Safety and Efficacy Evaluation of Antithrombotic Therapy with Rivaroxaban and Clopidogrel After PCI in Chinese Patients.

OBJECTIVE: To investigate the efficacy and safety of the antithrombotic therapy using the oral anticoagulant rivaroxaban and clopidogrel in Chinese patients with acute coronary syndrome complicated with atrial fibrillation after percutaneous coronary intervention. METHODS: A total of 100 patients were selected. Patients were randomly divided into two groups: the treatment group (rivaroxaban group) received a therapy of rivaroxaban and clopidogrel. The control group (warfarin group) receivied a combined treatment of warfarin, clopidogrel, and aspirin. The primary outcome endpoint was evaluated based on the adverse cardiac and cerebrovascular events within 12 months. RESULTS: A total of 8 (8.00%) main adverse cardiac and cerebrovascular events occurred during the 12 months of follow-up, including 5 (9.80%) in the warfarin group and 3 (6.10%) in the rivaroxaban group. The risk of having main adverse cardiac and cerebrovascular events in the two groups was comparable (P = 0.479). A total of 9 patients (9.00%) were found to have bleeding events, among which 8 patients (15.7%) were in the warfarin group, whereas only 1 patient (2.00%) was in the rivaroxaban group. Therefore, the risk of bleeding in the warfarin group was significantly higher than that in the rivaroxaban group (P = 0.047). CONCLUSIONS: In Chinese patients with acute coronary syndrome complicated with atrial fibrillation, the efficacy of the dual therapy of oral anticoagulant rivaroxaban plus clopidogrel after percutaneous coronary intervention was similar to that of the traditional triple therapy combined with warfarin, aspirin and clopidogrel, but it has a better safety property, which has potential to widely apply to antithrombotic therapy after PCI.

Panax notoginseng saponins inhibits atherosclerotic plaque angiogenesis by down-regulating vascular endothelial growth factor and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 expression.

OBJECTIVE: To investigate the mechanism of Panax notoginseng saponins (PNS), an effective component extracted from Panax notoginseng, on atherosclerotic plaque angiogenesis in atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) mice fed with high-fat, high-cholesterol diet. METHODS: Twenty ApoE-KO mice were divided into two groups, the model group and the PNS group. Ten normal C57BL/6J mice were used as a control group. PNS (60 mg/kg) was orally administered daily for 12 weeks in the PNS group. The ratio of plaque area to vessel area was examined by histological staining. The tissue sample of aortic root was used to detect the CD34 and vascular endothelial growth factor (VEGF) expression areas by immunohistochemistry. The expression of VEGF and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (NOX4) were measured by reverse transcription polymerase chain reaction and Western blotting respectively. RESULTS: After treatment with PNS, the plaque areas were decreased (P<0.05). CD34 expressing areas and VEGF expression areas in plaques were significantly decreased (P<0.05). Meanwhile, VEGF and NOX4 mRNA expression were decreased after treatment with PNS. VEGF and NOX4 protein expression were also decreased by about 72% and 63%, respectively (P<0.01). CONCLUSION: PNS, which decreases VEGF and NOX4 expression, could alleviate plaque angiogenesis and attenuate atherosclerosis.

Flavonoids from Podocarpus macrophyllus and their cardioprotective activities.

One new 8-aryl flavone, podocarflavone A (1), together with 15 previously reported flavonoids were isolated from the twigs and leaves of Podocarpus macrophyllus. Their structures were established on the basis of extensive spectroscopic analysis and by the comparison with spectroscopic data reported in the literature. Antioxidant capacities of the isolated substances were determined using the 1,1-diphenyl-2-picrylhydrazyl, ferrous ions, and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical in vitro assays, and their cytoprotective activities were also tested on H2O2-induced apoptosis in H9c2 cardiomyocytes. The results showed that those flavonoids exhibited significant cardioprotective effects by decreasing the H2O2-induced death of H9c2 cell, and the levels of lactate dehydrogenase and creatine kinase, and by inhibiting the elevated intracellular concentration of reactive oxygen species.

Qindan capsule changes adventitial collagen synthesis in spontaneously hypertensive rats.

