Role of CACNA1C in Brugada syndrome: Prevalence and phenotype of probands referred for genetic testing.

BACKGROUND: Evidence for the role of the CACNA1C gene, which encodes for the α-subunit of the cardiac L-type calcium channel CaV1.2, as a cause of the BrS3 variant of Brugada syndrome (BrS) is contradictory. OBJECTIVE: The purpose of this study was to define in a large BrS cohort the yield of molecular screening and to test whether appropriate patient selection could improve clinical utility. METHODS: A total of 709 patients were included in this study. BrS probands (n = 563, consecutively referred) underwent CACNA1C sequencing. Two matched cohorts where defined: discovery cohort (n = 200) and confirmation cohort (n = 363). In addition, the clinical phenotypes of a matched SCN5A-positive BrS cohort (n = 146) were included for comparative genotype-phenotype correlation. RESULTS: In the discovery cohort, we identified 11 different rare variants in 9 patients; 10 of the variants (5%) were considered potentially causative based on their frequency in the general population. However, American College of Medical Genetics criteria were unable to classify the majority (80%) of them, which eventually were labeled as variants of unknown significance (VUS). Functional studies revealed a loss of function for 9 variants, pointing to a prevalence of CACNA1C causative variants in 4% of the discovery cohort. Genotype-phenotype correlation showed that pathogenic variants are significantly more frequent in patients with shorter QTc (12.9% vs 2.2% in patients with QTc <390 ms). CONCLUSION: CACNA1C is an infrequent but definitive cause of BrS typically associated with short QT. Functional studies are highly relevant to improve variant interpretation.

Clinical analysis of cardiac tamponade complicating radiofrequency ablation of atrial fibrillation in elderly patients / 中华老年医学杂志

Objective:To investigate the association between age and cardiac tamponade after radiofrequency ablation of atrial fibrillation(RAAF).Methods:Clinical data of patients undergone de novo AF ablation procedures at Beijing Anzhen Hospital from January 2013 to December 2016 were retrospectively collected.Patients were divided into an elderly group(age ≥60 years)and a non-elderly group(age <60 years). Logistic regression analyses were used to evaluate the association between old age and the risk of cardiac tamponade complicating RAAF.Results:A total of 5 313 patients were involved in this study, including 41 patients(0.77%)with cardiac tamponade.The proportion of cardiac tamponade was higher in the elderly group than in the non-elderly group(1.1% or 32/2 950 vs.0.4% or 9/2 363, χ2=8.489, P=0.004). One patient with cardiac tamponade in the elderly group required immediate surgical repair whereas none in the non-elderly group did.No patient died in hospital.Multivariate Logistic regression analysis showed that the risk of cardiac tamponade increased in the elderly group, compared with the non-elderly group( OR=2.570, 95% CI: 1.190-5.570, P=0.017). Stratified analysis revealed that among females and patients with oral anticoagulants, left atrium dimension < 40 mm or procedure duration≥ 120 min in the elderly group carried a higher risk of cardiac tamponade than those in the non-elderly group( OR=1.011, 2.914, 3.922 and 3.244, P<0.05). Conclusions:Old age(age ≥60 years)is an independent risk factor for cardiac tamponade complicating RAAF.

Clinical characteristics of left atrial appendage thrombus in patients with hypertrophic cardiomyopathy and non-valvular atrial fibrillation / 中华心血管病杂志

