Mechanism of drug-induced torsade de pointes: an experimental study in dogs / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of drug-induced torsade de pointes (Tdp) in dogs.</p><p><b>METHODS</b>In 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.</p><p><b>RESULTS</b>D-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.</p><p><b>CONCLUSION</b>EAD 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.</p>

Effects of electric stimulations applied during absolute refractory period on cardiac function of rabbits with heart failure / 华中科技大学学报（医学）（英德文版）

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.

Identification of a novel KCNH2 mutation in a family with congenital long QT syndrome and prediction of the secondary structure of its encoding protein / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Polymerase 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.</p><p><b>RESULTS</b>A 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.</p><p><b>CONCLUSION</b>The 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.</p>

Effect of ABCA1-V771M polymorphism on plasma lipid levels and its relationship with coronary atherosclerotic heart disease / 药物分析学报

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.

Clinical characteristics of 5 Chinese LQTS families and phenotype-genotype correlation / 华中科技大学学报（医学）（英德文版）

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.

Clinical characteristics of 5 Chinese LQTS families and phenotype-genotype correlation / 华中科技大学学报（医学）（英德文版）

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.

Effect of Pioglitazone on Blood Pressure and Beta Cell Function and the Mechanism of Oxidative Stress in Hypertensive Patients With Impaired Glucose Tolerance / 中国循环杂志

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

The effects and mechanism of Alprostadil combined with Shuxuetong treatment on diabetic peripheral neuropathy / 西安交通大学学报(医学版)

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

Clinical characteristics of congenital long QT syndrome families / 西安交通大学学报(医学版)

Objective To elucidate the clinical manifestati on s and electrocardiogram characteristics of congenital long QT syndrome families and try to find out the genotype of the long QT syndrome(LQTS) patients. Methods The routine clinical check up and ECG recordings we re done for the 3 family members. Both QT interval and QTc were measured. Diagno stic criteria for LQTS were defined by Schwartz. Results Fifteen family members were identified as with LQTS and 11 members with intermediate probability to LQTS. The clinical manifestatio ns and ECG characteristics were different from each other. Conclusion The clinical manifestations and ECG characterist ics of LQTS patients from family 1,family 2 and family 3 correspond with LQT2, L QT1 and LQT3, which is caused by HERG,KVLQT1 and SCN5A gene mutation.

Effects of electric stimulation applied during absolute refractory period on contraction and relaxation of ventricular myocytes in normal and failure guinea-pigs / 西安交通大学学报(医学版)

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.

Effects of non-excitatory electric stimulation on cardiac function in normal and infarcted heart rabbits and it's regional effect on myocardium / 中国病理生理杂志

AIM: To investigate the influences of electric stimulation applied during the absolute refractory period (ARP) on the cardiac function of normal rabbits and rabbits after myocardial infarction (MI) and to observe the regional effects of this electric stimulation. METHODS: 64 rabbits were randomly assigned to normal and MI groups and each group was then divided into the anterior and posterior groups. A thoracotomy was performed 4 weeks after MI in rabbits. One set of electrodes was inserted into the anterior and posterior wall of left ventricle of the anterior and posterior groups, respectively. Current pulses were delivered during the ARP (called CCM) during sinus rhythm in rabbits. The left ventricular systolic pressure (LVSP) and the left ventricular end diastolic pressure(LVEDP) as well as maximum positive and negative left ventricular pressure change (?dp/dt_(max)) were observed. RESULTS: In the normal and MI groups, LVSP, +dp/dt_(max) significantly increased, and LVEDP, -dp/dt_(max) were reduced during CCM stimulation compared with the baseline (P0.05). CONCLUSION: Electric stimulation delivered during the ARP significantly enhances the contractility and the relaxation of myocardium in normal rabbits and rabbits after MI, and the effects of CCM stimulation on heart are regional. [

?-Irradiation with a liquid ~(188)Re-filled balloon prevents neointimal proliferation in the carotid rabbit / 中国介入心脏病学杂志

Objective To evaluate the role of ?-irradiation with a liquid 188Re-filled balloon for limiting neointimal proliferation. Methods Balloon overstretch injury was performed in carotid arteries of 12 rabbits and randomly assigned to two groups: the control group (n=6) and the radiation group (n=6), using the liquid 188Re-filled balloon designed to deliver 15 Gy at 0.5 mm from the surface of vessel. All animals survived and were sacrificed in 1 week. Histopathologic analysis was performed. Results The intimal area of radiation group was significantly smaller than that of the control group [(0.04?0.06) mm 2 vs (0.16?0.04) mm 2, P

Tp-e/QT ratio as a predictive index of sudden cardiac death in patients with ST-segment elevation myocardial infarction / 西安交通大学学报(医学版)

Objective To detect Tp-e/QT ratio in patients with acute ST-segment elevation myocardial infarction (STEMI) and explore its clinical significance. Methods Healthy individuals and patients with acute STEMI were recruited in this study. Their first QTc,QTd and Tp-e were measured within 24 h after admission to hospital,and Tp-e/QT ratio was calculated so as to analyze the relation between Tp-Te/QT ratio and malignant ventricular arrhythmia. Results Compared with those of the healthy individuals,the intervals of QTd,Tp-e and QTc were significantly lengthened \[(33.66?16.76)ms vs. (55.29?31.12)ms,(89.55?12.61)ms vs. (142.65?39.33)ms,and (426.57?65.03)ms vs. (482.26?48.03)ms,P

Effects of pulse pressure on coronary artery disease / 西安交通大学学报(医学版)

Objective To study the effects of pulse pressure (PP) on coronary artery disease. Methods High and low systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were measured in 221 cases with coronary heart disease diagnosed by coronary artery radiography, and the differences of coronary artery count, score, and clinic features were analyzed. Results ① Compared with low SBP group \[81mmHg)) were older in age, with higher percentage of females and lower incidence of unstable angina pectoris(UA) and acute myocardial infarction(AMI). ② Compared with low PP group(

Clinical study on the relationship between PON_1 192 Gln-Arg polymorphism and Han patients with Coronary heart disease in Shaanxi / 西安交通大学学报(医学版)

Objective To investigat the relationship between PON_1 192 Gln-Arg gene polymorphisms and coronary artery lesions in Shaanxi Han Chinese.Methods A total of 222 cases with one or more than two branches narrow(≥50%) and 164 cases with no coronary artery narrow(0.05).Conclusion There was no relationship between PON_(1) 192 Gln-Arg gene polymorphisms and Shaanxi Han patients with coronary heart disease.