Prevalence and risk factors for acquired long QT syndrome in the emergency department:a retrospective observational study

BACKGROUND: Long QT syndrome(LQTS) is a heterogeneous syndrome that may be congenital or, more frequently, acquired. The real-world prevalence of acquired LQTS(aLQTS) in the emergency department(ED) remains to be determined. The aim of this study was to determine prevalence of aLQTS and its impact on symptoms on ED admissions.METHODS: Electrocardiograms(ECG) of 5,056 consecutively patients admitted in the ED of a tertiary hospital between January 28th and March 17th of 2020 were reviewed. All patients with aLQTS were included. Clinical data with a focus on QT prolonging drugs and clinical factors were recorded. Statistical comparison was made between the groups with and without corrected QT(QTc) interval greater than 500 ms(value that is considered severely increased).RESULTS: A total of 383 ECGs with prolonged QTc were recognized, corresponding to a prevalence of aLQTS at admission of 7.82%. Patients with aLQTS were more commonly men(53.3%) with an age of(73.49±14.79) years old and QTc interval of(505.3±32.4) ms. Only 20.4% of these patients with aLQTS were symptomatic. No ventricular arrhythmias were recorded. Patients with QT interval greater than 500 ms were more frequently female(59.5%;P<0.001) and were more frequently on QT prolonging drugs(77.3%;P=0.025). Main contributing factor was intake of antibiotics(odds ratio [OR] 4.680) followed by female gender(OR 2.473) and intake of antipsychotics(OR 1.925).CONCLUSION: aLQTS is particularly prevalent in the ED. Female patients on antibiotics and antipsychotics are at particularly high risk. Efforts must be made to avoid, detect and treat aLQTS as early as possible.

Drugs to be avoided in patients with long QT syndrome:Focus on the anaesthesiological management

Long QT syndrome incidence is increasing in general population.A careful pre-,peri-and post-operative management is needed for patients with this syndrome because of the risk of Torsades de Pointes and malignant arrhythmias.The available data regarding prevention of lethal Torsades de Pointes during anesthesia in patients with long QT syndrome is scant and conflicting:only case reports and small case series with different outcomes have been published.Actually,there are no definitive guidelines on pre-,peri-and post-operative anesthetic management of congenital long QT syndrome.Our review focuses on anesthetic recommendations for patients diagnosed with congenital long QT syndrome furnishing some key points for preoperative optimization,intraoperative anesthetic agents and postoperative care plan,which could be the best for patients with c-long QT syndrome who undergo surgery.

Genotypic diagnosis of long QT syndrome by analysis of candidate genes

Objective To diagnose 6 LQTS families by genetic analysis.Methods A total aof 6 LQTS pedigrees with 43 family members were brought together for genetic diagnosis by using short-sequence tandem-repeat(STR)markers or sequencing.Genomic DNA was extracted from blood samples by standard procedure.STR markers or KCNQ1,KCNH2 and SCN5A were amplified.The haplotype analysis for LQTS was performed.If the family got the negative haplotype analysis,the sequencing was performed.Results LQTS patients were always linkaged with the SCN5A gene in family 1.KCNH2 was linkaged with the disease in family 2 to 5.21 gene carriers were identified from these 5 families.A mutation(A561V-KCNH2)was only found in the proband of family 6 and an SNP(G1691A)was found in all the members of the family.Conclusion Genetic diagnosis can not only improve presymptomatic diagnosis,but also provide the basis for personal therapy and research on disease-causing mutations.

