Contributions of Purkinje-myocardial coupling to suppression and facilitation of early afterdepolarization-induced triggered activity

Electrical loading by ventricular myocardium modulates conduction system repolarization near Purkinje-ventricular junctions (PVJs). We investigated how that loading suppresses and facilitates early afterdepolarizations (EADs) under conditions where there is a high degree of functional coupling between tissue types, which is consistent with the anatomic arrangement at the peripheral conduction system-myocardial interface. Experiments were completed in eight rabbit right ventricular (RV) free wall preparations. Free-running Purkinje strands were locally superfused, and action potentials were recorded from strands. RV free walls were bathed in normal solution. Surface electrograms were recorded near strand insertions into downstream free wall myocardium. Detailed histology was performed to assemble a computer model with interspersed Purkinje and ventricular myocytes weakly coupled throughout the region. Delays from Purkinje upstrokes to downstream peripheral conduction system and myocardial activation were comparable between experiments and simulations, supporting model node-to-node electrical coupling, i.e., the functional coupling. Purkinje action potential duration (APD) prolongation with localized isoproterenol in experiments and calcium current enhancement in simulations failed to establish EADs. With myocardial APD prolongation by delayed rectifier potassium current inhibition or L-type calcium current enhancement accompanying Purkinje APD prolongation in simulations, however, EAD-induced triggered activity developed. Collectively, our findings suggest competing contributions of the myocardial sink when there is a high degree of functional coupling between tissue types, with the transition from suppression to facilitation of EAD-induced triggered activity depending critically upon myocardial APD prolongation.     

Modulation of spiral-wave dynamics and spontaneous activity in a fibroblast/myocyte heterocellular tissue--a computational study

Fibroblasts make for the most common nonmyocyte cells in the human heart and are known to play a role in structural remodeling caused by aging and various pathological states, which can eventually lead to cardiac arrhythmias and fibrillation. Gap junction formed between fibroblasts and myocytes have been recently described and were shown to alter the cardiac electrical parameters, such as action potential duration and conduction velocity, in various manners. In this study, we employed computational modeling to examine the effects of fibroblast-myocyte coupling and ratio on automaticity and electrical wave conduction during reentrant activity, with specific emphasis on dynamic phenomena and stability. Our results show that fibroblast density and coupling impact wave frequency in a biphasic way, first increasing wave frequency and then decreasing it. This can be explained by the dual role of the fibroblast cell as a current sink or a current source, depending on the coupled myocytes intracellular potential. We have also demonstrated that wave stability as manifested by the spiral-wave tip velocity and reentrant activity lifespan depends on fibroblast-myocyte coupling and ratio in a complex way. Finally, our study describes the required conditions in which spontaneous activity can occur, as a result of the fibroblasts depolarizing the myocytes' resting potential sufficiently to induce rhythmic pulses without any stimulation applied.     

Stimulation of isolated ventricular myocytes within an open architecture microarray

