RESUMO
OBJECTIVE: To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). METHODS: Twenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA). RESULTS: Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01). CONCLUSIONS: Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.
Assuntos
Compostos Alílicos/uso terapêutico , Cardiotônicos/uso terapêutico , Dissulfetos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica , Fenômeno de não Refluxo/tratamento farmacológico , Compostos Alílicos/farmacologia , Animais , Benzotiazóis , Cardiotônicos/farmacologia , Meios de Contraste , Modelos Animais de Doenças , Dissulfetos/farmacologia , Hemodinâmica/efeitos dos fármacos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Fenômeno de não Refluxo/complicações , Fenômeno de não Refluxo/diagnóstico por imagem , Fenômeno de não Refluxo/patologia , Suínos , Porco Miniatura , Tiazóis/metabolismo , UltrassonografiaRESUMO
OBJECTIVE: To evaluate the effect of aranidipine enteric-coated capsules on 24 h blood pressure and blood pressure variability (BPV) in patients with mild to moderate essential hypertension. METHODS: This was an open clinical trial with 2 weeks of placebo run-in period. A total of 74 patients with blood pressure (140-180/95-110 mm Hg (1 mm Hg = 0.133 kPa) were treated by aranidipine (5 mg/d) for 4 weeks.If clinical sitting blood pressure < 140/90 mm Hg at 4th week, aranidipine at 5 mg/d would be continued for another 8 weeks.If not, the dosage would be increased to 10 mg/d.If blood pressure <140/90 mm Hg at 8th week, aranidipine at 5 mg/d or 10 mg/d would be given constantly.If not, the dosage would be increased to 20 mg/d and given for another 4 weeks. All patients performed 24 h ambulatory blood pressure monitoring (ABPM) before and after the treatment with BPV evaluated by the average 24 h per unit time blood pressure standard deviation and morning blood pressure surge (MBPS). RESULTS: (1) After 12 weeks' treatment with aranidipine, the mean 24 h blood pressure was reduced significantly compared with the baseline [(14 ± 13)/(11 ± 9) mm Hg, both P < 0.05] with trough/peak (T/P) ratio of SBP and DBP in responders of 75.31% and 78.15%, respectively.(2) After 12 weeks' treatment, standard deviations of 24 h, daytime SBP/DBP and nighttime SBP/DBP were reduced significantly[(25 ± 3)/(14 ± 4) mm Hg vs (11 ± 3)/(8 ± 2) mm Hg, (24 ± 5)/(14 ± 4) mm Hg vs (11 ± 3)/(8 ± 2) mm Hg, (10 ± 3)/(8 ± 4) mm Hg vs (8 ± 3)/(6 ± 3) mm Hg], respectively with all P < 0.05.Significant decrease was shown in MBPS compared to the baseline [(27 ± 11) mm Hg vs (19 ± 9) mm Hg, P < 0.05]. (3) The incidence of adverse events was 13.4%, including mild dizziness, flushing and palpitation. CONCLUSION: Administration of aranidipine enteric-coated capsules can control 24 h blood pressure effectively and reduce BPV significantly in patients with mild to moderate essential hypertension with good safety profile.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , Monitorização Ambulatorial da Pressão Arterial , Di-Hidropiridinas/administração & dosagem , Hipertensão Essencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension. METHODS: Left ventricular diastolic function of 252 hypertensive patients were assessed by early (E) diastolic transmitral flows to early diastolic mitral annular velocity (Ea) (E/Ea) ratio derived from Doppler echocardiography. Patients were divided into two groups according to normal left ventricular diastolic function group (E/Ea<15, n = 168) and left ventricular diastolic dysfunction group (E/Ea ≥ 15, n = 84). All patients were monitored by ambulatory blood pressure. Standard deviation (SD) and coefficient of variation (CV) of blood pressure were calculated as the BPV. Relationship between BPV and left ventricular diastolic function were analyzed by multivariate logistic regression analysis. RESULTS: All-day average diastolic blood pressure(DBP), the day systolic blood pressure (SBP), night SBP, night DBP, SBPSD, DBPSD and DBPCV in the left ventricular diastolic dysfunction group were significantly higher than in the normal diastolic function group (all P < 0.05). Multivariate