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<p><b>BACKGROUND</b>Matrix metalloproteinase (MMP)-2 plays an important role in the remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated the differences of MMP-2 expression between LV and RV in response to nandrolone decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice, based on their structural, functional, and biochemical characteristics.</p><p><b>METHODS</b>Totally 28 male C57B1 mice (6 weeks old; 20-23 g) were divided into four groups, including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups. After respective treatments for 8 weeks, echocardiographic examination was used to assess the cardiac structure and function. Van Gieson stain was used to examine the fibrosis of LV and RV in response to different treatments, and Western blotting analysis was performed to explore different MMP-2 expressions between LV and RV in response to ND and/or ST. Analysis of variance was used for comparing the four groups.</p><p><b>RESULTS</b>At 8 weeks, right ventricular dimension/body weight in the ND group was larger than the other three groups (F = 7.12, P < 0.05) according to the echocardiographic examination. Fibrosis induced by ND administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2 expression of the ND group in RV was significantly greater than the control and NS groups in RV and the corresponding ND group in LV.</p><p><b>CONCLUSION</b>The experimental data support the hypothesis that ND administration induces greater MMP-2 expression increase in RV compared to LV, leading to consequent RV dilation.</p>
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OBJECTIVE: To evaluate the effect of exogenous creatine phosphate (CP) on myocardial injury after percutaneous coronary intervention (PCI). METHOD: Four hundred patients were divided to receive conventional therapy (control group) or 3-day intravenous infusion of CP after PCI (CP group). Levels of creatine kinase MB (CK-MB) and troponin I (TnI) were measured before and on postprocedural day 3. RESULTS: Postprocedural CK-MB and TnI in the CP group were significantly increased compared to the control group. In the CP group, 8.0% and 5.0% of patients had an increase in CK-MB 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (19.0% and 9.0%, respectively); 12.0% and 10.0% of patients had an increase in TnI 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (21.0% and 18.0%, respectively). CONCLUSION: Exogenous CP was helpful to reduce myocardial injury after PCI.
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Daño por Reperfusión Miocárdica/prevención & control , Intervención Coronaria Percutánea/efectos adversos , Fosfocreatina/administración & dosificación , Anciano , Biomarcadores/sangre , China , Forma MB de la Creatina-Quinasa/sangre , Citoprotección , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Daño por Reperfusión Miocárdica/sangre , Daño por Reperfusión Miocárdica/diagnóstico , Daño por Reperfusión Miocárdica/etiología , Factores de Tiempo , Resultado del Tratamiento , Troponina I/sangre , Regulación hacia ArribaRESUMEN
<p><b>BACKGROUND</b>Due to lack of point-of-care testing, the use of low-molecular-weight heparin (LMWH) therapy in some special patients is restricted. This study was designed to explore the effects of LMWH on clot rate (CR) and activated clotting time (ACT), and to search for an appropriate method for bedside monitoring of anticoagulant activity of LMWH.</p><p><b>METHODS</b>Thirty-two healthy volunteers were selected from the staff of Beijing Tongren Hospital. CR and ACT were measured with different reagents (glass beads, diatomite, kaolin and magnetic bar) on blood samples spiked with increasing concentrations of LMWH (dalteparin, 0.2-1.8 IU/ml). Correlations between concentrations of LMWH and values of CR and ACT were analysed based on the data obtained and regression analysis was performed to establish a regression equation.</p><p><b>RESULTS</b>With the increase in doses of dalteparin, CR values reduced gradually. The values of CR of four reagents (glass beads, diatomite, kaolin and magnetic bar) were 20.4-4.5 IU/min, 27.4-6.9 IU/min, 27.5-7.9 IU/min and 7.8-0.1 IU/min respectively and an linear relationship was observed between the CR values and dalteparin concentrations (P < 0.05). The values of ACT were 173-615 seconds, 130-270 seconds, 123-226 seconds, 337-1411 seconds respectively, which showed a linear regression between the ACT values and dalteparin concentrations (P < 0.01). Differences in slope of the regression curves of ACT were observed with all the reagents tested (glass beads 248.2 s/IU, diatomite 74.8 s/IU, kaolin 58.2 s/IU and magnetic bar 1112.2 s/IU, P < 0.01). While the minimum concentration of dalteparin was 0.2 IU/ml, 0.4 IU/ml, 1.4 IU/ml and 0.2 IU/ml separately, the ACT values of the four coagulants (glass beads, diatomite, kaolin and magnetic bar) were beyond the normal limit and showed a noticeable increase respectively (P < 0.01).</p><p><b>CONCLUSIONS</b>This study showed that there was an excellent linear relationship between the CR and ACT values and dalteparin concentrations for all the four reagents (glass beads, diatomite, kaolin and magnetic bar) in vitro. The sensitivity of different coagulation reagents to LMWH different. Choosing a suitable reagent, both CR and ACT were possible to be used as a convenient bedside test for LMWH.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticoagulantes , Farmacología , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Heparina de Bajo-Peso-Molecular , FarmacologíaRESUMEN
