RESUMO
OBJECTIVE: To evaluate the association between homocysteine level and prethrombotic status and long-term thromboembolic events in patients with primary hypertension. METHODS: Results between 110 hypertensive patients with elevated homocysteine (HCY) level were compared with 110 hypertensive patients with normal HCY level which were enrolled from October 2003 to November 2009. Fibrinogen (FIB), viscosity, thrombomodulin (TM), granule membrane protein (GMP-140), prethrombin F1+2 fragment (F1+2), D-dimer fragment (D-Dimer) and antithrombin III (AT-III) were measured and correlated to HCY and prethrombotic state. The endpoints of the study were arterial and venous thromboembolic events. The variables linked with arterial and venous thromboembolic events were included in Cox proportional hazard models. The event-free survival was illustrated with Kaplan-Meier survival curves and compared by the Log-rank test. RESULTS: The patients were followed up for 8-122 months (median follow-up time was 85 months). Compared with hypertensive patients with normal HCY, the plasma level of TM ((4.8±1.2) µg/L vs. (4.5±1.0) µg/L, P = 0.045), GMP-140 ((18.8±3.2) µg/L vs. (17.1±4.3) µg/L, P = 0.001), F1+2 ((1.2±0.4) nmol/L vs. (1.0±0.6) nmol/L, P = 0.004) were significantly higher while the plasma level of AT-III ((95.3±10.4) % vs. (98.6±10.6)%, P = 0.021) was significantly lower in hypertensive patients with elevated HCY level. FIB, viscosity of plasma and D-dimer were similar between the two groups. Multiple regression analyses indicated that HCY level was negatively correlated with AT-III (ß = -0.199, P = 0.011) and positively correlated with age (ß = 0.217, P = 0.04), female gender (ß = 5.667, P = 0.001) and TM (ß = 2.341, P = 0.003). Cox multivariate analysis revealed that age and HCY level were independent prognostic risk factors of thromboembolic events (OR 1.046, 95% CI 1.013-1.082, OR 1.052, 95% CI 1.027-1.078, respectively) (all P < 0.05). Kaplan-Meier curves showed that there was a significant difference in the event-free survival between the two groups (Log-rank test, P = 0.027). CONCLUSIONS: Compared with normal HCY hypertensive patients, the levels of plasma prothrombin activators such as TM, GMP-140 and F1+2 were significant increased and anti-thrombin factor such as AT-III was significant decreased in hypertensive patients with elevated HCY. Old age and high HCY level were independent prognostic risk factors of thromboembolic events. The event-free survival in hypertensive patients with elevated HCY is lower than in hypertensive patients with normal HCY level.
Assuntos
Homocisteína/sangue , Hipertensão/complicações , Tromboembolia/complicações , Estudos de Casos e Controles , Hipertensão Essencial , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Estimativa de Kaplan-Meier , Selectina-P , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Fatores de RiscoRESUMO
OBJECTIVE: To assess the safety and efficacy of the StarClose device following intra-aortic balloon pump (IABP) counterpulsation using 8-Fr femoral sheaths. SUBJECTS AND METHODS: From June 2008 to August 2012, 42 consecutive patients who received IABP implantation via common femoral artery (CFA) punctures with an 8-Fr sheath (which were then sealed with the StarClose Vascular Closure System at the bedside) were included in this retrospective single-arm study. All the patients underwent duplex control of the puncture site 24 h after deployment of the device, in order to determine the presence or absence of vascular complications including hematoma, pseudoaneurysm, arteriovenous fistula and arterial/venous thrombosis or stenosis. The safety end points were the vascular complications during the hospital stay, and the efficacy end points included device and procedure success. RESULTS: The procedure success rate was 92.9% (39/42) and the device success rate was 88.1% (37/42). Major vascular complications occurred in 3 (7.1%) patients; 1 developed a massive hematoma >10 cm which was managed by blood transfusion and surgical reconstruction, and the other 2 developed pseudoaneurysm which was cured by ultrasound-guided thrombin injection or manual compression. Minor vascular complications occurred in 5 (11.9%) patients, including blood oozing in 2, hematoma <5 cm in 2 and severe pain in the remaining patient. CONCLUSION: CFA closure with the StarClose device was safe, feasible and effective in patients undergoing IABP support using 8-Fr sheath sizes.
