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Risk Factor Research Of Malignant Arrhythmia

Posted on:2010-10-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:L FengFull Text:PDF
GTID:1114360275975361Subject:Medical cardiovascular disease
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Background:Ventricular fibrillation(VF) and myocardial ischemia are inseparable.In clinic,the patients with acute myocardial infarction(AMI) are at high risk to develop ischemia-induced ventricular arrhythmias leading to sudden cardiac death(SCD).Some studies suggest that individual susceptibility to ischemia-induced arrhythmia may be related to the gene encoding ion channels.One of them is the cardiac ATP-sensitive potassium channel(KATP),which plays important roles in the physiology and pathophysiology of cardiovascular system by coupling the metabolic state of the cells to cellular electrical activity.This study aimed to investigate the association of genetic variants of KATP and ischemia-induced ventricular arrhythmia.Methods:A case control study,including 238 patients diagnosed with coronary heart disease(CHD) and ventricular arrhythmias,250 age-and-sex matched patients diagnosed with CHD only as CHD control,and 250 age-and-sex matched community people as general control.Two tag single nucleotide polymorphisms(SNP)(rs 5215 T/C; rs2285676 C/T) in Kir6.2/KCNJ1l gene and one SNP(rs 7316271 C/T) in the promotor region of SUR2A/ABCC9 gene was detected with polymerase chain reaction and restriction fragment length polymorphism technique.Results:SNP rs2285676(C/T) was significantly associated with ventricular arrhythmia event in CHD patient with/without adjust with age and sex(OR:1.331,adjusted OR:1.558,P<0.05).rs2285676 TT genotype was significantly higher in CHD patients with ventricular arrhythmia than two control groups(CHD with ventricular arrhythmia: 17.72%;CHD control:10.89%;general control:12.05%,P<0.05).QTc was statistically different in each genotype of tag SNP rs2285676(C/T),(CC:386.56±72.48 ms;CT: 392.66±52.51 ms;TT:418.34±72.12 ms,P=0.007).Conclusion:Genetic variation of tag SNP rs2285676(C/T) in Kir6.2/KCNJ11was strongly associated with ventricular arrhythmia event in CHD,and has different phenotype of QTc interval in electrocardiogram. Objective:The goal of this study was to study the relationship between NT-proANP,NT-proBNP or left ventricular ejection fraction(LVEF) and risk of ventricular arrhythmia in patient with coronary artery disease.Method:Concentration of plasma N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide(NT-proBNP) were measured by enzyme-linked immunosorbent assay in 400 patients with coronary heart disease(CHD) and 136 health people as control.LVEF was measured by the modified Simpson 8 equation with echocardiography.Patients were separated into two groups according to ventricular arrhythmia events.Results:The plasma concentrations of NT-proANP and NT-proBNP were much higher in patients with CHD than those in healthy controls[NT-proANP: (4001.13±4421.42) fmol/m and(1043.75±523.08) fmol/ml,P<0.01; NT-proBNP(706.94±770.44) fmol/ml and(327.31±103.87) fmol/ml,P<0.01].Both NT-proANP and NT-proBNP were positively correlated with NYHA classification(NT-proANP:r = 0.659,NT-proBNP:r=0.690,P<0.01),and negatively correlated with LVEF(NT-proANP:r =-0.493,NT-proBNP:r = -0.491, P<0.01).The area of receiver-operating characteristic(ROC)curve were larger with NT-proANP than NT-proBNP for diagnose mild to moderate LVSD(LVEF<50%:0.799 and 0.767,P<0.01:LVEF<40%:0.820 and 0.738,P<0.01).Patients wish ventricular arrhythmia has lower LVEF compared to that in patients without ventricular arrhythmia(CHD-ventricular arrhythmia:54.31±12.025%;CHD-Control:62.21±7.571%.P=0.011). NT-proANP,NT-proBNP were not significantly different between these two groups.Multiple logistic regression analysis revealed that LVEF and age were risk factor of ventricular arrhythmic event in CHD patient.On the other hand,NT-proBNP and Nt-proANP could not predict ventricular arrhythmic event in CHD patient.Conclusions:NT-proANP and NT-proBNP can reflect cardiac function of patients with CHD.Both of them can be used to predict LVSD.Only LVEF but not NT-proBNP or NT-proANP was associated with ventricular arrhythmic event in CHD patient. Background The purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden death in Yunnan province.Method The electrocardiograms of 338 residents from three villages(Dayao,Ninglang, Heqing) with high incidence of unexplained sudden death and one control village(Dali) were analyzed[averaged age was(33.4±11.7) years,175 men and 163 women]. Results The incidence of cardiac arrhythmias was similarly low in all groups.The left ventricular hypertrophy was observed in 34.6%of residents from Dayao.QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali[control(386.8±27.22) ms,Ninglang(428.92±25.71 ) ms;Heqing (440.67±28.03) ms;Dayao(417.7±24) ms,P<0.05 vs control )].Incidence of U wave was significantly higher in Heqing village than that in control village(P<0.05 ). The QUc of these 3 villages was:(613.67±37.34) ms,(597.19±46.47) ms,(608.59±39.59) ms respectively,and also significantly longer than the control village of Dali (589.33±41.27)ms(P<0.05).The typical pattern of U wave presents as enlarged U wave and apparent T-U complex.In the 7 residents who have the family history of unexplained sudden death,6 residents have U wave,and 4 of them present typical U wave pattern.Conclusion The significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc,enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects. Background Shen song Yang xin(SSYX) was a compound of Chinese medicine with the effect of increasing heart rate(HR).This study aimed to evaluate its electrophysiological properties in heart and cellular levels.Methods The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks(n=8,per group).Cardiac electrophysiological study(EPS) was performed before and after drug administration.The Guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential(AP).Results SSYX treatment accelerated the HR from(141.8±36.0) beats per minutes to(163.0±38.0) beats per minutes(P= 0.013) without changing the other parameters in surface electrocardiogram.After blockage of the autonomic nervous system by metoprolol and atropin,SSYX had no effect on intrinsic HR(IHR),but decreased corrected sinus node recovery time(CSNRT) and sinus atrium conducting time(SACT).Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial(A),atrioventricular node(AVN) and ventricular(V) effective refractory period(ERP).In isolated guinea pig ventricular myocytes,the most obvious effect of SSYX on action potential was a shortening of the action potential duration(APD) without change in shape of action potential.The shortening rates of APD30,APD50 and APD90 were 19.5%,17.8%and 15.3% respectively.The resting potential(Em) and the interval between the end of APD30 and APD90 did not significantly change.Conclusions The present study demonstrated that SSYX increased the HR and enhanced the conducting capacity of the heart in the condition of the intact autonomic nervous system.SSYX homogenously decrease the ERP of the heart and shorten the APD of the myocytes,suggesting its antiarrhythmic effect without proarrhytnmia.
Keywords/Search Tags:Ventricular arrhythmia, ATP-sensitive potassium channel, single nucleotide polymorphisms, KCNJ11, ABCC9, Heart failure, NT-proANP, NT-proBNP, Left ventricular systolic dysfunction, arrhythmia, Sudden death, cardiac, Long QT syndrome, Electrocardiography
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