OBJECTIVE: To investigate the effect of Qindan capsule (QC) on collagen synthesis and the mechanism underlying the process in spontaneously hypertensive rats (SHRs). METHODS: Twentyfour SHRs were divided into three groups: the hypertension model group, the QC treatment group, and the losartan treatment group. Eight Wistar Kyoto (WKY) rats were used as the normal control group. The systolic blood pressure (SBP) of the rats was monitored, and the thoracic aorta adventitia of the rats was segregated. The expressions of transforming growth factor 1 (TGF-ß1), Smad3, and collagens I and were measured by histological staining and reverse transcription polymerase chain reaction. RESULTS: The SBP was significantly higher in the model group than in the normal control group (P<0.01). However, a significant SBP-lowering effect was observed in QC or losartan treatment groups (P<0.05 or P<0.01) after 3 weeks of treatment. QC-treated rats showed a decrease of approximately 40 mm Hg, and the losartan-treated rats showed a decrease of approximately 50 mm Hg at the end of treatment compared with the beginning of treatment. The protein and gene levels of TGF-ß1, Smad3, and collagens I and in the model group were significantly increased compared with those in the normal control group (P<0.01). However, the levels were significantly decreased in the QC or losartan treatment group compared with the model group (P<0.05 or P<0.01). However, there was no significant difference between the QC and losartan treatment groups (P<0.05). CONCLUSIONS: QC could exert its antihypertensive effect through down-regulating TGF-ß1-stimulated collagen expressions. The TGF-ß1/Smad3 signaling pathway may be involved in this process.

Effects of allicin on hyperhomocysteinemia-induced experimental vascular endothelial dysfunction.

This study was designed to investigate the effect and mechanism of allicin on hyperhomocysteinemia-induced experimental vascular endothelial dysfunction in rats. Fifty male Wistar rats were randomly divided into five groups: the normal control rats (NC), the high-methionine-diet rats (Met), the high-methionine-diet rats treated with folic acid, vitaminB6 and vitaminB12 (Met+F), or with low-dose allicin (Met+L), or with high-dose allicin (Met+H). After 6 weeks, we collected blood samples of all groups to determine plasma endothelin (ET), serum homocysteine (Hcy), nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and detected the expression of basic fibroblast growth factors (bFGF), transforming growth factor beta (TGF-ß), tumor necrosis factor-alpha (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in the aorta. The Hcy and the expression of TGF-ß in both the Met+L and Met+H groups were significantly lower than the Met and Met+F groups. The ET, ET/NO ratio and the MDA levels of the Met+L and Met+H groups were significantly lower than the Met group. The SOD and NO levels and the expression of bFGF, TNF-α and ICAM-1 of the Met+L and Met+H groups were significantly higher than the Met group. Our data indicate that allicin inhibits lipid peroxidation induced by hyperhomocysteinemia and regulates the excretion and equilibrium of ET and NO, and suggest that allicin might be useful in the prevention of endothelial dysfunction caused by hyperhomocysteinemia.

[Clinical effects of the treatment of gastrointestinal dysfunction after stable thoracolumbar fractures with Simo decoction oral liquid].

OBJECTIVE: To evaluate the clinical effects of Simo Decoction Oral Liquid for the treatment of gastrointestinal dysfunction after stable thoracolumbar fractures. METHODS: From May 2005 to July 2008, 81 patients with stable thoracolumbar fractures were randomly divided into treatment group (41 cases) and control group (40 cases) according to a random digits table. The treatment group included 32 males and 9 females with an average age of (47.19 +/- 5.18) years old ranging from 21 to 55 years, and the course was from 1 to 45 hours with an average of (7.83 +/- 1.29) hours. The control group included 30 males and 10 females with an average age of (46.31 +/- 3.72) years ranging from 20 to 54 years,and the course was from 1.5 to 43 hours with an average of (8.15 +/- 1.63) hours. The treatment group were dealed with Simo Decoction Oral Liquid,and the control group with neostigmine for acupoint block in bilateral Foot-Three-Li. The recovery of gastrointestinal function and the first passage of gas by anus were compared. RESULTS: The time of recovery of gastrointestinal function in treatment group (7.27 +/- 3.14) h was shorter than that in control group (10.12 +/- 3.62) h. The time of first passage of gas by anus in treatment group (15.39 +/- 13.70) h was significantly shorter than that in contral group (24.02 +/- 18.11) h. The total effective rate in treatment group was higher than that in control group. CONCLUSION: Both the treatment group and the control group have clinical effects in treatment of the restoration of gastrointestinal dysfunction after the stable thoracolumbar fractures, but the treatment group has more remarkable therapeutic effect and less side effects.

