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BACKGROUND: The induction of microvascular inflammation and the effects on cytokine production in blood due to hypoxia has been shown in the past. We have previously reported a statistically significant increase of the pro-inflammatory cytokine interleukin-8 (IL-8) in normobaric hypoxia in the setting of a hypoxia-chamber. In the present study, we sought to analyze plasma levels of inflammatory cytokines in a real-life stetting in order to foster our knowledge on hypoxia induced microvascular inflammation at moderate altitude. METHODS: Pro-inflammatory cytokines (IL-8, IL-6, TNF-α) were measured in an experimental field study, exposing 18 healthy volunteers to moderate hypoxia while staying at a mountain lodge in Diavolezza, Switzerland (2978 meters above sea level). Plasma cytokine levels were measured by ELISA. RESULTS: In contradiction to our results in a normobaric hypoxia-chamber, exposure to moderate hypoxia led to a significant decrease of plasma IL-8 levels in a real-life setting (from 2.902 (1.046 - 4.984) pg/mL to 1.395 (0.698 - 3.712) pg/mL, p = 0.034). Concentrations of IL-6 and TNF-α did not show statistically significant changes in comparison to baseline measurements. CONCLUSIONS: The results of this study show a decrease of proinflammatory cytokine IL-8 in a real life setting of moderate altitude in healthy individuals. Initiation of angiogenesis or subliminal stimulus for an altitude-induced inflammatory reaction may be explanations for this unexpected finding.
Assuntos
Altitude , Citocinas/metabolismo , Adulto , Voluntários Saudáveis , Humanos , Hipóxia , Interleucina-6 , Interleucina-8/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Degenerative aortic stenosis (AS) is the most frequent form of acquired valvular heart disease. AS is known to entail endothelial dysfunction caused by increased mechanical shear stress leading to elevated circulatory levels of microparticles. Endothelial and platelet microparticles (EMP and PMP) are small vesicles that originate from activated cells and thrombocytes. We sought to evaluate whether transcatheter aortic valve implantation (TAVI) procedure would elicit effects on circulating EMP and PMP. 92 patients undergoing TAVI procedure for severe AS were included in this study. Samples were obtained at each visit before TAVI, 1 week post-procedure and at 1, 3 and after 6 months after TAVI and were evaluated using flow cytometry. A 12 month clinical follow-up was also performed. CD62E+ EMP concentration before TAVI was 21.11 % (±6.6 % SD) and declined to 20.99 % (±6.8 % SD) after 1 week, to 16.63 % (±5.4 % SD, p < 0.0001) after 1 month, to 17.08 % (±4.6 % SD, p < 0.0001) after 3 months and to 15.94 % (±5.4 % SD, p < 0.0001) after 6 months. CD31+/CD42b-, CD31+/Annexin+/- EMP remained unchanged. CD31+/CD41b+ PMP evidenced a slight, but statistically significant increase after TAVI and remained elevated during the entire follow-up. Apart from a procedure-related improvement in echocardiographic parameters, TAVI procedure led also to a decline in CD62E+ EMP. The reduction in pressure gradients with less hemodynamic shear stress seems also to have beneficially affected endothelial homeostasis.