Objective@#To investigate the incidence and clinical characteristics of left atrial appendage (LAA) thrombus in patients with hypertrophic cardiomyopathy (HCM) and non-valvular atrial fibrillation (AF) .@*Methods@#Data from 10 440 patients with AF who had undergone transesophageal echocardiography (TEE) before cardioversion or catheter ablation at Beijing Anzhen Hospital from April 2006 to December 2018 were retrospectively screened. Two hundred and five HCM patients were included, 820 AF patients with the same CHA2DS2-VASc score over the same period were selected as the control group. HCM patients were divided into two subgroups based on presence or absence of LAA thrombus/sludge. The baseline of clinical information, transthoracic echocardiographic and TEE measures were compared among all the groups. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of left atrial diameter (LAD) for LAA thrombus/sludge. Multivariate logistic regression analysis was applied to analyze the correlative factors of LAA thrombus/sludge in HCM patients.@*Results@#The incidences of LAA thrombus or sludge were higher in HCM group than in control group (10.7% (22/205) vs. 0.7% (6/820); 8.8% (18/205) vs.7.0% (57/820), P<0.001) . In HCM patients, LAD was significantly larger in LAA thrombus/sludge subjects than in those without thrombus/sludge ((48.9±5.1)mm vs. (45.2±6.1) mm, P<0.001). CHA2DS2-VASc score was similar between the two subgroups ((2.0±1.4) vs. (1.8±1.4), P>0.05). There was no difference in the rate of patients with a CHA2DS2-VASc scores ≥2 between the subgroups(62.5% (25/40) vs. 57.0% (94/165), P=0.525). The incidences of LAA thrombus in HCM and AF patients with CHA2DS2-VASc scores of 0, 1 and 2 were 8.8% (3/34) , 9.6% (5/52) , 11.8% (11/119) , respectively; and the rate of LAA sludge were 8.8% (3/52) , 7.7% (4/52) , 9.2% (11/119) , respectively. The cut off value of LAD for the diagnosis of LAA thrombus/sludge was 44.5 mm. Multivariate logistic regression analysis showed that LAD≥44.5 mm (OR=5.134, 95%CI 1.862-14.156, P=0.002) , non-paroxysmal AF (OR=2.782, 95%CI 1.238-6.252, P=0.013) , previous thromboembolism or stroke (OR=1.820, 95%CI 0.774-4.227, P=0.017) were independent determinants of LAA thrombus/sludge.@*Conclusions@#The incidence of LAA thrombus/sludge is higher in patients with HCM and AF than in AF patients without HCM. The CHA2DS2-VASc score is similar between HCM and AF patients with LAA thrombus/sludge and those without thrombus/sludge. Patients with CHA2DS2-VASc score 0-1 are also likely to suffer LAA thrombus/sludge. Left atrial enlargement is associated with LAA thrombus/sludge.

Effect of adenosine kinase small interfering RNA modified corneal endothelial cells on the proliferation and secretion of regulatory T cells / 中华实验眼科杂志

