维拉帕米对触发活性的影响

本文使用经典细胞电生理方法,观察维拉帕米对后除极电位和触发活性的影响。4mMBa~(2 )灌注后,心肌标本(n=11)膜电位由83.1±4.4mV降至62.1±3.5mV,动作电位幅值也由119.3±10.1mV降至74.0±6.9mV,表现异常自律性占27.3%(3/11),EAD和DAD触发活性分别占45.4%(5/11)、27.3%(3/11)。维拉帕米灌注(1mg/L)后异常自律性明显减慢,EAD、DAD及相关的触发活性随之消失。这提示,异常自律性和触发活性可能与钙内流有关,维拉帕米具抑制作用。     

延迟后除极与洋地黄所致室性心律失常机制的在体实验研究

目的 研究洋地黄类药物所致在体延迟后除极(DAD)和触发活动的特征，评价延迟后除极与室性心律失常的关系。方法 静脉注射哇巴因结合程序电刺激建立三度房室阻滞犬室性心律失常模型，并采用Franz接触电极记录13只犬左室心内膜单相动作电位(MAP)。结果 10／13(77％)的犬在MAP记录中观察到DAD，DAD幅度为1．09±0．53mV．DAD的发生率呈现快频率依赖性。起搏周长与DAD配对间期呈直线正相关(r=0．877，P<0．01)。62．8%室性早搏(室早)记录到DAD，室早出现于DAD峰上或稍后出现。室早配对间期与DAD配对间期存在显著直线正相关r=0．9875，P<0．01)。在诱发的54次非持续性室性心动过速(室速)中42次(78％)表现为每个室性异位激动起自MAP上DAD的峰顶或稍后，在非持续性室速终止时MAP记录到DAD。9／12(75％)的犬持续性室速中记录刊DAD。结论 哇巴因所致在体犬室性心律失常的机制是延迟后除极所致的触发活动。在体MAP记录技术为延迟后除极和触发活动提供了直接证据。     

弥漫性肺泡损伤增加急性呼吸窘迫综合征患者的死亡风险

目的:研究弥漫性肺泡损伤(DAD)与急性呼吸窘迫综合征(ARDS)患者死亡率的相关性。方法:回顾性分析2016年1月-2019年12月成都市第三人民医院20例接受开放式肺活检(OLB)的ARDS患者的病例资料。依次分析ARDS患者的基本特征及病理诊断,将存活者与死亡者资料进行对比分析。根据有无肺泡弥漫性损伤将患者分成2组:DAD组和非DAD组,对比分析人口学和临床特征;对医院死亡率相关临床变量进行logistic回归分析。结果:ARDS患者病理诊断中11例诊断为DAD,其中7例仅有DAD,4例有DAD合并其他疾病。9例诊断为非DAD,其中4例被归类为感染,3例为肺间质型,2例被归类为混合感染复杂性疾病;存活组和死亡组在开胸肺活检当天的序贯性器官衰竭评估(SOFA)评分和氧合指数(Pa O2/Fi O2)比值比较,差异有统计学意义(P 0. 01或P 0. 05),有ARDS且病理诊断为DAD的患者死亡率明显高于无DAD患者(P 0. 01); logistic回归分析显示,ARDS患者DAD的发生率(比值:3. 554,95%CI:1. 385,9. 120; P 0. 01)和活检日SOFA评分(比值:1. 424,95%CI:1. 187,1. 707; P 0. 01)与医院死亡率显著独立相关。结论:DAD-ARDS患者Pa O2/Fi O2低、高SOFA评分,更易死于难治性低氧血症,而非休克;难治性休克是无DAD患者主要死因。DAD患者的预后比无DAD患者差。DAD发生率与ARDS患者死亡率显著相关。     

急性呼吸窘迫综合征与弥漫性肺泡损伤关系的新认识

急性呼吸窘迫综合征(ARDS)是一种高发病率、高病死率的异质性临床综合征。弥漫性肺泡损伤(DAD)是ARDS典型病理特征,但肺尸检和肺活检发现大约只有一半符合柏林ARDS定义的患者存在DAD。与非DAD-ARDS患者相比,DAD-ARDS患者死亡率显著增高,二者可能存在不同的细胞和分子机制。本文旨在探讨ARDS与DAD的关系及其临床意义,以期为临床上更好地诊治ARDS提供新的思路。     

