Molecular Mechanisms of Increased Heart Rate in Shenxianshengmai-treated Bradycardia Rabbits.

BACKGROUND: The molecular mechanisms of Shenxianshengmai (SXSM), a traditional Chinese medicine, on bradycardia have been incompletely understood. The study tried to investigate the gene expression profile and proteomics of bradycardia rabbits' hearts after SXSM treatment. METHODS: Twenty-four adult rabbits were randomly assigned in four groups: sham, model, model plus SXSM treatment, and sham plus SXSM treatment groups. Heart rate was recorded in all rabbits. Then, total RNA of atria and proteins of ventricle were isolated and quantified, respectively. Gene expression profiling was conducted by gene expression chip, and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to confirm the results of gene expression chip. We used isobaric tags for elative and absolute quantitation and Western blotting to identify altered proteins after SXSM treatment. RESULTS: There was a constant decrease in the mean heart rate (32%, from 238 ± 6 beats/min to 149 ± 12 beats/min) after six weeks in model compared with that in sham group. This effect was partially reversed by 4-week SXSM treatment. Complementary DNA microarray demonstrated that the increased acetylcholinesterase and reduced nicotinic receptor were take responsibility for the increased heart rate. In addition, proteins involved in calcium handling and signaling were affected by SXSM treatment. Real-time RT-PCR verified the results from gene chip. Results from proteomics demonstrated that SXSM enhanced oxidative phosphorylation and tricarboxylic acid (TCA) cycle in ventricular myocardium to improve ATP generation. CONCLUSIONS: Long-term SXSM stimulates sympathetic transmission by increasing the expression of acetylcholinesterase and reduces the expression of nicotinic receptor to increase heart rate. SXSM also restored the calcium handling genes and altered genes involved in signaling. In addition, SXSM improves the ATP supply of ventricular myocardium by increasing proteins involved in TCA cycle and oxidation-respiratory chain.

Incidence of ischemic stroke and systemic embolism in patients with hypertrophic cardiomyopathy, nonvalvular atrial fibrillation, CHA2DS2-VASc score of ≤1 and without anticoagulant therapy.

Data on the risk of ischemic stroke and systemic embolism (iSSE) events in patients with nonvalvular atrial fibrillation (NVAF), a CHA2DS2-VASc score of ≤1, hypertrophic cardiomyopathy (HCM), and without anticoagulant therapy are still lacking. The aim of this study was to investigate the incidence of iSSE events in these patients. We consecutively screened medical records of patients with HCM and NVAF referred to Fuwai Hospital between January 1994 and March 2014. The primary end point was iSSE events, defined as a composite of ischemic stroke and systemic embolism. Follow-up was carried out to ascertain end point status. Medical records of 522 patients with NVAF and HCM were screened. A total of 108 patients (20.7 %) with a CHA2DS2-VASc score of ≤1 and without anticoagulant therapy were enrolled and constituted our study population. After a median follow-up of 2.4 years (range 0.6-14.1 years; 376.2 patient-years), ischemic stroke occurred in 2 patients, resulting in death of 1 patient in the first year and paralysis of the other patient in the fourth year. No other iSSE events occurred. The incidence of iSSE was 0.9 % [95 % confidence interval (CI) 0.0-5.0 %] in the first year, and 0.5 % per 100 patient-years (95 % CI 0.1-1.9 %). The risk of iSSE events seems low in patients with NVAF, a CHA2DS2-VASc score of ≤1, HCM, and without anticoagulant therapy. Multicenter studies with sizeable study populations are needed to validate the risk of iSSE events in these patients.

Variations of electroanatomic substrates and markers of successful ablation in idiopathic left ventricular tachycardia: role of electroanatomic substrates and potential mechanism of tachycardia.

