1例长QT综合症的治疗与护理

长QT综合症是指在心电图上表现QT间期延长,易产生恶性室性心律失常,尤其是尖端扭转型室性心动过速,导致晕厥、癫痫样抽搐发作和心脏骤停,心脏性猝死的一组综合症,分先天性长QT综合症及获得性长QT综合症。我科于2014年8月成功救治1例长QT综合症并发恶性心律失常-室速、室颤,除颤4次,予临时起搏器置入及射频消融治疗后置入置入型心脏转除颤器（ICD）的患者。     

急性心肌梗死患者Q-Tc间期延长的意义

为了探讨急性心肌梗死心电图Q-Tc值延长的临床意义,本文分析了42例急性心肌梗死患者的体表12-导联心电图,结果显示:心律失常组Q-Tc间期较对照组显著延长;大面积梗死组的Q-Tc间期及心律失常的发生率均大于小面积梗死组.提示急性心肌梗死的Q-Tc间期与室性心律失常之间有密切的关系.     

第十五节 心电图重要概念

一、QT离散度 QT离散度或称QT间期离散度,是指体表12导联心电图各导联间QT间期存在差异,用反映体表12导联心电图各导联间QT间期的极差,即12导联中QT间期的最大值与最小值之差来表示.QT离散度主要反映心室肌复极的不均一性,可代表心室肌兴奋性恢复时间不一致的程度,或心室肌不应期差异的程度.心肌不应期显著差异是折返形成的重要条件,而折返是造成多数严重心律失常,如室性心动过速、心室扑动、心室颤动的主要机制.     

非典型抗精神病药物对首发儿童精神分裂症心电图QT间期的影响

目的评价新型非典型抗精神病药物对首发儿童精神分裂症患者心电图QT间期的影响。方法对237例单一口服非典型抗精神病药物治疗的首发儿童精神分裂症患者,分别在治疗前及治疗药物达到临床最大剂量时进行心电图检查,对心电图QT/QTC间期进行对比分析。结果非典型抗精神病药物奥氮平、喹硫平、利培酮、氯氮平、齐拉西酮治疗前后QT/QTC间期比较,差异均无显著性(P>0.05)。齐拉西酮治疗后QT较治疗前显著延长(t=-4.307,P=0.000)。齐拉西酮治疗后QTC较治疗前相比,虽然有延长,但无显著性差异(t=-0.786,P=0.439)。不同组药物治疗后QT/QTC间期平均值长短顺序依次为:齐拉西酮>利培酮>奥氮平>喹硫平>氯氮平。不同药物组治疗前后QTC间期无显著性差异(F=1.477,P=0.208),不同药物组间差异无显著性(F=0.179,P=0.673)。不同药物组治疗前后QT间期无显著性差异(F=2.833,P=0.090),不同药物组间差异有显著性(F=4.929,P=0.001)。结论不同的非典型抗精神病药物对儿童精神分裂症患者心电图QT/QTC间期有不同的影响。其中齐拉西酮组的QT/QTC间期最长,氯氮平组最短,无QTC间期延长达到异常标准的病例。     

急性心肌梗死QT离散度与预后相关性研究

目的 分析急性心肌梗死（AMI）后QT分布规律，计算出数据。了解QTd，QTcd与AMI患者并发恶性心律失常，心血管事件的关联性及数据范围，估计近期临床预后，并为开发有关计算机诊断软件提供数据。方法 AMI组入院时前3d每天至少测量一份心电图QT间期。一周时再测量一份心电图QT间期，并同时同份心电图记录R-R间期。死亡病例测至死亡时。生存者再测量出院时心电图的QT间期。以分规测Qp．S波起点至T波终点（T波回到TP基线时）的距离为QT间期，若有u波则取Tu波间的最低点为T波终点。依次测量12导联的QT间期，每导联至少测量3个心动周期，取其平均值。对照组做常规12导联心电图，测量方法相同。结果 AMI患者住院期间的平均QTd及QTcd值均显著大于对照组及出院时的数值，死亡组显著大于生存组。发现最长的QT间期82％见于梗塞区或缺血区导联，而最短的QT间期95％见于非梗塞区或非缺血区导联。QTd及QTcd最大值均在心肌梗塞发生后1～3d内，且有动态改变，表现为第一天升高，第三天最高，一周后趋于稳定，其QTd49＋14ms，QTcd51＋18ms，与出院时比较无显著性差异（p〉0．05）。在QTd≥80ms患者中，其死亡率、多部位梗塞、泵功能衰竭、室性心律失常及房室传导阻滞发生率均大于QTd〈80ms，且有显著差异。结论 对AMI患者动态观察其QTd及QTcd，对QTdt〉80ms。尤其是〉100ms时，应采取积极预防猝死措施．对于心律失常。心泵功能不全的防治和识别高危患者以及获得疾病转归的信息提供了一种无创、简便、可重复的检测手段。对估计近期临床预后，特别是AMI后对判断心肌缺血程度、预测心血管事件、抗心律失常药物药效评估及指导治疗均有重要临床意义，并为开发有关诊断软件提供数据范围。     