Assuntos
Artéria Femoral , Balão Intra-Aórtico/métodos , Complicações Pós-Operatórias/epidemiologia , Idoso , Equipamentos e Provisões , Feminino , Humanos , Balão Intra-Aórtico/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the efficacy of coronary stenting in patients with variant angina refractory to medical treatment. SUBJECTS AND METHODS: Variant angina was diagnosed in 81 patients admitted to the Department of Cardiology between January 2003 and June 2011. However, coronary stenting was performed in 21 patients refractory to medical treatment, but coronary angiography and intravascular ultrasound were performed in all patients, and acetylcholine provocative test was performed in 11 of the 21 patients refractory to medical treatment. Coronary angiography was repeated after 9-12 months in the 21 patients with coronary stents. Clinical follow-up time was 2.5 ± 3.1 years (range 1-8). RESULTS: Of the 81 patients, coronary angiography and intravascular ultrasound did not reveal significant stenosis in 13 (16.0%), but revealed 20-75% fixed stenosis in the remaining 68 (84.0%) patients. The acetylcholine provocative test was positive in the 11 patients. Of the 21 patients with coronary stents, the spasm site was located in the right coronary artery in 16 (76.2%) and in the left anterior descending artery in the remaining 5 (23.8%) patients. During the 1- to 8-year follow-up period, 1 of the 21 patients with stents developed recurrent episodes of variant angina, 5 patients had occasional chest pain, and the other 15 were asymptomatic. Coronary angiography at 9-12 months after initial evaluation demonstrated no stenosis in 3 patients, 20-40% in-stent mild intimal hyperplasia in 15 patients, and 50-80% in-stent restenosis in 3 patients. Coronary stenting was performed again in 2 patients. CONCLUSIONS: The present study showed that coronary stenting for severe refractory coronary vasospasm was effective and without serious complications. It can be an alternative and viable option for some patients who are refractory to medical therapy and at a high risk of acute coronary syndrome recurrence.
Assuntos
Angina Pectoris Variante/terapia , Angioplastia Coronária com Balão , Vasoespasmo Coronário/terapia , Stents , Idoso , Angina Pectoris Variante/diagnóstico por imagem , Angina Pectoris Variante/etiologia , Angiografia Coronária , Vasoespasmo Coronário/complicações , Vasoespasmo Coronário/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIMS: This study aimed to explore if the right ventricular outflow tract (RVOT) pacing is superior to right ventricular apical (RVA) pacing on the overall left ventricular (LV) function and regional wall motion. METHODS AND RESULTS: Sixty patients with atrio-ventricular (AV) block and normal ejection fraction undergoing dual-chamber pacemaker implantation were randomized to permanent ventricular stimulation either in the RVOT or the RVA. Left ventricular volume, ejection fraction, and LV regional wall motion were assessed by echocardiography. Right ventricular apical pacing had prolonged QRS duration, compared with RVOT pacing (154.1 ± 26.5 vs. 120.9 ± 22.3, P< 0.05). There were also significant differences in LV pre-ejection interval and interventricular mechanical delay (IVMD) at 12-month follow-up between the two groups, but none in the LV volume, left ventricular ejection fraction, and index of systolic synchrony (Ts-SD). During RVA pacing, the average peak systolic velocity (Sm) of 12 LV segments [3.5, 95% confidence interval (CI) 3.2-3.8 cm/s] had a trend of being lower compared with RVOT pacing (3.9, 95% CI 3.5-4.1 cm/s) (P= 0.09). Further analysis showed that the Sm at the inferior wall and posterior-septum wall was significantly decreased during RVA pacing compared with RVOT pacing. There were no significant differences for other LV segments. CONCLUSION: The RVOT pacing in AV block patients over 1 year may be superior to RVA pacing in terms of regional LV performance, LV global electromechanical delay, and IVMD, although intraventricular dyssynchrony and LV volumes do not differ. Larger trials with clinical endpoints are warranted to conclusively define the advantages of RVOT or RV septal pacing.
Assuntos
Bloqueio Atrioventricular/terapia , Estimulação Cardíaca Artificial/métodos , Disfunção Ventricular Esquerda/terapia , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia , Resultado do Tratamento , Ultrassonografia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
AIM: To investigate the potential of propofol in suppressing ventricular arrhythmias and to examine whether mitochondrial ATP-sensitive potassium channels are involved. METHODS: Male Sprague-Dawley rats were pretreated with intravenous infusion of propofol (Prop), a selective mitochondrial KATP channel inhibitor 5-hydroxydecanoate (5-HD), propofol plus 5-HD (Prop+5-HD), a potent mitochondrial K(ATP) channel opener diazoxide (DZ) or NS, respectively. The dosage of each drug was 10 mg/kg. The animals then underwent a 30 min-ligation of the left anterior descending artery. The severity of arrhythmias, the incidence of ventricular fibrillation (VF), and the time of the first run of ventricular arrhythmias were documented using an arrhythmia scoring system. Mitochondrial membrane potential (ΔΨm) was measured in freshly isolated rat cardiomyocytes with a fluorescence microscope. RESULTS: The arrhythmia scores in the Prop and DZ group were 2.6(0-5) and 2.4(0-5), respectively, which were significantly lower than that in the control group [4.9(2-8)]. VF was not observed in both Prop and DZ groups. The first run of ventricular arrhythmias was significantly postponed in the Prop group (10.5±2.2 vs 7.3±1.9 min). Bracketing of propofol with 5-HD eliminated the anti-arrhythmic effect of propofol. In isolated rat cardiomyocytes, propofol (50 µmol/L) significantly decreased ΔΨm, but when propofol was co-administered with 5-HD, the effect on ΔΨm was reversed. CONCLUSION: Propofol preconditioning suppresses ischemia-induced ventricular arrhythmias in the rat heart, which are proposed to be caused by opening of mitochondrial K(ATP) channels.
