兔心房室结细胞的分离及鉴定

为进一步从细胞水平研究房室结区的特点和功能，需获得形态和功能正常房室结区细胞。本文用快速，恒压的低钙，无钙和胶原酶Tyrode液相继灌流家兔心脏冠脉系统后，结合解剖部位再经KB液或低钙台氏液存放，可获得耐钙的游离的房室结细胞、心房肌和心室肌细胞。用全细胞电流记录房结内梭状和柱状细胞的动作电位参数。此细胞保持了在未损伤的房室结区细胞的电流特性，且与心房肌、心室肌比较明显较短和薄，很多细胞保持了良好的自主活动性，为在细胞水平上研究房室结电生理特性提供了可能。     

大鼠房室结区的特化心肌纤维构筑

目的：为探讨心传导系房室结区双（多）径路传导、折返等复杂电生理的形态学基础。方法：本文采用连续切片的方法观察了18例SD大鼠房室结区的特化心肌纤维构筑。结果：①大鼠房室结位置较恒定贴于中心纤维体的右侧,大小约为0.97mm×0.51mm×0.13mm,后份薄而宽,中份厚,前份窄。③房室结可分为浅、深两层.浅层包裹深层.为上下方向的特化纤维;深层由上、下两部前后走向的细胞束组成.下部较粗大并延伸为房室柬。③房室结可明确区分出四种细胞：P细胞、T细胞、浦氏细胞及普通心肌细胞.④房室结的覆盖层为心房肌与房室结之间的特化过渡区,与房室结有较多联系,部分可穿房室环联系心室肌。⑤房室结与心房肌之间有多条路径相连.有的还与心室肌直接联系。结论：房室结内部的分层、分部及其周围与心房或心室肌的联系可能与多路径传导和折返有关。     

心脏房室交界区传导延搁的形态学基础

心脏房室交界区(Atrioventricular Junction Area,AVJ)是指心脏传导系在心房与心室之间的连接部分,形态学将其分成房室结和房室束两部分;电生理的研究将心房肌与房室结直接相连的部分也归入AVJ,称之为房室结的心房扩展部、移行区或房结区.移行区与心房肌的分界不明,大小无法确定.成人房室结的长度约7mm,房室束为10～20mm[1];成年大鼠房室结的长度约0.97mm,房室束约1.08mm[2～3].传导延搁是AVJ最主要的生理特征.     

间隔部房室交界区解剖

正间隔部房室交界区主要包括Koch三角(内含房室结)、膜部室间隔、希氏束、左右束支等重要解剖结构。希氏束-浦肯野纤维传导系统的最重要解剖结构是:被分割成两部分的希氏束(包括希氏束的穿越部分和希氏束的分支部分)。房室交界区是心房与心室之间唯一的电通路,从组织学的角度上讲,它是指连接心房工作肌与希氏束之间的3种不同的特化组织:(1)心房肌和致密结之间的过渡细胞区;     

1例Ⅲ度房室传导阻滞并阿-斯综合征护理体会

房室传导阻滞即指当房室结未处于不应期时心房激动向心室传导延迟或完全不能传至心室。依其严重性可分为Ⅰ度，Ⅱ度和Ⅲ度。其中Ⅲ度房室传导阻滞是最严重的类型。Ⅲ度房室传导阻滞又称完全性房室传导阻滞。当完全性房室传导阻滞时心房活动不能传至心室，心房与心室被不同的起搏点控制，造成完全性房室分离，心室率慢于心房率。临床表现不一，最严重的表现为阿-斯综合征发作即急性心脑缺氧综合征。因Ⅲ度房室传导阻滞时心室收缩减慢，心输出量明显减少，造成心脏及其他组织发生严重缺血缺氧，导致突然晕厥，肢体抽搐，患者意识丧失甚至死亡，故应高度重视。     