钙调蛋白激酶Ⅱ信号转导途径在儿茶酚胺敏感性室性心动过速中的作用

目的研究钙调蛋白激酶Ⅱ(CaMKⅡ)特异性抑制剂KN-93对异丙肾上腺素和咖啡因诱导的晚期后除极(DAD)和触发活动的影响,探讨CaMKⅡ磷酸化途径在儿茶酚胺敏感性室性心动过速(CPVT)发生中的作用。方法酶解法分离家兔心室肌细胞,应用全细胞膜片钳技术记录动作电位(AP),采用含1μmol/L异丙肾上腺素和0.3mmol/L咖啡因的正钙台氏液灌流心室肌细胞,在快频率(3Hz)电刺激下,诱发DAD和触发活动,建立CPVT细胞模型。在此基础上应用KN-93(1μmol/L)和KN-92(1μmol/L)进行灌流,观察KN-93和KN-92对DAD和触发活动诱发率的影响。结果在1μmol/L异丙肾上腺素和0.3mmol/L咖啡因的正钙台氏液灌流下,3Hz时DAD和触发活动的诱发率达到18/20和6/20,建模成功。KN-93组、KN-92组DAD的发生率为8/20、18/20,触发活动的发生率为6/20、19/20。结论CaMKⅡ信号转导途径可能是CPVT发生的主要作用机制之一。     

心肌组织多普勒评价急性下壁心肌梗死的右心功能

目的　应用心肌组织多谱勒技术 (TDI)结合 M型超声评价急性下壁心肌梗死 (AIWMI)患者右心室整体功能。方法　正常对照组 2 0例 ,AIWMI2 0例 ,在标准心尖四腔心切面 ,采用 M超记录三尖瓣环右心室游离壁处运动曲线 ,测量右心室收缩期、舒张早期与晚期最大运动幅度 (SD、DED、DAD)及其平均速度 (SV、DEV、DAV ) ,求出舒张早期和舒张晚期最大运动幅度比值 (DED/ DAD)。应用 TDI技术测量上述各期峰值运动速度 (Sm、Em和 Am ) ,求出舒张早期峰值运动速度 (Em)和舒张晚期峰值运动速度 (Am )的比值 (Em / Am )。结果　与对照组相比 ,AIWMI组 SD、DED、SV、DEV、DED/ DAD均显著降低 ,Sm、Em及 Em/ Am比值也显著降低。结论　 TDI可以评价心肌梗死后右心室整体功能     

住院老年跌交病人的隐匿性肌肉损伤

自1960年起,血清肌酸激酶(CK)活性作为肌肉损伤的敏感指示剂已广泛应用,随后认识到CK异构酶(MM,MB和BB)可增加诊断的特异性。     

自噬在糖尿病心肌病发病机制中的作用研究进展

糖尿病心肌病(diabetic cardiomyopathy,DCM)是糖尿病患者发生心力衰竭和死亡的重要原因.过度自噬导致心肌受损,可能是DCM的发生发展机制之一.本文对自噬在DCM发生发展机制中的作用进行综述.NF-E2相关因子2(Nrf2)除对抗氧化损伤,还可通过负性调控AMPK抑制过度自噬.增加Nrf2活性可抑制AMPK-ULK1-Beclin1通路,降低自噬活性,减轻DCM所致心肌损伤,有望为DCM的防治提供新方向.     