Assuntos
Canais KATP/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Isquemia Miocárdica/complicações , Propofol/uso terapêutico , Fibrilação Ventricular/prevenção & controle , Animais , Células Cultivadas , Eletrocardiografia , Hemodinâmica/efeitos dos fármacos , Canais KATP/antagonistas & inibidores , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia de Fluorescência , Mitocôndrias Cardíacas/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Propofol/administração & dosagem , Propofol/farmacologia , Ratos , Ratos Sprague-Dawley , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/metabolismoRESUMO
The hypnotic agent propofol is effective for the induction and maintenance of anesthesia. However, recent studies have shown that propofol administration is related to arrhythmias. Propofol displays both pro- and anti-arrhythmic effects in a concentration-dependent manner. Data indicate that propofol can convert supraventricular tachycardia and ventricular tachycardia and may inhibit the conduction system of the heart. The mechanism of the cardiac effects remains poorly defined and may involve ion channels, the autonomic nervous system and cardiac gap junctions. Specifically, sodium, calcium and potassium currents in cardiac cells are suppressed by clinically relevant concentrations of propofol. Propofol shortens the action potential duration (APD) but lessens the ischemia-induced decrease in the APD. Furthermore, propofol suppresses both sympathetic and parasympathetic tone and preserves gap junctions during ischemia. All of these effects cumulatively contribute to the antiarrhythmic and proarrhythmic properties of propofol.
Assuntos
Antiarrítmicos , Arritmias Cardíacas/induzido quimicamente , Hipnóticos e Sedativos , Propofol , Animais , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Relação Dose-Resposta a Droga , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Canais Iônicos/metabolismo , Propofol/efeitos adversos , Propofol/farmacologiaRESUMO
OBJECTIVE: The goal of this study was to investigate the crosstalk between vascular endothelial cells (ECs) and smooth muscle cells (SMCs) using a three-dimensional (3-D) co-culture model. In addition, the role of IL-8 in this crosstalk was investigated. METHODS: A 3-D co-culture model was constructed using a Transwell chamber system and type I collagen gel. Human umbilical artery smooth muscle cells (HUASMCs) were suspended in the gel and added to the upper compartment of the Transwell. Human umbilical vein endothelial cells (HUVECs) were then grown on the surface of the gel. The growth of HUASMCs was tested with a CFDA SE cell proliferation kit. IL-8 and other bioactive substances were investigated by ELISA and real-time PCR. The alteration of p-ERK expression related to the change in IL-8 levels was also examined by Western blot analysis. RESULTS: The proliferation rate of HUASMCs in the 3-D co-culture model was 0.679 ± 0.057. Secretion and transcription of VEGF, t-PA, NO and VCAM-1 in the 3-D co-culture model were different than in single (2-D) culture. When 3-D co-cultured, IL-8 released by HUVECs was significantly increased (2.35 ± 0.16 fold) (P﹤0.05) and the expression of VCAM-1 from HUASMCs was reduced accordingly (0.55±0.09 fold). In addition, increasing or decreasing the level of IL-8 changed the level of p-ERK and VCAM-1 expression. The reduction of VCAM-1, resulting from increased IL-8, could be blocked by the MEK inhibitor, PD98059. CONCLUSION: Crosstalk between HUVECs and HUASMCs occurred and was probably mediated by IL-8 in this 3-D co-culture model.
