脊椎动物心传导系统的发生

在成熟的心脏中,人们一般将心脏的工作肌与传导系统区分开来.成熟的传导系统由窦房结、房室结、房室束、束分支以及浦肯野纤维组成.每一部分都有不同的功能并有不同的基因表达.主要对心传导系统的主要组成结构和各部分的发生发育模式进行了综述.     

Cell Junctions in the Specialized Conduction System of the Heart

Abstract

Anchoring cell junctions are integral in maintaining electro-mechanical coupling of ventricular working cardiomyocytes; however, their role in cardiomyocytes of the cardiac conduction system (CCS) remains less clear. Recent studies in genetic mouse models and humans highlight the appearance of these cell junctions alongside gap junctions in the CCS and also show that defects in these structures and their components are associated with conduction impairments in the CCS. Here we outline current evidence supporting an integral relationship between anchoring and gap junctions in the CCS. Specifically we focus on (1) molecular and ultrastructural evidence for cell–cell junctions in specialized cardiomyocytes of the CCS, (2) genetic mouse models specifically targeting cell–cell junction components in the heart which exhibit CCS conduction defects and (3) human clinical studies from patients with cell–cell junction-based diseases that exhibit CCS electrophysiological defects.     

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.     

科学典故在组织胚胎学教学中的应用

人体组织胚胎学是一门医学形态学课程,也是医学生进入人体奥秘大门的一把重要钥匙,但形态结构中繁多的记忆内容常常让学生感到学习枯燥,因而更需要授课教师通过不同形式的教学策略引导学生领会其中的乐趣和科学意义。在众多的教学方法和教学手段中,适当引用教学内容相关的科学典故和科学名人,能在潜移默化中培养学生的学习兴趣,理解相关的理论知识,改善教学效果。本文作者整理了一些组织胚胎学教学内容相关的科学典故及其在教学中的应用,供同行交流和医学生参考学习。     

新疆阿魏的胚胎学研究

采用常规石蜡制片技术,对新疆阿魏不同发育时期的花和果实进行了显微切片观察.结果表明:新疆阿魏小孢子母细胞的减数分裂为同时型,小孢子四分体为四面体型和十字交叉型,成熟花粉粒为3-细胞型.雌蕊2心皮合生成2室,中轴胎座,每子房室内产生上、下2个胚珠原基,其中,下方的原基正常发育,而上方的原基停止发育并最终解体,因此,每室仅产生一枚发育正常的倒生胚珠,单珠被,薄珠心,胚囊发育为蓼型;珠被绒毡层和珠孔塞发生于大孢子四分体时期,并于四核胚囊时分化完全,八核胚囊时珠被绒毡层细胞径向延长;3个成熟的反足细胞具双核.胚乳发育为核型,细胞壁较厚,细胞排列紧密,可保护胚免受机械损伤及防止胚失水.胚乳细胞中含有大量PAS染色呈正反应的物质,一些胚乳细胞异常生长形成细胞体积大、核及核仁均较大的巨形细胞.胚胎发生为茄型,四细胞原胚为直线形,十六细胞原胚的顶部由2排各4个细胞组成.成熟种子具胚乳.     

Embryology of the Turbellaria and its phylogenetic significance

Developmental characters — including oocyte and yolk cell structure, patterns of cleavage, and modes of gastrulation — are presented and examined in relation to the phylogeny of the Turbellaria. Eggshell granules, which have been demonstrated to occur in the oocytes of entolecithal eggs and the yolk cells of ectolecithal eggs, are compared among species, and their potential value as a taxonomic character is discussed. The quartet 4d spiral cleavage of the entolecithal egg of polyclads is described as reminiscent of the primitive pattern of early development for the Turbellaria. This is compared to duet spiral cleavage of acoels, and possible phylogenetic schemes involving the two types of spiral cleavage are reviewed. The link between the precise spiral cleavage, which characterizes development of most archoophorans, and blastomere separation (Blastomeren-Anarchie), which occurs in several neoophoran orders, is established by the occurrence of quartet 4d spiral cleavage in one neoophoran order, and of both quartet spiral cleavage and Blastomeren-Anarchie in different species of a second neoophoran order. The epibolic gastrulation of polyclads is described as primitive for the Turbellaria because of its similarity to that of other members of the Spiralia. Although no identical process occurs in neoophoran development, the earlier event of formation of the hull membrane in some neoophorans, and the later event of formation of the definitive epidermis in all neoophorans studied are presented as processes of possible homology to the epibolic gastrulation of polyclads. The lack of correspondence between polyclads and neoophorans in the relationship of the definitive body axes to the egg axis is discussed, and an hypothesis is advanced to account for the differences. The phylogenetic relationships indicated by known developmental phenomena differ only slightly from the scheme presented by Karling in 1974.     

