长QT综合征与心律失常

长QT综合征(LQTS)是以心电图QT间期延长，临床反复发生尖端扭转型室速(Tdp)和晕厥为特征的一组综合征。遗传性和获得性两类，长QT间期综合征可以相互重叠。QT间期延长和心律失常二者可以互为因果。遗传性长QT综合征本身可以导致尖端扭转型室速和室颤，获得性长QT综合征通常由于抗心律失常药物和吩噻嗪类药物、低     

中层心肌细胞分布与长QT综合征中折返激动发生机制的计算机仿真研究

中层心肌 (M)细胞的分布是决定心室不应期空间分布的重要参数。特定离子通道的基因突变是产生遗传性长QT综合征的基础。但在离子通道水平上对M细胞分布状态与长QT综合征中尖端扭转型室性心动过速 (Tdp)折返机制关系的理论研究甚少。用Luo Rudy心室肌细胞动作电位模型LRd0 0进行二维心室肌组织仿真研究。采用特定M细胞岛形分布观察心室激动的跨壁传播特点。通过设置快速延迟整流钾电流 (IKr)通道的电导为零 ,模拟动物实验中灌注d sotalol阻断IKr形成LQT2模型 ,并在四种仿真条件下观察复极跨壁异质性的特征。在LQT2模型中 ,动作电位的时程延长 ,复极跨壁分布的最大值从对照条件下的 1 5ms/mm延长至 2 5ms/mm ,提示动作电位跨壁复极离散度增大。在LQT2模型中 ,M细胞岛形分布形状对不应期的空间分布起着重要的决定性作用。传导阻滞、Tdp形成、以及壁内折返环的维持均与M细胞的分布形状有关。结论 :M细胞的特征分布是产生不应期在空间上异质性的基础。不应期的局部延长是产生功能性折返的基础。在长QT综合征中 ,M细胞的特征分布对Tdp的折返形成起着重要的作用     

钠通道阻断剂对模拟在体犬LQT3跨室壁复极离散影响的实验研究

目的:观察心率减慢时模拟体内长QT综合征第3型(LQT3)动作电位时程(APD)和跨室壁复极离散(TDR)的变化及钠通道阻断剂美西律对这种变化的影响,为先天性LQT3室性心律失常的防治提供实验依据。方法:采用自制电极记录犬体内左心室前壁跨室壁单相动作电位,静脉注射海葵毒素(ATX-Ⅱ)模拟LQT3,消融窦房结后改变心房起搏周长(PCL)控制心室率。结果:静脉注射ATX-Ⅱ(3μg／kg)后成功模拟出LQT3模型; PCL为500 ms和1000 ms时ATX-Ⅱ使TDR均显著性增加[分别为(20±4)ms:(41±9)ms和(39±5)ms:(83 ±10)ms,均P<0．05],但PCL为1 000 ms比500 ms时TDR的增加幅度(ATDR)更为明显[(44±13);(20± 12)ms,P<0．05],伴随起源于中层心肌细胞的早期后除极和自发性室性心动过速发生;美西律(20μg／kg)能逆转ATX-Ⅱ的这种电生理作用。结论:LQT3室性心律失常的发生呈慢心室率依赖性,美西律可能对先天性 LQT3猝死的防治有一定的作用。     

LQT2模型室性心律失常电生理机制研究

为探讨心室肌跨壁复极离散度 (TDR)和心脏兴奋的恢复性质在长QT综合征 (LQTS)室性心律失常发生过程中的作用 ,应用冠状小动脉灌流的兔左室肌楔形组织块标本 ,分模型组和对照组 ,采用浮置玻璃微电极法同步记录心室肌内、外膜心肌细胞动作电位和跨壁心电图。模型组以 30 μmol/L的d sotalol台氏液灌流 ,制备LQT2模型。对照组以标准台氏液灌流。结果 :模型组和对照组比较TDR有显著性差异 (83.6± 14 .0msvs 4 8.6± 5 .3ms,P <0 .0 1,n =10 )。模型组内、外膜动作电位时程 (APD)恢复曲线最大斜率均大于 1,而对照组均小于 1,两组间APD恢复曲线最大斜率比较有显著性差异 (P <0 .0 1,n =2 0 )。模型组在S1S2 程序刺激下尖端扭转型室性心动过速的发生率为70 %。对照组无 1例发生室性心律失常。结论 :心脏兴奋的恢复性质和心室肌TDR均参与了LQT2室性心律失常的发生。     

