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Studies Of Hemodynamic Characteristics In Vasovagal Syncope Patients And Prediction Of Tilt Table Test Result And Research Of C825T SNP In The GNB3 Gene

Posted on:2009-11-22Degree:MasterType:Thesis
Country:ChinaCandidate:X G FengFull Text:PDF
GTID:2144360272961859Subject:Department of Cardiology
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Background:Vasovagal syncope is a kind of neurally mediated reflex, which induced by nervous reflection and displayed bypotension or bradycardia.It is characterized by hypopiesia,bradycardia or appearance of autonomic nerve excitation such as pallor,nausa,sweating, hyperventilate,and so on.The diagnosis of vasovagal syncope is based on case history and confirmed by the head-up tilt table test.Vasovagal syncope is particularly prevalent in the younger patients,especially in young women.The morbidity is about 44%of all syncope patients and 70%of unexplained syncope patients.The vasovagal syncope is divided into three types according to the head-up tilt table test of character of hemodynamics:type1 mixed,type2:cardioinhibitory,type3:pure vasodep- resssor.Although it rarely threatening life,vasovagal syncope may affect quality of life such as frequent seizures occur in some patients and even lead to serious accidents,such as falls,head trauma especially in the elderly.It is circumscribed for tilt table test to diagnosis vasovagal syncope because of the sensitivity of 26-80%and the specificity of 90%.Detailed case history of unexplained syncope patients is significant and is helpful to diagnosis and understand the charact eristic of the pathogenesis.Therefore,we collected 10 significant symp tom in vasovagal patients and combine with the hemodynamic characteristics of HUTT to predict tilt table test results.With the constantly progressing of molecular biology,electrophysiology and experiment techniques,the pathogenes of vasovagal syncope is been deepening awareness,lt is found that theheterotrimeric G protein, which involving in regulating blood pressure and deciding the plasma renin activity and serum Na~+,K~+ concentration by effecting the natriumhydrogen exchange of cells,is the idioreceptor's catenation proteinum of automatic nervous system,angiotensin angiotonin system and endothelin system,It is reported that the GNB3 gene is associated with vasovagal syncope.However,the investigation to the relationgship between vasovagal syncope and gene GNB3 is not enough.It is difficult to determine the probability of the disease according to the GNB3 polymorphism.Gene detection is just a pathway that could provide evidence for clinical diagnosis,And it is helpful for us to evaluate early the risk of the disease and understand the relationship between genetype and phenotype.Collecting the clinical data of unexplained syncope and analyzing the result of the basis tilt test and nitroglycerin provocation test are helpful to understand the clinical characteristics,etipathogenisis, nosogenesis,diagnose of vasovagal syncope and the hemodynamic features in tile testing,as well as the correlation analysis among them.These also benefit to predict the tilt table test results and provide the theoretical basis for the treatment and lay preliminary basis for the future of gene therapy and gene diagnosis.Objectives:To study the features of hemodynamic patterns displayed over the course of head-up tile testing and evaluate the predicting value in patients who related clinical characteristics and estimate GNB3 C825T polymorphism manifestation in vasovagal patients.Methods:One hundred and twenty-four unexplained syncope patients were made basis tilt test and nitroglycerin provocation test.A multifunctional monitor was used for the measurement of changes of blood pressure and electrocardiogram automatically.According to VASIS(vasovagal syncope internationgal study),the tilt test positive type are as follows:typel mixed,type2A cardioinhibitory without asystole,type2B cardioinhibitory with asystole,type3,vasodepressor.Exceptions to this classification,include chronotropic incompetence,excessive heart rate rise(heart rate>130bpm).Some significant symptoms in vasovagal patients(such as dizziness,diaphoresis,collapse,sicchasia,disgorging, cacesthesia,gatism,pallescence,convulsion and surgical trauma) were collected for predicting the results of HUUT.In 89 positive tilted patients(B group,typical vasovagal patients 74,non-typical history vasovagal patients 15) and 151 healthy Han people controled(A group),the genomic DNA was extracted from blood and the GNB3 C825T polymorphism was diagnosed by restriction of the PCR amplicon with BseDI(MBI).All patients were genotyped and next analyzed in regard to typical vasovagal history.We have compared the distribution features of CC,CT,TT allele between the two groups.the statistical analysis of results:All data are presented as mean value±standard of the mean.The significance of differences between groups was assessed using Chi-square test.Qualitative data expressed as a percentage were compared by Chi-square test with Yates correction. Logistic regression was used for multivariate analysis.Statistically significant difference was defined as P<0.05.All analyses were performed using the Statistica version 5.0 PL(StatSoft Poland) statistical software.Results:All patients were able to tolerate tilt testing.89(72%) of 124 unexplained syncope patients displayed hemodynamic pattern of vasovagal response,among which 54(60.7%) displayed pattern of mixed vasovagal response,14(15.7%) cardioinhabitory response and 21(23.4%) vasodepressor response,and 35(28.2%)patients are negative to this test.The majority of patients overed(older than) 45-year-old displayed vasodepressor response(25.4%,P=0.090) and straighten intolerance(22.2 %,P=0.040).Vasodepressor response and straighten intolerance have significant effect on age group.Older age was concerned with cacergasia of autonomic nerve.Younger age has significant effect on cardioinhabitory response(P=0.010) and the age has no significant effect on ofmixed vasovagal response(P=0.336).Gender has no significant effect on hemodynamic response during tilt(P=0.656)we have summarized ten symptoms of all the patients' s case history who suffered from syncope or premonitory syncope,and these items could be predicting factors to the results of tilt test including dizziness(65%), collapse(48%),sicchasia(50%) and diaphoresis(48%)(dizziness P=0.001, collapse P=0.035,sicchasia P=0.012,diaphoresis P=0.039). There were 74 patients have typical vasovagal history of 89 positive tilted ones,and 36 of them present genotype CC,it account 48.6%(36/74) percent.The prevalence of genotypes CC in typical patients was significantly higher than that in control group.There were significant differences in the distribution rate of C and T allele between the two groups(P=0.012).The frequency of C allele that appeared in typical vasovagal patients was significantly higher than that in control group,which prompted that C allele might be a susceptibility gene for typical history vasovagal patients.The prevalence of genotypes TT in unrepresentative vasovagal patients was significantly higher than that in control group.There were significant differences in the distribution rate of C and T allele between the two groups(P=0.000).The frequency of T allele that appeared in non-typical history vasovagal patients was significantly higher than that in control group.Conclusion:Vasovagal syncpe patients occupy a substantial proportion of unexplained syncope patients.The majority of them is mixed vasovagal response,followed by cardioinhabitory response and vasodepressor response.Chronotropic incompetence was predicted by increasing age.Most of vasovagal syncpe patients made HUTT displayed hemodynamic pattern of vasovagal response.The result of HUTT could be predicted by some significant symptoms such as dizziness,collapse,sicchasia and diaporesis,which could be learned by inquiring about the case history of syncope patients.The GNB3 C825T polymorphism is concerned with the occurrence of vasovagal syncpe.The frequency of C allele that appeared in typical history vasovagal patients.T allele seems to be susceptibility gene for non-typical history vasovagal patients.
Keywords/Search Tags:syncope, vasovagal syncope, polymorphism, head-up tilt test, C825T
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