[Effect of Qindan Capsule on expression of vascular adventitial collagen I and III in old spontaneous hypertensive rats].

OBJECTIVE: To investigate the effect of Qindan Capsule (QDC) on gene and protein expression of vascular adventitial collagen I and III (VAC1 and VAC3) in spontaneously hypertensive rats (SHR), for further research the possible mechanism of vascular adventitial fibroblasts remodeling. METHODS: Thirty-two SHR, 40 weeks old, were equally randomized into the model group and the three treated groups treated respectively with high (750 mg/Kg x d) and low dosage QDC (150 mg/Kg x d), and losartan (30 mg/Kg x d), once a day for 12 weeks. Besides, a normal blank control group and a normal QDC (750 mg/Kg x d) medicated group were set up with same aged Wistar-Kyoto rats. Systolic blood pressures of rats were monitored, gene and protein expressions of VAC1 and VAC3 in rats' thoracic aortic adventitia were detected at the end of experiment using immune-histochemical staining and real-time quantitative fluorescent PCR respectively. RESULTS: Compared with the model group, blood pressure as well as the gene and protein expressions of VAC1 and VAC3 were all lower in the two QDC (high and low dosage) treated groups (P < 0.05). CONCLUSION: QDC could not only effectively reduce the blood pressure in SHR, but also suppress and even reverse their thoracic aorta adventitial vascular remodeling, which is displayed by the obvious lowering of VAC1 and VAC2 expression levels.

Effect of traditional Chinese medicine Shu-Mai-Tang on attenuating TNFalpha-induced myocardial fibrosis in myocardial ischemia rats.

Shu-Mai-Tang (SMT) is a traditional Chinese medicine for treatment of ischemic heart disease. The effect of SMT on inflammation-induced myocardial fibrosis, left ventricular (LV) remodeling, and the potential mechanism in myocardial ischemia (MI) rats were investigated. Rats with ligated left anterior descending coronary artery (MI model) were randomly divided into three groups (SMTL, SMTH, and MIR). A group undergoing Sham operation (Sham; n=16) was also included. SMT (342 or 1710 mg/kg for SMTL or SMTH groups, respectively) was orally administered daily for 1 and 6 weeks. Cardiac function, myocardial fibrosis, serum tumor necrosis factor-alpha (TNFalpha) concentration, the cardiac expressions of phosphorylated p38 MAPK and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TNFalpha were examined by echocardiography, histological staining, radioimmunoassay, western blot, respectively. In the present study, significant reduced myocardial fibrosis, as well as decreased phospho-p38 MAPK, TIMP-1, and TNFalpha proteins, and serum TNFalpha level, accompanied by improved cardiac function in the SMT-treated rats in a dose-dependent manner as compared with the MIR. These results suggested that SMT could anti-inflammation-induced myocardial fibrosis and reverse LV remodeling in MI rats, and the mechanism may be related to the effect of SMT on inhibiting p38 MAPK signaling pathway.

Improvement of vascular remodeling in spontaneous hypertensive rats with traditional Chinese medicine.