This paper is concerned with the physiological responses of single heart cells within microfluidic chambers, in response to stimulation by integrated microelectrodes. To enable these investigations, which included the measurement of action potential duration, intracellular Ca2+ and cell shortening, a series of microfluidic chambers (50 microm wide, 180 microm long, 400 microm high, 500 microm pitch) and connecting channels (200 microm wide, 5000 microm long, 50 microm high, 500 microm pitch) were replica-moulded into the silicone elastomer, polydimethylsiloxane (PDMS). The structures were formed against a master of posts and lines, photolithograhically patterned into the high aspect ratio photoresist SU-8. The chambers within the slab of PDMS were aligned against pairs of stimulating gold microelectrodes (50 microm long, 20 microm wide, 0.1-10 microm thick, 180 microm apart) patterned on a microscope coverslip base, thus defining cavities of approximately 4 nL volume. The assembly was filled with physiological saline and single isolated rabbit ventricular myocytes were introduced by micropipetting, thus creating limited volumes of saline above individual myocytes that could be varied between 4 nL and > or = 4 microL. The application of transient current pulses to the cells via the electrodes caused transient contractions with constant amplitude (recorded as changes in sarcomere length), confirming that excitation contraction coupling (EC coupling) remained functional in these limited volumes. Continuous monitoring of the intracellular Ca2+ (using calcium sensitive dyes) showed, that in the absence of bath perfusion, the amplitude of the transients remained constant for approximately 3 min in the 4-nL volume and approximately 20 min for the 4 microL volume. Beyond this time, the cells became unexcitable until the bath was renewed. The action potential duration (APD) was recorded at stimulation frequencies of 1 Hz and 0.5 Hz using potential sensitive dyes and was prolonged at the higher pacing rate. These studies show the prolonged electrical stimulation of isolated adult cardiac myocytes in microchambers with unimpaired EC coupling as verified on optical records of the action potential, Ca2+ transients and cell shortening. The open architecture provided free (pipetting) access for drug dispensation without cross talk between neighboring microwells, and multiplexed optical detection can be realized to study EC coupling on arrays of cells under both control and experimental conditions.     

Ultrasonically actuated silicon microprobes for cardiac signal recording

In this paper, we report on ultrasonically actuated silicon thin microprobes that successfully penetrated canine cardiac tissue in vitro, and recorded the electrophysiological signals from multiple sites simultaneously within the heart wall. The penetration force--maximum force encountered by the probe during penetration--is found to reduce with increasing ultrasonic driving voltage, on both excised canine right ventricular muscle and chicken breast muscle. The rate of force decrease varies with tissue type and microprobe dimension. With ultrasonic actuation, the silicon microprobes are inserted into isolated perfused canine heart without breakage or significant buckling, under 10Vpp actuating voltage. Recordings were obtained from isolated perfused canine heart during pacing, following the induction of ventricular tachycardia, and during the transition from ventricular tachycardia to ventricular fibrillation. Local conduction velocity of 0.60 +/- 0.03 m/s was observed from the multichannel recordings from the canine right ventricular wall under epicardial pacing. The application of the ultrasonic microprobes in cardiac electrophysiology study can provide information for reconstruction of electrical wave propagation within the heart, which is important to understanding the mechanisms of cardiac arrhythmias.     

Effects of strong pulsed magnetic fields on the cardiac activity ofan open chest dog

The heart of an open chest dog was stimulated by strong magnetic fields which were damped sinusoidal pulses with the one-cycle period of 1.47 ms. Stimulation effects were detected by electrocardiograph (ECG) and arterial blood pressure as a function of the strength of the field, the triggering point in the cardiac cycle, and the position of a stimulating coil. The threshold for arrhythmias was a minimum for the stimuli triggered at the apex of the T wave and on the P wave in the ECG. Premature ventricular and premature atrial contractions occurred according to whether the coil was placed over the ventricles or the atria. Ventricular defibrillation can not be attained by the magnetic stimulus with the flux density of 9.2 T which was the maximum field used     

Sensitive detection of infrared photons using a high-Q microcantilever

A new approach based on microcantilevers is presented to detect infrared photons with high sensitivity. Infrared photons are measured by monitoring the amplitude change of a vibrating microcantilever under light pressure force.The irradiating light is modulated into sinusoidal and pulsed waves,and to be in-phase and anti-phase with the cantilever driving signal.A linear relationship between the amplitude change of the cantilever and the light power distributing on the cantilever was observed.Under a vacuum of 10^-4 Pa,an infrared light power of 7.4 nW was detected with the cantilever.The in-phase and anti-phase modulation to the cantilever vibration using a pulsed light results in an enhanced response of the cantilever.     