A novel mutation—L539fs/47 of hERG in a Chinese long QT syndrome family

Objective To identify the mutation of human ether-a-go-go-related gene(hERG)and analyze the clinical characteristics of a Chinese family with long ST syndrome(LQTS).Methods The electrocardiogram and DNA samples were obtained from a Chinese LQTS family of 26 members.Genotype was performed with polymorphic short tandem repeat(STR)markers at the known LQT1,LQT2,and LQT3 loci.SSCP analysis was used to find aberrant conformers.hERG mutation was confirmed by cloning and sequencing.Results Three gene carriers were linked to chromosome 7q35-36,where the potassium channel gene hERG was encoded.A 19-base pair deletion was identified.The mutation was located at nucleotide position 1 619-1 637 between transmembrane domains S4 and S5.Furthermore,A1692G polymorphism was found both in the normal control and patients.Conclusion A novel 19 bp deletion mutation of hERG is identified in a Chinese family.All gene carriers are demonstrated to be typical LQT2 ECG phenotype.

Discovery of Digenic Mutation, KCNH2 c.1898A > C and JUP c.916dupA, in a Chinese Family with Long QT Syndrome via Whole-Exome Sequencing

Long QT syndrome(LQTS),which is caused by an ion channel–related gene mutation,is a malignant heart disease with a clinical course of a high incidence of ventricular fi brillation and sudden cardiac death in the young.Mutations in KCNH2(which encodes potassium voltage-gated channel subfamily H member 2)are responsible for LQTS in many patients.Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing.The c.916dupA mutation in JUP(which encodes junction plakoglobin)is also discovered.Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy.The double mutation in the proband may help explain his severe clinical manifestations,such as sudden cardiac death at an early age.Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line,while the mutation in JUP came from his maternal line.The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias.

A novel splice mutation of HERG in a Chinese family with long QT syndrome

Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was identified in this Chinese LQTS family,leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (-12→-2)]. The mutation might affect,through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K+ channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.

The Relationship between T-Wave Alternans and Adverse Cardiac Events in Patients with Congenital Long QT Syndrome:A Systematic Review and Meta-Analysis

Background:T-wave alternans(TWA)is a risk factor of ventricular arrhythmias or sudden cardiac death(SCD)in patients with ischemic cardiomyopathy.Nevertheless,the relationship between TWA and adverse cardiac events(ACE)in patients with congenital long QT syndrome(LQT)remains controversial.Methods:A systematic electronic search of PubMed,Embase and the Cochrane Library was conducted from database inception dates to 28 April 2021 and assessed the relationship between TWA and ACE in patients with LQTS.Sub-group analysis evaluated the association between microvolt TWA(MTWA)and ACE in different monitoring models and ECGlead numbers.Results:A pooled analysis of seven studies of 625 patients with LQTS showed that TWA was significantly associated with ACE(OR 3.16,95%CI 1.86–5.37,P<0.001).Advanced analysis showed that macroscopic TWA was significantly related to ACE(OR 6.01,95%CI 2.96–12.21,P<0.001),while MTWA did not(OR 0.92,95%CI 0.37–2.30,P=0.85).Sub-group analysis showed that MTWA recorded in 24 h continuous ECG(OR 6.79,95%CI 0.80–57.75,P=0.08)might have a stronger association with ACE than recorded in stress ECG(OR 0.28,95%CI 0.07–1.10,P=0.07).No difference was observed between MTWA measured in multi-lead ECG and limited ECG leads(P=0.15).Conclusions:Macroscopic TWA was significantly related to ACE in patients with LQTS.In terms of MTWA,MTWA recorded in 24 h continuous ECG might have a stronger association with ACE than stress ECG,but still deserves further evaluation.

Diagnosis of long QT syndrome via support vector machines classification

Congenital Long QT Syndrome (LQTS) is a genetic disease and associated with significant arrhythmias and sudden cardiac death. We introduce a noninva-sive procedure in which Discrete Wavelet Trans-form (DWT) is used to extract features from elec-trocardiogram (ECG) time-series data first, then the extracted features data is classified as either abnormal or unaffected using Support Vector Machines (SVM). A total of 26 genetically identified patients with LQTS and 19 healthy controls were studied. Due to the limited number of samples, model selection was done by training 44 instances and testing it on remaining one in each run. The proposed method shows reasonably high average accuracy in LQTS diagnosis when combined with best parameter selection process in the classifica-tion stage. An accuracy of 80%is achieved when Sigmoid kernel is used in v-SVM with parameters v = 0.58 and r = 0.5. The corresponding SVM model showed a classification rate of 21/26 for LQTS pa-tients and 15/19 for controls. Since the diagnosis of LQTS can be challenging, the proposed method is promising and can be a potential tool in the correct diagnosis. The method may be improved further if larger data sets can be obtained and used.

