RESUMO
Objective: To evaluate the acute and long-term outcome of patients with ST segment elevation myocardial infarction (STEMI) concurrent with chronic total occlusion (CTO) undergoing primary percutaneous coronary intervention (PCI). Methods: 11 905 STEMI patients from the China Acute Myocardial Infarction Registry were enrolled in this study and divided into CTO group and non-CTO group according to the angiography results of primary PCI. 1∶3 propensity score matching was used to match the patients between the two groups. The primary endpoint was in-hospital mortality and mortality at 1-year post PCI. The secondary endpoint was major adverse cardiovascular events (MACE) including death, re-myocardial infarction, revascularization, heart failure associated readmission, stroke and major bleeding at 1-year post PCI. Results: There were 931 CTO patients (7.8%) in this cohort (male=755 (81.1%), mean age (62.2±11.4 years)). The rest 10 974 patients were STEMI without CTO (male=8 829 (80.5%),mean age (60.0±11.8) years). After propensity score matching, 896 patients were enrolled in CTO group and 2 688 in non-CTO group. In-hospital mortality was significantly higher in the CTO group than in non-CTO group (4.2% vs. 2.4%, P=0.006). The ratio of all cause death, cardiac death, and MACE at 1-year follow up was also significantly higher in the CTO group than in non-CTO group (8.5% vs. 4.4%, P<0.001, 5.3% vs. 2.6%, P=0.001, 35.1% vs. 23.3%, P<0.001, respectively). Multiple regression analysis showed that CTO (HR=1.54, 95%CI 1.06-2.22, P=0.022), advanced age (HR=1.06, 95%CI 1.04-1.08, P<0.001), and previous heart failure history (HR=4.10, 95%CI 1.90-8.83, P<0.001) were independent risk factors of 1-year mortality. Conclusions: The in-hospital and 1-year mortality increased significantly in STEMI patients concurrent with CTO. CTO, advanced age and history of heart failure are independent risk factors of 1-year death among STEMI patients.
Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , China , Doença Crônica , Oclusão Coronária/complicações , Infarto do Miocárdio , Intervenção Coronária Percutânea , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do TratamentoRESUMO
AIMS: We previously demonstrated that resveratrol (RSV) administration causes cardiac stromal cell-derived factor (SDF)-1 upregulation and can enhance the mobilization of stem cells in mice with acute myocardial infarction (AMI). However, the upstream signal transduction involved in SDF-1 regulation in the setting of AMI and RSV administration remains unclear. Because RSV is a sirtuin 1 (SIRT1) activator and SIRT proteins act as deacetylases, we investigated the role of SIRT1 in SDF-1 upregulation and its subsequent effects. METHODS AND RESULTS: In vitro experiments with H9C2 cardiomyocytes under hypoxia and serum-deprivation conditions showed that p53 acted upstream of SDF-1. RSV could not regulate SDF-1 effectively after SIRT1 silencing, indicating that it is dependent on SIRT1. Subsequently, male C57BL/6 mice were divided into four groups: 1) sham, 2) MI, 3) MI+RSV, and 4) MI+RSV plus nicotinamide, an inhibitor of the deacetylase activity of SIRT (MI+RSV+NAM). Compared with the sham mice, AMI caused a slight increase in the cardiac p53 level and resulted in significant SIRT1 downregulation and p53 acetylation or activation. Compared with the MI mice, MI+RSV administration improved the cardiac SDF-1 level and reversed the reduction of SIRT1 and the activation of p53. Furthermore, we observed less cardiac dysfunction in MI+RSV mice and determined that NAM abolished the effects of RSV. CONCLUSIONS: RSV enhances cardiac SDF-1 excretion after AMI partially through a SIRT1 normalization/p53 inactivation pathway.