Assuntos
Células Endoteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Interleucina-8/farmacologia , Miócitos de Músculo Liso/metabolismo , Veias Umbilicais/citologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , MAP Quinases Reguladas por Sinal Extracelular/genética , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ativador de Plasminogênio Tecidual/genética , Ativador de Plasminogênio Tecidual/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To study the safety and efficacy of control-releasing arsenic trioxide (As2O3)-eluting stent on intimal smooth muscle cells (SMC) and type III collagen (CIII) in canine coronary artery post-stent model. METHODS: Twenty-four experimental canines were equally divided into 4 groups, the three tested groups were deployed by stents with different dosage of As2O3 (1.6 microg/mm2, 2.4 microg/mm2 and 3.2 microg/mm2 in low, median and high dose groups, respectively) and coated with polybutyl methacrylate/nano silica and poly-lactide-coglycolide in mild oversizing (stent/vessel ratio of 1.3:1) in left anterior descending (LAD) or circumflex coronary arteries (LCX), while the control group only by simple coated stent without As2O3. The effect was assessed 4 weeks after stent implantation in terms of vascular histomorphology, and changes of SMC and C III expressions were detected using immunohistochemical analysis. RESULTS: Subintimal hemorrhage, medial/adventitial necrosis, thrombosis and inflammatory cell infiltration were not found and integral endothelium could be seen under screening electron microscopy in all groups. Positive expression of SMC and CIII in the tested groups, especial in the high dose As2O3 group, was more weaker than that in control group. Histo-morphological analysis showed that the neo-genetic intimal area and vascular stenosis were lower, but the mean luminal diameter was larger in the three tested groups than that in the control group (P < 0.01). Comparisons of various indices between tested groups treated by different doses of As2O3 showed that the difference between high/median dose vs. low dose was significant (P < 0.01), but that between high dose vs. median dose was insignificant (P > 0.05). CONCLUSION: Control-releasing As2O3-eluting stent shows a reliable and safe effect in preventing and treating post-stent restenosis by its dose-dependent inhibition on expressions of SMC and CIII to suppress the neo-genesis of intimal hyperplasia.
Assuntos
Arsenicais/farmacologia , Colágeno Tipo III/metabolismo , Reestenose Coronária/prevenção & controle , Stents Farmacológicos , Músculo Liso Vascular/patologia , Óxidos/farmacologia , Animais , Trióxido de Arsênio , Arsenicais/administração & dosagem , Reestenose Coronária/etiologia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Cães , Feminino , Implantes Experimentais , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Óxidos/administração & dosagem , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologiaRESUMO
1. The beneficial effects of pravastatin, beyond that of lowering cholesterol in atherosclerosis, include reducing the action of interferon (IFN)-gamma. Interferon-gamma activates the signal transducer and activator of transcription 1 (STAT1), but it is unclear whether the inhibitory effect of pravastatin in atherosclerosis is via modulation of the IFN-gamma/STAT1 pathway. Thus, the aim of the present study was to determine whether the action of pravastatin in preventing aortic atherosclerosis by attenuation of IFN-gamma action is dependent on STAT1. 2. Male apolipoprotein E-knockout (apoE(-/-)) mice were fed a diet containing 1.25% cholesterol (w/w). Mice were divided into two groups, one of which was supplemented with pravastatin (80 mg/kg per day). Male C57BL/6J mice were fed a normal diet and served as the control group (n = 12 per group). 3. Atherosclerotic lesions in the aortic root were assessed by staining sections haematoxylin and eosin. Serum concentrations of IFN-gamma and IFN-gamma mRNA expression in the thoracoabdominal aorta were determined by ELISA and real-time quantitative polymerase chain reaction methods, respectively. Expression of phosphorylated STAT1 (pSTAT1), interferon regulating factor (IRF)-1 and suppressors of cytokine signalling 1 (SOCS1) was determined in the thoracoabdominal aorta using Western blot analysis. 4. After 8 weeks, pravastatin treatment significantly prevented the formation of atherosclerotic lesions (P < 0.05) and reduced serum IFN-gamma concentrations (P < 0.05) and levels of IFN-gamma mRNA within the aorta (P < 0.01). Pravastatin significantly decreased the expressions of pSTAT1 and IRF-1 within the aorta and significantly increased expression of SOCS1. 5. These results suggest that the actions of pravastatin in attenuating the action of IFN-gamma and subsequently preventing aortic atherosclerosis may depend, at least in part, on modulation of STAT1 activity. This providing us with a new therapeutic approach and a clearer insight into the clinical benefits of pravastatin.
Assuntos
Apolipoproteínas E/genética , Aterosclerose/prevenção & controle , Interferon gama/fisiologia , Pravastatina/farmacologia , Fator de Transcrição STAT1/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Fator Regulador 1 de Interferon/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pravastatina/uso terapêutico , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
Statins, inhibitors of 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, have been recognized as a new type of immunomodulator and reported to have anti-inflammatory effect. To investigate the effect of simvastatin, a lipophilic statin, on myocarditis, we explored whether simvastatin is able to inhibit experimental autoimmune myocarditis (EAM) and adoptive transfer of EAM in rats. We found that administration of simvastatin not only interfered with the development of EAM, but also inhibited the transfer. Antigen presenting cells (APCs) were proved to be important for the development of EAM. The ability of myocarditic splenocytes to transfer myocarditis was enhanced after co-culture with APCs. During co-culture of the myocarditic splenocytes and the APCs, simvastatin not only decreased percentages of CD28 expression in CD4-positive myocarditic splenocytes, and CD80 and CD86 expressions in APCs, but also inhibited the production of tumor necrosis factor (TNF)-partial differential in the CD4-positive myocarditic splenocytes and the APCs. These results indicate that simvastatin was able to ameliorate EAM through the inhibition of cross-talk between lymphocytes and APCs, suggesting beneficial role of simvastatin in the treatment of autoimmune myocarditis.