Objective To investigate the role of adenosine kinase (ADK) small interfering RNA (siRNA) modified corneal endothelial cells on the proliferation and secretion of regulatory T cells (Treg cells).Methods The experiment was divided into transfected group and non-transfected group,FAM-ADK siRNA was transfected into corneal endothelial cells with Lipofectamine 3000 in transfected group,and the average mass concentration of adenosine was detected by high performance liquid chromatography in both groups.The experiment was divided into control group (transfected with control siRNA),rapamycin group (added 10 ng/ml rapamycin to culture supernatant after transfected with control siRNA) and ADK siRNA group (added 10 ng/ml rapamycin to culture supernatant after transfected with ADK siRNA).TUNEL staining was used to detect the proportion of apoptosis.Flow cytometry was used to detect the expressions of intercellular adhesion molecule-1 (ICAM-1),vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in corneal endothelial cells.The cells were divided into single cultured group (lymphocytes were cultured separately),co-culture group (lymphocytes were co-cultured with corneal endothelial cells) and ADK siRNA group (lymphocytes were co-cultured with ADK siRNA transfected corneal endothelial cells),and the proportion of CD4+ CD25+ Foxp3 + Treg cells was detected by flow cytometry,and the content of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in the supernatant was detected by ELISA in the three groups.The access and use of clinical specimens was approved by Ethic Committee of Tianjing Taida Hospital (TD201705140901).Results Flow cytometry showed that 95.1％ of the endothelial cells expressed siRNA.The average mass concentration of adenosine in the supernatant of the transfection group was significantly higher than that in the control group ([38.020±6.658] ng/ml vs.[1.663 ±0.581] ng/ml) (t =5.437,P =0.006).TUNEL staining showed that the average apoptotic cell proportion of corneal endothelial cells in the rapamycin group was significantly higher than that in the control group,and the average apoptotic cell proportion of corneal endothelial cells in the ADK siRNA group was significantly lower than that in the rapamycin group,with significant differences between them (t =3.763,P =0.020;t =4.405,P =0.012).Flow cytometry showed that the average fluorescence intensities of ICAM-1,VCAM-1 and E-selectin in the ADK siRNA group was weaker than that in the control group (4.060± 1.179 vs.11.600±2.427,3.600 ± 1.234 vs.11.030 ± 2.291,5.223 ± 1.734 vs.24.270 ± 4.332),with significant differences between them (t =2.794,P =0.049;t =2.857,P =0.046;t =4.081,P =0.015).The proportions of Treg cells in the single cultured group,co-culture group and ADK siRNA group was significantly different (F =12.890,P =0.007),and the proportion of Treg cells in the ADK siRNA group was significantly lower than that in the co-culture group (t =3.650,P =0.022).ELISA assay showed that,the contents of IL-10 and TGF-β in the supernatant in the single cultured group,co-culture group and ADK siRNA group were significantly different (F =20.960,P =0.003;F =27.320,P=0.001),and the content of IL-10 and TGF-β in the supernatant in the ADK siRNA group was significantly higher than that in the co-culture group,respectively (t =4.492,P =0.011;t =5.280,P =0.006).Conclusions ADK siRNA modified corneal endothelial cells can induce Treg cells to proliferate and secrete IL-10 and TGF-β,which provides a new method for induction of corneal allograft immune tolerance.

Performance of interpreting the variants of long QT syndrome according ACMG guidelines by four clinical gene screening agencies from Beijing / 中华心血管病杂志

Objective@#To analyze the interpretation results on the pathogenic classification of KCNH2 variants and SCN5A variants of long QT syndrome (LQTS) based on American College of Medical Genetics and Genomics (ACMG) guidelines by 4 clinical gene screening agencies from Beijing.@*Methods@#Pathogenic classification of 16 variants in KCNH2 and SCN5A was made by 4 clinical gene screening agencies from Beijing based on ACMG guideline. Krippendorff's alpha was used to assess the inter-agency variation consistency.@*Results@#All 4 agencies made pathogenic assessment on all the variants and provided the interpretation results for the classification. For the eight variants from the patients with LQTS, the consistency of classification was only 1/8 and the alpha test value was - 0.01. For the eight variables from incidental findings, the consistency of classification was 4/8 and the alpha test value was 0.407. Evidence analysis of the 4 variants with large differences in classification among agencies showed that the main reasons for the discrepancies originated from the comprehensiveness of the literature search and the inconsistency of the subjective determination of the evidence grade.@*Conclusion@#The consistency of the pathogenic classification of LQTS gene variants based on ACMG guidelines among clinical gene screening agencies from Beijing is poor, which will result in great impact on the clinical treatment strategies of the patients with LQTS. The standardization of pathogenic evaluation of variants in clinical gene screening agencies needs to be improved urgently.

Association between herpes simplex virus infection and atrial fibrillation in elderly individuals / 中华老年医学杂志