logistic regression analysis showed that left ventricular diastolic dysfunction was associated with SBPSD (OR:1.126, 95%CI:1.054-1.203, P < 0.01), SBPCV (OR:1.127, 95%CI:1.036-1.225, P < 0.01) in this patient cohort. CONCLUSION: High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Função Ventricular Esquerda/fisiologia , Adulto , Idoso , Diástole/fisiologia , Hipertensão Essencial , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To assess the efficacy and safety of aranidipine versus retard-released felodipine in Chinese patients with mild-to-moderate essential hypertension. METHODS: This was a multicenter, randomized, double-blind, placebo and active antihypertensive drug parallel-controlled study. After 2 weeks of placebo run-in period, 315 patients at 6 centers with diastolic blood pressure (DBP) between 95 to 109 mm Hg (1 mm Hg = 0.133 kPa) while systolic blood pressure (SBP) below 180 mm Hg were randomized to receive aranidipine 5-20 mg/d (n = 126) or retard-released felodipine 5-10 mg/d (n = 126) for 12 weeks. Others (n = 63) received placebo for 4 weeks. Their blood pressures were evaluated at baseline and the end of Weeks 4, 8 and 12. RESULTS: After a 12-week treatment, SBP decreased from 148.8 ± 10.7 mm Hg to (132.8 ± 11.2) mm Hg while DBP dropped from ( 98.4 ± 2.8) mm Hg to (83.9 ± 7.5) mm Hg. There were significant differences with the baseline values (P < 0.0001). After a 4-week treatment, the reductions of SBP in aranidipine and retard-released felodipine groups were (12.1 ± 11.0) mm Hg and (12.2 ± 11.2) mm Hg while the reductions of DBP in two groups (11.8 ± 6.9) mm Hg and (12.1 ± 7.9) mm Hg respectively. The reductions of SBP and DBP in two groups were (2.3 ± 8.4) mm Hg and (4.0 ± 5.1) mm Hg and they were significantly superior to that in placebo group (P < 0.0001). But no significant difference existed between aranidipine and retard-released felodipine groups. Also no significant differences were found between these two antihypertensive therapy groups at the end of Weeks 4, 8 and 12 in the reduction of blood pressure, total response rate and blood pressure control rate. But 20 mg daily aranidipine was significantly superior to 10 mg daily retard-released felodipine in the control rates of SBP and DBP. Adverse events occurred at 24.22% and 29.92% in aranidipine and retard-released felodipine groups respectively (P = 0.305). CONCLUSION: Administration of aranidipine 5-20 mg/d can effectively control blood pressure and is not inferior to retard-released felodipine 5-10 mg/d. The efficacy of 20 mg/d aranidipine is superior to that of retard-released felodipine 5-10 mg/d. And the effectiveness and safety of aranidipine are similar to those of retard-released felodipine.
Assuntos
Anti-Hipertensivos/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Di-Hidropiridinas/administração & dosagem , Método Duplo-Cego , Hipertensão Essencial , Felodipino/administração & dosagem , Felodipino/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation (ALMP) on vulnerable plaques in the brachiocephalic artery of apolipoprotein E (Apo E) knockout mice. METHODS: Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose (3.6 µg×kg(-1)×d(-1)) or low dose (1.8 µg×kg(-1)×d(-1)) of an ALMP, or 0.2 ml/d normal saline (control group). The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody (MOMA-2) and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 (ICAM-1) expression was measured by ELISA, and the expression of matrix metalloproteinase-9 (MMP-9) and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 (TSP-1) expression was detected using Western blotting. RESULTS: Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery (P < 0.01), significantly lowered the contents of the lipid core (P < 0.01), significantly reduced the number of ruptured fibrous caps (P < 0.05), and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage (P < 0.05). ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques (P < 0.01), decreased plasma ICAM-1 expression (P < 0.01), and increased the expression of TSP-1. CONCLUSIONS: Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.
