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Sample records for pulmonary vascular resistance

  1. Echocardiographic assessment of pulmonary vascular resistance in pulmonary arterial hypertension

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    Bergot Emmanuel

    2010-06-01

    Full Text Available Abstract Background Echocardiographic ratio of peak tricuspid regurgitant velocity to the right ventricular outflow tract time-velocity integral (TRV/TVI rvot was presented as a reliable non-invasive method of estimating pulmonary vascular resistance (PVR. Studies using this technique in patients with moderate to high PVR are scarce. Left ventricular outflow tract time-velocity integral (TVI lvot can be easier to measure than TVI rvot, especially in patients with severe pulmonary hypertension (PH with significant anatomical modifications of the right structures. Aims We wanted to determine whether the TRV/TVI rvot and TRV/TVI lvot ratios would form a reliable non-invasive tool to estimate PVR in a cohort of patients with moderate to severe pulmonary vascular disease. Methods Doppler echocardiographic examination and right heart catheterisation were performed in 37 patients. Invasive PVR was compared with TRV/TVI rvot and TRV/TVI lvot ratios using regression analysis. Two equations were modelled and the results compared with invasive measurements using the Bland-Altman analysis. Using receiver-operating characteristics curve analysis, a cut-off value for the two ratios was generated. Results Correlation coefficients between invasive PVR and TRV/TVI rvot then TRV/TVI lvot were respectively 0.76 and 0.74. Two new equations were found but the Bland-Altman analysis showed wide standard deviations (respectively 3.8 and 3.9 Wood units. A TRV/TVI rvot then TRV/TVI lvot ratio cut-off value of 0.14 had a sensitivity of 93% and a specificity of 57% for the first and a sensitivity of 87% and a specificity of 57% for the second to determine PVR > 2 Wood units. Conclusion Echocardiography is useful for the screening of patients with pulmonary hypertension and PVR > 2 WU. It remains disappointing for accurate assessment of high PVR. TVI lvot may be an alternative to TVI rvot for patients for whom accurate TVI rvot measurement is not possible.

  2. Oxygen therapy improves cardiac index and pulmonary vascular resistance in patients with pulmonary hypertension.

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    Roberts, D H; Lepore, J J; Maroo, A; Semigran, M J; Ginns, L C

    2001-11-01

    We tested the hypothesis that breathing 100% oxygen could result in selective pulmonary vasodilatation in patients with pulmonary hypertension, including those patients who would not meet current Health Care Finance Administration guidelines for long-term oxygen therapy. From 1996 to 1999, 23 adult patients (mean +/- SEM age, 51 +/- 4 years) with pulmonary arterial hypertension without left-heart failure underwent cardiac catheterization in a university teaching hospital while breathing air and then 100% oxygen. Treatment with 100% oxygen increased arterial oxygen saturation (91 +/- 1% to 99 +/- 0.1%, p < 0.05) and PaO(2) (64 +/- 3 to 309 +/- 28 mm Hg, p < 0.05). Treatment with 100% oxygen also decreased mean pulmonary artery pressure (56 +/- 3 to 53 +/- 2 mm Hg, p < 0.05) and increased cardiac index (2.1 +/- 0.1 to 2.5 +/- 0.2 L/min/m(2), p < 0.05). Calculated mean pulmonary vascular resistance (PVR) decreased from 14.1 +/- 1.4 to 10.6 +/- 1.0 Wood units (p < 0.05). Vasodilatation with 100% oxygen occurred preferentially in the pulmonary circulation (PVR/systemic vascular resistance, 0.53 +/- 0.04 to 0.48 +/- 0.03; p < 0.05). The magnitude of the PVR response to oxygen therapy was correlated only with decreasing patient age (r = 0.45, p < 0.05). Treatment with 100% oxygen is a selective pulmonary vasodilator in patients with pulmonary hypertension, regardless of primary diagnosis, baseline oxygenation, or right ventricular function. Development of disease-specific oxygen prescription guidelines warrants consideration.

  3. 4D magnetic resonance flow imaging for estimating pulmonary vascular resistance in pulmonary hypertension.

