A Clinical And Experimental Research On Chronic Heart Failure Using Yangxinkang Tablet

Part one Literature ResearchThis research based on referring to domestic and international literature and observing the current research situation of chronic heart failure (CHF) and mastered the cognition of etiology, pathogenesis, treatment of CHF from the period of Huangdineijing to tang, song, yuan, ming, qing dynasty and the clinical experience of modern traditional Chinese physician. We also summarized the research method and achievements of TCM and western medicine in treating CHF for the past few years and provided solid theory support for clinical and experimental study.Part two Clinical Research1.ObjectiveTo objectively evaluate clinical effect and safety on treatment of CHF using yangxinkang tablet and to provide the theoretical basis for yangxinkang tablet being approved by the State for production and sale.2. MethodTaking the currently accepted treatment of CHF as a control, We carried out a prospective, randomized, double-blind, multi-center controlled clinical study. Cases included in this study were randomly divided into control group and treatment group. Cases of control group received basic therapy plus analog Yangxinkang tablet, and cases of treatment group received basic therapy plus Yangxinkang tablet,3 tablets each time,3 times each day, for 4 weeks. We observed the changes in cardiac function, TCM Syndroms, and Minnesota Satisfaction Questionnaire Scales of patients with heart failure before and after treatment.3. Result(1) comparison of curative effect on cardiac function:the total effective rate was 83.5% in the treatment group and 71.3% in the control group, and there was a statistically significant difference in efficacy between the two groups (P<0.05)(2) comparison of curative effect on TCM Syndroms:the total effective rate was 88.7% in the treatment group and 77.7% in the control group, and there was a statistically significant difference in efficacy between the two groups (P<0.05)(3) comparison of symptoms scores of gasp, fear of cold and cold in the extremities, swollen of face and limbs, cough and expectoration:after treatment, symptom scores of two groups had a significantly lower, and comparing with before treatment, the difference was statistically significant (P<0.01).Symptom scores in treatment group decreased more significantly, and there were statistically significant differences in the change value between the two groups (P<0.05)(4) comparison of total dimension scores and physical dimension scores of Minnesota Satisfaction Questionnaire Scale:after treatment, scores of two groups had a significantly lower, and comparing with before treatment, the difference was statistically significant (P<0.01). Scores of treatment group decreased more significantly than that of control group, and there were statistically significant difference in scores after treatment and in the change value between the two groups (P<0.01 or P<0.05)4. Conclusion(1) Yangxinkang tablet can improve cardiac function and relieve clinical symptoms of patients with CHF, so it is an effective drug for treating CHF.(2) Yangxinkang tablet can improve TCM syndrome of patients with CHF, and especially in the improvement of gasp, fear of cold and cold in the extremities, swollen of face and limbs, cough and expectoration is highly effective.(3) Yangxinkang tablet can increase exercise tolerance in patients with CHF, and improve the life quality of patients with CHF.(4) Yangxinkang tablet possess good security and compliance.Part three Experimental Research1. ObjectiveObserved the protective effect of yangxinkang tablet for heart structure and function of rabbit model with CHF and it's influence on neuroendocrine system, inflammation factor, endothelial function and antioxidation. In-depth investigated the mechanism of action of Yangxinkang tablets in the treatment of heart failure. Evaluated effect in preventing ventricular remodeling and systolic asynchronous of animal model of heart failure by Yangxinkang tablet.2. MethodMaking heart failure animal model by blocking rabbit left anterior descending coronary artery. The experimental animals were divided into control group, experimental control group, captopril group, Yangxinkang tablet low dose group, Yangxinkang tablet middle dose group and Yangxinkang tablet high dose group, and were given appropriate treatment measures for 4 weeks. Investgated the effects of yangxinkang tablet on echocardiography, B-type natriuretic peptide (BNP), Cardiac troponin I (cTnⅠ), Interleukin-6 (IL-6) Tumor necrosis factor-α(TNF-α) and myocardial ultrastructure,etc. of rabbit model with heart failure.3. Result(1) After treatment, the interventricular septum (IVS) of experimental control group was thinnest, the interventricular septum (IVS) of control group was thickest, the difference between them was statistically significant (P< 0.01). The LVEDd of experimental control group was maximum, compared with that of middle dose group and high dose group, the difference among them were statistically significant(P<0.05).