双孔脑片电生理实验系统及其在脑缺氧研究中的应用

脑片标本兼有在体和离体细胞培养的某些特点。与离体细胞培养相比,其神经环路较完整,可研究原有神经环路不同神经元之间的相互作用,已经证明离体脑片能重复出整体动物大多数电生理现象。与整体动物相比,离体脑片排除了血脑屏障,可在解剖显微镜直视下将电极插到特定部位,不需立体定位;改变灌流人工脑脊液或气体成分即可控制标本环境、调节或改变神经元兴奋性;有较高的机械稳定性,有利于长时间观察。由于上述优点,近年来国内外越来越多的实验室建立起脑片实验方法,用于生理、病理和药物学研究。     

心脏起搏与电生理专业委员会召开学术会

在瑞金医院举办——2008上海心脏节律论坛之际,上海市生物医学工程学会心脏起搏与电生理专业委员会于2008年于12月7日上午在瑞金医院科技楼召开学术会。来自全国及上海的电生理同行,包括上海起搏与电生理界的老前辈约200人出席本次学术会。     

基于心脏电生理模型的心律失常机制研究进展

揭示发病机制是心律失常诊断、治疗、药物研发和设备设计的关键.整合当前在心脏分子生物学、生物化学、生理学及解剖学方面的最新成果,构建从离子通道、心肌细胞、心肌纤维、心肌组织、心脏器官到躯体各个层次的多尺度多模态心脏电生理模型,用于系统研究微观局部变化发生、发展、转化为宏观心律失常表现的过程,将彻底改变传统从基因突变、蛋白质表达、细胞电生理、临床表现单独研究心律失常的方式,实现微观与宏观研究的统一,使心脏电生理模型成为系统研究心律失常发病机制的有力手段.本文综述了心脏电生理模型的构建方法和研究进展,讨论了多尺度心脏电生理模型在揭示心律失常机制研究中的作用和地位,给出了基于心脏电生理模型心律失常研究的挑战和重要发展方向.     

在体心脏后去极化及触发性心律失常细胞电生理学研究

CsCl triggered activities in cat heart in vivo were studied by using floating microelectrode and contact electrode to record transmembrane and monophasic action potentials (TAP and MAP). Ten seconds after CsCl (0.5 m mol/kg, i.v.), early after depolarization (EAD) appeared in the middle-later period of phase 3 in both TAP and MAP. Thirty seconds after CsCl, the amplitude of TAP-EAD was 25.6 +/- 9.3 mV and that of MAP-EAD was 3.4 +/- 1.3 mV. The potential changes of the EADs could be divided into three kinds, i.e. the "tail", the "plateau" and "peak" types. Delayed after depolarization (DADs) could also be induced by CsCl in the phase 4 of the TAP and MAP in two cats. The amplitudes of TAP-DAD and MAP-DAD were 13.0 +/- 5.3 mV and 3.3 +/- 0.6 mV respectively. The types of the afterdepolarizations in MAP were very similar to those in TAP. The ventricular extrasystole and/or tachycardias could be induced by repeated injections of CsCl. According to the occurrence of after depolarization (AD) and the relationship between the coupling interval of the AD and that of the ventricular beat, two kinds of generation of arrhythmias were suggested, i.e. one triggered by AD of the myocardium under the electrode and the other induced by AD originating from the other sites of the myocardium.     

江苏省第二届心脏生理性起搏研讨会在宁召开

由南京大学医学院附属鼓楼医院主办的江苏省第二届心脏生理性起搏研讨会于6月7日在宁召开。中华医学会心电生理和起搏分会主任委员、全国心脏起搏专家张澍教授表示,我国心脏性猝死的年发生率为0．04％,每年死于心脏猝死的人数高达54．4万。由于发病突然、进展迅速,具有无法预测的特点,发生心脏骤停的患者经心肺复苏生存率不到5％。因此心脏性猝死的预防显得非常重要。     

