Guo Shuzhen

GW24-e2910 Research on Effects of Qishen Granule on Hemodynamics in Mini Pigs with Cardiac Functional Insufficiency and Qi-deficiency and Blood Stasis Syndrome Induced by Ameroid Constricting Ring

Objectives To explore the effects of Qishen Granule, a compound Chinese herbal medicine, on hemodynamics in a mini pig model of cardiac functional insufficiency and qi-deficiency and blood stasis syndrome induced by Ameroid constricting ring. Moreover, the therapeutic effects in improving the symptoms were also studied. Methods Establishment and assessment of a qi-deficiency and blood stasis syndrome model with cardiac functional insufficiency experimental mini pigs (20 ± 5 kg) were instrumented with a size-matched Ameroid constrictor on the anterior descending branch under general anaesthesia in sterile conditions. Sham group didn’t place the Ameroid constrictor, the other were the same to the model group. And the experimental mini pigs of animal models were randomly divided into model group, positive control (Qishenyiqi pill) group, positive control (digoxin tablet) group, Qishen granule group with different dose with 6 in each group, sham operation group with 6 at the end of the experiment. 3 weeks after the operations, the animals were assessed with echocardiography and electrocardiogram test, and also collected the four diagnostics information. The day after the 3 weeks assessment, the animals in different groups received different treatments. All the therapeutic drugs stirred well respectively with their normal feed then delivered for 8 weeks. The pigs were dynamically observed the echocardiography and four diagnostics information after treatments. At the end of the experiment also 8 weeks after the treatments, the pigs were received the hemodynamic tests under general anaesthesia in sterile conditions. Results After 8weeks, pigs in the Qishen granules groups and the positive control groups were more active than pigs in the model group. Compared with pigs in the sham-operated group, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of the model group decreased significantly (P < 0.01); pigs in the Qishen granules groups and the positive control groups showed significant improvement on SBP, DBP and MAP (P < 0.05, P < 0.01). In vertricular hemodynamic, left vertricular systolic pressure (LVSP), maximal rate of left vertrcular systolic pressure (+ dP/dt max) and maximal rate of left ventricular diastolic blood pressure (-dP/dt max) of the model group were significantly down-regulated when compared with the sham-operated group (P < 0.05); the Qishen granules group with a high does and sodium digoxin tablet increased the LVSP, +dP/dt max and-dP/dt max (p < 0.05), and thus improved ventricular hemodynamic in pigs with cardiac functional insufficiency. Compared with pigs in the sham-operated group, left ventricular ejection time (LVET) of the model group decreased. Compared with the model group, medication administration groups showed no significant difference. And myocardial oxygen consumption is based on heart rate (HR), MAP, LVET multiplied by three to count. Compared with pigs in the sham-operated group, the myocardial oxygen consumption of the model group and sodium digoxin tablet significantly increased (P < 0.01, P < 0.05). Conclusions The Qishen granules groups can strengthen left ventricular contractile force, especially the Qishen granules group with a high does can increase LVSP, +dP/dt max and-dP/dt max SBP and DBP, and MAP, and improve the hemodynamic indicators in pigs with cardiac functional insufficiency after myocardial infarction. The Qishen granules can also relieve the symptoms of qi deficiency and blood stasis syndrome.

GW24-e3111 Comparations of two common mouse models of chronic heart failure by echocardiography

Objectives To compare the recorded echocardiographic parameters in two common mouse models of chronic heart failure. Methods KM mice were subjected to transverse aortic constriction (TAC), myocardial infarction induced by coronary artery ligation (CAL), or sham operation. Mice were characterised by echocardiography 4- to 8-week post-surgery. Results Early operative mortality (within 24 h) was not significantly different between CAL (5/14) and TAC (3/10). No mortality was achieved during 7 days after the surgical procedure. The mice died from LV rupture in MI cases, defined by excessive blood filling the chest cavity. No mice died between 2 and 4 weeks after surgery. All mice had severe left ventricular hypertrophy, impaired systolic function and pulmonary congestion compared with sham controls. 4-week after surgery TAC-operated and sham-operated mice showed significant changes in diastolic interventricular septum thickness (IVSd); CAL-operated and sham-operated mice showed significant changes in systolic and diastolic left ventricular internal diameter (LVIDd and LVIDs). 4-week’s ejection fraction (EF) of the CAL-operation group is (47.71 ± 8.07)% compared with (58.33 ± 6.31)% of the TAC-operation group and (76.53 ± 5.96)% of the sham operation group; fraction shortening (FS) of the CAL-operation group is (24.26 ± 4.34)% compared with (30.27 ± 4.08)% of the TAC-operation group and (44.54 ± 5.14)% of the sham operation group. While 8-week’s ejection fraction (EF) of the TAC-operation group is (36.12 ± 13.35)%; fraction shortening (FS) of the TAC-operation group is (17.53 ± 6.69)%. Conclusions CAL-operation group shared a higher mortality because of the direct damage to the myocardium, which leads to postoperative arrhythmias and other adverse events. Cardiac function decline sharply in MI group, while TAC postoperative cardiac decompensation performance after 8 weeks. Characteristics of these two models in morphology: CAL-operated mice occupy the thinner wall and enlarged ventricular cavity; while septal hypertrophy and ventricular chamber volume changes can be observed in TAC-operated mice.