Assuntos
Anti-Inflamatórios/farmacologia , Células Apresentadoras de Antígenos/imunologia , Doenças Autoimunes/tratamento farmacológico , Linfócitos T CD4-Positivos/imunologia , Comunicação Celular/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Miocardite/tratamento farmacológico , Sinvastatina/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Linfócitos T CD4-Positivos/transplante , Comunicação Celular/imunologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Miocardite/induzido quimicamente , Miocardite/imunologia , Ratos , Ratos Endogâmicos Lew , Sinvastatina/uso terapêutico , Baço/imunologia , Suínos , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVE: To investigate the effect and safety of Zedoary Turmeric Oil (ZTO)-eluting stents for post-coronary stenting restenosis prevention and treatment in the experimental dogs. METHODS: Bare stents, stents coated with polybutyl methacrylate/Nano silica, and stents eluted with 100 microg ZTO were randomly deployed in canine anterior descending or circumflex coronary artery. Four weeks after stent implantation, the dogs were sacrificed and the vascular histomorphologic changes in the stenting segment analyzed. RESULTS: Thickened intima could be seen under light microscope in the bare or coated stents, but thinner in ZTO-duting stent, with no sub-intimal hemorrhage, medial or adventitial necrosis, wall adhesive thrombus, or infiltration of inflammatory cells. Scanning electric microscopy showed the intima was intact. Histomorphologic analysis showed that the thickness and area of neo-intima, and the lumen stenosis percent in artery stented with ZTO eluting stents were significantly lower than those stented with bare or coated stents (P <0.01), and thus the lumen cavity was expanded (P < 0.01), while no statistic significant difference between polymer and bare stents was found (P > 0.05). CONCLUSION: ZTO-eluting stent is available and safe, and it could significantly inhibit the growth of neo-intimal in canine coronary mode after stenting, showing a restenosis preventive and treatment effect.
Assuntos
Reestenose Coronária/tratamento farmacológico , Reestenose Coronária/prevenção & controle , Curcuma/química , Extratos Vegetais/administração & dosagem , Óleos de Plantas/administração & dosagem , Animais , Modelos Animais de Doenças , Cães , Stents Farmacológicos , Feminino , Humanos , Masculino , Distribuição AleatóriaRESUMO
The purpose of this study was to observe whether human peripheral dervied monouncleas cells (hMNCs) could participate in the regeneration process of the ischemic hearts in the way of differentiating into cardiomyocytes, vascular endothelial cells and smooth muscle cells. hMNCs were transplanted into the bodies of the mice with myocardial infarction through the tail vein injection. Hearts were harvested 2-12 weeks after injection then sliced up into frozen sections of 5 micron thickness. Double immunofluorescence staining was used to test the differentiation of the grafted cells into cardiomyocytes, smooth muscle cells and vascular endothelial cells which revealed that cells expressing both HLA and TNT, HLA and alpha-SMA, HLA and vWF existed in the hearts of the mice. According to the study, it is probable that hMNCs could participate in the regeneration process of the infarcted hearts in the way of differentiation.