Assuntos
Alprostadil/química , Alprostadil/uso terapêutico , Lipossomos/química , Microesferas , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/patologia , Animais , Ensaio de Imunoadsorção Enzimática , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Placa Aterosclerótica/metabolismo , Reação em Cadeia da PolimeraseRESUMO
AIMS: ADVISE was a 12-week, multicenter, randomized, prospective, open-label, parallel-group study comparing combination therapy of nifedipine GITS 30 mg plus valsartan 80 mg (N + V) with high-dose valsartan (160 mg) monotherapy (V160) in Asian patients with hypertension. METHODS: Patients with hypertension inadequately controlled with valsartan 80 mg for at least 4 weeks were randomized. The coprimary endpoints were the mean changes in clinic systolic and diastolic blood pressures (SBP and DBP, respectively) at Week 12. Other endpoints included blood pressure (BP) control rate, response rate, and adverse events. RESULTS: The full analysis set (FAS) comprised 359 patients. Least squares (LS) mean changes in SBP were -18.3 mmHg (N + V; n = 177) and -16.5 mmHg (V160; n = 182) (difference: -1.9 mmHg; P = 0.0998). DBP LS mean changes were -9.8 mmHg (N + V) and -7.4 mmHg (V160) (difference: -2.4 mmHg; P = 0.0011). BP control rates were significantly higher in the N + V group (Week 4: 51.2% vs. 38.4%, P = 0.0138; Week 8: 68.3% vs. 50.3%, P = 0.0004; and Week 12: 71.2% vs. 55.5%, P = 0.0024). Similar findings were observed when patients were stratified according to smoking status, SBP baseline quartiles, and ESC/ESH guideline-defined added-risk category. The BP response rate was also higher in the N + V group compared with the V160 group. Rates of adverse drug reactions (all mild-to-moderate) were similar: 4.5% (N + V) and 4.4% (V160). CONCLUSIONS: Although one of the coprimary endpoints did not reach statistical significance, combination treatment with N + V provided a greater early and more consistent BP-lowering effect than monotherapy with V160, including superior reduction in DBP and BP control rates.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Nifedipino/uso terapêutico , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Adolescente , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Povo Asiático , Comorbidade , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Nifedipino/administração & dosagem , Nifedipino/efeitos adversos , Estudos Prospectivos , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversos , Valina/administração & dosagem , Valina/efeitos adversos , Valina/uso terapêutico , Valsartana , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: There is limited information on the long-term efficacy and safety of olmesartan medoxomil in the management of hypertension in Chinese patients. We therefore conducted the present multicentre, single-arm, prospective, observational study to investigate the 24-week efficacy and safety of olmesartan medoxomil in patients with mild to moderate hypertension. METHODS: Eligible patients (diastolic blood pressure [BP] 90-109 mmHg and systolic BP <180 mmHg off antihypertensive medication) were started on olmesartan medoxomil 20 mg once daily, with the possible up-titration to 40 mg once daily during 24 weeks of follow-up, to control clinic BP to the target level (<140/90 and <130/80 mmHg in diabetes mellitus). In a subset of enrolled patients, 24-h ambulatory and home BP monitoring were also performed. RESULTS: In the intent-to-treat analysis (n = 348), at 24 weeks of follow-up, the mean ± SD changes from baseline in clinic systolic/diastolic BP were 21.2 ± 14.2/16.0 ± 8.8 mmHg (p < 0.001). The proportions of patients who achieved the goal BP for systolic, diastolic and both were 81, 80 and 75 %, respectively. Olmesartan medoxomil also significantly (p < 0.001) reduced systolic/diastolic BP measured at patients' homes by 17.7 ± 13.1/12.1 ± 7.9 mmHg from baseline (n = 109), and reduced mean 24-h, daytime and night-time ambulatory BP by 13.3 ± 16.3/7.6 ± 9.5 mmHg, 13.9 ± 17.4/8.0 ± 10.4 mmHg and 12.3 ± 18.1/6.8 ± 10.2 mmHg, respectively (n = 87). Seven (2.0 %) serious adverse events were reported during follow-up. CONCLUSION: In Chinese hypertensive patients, olmesartan medoxomil is efficacious in lowering BP as assessed by three different BP-measuring methods and has an acceptable long-term safety and tolerability profile.