腺苷对家兔心脏房室结区不同细胞的动作电位的影响

为探讨房室交界区各部位的电生理特性以及腺苷对各部位的动作电位特性的影响，本文对20只家兔制作了房室结立体标本，用标准微电极技术法记录了不同部位房结区（AN）、结区（N）、结希区（NH）以及冠状窦口周围和三尖瓣，二尖瓣房室环上的动作电位形态及腺苷对其的影响。结果表明似房结区，似结区及似结希区的动作电位图形分布广泛，除在传统的房室结可记录到此组动作电位图形外，在冠状窦及房室环周围也可记录到类似图形。腺苷对各区细胞的作用也明显不同，其共同的作用为缩短动作电位时程，减慢心率。结果提示房室交界区或称为广义的房室结是一结构和功能复杂的结合体，对其结构和功能结合起来研究才能真正了解其电生理特性。     

家兔房室交界区的形态学观察及其意义

目的:观察家兔心房室结周围的纤维联系,探讨结间传导及折返机制。方法:选20只家兔心脏做房室交界区水平面及矢状面连续切片,HE染色光学显微镜下观察并拍照。结果:房间隔主要观察到3种形态的细胞,P细胞、T细胞和普通心房肌细胞。房室结由致密结和后延伸两部分组成。致密结分浅、深两层。房室结周围有3条纤维与之相连。后方为两束过渡纤维,分别源于冠状窦口及其下方,上方通过普通房肌与下房间隔相连。各肌纤维之间形成回路。结论:结间传导存在着形态学证据,肌纤维形成的回路很可能成为兴奋发生转折的部位。     

长RP间期阵发性室上性心动过速的电生理鉴别方法

阵发性室上性心动过速包括房室结折返性心动过速、房室折返性心动过速及房性心动过速等多种类型。目前临床上常用的鉴别方法包括心动过速时应用心室起搏拖带、希氏束不应期/非不应期的心室期前刺激及心房不同部位起搏的方法,窦性心律下应用希氏束旁起搏、心室不同部位/频率刺激等方法。心室起搏拖带可观察多个指标,为临床最常用的鉴别方法之一...     

预激综合征合并室上性心动过速应怎样治疗?

预激综合征是指心房冲动提前激动心室的一部分或全体,或心室冲动提前激动心房的一部分或全体。发生激动的解剖学基础是,在房室传导组织以外,还存在着一些连接房室之间的肌束,称为房室旁路通道。1　预激综合征伴发心动过速的几种形式1.1　房室折返性心动过速　①正向传导型:此类较为常见,其折返环的前传支为房室结,逆传支为旁路。适时的期前收缩经房室结前向传导,经旁路逆向传导而构成折返激动并导致心动过速。心电图的ＱＲＳ波群通常是“窄”的。②逆传型:较少见,其折返环的前传支为旁路,逆传支为房室结,激动在折返环中沿旁路前传,沿房室结…     

房室结折返性心动过速时房室非同步兴奋的电生理机制

13倒房室结折返性心动过速（AVNRT）,其心动过速时表现为房室非同步兴奋,其中房室2：1传导11例,房室分离2例。房室非同步现象说明心房和心室并非AVNRT折返环路的必须部分。心房参与心动过速取决于结周心房组织的不应期,心室参与心动过速取决于希浦系统的不应期,由于心房组织的不应期通常较短,而希浦系统的不应用相对较长,因此非同步现象以房室阻滞或分离多见,室房阻滞或分离少见。正确识别AVNRT时房室非同步兴奋现象对于AVNRT的正确诊断及导管消融治疗有非常重要的意义。     

Multiple cellular electrophysiological effects of a novel antiarrhythmic furoquinoline derivative HA-7 [N-benzyl-7-methoxy-2,3,4,9-tetrahydrofuro[2,3-b]quinoline-3,4-dione] in guinea pig cardiac preparations