OBJECTIVES: The variation of the substrates of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) was not understood. The purpose of this study was to investigate the variation of electroanatomic substrate [slow conduction zone (SCZ) and left ventricular conduction system (LVCS)] in ILVT and control individuals and markers of successful ablation. METHODS: Electroanatomical mapping was performed during sinus rhythm in 20 ILVT patients and 26 control individuals with paroxysmal supraventricular tachycardia. LVCS and SCZ were tagged in geometry and the anatomic aspects were investigated. RESULTS: According to the distribution of Purkinje potential, LVCS was distinguished into three types: left bundle branch (LBB) was divided into two discrete fascicles without interconnections; divided into three separate fascicles; and fanlike structure distribution over septum broadly. The length of LBB and its fascicles in patients with ILVT were slightly longer than those of controls (P > 0.05). In the ILVT group, the SCZ was located at the inferoposterior septum in 17, inferior apical septum in one and two SCZs were located at the posterior and mid-septal in the other two patients, which were greater in size and longer in length than those of six controls (P < 0.05). At the crossover junction area with diastolic potential and Purkinje potential, with the size of 1.5 ± 0.4 cm(2), concealed entertainment and ablation were obtained successfully in all patients with ILVT. CONCLUSION: The anatomy of the LVCS and SCZ is highly variable in patients with ILVT, and the crossover junction area with diastolic potential and Purkinje potential might be a marker of ablation.

The electrophysiological characteristics of isolated diastolic potentials in idiopathic ventricular arrhythmias arising from the right ventricular outflow tract.

OBJECTIVE: The significance of isolated diastolic potentials (IDPs) in patients with idiopathic ventricular arrhythmias (IVAs) arising from right ventricular outflow tract (RVOT) is currently unknown. The objective of this study was to clarify the characteristics of IDPs and its role in guiding ablation in RVOT-IVAs. METHODS AND RESULTS: Twenty-five consecutive patients with RVOT-IVAs and ten control subjects were studied. Electro-anatomical mapping was performed in RVOT during sinus rhythm. The electrophysiological characteristics of IDPs and its relation to successful ablation site were evaluated. Successful ablation was achieved during IVAs in 22 patients and during sinus rhythm in the remaining three. IDPs were recorded in all patients in the vicinity of successful ablation sites during sinus rhythm before ablation, with the area of 1.44 /- 0.28 cm2, maximal amplitude of 0.32 +/- 0.06 mV and the distance to pulmonary valve of 1.39 +/- 0.25 cm. IDPs could still be recorded after ablation except one. Moreover, IDPs were characterized by decremental and/or automatic property by studying intervals between ventricular activation and IDPs (V-IDPs) during sinus rhythm. And V-IDPs intervals during sinus rhythm were longerthan those during IVAs (P = 0.012). However, IDPs were only recorded in one patient in the control group and the incidence of IDPs was remarkably lower than that in the RVOT-IVAs group (1/10 vs. 25/25, P < 0.001). CONCLUSIONS: IDPs were present in patients with RVOT-IVAs. IDPs area and/or border region might be the successful ablation site and their precise mechanism remains to be clarified.

[Value of identifying the slow conduction zone of idiopathic left ventricular tachycardia by electroanatomic mapping].

OBJECTIVE: To explore the value of identifying slow conduction zone(SCZ) of idiopathic left ventricular tachycardia(ILVT) by electroanatomic mapping. METHODS: Twelve patients with ILVT were mapped by a 3-dimensional electroanatomic (EA) mapping system. Left posterior fascicular potential (PP) and the SCZ with diastolic potential (DP) in LV during sinus rhythm (SR) and ventricular tachycardia (VT) were mapped after a three-dimensional endocardial geometry of the left ventricular was established. Then we investigated the electrophysiological and anatomic characteristics of SCZ. RESULTS: EA mapping was successfully performed in 9 patients during SR and VT, and in 3 patients during VT. The SCZ with DP was located at the inferoposterior septum, and the length of the SCZ was (25.1 ± 2.2) mm with a conduction velocity of (0.08 ± 0.01) m/s. There was no difference in these parameters between patients during SR and VT (P > 0.05). There was one area with PP located at the posterior septum. The areas with both DP and PP were found in 9 patients during SR and VT. In addition, this area was coincided with such area during VT during SR and radiofrequency ablation targeting the site within the area abolished VT in all patients. CONCLUSIONS: The ILVT substrate within the junction area of the SCZ and the posterior fascicular can be identified by EA mapping and used to guide the ablation of ILVT.