利用普通电极导管测定在体心脏单相动作电位的研究

采用吸引电极记录的在体心脏单相动作电位(MAP)与同时用玻璃微电极记录的单个心肌细胞的跨膜动作电位(TAP)具有同样的形态。然而,因吸引部位心肌损伤、出血、MAP波形畸变、振幅下降等,限制了实验,尤其是临床研究的应用。1983年国外有人利用特制的接触电极导管稳定地记录了人的在体心脏MAP。我们利用普通国产电极导管也较理想地测定到了兔和人的在体心脏MAP。现介绍如下。     

全国现代电生理实验技术学习班在泸州医学院成功举办

由中国生理学会组织的全国现代电生理实验技术学习班,于2006年7月9—15曰在泸州医学院成功举办。来自南开大学、华东师范大学、上海中医药大学、广西医科大学、航空医学研究所和延边大学等26所院校的33名学员参加了该班的学习。     

细胞电生理技术在昆虫抗药性研究中的应用

害虫几乎对所有化学农药及Bt等生物农药都产生了抗性。离子通道是多种杀虫剂的作用靶,因此作为研究离子通道基本手段的电压钳与膜片钳技术在害虫抗性检测与抗性机理研究中越来越受到重视。该文综述了细胞电生理技术在害虫抗性机理、杀虫剂作用机理以及药物筛选中的应用。     

Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides

It is well-known that micromolar to millimolar concentrations of cardiac glycosides inhibit Na/K pump activity, however, some early reports suggested nanomolar concentrations of these glycosides stimulate activity. These early reports were based on indirect measurements in multicellular preparations, hence, there was some uncertainty whether ion accumulation/depletion rather than pump stimulation caused the observations. Here, we utilize the whole-cell patch-clamp technique on isolated cardiac myocytes to directly measure Na/K pump current (I(P)) in conditions that minimize the possibility of ion accumulation/depletion causing the observed effects. In guinea pig ventricular myocytes, nanomolar concentrations of dihydro-ouabain (DHO) caused an outward current that appeared to be due to stimulation of I(P) because of the following: (1) it was absent in 0 mM [K(+)](o), as was I(P); (2) it was absent in 0 mM [Na(+)](i), as was I(P); (3) at reduced [Na(+)](i), the outward current was reduced in proportion to the reduction in I(P); (4) it was eliminated by intracellular vanadate, as was I(P). Our previous work suggested guinea pig ventricular myocytes coexpress the alpha(1)- and alpha(2)-isoforms of the Na/K pumps. The stimulation of I(P) appears to be through stimulation of the high glycoside affinity alpha(2)-isoform and not the alpha(1)-isoform because of the following: (1) regulatory signals that specifically increased activity of the alpha(2)-isoform increased the amplitude of the stimulation; (2) regulatory signals that specifically altered the activity of the alpha(1)-isoform did not affect the stimulation; (3) changes in [K(+)](o) that affected activity of the alpha(1)-isoform, but not the alpha(2)-isoform, did not affect the stimulation; (4) myocytes from one group of guinea pigs expressed the alpha(1)-isoform but not the alpha(2)-isoform, and these myocytes did not show the stimulation. At 10 nM DHO, total I(P) increased by 35 +/- 10% (mean +/- SD, n = 18). If one accepts the hypothesis that this increase is due to stimulation of just the alpha(2)-isoform, then activity of the alpha(2)-isoform increased by 107 +/- 30%. In the guinea pig myocytes, nanomolar ouabain as well as DHO stimulated the alpha(2)-isoform, but both the stimulatory and inhibitory concentrations of ouabain were approximately 10-fold lower than those for DHO. Stimulation of I(P) by nanomolar DHO was observed in canine atrial and ventricular myocytes, which express the alpha(1)- and alpha(3)-isoforms of the Na/K pumps, suggesting the other high glycoside affinity isoform (the alpha(3)-isoform) also was stimulated by nanomolar concentrations of DHO. Human atrial and ventricular myocytes express all three isoforms, but isoform affinity for glycosides is too similar to separate their activity. Nevertheless, nanomolar DHO caused a stimulation of I(P) that was very similar to that seen in other species. Thus, in all species studied, nanomolar DHO caused stimulation of I(P), and where the contributions of the high glycoside affinity alpha(2)- and alpha(3)-isoforms could be separated from that of the alpha(1)-isoform, it was only the high glycoside affinity isoform that was stimulated. These observations support early reports that nanomolar concentrations of glycosides stimulate Na/K pump activity, and suggest a novel mechanism of isoform-specific regulation of I(P) in heart by nanomolar concentrations of endogenous ouabain-like molecules.     