We studied the electrophysiological and antiarrhythmic actions of HA-7 [N-benzyl-7-methoxy-2,3,4,9-tetrahydrofuro[2,3-b]quinoline-3,4-dione], a furoquinoline alkaloid derivative, in guinea pig heart preparations. In the perfused whole heart model, HA-7 caused a prolongation in the basic cycle length, ventricular repolarization time, and the atrioventricular (AV) nodal Wenckebach cycle length and prolonged the refractory period of the atrium, AV node, and His-Purkinje system. The atrioventricular conduction interval was also prolonged in a frequency-dependent manner. In isolated hearts, HA-7 significantly raised the threshold for experimental atrial fibrillation and reduced the occurrence of reperfusion-induced ventricular fibrillation. Conventional microelectrode-recording study shows that HA-7, but not d-sotalol, prolonged the action potential duration (APD) and decreased the maximum rate of depolarization in isolated atrial strips. In ventricular papillary muscles, higher concentrations of HA-7 caused a prolongation of APD(90) in a frequency-independent manner, whereas d-sotalol exerted a reverse frequency-dependent action on this parameter. Whole-cell patch clamp results on ventricular myocytes indicate that HA-7 decreased both the slow (I(Ks)) (IC(50) = 4.8 muM) and fast component (I(Kr)) (IC(50) = 1.1 muM) of the delayed rectifier K(+) currents. Similar results could also be observed in atrial myocytes. The inward rectifier K(+) current (I(K1)) was also reduced somewhat by HA-7. HA-7 also suppressed the Na(+) inward current (I(Na)) (IC(50) = 2.9 muM) and inhibited the L-type Ca(2+) current (I(Ca)) (IC(50) = 4.0 muM, maximal inhibition = 69%) to a lesser extent. We conclude that HA-7 blocks multiple ionic currents and that these changes affect the electrophysiological properties of the conduction system as well as the myocardial tissues and may contribute to its antiarrhythmic efficacy.     

腺苷对心房肌细胞钾钙通道的影响及受体机制

运用膜片钳全细胞记录方式，研究腺着（Ado）及选择性腺着A;受体阻滞剂8-环戊基-1，3-二丙基黄嘌呤（DPCPX）对豚鼠心房肌细胞延迟整流性怀通道电流（IK）和L-型钙通道电流（L－ICA）的影响及受体机制。结果表明：3μmol／LAdo可加强IK，其峰值电流增大（P＜0.01），LK尾电流Ik．tail亦增大，Ik.tail的快、慢失活时间常数均减少。同时Ado可抑制L－ICa，峰值电流减少36.9％．其激活和失活时间常数均增大。Ado对两者的峰值电压、激活电位、反转电位及时间和电压依赖性均无影响。DPCPX可基本消除Ado对IK、L-ICa的作用，表明Ado对心房肌细胞钾、钙通道的影响由A1受体介导实现的。     

Inhibition of G protein-coupled and ATP-sensitive potassium currents by 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015), an amiodarone derivative

2-Methyl-3- (3,5-diiodo-4-carboxymethoxybenzyl) benzofuran (KB130015; KB), a novel compound derived from amiodarone, has been proposed to have antiarrhythmic properties. Its effect on the G protein-coupled inward rectifying K+ current [IK(ACh) or IK(Ado)], ATP-sensitive K+ current [IK(ATP)], and background inward rectifying current (I(K1)) were studied in guinea pig atrial and ventricular myocytes by the whole-cell voltage-clamp technique. Receptor-activated IK(ACh/Ado), induced in atrial myocytes by the stimulation of either muscarinic or Ado receptors was concentration dependently (IC50 value of approximately 0.6-0.8 microM) inhibited by KB. Receptor-independent guanosine 5'-O-(3-thio)triphosphate-induced and background IK(ACh), which contributes to the resting conductance of atrial myocytes, were equally sensitive to KB (IC50 value of approximately 0.9 microM). IK(ATP) induced in atrial myocytes during metabolic inhibition with 2,4-dinitrophenol (DNP) was also suppressed by KB, whereas IK1 measured in ventricular myocytes was insensitive to the drug (KB < or =50 microM). Although being effective when applied from the outside, intracellular application of KB via the patch pipette affected neither IK(ACh) nor IK(ATP). 3,3',5-triodo-L-thyronin, which shares structural groups with KB, did not have an effect on the K+ currents. Consistent with the effects on single myocytes, KB did not depolarize the resting potential but antagonized the shortening of action potential duration by carbamylcholine-chloride or by DNP in multicellular preparations and antagonized the shortening of action potential duration by acetylcholine in single myocytes. It is concluded that KB inhibits IK(ACh) and IK(ATP) by direct drug-channel interaction at a site more easily accessible from extracellular side of the membrane.     