BACKGROUND: Atherosclerosis is a chronic inflammatory disease. Accumulated evidences suggest a deep involvement of oxidative damage in the development of atherosclerosis, but little is discussed over the relationship between plasma glutathione redox status as the most important intrinsic antioxidant defensive mechanism and the atherosclerosis. METHODS: A total of 132 patients suspected with atherosclerosis were assigned to three groups by high frequency ultrasonic examination of the carotid artery. With the thickness of intima of the carotid artery as an index of degree of atherosclerosis progression, 56 were included in plaque-forming group (A), 42 in carotid artery intima-thickening group (B), and 34 in normal carotid artery intima-thickness group (C). All patients were subjected to the measurement of plasma glutathione (GSH) (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (NADP) (reduced form NADPH and oxidized form NADP(+)), oxidized low density lipoprotein (oxLDL), and malondialdehyde (MDA). The GSH/GSSG and NADPH/NADP(+) redox potentials were calculated according to the Nernst equation, and their correlation with intima thickness and oxLDL was analyzed. RESULTS: With the thickening of artery intima (from group C to A), GSH concentration and the ratio of GSH/GSSG gradually reduced, and GSSG and GSH/GSSG redox potential gradually increased (more positive) (P < 0.05). The NADPH and NADPH/NADP(+) redox status also showed similar but milder changes. The products of oxidative stress oxLDL and MDA increased significantly along with the thickening of artery intima (P < 0.05). The analysis of the relationship between GSH/GSSG redox potential, intima thickness, and oxLDL showed positive correlations (P < 0.05). The plasma GSH/GSSG redox status was positively correlated with the intima thickness of the carotid artery and the oxidized injury of LDL. The redox status shifted to oxidizing direction along with the intima thickening and plaque-forming. CONCLUSION: Elevated peroxidative glutathione redox status was deeply implicated in atherosclerosis progressing, and it may be a sensitive and reliable index for monitoring oxidative status in atherosclerosis.
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Aterosclerosis/metabolismo , Arterias Carótidas/patología , Disulfuro de Glutatión/sangre , Glutatión/sangre , Túnica Íntima/patología , Túnica Media/patología , Adulto , Anciano , Aterosclerosis/patología , Femenino , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , NADP/sangre , Estrés OxidativoRESUMEN
<p><b>BACKGROUND</b>Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxaparin, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.</p><p><b>METHODS</b>A total of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied.</p><p><b>RESULTS</b>The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r = 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU, diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.</p><p><b>CONCLUSIONS</b>The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin. The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-IIa activities.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticoagulantes , Farmacología , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Coagulantes , Farmacología , Vidrio , Heparina de Bajo-Peso-Molecular , Farmacología , Caolín , Farmacología , Nadroparina , FarmacologíaRESUMEN
<p><b>OBJECTIVE</b>In this randomized, open-label, multicenter, angiographic trial, we compared the efficacy and safety of tenecteplase (TNK-tPA) with alteplase (rt-PA) in Chinese patients with acute myocardial infarction.</p><p><b>METHOD</b>Patients with acute ST-elevation myocardial infarction and pain to hospital time within 6 hours from October 2002, to March 2004 were randomly assigned a body weight-adjusted bolus of TNK-tPA (0.53 mg/kg over more than 10 s, n = 58) or front loaded rt-PA (< or = 100 mg, n = 52). Coronary angiography was performed at 90 min after initiating study drugs. All patients received aspirin and heparin (target activated partial thromboplastin time: 50-70 s). The primary end point of the trial was the rate of TIMI grade 3 flow at 90 minutes. Other end points included the rate of TIMI grade 2/3 flow at 90 minutes, all cause mortality at 30 days, the moderate/severe hemorrhage without intracranial hemorrhage (ICH) and ICH within 30 days.</p><p><b>RESULTS</b>TIMI grade 3 flow at 90 minutes (68.4% vs. 66.7%, P = 1.00), TIMI grade 2 or 3 at 90 minutes (89.5% vs. 80.4%, P = 0.278), total mortality at 30 days (13.8% vs. 9.6%, P = 0.565), the rate of moderate/severe hemorrhage (8.6% vs. 5.8%, P = 0.72) and incidence of ICH (3.5% vs. 1.9%, P = 1.00) were all similar in TNK-tPA treated patients compared to rt-PA treated patients.</p><p><b>CONCLUSION</b>The efficacy of single-bolus, weight-adjusted TNK-tPA fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, TIMI 2 or 3 flow. Incidences of moderate/severe hemorrhage, ICH and 30-days mortality were similar in TNK-tPA and rt-PA treated patients.</p>