The Myoelectric Signal of Electrically Stimulated Muscle During Recruitment: An Inherent Feedback Pareter for a Closed-Loop Control Scheme

The myoelectric profile of an electrically stimulated muscle with separate and simultaneous control of firing rate and recruitment was determined. The signal consists of low amplitude, desynchronous discharge at low recruitment levels and exhibits monotonic, distinct compound action potentials at moderate to full recruitment. The myoelectric signal-force model is described by sigmoidal function when the signal is represented by its median frequency (MF), rms, or mean absolute value (MAV) at firing rates inducing just above fused force response (~28 pps). At firing rates corresponding to the maximal tetanic force of the muscle (~51 pps) the MES-force model is represented by a second-order polynomial for MF, rms, and MAV. Dynamic tracking of force induced by a sinusoidal recruitment/derecruitment of the muscle's motor unit pool at frequencies in the range of 0-1 Hz show that the MAV is independent, whereas the rms and MF are dependent on tracking frequency. The linearized MAV-force model was found superior for use as a sensorless force feedback measurement in a closed-loop control scheme aimed at restoration of regulated movement to a paralyzed limb joint.     

半导体激光器驱动电路设计及环路噪声抑制分析

为了防止驱动电流的波动会影响半导体激光器激射波长及发光功率,设计了一款具有较强抗干扰能力的半导体激光器驱动电路。该驱动电路以深度负反馈架构为核心,通过STM32控制器调节输出电流直流信号的大小以及调制波信号的频率与幅值。对整个环路进行一阶人工分析,并且结合Tina-TI仿真引入参数可调的噪声抑制网络,保证目标设置频率下环路响应能力的同时具有较强的抗干扰能力。实验表明,该激光器电流驱动电路对目标频率10 倍频程以上环路噪声的抑制可达到20 dB以上,并且对目标频率的调制波响应良好,频率的输出值与设定值最大偏差为0.001 Hz,控制线性度为0.999 9,直流偏置下驱动电流2 h短期稳定度优于0.005 6%,63 h长期稳定度优于0.011%,激光器功率控制线性度为0.999 4,标准误差为0.092 87。     

Effects of gap junction conductance on dynamics of sinoatrial nodecells: two-cell and large-scale network models

A computational model of single rabbit sinoatrial (SA) node cells has been revised to fit data on regional variation of rabbit SA node cell oscillation properties. The revised model simulates differences in oscillation frequency. Maximum diastolic potential, overshoot potential, and peak upstroke velocity observed in cells from different regions of the node. Dynamic properties of electrically coupled cells, each with different intrinsic oscillation frequency, are studied as a function of coupling conductance. Simulation results demonstrate at least four distinct regimes of behavior as coupling conductance is varied: (a) independent oscillation (G_c<1 pS); (b) complex oscillation (1⩽G_c<220 pS); (c) frequency, but not waveform entrainment (G_c⩾220 pS); and (d) frequency and waveform entrainment (G_c⩾50 nS). The conductance of single cardiac myocyte gap junction channels is about 50 pS. These simulations therefore show that very few gap junction channels between each cell are required for frequency entrainment. Analyses of large-scale SA node network models implemented on the Connection Machine CM-200 supercomputer indicate that frequency entrainment of large networks is also supported by a small number of gap junction channels between neighboring cells     

Imaging and visualization of 3-D cardiac electric activity

Noninvasive imaging of cardiac electric activity is of importance for better understanding of the underlying mechanisms and for aiding clinical diagnosis and intervention of cardiac abnormalities. We propose to image the 3D cardiac bioelectric source distribution from body-surface electrocardiograms. Cardiac electrical sources were modeled by a current dipole distribution throughout the entire myocardium, and estimated by using the Laplacian weighted minimum norm (LWMN) algorithm from body-surface potentials. The estimated inverse solution of the current distribution was further improved by using a recursive weighting strategy for localized sources, such as origins of cardiac arrhythmias. Computer simulations were conducted to test the feasibility of the proposed approach by using a 3D ventricle model embedded in a realistically shaped torso model. The boundary element method was used to solve the forward problem from assumed cardiac sources to the body-surface potentials. Two test dipoles were placed in the left and right ventricles, simulating the early activation associated with ventricular arrhythmias. The LWMN inverse solution showed an equivalent source distribution over both ventricles, with spread areas of activity overlying the positions of the test dipoles. The sharpened inverse image provides well-localized focal sources near the test dipole positions. In summary, the presented computer simulation suggests that the proposed 3D cardiac current source imaging and localization approach appears to be a promising candidate for localizing and imaging sites of origins of cardiac activation     