单纯急性下壁心肌梗死及其合并右心室心肌梗死对右心长轴功能的影响

目的应用心肌组织多普勒技术结合M型超声心动图,评价单纯急性下壁心肌梗死及其合并右心室心肌梗死对右心室长轴功能的影响。方法选择首次急性下壁心肌梗死患者28例,分为单纯急性下壁心肌梗死18例(Ⅰ组),急性下壁心肌梗死伴右心室心肌梗死10例(Ⅱ组),另选健康体检者20例(Ⅲ组)。在标准心尖四腔心切面二维图像指引下,应用M型超声记录右心房室环右心室游离壁及中心纤维支架处运动曲线,测量收缩期、舒张早期、舒张晚期最大运动幅度(SD,DED,DAD)及收缩期、舒张早期、舒张晚期平均运动速度(SMV,DEMV,DAMV),计算DED/DAD比值。心肌组织多普勒记录该处运动速度曲线,测量上述各期最大运动速度(Sm、Em、Am)及Em/Am比值。结果与Ⅲ组比较,Ⅰ组和Ⅱ组右心房室环右心室游离壁处SD、DED、DED/DAD、SMV、DEMV、Sm及Em均明显下降。DAD、DAMV、Am虽有下降,但差异无统计学意义。结论急性下壁心肌梗死无论是否合并右心室心肌梗死均可影响右心室长轴功能,导致右心室整体功能降低。     

钙调蛋白激酶Ⅱ信号途径与肥厚心肌心律失常

多种心血管疾病均可引起心肌肥厚,严重者可导致恶性室性心律失常,引起心源性猝死。室性心律失常发生与肥厚心肌电重构有密切关系,肥厚心肌更易发生早期后除极(EAD)或延迟后除极(DAD)。Ca2 作为第二信使,通过其浓度在空间和时间上的变化将信号转化为广泛多样的生物化学效应,如维     

维拉帕米对缺血-再灌注豚鼠乳头肌电生理的保护作用

目的:研究再灌注心律失常发生机制及维拉帕米的保护作用.方法:采用标准微电极细胞电生理方法.结果:对照组RMP,APA,APD50,Vmax,ERP随缺血时间的延长而降低,随正常充氧台氏液的复灌而回复,20分钟后恢复对照状态.维拉帕米治疗组复灌20分钟除ERP,APD90外APA,APD50,Vmax未恢复至对照状态.对照组10例标本均发生了再灌注心律失常,6/10例为室早,5/6例于复灌4.5±2.6分钟时出现DAD或EAD,并发生触发性室早.4/10例发生持续性心动过速,持续10.4±5.0分钟.快速起搏可以超速抑制,但不能终止.治疗注组8/10例未出现心律失常,仅2/10例发生室早,均未记录到EAD或DAD.结论:触发活动及自律性增高是再灌注心律失常的主要发生机制,维拉帕米可有效地拮抗再灌注心律失常的发生.     

Relation of monophasic action potential recorded with contact electrode to underlying transmembrane action potential properties in isolated cardiac tissues: a systematic microelectrode validation study

Monophasic action potentials, recorded with contact non-suction electrodes, have been used both clinically and experimentally. However, to date no systematic microelectrode validation studies have been done to underlying myocardial cell populations from different myocardial regions with different transmembrane potential profiles. In the present study transmembrane action potential properties, recorded with standard microelectrodes, were compared with monophasic action potentials recorded with contact electrodes in three different (endocardium, epicardium, and free running Purkinje fibre) isolated canine preparations during pacing and during spontaneous automatic activity. The mean transmembrane durations at 50% and 90% repolarisations (APD50 and APD90) of 19-30 cells at a monophasic action potential recording site was not statistically significant from monophasic action potential duration in all three tissue preparations studied. However, in endocardial preparations, composed of superficial (1-2 cell layers) Purkinje fibres with deeper ventricular muscle cells, the APD50 (139(17) ms) and APD90 (181(26) ms) of monophasic action potentials more closely reflected (but not significantly different) the underlying deeper ventricular muscle cells (APD50 134(14) ms and APD90 167(15) ms) rather than the mean transmembrane action potential durations of the underlying most superficial Purkinje fibres (166(22) ms for APD50 and 210(30) ms for APD90) (p less than 0.025). Tetrodotoxin (TTX) at 1 x 10(-6) mol.litre-1 shortened Purkinje fibre action potential duration and slightly lengthened that of ventricular muscle. Simultaneously recorded monophasic action potential showed an intermediate change in action potential duration. Incremental pacing and applied single premature stimuli resulted in similar degrees of shortening of action potential duration for both monophasic action potential and transmembrane potential in all three preparations. In endocardial preparations, barium chloride (4 mmol.litre-1) superfusion induced early afterdepolarisations, and spontaneous phase 4 depolarisations (n = 6) in both Purkinje and ventricular muscle cells giving rise to spontaneous automatic activity. These abnormal automatic activities were accurately detected by simultaneous monophasic action potential recordings. Suppression of automaticity by verapamil (0.2-0.5 micrograms.ml-1) as confirmed by transmembrane action potential recordings were similarly detected by monophasic action potential recordings (ABSTRACT TRUNCATED AT 250 WORDS)     