ASSA13-13-5 Investigation of Clinical Features and Treatments of Chronic Heart Failure Patients in 17 Chinese Medicine Hospitals in China

Objective To investigate the clinical features and treatments of Chronic Heart Failure (CHF) patients in 17 three-level class A Chinese medicine (CM) hospitals in China. Methods The case-observed table was designed and used in this research, and 1088 patients were admitted to the cardiovascular department in above hospitals. Inducements, Fundamental causes, levels of cardiac function, combined diseases, and types of syndrome were observed in CHF patients. Treatments by Western medicine (WM), traditional Chinese medicine (TCM) therapy and Chinese patent medicine were also observed. Results The average age of patients was (66.99 ± 10.33) years, and 622 patients (57.17%) were males. Coronary heart disease (924 cases, 84.93%), hypertensive heart disease (381 cases, 35.02%) and dilated cardiomyopathy (73 cases, 6.71%) were the fundamental causes. There were 15 patients (1.38%) with New York Heart Association (NYHA) class IHF, 279 (25.64%) with NYHA class II HF, 634 (58.27%) with NYHA III HF, 150 (13.79%) with IV HF, and 10 (0.92%) without the valid information of heart function. Overtired (491 cases, 55.42%), cardiopathy exacerbation (243 cases, 27.43%), infection (204 cases, 23.02%), no obvious precipitating factor (192 cases, 21.67%) and emotional fluctuation (191 cases, 21.56%) are the main inactive of CHF. Arrhythmia (242 cases, 22.24%), type 2 diabetes mellitus (226 cases, 20.77%), cerebrovascular disease (108 cases, 9.93%) and dyslipidemia (97 cases, 8.92%) were the main combined diseases. The top 5 western drugs were ACEI/ARB (550 cases, 50.55%), aspirin (524 cases, 48.16%), β-blocker (485 cases, 44.58%), diuretic (433 cases, 39.80%) and nitrates (353 cases, 32.44%). Qi deficiency (887cases, 81.53%), blood stasis (832 cases, 76.47%), fluid-retention (339 cases, 31.16%) and yin deficiency (294 cases, 27.02%) were dominated in CHF syndrome factors. Totally 256 patients (23.53%) were treated with Chinese patent medicine. Conclusions The normalised treatments of WM in CM hospitals were similar in WM hospitals. Qi deficiency, blood stasis, fluid-retention and yin deficiency were the main syndrome factors of CHF patients in CM hospitals. Besides the treatments according to syndrome differentiation, doctors in CM hospitals should improve the normalised WM treatment of CHF.

INTEGRATED PROTEOMIC AND METABOLOMIC ANALYSIS REVEALS NADH-MEDIATED TCA ENERGY METABOLISM DISORDER IN CHRONIC PROGRESSIVE HEART FAILURE

Objectives Although great progress has been made in heart failure (HF), it is still the major cause of mortality and morbidity worldwide. Typically, research associated with heart failure has focused on heart failure induced by acute myocardial infarction. However, most clinical HF is gradually generated by chronic progressive heart Failure (CHF). A proper model is needed to reveal its identification, quantification, and characterisation, understand the mechanism of heart failure (HF). The initial goal of the present study is to build up a chronic progressive Heart Failure model, characterise the time course and the pattern of regional myocardial contractile function during the development of progressive coronary artery stenosis, since most prior studies on this topic have only collected infrequent measurements. The second goal is to determine the underlying molecular mechanism for CHF. Methods Here we place ameriod constrictor on the left anterior descending coronary artery (LAD) of the mini-swine. It has a tendency to slowly absorb fluid and swell, thus slowly obstructing the vessel inside the constrictor lumen, which is more in line with changes in clinical development of CHF. Dynamic detection of electrocardiogram, echocardiography and coronary angiography are applied to diagnosis the chronic progressive Heart Failure model. Then two-dimensional gel electrophoresis (2-DE)-based proteomics and nuclear magnetic resonance (NMR) and Gas chromatography coupled with mass spectrometry (GC-MS) based metabolomics are applied to investigate its characterisation of the ischaemia tissue, and bioinformatic analysis including Gene Ontology (GO) and KEGG pathway analysis is used to understand the mechanism of chronic progressive heart failure. Results Based on dynamic detection of electrocardiogram, echocardiography and coronary angiography, the model shows a steady cardiac function from 8 weeks to 12 week, which EF value is about 50%, can be diagnosed as Chronic progressive Heart Failure. What is more, the model shows specific and interesting pathological changes, which ischaemia region only involve bellowing the mitral lesions. Then two-dimensional gel electrophoresis (2-DE)-based proteomics and nuclear magnetic resonance (NMR) and Gas chromatography coupled with mass spectrometry (GC-MS) based metabolomics are applied to investigate its characterisation of the ischaemia tissue, and bioinformatic analysis including Gene Ontology (GO) and KEGG pathway analysis is used to understand the mechanism of chronic progressive heart failure. We find that mitochondrial respiratory chain mediated by NADH is the critical pathway; it leads to down-regulation of important rate-limiting enzyme of citric acid cycle- malate dehydrogenase, which causes insufficient energy supply to the cardiac contractility and relaxation. And what more, we find that the CHF model is not dealt with any lipid intervention, even no high fat diet, the results of proteomics and metabolomics show that visible changes of ApolipoproteinA-I, LDL and VLDL in plasma are seen, myocardial ischaemia can lead to the disorder of lipid metabolism in plasma conversely through glycerolipid metabolism. Conclusions In present study, we describe a stable and easily reproducible technique to induce CHF model by Ameriod constrictor placing on the LAD. The model closely resembles the CHF in human with respect to structural and functional characteristics which is consistent with the progress of chronic progressive heart failure. NADH-mediated TCA and energy metabolism disorders are the key pathophysiological mechanisms for CHF. Myocardial ischaemia can lead to the disorder of lipid metabolism in turn. Overall, these results provide potential biomarkers for monitoring the therapeutic intervention of CHF and offer important new knowledge for gaining insights into the molecular mechanisms of CHF.