Qin-Dan-Jiang-Ya-Tang (QDJYT) is a traditional Chinese herbal medicine for the treatment of hypertension. The effect of QDJYT on blood pressure (BP) and vascular remodeling in hypertension was investigated in the model of spontaneous hypertensive rats (SHR). Sixteen SHRs were divided into two groups: the SHR group and the SHR+ QDJYT group. Eight Wistar-Kyoto (WKY) rats were in the normal control group. QDJYT (750 mg/kg) was orally administered daily for 12 weeks to the SHR+QDJYT group. After 12 weeks, thoracic aortas were segregated. The media thickness (MT) and the lumen diameter (LD) of the aortic wall, the ratios of MT to LD, the expression of basic fibroblast growth factor (bFGF) mRNA, and the level of its proteinic production were examined by histology, real-time PCR, and Western blot analysis, respectively. It was observed in our study that MT, MT/LD, the expression of bFGF mRNA, and the level of its proteinic production in aortic walls were higher in SHRs than in WKY rats. However, in the SHRs treated with QDJYT, we found MT, MT/LD, the expression of bFGF mRNA and the level of its proteinic production were lower than SHRs. These results suggest that QDJYT can improve the vascular remodeling in SHRs, and the mechanisms may be related to the suppressive effect of QDJYT on bFGF mRNA and its proteic productions in the aortic walls of SHRs.

[Experimental study on effect of Shumai capsule in promoting angiogenesis in rats with myocardial ischemia].

OBJECTIVE: To study the effect of Shumai Capsule (SMC) on angiogenesis and expression of relevant growth factor in rats with myocardial ischemia (MI). METHODS: Model rats of MI were duplicated and treated with SMC (SMC group), bFGF + calparine (positive control group) and normal saline (model group) respectively. Besides, a sham-operative group was set up and treated with normal saline. The rats were sacrificed in batches at the time after being medicated for 1, 2 and 4 weeks, for determining von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) protein expression in ischemic myocardium by immuno-histochemical staining, myocardial micro-vessel density (MVD) using digital analysis system, and the gene expression of VEGF by quantitative real-time PCR. RESULTS: Compared with the sham-operative group and the model group, levels of MVD, protein and gene expression of VEGF in the SMC group were higher respectively at three time segments (all P <0.01), but showed insignificant difference to those in the positive control group. CONCLUSION: SMC could promote angiogenesis in ischemic myocardium of rats, the up-regulation on VEGF mRNA and protein expression might be one of the potential mechanisms of SMC in promoting angiogenesis.

Effect of traditional Chinese medicine Qin-Dan-Jiang-Ya-Tang on remodeled vascular phenotype and osteopontin in spontaneous hypertensive rats.

Qin-Dan-Jiang-Ya-Tang (QDJYT) is a traditional Chinese herbal medicine for the treatment of hypertension. The effect of QDJYT on blood pressure and on vascular remodeling in hypertension was investigated in the model of spontaneous hypertensive rats (SHR). Sixteen SHRs were divided into two groups, the SHR group and the SHR+QDJYT group. Eight WKY rats were a normal control group. QDJYT (750 mg/kg) was orally administered daily for 12 weeks in SHR+QDJYT group. After 12 weeks, thoracic aortas were segregated. Media thickness (MT), lumen diameter (LD), the ratio of MT to LD, the volume fraction of collagen (VFC) in media, the ultrastructure of vascular smooth muscle cells (VSMCs) and the expression of osteopontin (OPN) mRNA were examined by histological staining, transmission electron microscope (TEM), and real-time PCR, respectively. It was observed in our study that MT, MT/LD, VFC and the expression of OPN mRNA were higher in the SHRs than in the WKY rats, volume and numeral density of mitochondria in vascular smooth muscle cells (VSMCs) in media increased obviously. However, in the SHRs treated with QDJYT, we found MT, MT/LD, VFC and the expression of OPN gene were lower than in the SHRs, and the phenotype of VSMCs were close to normal. These results suggest that QDJYT could reverse the vascular remodeling in SHR, and the mechanisms may be related to the suppressive effect of QDJYT on the expression of OPN mRNA in arterial wall.

[Protective and reverse effects of qindan capsule on aortic lesion in spontaneously hypertensive rats].