Electrophysiologic effects of ketanserin on canine Purkinje fibers, ventricular myocardium and the intact heart

We studied the actions of ketanserin (KT) on transmembrane action potentials (AP) of canine Purkinje fibers (PF) and ventricular muscle (VM) and on rhythm in vivo. PF AP duration (APD) was increased by KT (10(-8) to 10(-6) M) and shortened at 10(-5) M. KT effect on APD was greater during stimulation at longer cycle lengths and KT induced early afterdepolarizations in two of six PF at [K+]0 = 2.7 mM. Maximum diastolic potential, AP amplitude and Vmax were not changed by KT. In VM, KT (10(-8) to 10(-6) M) prolonged APD; but 10(-5) M KT did not shorten APD, reducing the difference in APD between VM and PF. KT had no effect on slow response Vmax or amplitude but prolonged APD. To analyze whether changes in Na plateau current or transient outward current contributed to KT effects on APD, we used tetrodotoxin (TTX) and 4-aminopyridine. TTX shortened APD and in its presence, KT (10(-5) M) induced no further shortening. In contrast, the effect of KT persisted in the presence of 4-aminopyridine. In six anesthetized, open chest dogs, KT prolonged the QT interval, but did not modify QRS duration and epicardial conduction time or induce arrhythmias. KT facilitated the onset of torsades de pointes during epicardial aconitine application.(ABSTRACT TRUNCATED AT 250 WORDS)     

二十二碳六烯酸对大鼠心室肌细胞通道的影响

目的 探讨二十二碳六烯酸(DHA)对大鼠心室肌细胞动作电位(AP)及瞬时外向钾通道电流(Ito)的影响.阐述DHA抗心律失常的机制.方法 采用酶消化法获得SD大鼠心室肌细胞,用膜片钳技术全细胞模式分别记录0,20,40,60,80,100,120μmol/L DHA对大鼠心室肌细胞AP复极25%,50%和90%时程(APD25,APD50和APD90),对AP最大上升速率(Vmax)、幅值(APA)、超射值(OS)及对Ito的影响.结果 不同浓度DHA对APD25、APD50和APD90呈浓度依赖性延长(P＜0.05,n=20),对Vmax、APA和OS的影响差异无统计学意义(P＞0.05,n=20).不同浓度DHA对Ito呈浓度依赖性阻滞、I-V曲线下移、稳态失活曲线左移、失活后恢复时间延长,对稳态激活曲线无影响.在指令电压+70 mV,上述浓度DHA对Ito阻滞分别为(2.61±0.26)%,(21.79±4.85)%,(63.11±6.57)%,(75.52±7.26)%,(81.82±7.63)%和(84.33±8.25)%(P＜0.05,n=20),DHA对Ito的半效作用浓度(EC50)为(49.11±2.68)μmol/L.结论 DHA对APD及瞬时外向钾通道的作用可能是其抗心律失常机制之一.     

A sodium channel blocker, pilsicainide, produces atrial post-repolarization refractoriness through the reduction of sodium channel availability