Assuntos
Diferenciação Celular/fisiologia , Leucócitos Mononucleares/transplante , Infarto do Miocárdio/terapia , Miócitos Cardíacos/citologia , Animais , Humanos , Camundongos , Camundongos Nus , Infarto do Miocárdio/patologia , Transplante HeterólogoRESUMO
OBJECTIVE: To study the safety and efficacy of controlled-release arsenic-trioxide (As(2)O(3))-eluting stents to reduce in-stent neointimal hyperplasia in coronary artery. METHODS: As(2)O(3) was sprayed onto the stainless steel coated with polybutyl methacrylate/nano-silica and poly-lactide-co-glycolide so as to make the controlled-release As(2)O(3)-eluting stents with the As(2)O(3) concentrations of 0, 1.6, 2.4, and 3.2 microg/mm(2). Thirty adult dogs were randomly divided into 5 equal groups to undergo deployment of bare stent, coated stent, and As(2)O(3)-eluting stent of low dose (1.6 microg/mm(2)), medium dose (2.4, microg/mm(2)), and high dose (3.2 microg/mm(2)) into the left anterior descending artery or circumflex coronary artery respectively, and aspirin 250 mg/day was given 3 days before operation until 4 weeks after operation. Four weeks after the operation the dogs underwent angiography and then killed. The coronary artery, heart, liver, spleen, lung, kidney, and brain were taken out for pathological examination. RESULTS: The mean injury scores were similar in all groups. The values of mean neointimal thickness of the high-, medium-, and low-dose groups were (0.14 +/- 0.05) mm, (0.15 +/- 0.04) mm, and (0.27 +/- 0.03 mm) respectively, all significantly lower than those of the coated stent and bare stent groups [(0.39 +/- 0.06) mm and (0.33 +/- 0.02) mm respectively, all P < 0.01], with significant differences between the high and medium groups and low dose group (both P < 0.01). The neointimal areas of the high, medium, and low dose groups were (1.09 +/- 0.11) mm(2), (1.33 +/- 0.10) mm(2), and (1.93 +/- 0.29) mm(2) respectively, all significantly smaller than those of the coated stent and bare stent groups [(2.44 +/- 0.15) mm(2) and (2.40 +/- 0.32) mm(2), all P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). The stenosis rates of the high, medium, and low dose groups were (19.54 +/- 3.59)%, (22.18 +/- 3.3)%, and (36.22 +/- 5.17)% respectively, all significantly lower than those of the coated stent and bare stent groups [(50.39 +/- 3.03)%, and (46.88 +/- 5.85)% respectively, all P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). The luminal areas of the high, medium, and low dose groups were (5.14 +/- 0.55) mm(2), (4.97 +/- 0.38) mm(2), and (3.75 +/- 0.39) mm(2) respectively, all significantly larger than those of the coated stent and bare stent groups [(2.62 +/- 0.22) mm(2) and (3.10 +/- 0.66) mm(2) respectively, both P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). Pathological examination did not find intraintimal hemorrhage, medial and adventitial necrosis, aneurysm, thrombosis, and inflammatory cell infiltration in all groups. CONCLUSION: Capable of inhibiting neointimal hyperplasia in the coronary arteries dose-dependently after implantation, controlled-release As(2)O(3)-eluting stents is safe and applicable in treating coronary diseases.
Assuntos
Arsenicais/farmacologia , Stents Farmacológicos , Óxidos/farmacologia , Túnica Íntima/efeitos dos fármacos , Angioplastia Coronária com Balão , Animais , Trióxido de Arsênio , Arsenicais/administração & dosagem , Cães , Relação Dose-Resposta a Droga , Hiperplasia , Óxidos/administração & dosagem , Período Pós-Operatório , Túnica Íntima/patologiaRESUMO
OBJECTIVE: To investigate electrocardiographic (ECG) and angiographic characteristics of patients with acute solitary posterior myocardial infarction. Patients complicated by inferior wall or right ventricular infarction were excluded. METHOD: ECG and angiographic changes in 11 patients with acute solitary posterior myocardial infarction admitted to our emergency room from 2001 to 2006 were analyzed. RESULTS: Besides typical ST segment elevation in V(7)-V(9) leads, other ECG manifestations in these patients included V(1)-V(2) R/S > or = 1 (9/11, 81.8%), 1 - 2 mm ST depression in V(1)-V(4) (5/11, 45.5%), 0.5 - 1.5 mm ST elevation in I, aVL leads (4/11, 36.4%) and 0.5 - 1.5 mm ST elevation in V(5)-V(6) leads (5/11, 45.5%). Coronary angiography showed that left circumflex artery (LCX) was the infarction related artery in all cases. The infarction area located before OM1 origination in 1 patient with a 95% pipe-like stenosis (1/11), after OM1 origination in 6 patients (6/11, 4 with total occlusion, 1 with sub-total occlusion and 1 with 90% long length stenosis), in OM1 in 4 patients (4/11, 2 with total occlusion, 1 with sub-total occlusion and 1 with 95% local stenosis). There were 3 patients (27.3%) with single vessel lesion, 4 patients (36.4%) combined with left anterior descending artery (LAD) lesion, 2 patients (18.2%) combined with right coronary artery (RCA) lesion and 2 patients (18.2%) combined with LAD and RCA lesions. CONCLUSIONS: Acute posterior myocardial infarction should be suspected with V(1)-V(2) R/S > or = 1 and V(1)-V(4) ST depression in standard 12 leads ECG. Besides symptoms and cardiac enzyme measurements, recording posterior leads electrocardiogram and performing coronary angiography will help to make the correct diagnosis.