Objective To investigate associations of herpes simplex virus(HSV)infection with elevated high-sensitivity C-reactive protein(hsCRP)level and the development of atrial fibrillation(AF) in elderly individuals.Methods Through screening a total of 2,603 individuals,49 patients aged 60 years or over with AF and without structural heart diseases and known risk factors for AF were selected for data collection.Fifty-five elderly healthy control subjects were selected from a population based Chinese Arrhythmia Registry.Baseline characteristics,plasma antibody levels against HSV-1 and-2,and level of hsCRP were analyzed.Results Level of antibodies against HSV-1 was significantly higher in AF patients[(314.5±63.6)mg/L than in control subjects(216.0±50.7) mg/L,P＜0.01].Level of antibodies against HSV-2 was significantly higher in AF patients[(400.1±50.7) mg/L than in control subjects (306.3 ± 64.5) mg/L,P ＜ 0.01].Linear regression analysis demonstrated a positive correlation of plasma levels of hsCRP with both anti-HSV-1 and anti-HSV-2 IgG antibodies (r =0.291,0.188,all P ＜ 0.01).In multiple logistic regression analysis,HSV-1 and HSV-2 antibody levels were significantly associated with AF occurrence(OR =1.035 and 1.034,all P ＜0.01).The optimal cut-off point for predicting AF occurrence was 284.96 mg/L for anti-HSV-1 with sensitivity of 67.3％ and a specificity of 92.7％,and was 366.26 mg/L for anti-HSV-2 with a sensitivity of 67.3％ and a specificity of 85.5％,respectively.Conclusions The increased plasma levels of anti-HSV-1 and anti-HSV-2 antibodies are significantly associated with AF occurrence in elderly adults.

False-negative Possibility in Genetic Test of Congenital Long QT Syndrome by Next-generation Sequencing / 中国循环杂志

Objective: To explore the false-negative possibility in genetic test of congenital long QT syndrome (LQTS) by next-generation sequencing (NGS). Methods: A total of 28 genomic DNA samples were collected from 4 laboratories including 2 commercial medical laboratories using HiSeq2000 platform as Lab1,n=6 and Lab2,n=8; 1 commercial research service laboratory using Ion-torrent platform as Lab3,n=8 and 1 academic laboratory using HiSeq2000 platform as Lab 4,n=6. Sequencing coverage in the exons of protein-coding region in 3 main LQTS pathogenic genes as KCNQ1, KCNH2, SCN5A and possible pathogenic variants were quantitatively analyzed. Results: In Lab1, Lab 2 and Lab 4 with HiSeq2000 platform, above 98% protein coding regions in 3 pathogenic genes were covered with>10-fold reads and 90%-95% were covered with>30-fold reads. In 2 commercial medical laboratories, 3.63% and 9.84% protein coding regions of KCNQ1 gene in 14 samples were covered with<10-fold reads and with<30-fold reads; lower than 10-fold covering region was focused in the 1st exon including about 2% known or likely pathogenic variants. In 2 commercial medical laboratories, 2.64% and 15.76% protein coding regions of KCNH2 gene in 14 samples were covered with<10-fold reads and with<30-fold reads; low covering region was located in multiple exons. For the data from Lab 1, as high as 28.56% protein coding regions of KCNH2 gene were covered with<30-fold reads including 113 (19.79%) known or likely pathogenic variants. SCN5A gene had the best coverage of protein coding region, with no<10-fold reads in all 4 Labs and no<30-fold reads in 2 commercial medical laboratories. Conclusion: Currently, NGS has low coverage region in both KCNQ1 and KCNH2 genes, pathogenic variants could be missed and false-negative possibility should be highly alert.