Effect of Calcium-Channel Antagonist on Repolarization Heterogeneity of Ventricular Myocardium in an in Vitro Rabbit Model of Long QT Syndrome

Intracellular Ca2＋ and Ca2＋-dependent signaling molecule play an essential role in the genesis of long-QT （LQT） syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential （MAP） recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts purfused by Langendorff method with standard Tyrode＇s solution. Bradycardia was induced by com- plete ablation of atrioventricular node. A catheter was introduced into the right ventricle to pace at the cycle lengths （CLs） of 1500, 1000, and 500 ms, successively. Quinidine （2 μmol/L） prolonged QT interval and ventricular MAP duration （MAPD）, and increased transmural dispersion of repolarization （TDR） in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil （0.01--0.05μmol/L） used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syndrome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.

Non genetic risk factors of long-QT syndrome

The purpose of the present study is to provide guidelines regarding risk factors that may worsen the Long-QT Syndrome (LQTS), based on available literature. This review evaluates the current knowledge on these risk factors of acquired LQTS, with an emphasis on non genetic risk factors, including environmental factors. PubMed was searched for literature in English from 1999 to 2011 on the molecular and clinical studies of Long-QT syndrome. We agree, with recent investigations described in the literature, that variety of factors, inherited or environmental, can influence expression of ion channel proteins with impact on repolarization.

The Notched T Waves Associated With HERG Gene Ala561Val Mutation in Congenital LQT Syndrome

Objectives To study the phenotype of a China LQT family and investigate the relationship of phenotype and gene. Methods The clinical materials were analyzed and gene mutations were screened by sequencing. Results A distinctive biphasic T wave pattern was shown in the left precordial leads of all patients. The LQT2 related HERG gene Ala561Val mutation was found. Conclusions A prolonged QT interval accompanied biphasic T wave indicates HERG mutation.

抗结核药物所致QTc间期延长临床监测和管理专家共识

贝达喹啉、德拉马尼、氯法齐明及氟喹诺酮类药物(如左氧氟沙星、莫西沙星)对于提高耐多药和广泛耐药结核病的治疗成功率至关重要。然而,这些药物可能导致心电图的QTc间期延长,若不及时发现和处理,严重者可危及患者生命。因此,临床医师需要采取积极措施进行预防、监测和妥善处理。本共识旨在解决抗结核药物引发的QTc间期延长的临床监测和管理问题。依托公开发表的研究数据,以及参与专家的应用经验,经过深入的讨论,形成了关于抗结核药物导致的QTc间期延长的临床监测和管理的专业建议。希望本共识能够指导医生及时和规范地预防、发现、处理抗结核治疗过程中可能出现的QTc间期延长的不良反应。

2例先天性长QT综合征病人因听觉刺激诱发尖端扭转性室速的护理

总结2例先天性长QT综合征病人因听觉刺激诱发尖端扭转性室速的护理经验。针对病人病程长、病情变化突然、进展迅速、易导致猝死等特点,采取严密病情监测、早期识别高危心电图表现及尖端扭转性室速发作先兆;规范致命性心律失常应对流程,出现异常迅速响应;避免基因特异性诱发因素、实施精准护理;做好用药护理、临时及永久起搏器护理、左心交感神经切除术的围术期护理;加强心理支持及生活方式指导等护理措施。经过精心的治疗和护理,2例病人均好转出院。

Comparison of QT Correction Methods in the Pediatric Population of a Community Hospital: A Retrospective Study

Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in measurement.The authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR interval.Methods:Descriptive Retrospective Study.We included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in 2017.All participants were healthy patients with no past medical history and no regular med-ications.Results:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically significant difference was observed between every combination of two QTc formulae.The Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each formula.Fridericia method was most independent of HR and RR with the lowest absolute value of correlation coefficients.Bazett and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong correlations.Correlations were positive for Bazett and Computer,reflecting results from prior studies demonstrating an over-correction of Bazett at higher HRs.In the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable values.Alternatively,Fridericia had the linear QTc/RR regression coefficient closest to zero.The Bland-Altman method assessed for bias and the limits of agreement between correction formulae.Bazett and Computer exhibited good agreement with minimal bias along with Framingham and Rautaharju.To account for a possible skewed distri-bution of QT,all the above analyses were also performed excluding the top and bottom 2%of data as sorted by heart rate ranges(N=90).Results from this data set were consistent with those derived from all participants(N=95).Conclusions:Overall,the Fridericia correction method provided the best rate correction in our pedia-tric study cohort.

The Novel Long QT Syndrome Type 2-associated F129I Mutation in the KCNH2 Gene Significantly Affects IKr Through the hERG1 Homomeric and Heteromeric Potassium Channels

Objective:The long QT syndrome type 2 is caused by the loss-of-function mutations in the KCNH2 gene,which encodes hERG1,the voltage-gated potassium channel.The hERG1 channels conduct rapid delayed rectifier K^(+)currents(I_(Kr))in the human cardiac tissue.KCNH2 encodes 2 main isoforms-hERG1a and hERG1b,which assemble to form the homomeric or heteromeric hERG1 channels.However,the functional characteristics of the heteromeric hERG1 channels in long QT syndrome type 2 are not clear.In this study,a novel mutation in the N-terminus of hERG1a(F129l)was identified in a proband of long QT syndrome type 2.The purpose of this study was to identify the electrophysiological change of homomeric and heteromeric hERG1 channels with theF129l-hERG1a.Methods:Candidate genes were screened by direct sequencing.F129l-hERG1a was cloned in the pcDNA3.1 vector by site-directed mutagenesis.Then,the wild-type(WT)hERG1a and/or F129l-hERG1a were transiently expressed in the HEK293 cells with or without hERG1b co-expression.The expression levels of the transgenes,cellular distribution of hERG1a and hERG1b,and the electrophysiological features of the homomeric and the heteromeric hERG1 channels with the WT-hERG1a or F129l-hERG1a were analyzed using whole-cell patch-clamp electrophysiology,western blotting,and immunofluorescence techniques.Results:The proband was clinically diagnosed with long QT syndrome type 2 and carried a heterozygous mutation c.385T>A(F1291)in the KCNH2 gene.Electrophysiology study proved that the F129l substitution in hERG1a significantly decreased I_(Kr) in both the homomeric and heteromeric hERG1channels by 86%and 70%,respectively(WT-hERG1a(54.88±18.74)pA/pF vs.F129l-hERG1a(7.34±1.90)pA/pF,P<0.001;WT-hERG1a/hERG1b(89.92±24.51)pA/pF vs.F129l-hERG1a/hERG1b(26.54±9.83)pA/pF,P<0.001).The voltage dependence of I_(Kr) activation(V_(1/2) and k)was not affected by the mutation in both the homomeric and heteromeric hERG1 channels.The peak current densities and the kinetic characteristics of I_(Kr) were comparable for both WT/F129l-hERG1a and WT-hERG1a.The channel inactivation and deactivation analysis showed that F129l substitution did not affect deactivation of the homomeric hERG1a channel,but significantly accelerated the deactivation and recovery from inactivation of the heteromeric hERG1a/hERG1b channel based on the time constants of fast and slow recovery from deactivation F129l-hERG1a/hERG1b vs.WT-hERG1a/hERG1b(P<0.05).Western blotting and immunofluorescence labeling experiments showed that maturation and intracellular trafficking of the F129l-hERG1a protein was impaired and potentially increased the ratio of hERG1b to hERG1a in the F129l-hERG1a/hERG1b tetramer channel,thereby resulting in electrophysiological changes characteristic of the long QT syndrome type 2 pathology.Conclusions: I_(Kr) Was significantly reduced in the homomeric and heteromeric hERG1 channels with F129l-hERG1a.The F129l mutation significantly accelerated the deactivation and recovery from inactivation of the heteromeric F129l-hERG1a/hERG1b channel.F129l-hERG1a exhibited impaired maturation and intracellular trafficking,thereby potentially increasing the ratio of the hERG1b to hERG1a stoichiometry in the hERG1 tetrameric channel.These changes demonstrated the importance of the heteromeric hERG1 channel in long QT syndrome type 2 pathophysiology.