QT间期的检测与分析

心电图中的QT间期主要反映了心室复极化的时程,而QT间期的变异蕴含了心室复极变化的重要信息,对这些信息的提取和分析对研究心肌缺血、恶性心律失常等疾病有重要的意义.文中针对QT间期自动检测算法、QT离散度分析和QT变异性分析,分别介绍了它们的研究方法和研究进展,并指出了今后的发展方向.     

表征心室复极不一致的有效参数的研究进展

心室复极不一致与室性心律失常直接相关,文章介绍了一些表征心室复极不一致的心电图参数,包括QT离散度、兴奋—恢复间期离散度和T波形态方面的参数,回顾了近年来这方面的研究成果和进展,并简单讨论了这类研究的发展趋势。     

QT离散度的临床研究进展

QT离散度（QTd）是指标准12导联心电图中最大QT间期与最小QT间期之差。1990年Day和Campbell^[1]等首先提出QT离散度的概念。认为QTd反映了心室复极的不一致性和心电的不稳定性。随后的大量实验及临床研究报告了QTd的生理学意义及临床应用价值，并将其作为反映心室复极的不均一性的一种无创伤性指标，广泛应用于心脏的各种病理状态及抗心律失常药物的评价，受到越来越多的关注和重视。     

益心舒胶囊联合艾司洛尔治疗快速性心律失常的疗效观察

目的观察益心舒胶囊联合艾司洛尔治疗快速性室性心律失常的效果,分析益心舒胶囊辅助治疗快速性室性心律失常的价值。方法选取2017年1月至2018年6月本院收治的159例心律失常患者作为研究对象,所有患者在电复律或电除颤治疗同时服用药物,根据用药情况分为对照组(81例,采用单纯艾司洛尔治疗)和观察组(78例,采用益心舒胶囊联合艾司洛尔治疗)。比较两组患者主要证候积分、心电图、近期疗效以及不良反应发生情况。结果治疗后两组患者心率、PR间期、QT间期明显优于治疗前,且观察组患者心率、PR间期、QT间期改善幅度大于对照组,差异有统计学意义(P0.05);治疗后两组患者心悸、胸痛、神疲乏力、气短证候积分明显降低,且观察组患者心悸、胸痛、神疲乏力、气短证候积分降低幅度大于对照组,差异有统计学意义(P0.05);观察组患者临床总有效率明显高于对照组,差异具有统计学意义(P0.05);随访期间两组患者总体不良反应发生率比较,差异无统计学意义(P0.05)。结论益心舒胶囊联合艾司洛尔治疗能有效抑制快速性室性心律失常发作,减轻临床症状,改善心电图,增强临床疗效。     

QT 间期对RR 间期变化的响应及HRV 与QTV 的关联性分析

体表心电图作为无创和连续的监测手段,在心脏安全评测方面具有重要而不可替代的位置。心电图中的间期时间序列包含着重要信息,其中以反映心动周期的RR间期序列,以及以QT间期为代表的反映心室复极化时程的间期序列,在临床上最为基础,相关的研究具有更为重要的意义。文中从应用基础研究的角度,就QT间期对于RR间期变化的响应,以及心率变异性（HRV）和QT间期变异性（QTV）关联性分析,分别介绍了其分析方法和研究进展,并且展望了可能的应用前景。     