基于FPGA的多路信号源设计与实现

某型号遥测数据采集器在实验和测试时,需要开发一种能够产生多种输入信号的信号源。由单片机作为控制核心,基于FPGA、利用直接频率合成技术产生8路正弦信号。信号源各路信号的频率和幅度均可调,通过键盘设置可以5Hz为一个步进设定各个正弦信号的频率,液晶显示器能够显示当前状态和各个信号的频率。此信号源能同时实现多路信号的输出,信号精度高,在其他测试实验中也具有良好的应用前景。     

一种新型硅微陀螺仪闭环驱动方案的研究

研究了一种新的硅微陀螺仪闭环驱动方案,对推挽驱动方式的性能进行了分析,结果表明驱动力矩的频段与噪声信号频段是分离的,因此噪声信号不会影响到驱动效果。在此基础上,利用锁相技术满足正弦自激振荡的相角和增益条件,建立环路的自激振荡,实现了闭环控制。同时在闭环回路中利用正弦自激振荡的相角条件和锁相环的鉴相特性,消除了驱动信号对敏感信号的同频干扰,并抑制了环路中的噪声干扰,明显提高闭环性能。试验结果显示在1小时内交流信号频率和幅度的标准方差分别为0.132 H z和0.258 mV,实现了驱动稳幅稳频的目的,从而使陀螺仪精度和可靠性得到了显著提高。     

A temperature-stable RC transistor oscillator

Generation of stable sinusoidal oscillations of fairly good waveform has been realized in a basic multivibrator circuit by optimizing load and coupling elements and introducing an amplitude defining mechanism with the use of emitter coupling. The resulting differential operation introduces an inherent tendency of self-compensation against changes of active circuit parameters, and the frequency remains practically independent of temperature change even though transistors are used.     

The role of the hyperpolarization-activated inward current If in arrhythmogenesis: a computer model study.

Atrial fibrillation is the most common cardiac arrhythmia. Structural cardiac defects such as fibrosis and gap junction remodeling lead to a reduced cellular electrical coupling and are known to promote atrial fibrillation. It has been observed that the expression of the hyperpolarization-activated current If is increased under pathological conditions. Recent experimental data indicate a possible contribution of If to arrhythmogenesis. In this paper, the role of If in action potential propagation in normal and in pathological tissue is investigated by means of computer simulations. The effect of diffuse fibrosis and gap junction remodeling is simulated by reducing cellular coupling nonuniformly. As expected, the conduction velocity decreases when cellular coupling is reduced. In the presence of If the conduction velocity increases both in normal and in pathological tissue. In our simulations, ectopic activity is present in regions with high expression of If and is facilitated by cellular uncoupling. We conclude that an increased If may facilitate propagation of the action potential. Hence, If may prevent conduction slowing and block. Overexpression of If may lead to ectopic activity, especially when cellular coupling is reduced under pathological conditions.     

微机械光调制器的制备及其在不同激励条件下的响应研究

本文主要讨论了具有机械式抗反射开关(即MARS)结构的新型微机械光调制器.MARS结构光调制器由表面微机械工艺制备.测量结果表明,微机械光调制器有一系列的固有频率.当器件被正弦信号激励时,其响应信号也是正弦信号.当器件被方波信号激励时,响应信号和激励频率有关.当激励方波频率远低于器件固有频率时,器件响应实际上是对上下两个阶跃信号的响应:出现明显的阻尼振荡效应.当激励频率在固有频率附近时,器件实际只对方波的基频效应:响应为正弦信号.     