[Radiofrequency catheter ablation of the premature ventricular contractions originating from His bundle region].

OBJECTIVE: To explore the electrocardiogram and 3-dimensional electroanatomic mapping features and radiofrequency catheter ablation efficacy of patients with premature ventricular contractions (PVCs ) originating from His bundle region. METHODS: Between February 2009 and February 2011, 10 consecutive patients ( 4 male, aged from 19 to 59 years) who underwent ablation for frequent PVCs originating close to His bundle region in our department were included. Electroanatomic mapping of RVOT and ASC, ablation was performed with the 7F 4-mm-tip ablation catheter. RESULTS: Among these 10 patients with PVCs originating from His bundle region, 6 originated from the RVOT, 1 from NCC and 3 from RCC. Eight patients showed LBBB morphology,1 patient with PVCs originated from RCC and 1 patient with PVCs originated from NCC showed RBBB morphology. At the successful ablation sites, local ventricular activation v wave was detected 22-52 (32.6 ± 10.2) ms earlier than the QRS wave in the surface electrocardiogram. The distance between target and His bundle was 5.0-8.4(7.0 ± 1.1)mm. Ablation was successful in all 10 patients without complications (PVCs < 500 beats/24 h post ablation). CONCLUSION: PVCs originating near the His bundle have similar electrocardiographic and electrophysiological characteristics for PVSc originated from the RVOT or ASC. Because of the close anatomical relationship between RVOT and ASC, it is necessary to mapping both RVOT and ASC to accurately identify the site of PVCs origin and to guild successful ablation.

[Preferential conduction to right ventricular outflow track leads to left bundle-branch block morphology in patient with premature ventricular contraction originating from the aortic sinus cusp].

OBJECTIVE: The purpose of this study was to explore the relationship between originate and breakout and radiofrequency catheter ablation strategy in patients undergoing radiofrequency ablation for premature ventricular contractions originating from the aortic sinus cusp (ASC) using 3-dimensional electro anatomic mapping. METHODS: This study included 21 consecutive patients (10 male) underwent ablation for frequent PVCs originating from ASC in our hospital between May 2009 and February 2012. Electro anatomic mapping and ablation of right ventricular outflow track (RVOT) and left ventricular outflow track (LVOT) were performed with the 7F 4-mm-tip ablation catheter from right femoral vein and artery. Activation mapping and pacing mapping were performed in all patients. RESULTS: Ablation was successful in all 21 patients successful ablation target in left coronary sinus cusp (LCC, n = 17), in right coronary sinus cusp (RCC, n = 2) and in noncoronary sinus cusp (NCC, n = 2). Seven patients showed a RBBB morphology (group A) and 14 patients showed a LBBB morphology (group B). In group A, earliest ventricular activation (EVA) was recorded 22 - 34 (27.4 ± 4.6) ms earlier before QRS at the site of catheter ablation in ASC. In group B, EVA was later in RVOT than that in ASC in 5 patients and EVA at the site of catheter ablation in RVOT and ASC was 22 - 28 (25.2 ± 2.7) ms and 26 - 40 (32.8 ± 5.2) ms, respectively (t = -3.6, P = 0.024) while EVA was earlier in the remaining 9 patients and EVA recorded in RVOT and ASC was 22 - 38 (28.7 ± 5.9) ms and 18 - 28 (22.7 ± 3.6) ms, respectively (t = 3.8, P = 0.005). CONCLUSION: Patients with premature ventricular contractions originating from the ASC often show preferential conduction to the RVOT, which may explain the LBBB morphology of ECG in these patients.

[Retrospective analysis on the clinical features and management of acute and subacute right ventricular perforation by pacemaker lead].

