The Study Of Yangxinkang Tablet For Heart Failure With Heart-qi Deficiency Syndrome

1.Theory ResearchWe briefly introduce modern western medical progress,as well as modern Traditional Chinese Medicine(shortened as TCM)research and its advantages of on heart failure(shortened as HF),then we detailedly discuss both western medicine and TCM therapy progress on asymptomatic HF,review the past researches of Yangxinkang tablet on HF in order to show the existing problems and the research direction.2.Experiment Research2.1 ObjectiveBy making animal models through complex modeling method,we try to explore the Yangxinkang tablet protection effect for heart structure and function and the mechanism so as to provide proof evidence for preventing HF from happening,treating asymptomatic HF and improving HF patients long-term prognosis2.2 Animal Model Making,Grouping Method90 SPF grade Wistar rats are randomly divided into 2 groups,18 in control group and 72 in experimental group.The 72 rats will be again averagely divided into blank group,Yangxinkang tablet low dose group,high dose group by using "diet-control+exhaustive swimming+propranolol" modeling method2.3 Administration MethodRats in each experiment group were intragastrically adminstrated the corresponding dose,while control group and blank group rats were intragastrically administrated with distilled water2.4 Detection IndexWe observed the rats height,exhaustive swimming time,breath rate,Urine volume and heart color ultrasound detection index,Brain Natriuretic Peptide (BNP),Myocardial Troponin I(shortened as CtnI),soluble Fas(shortened as sFas),super oxide dismutase(shortened as SOD),Assay of Malondialdehyde (shortened as MDA),the concentration of myocardial ATP,ADP,AMP and Na +-K +-ATPase activities inside myocardial mitochondria,the mitochondrial respiratory function,pathological sections of myocardial tissues observed by transmission electron microscope2.5 Results2.5.1 The establishment of HF animal model and evaluationBy using "diet-control+exhaustive swimming+propranolol" modeling method,rats in modeling group gradually showed tiredness and asthenia,and their noses as well as tails became cyan but without limbs edema,and exhaustive swimming time became much shorter;in blank group rats breath rate got faster and showed significant decrease in EF and FS and had larger left ventricular end-systolic diameter(shorten as LVESD),the BNP level also showed significant difference compared with normal group.pathological sections observed by transmission electron microscope indicated that there is an obviously pathogenic change inside rats myocardial tissue of blank group,all these show that we had got successful HF modeling,a mild HF model.2.5.2 Heart-qi deficiency animal model evaluationCompared with the control group,model group showed obvious heart-qi deficiency manifestations,SOD activity decreased while the MDA level rised obviously,which showed highly significant difference from the control group. Though the index of breath rate,EF,FS,LVESD,SOD,MDA,we consider that we has got successful,durable and stable animal model.2.5.3 the changes of Neuroendocrine Cytokines inside HF rats with Heart-qi deficiency syndromeAfter modeling BNP,sFas,cTnI level in blank group showed significant rise,compared with the control group,which indicated that heart-qi deficiency rats had neuroendocrine dysfunction,cardiac myocyte injury and myocardial apoptosis etc.2.5.4 The Free Radical Metabolism In Heart-Qi Deficiency RatsCompared with the control group,in blank group rats of all stages appeared SOD activities decreasing while the MDA level rising obviously,which showed there were free radical metabolism disorder and disequilibrium between oxidative and anti-oxidative inside the rats bodies. 2.5.5 The Change Of Mitochondrion Structure And Function In HF Rats With Heart-Qi Deficiency SyndromeAfter successfully modeling,we can see in blank group myocardium mitochondrion hyperplasia,increased volume with myofibrils compressed, shapes were all in different size and unclear internal composition,cristae became sparse and part were extincted.2 weeks later numbers of myocardium mitochondrion decreased evidently.12 weeks later mitochondrion were hyperplasia and having unclear internal composition.All indicated that rats with heart-qi deficiency syndrome had the ultrastructure changes of mitochondrion swelling,cristae disrupting and parts being extinctedIn blank group the Na +-K +-ATPase activities of all rats in every stage decreased,mitochondrial respiratory control rate and oxidative phosphorylation rate declined,much different from that of normal group rats(P＜0.05),which indicated that rats of the syndrome were in low mitochondrion respiratory function,result in decreasing the content of myocardial ATP and ADP but increasing AMP.Therefore rats of the syndrome appeared abnormalities in the functions and the structures of mitochondrion2.5.6 The Results of Electron Microscopy And Pathological changes In HF Rats Of Heart-Qi Deficiency SyndromeRats in normal group did not have that pathological and ultrastructure changes,while rats of blank group appeared disorderly myocardial myofibers and granular degeneration and lymphocytic infiltration in mesenchyma,the observations through Electron Microscopy showed that the myofibrils arranged disorderly,the dark and bright bands became instincts or even dissolve and dissipate,large vacuolization.Mitochondrion were