Mouse models of long QT syndrome

Congenital long QT syndrome is a rare inherited condition characterized by prolongation of action potential duration (APD) in cardiac myocytes, prolongation of the QT interval on the surface electrocardiogram (ECG), and an increased risk of syncope and sudden death due to ventricular tachyarrhythmias. Mutations of cardiac ion channel genes that affect repolarization cause the majority of the congenital cases. Despite detailed characterizations of the mutated ion channels at the molecular level, a complete understanding of the mechanisms by which individual mutations may lead to arrhythmias and sudden death requires study of the intact heart and its modulation by the autonomic nervous system. Here, we will review studies of molecularly engineered mice with mutations in the genes (a) known to cause long QT syndrome in humans and (b) specific to cardiac repolarization in the mouse. Our goal is to provide the reader with a comprehensive overview of mouse models with long QT syndrome and to emphasize the advantages and limitations of these models.     

参松养心胶囊对糖尿病大鼠心室电生理特性及结构功能变化的影响

 目的：探讨参松养心胶囊（SSYX）对糖尿病（DM）大鼠心室电生理特性与结构功能变化的影响。方法：雄性SD大鼠45只，随机分为对照组（CTL组，n=15）、DM组（n=15）和SSYX组（n=15）。DM组和SSYX组采用一次性腹腔注射链脲佐菌素（60 mg/kg）制备糖尿病模型，CTL组则给予腹腔注射生理盐水（1 mL/kg），72 h后检测血糖评价造模结果，将造模成功的动物纳入本研究。SSYX组连续6周给予SSYX灌胃（1 g·kg-1·d-1）治疗，DM组和CTL组则给予生理盐水灌胃（2 mL·kg-1·d-1）。动物完成药物治疗后，采用超声心动图检测心功能并记录II导联体表心电图；采用放射免疫法检测血浆的内皮素1（ET-1）水平；随后在整体心脏Langendorff灌流条件下行离体电生理研究，分别记录和测量左室前游离壁（LAF）心外膜单相动作电位（MAP）和有效不应期（VERP），同时给予Burst快速电刺激用以进行室性心律失常（VA）的诱发；采用Masson染色对3组动物心肌纤维化程度进行评价。结果：与CTL组相比，DM组心功能下降（P<001），而QT间期、VERP、动作电位时程、VA诱发率、心肌纤维化程度和血浆ET-1水平均增加（均P<001）；与DM组相比，SSYX组的心功能得到改善（均P<001），且 QT间期、VERP、动作电位时程、VA诱发率、心肌纤维化程度和血浆ET-1水平均降低（均P<005）。结论：SSYX具有减轻DM大鼠心室电重构和结构重构及改善心功能的作用。     

G-CSF对豚鼠单个缺血心房肌细胞钙、钠、钾电流的影响

目的:采用膜片钳全细胞记录方法,观察粒细胞集落刺激因子(G-CSF)急性干预对分离的豚鼠单个缺血心房肌细胞钙、钠、钾电流的影响。方法:使用酶解方法获得豚鼠单个心房肌细胞,在缺血缺氧条件下,采用全细胞膜片钳技术观察记录不同浓度G-CSF急性干预对钙通道电流-电压曲线、激活曲线、失活曲线,钠通道电流-电压曲线、激活曲线、失活曲线、静态失活曲线,延迟整流钾通道及其快成分、慢成分电流-电压曲线的影响。结果:随G-CSF浓度的增加,缺血心房肌细胞膜L型钙通道电流较缺血对照组有明显增大。当G-CSF浓度超过100μg/kg后,L型钙通道电流的增强维持于同一水平。当给予G-CSF浓度为300μg/kg时最大激活电压发生改变,较前有所增加。激活曲线与失活曲线未见明显改变。不同浓度G-CSF对缺血心房肌细胞膜钠离子通道电流无明显影响。G-CSF干预缺血心房肌细胞膜延迟整流钾电流未见明显改变,但延迟整流钾电流快成分在G-CSF 100μg/kg干预后明显增加,而延迟整流钾电流慢成分未见明显改变。结论:G-CSF对于缺血心房肌细胞部分通道的作用影响基本为非电压依赖性,但具有浓度依赖性,可能减少缺血心房心律失常的发生率。     