OBJECTIVE: To describe the clinical characteristics and management of the acute and subacute cardiac perforation by pacing leads. METHODS: We retrospectively analyzed clinical data of patients with acute and subacute right ventricular perforation by pacemaker lead occurred in our hospital between 2006 and 2011. RESULTS: Seven cases of confirmed acute and subacute right ventricular perforation by pacemaker lead were enrolled. The perforation rate was 0.15%, 2 cases of perforation occurred during the procedure. The main manifestation was low blood pressure and pericardial effusion. These two patients with cardiac tamponade underwent urgent percutaneous pericardiocentesis and patients recovered without complication. The remaining 5 cases of perforation occurred within 4-16 days after the pacemaker implantation. The main symptoms were diaphragm stimulation and chest pain. Signs of leads dysfunction were observed in all 5 patients. The diagnosis of cardiac perforation was confirmed by chest X-ray, echocardiography, or computed tomography. In all these 5 patients, the leads were removed by simple traction under fluoroscopic guidance with surgical backup support, no complication was observed. CONCLUSION: Acute and subacute right ventricular perforation is a rare but serious complication of pacemaker implantation. In most patients, the leads can be safely removed under fluoroscopic guidance with surgical backup support and close monitoring.

[Management of refractory ventricular tachycardia in patients with non-myxomas primary cardiac tumors].

OBJECTIVE: To summarize the clinical characteristics and treatment experience of patients with non-myxomas primary cardiac tumors accompanied with refractory ventricular tachycardia (VT). METHODS: Clinical and imaging data as well as therapy efficacy and outcome were analyzed in 10 patients with non-myxomas primary cardiac tumors accompanied with refractory VT. RESULTS: There were 5 male and 5 female patients in this cohort [mean age (37.6±18.2) years]. Palpitation was presented in all 10 patients, 7 patients experienced syncope, and 2 patients suffered from amaurosis. The diagnosis was made by combined use of transthoracic echocardiograms, MRI, and CT scan. The time from symptom to diagnosis was (33.2±36.7) months. Symptom-related VT was documented by ECG or Holter monitoring. MRI suggested lipoma in 7 patients, lymphoma in 1 patient and fibroma in another patient. Seven tumors were located in the left ventricle, 1 in right atria, 1 at peri-aortic root and 1 near right ventricular outflow tract. Nine out of 10 patients received anti-arrhythmic drug therapy. The ventricular tachyarrhythmia disappeared after surgical tumor resection in 4 patients. All other patients who were treated with antiarrhythmic drugs, radiofrequency ablation or subtotal excision showed only suboptimal efficacy during (39.4±25.1) months follow-up. CONCLUSION: Surgical tumor removal is the best treatment strategy for the treatment of refractory ventricular tachycardia in patients with primary cardiac benign tumors.

Idiopathic ventricular fibrillation with fragmented QRS complex and J wave in resting electrocardiogram.

OBJECTIVE: To describe the clinical characteristics of idiopathic ventricular fibrillation (IVF) with fragmented QRS complex (f-QRS) and J wave in resting electrocardiogram. METHODS: We reviewed data from 21 case subjects in our hospital who were resuscitated after cardiac arrest due to IVF and assessed the prevalence of f-QRS and J wave in resting electrocardiogram (ECG). All the case subjects were classified among three groups based on the electrocardiographic morphology: group I, both f-QRS and J wave were observed (n = 6), group II, only J wave was observed (n = 9), group III, neither f-QRS nor J wave was observed (n = 6). Population characteristics, history of syncope or sudden cardiac arrest, incidence of ventricular fibrillation (VF), and circumstance of VF were evaluated among the three groups. RESULTS: The incidence of index events (syncope, survived cardiac arrest and VF episodes recorded in implantable cardioverter defibrillator (ICD) or pacemakers) was 13.4 ± 5.6 per-year in group I, 10.8 ± 3.9 per-year in group II, and 9.8 ± 4.2 per-year in group III. There were significant differences in incidences among the three groups, the most frequent index events were observed in group I. The hazard ratio for incidence was 3.2 (95%CI, 1.1-7.9; P = 0.01). The history and circumstance of the index events were different among the groups. In group I, all the index events occurred during sleep in early morning. In group II, four subjects suffered VF during strenuous physical activities or agitation state, two during sleep in early morning, three in usual activity. In group III, one subject suffered VF during sleep in early morning, one in agitation state, four in usual activity. CONCLUSIONS: This study suggests that the IVF patients with the combined appearance of f-QRS and J wave in the resting ECG suffer an increased risk of VF, this subgroup of IVF patients has a unique clinical feature.

The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels.