Assuntos
Quimiocina CXCL12/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Estilbenos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Animais , Hipóxia Celular/efeitos dos fármacos , Fibrose , Inativação Gênica/efeitos dos fármacos , Testes de Função Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Resveratrol , Sirtuína 1/metabolismo , UltrassonografiaRESUMO
<p><b>BACKGROUND</b>The aim of this research was to investigate the changes in the vision-related resting-state network (V-RSN) in pituitary adenoma (PA) patients after vision improvement, which was induced by operative treatment.</p><p><b>METHODS</b>Ten PA patients with an improved visual acuity or/and visual field after transsphenoidal pituitary tumor resection were recruited and underwent a complete neuro-ophthalmologic evaluation, as well as an magnetic resonance imaging (MRI) protocol, including structural and resting-state functional MRI sequences before and after the operation. The regional homogeneity (ReHo) of the V-RSN was evaluated. Two sample t-test was performed to identify the significant differences in the V-RSN in the PA patients before and after transsphenoidal pituitary tumor resection.</p><p><b>RESULTS</b>Compared with the preoperation counterparts, the PA patients with improved vision after the operation exhibited reduced ReHo in the bilateral thalamus, globus pallidus, caudate nucleus, putamen nucleus, supplementary motor area, and left hippocampal formation, and increased ReHo in the bilateral cuneus gyrus, calcarine gyrus, right lingual gyrus, and fusiform gyrus.</p><p><b>CONCLUSIONS</b>PA patients with improved vision exhibit increased neural activity within the visual cortex, but decreased neural activity in subareas of the multisensory and multimodal systems beyond the vision cortex.</p>
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Adenoma , Patologia , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias , PatologiaRESUMO
<p><b>OBJECTIVE</b>The effect of mesenchymal stem cells (MSCs) transplantation is poor because of the harsh environment post infarction. Our previous studies have proven that Statins could enhance the implanted bone marrow MSCs survival, but the exact mechanism remained to be clarified. We hypothesized that atorvastatin (Ator) could protect MSCs from hypoxia and serum-free (H/SF) induced apoptosis and investigated the potential mechanisms.</p><p><b>METHODS</b>Chinese mini-swine's bone marrow derived MSCs were cultured in vitro and exposed to hypoxia and H/SF, Ator of various concentrations (0.001 - 10 µmol/L), AMPK inhibitor-compound C (CC), PI3K inhibitor-LY294002 (LY), Ator + CC and Ator + LY. Cell apoptosis was assessed using Annexin V/Prospidine Iodine kit by flow cytometry. Phosphorylation of AMPK, Akt, endothelial nitric oxide synthase (eNOS) level and phosphorylation were tested with Western blot. Real Time-PCR was performed to analyze the gene expression of AMPK, Akt and eNOS.</p><p><b>RESULTS</b>MSCs apoptosis in Ator (0.01 - 10 µmol/L) treated H/SF groups was significantly reduced compared with H/SF group (1.94% - 6.10% vs. 10.94%, P < 0.01 or 0.05). Apoptosis was higher in Ator + CC group than in 1 µmol/L Ator group (4.94% ± 0.98% vs. 2.59% ± 0.84%, P < 0.01) and similar between Ator + LY and 1 µmol/L Ator group (2.02% ± 0.45% vs. 2.59% ± 0.84%, P > 0.05). The gene expressions of AMPK, Akt and eNOS were significantly upregulated in atorvastatin treated groups. Meanwhile, phosphorylation of AMPK and eNOS increased in MSCs treated with atorvastatin (P < 0.01 or 0.05). Phosphorylation of eNOS significantly correlated with AMPK phosphorylation (r = 0.599, P = 0.004), but not with Akt phosphorylation (P = 0.263).</p><p><b>CONCLUSIONS</b>Atorvastatin can protect MSCs from H/SF induced apoptosis through AMPK pathway, which resulting in activation of eNOS.</p>
Assuntos
Animais , Adenilato Quinase , Metabolismo , Apoptose , Atorvastatina , Células da Medula Óssea , Biologia Celular , Metabolismo , Meios de Cultura Livres de Soro , Ácidos Heptanoicos , Farmacologia , Células-Tronco Mesenquimais , Biologia Celular , Metabolismo , Óxido Nítrico Sintase Tipo III , Metabolismo , Fosfatidilinositol 3-Quinases , Metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt , Metabolismo , Pirróis , Farmacologia , Transdução de Sinais , SuínosRESUMO