早期后除极与再灌注心律失常机理的实验研究

再灌注心律失常已引起日益广泛的重视,但其发生机理尚未完全阐明。笔者应用心内膜接触电极导管,记录犬缺血及再灌注时在体心脏左室心内膜单相动作电位(MAPs)。10只犬,建立缺血(20分钟)—再灌注模型18次,66％(12/18)于再灌注时记录到早期后除极(EADs),其平均振幅为3.9±1.2mV,占MAPs振幅的22％。其中75％(9/12)发生与EADs有关的心律失常,EADs的耦联间期与室性早搏的耦联间期高度相关(r=0.71,P<0.01)。3只犬EADs振幅呈高低变化时,伴有左心腔电图T波电压交替变化。研究结果表明,EADs诱发的触发活动可能为再灌注心律失常的主要发生机理。MAPs技术是研究在体心脏触发活动的可靠方法。在某些特殊病例,EADs振幅的交替变化,可能是体表心电图T波电交替的发生机理。     

兔LQT2模型时空复极异质性变化与室性心律失常发生的关系

为探讨心室跨壁复极离散度(TDR)和动作电位时程(APD)恢复性质的变化在LQT2室性心律失常发生中的作用,笔者采用冠状动脉灌注的兔左室肌楔形组织块制备LQT2模型。标本随机分四组:对照组(标准台氏液灌注);LQT2模型(简称模型)组(100μmol/Ld,l-sotalol灌流);模型+低钾(3mmol/L)组和模型+低钾+维拉帕米(2μmol/L)组。观察不同基础周长(BCL)刺激(500,1000和2000ms)条件下,四组标本APD90、TDR和APD恢复性质的变化与室性心律失常发生的关系。结果:①在不同BCL条件下,与对照组相比,模型组、模型+低钾组及模型+低钾+维拉帕米组的内外膜心肌细胞的APD90均增大,以内膜心肌细胞的APD90增大显著,导致TDR增加。②BCL为500和1000ms时,与对照组相比,模型组、模型+低钾组的APD恢复曲线斜率显著增加,而模型+低钾+维拉帕米组,差异无显著性。③在BCL为1000和2000ms时,给予S1S2程序刺激,模型+低钾组尖端扭转性室性心动过速发生率为5/7。结论:TDR增大和APD恢复性质的变化在室性心律失常的发生中均起着重要的作用。     

长QT综合征复极化离散与早期后除极致心律失常机制的跨壁光学标测研究

目的　尖端扭转性室性心动过速 (室速 )是长QT综合征 (LQTS)的致命性心律失常 ,相关机制的细胞学水平研究还不十分清楚。本文报道对复极化离散和触发机制在尖端扭转性室速发生中的作用的研究结果。方法　动脉灌注的犬左心室楔形心肌块 ,经电压敏感性荧光染色后 ,行跨壁包括百余位点跨膜动作电位的同步光学标测研究。d 索他洛尔、海银花 (ATX Ⅱ)分别用来模拟LQT2和LQT3。对照组、LQT2组、LQT3组各 6块。结果　正常对照组的平均动作电位时限 (APD)为 (2 91± 2 7)ms,跨壁复极化的离散(DOR)为 (2 4± 6 )ms;LQT2组APD为 (35 6± 2 0 )ms,DOR为 (35± 9)ms,与对照组相比差异有显著性 (P <0 0 5 ) ;LQT3组APD为 (6 0 9± 92 )ms,DOR为 (12 1± 85 )ms,与对照组相比差异有显著性 (P <0 0 5 )。在LQT3组 ,早期后除极现象可见于所有类型的心肌细胞 ,但以心内膜和中层心肌细胞多见。触发活动常常起源于中层心肌细胞部位。结论　在LQT条件下 ,跨壁动作电位不均一地延长是导致复极化离散的重要原因 ,为心律失常的发生提供了基质。早期后除极诱导的触发活动触发了尖端扭转性室速     