hyperplasia,swelling at early stage and decreased at late stage.Such apoptosis and injures as karyopyknosis,unclear nucleolus and nuclear membrane could be observed,which showed that inside the myocardial cell of the modeled rats,there were obvious inflammatory reaction,necrosis and ultrastructure abnormal as well as myocardial apoptosis.2.5.7 The Effect And Mechanism Of Yangxinkang tablet for HF with Heart-Qi Deficiency SyndromeIn High and low dose of experiment group(Yangxinkang group),the syndrome improved 16 days earlier than that of blank group;breath rate did not rise remarkly;heart did not appear any change in the structure and function, BNP,cTnI,sFas has dropped while SOD and MDA has rised,which helps to improve the Na +-K +-ATPase activities,the mitochondrion respiratory function and increase myocardial ATP content.Yangxinkang tablet can not only invigorate heart-qi,prevent heart-qi from exhausting,improve rats exercise tolerance, promote the recovery of heart-qi deficiency syndrome.The mechanism maybe it improve the neuroendocrine system and the myocardial energy metabolism, regulate the balance of oxidative and anti-oxidative,relieve the myocardial injures,prevent cardiac myocyte from apoptosis and remodeling so as to improve the cardiac structure and function2.6 Summary"diet-control+exhaustive swimming+propranolol" modeling method can be used to establish heart-qi deficiency model.The research showed that Yangxinkang tablet can not only invigorate heart-qi,prevent heart-qi from exhausting,promote the recovery of heart-qi deficiency syndrome,but also prevent heart failure from Deterioration by protecting heart structure and function,which provides proof evidence for the use of Yangxinkang in primary and secondary prevention for HF,which can Interference asymptomatic HF in advance,inhibited or slowdown ventricular remodeling progress,improve the patients long-term prognosis3 Clinical Retrospective Analysis3.1 ObjectiveWe try to explore the relationship between TCM syndrome and HF ABCD stage,NYHA gradation,HF clinical types so as to provide evidence the treatment of heart failure by differentiation of TCM.3.2 MethodWe made TCM and western diagnosis criterion followed by《Principle on New Chinese Traditional Medicine Clinical Research》and the chapter about SHE diagnosis criterion in《Congestive Heart Failure》published by Science and Technology Literature Press,we have collected 255 HF cases of all stage, statistics analyzed by SPSS 11.5,and rank sum test3.3 Results3.3.1 Total features of all casesAmong all patients,the most common TCM syndrome is qi deficiency and blood stasis accompanied with phlegm;the cause is hypertension and coronary heart disease;1-3 risk factors are most common.Most HF patients are of B stage and GradeⅠprevalence rate of diastolic dysfunction is much higher than others,most of them are asymptomatic3.3.2 The relationship between TCM syndrome and ABCD stageWith the TCM syndrome qi deficiency,blood stasis,turbid-phlegm developing toward deficiency of both qi and yin syndrome and edema syndrome due to yang deficiency,the HF rank rised.qi deficiency,blood stasis,turbid - phlegm syndrome are mainly at B stage;while qi and yin deficiency syndrome at C stage and Yang deficiency and water overflowing syndrome at D stage3.3.3 The relationship between all TCM syndrome type and the heart function gradationThe heart function grade increased with the TCM syndrome qi deficiency,blood stasis,turbid - phlegm developing toward deficiency of both qi and yin syndrome and edema syndrome due to yang deficiency.GradeⅠconsist of patients of qi deficiency and accompanied with blood stasis,turbid - phlegm,while patients of qi-yin deficiency syndrome are particularly at GradeⅢ,Ⅳand Yang deficiency and water overflowing syndrome at GradeⅣ.3.3.4 The relationship between all TCM syndrome type and HF typeThe HF type changed from diastolic dysfunction to systolic dysfunction or both with the TCM syndrome qi deficiency,blood stasis,turbid - phlegm developing toward deficiency of both qi and yin syndrome and edema syndrome due to yang deficiency.qi deficiency,blood stasis,turbid - phlegm manifest mainly as simple diastolic dysfunction;while qi-yin deficiency Yang deficiency and water overflowing syndrome manifest as systolic dysfunction or accompanied with diastolic dysfunction3.3.5 The relationship between TCM syndrome and risk factor numberThe risk factor number change with the accompanying syndromes,which increase as the higher extent of accompanying syndromes;and approximately the same as the similar accompanying syndromes3.3.6 the relationship between TCM syndrome and basic diseasesTCM syndrome of qi deficiency,blood stasis,turbid - phlegm are mainly associated with hypertension and coronary disease,while of qi-yin deficiency syndrome and edema syndrome due to yang deficiency are mainly associated with dilated cardiomyopathy,congenital heart disease,rheumatic heart disease and other basic diseases 3.3.7 The analysis about the accompanied TCM syndromesQi deficiency,blood stasis,turbid-phlegm are most accompanied TCM syndromes among HF patients,but there is no significant difference between all accompanied TCM syndromes and HF stage,gradation4.summaryThere are close relationships between HF TCM syndrome and HF stage,gradation,type,basic diseases and the proportion of risk factors,patients of HF B stage,gradeⅠare the most common,and heart-qi deficiency syndrome is the main TCM syndrome.