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Estenose da Valva Aórtica/cirurgia , Biomarcadores/metabolismo , Plaquetas/metabolismo , Micropartículas Derivadas de Células/metabolismo , Células Endoteliais/metabolismo , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Ecocardiografia , Feminino , Citometria de Fluxo , Alemanha , Hemodinâmica , Humanos , Masculino , Ativação Plaquetária , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Increased levels of endothelial cell microparticles (EMP) are known to reflect endothelial dysfunction (ED). In diabetes mellitus type 2 (T2DM), the expression of endothelin (ET)-1 is increased. As treatment with an ET-1 antagonist significantly inhibited atherosclerosis in animal models, we sought to investigate whether treatment with ET-1 antagonists affects EMP levels in vitro and in vivo in patients with T2DM. MATERIALS AND METHODS: In vitro study: Human umbilical vein endothelial cells (HUVEC) were stimulated with ET-1 alone and ET-1 in combination with a dual ET-A and ET-B endothelin receptor blocker. In vivo study: Patients with T2DM were randomized to treatment with the ET receptor antagonist bosentan or placebo. After 4 weeks, the patients were re-examined and blood samples were obtained. EMP counts in supernatants and plasma samples were determined using flow cytometry. RESULTS: In vitro study: In supernatants of ET-1-stimulated HUVECs, the increased release of EMP was reduced significantly by co-incubation with an ET-1 receptor antagonist (e.g. CD31+/CD42b-EMP decreased from 37·1% ± 2·8 to 31·5% ± 2·8 SEM, P = 0·0078). In vivo study: No changes in EMP levels in blood samples of patients with T2DM were found after 4 weeks of bosentan treatment (n = 36, P = ns). CONCLUSIONS: Our in vitro results suggest that ET-1 stimulates the release of EMP from HUVECs via a receptor-dependent mechanism. Co-incubation with an endothelin receptor blocker abolished ET-1-dependent EMP release. However, treatment with bosentan for 4 weeks failed to alter EMP levels in patients with T2DM. Other factors seem to have influenced EMP release in patients with T2DM independent of ET-1 receptor-mediated mechanisms.
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Micropartículas Derivadas de Células/efeitos dos fármacos , Antagonistas do Receptor de Endotelina A/farmacologia , Receptor de Endotelina A/fisiologia , Bosentana , Diabetes Mellitus Tipo 2/metabolismo , Método Duplo-Cego , Antagonistas dos Receptores de Endotelina/uso terapêutico , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Pessoa de Meia-Idade , Sulfonamidas/farmacologiaRESUMO
BACKGROUND: Hypoxia has been shown to induce a microvascular inflammation, affect the cell count of different types of immune cells, and influence cytokine production in blood. In the present study, serum levels of different cytokines were investigated to achieve insights into the effect of hypoxia on the balance of inflammation and anti-inflammation. METHODS: Pro- (IL-8) and anti-inflammatory (IL-10) cytokines were measured in an experiment exposing 12 healthy subjects (35 ± 9 yr, 176 ± 7 cm, 73 ± 16 kg, BMI 23 ± 4 kg/m2) to systemic, normobaric hypoxia in a hypoxic chamber. In this chamber oxygen was replaced by nitrogen to reach an oxygen content of 9.9% that is equivalent to an altitude of 5500 m during 7 hours. Serum cytokine concentrations were analyzed using ELISA. RESULTS: As expected, a significant decrease in peripheral oxygen saturation accompanied by a significant increase in breathing frequency and heart rate were observed in the subjects during hypoxia compared to baseline (BL). Blood leukocytes increased slightly, but significantly in the course of hypoxia. A statistically significant increase was measured for IL-8 serum level during hypoxia compared to the baseline measurements (BL 12.0 ± 1.1 pg/mL, hypoxia 16.2 ± 1.6 pg/mL, p = 0.006). For IL-10 a statistically significant decrease was measured upon hypoxia compared to baseline (BL 11.6 [6.2 - 43.31 pg/mL, hypoxia 8.3 [4.4 - 26.6] pg/mL, p = 0.016). Additionally, a significant inverse correlation was found comparing the anti-inflammatory cytokine IL-10 with the pro-inflammatory cytokine IL-8 (r = -0.69, p < 0.001). CONCLUSIONS: The results of this study demonstrate a hypoxia-induced increase in pro- and decrease in anti-inflammatory cytokines reflecting an increased pro-inflammatory status during hypoxia.