Predictors of atrial fibrillation recurrence after catheter ablation in hypertrophic cardiomyopathy patients with atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of catheter ablation in Chinese hypertrophic cardiomyopathy (HCM) patients with atrial fibrillation (AF), and to determine the risk factors of AF recurrence.</p><p><b>METHODS</b>This study enrolled 40 HCM patients with AF who underwent primary AF ablation at Beijing Anzhen Hospital from June 2005 to June 2013. Ablation strategy included bilateral pulmonary vein isolation (PVI) for paroxysmal AF (n = 27) and PVI plus left atrial roof, mitral isthmus and tricuspid isthmus linear ablations for persistent AF (n = 13). AF recurrence was followed-up by means of electrocardiography or Holter monitoring. Risk factors associated with AF recurrence were determined by a Cox regression model and the predictive power was evaluated by receiver operating characteristic (ROC) curve.</p><p><b>RESULTS</b>After (34 ± 18) months follow-up, 30% (12/40) cases remained in sinus rhythm off antiarrhythmic drug, most AF recurrence (18/28, 64.3%) occurred within 1 year post ablation. Multivariate Cox regression demonstrated that left atrial dimension (LAD, HR = 1.124, 95% CI 1.051-1.202, P = 0.001) and female gender (HR = 3.304, 95% CI 1.397-7.817, P = 0.007) were independent risk factors of AF recurrence. The cut-off value of LAD at 43.5 mm predicted AF recurrence with sensitivity of 93.5% and specificity of 60.0%. Every 1 mm enlargement in LAD was associated with an increased risk of arrhythmia recurrence (HR = 1.095, 95% CI 1.031-1.163, P = 0.003).</p><p><b>CONCLUSIONS</b>AF ablation in Chinese HCM patients is safe and feasible. However, sinus rhythm maintenance rate is low at long-time follow-up. Most of the recurrent AF occurs within 1 year post AF ablation procedure. Left atrial diameter and female gender are independent risk factors of AF recurrence.</p>

Effects of potassium aspartate and magnesium on ventricular arrhythmia in ischemia-reperfusion rabbit heart / 华中科技大学学报（医学）（英德文版）

The aim of this study was to determine if the potassium aspartate and magnesium (PAM) prevent reperfusion-induced ventricular arrhythmias (RIVA) in ischemia-reperfusion (IR) rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode's solution, and in ischemia group and PAM groups the perfusion of Tyrode's solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode's solution and the PAM group with Tyrode's solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion (TDR) and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group (P<0.05). The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group (P<0.05). Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.

Antiarrhythmic peptide AAPl0 prevents ventricular arrhythmia in rabbit LQT2 model / 老年心脏病学杂志（英文版）

Background and Objective Increased transmural dispersion of repolarization (TDR) has been shown to contribute toinitiation and maintenance of ventricular arrhythmia in long QT syndromes(LQTS).Intercellular uncoupling through gap junctions isan important mechanism for maintaining TDR in both intact and diseased heart.The present study was to test the hypothesis thatimproving gap junction communication reduces TDR and prevents ventricular arrhythmia in rabbit LQT2 model.Methods Anarterially perfused rabbit left ventricular preparation and E-403 (0.5μmol/L)were used to establish a model of LQT2.Preparationswere randomly assigned to control(n=10),AAP-100nmol/L(n=10),AAP-500nM(n=10)groups.Transmural ECG as well as actionpotentials from both endocardium and epieardium was simultaneously recorded. Resuits In LQT2 model.presence of 500nmol/LAAP10 reduced endocardial action potential and TDR and prevented ventricular arrhythmia comparing with the control and AAP 100nmol/Lgroups(P＜0.05).Conclusions The presence of 500 nmol/LAAP10 reduces TDR and prevents ventricular arrhythmia in rabbitventricular model of LOT2.This study suggests a possible role of GJs in TDR in rabbit LQT2 model and indicates a new clinicalapproach to the management of LQTS.

Changes in Phosphorylation of Connexin43 in Rats during Acute Myocardial Hypoxia and Effects of Antiarrhythmic Peptide on the Phosphorylation / 华中科技大学学报（医学）（英德文版）