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Povo Asiático , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Visita a Consultório Médico , Tetrazóis/uso terapêutico , Análise de Variância , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Distribuição de Qui-Quadrado , China/epidemiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/etnologia , Hipertensão/fisiopatologia , Imidazóis/efeitos adversos , Análise de Intenção de Tratamento , Pessoa de Meia-Idade , Olmesartana Medoxomila , Valor Preditivo dos Testes , Estudos Prospectivos , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation of the apolipoprotein (Apo E) deficient mice with or without experimental hypertension. METHODS: Eighty male Apo E deficient mice were fed with high-fat diet beginning at six weeks of age. At 8-week old, they were randomly divided into hypertension group and control group (n=40 each), the mice in hypertension group were subjected the suprarenal aortic constriction operation and then randomly divided into two subgroups: 15 weeks age and 30 weeks age groups. At the end of experiment, the vascular elastic lamina degradation and the content of collagen were determined by morphological method, plasma ICAM-1 level was measured by ELISA, and the rennin activity measured by radioimmunoassay, the superoxide anion detected by fluorescence, the MOMA-2 observed by immunofluorescence in all animals. mRNA expression of NF-κB P65 and MMP9 was detected by real-time PCR. RESULT: In 15-week old group, the elastic lamina degradation Grade II and the intima-media thickness in the hypertension group were significantly higher than in the control group [(5.4±3.3)% vs. (8.9±2.5)%, P<0.05; (98.66±18.90) µm vs. (70.08±11.71) µm, P<0.05]. In 30-week old group, the elastic lamina degradation Grade III, the III type of collagen and the intima-media thickness were also significantly higher than in the control group [(15.2±3.7)% vs. (8.1±3.3)%, P<0.01; (23.00±7.73)% vs. (11.00±3.82)%, P<0.05; (147.31±22.60) µm vs. (103.98±17.21) µm, P<0.01]. The level of ICAM-1 in hypertension group was significantly higher than that of control group in both 15-week old and in 30-week old mice [(46.3±3.7) µg/ml vs. (40.6±5.7) µg/ml, P<0.05; (56.0±3.1) µg/ml vs. (45.2±2.8) µg/ml, P<0.05]. The superoxide anion, the MOMA-2, mRNA expression of NF-κB P65 and MMP9 in the hypertension group were significantly higher than in the control group in both 15-week old and in the 30-week old mice. The increase in hypertension group was more pronounced in the 30-week old mice than in the 15-week old mice. CONCLUSION: The elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation are more significant in the Apo E deficient mice with hypertension than in control Apo E deficient mice.
Assuntos
Aorta/fisiopatologia , Apolipoproteínas E/genética , Hipertensão/patologia , Inflamação/patologia , Estresse Oxidativo , Animais , Colágeno/metabolismo , Hipertensão/metabolismo , Masculino , Camundongos , Camundongos KnockoutRESUMO
OBJECTIVE: To evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension using different methods according to ambulatory blood pressure monitoring. METHODS: Chinese patients 18-75 years of age with clinic diastolic blood pressure (BP) 90-109 mmHg and systolic BP less than 180 mmHg were treated with olmesartan medoxomil 20-40 mg once daily for 24 weeks to reach the goal BP (< 140/90 and < 130/80 mmHg in diabetes) in a multicenter study. The trough-to-peak ratio (T/P ratio) and the smoothness index (SI) for systolic/diastolic BP were calculated using different methods according to ambulatory blood pressure monitoring. RESULT: Olmesartan medoxomil 20-40 mg once daily reduced the systolic/diastolic ambulatory BP for 24-h, daytime, and night-time by 13.3 ± 16.3/7.6 ± 9.5, 13.9 ± 17.4/8.0 ± 10.4, and 12.3 ± 18.1/6.8 ± 10.2 mmHg in all eligible patients at week 24 from baseline (n = 87, P < 0.0001). The global and individual T/P ratios were 0.64/0.62 and 0.32/0.30 (n = 87) for systolic/diastolic BP, whereas these were 0.71/0.70 and 0.31/0.39 in fair responders (n = 71). Global and individual SI were 6.81/5.37 and 0.92/0.67 (n = 87) for systolic/diastolic BP, whereas these were 7.04/5.44 and 1.03/1.03 in fair responders (n = 71). Global and individual T/P ratios for systolic/diastolic BP were 0.75/0.82 and 0.45/0.46 in the 20 mg subgroup (n = 41), whereas these were 0.44/0.59 and 0.30/0.29 in the 40 mg subgroup (n = 30). Global and individual SI were 5.70/5.32 and 1.03/0.87 for systolic/diastolic BP in the 20 mg subgroup (n = 41), but these were 3.64/2.46 and 1.01/0.60 in the 40 mg subgroup (n = 30). CONCLUSION: The duration of the antihypertensive action of olmesartan medoxomil with 20-40 mg once daily can be assessed by the global T/P ratio and SI rather than the individual values, even in different populations and dosages.