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Hipóxia/complicações , Mediadores da Inflamação/sangue , Inflamação/etiologia , Interleucina-10/sangue , Interleucina-8/sangue , Adulto , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Voluntários Saudáveis , Humanos , Hipóxia/sangue , Hipóxia/imunologia , Inflamação/sangue , Inflamação/imunologia , Masculino , Fatores de TempoRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a worldwide burden. We have previously shown that elevated levels of heat shock protein-27 (HSP27), -70 (HSP70), and caspase-cleaved cytokeratin 18 (ccCK-18) were found in serum of COPD patients correlating with disease severity. We hypothesized that transient hypoxia triggers the release of HSPs and ccCK-18. METHODS: Fourteen healthy volunteers were subjected to transient normobaric hypoxia in an air-conditioned hypoxia chamber simulating an oxygen concentration at an altitude of up to 5500 meters. Serum samples were evaluated for HSP27, -70, and ccCK-18. RESULTS: Baseline concentrations were 2760 pg/mL +/- 517 SEM for HSP-27, 49 pg/mL +/- 22 SEM for HSP-70, and 226 U/L +/- 20 SEM for ccCK-18. After eight hours and an altitude equivalent of 5500 meters a significant increase was recorded, depicted by serum levels of 3737 pg/mL +/- 571 SEM for HSP-27, 202 pg/mL +/- 81 SEM for HSP-70, and 244 U/L +/- 20 SEM for ccCK-18 (p < 0.05). CONCLUSIONS: These results provide an explanation for the elevated serum levels of HSP-27, HSP-70, and ccCK-18 found in COPD patients, indicating that hypoxic conditions can trigger the release of the aforementioned factors.
Assuntos
Proteínas de Choque Térmico HSP110/sangue , Proteínas de Choque Térmico HSP27/sangue , Hipóxia/sangue , Queratina-18/sangue , Adulto , Altitude , Feminino , Saúde , Proteínas de Choque Térmico , Humanos , Masculino , Chaperonas MolecularesRESUMO
AIMS: Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. METHODS AND RESULTS: Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). CONCLUSIONS: T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.
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Elevation of cardiac troponin I (cTnI) is a well-known complication after percutaneous coronary interventions (PCI). The aims of this study were to quantify the extent of coronary microembolization during elective PCI, to identify predisposing anatomical and procedural factors, and to evaluate its impact on long-term outcome in diabetic patients with a high cardiovascular risk. 48 patients (pts, median 66.7 years) with type 2 diabetes and coronary artery disease underwent elective PCI with stenting to treat single-vessel lesions. Real-time microembolization during PCI ("HITS") was detected by an intracoronary Doppler guide wire. Peak levels of cTnI were measured within 24 h after PCI. Pts were followed for 2 years to record major cardiac events (MACE: death, myocardial infarction, revascularization of target and non-target vessels). In 47 patients microemboli were detected during PCI. Nineteen patients showed pathologic cTnI elevation (0.13-28.9, median 0.39 µg/l). The amount of HITS correlated with cTnI levels (r = 0.43, p = 0.003), but not with other clinical or angiographic data. Within 2 years MACE were detected in 9 patients, who had significantly more microemboli (15.4 ± 11.8 vs. 28.2 ± 16.0 HITS; p = 0.009, OR 1.07; 95 % CI 1.011-1.13) during PCI. HITS >23, but not cTnI elevation, predicted later MACE (ROC analysis, p = 0.025). A high amount of microembolization during elective PCI in diabetic patients appears to be an indicator of greater atherosclerotic burden and accelerated coronary artery disease progression, associated with acute biomarker elevation and adverse long-term outcomes.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Doença da Artéria Coronariana/terapia , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/terapia , Embolia/diagnóstico por imagem , Miocárdio/patologia , Ultrassonografia Doppler , Idoso , Procedimentos Cirúrgicos Eletivos , Embolia/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Estudos Prospectivos , Troponina I/sangueRESUMO
BACKGROUND: Endothelial progenitor cells (EPCs) are thought to contribute to reendothelialization and neoangiogenesis. Since it is known that EPCs express a testosterone receptor, we wanted to assess the prevalence of testosterone deficiency in patients with CHF and its impact on circulating EPCs. METHODS: 137 male patients with chronic heart failure (CHF) were included (age 61 ± 13 years; BMI 29 ± 5 kg/m(2); New York Heart Association classification (NYHA) I: n = 47, NYHA II: n = 51, NYHA III: n = 39). Numbers of different populations of circulating EPCs were quantified using flow cytometry. Levels of free testosterone and EPC-regulating cytokines were determined using ELISA. RESULTS: The prevalence of testosterone deficiency in our University CHF clinic was 39%. However, there was no difference between patients with and without testosterone deficiency regarding their levels of EPCs. Testosterone levels were inversely correlated with age (R(2) = -0.32, p = 0.001) and NYHA status (R(2) = 0.28, p = 0.001) and correlated with cardiorespiratory capacity (R(2) = 0.26, p = 0.03). CONCLUSION: Testosterone deficiency is frequent in male patients with CHF but does not appear to impact the regenerative EPCs.