The Role of the Hyperpolarization-Activated Inward Current$I_rm f$in Arrhythmogenesis: A Computer Model Study

Atrial fibrillation is the most common cardiac arrhythmia. Structural cardiac defects such as fibrosis and gap junction remodeling lead to a reduced cellular electrical coupling and are known to promote atrial fibrillation. It has been observed that the expression of the hyperpolarization-activated current$I_ f$is increased under pathological conditions. Recent experimental data indicate a possible contribution of$I_ f$to arrhythmogenesis. In this paper, the role of$I_ f$in action potential propagation in normal and in pathological tissue is investigated by means of computer simulations. The effect of diffuse fibrosis and gap junction remodeling is simulated by reducing cellular coupling nonuniformly. As expected, the conduction velocity decreases when cellular coupling is reduced. In the presence of$I_ f$the conduction velocity increases both in normal and in pathological tissue. In our simulations, ectopic activity is present in regions with high expression of$I_ f$and is facilitated by cellular uncoupling. We conclude that an increased$I_ f$may facilitate propagation of the action potential. Hence,$I_ f$may prevent conduction slowing and block. Overexpression of$I_ f$may lead to ectopic activity, especially when cellular coupling is reduced under pathological conditions.     

一种新型EL冷光驱动芯片的设计

阐述了一种新型EL冷光驱动芯片的设计.该电路内部采用两级升压结构和SPWM控制策略,以及可以与低压工艺兼容的高压管结构.详细描述了各个模块电路的设计,完成了版图布局.仿真结果表明,该电路可以产生符合幅度和频率要求的正弦驱动信号.     

Filter design method for a PWM feedback inverter system

A novel approach to filter design for a closed-loop, pulse-width-modulated (PWM) DC-AC inverter system driving an RL load is investigated. The system has a rectangular hysteresis in the forward path and it is closed by current feedback. When it is excited by a sinusoidal input reference, it provides square pulses that produce a nearly sinusoidal current in the load. Using a describing function technique, design equations for the filter are derived. The data needed for the filter evaluation are the amplitude of current ripple and the frequency of square pulses delivered by the power bridge. System simulation and experimental results show that the design of the filter can be based on the method proposed and that the filter can provide a significant reduction of current ripple, or otherwise a significant reduction of switching frequency     

Dual Extra Cardiac Pacemaker

A cardiac stimulator for evaluation of mechanical and electrical response to arrhythmias is described. It drives the heart at preselected rates and can stop the basic driving, introduce two extra stimulations and return to basic rate with a single switch. Three output circuits enable independent amplitude regulation for the basic pacing and each extra stimuli. The two extra pulses can be transferred to the heart through either single or separate electrodes.     

Classification of cardiac arrhythmias using fuzzy ARTMAP

The authors have investigated the QRS complex, extracted from electrocardiogram (EGG) data, using fuzzy adaptive resonance theory mapping (ARTMAP) to classify cardiac arrhythmias. Two different conditions have been analyzed: normal and abnormal premature ventricular contraction (PVC). Based on MIT/BIH database annotations, cardiac beats for normal and abnormal QRS complexes were extracted from this database, scaled, and Hamming windowed, after bandpass filtering, to yield a sequence of 100 samples for each QRS segment. From each of these sequences, two linear predictive coding (LPC) coefficients were generated using Burg's maximum entropy method. The two LPC coefficients, along with the mean-square value of the QRS complex segment, were utilized as features for each condition to train and test a fuzzy ARTMAP neural network for classification of normal and abnormal PVC conditions. The test results show that the fuzzy ARTMAP neural network can classify cardiac arrhythmias with greater than 99% specificity and 97% sensitivity