Atrial fibrillation (AF) is the most common tachyarrhythmia. Shortening of atrial action potential duration (APD) and effective refractory period (ERP) is one of the crucial factors in the occurrence and maintenance of AF. ERP is usually shorter than APD, but ERP can be prolonged beyond action potential repolarization in some situations. It is termed as post-repolarization refractoriness (PRR) that is thought to be one of main anti-arrhythmic mechanisms of class I sodium channel blockers (SCBs). Most of anti-arrhythmic agents, including SCBs, have multi-channel blocking effects. It is unknown whether atrial PRR with SCBs is associated with the reduction of sodium channel availability. We therefore explored the relationship between the reduction of sodium channel availability with a pure SCB (pilsicainide or tetrodotoxin) and atrial PRR using the left atrial appendage from male guinea pigs (each group, n = 3~10). Employing a standard microelectrode technique, we evaluated APD measured at 90% repolarization (APD(90)) and the sodium channel availability, judged from the maximal rate of rise of action potential (Vmax). At a 500-msec basic cycle length (BCL), pilsicainide prolonged atrial ERP assessed by a single extra-stimulus in response to the decrement of the Vmax in a dose-dependent manner without affecting APD(90). Furthermore, pilsicainide increased the ERP and decreased the Vmax in a rate-dependent manner without APD(90) prolongation at a shorter BCL (200 msec). Importantly, tetrodotoxin reproduced the effects of pilsicainide on atrial ERP, APD(90), and Vmax. These results indicate that SCBs produce atrial PRR through the reduction of sodium channel availability.     

Electrophysiological actions of BRB-I-28 in canine myocardial tissues

To obtain a better understanding of the possible electrophysiological bases of the antiarrhythmic actions of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate (BRB-I-28), microelectrode recordings of myocardial electrical activity were obtained in canine Purkinje and ventricular tissue, and in isolated canine ventricular myocytes. BRB-I-28 (1.0 and 3.2 mg/l) reduced Vmax, action potential amplitude, overshoot potential and conduction velocity in Purkinje tissues without altering action potential duration or spontaneous automaticity. Vmax and conduction velocity were reduced only at paced cycle lengths of 500 msec or less. BRB-I-28 (3.2 and 10 mg/l) also reduced Vmax, action potential amplitude and overshoot potential in subendocardial and epicardial ventricular muscle, with Vmax reduced only at cycle lengths of 500 msec or less. Recovery half-times for Vmax estimated in canine subendocardium were 330 +/- 28 and 336 +/- 25 msec at BRB-I-28 concentrations of 3.2 and 10 mg/l, respectively. In epicardium, conduction velocity longitudinal to fiber orientation was depressed more than conduction velocity transverse to fiber orientation, despite similar changes in Vmax. In both epicardial and subendocardial ventricular muscle, a reduction in Vmax is observed in the absence of alterations in action potential duration. Experiments using myocytes isolated from canine epicardial tissue demonstrated similar rate-dependent changes in Vmax as ventricular epicardium. The data demonstrate a rate-dependent depression of Vmax by BRB-I-28 in canine ventricular tissues. The depression of conduction occurs only at rapid paced rates and occurs in the absence of changes in Purkinje cell automaticity or action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiological effects of ACC-9358, a novel class I antiarrhythmic agent, on isolated canine Purkinje fibers and ventricular muscle

Class I antiarrhythmic agents are heterogeneous with respect to their cardiac electrophysiological effects and have been subdivided into three categories: la, lb and lc. The purpose of the present study was to determine the classification and investigate the mechanism of action of ACC-9358 [4-hydroxy-N-phenyl-3,5-bis (1-pyrrolidinyl-methyl)benzamide], a novel class I antiarrhythmic agent currently under clinical investigation. The effects of ACC-9358 on action potentials from isolated canine Purkinje fibers and ventricular muscle were examined using standard microelectrode techniques. In Purkinje fibers, ACC-9358 (1-50 microM) exerted a dose-dependent reduction in maximum upstroke velocity (Vmax) and action potential duration at 50 and 90% repolarization (APD50 and APD90). The reduction of Vmax was voltage-dependent (greater at an extracellular potassium concentration of 6 mM than at 2.7 mM), frequency-dependent (greater at a basic cycle length of 500 than at 2000 msec) and very slow in onset (rate constant of 0.017 action potentials-1) and offset (recovery half-time of 66.9 sec). In Purkinje fibers, ACC-9358 attenuated the action potential shortening effects of lidocaine but not that of nicardipine or nicorandil and shortened APD50 to a greater extent at a basic cycle length of 2000 than at 500 msec. In ventricular muscle, ACC-9358 (1-50 microM) exerted a dose-dependent reduction in Vmax and prolongation of APD50 and APD90.(ABSTRACT TRUNCATED AT 250 WORDS)     