Assuntos
Insuficiência Cardíaca/fisiopatologia , Células-Tronco/fisiologia , Testosterona/deficiência , Adulto , Idoso , Citocinas/sangue , Endotélio/fisiologia , Citometria de Fluxo , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Congestive heart failure (CHF) and diabetes mellitus (DM) are increasing in prevalence. There are conflicting data regarding the crosstalk of DM and CHF with respect to the prognostic impact for the patients. Health-related quality of life (Hr-QoL) has been reported to be useful for risk stratification. The purpose of this study was to investigate the impact of DM on Hr-QoL in a CHF population. METHODS: 325 consecutive patients with CHF were retrospectively analyzed (age 49 ± 12 years, 74.2% male, 18% had diabetes). After a median follow-up time of 7.4 years, we compared Hr-QoL of patients with and without DM. Hr-QoL was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Kaplan-Meier curves were used to compare survival. RESULTS: The presence of DM reduced Hr-QoL in patients with CHF, indicated by a higher overall MLHFQ score (43.5 vs. 21, P = 0.013). Kaplan-Meier survival curves showed a significant survival difference (P = 0.024). Survival rates of both groups differed significantly after 3 (P = 0.031), 5 (P = 0.006), and 10 years (P = 0.047) favoring the group without DM. CONCLUSIONS: In patients with CHF, the coexistence of DM is associated with a reduced Hr-QoL and a particularly poor long-term survival. Our results indicate that CHF patients with DM are at increased risk.
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Complicações do Diabetes/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Qualidade de Vida , Adulto , Complicações do Diabetes/mortalidade , Feminino , Nível de Saúde , Insuficiência Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4(+) T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB .
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Citocinas/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Hipóxia/imunologia , Subunidade p50 de NF-kappa B/imunologia , Fagocitose/imunologia , Fator de Transcrição RelA/imunologia , Adulto , Pressão Atmosférica , Linfócitos T CD4-Positivos/fisiologia , Citocinas/genética , Eritropoetina/sangue , Feminino , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Humanos , Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Ácido Láctico/sangue , Masculino , Monócitos/fisiologia , Subunidade p50 de NF-kappa B/genética , Neutrófilos/fisiologia , Fagocitose/genética , Fator de Transcrição RelA/genética , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem , Zimosan/imunologia , Zimosan/metabolismoRESUMO
Thrombosis of the superior vena cava leads to obstruction of venous outflow of the head and upper extremities and causes severe clinical symptoms. The management of SVC syndrome depends on aetiology and acuity at clinical presentation and ranges from conservative medical treatment to bypass surgery. Endovascular treatment can provide rapid relief of symptoms and substantial clinical improvement independent of aetiology. We report a case of successful interventional treatment in a patient with catheter-induced SVC thrombosis and present a review of the literature.