Clinical Characteristics of 5 Chinese LQTS Families and Phenotype-genotype Correlation

Summary: In order to assess the clinical manifestations and electrocardiogram (ECG) characteristics of Chinese long QT syndrome (LQTS) patients and describe the phenotype-genotype correlation, the subjects from 5 congenital LQTS families underwent clinical detailed examination including resting body surface ECG. QT interval and transmural dispersion of repolarization (TDR) were manually measured. Five families were genotyped by linkage analysis (polymerase chain reacting-short tandem repeat, PCR-STR). The phenotype-genotype correlation was analyzed. Four families were LQT2, 1 family was LQT3. Twenty-eight gene carriers were (14 males and 14 females) identified from 5 families. The mean QTc and TDRc were 0.56±0.04 s (range 0.42 to 0.63) and 0.16±0.04 s (range 0.09 to 0.24) respectively. 35.7 % (10/28) had normal to borderline QTc (≤ 0.460 s). There was significant difference in QTc and TDRc between the patients with symptomatic LQTS and those with asymptomatic LQTS, and there was significant difference in TDRc between the asymptomatic patients and normal people also. A history of cardiac events was present in 50 % (14/28), including 9 with syncope, 2 with sudden death (SD) and occurred in the absence of β-blocker. Three SDs occurred prior to the diagnosis of LQTS and had no ECG record. Two out of 5 SDs (40 %) occurred as the first symptom. Typical LQT2 T wave pattern were found in 40 % (6/15) of all affected members. The appearing-normal T wave was found in one LQT3 family. Low penetrance of QTc and symptoms resulted in diagnostic challenge. ECG patterns and repolarization parameters may be used to predict the genotype in most families. Genetic test is very important for identification of gene carriers.

兔LQT2模型心室肌复极化的性别差异(英文)

小研究旨在探讨长QT综合征(long QT syndromes,LQTS)室性心律失常发生的性别差异及其电生理机制,初步观察了不同性别兔LQT2模型左心室原已存在的电生理异质性和心室复极动力学的特征。实验分为3组,正常组以标准台氏液灌流; LQT2模型组给了含100μmol／dl-sotalol的台式液灌流;LQT2模型+低钾组给予含3．0mmol／L KCl、100μmol／L dl-sotalol的台式液灌流。采用冠状动脉旋支灌注兔左室心肌楔形组织块标本,应用浮置玻璃微电极记录技术进行记录。给予基础刺激周长 (basic cycle length,BCL)为500、1000和2000 ms的S1刺激,同步记录心室肌内膜侧、外膜侧细胞动作电位,并记录跨壁心电图;在BCL为500和1000ms时加用S2程序刺激以记录动作电位时程(action potential duration,APD)恢复曲线。研究发现: 在不同刺激频率时,3组实验雌兔心肌细胞的跨壁复极化离散(transmural dispersion of repolarization,TDR)、APD恢复曲线斜率均大于雄兔,有显著性差异(P<0．05),并呈频率依赖性:LQT2模型组及LQT2模型+低钾组雌雄兔TDR、APD恢复曲线斜率较正常组明显增大(P<0．01)。BCL为1000 ms时,LQT2模型组雌兔7例中1例发生尖端扭转性室性心动过速(torsade de pointes,TdP);LQT2模型+低钾组雌兔7例中5例诱发TdP,雄兔7例中2例诱发TdP,有显著性差异(P<0．05)。结果提示: LQT2模型心肌原已存在的电生理异质性和动态异质性均有明显的性别差异,并呈频率依赖性。在LQT2模型中,TDR以及 APD恢复曲线斜率的增大可能是雌性动物较雄性更易发生尖端扭转性心律失常的原因。

