虚拟生理心脏模型及房颤机制研究进展

房颤是临床上最常见的持续性心律失常.揭示房颤的发病机制和病理生理过程是其诊断、预防、治疗、药物研发及临床设备设计的关键,而实验和临床只能呈现细胞或亚细胞的局部特性及房颤病症的宏观结果.随着生物信息技术、统计分析技术等的发展,运用多物理尺度的虚拟生理心脏模型,来实现宏观结果与微观机制相统一的研究方法备受关注.本文综述了离子通道、心肌细胞、心脏组织及器官等多尺度的虚拟生理心脏模型研究进展,探讨了近年来基于虚拟生理心脏模型的房颤机制研究以及房颤的治疗手段,提示了房颤研究的挑战和未来的发展方向.     

心脏电活动的计算机仿真模型

一、前言 自从100多年前人们发现体表心电以来在心脏电生理学方面和心电诊断学方面进行了大量的研究和临床的实践。尤其是心脏电生理学方面的研究十分细致、深入。从心肌细胞的电生理特性到细胞的除极和复极。以致兴奋在整个心脏中的传播机理和过程等都进行了很仔细的研究。另一方面,心电诊断学的发展相对比较粗糙和缓慢。究其原因,可以认     

基于机制的生理药动- 药效学模型研究进展

生理药动- 药效学模型通过对生物学过程的描述,可预测体内药物的吸收、分布、代谢、排泄以及进一步的生理生化反应。这类模型是通过已知的生化/ 生理基础来构建,采用了一种“自下而上”的建模方法,并利用数学方法对生理过程及药物的作用机制作出准确的描述。其中药效学部分,根据预测目的和药物作用的复杂性,可进一步分为基于经验的和基于机制的效应模型,这两种模型均可与基于机制的生理药动学模型相连接,最终预测药物的体内处置和效应。基于机制的生理药动- 药效学模型的优势在于：可外推性、新的影响因素的可纳入性以及可用于未知领域的预测等。随着实验技术的不断革新,药物作用机制的逐渐明确,这类模型越来越多的被成功应用于药物研发及风险评估中。综述生理药动- 药效学模型的构建策略与分类以及在药物研发和风险评估中的应用研究。     

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.     

心肌细胞电生理建模进展

心脏兴奋收缩的微观基础是心肌细胞的电生理活动,心肌细胞的电生理模型在解剖实验基础上提供了更为全面有力的数据.是研究心肌细胞最有效的方法之一.近年来单细胞意义上的电生理模型越来越精细,使得心肌细胞的工作原理以不同角度在微观领域得以进一步阐述.本文就不同时期有代表性的模型进行了研究和比较,总结了这一领域的发展,并对发展趋势作了进一步的展望.     

基于生理解剖知识的入睡机制神经元群网络模型研究

以生理解剖知识为基础,在已有的丘脑网状核细胞和丘脑皮质细胞间组成的入睡机制的两细胞环路模型［１］和由此两细胞环路组成的网络模型［２］的基础上,提出了增加皮层细胞在内的三种细胞组成的环路模型和网络模型,以使模型更符合近来认为睡眠机制是皮层和丘脑环路中出现特定的同步振荡的看法［３］。并能使模型的仿真结果可以和规定人体睡眠分期的脑电特征波相对应。这一网络模型的仿真结果,在一定条件下,确能在皮层细胞处出现符合睡眠分期中规定的标志入睡的纺锤波,这一初步结果,启示我们用模型仿真方法来进一步探讨睡眠机制和用模型仿真方法来进一步探讨人脑的微观神经元的电活动是如何通过同步振荡整合到宏观功能状态的某些信息处理过程的可能性。     

面向短QT综合征的药物作用建模与仿真研究

短QT综合征(short QT syndrome,SQTS)是以心电图QT间期、心室和心房不应期明显缩短为主要显性特征,并伴有晕厥、高发心源性猝死(sudden cardiac death,SCD)和恶性心律失常风险的一类遗传性心肌离子通道病.据目前资料信息,关于SQTS致病机理的报道比较多,而对SQTS药物治疗的报道罕见.为了揭示在SQTS下的药物作用,本文通过计算机仿真构建人体心室细胞和组织的药物作用模型,利用该模型,从亚细胞、细胞、组织三个尺度,模拟SQT1、SQT2和SQT3下的普罗帕酮药物作用过程,并仿真心电图的变化情况.仿真结果表明:在SQT1下普罗帕酮延长了动作电位时程(action potential duration,APD)和心电图QT间期,并降低T波幅值;相反,在SQT2和SQT3下普罗帕酮缩短了APD和QT间期.计算使用药物前后细胞间膜电压和APD空间离散度的变化,定量分析了普罗帕酮降低T波振幅的原因.总之,对SQT1,普罗帕酮有效;对SQT2和SQT3,普罗帕酮没有改变其致心律失常的危险.仿真结果为普罗帕酮用于临床治疗SQTS提供理论参考.     