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Angioplastia/métodos , Síndrome da Veia Cava Superior/cirurgia , Idoso , Humanos , Síndrome da Veia Cava Superior/etiologia , Trombose Venosa Profunda de Membros Superiores/complicaçõesRESUMO
OBJECTIVES: Orthogonal polarized spectral imaging- and sidestream darkfield-technique have enabled visual evaluation of the microcirculation. Different investigators described microcirculatory alterations, especially in surgical patients suffering from septic shock. We investigated the sublingual microcirculation in non-surgical patients admitted to our medical, intensive care unit (ICU). METHODS: In 24 severely ill (APACHE-II Score: 27.8+/-11.3), intubated patients admitted to our ICU the sublingual microcirculation was recorded with a handheld intravital microscope. Sublingual vessels were categorized according to their size (small: 10-25 microm; medium: 26-50 microm; large: 51-100 microm) and the flow in semiquantitative categories (0: no flow; 1: intermittent flow; 2: sluggish flow; 3: continuous flow). RESULTS: Patients with cardiogenic shock (n=7) had lower microflow compared with patients without cardiogenic shock (small p<0.001, medium p<0.001, large p=0.003). Several other diseases, including diabetes and arterial hypertension, age, gender, had no influence. In general, patients with a flow less than 3 in the small vessels showed higher arterial blood lactate levels (p=0.043) compared to continuous flow. CONCLUSIONS: A consequence of cardiogenic shock is the impairment of microcirculation with organ hypoperfusion. We observed that cardiac output is correlated to disturbance in microflow in the smallest vessels. On-line evaluation of microcirculation in vivo may be a valid tool for optimizing therapeutic measures in high risk patients. Additional online material may be found at: http://www.kim1.uniklinik-jena.de/Microcirculation.html.
Assuntos
Microcirculação , Soalho Bucal/irrigação sanguínea , Choque Cardiogênico/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Unidades de Terapia Intensiva , Microscopia de Vídeo , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Choque Cardiogênico/mortalidadeAssuntos
Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Comunicação Interatrial/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Valva Mitral/anormalidades , Valva Mitral/diagnóstico por imagem , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , HumanosRESUMO
BACKGROUND: Endothelial dysfunction is accompanied by the release of microparticles (MP). OBJECTIVE: We sought to investigate the effect of moderate hypoxia on circulatory levels of microparticles, biomarkers of cardiovascular function and inflammation and on echocardiographic parameters in healthy volunteers staying at an altitude of 2978âm. METHODS: Eighteen healthy volunteers were subjected to moderate hypoxia by staying at 2978âm above sea level for three days. Blood samples were evaluated for MP using flow cytometry. ELISA analysis was performed for sST2, H-FABP, suPAR and GDF-15. Moreover, the effect of dual endothelin-receptor blockade was investigated. RESULTS: Oxygen saturation decreased to 93%. A significant decrease of endothelial and platelet MP levels was found. These results were corroborated by a similar response in sST2 and suPAR plasma concentration. Endothelin-receptor blockade by macitentan only had a marginal influence on MP, sST2, H-FABP, suPAR and GDF-15 levels, though it led to a significant amelioration of echocardiographic parameters of right heart function. CONCLUSIONS: These experimental results show that moderate hypoxia due to altitude exposition led to a reduction in parameters of endothelial dysfunction as shown by a decrease in endothelial and platelet MP, sST2 and suPAR levels. A slight increase in pulmonary pressure at moderate altitude was decreased by dual endothelin receptor blockade.
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Altitude , Biomarcadores/metabolismo , Infecções Cardiovasculares/sangue , Inflamação/metabolismo , Receptores de Endotelina/metabolismo , Adulto , Diferenciação Celular , Feminino , Humanos , MasculinoAssuntos
Dispneia/diagnóstico por imagem , Dispneia/etiologia , Ecocardiografia , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
The aim was to study impacts of mild to severe hypoxia on human red blood cell (RBC)-nitric oxide synthase (NOS)-dependent NO production, protein S-nitrosylation and deformability.Ambient air oxygen concentration of 12 healthy subjects was step-wisely reduced from 20.95% to 16.21%, 12.35%, 10% and back to 20.95%. Additional in vitro experiments involved purging of blood (±sodium nitrite) with gas mixtures corresponding to in vivo intervention.Vital and hypoxia-associated parameters showed physiological adaptation to changing demands. Activation of RBC-NOS decreased with increasing hypoxia. RBC deformability, which is influenced by RBC-NOS activation, decreased under mild hypoxia, but surprisingly increased at severe hypoxia in vivo and in vitro. This was causatively induced by nitrite reduction to NO which increased S-nitrosylation of RBC α- and ß-spectrins -a critical step to improve RBC deformability. The addition of sodium nitrite prevented decreases of RBC deformability under hypoxia by sustaining S-nitrosylation of spectrins suggesting compensatory mechanisms of non-RBC-NOS-produced NO.The results first time indicate a direct link between maintenance of RBC deformability under severe hypoxia by non-enzymatic NO production because RBC-NOS activation is reduced. These data improve our understanding of physiological mechanisms supporting adequate blood and, thus, oxygen supply to different tissues under severe hypoxia.