In order to confirm the hypothesis that during acute hypoxia, the antiarrhythmic peptide (AAP10) could improve conductance by changing the phosphorylation state of connexin43 (Cx43),isolated perfused rat hearts were randomly divided into three groups: control, hypoxia and AAP10 (n=9 in each group). The change in Cx43 phosphorylation was tested by Western-blot; the distribution of Cx43 was observed by confocal immunofluorescence microscopy. Western-blot analysis revealed that the expression of total Cx43 protein was significantly decreased during acute hypoxia,while nonphosphorylated Cx43 (NP-Cx43) was unchanged. AAP10 could increase the expression of total Cx43 protein, but had no effects on the NP-Cx43 protein. Immunofluorescence study showed that during acute hypoxia, both total Cx43 and NP-Cx43 proteins were greatly decreased, while AAP10 only increased the expression of total Cx43 protein, but had no effect of the NP-Cx43 protein expression. These findings suggested that the decrease of intercellular communication may be associated with the reduction of phosphorylated Cx43 (p-Cx43) and translocation of NP-Cx43 from the surface of gap junction into intracellular pools during acute hypoxia. AAP10 can improve intercelluar communication by enhancing phosphorylation of Cx43.

Changes in phosphorylation of connexin43 in rats during acute myocardial hypoxia and effects of antiarrhythmic peptide on the phosphorylation / 华中科技大学学报（医学）（英德文版）

In order to confirm the hypothesis that during acute hypoxia, the antiarrhythmic peptide (AAP10) could improve conductance by changing the phosphorylation state of connexin43 (Cx43), isolated perfused rat hearts were randomly divided into three groups: control, hypoxia and AAP10 (n=9 in each group). The change in Cx43 phosphorylation was tested by Western-blot; the distribution of Cx43 was observed by confocal immunofluorescence microscopy. Western-blot analysis revealed that the expression of total Cx43 protein was significantly decreased during acute hypoxia, while nonphosphorylated Cx43 (NP-Cx43) was unchanged. AAP10 could increase the expression of total Cx43 protein, but had no effects on the NP-Cx43 protein. Immunofluorescence study showed that during acute hypoxia, both total Cx43 and NP-Cx43 proteins were greatly decreased, while AAP10 only increased the expression of total Cx43 protein, but had no effect of the NP-Cx43 protein expression. These findings suggested that the decrease of intercellular communication may be associated with the reduction of phosphorylated Cx43 (p-Cx43) and translocation of NP-Cx43 from the surface of gap junction into intracellular pools during acute hypoxia. AAP10 can improve intercellular communication by enhancing phosphorylation of Cx43.

Value of Acceleration Flow in the Left Anterior Descending Coronary Artery for the Detection of Coronary Artery Stenosis by Transthoracic Coronary Color Doppler Echocardiography / 华中科技大学学报（医学）（英德文版）

Whether the localized flow acceleration occurs in the resting stenotic left anterior descending coronary artery was explored and its value for detection of coronary stenosis estimated.Blood flow in the left anterior descending coronary arteries in 45 patients was detected by transthoracic color Doppler echocardiograph and multipoint pulse Doppler spectrums were recorded in the same segment. The ratio of the maximal peak diastolic velocity to the minimal peak diastolic velocity was calculated. The ratio ≥1.5 was the cutoff value for the presence of localized acceleration flow.There were 23 patients with localized acceleration flow examined by echocardiography. Twenty of them were found to have luminal diameter stenosis (60 %- 98 %) in the left anterior descending coronary arteries by coronary angiography and 3 patients were normal. There were 22 patients without localized acceleration flow examined by echocardiography. Eighteen of them had no or ＜60% stenosis. Four patients had serious stenosis (≥95 %) or occluded segments in the left anterior descending coronary arteries on coronary angiography. The ratio of the maximal peak diastolic velocity to the minimal peak diastolic velocity was significantly higher in patients with left anterior descending coronary artery stenosis than that in those without stenosis (1.9±0.3 vs 1.3±0.2, P＜0.01) and it correlated significantly with left anterior descending coronary artery stenosis (r=0.77, P＜0.01). The specificity by using the ratio≥1.5 for stenosis detection was 85.7 % (18/21), and the sensitivity was 83.3 % (20/24). This study demonstrated that local blood flow velocity was increased in the resting stenotic left anterior descending coronary artery. Transthoracic color Doppler echocardiography is a reliable noninvasive method to detect localized acceleration flow in the left anterior descending coronary artery stenosis and it is useful in the noninvasive diagnosis of stenosis in the left anterior descending coronary artery.