<p><b>OBJECTIVE</b>To observe in vivo stem cell distribution and viability after transplantation by noninvasive imaging of 18F-fluorodeoxyglucose (18F-FDG) labeled autologous mononuclear bone marrow cells.</p><p><b>METHODS</b>Myocardial infarction was established in 8 swine by ligating left anterior descending coronary artery after anesthesia. Bone marrow (20 ml) was drawn through ileum. After isolation, mononuclear bone marrow cells were labeled by radionuclide 18F-FDG and intramyocardially injected into infarction region. Whole body planar scan and myocardial tomography scan were performed immediately, 1 h, 2 h, and 3 h post stem cell injection. Viability and stability of radionuclide labeled stem cells were determined at 3 h post labeling in vitro.</p><p><b>RESULTS</b>The labeling efficiency was (67 +/- 14)%. Mean dose of radioactive in marrow cells was (32 +/- 7) MBq. Trypan blue staining showed in vitro viability was (95 +/- 3)% at 3 h post labeling. After intramyocardial injection, labeled mononuclear bone marrow cell retention rate in infarction region was (83 +/- 6)%, (49 +/- 8)%, (32 +/- 6)% and (24 +/- 5)% immediately, 1 h, 2 h, and 3 h post injection, respectively.</p><p><b>CONCLUSIONS</b>Distribution and viability of stem cell after cardiac transplantation could be effective monitored by 18F-FDG labeled autologous mononuclear bone marrow cell technique in acute stage in this model.</p>
Assuntos
Animais , Células da Medula Óssea , Biologia Celular , Diagnóstico por Imagem , Sobrevivência Celular , Fluordesoxiglucose F18 , Sobrevivência de Enxerto , Transplante de Coração , Infarto do Miocárdio , Diagnóstico por Imagem , Cirurgia Geral , Cintilografia , Transplante de Células-Tronco , Métodos , SuínosRESUMO
<p><b>BACKGROUND</b>The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo.</p><p><b>METHODS</b>Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.</p><p><b>RESULTS</b>Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA.</p><p><b>CONCLUSIONS</b>Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.</p>
Assuntos
Animais , Antígenos CD , Pressão Sanguínea , Caderinas , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Frequência Cardíaca , Microscopia de Fluorescência , Infarto do Miocárdio , Tratamento Farmacológico , Traumatismo por Reperfusão Miocárdica , Miocárdio , Patologia , Infiltração de Neutrófilos , Óxido Nítrico , Fisiologia , Óxido Nítrico Sintase , Metabolismo , Peroxidase , Metabolismo , Suínos , Porco MiniaturaRESUMO
<p><b>BACKGROUND</b>Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion.</p><p><b>METHODS</b>Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint.</p><p><b>RESULTS</b>At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL.</p><p><b>CONCLUSIONS</b>Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.</p>
Assuntos
Animais , Apoptose , Cardiomioplastia , Métodos , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Imageamento por Ressonância Magnética , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio , Patologia , Terapêutica , Miocárdio , Patologia , Estresse Oxidativo , Suínos , Porco Miniatura , Tomografia Computadorizada de Emissão de Fóton Único , Transplante AutólogoRESUMO
· AIM: To study the in situ relative intraocular position of the iris-claw phakic intraocular lens (PIOL)for high myopia using an anterior chamber optical coherence tomography (AC OCT)prototype.· METHODS: Six PIOLs (11.50 to 22.00D lens powers) were implanted in phakic myopic eyes. Using AC OCT, tomography was taken in the anterior chamber to measure the preoperative anterior chamber depth, postoperative distance between the PIOL and the corneal endothelium (endothelial-optic distance), and the postoperative distance between the PIOL and the crystalline lens.· RESULTS: Preoperative anterior chamber depth ranged from 3.27 to 3.91 mm and the postoperative endothelial-optic distance measured 2,07 to 2,24 mm. The distance between the crystalline lens and the posterior surface of the IOL ranged from 0.82 to 1.32 mm. Several tomography revealed the position of the PIOL on the iris, The pigment layer of the iris did not seem to be disturbed by the presence of the PIOL.· CONCLUSION, The original anterior chamber depths were reduced by 36,1% to 44.6% after implantation. This study of 6 eyes revealed that tomography taken by AC OCT are useful in verifying the intraocular position of the PIOL within the anterior chamber. Adequate space was maintained between the iris-fixated phakic intraocular lens and the corneal endothelium, angle, and crystalline lens.