基于能量融合积分模型的心脏生理物理活动研究

为了更深入地了解目前靠生理实验及临床手段无法洞察的心脏三维空间的电生理运行机制,分析和表现心脏复杂的电生理活动,从而揭示心脏的生理物理特性,本研究通过人类心肌细胞的动作电位传导数学模型,结合基于心脏解剖数据所建立的真实心脏组织结构的三维空间模型,构建出精细的心脏生物物理融合模型,并将心脏在三维空间中的生物物理活动表现出来.实验结果表明,基于心脏动作电位传导的融合模型,不同时刻的动作电位传导在非匀质性组织内的三维空间中的传播位置、空间关系以及生物物理过程被清晰地显示出来,心脏研究人员从而能够以视觉感知的方式认识和深入理解人类心脏电生物物理系统的功能机制,并有助于进一步推测心脏的生理和病理反应.     

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。     

氟喹诺酮类抗生素心脏毒性机制的研究进展

氟喹诺酮类抗生素的心脏不良反应较为罕见,但产生的后果严重,所以倍受关注。本文从离子通道角度、动作电位水平和心电图表现等方面对氟喹诺酮类药物心脏毒性电生理机制的研究进展进行综述。     

Coarse-grained Modeling and Simulation of Actin Filament Behavior Based on Brownian Dynamics Method

The actin filament, which is the most abundant component of the cytoskeleton, plays important roles in fundamental cellular activities such as shape determination, cell motility, and mechanosensing. In each activity, the actin filament dynamically changes its structure by polymerization, depolymerization, and severing. These phenomena occur on the scales ranging from the dynamics of actin molecules to filament structural changes with its deformation due to the various forces, for example, by the membrane and solvent. To better understand the actin filament dynamics, it is important to focus on these scales and develop its mathematical model. Thus, the objectives of this study were to model and simulate actin filament polymerization, depolymerization, and severing based on the Brownian dynamics method. In the model, the actin monomers and the solvent were considered as globular particles and a continuum, respectively. The motion of the actin molecules was assumed to follow the Langevin equation. The polymerization, which increases the filament length, was determined by the distance between the center of the actin particle at the barbed end and actin particles in the solvent. The depolymerization, which decreases the filament length, was modeled such that the number of dissociation particles from the filament end per unit time was constant. In addition, the filament severing, in which one filament divides into two, was modeled to occur at an equal rate along the filament. Then, we simulated the actin filament dynamics using the developed model, and analyzed the filament elongation rate, its turnover, and the effects of filament severing on the polymerization and depolymerization. Results indicated that the model reproduced the linear dependence of the filament elongation on time, filament turnover process by polymerization and depolymerization, and acceleration of the polymerization and depolymerization by severing, which qualitatively agreed with those observed in experiments.     

综述与专论: 脊髓星形细胞瘤研究进展

脊髓星形细胞瘤是一种罕见的中枢神经系统恶性肿瘤,在流行病学、肿瘤临床学表型、分子遗传标记、治疗及研究方面有着独特特征。虽然随着手术技术的进步以及分子病理的发展,脑胶质瘤的研究和治疗取得较大进展,但脊髓星形细胞瘤的研究和治疗却发展缓慢。其原因一方面在于临床样本较少,难以开展研究,另一方面因其分子遗传独特性,对脑胶质瘤一线化疗药替莫唑胺敏感性差。因而亟需理清脊髓星形细胞瘤的研究现状,为改善其临床疗效梳理潜在方向。基于此,本文综述脊髓星形细胞瘤的临床特征、病理分型、分子遗传特征和当前治疗方法等方面的研究进展,在描绘脊髓星形细胞瘤的临床治疗现状和研究进展的基础上,提出了未来研究和治疗潜在方向。