BACKGROUND: Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels. METHODS: Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current (I(Ca-L)), inward rectifier potassium current (I(K1)), and transient outward potassium current (I(to1)) were studied in rat ventricular myocytes and sodium current (I(Na)), slow delayed rectifier current (I(Ks)), and HERG current (I(Kr)) were investigated in transfected human embryonic kidney 293 cells. RESULTS: One hundred µmol/L paeoniflorin reduced the peak I(Ca-L) by 40.29% at the test potential of +10 mV (from (-9.78 ± 0.52) pA/pF to (-5.84 ± 0.89) pA/pF, n = 5, P = 0.028). The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were (-11.22 ± 0.27) mV vs. (-5.95 ± 0.84) mV (n = 5, P = 0.007), respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred µmol/L paeoniflorin completely inhibited the peak I(Na) and the effect was reversible. Moreover, paeoniflorin inhibited the I(K1) by 30.13% at the test potential of -100 mV (from -25.26 ± 8.21) pA/pF to (-17.65 ± 6.52) pA/pF, n = 6, P = 0.015) without effects on the reversal potential and the rectification property. By contrast, 100 µmol/L paeoniflorin had no effects on I(to1), I(Ks) or I(Kr) channels. CONCLUSIONS: The study demonstrated that paeoniflorin blocked I(Ca-L), I(Na), and I(K1) without affecting I(to1), I(Ks), or I(Kr). The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.

[Evaluation of shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation: a randomized, double-blind and controlled multicenter trial].

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicinal shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation. METHODS: From August 2007 to July 2008, Beijing Chaoyang Hospital conducted a multicenter study, select the eleven hospital's outpatient subjects, aged 18 to 75 years old, male or female, paroxysmal atrial fibrillation (at least one electrocardiogram diagnosis) seizure frequency ≥ 2 times/month, according to the ratio 1:1:1, subjects were randomly divided into three groups: a. shensongyangxin group, taking shensongyangxin capsule 4 + propafenone analogues 150 mg, 3 times a day; b. propafenone group, taking propafenone tablets 150 mg + 4 shensongyangxin analogues, 3 times a day; shensongyangxin capsule + propafenone group, taking shensongyangxin capsule 4 + propafenone 150 mg, 3 times a day. The treatment course is 8 weeks, with 3 times of follow-up. RESULTS: Total of 349 cases of paroxysmal atrial fibrillation, which 117 cases in shensongyangxin group, 115 cases in propafenone group; 117 cases in shensongyangxin + propafenone group. The baseline data analysis showed that there were no significantly difference (P > 0.05) among the three groups of atrial fibrillation seizure frequency, vital signs, general condition, medical history, 24-hour ambulatory ECG, 12-lead normal electrocardiogram, cardiac ultrasound and symptoms. The comparison before and after (8 weeks) treatment showed that the frequency (from 6 times/m to 2 times/m in each group, P < 0.01), number of cases [from 46 (43.3%) to 22 (20.8%), 43 (43.4%) to 25 (25.3%), and 40 (40.6%) to 31 (29.2%), respectively P < 0.01] and duration time of attack of atrial fibrillation (from 4 h to 0.5 h, 4 h to 0.5 h, and 4.25 h to 0.5 h, respectively P < 0.01) all decreased in three groups. No significant difference among the three groups comparing the overall effect (62.3%, 58.6%, and 58.5%, respectively, P > 0.05), while the efficacy of TCM symptoms in shensongyangxin group (80.2%) was better than that of propafenone group (67.7%) (P < 0.05). Safety evaluation showed that adverse reaction rate was 1.8% in shensongyangxin group, and 8.2% and 5.4% in propafenone group and shensongyangxin + propafenone group. CONCLUSION: Shensongyangxin capsules and propafenone have comparable efficacies in the treatment of PAF. The efficacy of TCM symptoms is better than propafenone. Shensongyangxin capsules have an excellent profile of safety.

[Clinical characteristics and outcome of 32 patients with long-QT syndrome accompanied with torsade de pointes].