Assuntos
Angiografia Coronária , Vasos Coronários/fisiopatologia , Eletrocardiografia , Infarto do Miocárdio/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/enzimologiaRESUMO
OBJECTIVE: To observe the safety and efficacy of early or non-early controlled-release arsenic-trioxide (As(2)O(3))-eluting stents on reducing in-stent neointimal hyperplasia. METHODS: Bare stents, stents coated with polybutyl methacrylate/Nano silica (containing 200 microg of As(2)O(3) per stent or not), stents coated with polybutyl methacrylate/Nano silica inside (containing 200 microg of As(2)O(3) per stent or not) and poly-lactide-co-glycolide (PLGA) outside were deployed with mild oversizing in left anterior descending (LAD) and circumflex coronary arteries (LCX)of 30 canines (n = 6, 12 stents for each group). RESULTS: The mean injury scores were similar in all groups at 4 weeks post stents implantation while the mean neointimal thickness, neointimal area and degree of stenosis were significantly reduced and the lumen area significantly increased in canines receiving single coating stents containing As(2)O(3) compared with single or double coating stents and bare stents groups (all P < 0.01). These effects were further enhanced in canines implanted with double coating stents containing As(2)O(3) (all P < 0.01 vs. single coating stents containing As(2)O(3)). No intraintimal hemorrhage, medial and adventitial necrosis, aneurysm, thrombosis, inflammatory cells infiltration were observed in all stenting groups. CONCLUSIONS: Controlled-release As(2)O(3)-eluting stents resulted in a significant inhibition of neointimal hyperplasia in the canine coronary arteries 4 weeks after stents implantation and the effects is more significant with controlled-release of As(2)O(3) at non-early stage than that at early stage.
Assuntos
Arsenicais/farmacologia , Reestenose Coronária/prevenção & controle , Stents Farmacológicos , Óxidos/farmacologia , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/métodos , Animais , Trióxido de Arsênio , Arsenicais/administração & dosagem , Reestenose Coronária/etiologia , Modelos Animais de Doenças , Cães , Óxidos/administração & dosagemRESUMO
In this study, we investigate Nitric oxide synthase (NOS) expressions in adriamycin (ADR)-induced cadiomyopathy in rats. Sixty male Wistar rats were randomly divided into two main groups: control and ADR groups. Myocardial histopathological observation was performed; Expressions of 3 isoforms of NOS genes were examined by RT-PCR analysis; Expressions of 3 isoforms of NOS protein was assessed by Western blot analysis. Myocardium exhibited intensive morphological changes after 8 weeks of ADR treatment. The expression levels of inducible NOS (iNOS) gene and protein were significantly increased in ADRtreated rats after 8 weeks of treatment and then slightly increased at weeks 9 and 10. No significantly difference of neuronal NOS (nNOS) or endothelial NOS (eNOS) gene and protein were observed in the myocardium obtained from the control rats and ADR-injected rats at any time point. iNOS gene expression is selectively induced by ADR in heart. The upregulation of iNOS gene and protein may be somehow correlated with morphological changes seen in heart of rat treated with ADR.
Assuntos
Cardiomiopatias/enzimologia , Doxorrubicina , Expressão Gênica/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Expressão Gênica/fisiologia , Masculino , Miocárdio/patologia , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo III/genética , Ratos , Ratos WistarRESUMO
OBJECTIVE: The purpose of this study was to observe the endothelial progenitor cells (EPCs) related gene expression changes before and early after revascularization in patients with acute myocardial infarction. METHODS: Peripheral blood samples were taken from patients with acute anterior myocardial infarction 6 hours and 7 days after PCI and stenting. Mononuclear cells (MNCs) were isolated by Ficoll-density centrifugation and cultured in M-199 medium. After 14 days culture, attaching cells incorporated DiI-acetylated low-density lipoprotein (EPCs) were collected and RNA was isolated by Trizol for microarray analysis on 24 genes associated with permissibility/vessel tone (angiotensin system: ACE, AGTR-1, AGTR-2; NO system: eNOS; prostacyclin system: COX-2; endothelin system: ET-1, ETA, ETB; superoxide anions system: SOD-1), angiogenesis (adhesion molecule: CDH5; growth factors and receptors: VEGFR1, VEGFR2, VEGF) and endothelial cell activation (adhesion molecules expression: ICAM1, ICAM2, ICAM3, PECAM-1, E-Selectin, L-Selection, VCAM1; change phenotype from antithrombotic to prothrombotic: tPA, uPA, PAI, vWF). VEGFR2, PECAM-1 and VE-cadherin positive cells were identified by flow cytometry. RESULT: Eight gene expressions (AGTR-1, AGTR-2, COX-2, eNOS, ET-1, ETA, VEGF) were significantly downregulated 7 days post PCI compared to pre-PCI (P < 0.05). Flow cytometry results showed that VEGFR2 positive cells were also significantly reduced post PCI than that of before PCI (P < 0.05). CONCLUSION: PCI down-regulated endothelial progenitor cells related gene expressions in patients with acute myocardial infarction.