牵张刺激对乳大鼠心房肌细胞瞬时外向钾电流和内向整流钾电流的影响

 目的：探究牵张刺激对乳鼠心房肌细胞瞬时外向钾电流（Ito）、内向整流钾电流（IK1）和动作电位时程（APD）的影响。方法：取1日龄SD乳大鼠心脏,分离、消化获得心房肌细胞。于细胞牵引装置培养24 h分组：对照组不予牵张刺激;牵张组予增加12%硅胶膜面积牵张刺激24 h。膜片钳全细胞记录方法记录细胞膜Ito、IK1和APD的变化。结果：在+60 mV刺激电压水平,牵张组Ito密度与对照组相比明显降低［(16±04）pA/pF vs (121±29) pA/pF,P<001］。在-120 mV刺激电压下,牵张组IK1密度较对照组增大［（-108± 08） pA/pF vs (-88±09)pA/pF,P<001］。牵张组动作电位复极50%（APD50）和复极90％（APD90）均较对照组明显缩短［(105±14）ms vs (155±24) ms,(300± 28) ms vs (563±36) ms,P<001］。结论：牵张刺激可降低乳大鼠心房肌细胞Ito密度,增大IK1密度,缩短APD,这可能是压力负荷增大致心房电重构的基础之一。     

Single Nucleotide Deletion Mutation of KCNH2 Gene is Responsible for LQT Syndrome in a 3-Generation Korean Family

Long QT syndrome (LQTS) is characterized by the prolongation of the QT interval in ECG and manifests predisposition to life threatening arrhythmia which often leads to sudden cardiac death. We encountered a 3-generation family with 5 affected family members in which LQTS was inherited in autosomal dominant manner. The LQTS is considered an ion channel disorder in which the type and location of the genetic mutation determines to a large extent the expression of the clinical syndrome. Upon screening of the genomic sequences of cardiac potassium ion channel genes, we found a single nucleotide C deletion mutation in the exon 3 of KCNH2 gene that co-segregates with the LQTS in this family. This mutation presumably resulted in a frameshift mutation, P151fs+15X. This study added a new genetic cause to the pool of mutations that lead to defected potassium ion channels in the heart.     

Characterization of stretch-activated ion currents in isolated atrial myocytes from human hearts

To explore further the mechanisms that may underlie cardiac arrhythmia, we analysed stretch-activated ion currents in human atrial myocytes. Longitudinal stretch of freshly isolated atrial myocytes prolonged the duration of action potentials, depolarized the resting membrane potential and caused extra action potentials. Under voltage-clamp conditions, the amplitude of stretch-induced transmembrane currents increased reversibly with the intensity of stretch. Stretch-activated currents ( I(SAC)) had a reversal potential of 0 mV and were insensitive to substitution of Cl(-) with aspartate ions in the extracellular fluid. I(SAC) was suppressed by 5 micro M gadolinium (Gd(3+)). Furthermore, mechanical stretch decreased transmembrane ion fluxes through L-type calcium channels (I(Ca,L)). This reduction of I(Ca,L) was inhibited by dialysing the cells for 5 min with 5 mM BAPTA prior to application of stretch. In contrast, both BAPTA and removal of Ca(2+) from the extracellular bathing solution had no significant effect on stretch activation of I(SAC). These findings suggest that non-selective cation channels in human atrial myocytes are sensitive to mechanical stimulation. We propose that activation of transmembrane influx of cations, preferentially Na(+), by local stretch may play a role in cardiac arrhythmia.     

缝隙连接蛋白43通过调控L型钙电流参与心房肌细胞的电重塑

目的:观察缝隙连接蛋白43(Cx43)是否通过与L型钙通道共定位,调控L型钙电流,参与房颤(AF)的发病机制。方法:使用蛋白免疫印迹和实时荧光定量PCR检测AF和窦性心律患者心房组织中Cx43的蛋白和mRNA表达差异;用RNA干扰技术沉默心房肌细胞的Cx43表达,实时荧光定量PCR和全细胞膜片钳实验观察对L型钙通道mRNA表达和L型钙电流的影响;免疫共沉淀和激光共聚焦显微成像观察心房肌细胞中Cx43与L型钙通道是否存在共定位。结果:AF患者心房组织中的Cx43表达明显低于窦性心律患者;干扰Cx43表达可明显抑制L型钙电流和L型钙通道α1c亚基的mRNA表达;且心房肌细胞中Cx43与L型钙通道存在共定位。结论:心房肌细胞中的Cx43可通过与L型钙通道形成分子复合物,调控L型钙电流,参与心房肌细胞的电重塑。     

Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias

The inherited long QT syndrome (LQTS), characterized by a prolonged QT interval in the electrocardiogram and cardiac arrhythmia, is caused by mutations in at least four different genes, three of which have been identified and encode cardiac ion channels. The most common form of LQTS is due to mutations in the potassium channel gene KVLQT1, but their effects on associated currents are still unknown. Different mutations in KVLQT1 cause the dominant Romano-Ward (RW) syndrome and the recessive Jervell and Lange-Nielsen (JLN) syndrome, which, in addition to cardiac abnormalities, includes congenital deafness. Co- expression of KvLQT1 with the IsK protein elicits slowly activating potassium currents resembling the cardiac Iks current. We now show that IsK not only changes the kinetics of KvLQT1 currents, but also its ion selectivity. Several mutations found in RW, including a novel mutation (D222N) in the putative channel pore, abolish channel activity and reduce the activity of wild-type KvLQT1 by a dominant-negative mechanism. By contrast, a JLN mutation truncating the carboxyterminus of the KvLQT1 channel protein abolishes channel function without having a dominant-negative effect. This fully explains the different patterns of inheritance. Further, we identified a novel splice variant of the KVLQT1 gene, but could not achieve functional expression of this nor of a previously described heart-specific isoform.      

Myotonic dystrophy protein kinase is expressed in embryonic myocytes and is required for myotube formation

Myotonic dystrophy (DM1) is a multi-systemic disease caused by a triplet nucleotide repeat expansion in the 3' untranslated region of the gene coding for myotonic dystrophy protein kinase (DMPK). The primary pathophysiology of DM1 is thought to result from RNA transport and processing defects. The function of DMPK in development or any potential role in DM1 remains unknown. Here we report a novel role for DMPK in myogenesis. We have discovered a specific expression pattern of DMPK in mouse and chick embryonic development. DMPK is expressed in postmitotic cardiac and skeletal myocytes and developmental signaling centers. During cardiac myocyte maturation, DMPK migrates from perinuclear to cellular membrane localization. Manipulating DMPK levels in cultured cardiac and skeletal myocytes has revealed a key role for DMPK in myocyte differentiation. Overexpression of DMPK induces cell rounding and apoptosis in myocytes. In addition, DMPK is necessary for myogenin expression in differentiating C2C12 myoblasts.     

The effects of intracellular Ca2+ on cardiac K+ channel expression and activity: novel insights from genetically altered mice

We tested the hypothesis that chronic changes in intracellular Ca²⁺ (Ca²⁺_i) can result in changes in ion channel expression; this represents a novel mechanism of crosstalk between changes in Ca²⁺ cycling proteins and the cardiac action potential (AP) profile. We used a transgenic mouse with cardiac-specific overexpression of sarcoplasmic reticulum Ca²⁺ ATPase (SERCA) isoform 1a (SERCA1a OE) with a significant alteration of SERCA protein levels without cardiac hypertrophy or failure. Here, we report significant changes in the expression of a transient outward K⁺ current ( I _to,f), a slowly inactivating K⁺ current ( I _K,slow) and the steady state current ( I _SS) in the transgenic mice with resultant prolongation in cardiac action potential duration (APD) compared with the wild-type littermates. In addition, there was a significant prolongation of the QT interval on surface electrocardiograms in SERCA1a OE mice. The electrophysiological changes, which correlated with changes in Ca²⁺_i, were further corroborated by measuring the levels of ion channel protein expression. To recapitulate the in vivo experiments, the effects of changes in Ca²⁺_i on ion channel expression were further tested in cultured adult and neonatal mouse cardiac myocytes. We conclude that a primary defect in Ca²⁺ handling proteins without cardiac hypertrophy or failure may produce profound changes in K⁺ channel expression and activity as well as cardiac AP.