犬双心室多点组合同步起搏的心肌力学效应研究

目的 :探讨多点组合同步心室起搏对犬心肌收缩 /舒张力学效应和心脏作功的影响。方法 :12只犬 ,随机进行 5种组合模式的双心室同步起搏 ,并以自身窦性心律状态 (SNR )作为对照。记录各起搏状态下 :左室内压上升和下降最大数率 (±dp/dtmax)、左室松弛时间常数 (τ)、左 /右室游离壁室壁肌张力 (L/RV tensileforce ,L/RV TF)、每搏量 (SV )、左室每搏功 (LVSW )和右室每搏功 (RVSW )等心肌收缩 /舒张力学和心脏作功参数。结果 :双室cHisB LVPL起搏和RVA LVPL起搏的心肌收缩力学参数 +dp/dtmax和L/RV TF较右室双点cHisB RVA起搏增加 ,前两组的心肌舒张力学参数 dp/dtmax也较cHisB RVA起搏增加 ,而τ值较后者缩短。双室三点cHisB RVA LVPL起搏和cHisB RVA LVA起搏的上述各参数均优于双室cHisB LVPL起搏和RVA LVPL起搏。而cHisB RVA LVPL起搏的 +dp/dtmax和L/RV TF均较cHisB RVA LVA起搏增加。cHisB RVA LVPL起搏 dp/dtmax较cHisB RVA LVA起搏提高 6.0 % ,τ值缩短 3 .7%。cHisB LVPL起搏和RVA LVPL起搏的SV、LVSW和RVSW等心室作功参数均较cHisB RVA起搏增加 ,而HisB RVA LVPL起搏的上述心脏作功各参数 ,亦分别较cHisB RVA LVA起搏和cHisB LVPL起搏有不同程度的增加。结论 :双室三点cHisB RVA LVPL组合同     

Towards real-time simulation of cardiac electrophysiology in a human heart at high resolution

We have developed the capability to rapidly simulate cardiac electrophysiological phenomena in a human heart discretised at a resolution comparable with the length of a cardiac myocyte. Previous scientific investigation has generally invoked simplified geometries or coarse-resolution hearts, with simulation duration limited to 10s of heartbeats. Using state-of-the-art high-performance computing techniques coupled with one of the most powerful computers available (the 20 PFlop/s IBM BlueGene/Q at Lawrence Livermore National Laboratory), high-resolution simulation of the human heart can now be carried out over 1200 times faster compared with published results in the field. We demonstrate the utility of this capability by simulating, for the first time, the formation of transmural re-entrant waves in a 3D human heart. Such wave patterns are thought to underlie Torsades de Pointes, an arrhythmia that indicates a high risk of sudden cardiac death. Our new simulation capability has the potential to impact a multitude of applications in medicine, pharmaceuticals and implantable devices.     

Implantation of the Micra transcatheter pacing system: A single center North India experience

BackgroundThe leadless pacemaking transcatheter system, Micra, is a miniaturized, single-chamber pacemaker system. We report herein our experience with implantation of the Micra TPS system.ObjectiveThe current study was conducted to evaluate the safety and efficacy of the leadless Micra Transcatheter Pacemaker System (Medtronic).Research design and methodsThis was a prospective single centre nonrandomized study without controls. A transcatheter pacemaker was implanted in patients who had guideline based indications for ventricular pacing. 28 subjects were screened based on the selection criteria. Mica TPS was implanted. Parameters assessed were: duration of procedure (from femoral vein puncture to venous access closure), fluoroscopy time, number of device repositions, periprocedural electrical measurements (sensing, threshold and impedance) and in-hospital, intermediate to long term adverse events related to procedure.Result and conclusions: The device was successfully implanted in 28 subjects. The mean intraoperative sensing value was 9.04 ± 1.5 mV and the impedance was 766.89 ± 213.9 Ω. At discharge from hospital, those values were 13.2 ± 15.83 mV and 855 ± 111.7, respectively. The recommended pacing threshold value as achieved in all subjects was 0.78 V, i.e. ≤ 1 V at 0.24 ms. There was no adverse event or complications reported for any of the subjects. Mean time from hospitalization to discharge was 1.5 days. Implantation of leadless pacemakers is feasible, safe and provides advantages over the conventional system.     