《组织学与胚胎学》双语教学模式的实践与探讨

《组织学与胚胎学》是医学生必修的医学基础课程之一,约有1/3医学英语词汇与其词汇直接相关,所以探讨其双语教学模式对促进医学双语教学尤为重要.我们先后从双语教学的英汉讲授比例、讲义准备、课件制作等方面探讨提高双语教学水平应注意的问题,并设计了双语教学的问卷调查,结果表明大部分同学认为双语教学对提高专业英语、普通英语水平和英语运用能力及专业课成绩有较大的帮助,并且用SPSS13.0软件将其平均分与传统教学的平均分进行了统计分析,P＜0.05,有统计学意义.该课程的双语教学,得到大多数医学生的肯定,教学水平也得到很大的提高.     

灯盏花大小孢子形成与胚胎发育

用石蜡切片法对灯盏花从花原基分化到胚胎形成的全过程进行系统观察,结果表明:灯盏花从初孕花序至头状花序的直径(d)在2.8～3.1 mm时为花器官分化期,包括花原基分化期、花萼与花冠分化期、雌雄蕊分化期以及分化完成期4个阶段;灯盏花花药4室,药壁发育属双子叶型,绒毡层细胞属于变形绒毡层;小孢子母细胞减数分裂为同时型,成熟花粉为3-细胞型;子房下位,1室,单珠被,薄珠心,胚珠倒生,胚囊发育为蓼型;珠孔受精,属于有丝分裂前类型,胚乳发育为细胞型,胚胎发育应属紫菀型.     

Embryology of Clitoria ternatea (Fabaceae)

ABSTRACT

The embryology of Clitoria ternatea was studied. Anthers contain four sporangia. The anther wall comprises an epidermis, an endothecium, a middle layer and a glandular tapetum. Microspore tetrads are tetrahedral and pollen grains are shed at the 2-cell stage. The ovule is campylotropous, bitegmic and crassinucellate. The micropyle is formed by both the integuments. The megaspore tetrad is linear or T-shaped. The chalazal megaspore is functional and embryo sac development follows the monosporic Polygonum type. Endosperm development is of the nuclear type. The chalazal part of the endosperm forms a haustorium. Embryo development follows the Onagrad type.     

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.     

一类神经传播方程的特征差分方法与分析

首先对给定的方程进行恒等变换,再把MMOCAA差分方法与UNO插值相结合,提出了方程的MMOCAA-UNO差分方法,避免了基于k次Lagrange插值的MMOCAA差分方法在方程的解的陡峭前沿附近产生振荡．通过引入插值算子等方法给出了格式的误差估计．数值实验说明理论分析的正确性和格式的有效性．     

Left cardiac sympathetic denervation in the Netherlands for the treatment of inherited arrhythmia syndromes

Introduction

Treating therapy-resistant patients with inherited arrhythmia syndromes can be difficult and left cardiac sympathetic denervation (LCSD) might be a viable alternative treatment option. We provide an overview of the indications and outcomes of LCSD in patients with inherited arrhythmia syndromes in the only tertiary referral centre in the Netherlands where LCSD is conducted in these patients.

Methods

This was a retrospective study, including all patients with inherited arrhythmia syndromes who underwent LCSD in our institution between 2005 and 2013. LCSD involved ablation of the lower part of the left stellate ganglion and the first four thoracic ganglia.

Results

Seventeen patients, 12 long-QT syndrome (LQTS) patients (71 %) and 5 catecholaminergic polymorphic ventricular tachycardia (CPVT) patients (29 %), underwent LCSD. Most patients (94 %) were referred because of therapy-refractory cardiac events. In 87 % the annual cardiac event rate decreased. However, after 2 years the probability of complete cardiac event-free survival was 59 % in LQTS and 60 % in CPVT patients. Two patients (12 %) had major non-reversible LCSD-related complications: one patient suffered from a Harlequin face post-procedure and one severely affected LQT8 patient died the day after LCSD due to complications secondary to an arrhythmic storm during the procedure.

