酸中毒后室性心律失常仿真研究

本文旨在分析酸中毒对心脏电生理活动的影响,探讨其诱发室性心律失常的机制.首先建立了具有pH和钙/钙调素依赖蛋白激酶Ⅱ(calcium/calmodulin dependent protein kinaseⅡ,Ca MKⅡ)调控作用的人体心室酸中毒计算模型,然后模拟了酸中毒过程中细胞和组织电活动的变化,并定量分析了心电图的改变情况.实验结果表明:在酸中毒期间,细胞动作电位时程的缩短和复极离散度的降低导致心电图QT间期缩短、T波幅值和宽度减小.同时,细胞静息电位的抬高和最大去极化速率的降低也促进了组织电兴奋的缓慢传导和传导阻滞.另外,酸中毒后的初期,肌浆网钙超载促进钙释放增多,导致细胞产生延迟后除极(delayed afterdepolarization,DADs),使心电图上表现为室性早搏.而缓慢传导、传导阻滞和室性早搏有利于折返波的产生,进而发展为室速.因此,酸中毒后细胞的触发活动是诱发室性心律失常的主要原因之一.     

单相动作电位技术在猫在体心脏触发性活动研究中的应用

应用接触电极记录心脏单相动作电位(MAP)是80年代发展起来的新技术。MAP是心肌局部细胞群的电活动,它与单细胞跨膜动作电位(TAP)具有基本相同的形态、间期和复极化过程。自1985年开始,很多研究者将其用于在体心脏触发性活动的研究。触发性活动是近年来提出的心律失常发生机制的新概念,包括早期后去极化(EAD)、延时性     

全心缺血早期阶段室性心律失常仿真研究

为了分析全心缺血早期阶段对心脏电生理活动的影响,以及探讨诱发的室性心律失常机制,本研究考虑了缺血情况下高钾、酸液过多、局部缺氧的情况,结合详细的人类心室细胞生物物理上的动力学特征,开发了一个人体心室细胞和组织全心缺血模型.实验结果表明,全心缺血缩短了动作电位时程(action potential duration,APD),且减缓了兴奋的传导速率(conduction velocity,CV).同时,由于全心缺血降低了动作电位时程曲线(action potential duration restitution,APDR)斜率,且增大了有效不应期(effective refractory period,ERP),因此有利于维持折返波的稳定传导,使得室速不易转化为室颤.另一方面,尽管全心缺血导致了组织易感性的增加,但是由于其需要更长的异位刺激长度来保证折返波的形成,因此也在一定程度上降低了心律失常的发生概率.     

用单相动作电位研究触发性心律失常

触发性心律失常(triggered arrhythmia)以冲动起源异常机制为特征受到临床的普通重视。近年来,接触电极或接触电极导管记录人或动物心内、外膜单相动作电位新技术的出现,为在整体动物或人心脏上获得触发性活动提供了前提。目前,单相动作电位(mono-phasic action Potential,MAP)已用于冠状动脉搭桥术中的局部心肌缺血、心肌电生理     

右室流出道室性心动过速的发生机制研究进展

右心室流出道室性心律失常是临床上常见的特发性心律失常,占特发性室速的60%~70%,绝大多数右心室流出道室速为腺苷敏感性,其发病机制为儿茶酚胺介导的延迟后除极和触发活动。其发生机制一直是电生理领域研究的热点问题,新近研究表明,L型钙通道的改变与特发性右心室流出道室性心动过速的发生密切相关,提示L型钙通道可能会成为特发性右心室流出道室性心动过速治疗的新靶点。     

组胺致豚鼠心室乳头肌早发后去极化和触发活动的研究

采用微电极细胞内记录和电子计算机实时采样技术,研究了组胺致豚鼠心室乳头肌早发后去极化和触发活动。组胺(6.0μmol/L)可使动作电位APD_(50)、APD_(90)明显缩短(数据取自无异常自律性和振荡电位的细胞)。组胺可诱发早发后去极化(发生率57％),振荡电位和触发活动。早发后电位在低频驱动(0.2～1.0Hz)时易于发生且常常伴有动作电位时程的延长。触发活动可表现为快速自发性动作电位(发生率14％)。结果提示,组胺诱发的早发后去极化和触发活动可能和心性过敏反应等疾病发生的快速自律型心律失常有关。     