Sex difference in the repolarization currents of rabbit ventricular cells / 华中科技大学学报（医学）（英德文版）

The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4+/-26.5 ms, n=15) than in male ones (489.0+/-20.7 ms, n = 14), P0.05). The lower IK.tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

Effect of Lidocaine and Amiodarone on Transmural Heterogeneityricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia / 华中科技大学学报（医学）（英德文版）

To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups: control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential (MAP) recording technique, MAPs of recorded across the left ventricular free wall in rabbit hearts perfused transmural dispersion of repolarization (TDR) and arrhythmic induced by ischemia. Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group (62.5 %), but no case in lidocaine group (P<0.01) and only 1 case in amiodarone group had ventrilar arrhythmia (P< 0.01). No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.

Sex Difference in the Repolarization Currents of Rabbit Ventricular Cells / 华中科技大学学报（医学）（英德文版）

Summary: The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P<0.05. In female rabbit myocytes, IK,tail, Ito, IK1 and ICa,L were 0.71±0.05 pA/pF (n=17), 8.28±1.03 pA/pF (n=18), 24.5±3.6 pA/pF (n=12) and 9.0±2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84±0.07 pA/pF (n=18), 8.60±1.20 pA/pF (n=18), 25.9±4.5 pA/pF (n=14) and 9.3±2.6 pA/pF (n=16) respectively. IK,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in Ito, IK1 and ICa,L between male rabbits and female rabbits (P>0.05). The lower IK,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

The changes of potassium currents in rabbit ventricle with healed myocardial infarction / 华中科技大学学报（医学）（英德文版）

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.

Protective effect of carvedilol on abnormality of L-type calcium current induced by oxygen free radical in cardiomyocytes / 华中科技大学学报（医学）（英德文版）

The protective effect of carvedilol on abnormality of L-type calcium current induced by oxygen free radical in single guinea pig ventricular myocytes was studied. Whole-cell patch clamp technique was used to study the effect of H2O2 (0.5 mmol/L) on L-type calcium current in single guinea pig ventricular myocytes and the action of pretreatment with carvedilol (0.5 micromol/L). 0.5 micromol/L carvedilol had no significant effect on ICa,L and its channel dynamics. In the presence of 0.5 mmol/L H2O2, peak current of ICa,L was reduced significantly (P<0.001), the I-V curve of ICa,L was shifted upward, steady-state activation curve and steady-state deactivation curve of ICa,L were shifted left and recovery time of ICa,L was delayed significantly (P<0.001). 0.5 micromol/L carvedilol significantly alleviated the inhibitory effect of H2O2 on ICa,L as compared with that in H2O2 group (P<0.01). In addition, carvedilol reversed the changes of dynamics of ICa,L induced by H2O2. It was concluded that carvedilol could alleviate the abnormality of L-type calcium current induced by oxygen free radical in cardiomyocytes. It shows partly the possible mechanism of the special availability of carvedilol in chronic heart failure.

The changes of potassium currents in rabbit ventricle with healed myocardial infarction / 华中科技大学学报（医学）（英德文版）

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.

Short-Coupled Variant of Torsade de Pointes / 华中科技大学学报（医学）（英德文版）

Presented in this paper were 3 cases of a special kind of polymorphic ventricular tachycardia (VT). The clinical manifestation was recurrent syncope without organic heart disease. The electrocardiogram (ECG) was characterized by normal QT intervals with short-coupled variant of torsade de pointes. The efficacy of treatment with class Ⅰ,Ⅱ,Ⅲ antiarrhythmic drugs was not apparent but verapamil had an excellent therapeutic effect for it. This kind of VT had a high incidence of sudden death, so it was very important for physicians to identify and treat it promptly with long-term verapamil. The mechanism of short-coupled variant of torsade de pointes was unclear. It probably had some relationship with triggered activity or imbalance of autonomic nervous system.