临床抗心律失常药物对牵张引起的豚鼠心房心肌细胞动作电位变化的影响

目的：研究机械牵张对离体豚鼠左心耳心肌细胞动作电位（AP）的影响，观察几类抗心律失常药物对机械牵张引起的心房心肌细胞AP改变的作用。方法：采用常规做电极技术记录心肌细胞AP,观察机械牵张对其的影响，并分析抗心律失常药物对机械牵张引起的心房心肌细胞AP和有效不应期（ERP）变化的作用。结果：①机械牵张可加快心房心肌细胞整个复极过程，牵张效果呈心肌牵张长度依赖性，但牵张刺激对静息膜电位（RMP）和动作电位幅度（APA）无影响；②进一步分析抗心律失常药物对机械牵张后的心房心肌细胞RMP、APA、动作电位时间（APD）和ERP的影响后发现，Ⅰa类抗心律失常药物奎尼丁可使该AP复极至90％所需的时间（APD50）和ERP均显著延长（P均〈0．01），APA显著降低（P均〈0．01）；Ⅰb类抗心律失常药物利多母因可使该AP复极至50％所需的时间（APD50）、APD50和ERP显著缩短（P均〈0．01）；Ⅰc类抗心律失常药物氟卡尼可使该APA、AP复极至20％，所需时间（APD20）和APD50进一步缩短，但未发现Ⅱ类抗心律失常药物普萘洛尔有改变机械牵张后的RMP、APD和ERP作用（P〉0．05）；Ⅲ类抗心律失常药物胺碘酮可使机械牵张后的APD20、APD50、APD90和ERP显著延长（P均〈0．01）；Ⅳ类抗心律失常药物维拉帕米可使该APD50和APD90显著延长（P均〈0．01）。结论：①Ⅰa、Ⅲ和Ⅳ类抗心律失常药物可防止机械牵张引起的心房心肌细胞APD和ERP缩短；②Ⅰb和Ⅰc类抗心律失常药物可促进机械牵张引起的心房心肌细胞APD和ERP的缩短；③Ⅱ类抗心律失常药物对牵张引起的心房心肌细胞APD和ERP改变无影响。     

Electrophysiological effects of LU111995 on canine hearts: in vivo and in vitro studies.

We studied the electrophysiological effects of LU111995 (1-15 mg/kg p.o.) in conscious dogs with chronic atrioventricular block and ventricular pacing at 50 to 130 beats/min. LU111995 had no effects on idioventricular rhythm, QRS duration, and ventricular conduction time. It significantly prolonged Q-T interval (by 5-8%) and effective refractory period (ERP) (by 5-12%) with the maximal effect at 4 h after a 10 mg/kg dose. At 10 and 15 mg/kg, it increased the ERP/Q-T ratio. In vitro, the effects of LU111995 (1 x 10(-7) to 1 x 10(-5) M) on action potentials of Purkinje fibers (PFs) and M cells were studied at cycle lengths (CL) of 300 to 2000 ms. It had no effects on maximum diastolic potential and action potential amplitude in either tissue. High concentrations induced a moderate, rate-independent decrease of Vmax in M cells. In PFs and M cells, it produced reverse use-dependent lengthening of action potential duration (APD). In PFs at long CL, the drug exhibited a biphasic concentration-dependent effect on APD: maximum prolongation (by 26% at a CL of 2000 ms) was attained at 1 x 10(-6) M, and a decrease of APD occurred at higher concentrations. In M cells, the maximum effect on APD occurred at 3 x 10(-6) M. Early afterdepolarizations were seen in 50% of M cell preparations but only at CL of 2000 ms. Triggered activity did not occur. In summary, LU111995 prolongs the Q-T interval to a limited degree and is not arrhythmogenic over the physiological range of CLs.