OBJECTIVE: To investigate the effects and mechanism of Qindan Capsule (QC) on aortic structure in spontaneously hypertensive rats (SHR). METHODS: Thirty-two SHR of 14 weeks old, were divided into the QC group, the Niuhuang Jiangya Capsule (NJC) group, the captopril group and the model group. Besides, Wistar-Kyoto (WKY) rats were taken as the normal control. All the others were administered with corresponding medicine and their blood pressure measured. After 12 weeks, the morphological changes of aorta were observed by HE and Masson staining, the level of angiotensin II (Ang II) in aorta was detected by radioimmunoassay, and the mRNA expression of basic fibroblast growth factor (bFGF) in aortic wall was analyzed by real-time quantitative fluorescent PCR. RESULTS: QC could reduce the blood pressure in SHR, improve their aortic structure, lower the Ang II level and inhibit the bFGF mRNA expression in aortic wall (P < 0.05 or P < 0.01), showing a good effect similar to that of captopril (P > 0.05) and better than that of NJC (P < 0.01). CONCLUSION: QC has a significant protective and reverse effect on aortic lesion in SHR. The mechanism may be related to its actions in reducing Ang II level and inhibiting bFGF mRNA expresion in aortic wall.

Effects of Qindan Capsule on blood pressure, endothelin, calcitonin gene-related peptide and angiotensin- II in spontaneous hypertensive rats.

OBJECTIVE: To observe the hypotensive effects of Qindan Capsule (QC) on spontaneous hypertensive rats (SHR) and its effect on the contents of endothelin (ET), calcitonin gene-related peptide (CGRP) and angiotensin-II (Ang-II ) in plasma and vascular tissues, and to investigate the possible mechanism of QC in lowering blood pressure. METHODS: Forty SHRs were divided into 5 groups: the high dosage QC group [QCHD, 750 mg/(kgxd)], the low dosage QC group [QCLD, 150 mg/(kgxd) ], the Niuhuang Jiangya Pill group [NJP, 200 mg/(kgxd) ], the Captopril group [ 15 mg/(kg d) land the model group, 8 in each group. Meanwhile, a normal control group consisting of 8 Wistar-Kyoto (WKY) rats was set up also. All the rats were administered with medicine through gastrogavage. Systolic blood pressure (SBP), level of ET, CGRP and Ang-II in plasma and Ang-II in tissues of mesenteric artery were detected in all the rats after 12 weeks of treatment. RESULTS: The level of SBP after treatment in the QCHD group was lower than that in the model group (P<0.01), but with no significant difference as compared with that in the Captopril group and the NJP group (P>0.05). After treatment, the plasma level of ET was lower and CGRP higher than those in the model group (both P<0.05), and also higher than those in the NJP and Captopril group (both P<0.05). As for the content of Ang-II , in mesenteric arterial tissues, it was lower in the QCHD group than that in the model group ( P<0.05), but in plasma, it showed no significant difference between the two groups (P>0.05). CONCLUSION: QC has a satisfactory hypotensive action on SHR rats, and its mechanism may be associated with the regulation on plasma vasoactive peptide and regional renin-angiotensin system.

[Study on correlation of insulin resistance with TCM syndrome type and activity of fibrinolytic system in patients with coronary arterial disease].

OBJECTIVE: To study the correlation of insulin resistance (IR) with TCM syndrome type and activity of fibrinolytic system in patients with coronary arterial disease (CAD). METHODS: One hundred and twelve CAD patients were classified according to TCM Syndrome into 4 types, the Xin-blood stasis (XBS) type, the phelgm blocking Xin-channel (PBXC) type, the Qi-insufficiency with blood stasis (QIBS) type and the both Qi-Yin deficiency (QYD) type. Patients' fasting blood glucose (FBG), fasting blood insulin (FIns) were measured, the insulin sensitive index (ISI) calculated. Data were compared between various types, also with those obtained from 30 healthy persons in the control group respectively. Moreover, activity of tissue plasminogen activator (t-PA) and content of plasminogen activator inhibitor-1 (PAI-1) were determined in 90 patients selected from the 112 to conduct linear correlation analysis of IR with t-PA activity and PAI-1 content. RESULTS: FBG and FIns levels in the CAD patients were higher than those in the healthy control significantly (P < 0.01); ISI in the 4 syndrome type of CAD patients were all lower than that in the control (P < 0.01). IR existed in all the 4 types, but the level in the XBS type and the PBXC type was more severe than in the other two types. Correlation analysis showed that IR was correlated with t-PA activity and PAI-1 content (P < 0.01). CONCLUSION: IR often exists in CAD patients, the severity of IR varies in patients of different TCM syndrome types, and IR is correlated with the abnormality of fibrinolytic system activity.