OBJECTIVE: To summarize the clinical characteristics and outcome of patients with long-QT syndrome (LQTs) accompanied with torsade de pointes. METHODS: Thirty-two eligible patients were included in this study. Clinical and electrocardiographic data were analyzed and telephone or out-patient follow-up were made in all patients. RESULTS: There were 15 patients with inherited LQTs (h-LQTs) and 17 patients with acquired LQTs (a-LQTs). There are more women (n = 24) than men (n = 8). ß blockers, potassium and magnesium supplement were the basic therapy for h-LQTs patients, bivent pacemaker was implanted in 2 patients and implantable cardioverter defibrillator was implanted in 5 patients. Ventricular tachyarrhythmias and syncope occurred in 4 patients during (39.4 ± 25.1) months follow-up. In 17 a-LQTs patients, one patient with dilated cardiomyopathy died suddenly and another patient with implanted cardioverter defibrillator experienced one ventricular tachycardia during (30.9 ± 13.3) months follow-up. CONCLUSIONS: The prognosis in h-LQTs and a-LQTs patients with structure heart disease is poor. ICD or CRT-D therapy is suggestive for a-LQTs patients with structure heart disease.

[Readthrough of nonsense mutation W822X in the SCN5A gene can effectively restore expression of cardiac Na+ channels W822X].

OBJECTIVE: In this study we investigated the functional restoration of nonsense mutations in the SCN5A gene. METHODS: The readthrough-enhancing reagents were introduced to HEK293 cells to suppress one nonsense mutation W822X in the SCN5A gene. Patch-clamp was used to record the whole-cell current and dynamics. Western blot and immunofluorescence staining were used to certify the expression and the location of the sodium channel. RESULTS: In transfected HEK293 cells, the nonsense mutation in SCN5A inhibited the expression level of full-length protein, and the sodium currents from the mutant channels were less than 3% of the wild-type level. Readthrough enhancement by decreasing translation termination efficiency with a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1), the sodium current from the mutant cDNAs was restored to as much as 30% of the wild-type. After the treatment by the readthrough-enhancing reagents, the channels from cDNA carrying W822X remained the features of wild-type phenotype, and Western blot and immunochemical staining also showed the expression of full-length channel proteins. CONCLUSION: Readthrough-enhancing reagents could effectively suppress nonsense mutations in SCN5A and partially restore the function of sodium channel and the expression of full-length channels.

Novel compound heterozygous mutations T2C and 1149insT in the KCNQ1 gene cause Jervell and Lange-Nielsen syndrome.

Mutations in the KCNQ1 gene account for more than 90% of the individuals with Jervell and Lange-Nielsen syndrome (JLNS). In this study, we identified and characterized two novel KCNQ1 mutations that caused JLNS. A 6-year-old deaf girl suffering from recurrent syncope had a documented electrocardiogram with polymorphic ventricular fibrillation since the age of 4 years. The baseline electrocardiogram showed a significantly prolonged corrected QT interval (524 msec). Genetic analysis revealed that the proband carried two heterozygous mutations of T2C and 1149insT in the KCNQ1 gene on separate alleles. Patch-clamp analysis demonstrated that the T2C mutation resulted in significant reduction in the slowly activated delayed rectifier current (IKs). Furthermore, western blot analysis and confocal imaging revealed that the T2C mutation produced a truncated protein with trafficking defects. In contrast, the 1149insT mutation failed to generate any measurable current, consistent with no protein expression in both the cell membrane and cytoplasm. Moreover, co-expression of the T2C and 1149insT mutations significantly reduced the peak tail current density to 8.27% of the wild-type (WT) current value, while co-transfected WT channels with either T2C or 1149insT mutant channels produced comparable current and channel kinetics to that of WT channels. Our study demonstrates that the compound heterozygous mutations T2C and 1149insT cause the 'loss-of-function' of the IKs that may account for the clinical phenotype of the proband. Multiple mechanisms have been involved in the pathogenesis of 'loss-of-function' of IKs.

Beta2-adrenoceptor gene variant Arg16Gly is associated with idiopathic ventricular outflow-tract tachycardia.