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Anciano , Humanos , Persona de Mediana Edad , Infarto del Miocardio , Quimioterapia , Terapia Trombolítica , Activador de Tejido Plasminógeno , Usos Terapéuticos , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the protective effects of potassium magnesium aspartate against oxidative stress status and lipid oxidative damage in the patients with angina and arrhythmia due to coronary artery disease, its therapeutic effect on arrhythmia and its possible mechanism. METHODS: With single blind protocol, 98 patients with angina and arrhythmia due to coronary artery disease were randomly divided into (1)Experiment group (n = 65), who received routine remedy for coronary heart disease plus potassium magnesium aspartate. (2)Control group (n = 33), who received only routine therapy for coronary heart disease without potassium magnesium aspartate. Reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA) and oxidized low density lipoprotein (ox-LDL) in plasma of all patients were examined before and one week after treatment, all patients with arrhythmia were equipped with Holter for continuous monitoring of cardiac rhythm. RESULTS: After one week's treatment, the GSH level in plasma of experiment group and the ratio of GSH and GSSG (GSH/GSSG) were significantly increased comparing with control group (both P<0.01), while GSSG, MDA and ox-LDL levels significantly lowered comparing with control group(all P<0.01). The premature beats diminished 86.5% in experiment group, but the decrease rate in control group was only 47.4% (P<0.01). The improvement in indexes of oxidative stress status (including GSH/GSSG, MDA and ox-LDL) and the reduction of premature beats showed close correlation with each other (all P<0.01). No adverse effects of the drug were found after one week of administration of Potassium magnesium aspartate. CONCLUSION: Potassium magnesium aspartate can strikingly improve oxidative stress status and decrease lipid oxidative damage in the patients with coronary heart disease, and the frequent premature beats were also significantly reduced by potassium magnesium aspartate. The analysis of above results reveals an intrinsic relationship between the improvement of oxidative stress status and the good therapeutic effects on frequent premature beats by potassium magnesium aspartate, which may suggest an involvement of oxidative stress in the pathogenesis of arrhythmias.
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Arritmias Cardíacas/tratamiento farmacológico , Cardiotónicos/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Aspartato de Magnesio y Potasio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Angina de Pecho/sangre , Angina de Pecho/tratamiento farmacológico , Arritmias Cardíacas/sangre , Femenino , Glutatión/sangre , Disulfuro de Glutatión/sangre , Humanos , Peroxidación de Lípido/efectos de los fármacos , Lipoproteínas LDL/sangre , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Método Simple CiegoRESUMEN
The standard samples of reduction form glutathione (GSH) and oxidization form glutathione (GSSG) were scanned with full-wavelength range to determine the excitation wavelength lambda(ex) 334.4 nm, the emission wavelength lambda(em) 424 nm, and the spectral bandwidth 5 nm respectively. Phosphate buffer saline (PBS) of pH 8. 3 served as buffer solution. GSH was incubated for 30 min with 100 microL o-phthaldehyde (OPA) of 10 mmol x L(-1) methyl alcohol solution for derivatization, and then fluorescence intensities were measured. With standard glutathione concentration being independent variable and fluorescence intensity being dependent variable, the linear equations for GSH and GSSG were deduced: Y(GSH) = 6.9 + 8.6X (r2 = 0.994) and Y(GSSG) = 6.2 + 17.2X (r2 = 0.999). Standard curves were done hereby. The plasma glutathione of three groups was then measured, and GSH/ GSSG redox potential was calculated according to Nernst equation. The results indicated that, from normal control group to prophase coronary heart disease group, then to coronary heart disease group, the GSH and GSH/GSSG ratio gradually reduced, GSSG and GSH/GSSG redox potential gradually increased (more positive) (all P < 0.05), and the redox potential shifted to oxidization direction along with the development of coronary heart disease. This fluorospectrophotometry method showed simple operation, and fine precision and accuracy.
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Enfermedad Coronaria/sangre , Glutatión/sangre , Espectrometría de Fluorescencia/métodos , Adulto , Anciano , Enfermedad Coronaria/diagnóstico , Disulfuro de Glutatión/sangre , Humanos , Masculino , Persona de Mediana Edad , Oxidación-ReducciónRESUMEN
OBJECTIVE: To explore the relationship between plasma redox status and atherosclerosis. METHODS: IVUS was performed in common carotid in the neck of 167 patients with heart diseases. Patients were divided into three groups: plaque-forming group (A, n = 79), intima-thickening group (B, n = 52) and control group (C, n = 36). Plasma glutathione (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (reduced form NADPH and oxidized form NADP(+)), oxidized low density lipoprotein (ox-LDL) and malondialdehyde (MDA) were measured in all patients. The GSH/GSSG and NADPH/NADP(+) redox potential were calculated according to Nernst equation, and correlation analysis performed. RESULTS: GSH and GSH/GSSG gradually reduced and GSH/GSSG redox potential gradually increased in proportion to the thickening of artery intima (from Group C to Group A, P < 0.05). Similar but milder results were shown for NADPH and NADPH/NADP(+) redox status. The products of oxidative stress ox-LDL and MDA also increased significantly (P < 0.05) in proportion to the thickening of artery intima. GSH/GSSG redox potential is positively correlated to ox-LDL (P < 0.05). The redox status shifted to oxidizing direction in proportion to the intima thickness. CONCLUSION: The imbalance of plasma redox status deviating to oxidation might be implicated in oxidized injury of lipid, intima thickening and atherosclerosis progress.