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Eritrócitos/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/sangue , Adulto , Hipóxia Celular , Deformação Eritrocítica/fisiologia , Humanos , MasculinoRESUMO
PURPOSE: The assessment of aortic annular size is critical, and inappropriate sizing is thought to be a main reason of paravalvular aortic regurgitation. Multidetector computed tomograph is associated with the risk of contrast nephropathy. For optimal evaluation of the complex structure of the aortic annulus, three-dimensional (3D)-methods should be used. We therefore sought to determine the value of 3D-transoesophageal echocardiography (3D-TEE) for appropriate sizing. METHODS: Hundred and one patients (mean age 81·4 years) with symptomatic aortic valve stenosis (AS) and high surgical risk profile (mean log. EuroScore 28·8%) being scheduled for transcatheter aortic valve implantation (TAVI) were included. 2D- and 3D-TEE were performed before the procedure to evaluate the aortic annulus diameter. RESULTS: Maximum, minimum and mean (max diameter + min diameter/2) annulus diameters were 24·7, 23·1 and 23. 9 mm in 3D-TEE and compared to 22·6 mm in 2D-TEE (P<0·001; 0·07; <0·001). The interobserver variability for 3D-TEE was low with a mean difference of 0·18 mm compared to 2D-TEE with 0·59 mm. The application of 3D-TEE caused a change of prosthesis size selection in 40% of patients compared to 2D-TEE. In this study, we implanted three different types of catheter-mounted valves (Edwards-SAPIEN(™) XT valve, CoreValve(™) and JenaValve(™) ). Final angiography confirmed valve competence (mild insufficiency) in 91%, and there was no aortic regurgitation greater than moderate in the follow-up echocardiographic evaluation. CONCLUSION: Assessment of aortic annulus dimensions for TAVI size selection can safely be performed with 3D-TEE only. Based on our results with significantly higher annulus diameter compared to 2D-TEE, we recommend 3D-TEE to reduce prosthesis undersizing.
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Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/terapia , Valva Aórtica/diagnóstico por imagem , Cateterismo Cardíaco/instrumentação , Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/etiologia , Estenose da Valva Aórtica/fisiopatologia , Cateterismo Cardíaco/efeitos adversos , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Variações Dependentes do Observador , Valor Preditivo dos Testes , Desenho de Prótese , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
INTRODUCTION: Hypoxia is known to affect the immune system. It leads to an increase in pro-inflammatory cytokines such as interleukin-6 and influences the number of different inflammatory cells. This study investigates the effect of hypoxia on the number of different subsets of circulating human dendritic cells (DCs) as professional antigen-presenting cells. METHODS: The number of circulating DCs was determined via Fluorescence activated cell sorting analysis in peripheral blood of 17 healthy volunteers (age 35.9±2.6 years) in normoxia (baseline, BL), hypoxia (altitude 3000âm, alpine passive escalation), and again normoxia (follow-up, FU). RESULTS: Exposure to hypobaric hypoxia in high altitude, 3000âm, led to a significant decrease in the participants' oxygen saturation, and an increase in the breathing frequency whereas blood pressure and heart rate were not significantly altered. FACS analysis revealed a significant hypoxia induced decrease in circulating plasmacytoid (p) DCs compared to baseline levels (BL: 0.10 [0.08-0.18] % of white blood cell count (WBC), 3000âm: 0.03 [0.02-0.06] % WBC, pâ<â0.001). During follow up, again a significant reconstitution of circulating pDCs was observed (FU: 0.16±[0.11-0.26] % WBC, pâ=â0.0013). CONCLUSION: Hypobaric hypoxia caused by exposure to altitude results in a significant reduction in the number of circulating pDCs.