Assuntos
Anti-Hipertensivos/administração & dosagem , Monitorização Ambulatorial da Pressão Arterial/métodos , Hipertensão/tratamento farmacológico , Imidazóis/administração & dosagem , Tetrazóis/administração & dosagem , Adolescente , Adulto , Idoso , Povo Asiático , Pressão Sanguínea/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Olmesartana MedoxomilaRESUMO
OBJECTIVE: To compare the physicians' lipid lowering drug prescribing behavior and knowledge on dyslipidemia before and at 8 months after new-issued blood-lipid reports in our hospital. METHOD: Blood-lipid reports in our hospital is newly modified in that the classification of dyslipidemia and lipid-lowering guideline and target lipid level are listed on the back of lipid report besides the normal lipid value listed immediately after the measured lipid levels. Physicians' lipid lowering drug prescribing behavior and knowledge on dyslipidemia before and at 8 months after new-issued blood-lipid reports were examined in 143 doctors from various departments before and at 8 months after new-issued lipid reports. RESULTS: At 8 months after the new issued lipid reports, doctors' cognition rate about the guideline was significantly increased [83.9% (120/143) vs. 67.1% (96/143), P < 0.001] and the guideline was considered more helpful on daily practice [75.3% (58/77) vs. 55.8% (43/77), P = 0.005] compared to baseline. However, the prescription rate of dyslipidemia therapy did not change significantly (69.2% vs. 63.2%, P = 0.117) at 8 months after the new issued lipid reports. CONCLUSIONS: The modification of the blood-lipid reports improved doctors' knowledge on dyslipidemia and on the "Chinese guidelines on prevention and treatment of dyslipidemia in adults". However, the lipid lowering drug prescribing behavior remained unchanged at 8 months after the modification of the lipid reports. Further investigation is warranted to see if the lipid lowering drug prescribing behavior could be changed in the long-term.
Assuntos
Dislipidemias/sangue , Conhecimentos, Atitudes e Prática em Saúde , Médicos , Padrões de Prática Médica , Relatório de Pesquisa , Dislipidemias/tratamento farmacológico , Fidelidade a Diretrizes , Humanos , Hipolipemiantes/administração & dosagem , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , PrescriçõesRESUMO
BACKGROUND: Few studies investigated serum uric acid levels in patients with acute Stelevation myocardial infarction (STEMI). The study was to assess the clinical value of serum uric acid levels in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Totally 502 consecutive patients with STEMI were retrospectively studied from January 2005 to December 2010. The level of serum lipid, echocardiographic data and in-hospital major adverse cardiovascular events (MACE) in patients with hyperuricemia (n=119) were compared with those in patients without hyperuricemia (n=383). The relationship between the level of serum uric acid and the degree of diseased coronary artery was analyzed. All data were analyzed with SPSS version 17.0 software for Student's t test, the Chi-square test and Pearson's correlation coefficient analysis. RESULTS: Serum uric acid level was positively correlated with serum triglyceride level. Hyperlipidemia was more common in hyperuricemia patients than in non-hyperuricemia patients (43.7% vs. 33.7%, P=0.047), and serum triglyceride level was significantly higher in hyperuricemia patients (2.11±1.24 vs. 1.78±1.38, P=0.014). But no significant association was observed between serum uric acid level and one or more diseased vessels (P>0.05). Left ventricular end-diastolic diameter (LVEDd) was larger in hyperuricemia patients than in non-hyperuricemia patients (53.52±6.19 vs. 52.18±4.89, P=0.041). The higher rate of left systolic dysfunction and diastolic dysfunction was discovered in hyperuricemia patients (36.4% vs. 15.1%, P<0.001; 68.2% vs. 55.8%, P=0.023). Also, hyperuricemia patients were more likely to have in-hospital MACE (P<0.05). CONCLUSIONS: Serum uric acid level is positively correlated with serum triglyceride level, but not with the severity of coronary artery disease. Hyperuricemia patients with STEMI tend to have a higher rate of left systolic dysfunction and diastolic dysfunction and more likely to have more in hospital MACE.