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    Kheyfets, Vitaly O; Schafer, Michal; Podgorski, Chris A; Schroeder, Joyce D; Browning, James; Hertzberg, Jean; Buckner, J Kern; Hunter, Kendal S; Shandas, Robin; Fenster, Brett E

    2016-10-01

    To develop an estimate of pulmonary vascular resistance (PVR) using blood flow measurements from 3D velocity-encoded phase contract magnetic resonance imaging (here termed 4D MRI). In all, 17 patients with pulmonary hypertension (PH) and five controls underwent right heart catheterization (RHC), 4D and 2D Cine MRI (1.5T) within 24 hours. MRI was used to compute maximum spatial peak systolic vorticity in the main pulmonary artery (MPA) and right pulmonary artery (RPA), cardiac output, and relative area change in the MPA. These parameters were combined in a four-parameter multivariate linear regression model to arrive at an estimate of PVR. Agreement between model predicted and measured PVR was also evaluated using Bland-Altman plots. Finally, model accuracy was tested by randomly withholding a patient from regression analysis and using them to validate the multivariate equation. A decrease in vorticity in the MPA and RPA were correlated with an increase in PVR (MPA: R(2) = 0.54, P < 0.05; RPA: R(2) = 0.75, P < 0.05). Expanding on this finding, we identified a multivariate regression equation that accurately estimates PVR (R(2) = 0.94, P < 0.05) across severe PH and normotensive populations. Bland-Altman plots showed 95% of the differences between predicted and measured PVR to lie within 1.49 Wood units. Model accuracy testing revealed a prediction error of ∼20%. A multivariate model that includes MPA relative area change and flow characteristics, measured using 4D and 2D Cine MRI, offers a promising technique for noninvasively estimating PVR in PH patients. J. MAGN. RESON. IMAGING 2016;44:914-922. © 2016 International Society for Magnetic Resonance in Medicine.

  4. Segmental pulmonary vascular resistances during oleic acid lung injury in rabbits.

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    Maarek, J M; Grimbert, F

    1994-10-01

    We studied in isolated rabbit lungs the effects of oleic acid (OA) injury on the segmental distribution of vascular resistance. Vascular occlusion pressures were measured in control and OA-injured preparations over 90 min. Capillary filtration coefficient KF,C increased from 0.61 (+/- 0.10) to 0.91 (+/- 0.14) g.min-1.mmHg-1.(100 g)-1 in OA-injured lungs whereas it remained constant in control lungs. Total pulmonary vascular resistance changed little in both control and OA-injured lungs. OA injury resulted in a 15% increase of the double occlusion capillary pressure. In addition, the contribution of the microvascular to the total vascular resistance rose from 8% to 22%. The increase in microvascular resistance was significant 15 min after OA on the arteriolar side and became significant 30 min later on the venular side. Oleic acid injury does not change the total pulmonary vascular resistance but alters the distribution of segmental resistances in the isolated rabbit lung, thereby contributing to the accumulation of lung water in this model of low pressure permeability edema.

  5. The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance.

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    Lili Li

    Full Text Available Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ mice. Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ mice. CREB(αΔ mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ. CREB(αΔ mice had larger lungs with reduced epithelial surface density suggesting increased pulmonary compliance. These findings show that α and Δ isoforms of CREB1 regulate homeostatic gene expression in the lung and that normal activity of these isoforms is essential to maintain low pulmonary vascular resistance in both normoxic and hypoxic conditions and to maintain the normal alveolar structure. Interventions that enhance the actions of α and Δ isoforms of CREB1 warrant further investigation in hypoxic lung diseases.

  6. Acetylcholine's effect on vascular resistance and compliance in the pulmonary circulation.

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    Barman, S A; Senteno, E; Smith, S; Taylor, A E

    1989-10-01

    Acetylcholine's effect on the distribution of vascular resistance and compliance in the canine pulmonary circulation was determined under control and elevated vascular tone by the arterial, venous, and double occlusion techniques in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given concentrations of acetylcholine ranging from 2.0 ng/ml to 200 micrograms/ml. The results of this study indicate that acetylcholine dilates large arteries at low concentrations (less than or equal to 20 ng/ml) and constricts small and large veins at concentrations of at least 2 micrograms/ml. Characterization of acetylcholine's effects at constant pulmonary blood flow indicates that 1) large artery vasodilation may be endothelial-derived relaxing factor-mediated because the dilation is blocked with methylene blue; 2) a vasodilator of the arachidonic acid cascade (blocked by ibuprofen), probably prostacyclin, lessens acetylcholine's pressor effects; 3) when vascular tone was increased, acetylcholine's hemodynamic effects were attenuated; and 4) acetylcholine decreased middle compartment and large vessle compliance under control but not elevated vascular tone. Under constant pressure at control vascular tone acetylcholine increases resistance in all segments except the large artery, and at elevated vascular tone the pressor effects were enhanced, and large artery resistance was increased.

  7. Comparison of the effect of inhaled anaesthetic with intravenous anaesthetic on pulmonary vascular resistance measurement during cardiac catheterisation.