Arrhythmogenic Effects of Quinidine on Catecholamine-Induced Delayed Afterdepolarizations in Canine Atrial Fibers

Arrhythmogenic Effects of Quinidine on Catecholamine-induced Delayed Afterdepolarizations. We studied the effects of quinidine and tetrodotoxin (TTX), two drugs that block Na⁺ channels, on delayed afterdepolarizations (DAD) caused by norepinepbrine in atrial fibers of the canine coronary sinus. At long stimulus cycle lengths of 10 seconds, quinidine increased the amplitude of the afterdepolarizations and caused triggered activity within 1–2 minutes. Simultaneously, action potential duration (APD) was lengthened but upstroke velocity was not decreased. Prolonged exposure to quinidine eventually decreased upstroke velocity but DAD amplitude remained larger than control and triggered activity was still induced more easily. The effects of quinidine to increase afterdepolarizations was partially related to its prolongation of the APD since shortening APD with repolarizing current decreased DAD amplitude. However, DAD amplitude remained larger than control indicating that quinidine caused triggering by other mechanisms as well. TTX, on the other hand, which blocks Na⁺ channels but shortens APD, decreased DAD amplitude and triggered activity. Part but not all of these effects resulted from the shortening of APD by TTX since prolongation of APD with depolarizing current only partially restored DAD amplitude. Anti-arrhythmic drugs, therefore, may have effects on DADs that partly result from changes in the APD. Quinidine may cause cardiac arrhythmias by virtue of its effects to potentiate triggered activity.     

Effects of tetrodotoxin on electrical and mechanical activity of cardiac Purkinje fibers

Canine Purkinje and ventricular muscle fibers were superfused in vitro and the actions of tetrodotoxin (TTX, 1.56 X 10(-5) - 3.2 X 10(-7) M) on both electrical and mechanical events were studied. Tetrodotoxin reduced the amplitude of the upstroke, markedly shortened the plateau, reduced the maximum diastolic potential and decreased contractile force in Purkinje fibers. Citrate (present in the TTX solution) did not have any effect on electrical and mechanical events. The modifications induced by TTX occurred whether external calcium concentration was normal, high or low. Furthermore, high calcium increased force by a similar extent whether TTX was present or not. TTX has little effect on slow action potentials due to the activation of the slow channel. Action potential duration and force were affected similarly by TTX as a function of concentration, of time of exposure and of rate of discharge. Also, TTX abolished action potentials due to a partially activated fast sodium current and reduced action potential duration and force much less in ventricular muscle than in Purkinje fibers. It is concluded that the effects of TTX are primarily related to a reduction of sodium influx during the action potential and that the fall in force is an indirect consequence of reduced sodium influx.     

Histamine induced or enhanced delayed afterdepolarization and triggered activity in guinea-pig papillary muscles. A preliminary study

We used standard microelectrode techniques to study the histamine induced or enhanced delayed afterdepolarization (DAD) and triggered activity (TA) of guinea-pig papillary muscle superfused with low-potassium Tyrode's solution. Before histamine, a series of driven action potentials did not induce DAD and TA. Immediately after histamine (10(-5)M), DAD was induced and, finally, TA was induced after high rate pacing (150/min to 300/min). The effect of histamine was antagonized by cimetidine (5 X 10(-6) to 5 X 10(-5)M) but not by diphenhydramine. Also, the amplitude of DAD decreased after verapamil (10(-7) to 3 X 10(-6)M) and lidocaine (4 X 10(-5) to 8 X 10(-5)M). To investigate indirect evidence of increased cyclic AMP mediation in this histamine induced DAD, we studied the effects of a phosphodiesterase inhibitor (papaverine 10(-5)M) or activator (N-methylimidazole 20 mM) on the histamine induced or enhanced DAD. The former enhanced and the latter depressed the histamine-induced (or enhanced) DAD. Thus, histamine may induce or enhance the DAD and TA by increasing the slow inward current. This mechanism may be mediated by histamine H2-receptors and the adenylate cyclase system in the cardiac ventricular muscle.     