LQT2模型尖端扭转型室性心动过速的发生机制

目的探讨LQT2模型早期后除极(EAD)、跨壁折返以及尖端扭转型室性心动过速(Tdp)的发生机制。方法采用冠状小动脉灌注兔左室心肌楔形组织块标本,应用浮置玻璃微电极动作电位及ECG同步记录技术,以IKr阻断剂d-sotalol作为工具药模拟LQT2,并与延迟整流钾电流IK阻滞剂azimilide对比,观察两者对兔心内膜和外膜层心肌细胞动作电位时程(APD)、跨壁复极离散度(TDR)、EAD、R-on-T早搏和Tdp的作用。结果d-sotalol和azimilide均显著延长心内膜和外膜层心肌细胞APD和QT间期;d-sotalol显著增加TDR,诱发EAD、R-on-T早搏和自发性Tdp的发生率分别为7/7,7/7和3/7;azimilide不增加TDR和不形成跨壁折返,但可诱发EAD和R-on-T早搏。结论通过冠状小动脉灌注兔左室心肌组织块LQT2模型,发现整体心室肌组织在QT延长的条件下,2相EAD是触发并引起Tdp的机制;TDR增加是产生EAD和形成折返的基础。     

低钾对长QT综合征心室肌组织易损窗的影响——计算机仿真研究

目的探讨细胞外低钾时长QT综合征(LQTS)室性心律失常发生率增高的原因。方法采用计算机仿真方法,分别观察了不同程度低钾对LR91一维非均质心室肌模型的时间、空间及电压易损窗的影响。实验分为正常组和LQTS组。以500,1000和2000ms的刺激周长对一维模型施加基础刺激S1(-70μA/μF、1.5ms)10次后,测量动作电位时程及传导速度。每10次S1后施加期前刺激S2,S1S2间期以1ms的步长递减测量易损窗。结果在不同刺激频率条件下,随[K+]O的减低,正常组和LQTS模型组的时间、电压、空间易损窗逐渐增大,且LQTS模型组易损窗均大于正常组。易损窗变化表现有频率依赖性。结论低钾增加了单向传导阻滞的发生机率,是导致室性心律失常发生率增高的重要原因。     

预激综合征旁道的心电图、心脏标测定位(附六例报告)

对6例预激综合征旁道进行心电图、电生理检查及心外膜标测定位和比较,结果提示综合二种心电图δ波极性作旁道定位的方法有较高的准确性。电生理检查对确定左或右旁道的存在有帮助,而作心内膜标测确定旁道位置较困难。认为显性预激综合征者,旁道切割术前不必强调作电生理检查,除非为隐匿性预激。用手指压迫预计的旁道部位,使δ波消失和/或阵发性室上性心动过速终止可能是心外膜标测的一种简便的方法。     

The Distribution and the Fibrotic Role of Elevated Inflammatory Th17 Cells in Patients With Primary Biliary Cirrhosis

T helper (Th) 17 cells were reported to have the property of proinflammation and profibrosis. We first investigate the levels of Th17 cells in primary biliary cirrhosis (PBC) patients, and then explore their distribution and fibrotic role in the disease.We compared the circulating Th17 and hepatic interleukin (IL)-17-positive cells between patients and healthy controls (HCs) at different disease stages by flow cytometry and immunohistochemistry, respectively. The levels of chemokine (c-c motif) ligand (CCL) 20 were then measured. For exploration of the reason why Th17 cells increased, CD4⁺CD161⁺ populations were sorted and cultured with IL-23 and IL-1β to analyze their proliferation and IL-17 secretions. The serum IL-23 and IL-1β were tested by enzyme-linked immunosorbent assay. The proliferation and expressions of α-smooth muscle actin and IL-8 of hepatic stellate cells (HSCs) were identified after stimulated by different concentrations of IL-17.Circulating and hepatic Th17 cells were elevated in PBC patients compared with HCs. Early PBC patients presented with more Th17 cells in periphery blood and less in the liver than advanced PBC patients. Accordingly, the levels of both serum and hepatic CCL20 for Th17 cells were higher, especially in those with advanced disease. The progenitor of Th17, CD4⁺CD161⁺ cell was increased in PBC. Moreover, the percentage of Th17 cells was positively related with CD4⁺CD161⁺ cell. After stimulation with IL-23 and IL-1β which were improved in PBC patients, CD4⁺CD161⁺ cells from PBC patients expressed more IL-17, although their proliferation were not different between 2 groups. IL-17 can promote the proliferation of HSCs at a dose-dependent method, and also increase the IL-8 expression in a dose/time-dependent way. Anti-IL-17 can neutralize the above reactions.CD4⁺CD161⁺ cells are a source of increased Th17 in PBC patients. With disease progression, Th17 population decreased in the circulation, accompanied by greater accumulation in the liver, which is regulated by CCL20 in advanced patients. IL-17 may be involved in the process of PBC fibrosis.     