BACKGROUND: Imbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia (IVOT). We aimed to investigate whether the major genetic variants in ß(1)- and ß(2)-adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia (ILVT). METHODS: Patients with IVOT and ILVT from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in the ß(1)-adrenoceptor, Arg16Gly and Gln27Glu in the ß(2)-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: A total of 227 patients with IVOT and 110 patients with ILVT were included. Genotyping revealed that the 16Gly allele of Arg16Gly variant of ß(2)-adrenoceptor was associated with a higher risk of IVOT (OR: 1.40, 95%CI: 1.12 - 1.75, P = 0.003 in the addictive model and OR: 1.62, 95%CI: 1.14 - 2.31, P = 0.007 in the dominant model). Patients with Gly16Gln27 haplotype also had a higher risk of IVOT (OR: 1.38, 95%CI: 1.11 - 1.73, P = 0.012). Other four variants, including Ser49Gly and Arg389Gly in ß(1)-adrenoceptor, Gln27Glu in ß(2)-adrenoceptor and GNB3 C825T, did not differ between patients with IVOT and controls. In patients with ILVT, no significant difference was found in these five variants compared with controls. CONCLUSIONS: Arg16Gly in ß(2)-adrenoceptor is significantly associated with IVOT in Chinese Han population. Major genetic variants in ß(1)- and ß(2)-adrenoceptor and GNB3 C825T may not be associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT.

Nifekalant hydrochloride terminating sustained ventricular tachycardia accompanied with QT dispersion prolongation.

BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation are the main reasons causing sudden cardiac death. This study aimed to investigate the effects of nifekalant hydrochloride (NIF) on QT dispersion (QTd) in treating VT. METHODS: A total of 16 consecutive patients suffered sustained VT was included and then randomly divided into two groups according to the administration duration of NIF. In long-time group (group L), patients were injected with NIF continuously for at least 12 hours after a bolus dose. The patients in short-time group (group S) were injected with NIF just for 1 hour. RESULTS: There were 7 of all 10 episodes of VT which were terminated by NIF, including 4 episodes in group L were stopped over 1 hour after continuous infusion of NIF. One patient suffered from torsade de pointes. Electrocardiography analysis indicated that QTd was significantly decreased 12 hours after stopping of infusing NIF compared with that when VT stopped ((45.4 +/- 22.1) ms vs. (73.4 +/- 33.2) ms, P < 0.01), and the corrected QTd (QTcd) decreased too ((47.8 +/- 22.9) ms vs. (78.3 +/- 36.5) ms, P < 0.01). There was a positive correlation between the increase in QTd and dose of administrating NIF (P < 0.01), so was QTcd (P < 0.01). CONCLUSIONS: More administration of NIF indicates higher terminating rate of VT and more QTd prolongation. However, the safety is acceptable if several important issues were noticed in using NIF, such as serum potassium concentration, stopping side-effect related agents, and carefully observing clinical responses.

Connexin 43 remodeling induced by LMNA gene mutation Glu82Lys in familial dilated cardiomyopathy with atrial ventricular block.

BACKGROUND: Mutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy) characterized by early onset atrio-ventricular block (A-V block) before the manifestation of dilated cardiomyopathy and high risk of sudden death due to ventricular arrhythmia, which is very similar to the phenotype of gap junction related heart disease. This study aimed to determine the expression and localization of connexins in neonatal myocytes transfected with wild-type (WT) or mutant LMNA to elucidate how these mutations cause heart diseases. METHODS: We studied the connexin 43 (Cx43) and connexin 40 (Cx40) expression in cultured neonatal myocytes transfected with wild-type (WT) or mutant LMNA (Glu82Lys (E82K) and Arg644Cys (R644C)) using confocal imaging and Western blotting analysis. RESULTS: Cx43 protein expression was reduced by 40% in cells transfected with LMNA E82K than that in cells transfected with WT LMNA cDNA. Confocal imaging showed that the Cx43 located inside the cells by LMNA E82K. By contrast, LMNA E82K mutation had no effect on expression and localization of Cx40. LMNA R644C transfection did not show any significant effects on gap junctions at all. CONCLUSIONS: Our findings suggest that LMNA E82K significantly reduced the Cx43 expression and altered its localization which may be one of the pathological mechanisms underlying LMNA-related heart disease.