CRT_D介导室性心动过速的研究进展

心室再同步心脏转复除颤器（CRT）可有效改善心力衰竭（CHF）患者的运动耐量和生活质量,预防猝死,提高生存率,但_DCHFCRTD植入后由于心室激动顺序的改变,使QT间期延长、跨室壁复极离散度（TDR）增加,潜在致室性心律失常风险;且CHF患者通常存在心肌解剖改变,传导的不均一性,也为折返性心动过速的发生提供了维持的机制;而多次电击也可导致肌钙蛋白升高,引起心肌损伤,局部心肌复极离散度增加（DRVR）和QT间期延长,以及电除颤后心肌纤维化和急性细胞损伤,反复室速、室颤也会引起进行性左心功能不全、心肌细胞凋亡、恶化心律失常基质和增加心律失常易感性。CRT_D潜在致室性心律失常作用逐渐引起人们的重视,本文就近年来CRTD致室性心律失常的电生理机制与临床防治对策等做一综述。     

CRT_D介导室性心动过速的研究进展

心室再同步心脏转复除颤器(CRT_D)可有效改善心力衰竭(CHF)患者的运动耐量和生活质量,预防猝死,提高生存率,但CRT_D植入后由于心室激动顺序的改变,使QT间期延长、跨室壁复极离散度(TDR)增加,潜在致室性心律失常风险;且CHF患者通常存在心肌解剖改变,传导的不均一性,也为折返性心动过速的发生提供了维持的机制;而多次电击也可导致肌钙蛋白升高,引起心肌损伤,局部心肌复极离散度增加(DRVR)和QT间期延长,以及电除颤后心肌纤维化和急性细胞损伤,反复室速、室颤也会引起进行性左心功能不全、心肌细胞凋亡、恶化心律失常基质和增加心律失常易感性。CRT_D潜在致室性心律失常作用逐渐引起人们的重视,本文就近年来CRT_D致室性心律失常的电生理机制与临床防治对策等做一综述。     

晚钠电流在获得性心血管病合并心律失常发生中的作用及其意义

心肌细胞的晚钠电流出现于动作电位的复极期,正常心肌细胞存在内源性晚钠电流,幅度小;晚钠电流幅度增大可见于长QT综合征3、4、9、10和12型,也见于多种病理及药物作用下,导致动作电位时程延长,诱发恶性室性心律失常,如尖端扭转型室性心动过速等;同时由于平台期延长,钙离子内流时间延长,改变心肌收缩力并参与钙相关心律失常的发生。近年来,随着对心血管疾病及其合并心律失常发病机制的深入认识,发现越来越多的获得性心血管疾病患者心律失常的发生与晚钠电流异常增大相关,极大地扩大了晚钠电流相关心律失常的范畴,选择性晚钠电流抑制剂已成为抗心律失常药物新的亚类。     

在体心脏后去极化及触发性心律失常的细胞电生理学研究

应用漂浮微电极记录跨膜动作电位(TAP)和接触电极记录单相动作电位(MAP)两项技术,研究了 CsCl 诱发的猫在体心脏的触发性活动。结果表明,静脉注射 CsCl(0.5mmol/kg)后10s,左心室外膜 TAP 和 MAP 的3相中晚期出现早期后去极化(EAD),在30s 时,TAP上 EAD 的振幅为25.6±9.3mV,MAP 上的 EAD 振幅为3.4±1.3mV。EAD 表现为拖尾、平台、凸起三种不同形态。在两例猫中出现延迟性后去极化 DAD,其在 TAP 和 MAP上的振幅分别为13.0±5.3mV 和3.3±0.omV。MAP 上后去极化的形态与 TAP 极为相似。CsCl 的重复注射可诱发室性早搏、室性心动过速等多种心律失常,根据后去极化的发生与否以及后去极化和室性心搏的耦联间期的关系,可将心律失常分为两种类型:一种是由记录部位的后去极化引起的触发性心律失常;另一类可能由非记录部位的后去极化或其它机制引起。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.