致LQT2的无义突变的HERG通道的表达和药物拯救研究

目的本研究旨在探讨氨基糖苷类抗生素庆大霉素在异源表达系统中对导致长QT综合征2型的无义突变的HERG通道的作用。方法采用聚合酶链反应法制备相关突变体——W927X、R863X和E698X,并克隆到真核细胞表达载体中。将突变体的cDNA瞬时转染至HEK293细胞,应用全细胞膜片钳技术记录通道电流。药物拯救采用将转染24h后的HEK293细胞在含庆大霉素(400μg/mL)的培养液中孵育24h。结果W927X能表达典型的HERG电流,尽管与野生型HERG相比,电流幅值明显下降;R863X和E698X仅表达与未转染细胞上类似的内生性电流,说明未能形成功能性的HERG通道。庆大霉素能增强W927X的功能性表达,使其最大尾电流密度由11.6±2.4pA/pF(n=8)增至19.5±2.7pA/pF(n=7,P<0.05)。通道激活动力学特征在野生型HERG、W927X和W927X加庆大霉素干预组均没有明显差异。然而,庆大霉素对R863X和E698X并无明显作用。结论氨基糖苷类抗生素能部分恢复无义突变的HERG通道的功能性表达,且对不同的突变体其作用效应不同。

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。

利用LQT2兔心脏模型研究吡那地尔对心室复极的影响

目的本研究通过制作一种模拟LQT2的动物模型——Langendorff离体灌流兔心脏LQT2的动物模型,然后用钾通道开放剂吡那地尔(pinacidil)干预,研究吡那地尔对离体LQT2兔心脏模型心室复极的影响,并探讨其作用机制。方法将30只体重为2.5～3.5kg的健康新西兰兔随机分为A、B、C三组,A组(对照组),B组(吡那地尔组),C组(吡那地尔+优降糖组)。取出心脏,立即行逆行主动脉灌注,然后用有齿镊钳夹房室结造成Ⅲ度房室传导阻滞,在Langendorff离体灌流兔心脏上同步记录左室心内膜及心外膜单相动作电位和容积传导心电图。分别用1000ms刺激周长(CLs)起搏至少100个心动周期,体表心电图提示无ST-T明显压低或抬高。然后用加有右旋索他洛尔(d-Sotalol)100μmol/L浓度的台氏液逆行Langendorff灌流30min后再分别用上述刺激周期进行刺激,观察:①90%动作电位时程(APD90);②90%复极时间(RT90);③跨室壁复极离散度(TDR);④早期后去极化(EAD)及尖端扭转型室性心动过速的发生率;⑤平均QT间期等的变化。并对A、B、C三组进行不同的药物制剂干预。结果右旋索他洛尔明显延长离体兔心脏心内膜及心外膜单相动作电位时程(P<0.001);TDR延长(P<0.001);同步记录容积传导心电图的QT间期延长(P<0.001);EAD发生率从0%到86.67%(P<0.01);TdP发生率从0%～43.33%(P<0.05)。吡那地尔缩短由d-Sotalol所引起的动作电位时程延长,使左室心内膜、心外膜的APD90缩短,缩短容积传导心电图QT间期,减少跨壁复极离散度TDR(P<0.001);消除早期后去极化EAD(P<0.01),并抑制触发性心律失常TdP(P<0.05)。吡那地尔+优降糖组的结果显示:APD90、TDR、EAD、TdP等指标在处理后与对照组相比,P>0.05,无统计学意义。结论吡那地尔能抑制LQT2兔心律失常的发生。