RESUMO
OBJECTIVE: To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). METHODS: Twenty-two male Chinese mini-swines were randomized into three groups: six in a sham-operation group, and eight each in the control and lipo-PGE1 groups. The distal part of the left anterior descending coronary artery (LAD) in the latter two groups was completely occluded for 2 h, and then reperfused for 3 h. Lipo-PGE1 (1 µg/kg) was injected 10 min before LAD occlusion until reperfusion for 1 h in the lipo-PGE1 group. Hemodynamic data and proinflammatory cytokines were examined before AMI, 2 h after occlusion, and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining were performed to evaluate the myocardial no-reflow area (NRA). RESULTS: Left ventricular systolic pressure and end-diastolic pressure significantly improved in the lipo-PGE1 group after reperfusion compared with the control group and also 2 h after AMI (P<0.05 for both). MCE and double staining both showed that lipo-PGE1 decreased reperfusion NRA after AMI (P<0.05, P<0.01). Lipo-PGE1 decreased serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) after myocardial infarction reperfusion (P<0.05 for both). CONCLUSIONS: Lipo-PGE1 is cardioprotective in our porcine model of myocardial infarction reperfusion no-reflow, decreasing NRA and attenuating the inflammatory response.
Assuntos
Alprostadil/metabolismo , Lipossomos/metabolismo , Infarto do Miocárdio/metabolismo , Algoritmos , Animais , Vasos Coronários/patologia , Modelos Animais de Doenças , Ecocardiografia/métodos , Interleucina-6/metabolismo , Masculino , Reperfusão Miocárdica , Miocárdio/metabolismo , Radioimunoensaio/métodos , Distribuição Aleatória , Suínos , Porco Miniatura , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: It has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning. METHODS: Sixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated. RESULTS: ADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats. CONCLUSIONS: Cardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.
Assuntos
Proteínas ADAM/metabolismo , Precondicionamento Isquêmico Miocárdico , Miocárdio/metabolismo , Proteína ADAMTS1 , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Animais , Imuno-Histoquímica , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/patologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the usability of laboratory test report from the angle of patients and understand to what degree the patients master the knowledge of lipid-lowering. METHODS: A total of 508 outpatients, selected from a Grade III-A general hospital, were queried by a questionnaire, their medical records and test reports were reviewed and their heights and weights were measured. In the study, 431 of them fulfilled the inclusion criteria and their information about lipid lowering treatment and treatment compliance were collected. RESULTS: Of the 508 subjects, 90.2% (458/508) read the report seriously; however, only 47.4% (240/508) took drugs according to the doctor's prescription even if the tests were "normal". Of the 431 lipid-lowering therapy related patients, only 26.4% (112/431) chose right in their cardiovascular risk classification, and less than 37.1% (160/431) agreed that "different people had different lipid lowering target". Of the 381 patients who needed the lipid-lowering treatment, 71.7% (273/381) recognized the need for treatment, but 98.7% (376/381) answered a wrong target for treatment; 60.9% (232/381) recognized that the reference values given in the laboratory test reports should be the target for treatment. Of the 246 patients under the lipid-lowering treatment, 35.4% (87/246)had reached their treatment goals, and only 52.0% (128/246) had a good compliance. CONCLUSION: Most patients read and trusted the laboratory test reports. However, dyslipidemia patients scarcely knew their lipid lowering treatment goals and their cardiovascular risk levels. The compliance of patients was poor, and the goal attainment was low. The laboratory medicine department should find out a simple and intuitional way to change the current situation.