全反式维甲酸对早期动脉粥样硬化大鼠模型外周调节性T细胞与辅助性T细胞17平衡的影响

目的 建立早期动脉粥样硬化大鼠模型,并探讨其外周CD4+ CD25+调节性T细胞(Treg)与辅助性T细胞17(Th17)平衡变化及全反式维甲酸对平衡的影响.方法 50只8周龄SD大鼠,随机分为对照组、高脂组、免疫组、免疫高脂组以及全反式维甲酸组,对照组、免疫组予正常饲料,其他三组予高脂饲料,免疫组、免疫高脂组以及全反式维甲酸组注射卵清白蛋白进行初始免疫和强化免疫.全反式维甲酸组同时予以全反式维甲酸灌胃,16周后获取血和动脉.检测血清脂质变化,主动脉HE染色以观察动脉病变;流式细胞术检测各组大鼠外周血Treg和Th17细胞表达率,酶联免疫吸附法检测血清相关细胞因子水平.结果 成功建立早期动脉粥样硬化大鼠模型.组织形态学显示免疫高脂组内膜增生;与免疫高脂组比较,免疫组及全反式维甲酸组程度较轻,对照组及高脂组动脉完好.高脂组及免疫高脂组血清胆固醇和低密度脂蛋白较对照组、免疫组有显著增加(均P＜ 0.05),而全反式维甲酸组与其他各组比较无统计学差异.与对照组及高脂组相比,免疫组及免疫高脂组大鼠Treg细胞表达及白细胞介素10(IL-10)、转化生长因子β水平显著降低,而Th17细胞表达及IL-17、IL-6水平明显增高(均P＜0.05),全反式维甲酸组Treg表达及相关细胞因子水平与免疫高脂组比较显著升高,而Th17表达及相关因子水平明显降低(均P＜ 0.05).结论 免疫损伤结合高脂喂养可形成早期动脉粥样硬化大鼠模型,该模型存在Treg与Th17细胞平衡失调,全反式维甲酸可通过影响Th17/Treg平衡发挥抗动脉粥样硬化效应.     

Effect of the Early Combination of Continuous Positive Airway Pressure and High-Flow Nasal Cannula on Mortality and Intubation Rates in Patients With COVID-19 and Acute Respiratory Distress Syndrome. The DUOCOVID Study

IntroductionNon invasive respiratory support (NIRS) is useful for treating acute respiratory distress syndrome (ARDS) secondary to COVID-19, mainly in mild–moderate stages. Although continuous positive airway pressure (CPAP) seems superior to other NIRS, prolonged periods of use and poor adaptation may contribute to its failure. The combination of CPAP sessions and high-flow nasal cannula (HFNC) breaks could improve comfort and keep respiratory mechanics stable without reducing the benefits of positive airway pressure (PAP). Our study aimed to determine if HFNC + CPAP initiates early lower mortality and endotracheal intubation (ETI) rates.MethodsSubjects were admitted to the intermediate respiratory care unit (IRCU) of a COVID-19 monographic hospital between January and September 2021. They were divided according to Early HFNC + CPAP (first 24 h, EHC group) and Delayed HFNC + CPAP (after 24 h, DHC group). Laboratory data, NIRS parameters, and the ETI and 30-day mortality rates were collected. A multivariate analysis was performed to identify the risk factors associated with these variables.ResultsThe median age of the 760 included patients was 57 (IQR 47–66), who were mostly male (66.1%). The median Charlson Comorbidity Index was 2 (IQR 1–3) and 46.8% were obese. The median PaO₂/FiO₂ upon IRCU admission was 95 (IQR 76–126). The ETI rate in the EHC group was 34.5%, with 41.8% for the DHC group (p = 0.045), while 30-day mortality was 8.2% and 15.5%, respectively (p = 0.002).ConclusionsParticularly in the first 24 h after IRCU admission, the HFNC + CPAP combination was associated with a reduction in the 30-day mortality and ETI rates in patients with ARDS secondary to COVID-19.