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Altitude , Células Dendríticas/metabolismo , Adulto , Hipóxia Celular , Feminino , Voluntários Saudáveis , Humanos , Inflamação , MasculinoRESUMO
INTRODUCTION: Endothelial microparticles (EMP) are small membrane vesicles that originate from activated or apoptotic endothelial cells. Although the exact mechanism of EMP function is still relatively unknown, it has been shown that they modulate inflammatory processes, coagulation and vascular function. In this study we hypothesized that transient hypoxia may act as a trigger for the release of EMP into circulation. MATERIALS AND METHODS: Fourteen healthy volunteers were subjected to transient normobaric hypoxia in an air-conditioned chamber simulating an oxygen concentration of a height of up to 5500 meters. Blood samples were evaluated for EMP using flow cytometry. RESULTS: During the experiment oxygen concentration was adjusted to a value equivalent to a height of 5500 meters to achieve hypoxic conditions. Oxygen saturation decreased to 78% . At the final height a significant increase of CD31+/Annexin+ EMP levels was evident (increase from 0.03% ± 0.01% SEM to 0.12% ± 0.04% SEM, pâ=â0.0188). CONCLUSIONS: These experimental results show that temporary hypoxic conditions can trigger the release of CD31+/ Annexin+ EMP also in healthy volunteers. In our previous studies we have shown that apoptotic bodies can confer pro-survival signals to cardiomyocytes during myocardial ischemia. Based on the experimental results of this current study we believe that the release of CD31+/Annexin+ EMP during hypoxia might act as an endogenous survival signal.
Assuntos
Anexinas/imunologia , Hipóxia Celular/imunologia , Células Endoteliais/imunologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/imunologia , Adulto , Micropartículas Derivadas de Células , Feminino , Citometria de Fluxo , Humanos , Masculino , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: Rapid ventricular pacing (RVP) is an established technique to temporarily reduce left ventricular output during transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the impact of RVP on microvascular tissue perfusion (MTP) in patients undergoing TAVI. METHODS AND RESULTS: We studied 42 patients (mean age 81.8 ± 6.9 years, n = 18 females. EuroSCORE 33 ± 12 %) during TAVI. MTP was analyzed using Sidestream-Darkfield imaging, of the sublingual microvasculature. Microvascular flow index (MFI) was continuously measured in small (10-25 µm)- and medium (26-50 µm)-sized vessels, starting 10 s before and ending 12 s after RVP. Further, perfused capillary density, total vessel density and the proportion of perfused vessels were assessed. After a mean RVP duration of 14.3 s (range 6-29), mean arterial pressure decreased from 68 ± 05 to 40 ± 7 mmHg (p < 0.001). This was associated with a significant decrease of MFI in small- and medium-sized vessels from 2.29 ± 0.64 and 2.36 ± 0.6 to 0.87 ± 0.66 (p < 0.001) and 1.0 ± 0.83 (p < 0.001), respectively. MFI remained significantly below baseline values (small: 1.75 ± 0.8, p = 0.001 vs. baseline; medium: 1.77 ± 0.85; p = 0.005 vs. baseline) at 12 s after end of RVP. CONCLUSIONS: The study demonstrates a time-dependent effect of RVP on microflow, leading to 50 and 25 % of baseline at 8 and 18 s of RVP, respectively. In a substantial proportion of patients, RVP is associated with microcirculatory arrest and a delayed recovery of microflow. Although the impact of these findings on outcome is yet unclear, TAVI operators should be aware of the potentially adverse effects of even short periods of RVP.