Assuntos
Dislipidemias/sangue , Conhecimentos, Atitudes e Prática em Saúde , Hipolipemiantes/uso terapêutico , Cooperação do Paciente/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Dislipidemias/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Cooperação do Paciente/psicologiaRESUMO
OBJECTIVE: To investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model. METHOD: Infarct size was measured by Masson's Trichrome staining, the expression of protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by immunohistochemistry and quantitative real time RT-PCR, plasma levels of adiponectin at above mentioned four time points after IPC were detected by ELISA in IPC and MI rats. RESULT: Infarct size was smaller in IPC than in MI rats (20% ± 2% vs. 31% ± 3%, P < 0.05). The expression of adiponectin mRNA at 6 h and 12 h after IPC was 2.2 and 2.1 times higher than in Sham rats at respective time points (P < 0.05). Immunohistochemistry staining evidenced increased adiponectin expression in the ischemic area and weak expression of adiponectin in non-ischemic area (P < 0.05). Compared to the sham group, the plasma level of adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h: 7.40 ± 0.47 vs. 10.90 ± 1.74; 6 h: 8.18 ± 1.41 vs. 10.98 ± 1.74; 12 h: 6.97 ± 1.02 vs. 9.31 ± 0.96, P < 0.05). CONCLUSION: IPC reduced infarction size, upregulated the myocardial expression of adiponectin at mRNA and protein levels, and increased plasma adiponectin concentration, suggesting that the adiponectin may play a critical role in the protective effect of IPC.
Assuntos
Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Adiponectina/metabolismo , Animais , Masculino , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/prevenção & controle , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: to observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis. METHODS: rat heart IPC model was made by 4 circles of occluding the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF-B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6, 12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD ligation 24 h after IPC, 14 days later, the anti-SM-α-actin antibody was used to detect the mature neovascularization in the border of the infracted area. RESULTS: VEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic area in IPC group compared with the control group (P < 0.05). Density of mature arteries was also significantly increased in IPC plus MI group than that in MI group (P < 0.05). CONCLUSION: IPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.
Assuntos
Artérias/metabolismo , Precondicionamento Isquêmico , Neovascularização Fisiológica , Proteínas Proto-Oncogênicas c-sis/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas ADAM/metabolismo , Proteína ADAMTS1 , Animais , Artérias/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
OBJECTIVE: To investigate the effect of Qingre Quyu Granule (æ¸ çç¥çé¢ç², QRQYG) on stabilizing vulnerable plaques in apolipoprotein E (ApoE) deficient mice. METHODS: Seventy-two male ApoE deficient mice were given a high-fat diet from 6 weeks of age. At the 16th week, all the mice were randomized into 3 groups: the QRQYG group, the simvastatin group, and the control group. Sixteen weeks after administration of 0.9 g/kg QRQYG, 3 mg/kg simvastatin or 10 mg/kg sodium chloride per day to the respective groups, the animals were euthanized. The pathological morphologic changes in the vulnerable plaques were evaluated, the matrix metalloprotease-9 (MMP-9) expression was measured by immunohistofluorescence, the soluble intercellular adhesion molecule 1 (ICAM-1) was determined by ELISA, the nuclear factor kappaB (NF-κB) subunit p65 was measured by quantitative RT-PCR, and, finally, thrombospondin-1 (TSP-1) was determined by the immunohistochemical method. RESULTS: The plaque cross-sectional area in the brachiocephalic artery (23.7%, P<0.01), the lipid core of the plaque (43.1%±3.1%), and the number of buried fibrotic caps of the plaque were significantly decreased in the QRQYG group compared to the control group (both P<0.01); furthermore, the thickness of the fibrotic cap of the plaque increased and the intra-plaque hemorrhage of the plaque decreased. The serum soluble ICAM-1 (27.1±5.1 µg/mL), the protein expression of MMP-9 and TSP-1 and the p65 mRNA expression increased in the QRQYG group in comparison with the control group (P<0.05 or P<0.01). CONCLUSION: QRQYG could stabilize the vulnerable plaque through inhibition of the inflammatory response.