The femoral route revisited: an alternative for pectoral pacing lead implantation

We describe the implantation via the femoral vein of a dual-chamber pacing system with lumenless, catheter-delivered pacing leads in a patient in whom subclavian access on both sides was obstructed. (Neth Heart J 2010;18:42-4.)     

Embryology of the Conduction System for the Electrophysiologist

It is critical for interventional electrophysiologists to thoroughly appreciate the topographic and developmental anatomy of the heart and its conduction system. Not only is understanding cardiac anatomy important to prevent complications from collateral damage and to help guide catheter placement, but developmental anatomy allows a deeper appreciation of the arrhythmogenic substrate. In this article, we briefly review the relevant stages of cardiac development for electrophysiologists. The potential location of normal and abnormal conduction patterns resulting from heterogeneous developmental origin is discussed.     

A device for separated and reversible co‐culture of cardiomyocytes

A novel technique is introduced for patterning and controllably merging two cultures of adherent cells on a microelectrode array (MEA) by separation with a removable physical barrier. The device was first demonstrated by separating two cardiomyocyte populations, which upon merging synchronized electrical activity. Next, two applications of this co‐culture device are presented that demonstrate its flexibility as well as outline different metrics to analyze co‐cultures. In a differential assay, the device contained two distinct cell cultures of neonatal wild‐type and β‐adrenergic receptor (β‐AR) knockout cardiomyocytes and simultaneously exposed them with the β‐AR agonist isoproterenol. The beat rate and action potential amplitude from each cell type displayed different characteristic responses in both unmerged and merged states. This technique can be used to study the role of β‐receptor signaling and how the corresponding cellular response can be modulated by neighboring cells. In the second application, action potential propagation between modeled host and graft cell cultures was shown through the analysis of conduction velocity across the MEA. A co‐culture of murine cardiomyocytes (host) and murine skeletal myoblasts (graft) demonstrated functional integration at the boundary, as shown by the progression of synchronous electrical activity propagating from the host into the graft cell populations. However, conduction velocity significantly decreased as the depolarization waves reached the graft region due to a mismatch of inherent cell properties that influence conduction. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010     

Non-invasive Determination of the Optimized Atrioventricular Delay in Patients with Implanted Biventricular Pacing Devices

Background

Biventricular (BiV) is extensively used in the treatment of congestive heart failure but so far no recommendations for optimized programming of atrioventricular-delay (AVD) settings have been proposed. Can AVD optimization be performed using a simple formula based on non-invasive doppler-echocardiography?

Methods

25 patients (ejection fraction 30±8%) received BiV ICDs. Doppler-echocardiographic evaluation of diastolic and systolic flow was performed for different AVDs (30ms to 150ms) and different stimulation sites (left ventricular (LV), right ventricular and BiV). The optimal atrioventricular delay was calculated applying a simple formula based on systolic and diastolic mechanical delays determined during doppler-echocardiography.

Results

The mean optimal AVD was calculated to be 112±29ms (50 to 180ms) for BiV, 95±30ms (65 to 150ms) for LV and 75±28ms (40 to 125ms) for right ventricular pacing with wide interindividual variations. Compared to suboptimal AVDs diastolic optimization improved preejection and ejection intervals independent to pacing site. Optimization of the AVD significantly increased ejection time during BiV pacing (279ms versus 266ms; p<0.05). Compared to LV or right ventricular pacing BiV pacing produced the shortest mean pre-ejection and longest ejection intervals as parameters of improved systolic ventricular contractile synchrony. Diastolic filling times were longest during BiV pacing compared to LV or RV pacing.

Conclusions

Individual programming of BiV pacing devices increases hemodynamic benefit when implementing the inter-individually widely varying electromechanical delays. Optimization applying a simple formula not only improves diastolic ventricular filling but also increases systolic functional parameters.