Conclusion

LSCD for inherited arrhythmia syndromes, which is applied on a relatively small scale in the Netherlands, reduced the cardiac event rate in 87 % of the high-risk patients who had therapy-refractory cardiac events, while the rate of major complications was low. Therefore, LSCD seems a viable treatment for patients with inherited arrhythmia syndromes without other options for therapy.     

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     

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.     

Antiarrhythmic effect of magnesium sulfate against occlusion-induced arrhythmias

The antiarrhythmic effect of magnesium sulfate (Mg) as well as the hemodynamics were studied using the coronary ligation and reperfusion models in rats.In the study on coronary ligation arrhythmia, i.v. administration of Mg (0.6, 2, 6, 20 and 60 \sgmaelig;mol) was conducted at 5 min after coronary ligation. Mg had an action to decrease the total number of premature ventricular contraction (PVC), the duration of ventricular tachycardia (VT), the frequency of VT and ventricular fibrillation (Vf) and the mortality ratio for 30 min after coronary ligation. In the 6-60 \sgmaelig;mol groups, significant antiarrhythmic action (p < 0.01 vs. control) was attained.In the study on reperfusion arrhythmia, i.v. administration of Mg (20, 60 and 200 \sgmaelig;mol) was conducted at 4 min after coronary ligation, and at 1 min after ligation, the coronary artery was reperfused. Mg had an action to decrease the frequency of Vf, the mortality ratio and the duration of VT and Vf and to extend the interval between the initiation of reperfusion and the occurrence of VT and Vf for 10 min after reperfusion. In the 200 \sgmaelig;mol group, significant antiarrhythmic action (p < 0.05 vs. control) was attained. Administration of Mg decreased the heart rate and blood pressure.We concluded that Mg can control myocardial ischemia-induced and reperfusion-induced arrhythmia and that sudden cardiac death which occurs as a result of arrhythmia can be prevented.     

Common molecular determinants of flecainide and lidocaine block of heart Na+ channels: evidence from experiments with neutral and quaternary flecainide analogues

Flecainide (pKa 9.3, 99% charged at pH 7.4) and lidocaine (pKa 7.6-8.0, approximately 50% neutral at pH 7.4) have similar structures but markedly different effects on Na(+) channel activity. Both drugs cause well-characterized use-dependent block (UDB) of Na(+) channels due to stabilization of the inactivated state, but flecainide requires that channels first open before block develops, whereas lidocaine is believed to bind directly to the inactivated state. To test whether the charge on flecainide might determine its state specificity of Na(+) channel blockade, we developed two flecainide analogues, NU-FL (pKa 6.4), that is 90% neutral at pH 7.4, and a quaternary flecainide analogue, QX-FL, that is fully charged at physiological pH. We examined the effects of flecainide, NU-FL, QX-FL, and lidocaine on human cardiac Na(+) channels expressed in human embryonic kidney (HEK) 293 cells. At physiological pH, NU-FL, like lidocaine but not flecainide, interacts preferentially with inactivated channels without prerequisite channel opening, and causes minimal UDB. We find that UDB develops predominantly by the charged form of flecainide as evidenced by investigation of QX-FL at physiological pH and NU-FL investigated over a more acidic pH range where its charged fraction is increased. QX-FL is a potent blocker of channels when applied from inside the cell, but acts very weakly with external application. UDB by QX-FL, like flecainide, develops only after channels open. Once blocked, channels recover very slowly from QX-FL block, apparently without requisite channel opening. Our data strongly suggest that it is the difference in degree of ionization (pKa) between lidocaine and flecainide, rather than gross structural features, that determines distinction in block of cardiac Na(+) channels. The data also suggest that the two drugs share a common receptor but, consistent with the modulated receptor hypothesis, reach this receptor by distinct routes dictated by the degree of ionization of the drug molecules.     

Calreticulin in the heart

Calreticulin is a Ca²⁺ binding/storage chaperone resident protein of the endoplasmic reticulum. This protein plays a key role in the calreticulin/calnexin cycle and the quality control pathways in the endoplasmic reticulum. Calreticulin deficiency is lethal due to impaired cardiac development. However, over-expression of the protein in developing and postnatal heart leads to bradycardia, complete heart block and sudden death. Ultrastructural evidence indicates that the deficiency associated with the absence of calreticulin in the heart may be due to a defect in the development of the contractile apparatus and/or a defect in development of the conductive system as well as a metabolic abnormality. Collectively, we postulate that calreticulin and endoplasmic reticulum plays an important role in cardiac development and postnatal pathologies. (Mol Cell Biochem 263: 137–142, 2004)