Assuntos
Endotélio Vascular/citologia , Expressão Gênica , Infarto do Miocárdio/metabolismo , Revascularização Miocárdica , Idoso , Idoso de 80 Anos ou mais , Centrifugação com Gradiente de Concentração , Células Endoteliais/citologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Análise de Sequência com Séries de Oligonucleotídeos , Receptor Tipo 1 de Angiotensina/biossíntese , Receptor Tipo 1 de Angiotensina/genética , Receptor de Endotelina A/biossíntese , Receptor de Endotelina A/genética , Células-Tronco/citologia , Superóxido Dismutase/biossíntese , Superóxido Dismutase/genéticaRESUMO
OBJECTIVE: To study the blood pressure (BP) changes in the liver transplant recipients. METHODS: A total of 206 patients without preoperation hypertension received liver transplantation in our hospital from February 2001 to July 2005. The BP level and serum immunosuppressant concentration at preoperation and various time points post operation were determined. RESULTS: Compared with the preoperation, the average systolic and diastolic pressure was significantly increased at the 2 week, 1, 2, 4 and 6 months post operation. The mobility of hypertension increased significantly after liver transplantation, with the highest mobility (46.49%) at the 1st month post operation. There was no linear correlation between the immunosuppressant (FK506) concentration and the BP level at any time point. CONCLUSION: There was a high hypertension incidence after liver transplantation. Although the use of immunosuppressive drugs accompanied with the BP increase, there was no linear correlation between the immunosuppressant concentration and the BP level post operation.
Assuntos
Pressão Sanguínea , Hipertensão/etiologia , Transplante de Fígado/efeitos adversos , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Estudos RetrospectivosRESUMO
OBJECTIVE: The purpose of this study was to observe histopathological changes post cryoablation in canine myocardium, to characterize the specific ablation lesion post cryoablation. METHODS: Cryothermal ablation was applied on myocardium (both epicardium and endocardium) of 14 mongrel dogs with different ablation parameters (-25 degrees C x 4 min, -50 degrees C x 4 min, -75 degrees C x 4 min, -75 degrees C x 2 min, -75 degrees C x 6 min, -75 degrees C x 8 min). Lesion dimensions and histopathologic changes were observed. RESULTS: The discrete, sharply delimited lesions were detected in cryoablated myocardium. Histologically, cryoablation in all temperatures studied induced heterogeneous necrosis of the myocardium. Lesion dimensions are related to freezing time and temperature. CONCLUSION: Cryoablation is a feasible and preferably choice for clinical application due to its controllable myocardium lesions.
Assuntos
Ablação por Cateter , Criocirurgia , Miocárdio/patologia , Animais , Cães , Endocárdio/patologiaRESUMO
OBJECTIVE: We observed the therapeutic effectiveness and safety of different antidepressants as well as the correlation between symptomatic improvement of depression and improvement of chest pain in patients with susceptible "angina pectoris" and negative coronary angiogram complicating comorbid depression. METHODS: In this double-blinded randomized study, a total of 123 eligible patients were allocated into three groups: (1) Group F: fluoxetine 20 mg QN (n = 41); (2) Group P: Placebo 1 tablet QN (n = 40); (3) Group F + O: fluoxetine 20 mg + olanzapine 2.5 mg QN for the former 2 weeks and only fluoxetine 20 mg QN for the latter 2 weeks (n = 42). The total therapy duration was 4 weeks. HAMD, HAMA and self-evaluation table of chest pain were obtained before therapy, at the end of 1 and 2 weeks after therapy. RESULTS: Baseline HAMD and HAMA scores and self-evaluation score of chest pain were similar among 3 groups and all scores were significantly improved post various therapies in the order of group F + O > group F > group P. The rate of score decrease were seen after 1 week treatment in group F + O and after 2 week treatment in group F. There was a significant positive correlation between the rates of self-evaluation chest pain score decrease and HAMD (r = 0.867, P < 0.001) and HAMA (r = 0.854, P < 0.001) score decreases after 4 weeks therapies (P < 0.05). During the whole course of treatment, no serious adverse reaction was found in all patients. CONCLUSION: In patients with suspected "angina pectoris" and negative coronary angiogram complicating comorbid depression, the antidepressants were safe and significantly improved the symptoms of depression and anxiety and chest pain. Low dose fluoxetine plus short term olanzapine regimen was superior to fluoxetine alone regimen in terms of stronger and quicker symptom improvement.