞的IKs尾电流密度明显小于外膜下细胞(P<0.05), 内膜下、中层及外膜下细胞的IKr尾电流密度无明显区别(P>0.05).结论 INa+/Ca2+与IKs在兔左室肌的分布具有异质性,并导致了跨壁复极异质性的形成.     

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.     

充血性心力衰竭跨室壁复极不均一性的改变

目的研究充血性心力衰竭模型左心室三层心肌之间单相动作电位的改变。以探讨充血性心力衰竭易发心室颤动的基础电生理机制。方法用阿霉素制作充血性心力衰竭家兔模型，测定其室颤阈值（VFT）以及心外膜、中层心肌和心内膜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）。结果充血性心力衰竭VFT明显降低，三层心肌细胞APD90均明显延长，但中层心肌细胞较心外膜、心内膜下心肌细胞延长更为显著；充血性心力衰竭跨室壁TDR增加。结论中层心肌细胞APD90明显延长、跨室壁TDR增加可能是充血性心力衰竭容易发生心室颤动的重要原因。     

Experimental study on the mechanism of sex difference in the risk of torsade de pointes

Torsadedepointes (TdP )isaformofpolymorphicventriculartachycardia (VT)accompaniedbyaprolongedQTinterval FemalesareathigherriskofdevelopingTdP ,especiallyinresponsetodrugsordiseasesthatcanprolongtheQTinterval 1 3　Thequestionofwhyfemalesareathigherriskhasarousedgreatinterest ExperimentsonthistopichavefocusedontheQTintervalaswomennaturallyhavealongerQTintervalthanmen 4 　Buttheresultsofpastexperimentshavebeeninconsistent,5,6 　andthemechanismsoffemalepredominanceinTdPremainunclear Itiskno…     

扩张型心肌病家兔左室壁复极异质性的改变及意义

目的：观察离体心脏左心室三层心肌的单相动作电位的改变，以探讨扩张型心肌病易发心室颤动与三层心肌跨室壁复极不均一性的关系。方法：用阿霉素制作扩张型心肌病家兔模型，测定其室颤阈值（VFT）以及心外膜、中层心肌和心内膜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）。结果：扩张型心肌病VFT明显降低（P＜0．001），三层心肌细胞APD90均明显延长（P＜0．001），中层心肌细胞较心外膜、心内膜下心肌细胞延长更为显著（P＜0．05）；扩张型心肌病跨室壁复极离散度增加（P＜0．01）。结论：中层心肌细胞APD90明显延长、跨室壁复极离散度增加、三层心肌复极不均一性增加可能是扩张型心肌病容易发生心室颤动的重要原因。     

高血压病人QT离散度及其临床观察

目的:为探讨QT离散度(QTd)在正常人及高血压病患者的意义。方法:观察120例正常人和81例高血压病人的QTd及相关指标并进行了对比研究。结果:正常人的QTd(39.94±12.13毫秒)小于高血压病组(44.05±16.66毫秒),结论:QTd是一项准确、无创评价心室复极状态的指标。高血压病病人的QTd的增大与心室负荷过重有关。     

雷米普利对兔心肌梗死后心室肌电生理的影响

目的:探讨血管紧张素转化酶抑制剂雷米普利对兔心肌梗死后室性心律失常发生的影响及其可能机制.方法:24只家兔随机分为假手术组(SHAM)、心肌梗死组(MI)和雷米普利组(RAM).3组均在无菌条件下开胸,其中心肌梗死组和雷米普利组分别结扎左冠状动脉前降支.雷米普利组术后第2天给予雷米普利[1 mg/(kg·d)],3组共...     

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。