Assuntos
Apolipoproteínas E/genética , Aterosclerose/patologia , Tronco Braquiocefálico/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Animais , Tronco Braquiocefálico/enzimologia , Tronco Braquiocefálico/metabolismo , Tronco Braquiocefálico/patologia , Ensaio de Imunoadsorção Enzimática , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sinvastatina/farmacologia , Cloreto de Sódio/farmacologia , Trombospondina 1/metabolismoRESUMO
1. Urotensin II (U-II) is a powerful vasoconstrictor peptide that stimulates cell proliferation. However, the systemic effects of U-II on cellular and extracellular matrix responses of vessel walls have not been investigated. The aim of the present study was to determine the effect of exogenous U-II on arterial neointimal hyperplasia after balloon injury. 2. A stenosis model of the thoracic aorta after balloon injury was established in male Wistar rats. Rats were divided into three groups (n = 5 in each): (i) uninjured; (ii) injured for 21 days; and (iii) injured and then treated with U-II (1 nmol/kg per h) via an osmotic minipump for 21 days. Another group of rats were killed on Days 7 and 14 after balloon injury for the analysis of in vitro collagen synthesis and secretion with U-II treated by [(3)H]-proline incorporation and determination of [(3)H]-hydroxyproline radioactivity, respectively. 3. Urotensin II immunoreactivity was 1.74-fold higher in vessels injured for 21 days than in uninjured vessels and mRNA levels of the urotensin UT receptor were upregulated by 55% following injury. After U-II treatment, the mRNA levels of the UT receptor were further upregulated (by 40%). In addition, U-II treatment increased the intimal area of injured aortas (13 +/- 5 vs 7 +/- 2% in group iii and ii, respectively), as well as increasing collagen content and cell proliferation. Protein levels of matrix metalloproteinase 1 were decreased in U-II-treated rats. In vitro, U-II treatment increased collagen synthesis and secretion in uninjured vessels in a concentration-dependent manner (10(-10), 10(-9) and 10(-8) mol/L U-II), especially in injured aortas on Day 7 after injury. 4. In conclusion, exogenous U-II may upregulate mRNA levels of the UT receptor, as well as increase collagen and cell proliferation, all of which would contribute to intimal hyperplasia after angioplasty.
Assuntos
Angioplastia com Balão/efeitos adversos , Hiperplasia/fisiopatologia , Túnica Íntima/lesões , Túnica Íntima/fisiopatologia , Urotensinas/fisiologia , Animais , Aorta Torácica/lesões , Aorta Torácica/patologia , Doenças da Aorta , Estenose Aórtica Subvalvar , Proliferação de Células , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Modelos Animais de Doenças , Hiperplasia/patologia , Masculino , Metaloproteinase 1 da Matriz/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Tempo , Túnica Íntima/patologia , Regulação para Cima , Urotensinas/administração & dosagem , Urotensinas/genética , Urotensinas/metabolismoRESUMO
OBJECTIVE: To determine whether the combination of traditional risk factors and quantitative coronary angiography (QCA) assessment could provide accurate prognostic information on a population-based study including 1137 adults with subclinical artherosclerosis and with coronary risk factors. METHODS: Participants underwent coronary angiography examination before the minimal stenotic diameters, segment diameters, percent stenosis, plaque areas. Other parameters were analyzed by the computer-assisted Coronary Angiography Analysis System. The Framingham Risk Score for each participant was assessed. During the 1 year follow-up period, all kinds of endpoint cardiovascular events were screened. Endpoint events were defined as death from coronary heart disease, nonfatal myocardial infarction (MI) or unstable angina pectoris. RESULTS: During the 1 year of follow-up period, a total of 124 participants developed an endpoint event, which was significantly associated with the Framingham Risk Score, calcium of plaques and the plaque areas (all Ps<0.05). The QCA score incorporated with the QCA parameters was related to the endpoint events. The Framingham Risk Score was combined with QCA score through logistic regression for prediction of end-point events. Data from the ROC analysis showed the accuracy of this prediction algorithm was superior to the accuracy when variables themselves were used. The event-free survival rate was inferior to the control group in participates under high risk, when being screened with this prediction algorithm (P<0.05). CONCLUSION: The risk of cardiovascular attack in subclinical artherosclerosis individual seemed to be associated with the Framingham Risk Score, calcium of plaques and the plaque areas. When the traditional risk factors (the Framingham Risk Score) were combined with QCA, the new method could provide more prognostic information on those adults with subclinical artherosclerosis.