Insight into the mechanism of torsade de pointes (TDP) induced by cesium chloride]

Standard intracellular potential recording technique was used in isolated guinea pig ventricular muscle and monophasic action potential (MAP) recording technique was performed on both the epicardium and endocardium of dog hearts in vivo. The results showed that CsCl lengthened action potential durations of ventricular muscle as well as QT intervals of dog hearts. The incidence of early after depolarization (EAD) induction was 71.4%. Ventricular tachycardia induced by CsCl manifested as typical TdP in 44.4% with EAD shown on epicardial MAP recording. This suggested that EAD and triggered activity might be an important mechanism of TdP. As verapamil could depress the induction of EAD, we believe that Ca++ inward currents was responsible for the induction of EAD and TdP by CsCl.     

普罗帕酮、维拉帕米对豚鼠乳头肌延迟后除极和触发电活动的影响

应用标准玻璃微电极技术，研究哇巴因诱发豚鼠心室乳头肌的延迟后除极（ＤＡＤ）和触发电活动（ＴＡ）的变化规律及特点；探讨普罗帕酮和维拉帕米对ＤＡＤ和ＴＡ的影响。结果表明：①心室肌细胞在高浓度Ｃａ２＋条件下加哇巴因灌流时可以出现ＤＡＤ及ＴＡ，ＴＡ的诱发率为７７．８％（７／９）。②心室肌细胞诱发的ＤＡＤ幅度（ＤＡＤ－Ａｍｐ）、ＤＡＤ偶联间期（ＤＡＤ－Ｃ）和ＤＡＤ升支上升速率（ＤＡＤ－ｄｖ／ｄｔ）呈明显的频率依赖性，即刺激频率愈快，ＤＡＤ－Ａｍｐ愈高、ＤＡＤ－ｄｖ／ｄｔ愈快，ＤＡＤ－Ｃ则愈短。③上述两种抗心律失常药物均通过降低ＤＡＤ－Ａｍｐ、减慢ＤＡＤ－ｄｖ／ｄｔ和延长ＤＡＤ－Ｃ而发挥其抗触发性心律失常作用；两者对哇巴因诱发的ＤＡＤ和ＴＡ的抑制作用无显著性差异，在普罗帕酮或维拉帕米的作用下，哇巴因对ＴＡ的诱发率分别为３３．３％（３／９）和２２．２％（２／９），与哇巴因的诱发率（高钙条件下，７７．８％）比较Ｐ＜０．０１。     

四氢巴马汀抗触发性室性心律失常作用机制的研究

目的 了解四氢巴马汀对哇巴因诱发家兔在体心脏延迟后除极和触发性室性心律失常的影响及作用机制。方法 家兔１４只,分为四氢巴马汀组和对照组,记录家兔右室单相动作电位和体表Ⅱ导联心电图,比较用哇巴因前后两组的单组动作电位和心电图变化。结果 两组的延迟后除极发生率和迟后除极配对间期差异无显著性,Ｐ〉０．０５,但四氢巴马汀组的迟后除极振幅和触发性室性心律失常的发生率明显低于对照组,Ｐ〈０．０５。结论 四氢巴     

醛固酮对心肌细胞钙稳态及电生理特性的影响

目的:探讨醛固酮致心律失常机制与钙稳态失调的关系。方法:分离心室肌细胞,随机分为对照组和醛固酮组,采用全细胞膜片钳记录方法记录延迟后除极(DAD)、触发活动,共聚焦显微镜记录钙火花。结果:醛固酮组发生DAD为24/30,对照组为7/30,P<0.05;对照组发生触发活动为5/30,醛固酮组为20/30,P<0.05。钙火花的空间范围:对照组为(0.011±0.001)s-1.m,醛固酮组为(0.024±0.001)s-1.m,P<0.05;钙火花幅度:对照组为(1.03±0.07)F/F0,醛固酮组为(1.46±0.10)F/F0,P<0.05。钙火花持续时间:醛固酮组为(7.0±0.9)ms,对照组为(13.0±1.2)ms,P<0.05。结论:醛固酮可能通过调节胞内钙产生促心律失常作用。