OBJECTIVETo investigate the mechanism of drug-induced torsade de pointes (Tdp) in dogs.

METHODSIn arterially perfused canine left ventricular wedge preparations, the action potential duration (APD) of the endocardial (Endo), midmyocardial (M) and epicardial (Epi) myocytes, and transmural electrocardiogram (ECG) were recorded simultaneously. The effects of different concentrations of D-Sotalol on APD, transmural dispersion of repolarization (TDR), early after depolarization (EAD) and Tdp were observed.

RESULTSD-Sotalol prolonged APD of the Endo, M and Epi cells in a concentration-dependent manner from 0-100 µmol/L, and increased TDR due to a preferential APD prolongation of the M cells relative to Epi and Endo cells. The application of D-Sotalol elicited EAD, R on T ventricular premature beats, transmural reentry and Tdp in the M cells.

CONCLUSIONEAD and R on T ventricular premature beats induced by D-Sotalol in M cells triggers Tdp, which is maintained by TDR increment and transmural reentry.

Animals ; Dogs ; Electrocardiography ; Heart Conduction System ; Torsades de Pointes ; chemically induced ; physiopathology

The effects of electric currents applied during absolute refractory period (ARP) on the cardiac function of rabbits with heart failure due to myocardial infarction (MI), and the safety of this method were investigated. Thirty rabbits were randomly assigned equally to 3 groups: sham-operated group, LV-anterior wall cardiac contractility modulation (LV-CCM) group, and septum-CCM (S-CCM) group. A thoracotomy was performed on all the rabbits. Electric pulses were delivered during the ARP on the anterior wall of left ventricle in CCM group and in the septum in S-CCM group, respectively. The left ventricular systolic pressure (LVSP) and maximum positive left ventricular pressure change (+dp/dt(max)), heart rates, ventricular tachycardia, ventricular fibrillation were observed. It was found that, as compared with the baseline, LVSP, and +dp/dtmax were significantly increased, on average, by 15.2% and 19.5% in LV-CCM group (P<0.05), and by 8.5% and 10.8% in S-CCM group (P<0.05). LVEDP was significantly decreased and -dp/dt(max) increased both in LV-CCM group and S-CCM group (P<0.05). CCM had no effect on heart rate and induced no arrhythmia in short time. It is concluded that electric currents delivered during the ARP could significantly enhance the contractility of myocardium safely, suggesting that CCM stimulation is a novel potent method for contractility modulation.

The effects of electric currents applied during absolute refractory period(ARP)on the cardiac function of rabbits with heart failure due to myocardial infarction(MI),and the safety of this method were investigated.Thirty rabbits were randomly assigned equally to 3 groups: sham-operated group,LV-anterior wall cardiac contractility modulation(LV-CCM)group,and septum-CCM(S-CCM)group.A thoracotomy was performed on all the rabbits.Electric pulses were delivered during the ARP on the anterior wall of left ventricle in CCM group and in the septum in S-CCM group,respectively.The left ventricular systolic pressure(LVSP)and maximum positive left ventricular pressure change(+dp/dtmax),heart rates,ventricular tachycardia,ventricular fibrillation were observed.It was found that,as compared with the baseline,LVSP,and+dp/dtmax were significantly increased,on average,by 15.2% and 19.5% in LV-CCM group(P<0.05),and by 8.5% and 10.8% in S-CCM group(P<0.05).LVEDP was significantly decreased and-dp/dtmax increased both in LV-CCM group and S-CCM group(P<0.05).CCM had no effect on heart rate and induced no arrhythmia in short time.It is concluded that electric currents delivered during the ARP could significantly enhance the contractility of myocardium safely,suggesting that CCM stimulation is a novel potent method for contractility modulation.

OBJECTIVETo identify the gene mutation in a Chinese family with congenital long QT syndrome (LQTS) and predict the changes of the secondary structure of the protein.

METHODSPolymerase chain reaction and DNA sequencing were used to screen for KCNH2 mutation in the proband. After the mutation was identified, KCNH2 gene of the family members was screened by multiplex PCR with site-specific primers. Network analysis software was used to predict the secondary structure of the KCNH2 protein.

RESULTSA novel heterozygous missense mutation of F463L(GenBank accession no.EU218526) located at the transmembrane domain S2 of KCNH2 was detected. The mutation did not result in the change of the transmembrane domain, but altered the hydrophobicity and secondary structure of the protein.

CONCLUSIONThe novel mutation identified in this study has enriched the GenBank data of ion channel gene mutation in LQTS. The changes of the secondary structure caused by the gene mutation were analyzed by Mfold and TMHMM software, which may help to understand LQTS.

Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA Mutational Analysis ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels ; chemistry ; genetics ; Female ; Humans ; Hydrophobic and Hydrophilic Interactions ; Long QT Syndrome ; congenital ; genetics ; Male ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Protein Structure, Secondary ; Protein Structure, Tertiary

Objective To explore the risk association of ABCA1-V771M polymorphism with coronary heart disease (CHD) in Hart nationality in Northwest of China. Methods With case-control study, ABCA1-V771M polymorphism was detected in 204 unrelated Hart nationality people in Northwest of China, and all the subjects by coronary angiography were grouped into 106 cases and 98 controls. The genotypes and alleles frequency distribution of ABCA1-V771M polymorphisms were analyzed by PCR-RFLP analysis, and the clinical statistics of serum lipids were compared and its effects of ABCA1-V771M polymorphism on the plasma lipid levels and coronary atherosclerotic heart disease were analyzed. Results The genotypic frequencies of ABCA1-V771M polymorphism matched well under Hardy-Weinberg equilibrium (P>0.05), V and M allelic frequencies were 33.3% and 66.7%. In comparison with VV+VM genotype carriers, MM genotypes carriers had much lower plasma levels of HDL-C (P<0. 001) and much higher plasma levels of TG (P<0. 05). M allelic frequency in CHD group was significantly higher than V allelic frequency (P<0. 05). M allele was related with more severity of atherosclerosis in the coronary artery than V allele (P<0.05). However, there was no obvious difference in the incidence of AMI among carriers with three genotypes of ABCA1-V771M polymorphism (P>0.05). Conclusion ABCA1-V771M polymorphism was not only associated with the plasma levels of HDL-C and TG, but also related to the susceptibility and severity of coronary atheroselerotic heart disease. Moreover, M771 allele appeared to be atherogenie among Han population in Northwest of China.

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 (< or = 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 beta-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.
Arrhythmias, Cardiac ; etiology ; genetics ; Asian Continental Ancestry Group ; Electrocardiography ; Female ; Genotype ; Humans ; Long QT Syndrome ; complications ; congenital ; genetics ; Male ; Pedigree ; Phenotype

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 (< or = 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 beta-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.
Arrhythmia/etiology ; Arrhythmia/genetics ; Asian Continental Ancestry Group ; Electrocardiography ; Genotype ; Long QT Syndrome/complications ; Long QT Syndrome/congenital ; Long QT Syndrome/*genetics ; Pedigree ; *Phenotype

Objective:To investigate the effect of pioglitazone on blood pressure,blood glucose and beta cell function and the mecha- nism of oxidative stress in hypertensive patients with impaired glucose tolerance(IGT). Methods:One hundred and sixty patients were divided into two groups:pioglitazone group and control group.The levels of fasting plasma glucose(FPC),2 hours postprandial glucose(2hPG),blood pressure,Homa I3,Homa IR,blood malondiahtehyde (MDA)and superoxide dismutase before and after pioglitazone treatment were compared. Results:After pioglitazone treatment for 8 weeks,FPG,2hPG,FInS,2hPInS,GHbAlc,mean systolic and diastolic blood pressure,Homa IR and blood MDA were significantly decreased(P

Objective To investigate the clinical effects of Alprostadil combined with Shuxuetong treatment on patients with diabetic peripheral neuropathy,and its influence on malondialdehyde(MDA),superoxide dismutase(SOD) and total antioxidative capability(TAOC).Methods Totally 160 patients with DPN were divided into two groups: treatment group(100 cases) and control group(60 cases).The levels of blood SOD activity,serum MDA and serum TAOC were determined before and after treatment.Results The symptoms in both groups were significantly improved,but the total effective rate in treatment group was significantly better than that in control group(80.0% vs.41.7%,P

Objective To investigate the effect of electric stimulation applied during absolute refractory period on contraction and relaxation and Ca 2+ transient of ventricular myocytes from normal guinea-pigs. Methods The ventricular myocytes of guinea-pigs were obtained by enzyme digesting, and the extent of the contraction and relaxation and Ca 2+ transient were recorded through the motion edge detection system. The Ca 2+ transient was reflected by fluorescence ratio (360/380) ( F 360/F 380). Results The ventricular myocytes from the normal guinea-pigs: ①The contraction extent of guinea-pig ventricular myocytes increased by (16.55?5.49)%. The peak velocity of shorting (contraction) and the peak velocity of relengthening (relaxation) increased by (17.43?7.08)% and (19.74?9.08)%, respectively(n=10); ②The extent of F 360/F 380 increased (25.79?6.88)%. The peak velocity of F 360/F 380 increased by (29.47?9.25)% and (22.52?7.81)% during shortening and relengthening, respectively(n=10). The ventricular myocytes from failure guinea-pigs: ①The contraction extent of guinea-pig ventricular myocytes increased by (15.53?5.31)%. The peak velocity of shortening (contraction) and the peak velocity of relengthening (relaxation) increased by (10.60?3.02)% and (23.32?8.26)%, respectively(n=6); ②The extent of F 360/F 380 increased (16.82?7.03)%. The peak velocity of F 360/F 380 increased by (16.27?5.91)% and (10.32?2.46)% during shorenting and relengthening, respectively(n=6). Conclusion Appropriate electric stimulation applied during absolute refractory period might strengthen the contracting and relaxing function of normal and failing ventricular myocytes in guinea-pigs.