(2) After treatment, the LVEF of experimental control group was lowest, compared with that of middle dose group and high dose group, the differences among them were statistically significant(P<0.01).(3) Comparison of BNP and cTNI in each groups, the experimental control group is highest, compared with other groups, the differences among them were statistically significant(P<0.05 or P<0.01).(4) Comparison of AngⅡin each groups, the experimental control group was highest, compared with other groups, the differences among them were statistically significant(P<0.05 or P<0.01).(5) Comparison of TNF-αin each groups, the control group was lowest, compared with high dose group, the difference between them was not statistically significant(P>0.05). the experimental control group was highest, compared with other groups, the differences among them were statistically significant(P<0.05或P<0.01). (6) Comparison of ET-1 in each groups, the experimental control group was highest, compared with other groups, the differences among them were statistically significant(P<0.01).(7) Comparison of IL-6 in each groups, the experimental control group was highest, compared with other groups, the differences among them were statistically significant(P<0.01).(8) Comparison of MDA in each groups, the experimental control group was highest, compared with other groups, the differences among them were statistically significant(P<0.01). Comparison of SOD in each groups, the experimental control group is lowest, compared with control group, middle dose group and high dose group, the differences among them were statistically significant(P<0.01).(9) Comparison of apoptosis index in each groups, the control group was lowest, the experimental control group was highest, compared with each groups, the differences among them were statistically significant (P<0.05 or P<0.01)(10) After treatment, the Tvr-SD of experimental control group was highest, the Tvr-SD of control group was lowest, compared with other groups, the differences among them were statistically significant (P<0.05 or P<0.01)(11) Results of transmission electron microscopy:in the high dose group, sarcomere can be found, myofibrils aligned regularly, Sarcomere structure was basically clear, myofilament were still intact, isotropic and anisotropic band structure were also clear, Z and M line can also be found. The number of mitochondria and sarcoplasmic reticulum increased, the structure of them were normal. The structure of crista and the nuclear membrane were clearly. The distribution of chromatin was basically normal. But in the experimental control group, the sarcomere was deformed, myofilament was fractured and disordered, sarcolemma was edema, the number of mitochondria increased, crista disappeared, endoplasmic reticulum distended, part of the muscle cell disintegrated, isotropic and anisotropic band structure were illegible, Z line was thickened, M line was illegible. The nuclear membrane were partly dissolved and disappeared, the edge of the nuclear membrane was irregular. The distribution of chromatin was abnormal.4. Conclusion(1) Blocking rabbit left anterior descending coronary artery can make heart failure animal model, and it's operating procedures was relatively simple and Success rate was higher.(2) Yangxinkang tablet can improve cardiac function of rabbit model with heart failure and reduce serum BNP, cTnⅠlevels.(3)Yangxinkang tablet can prevent IVS of rabbit model with heart failure thinning, reduce the diastolic volume and cardiac index, improve the heart ultrastructure, and prevent ventricular remodeling in rabbit model with heart failure.(4) Yangxinkang tablet can reduce serum AngⅡlevels of rabbit model with heart failure, and block the nerve-endocrine system's activation.(5) Yangxinkang tablet can reduce serum TNF-α,IL-6 levels of rabbit model with heart failure and be against inflammation factors.(6) Yangxinkang tablet can reduce serum ET-1 levels of rabbit model with heart failure, improve endothelial function.(7) Yangxinkang tablet can reduce serum MDA levels and elevate serum SOD levels of rabbit model with heart failure, and it is with antioxidant effect.(8) Yangxinkang tablet can reduce apoptosis of myocardial of rabbit model with heart failure.(9) Yangxinkang tablet can improve systolic synchronous of rabbit model with heart failure.