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    Giesen, Leonie A; White, Michelle; Tulloh, Robert M R

    2015-02-01

    Children with pulmonary hypertension routinely undergo pulmonary vascular resistance studies to assess the disease severity and vasodilator responsiveness. It is vital that results are accurate and reliable and are not influenced by the choice of anaesthetic agent. However, there are anecdotal data to suggest that propofol and inhalational agents have different effects on pulmonary vascular resistance. A total of 10 children with pulmonary hypertension were selected sequentially to be included in the study. To avoid confounding because of baseline anatomic or demographic details, a crossover protocol was implemented, using propofol or isoflurane, with time for washout in between each agent and blinding of the interventionalist. Pulmonary and systemic vascular resistance were not significantly different when using propofol or isoflurane. However, the calculated resistance fraction - ratio of pulmonary resistance to systemic resistance - was significantly lower when using propofol than when using isoflurane. Although no difference in pulmonary vascular resistance was demonstrated, this pilot study suggests that the choice of anaesthetic agent may affect the calculation of relative pulmonary and systemic vascular resistance, and provides some preliminary evidence to favour propofol over isoflurane. These findings require replication in a larger study, and thus they should be considered in future calculations to make informed decisions about the management of children with pulmonary hypertension.

  8. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

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    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    2012-01-01

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an impo

  9. Effects of nitric oxide inhalation on pulmonary serial vascular resistances in ARDS.

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    Rossetti, M; Guénard, H; Gabinski, C

    1996-11-01

    The pulmonary vasculature site of action of nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) is still unknown. Seven patients were studied during the early stage of ARDS. The bedside pulmonary artery single-occlusion technique, which allows estimation of the pulmonary capillary pressure (Pcap) and segmental pulmonary vascular resistance, was used without NO or with increasing inhaled NO concentrations (15 and 25 parts per million [ppm]). Systemic circulatory parameters remained unaltered during 15 ppm NO inhalation, whereas 25 ppm NO inhalation slightly decreased mean systemic arterial pressure from 76.7 +/- 5.1 (mean +/- SEM) to 69 +/- 5.2 mm Hg (p resistance decreased by 28% (p resistance of the capillary-venous compartment fell during 25 ppm NO inhalation from 100 +/- 16 to 47 +/- 16 dyn x s x m(2) x cm(-5) (p resistance was unchanged. In these patients NO inhalation during the early stage of ARDS reduces selectively Ppam and Pcapm by decreasing the pulmonary capillary-venous resistance. This latter effect may reduce the filtration through the capillary bed and hence alveolar edema during ARDS.

  10. The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults

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    Wright, Stephen P.; Granton, John T.; Esfandiari, Sam; Goodman, Jack M.

    2016-01-01

    Key points A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship.This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP.We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise‐associated increases in PAWP.Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP.Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. Abstract The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp‐time. The RpCp‐time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp‐time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non‐athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8–10 min stages of cycle ergometry, at targeted heart‐rates of 100 beats min–1 (Light) and 120 beats min–1 (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate

  11. Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress.

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    Haberzettl, Petra; O'Toole, Timothy E; Bhatnagar, Aruni; Conklin, Daniel J

    2016-12-01

    Epidemiological evidence suggests that exposure to ambient air fine particulate matter (PM2.5) increases the risk of developing type 2 diabetes and cardiovascular disease. However, the mechanisms underlying these effects of PM2.5 remain unclear. We tested the hypothesis that PM2.5 exposure decreases vascular insulin sensitivity by inducing pulmonary oxidative stress. Mice fed control (10-13% kcal fat) and high-fat (60% kcal fat, HFD) diets, treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) or mice overexpressing lung-specific extracellular superoxide dismutase (ecSOD) were exposed to HEPA-filtered air or to concentrated PM2.5 (CAP) for 9 or 30 days, and changes in systemic and organ-specific insulin sensitivity and inflammation were measured. In control diet-fed mice, exposure to CAP for 30 days decreased insulin-stimulated Akt phosphorylation in lung, heart, and aorta but not in skeletal muscle, adipose tissue, and liver and did not affect adiposity or systemic glucose tolerance. In HFD-fed mice, 30-day CAP exposure suppressed insulin-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation in skeletal muscle and increased adipose tissue inflammation and systemic glucose intolerance. In control diet-fed mice, a 9-day CAP exposure was sufficient to suppress insulin-stimulated Akt and eNOS phosphorylation and to decrease IκBα (inhibitor of the transcription factor NF-κB levels in the aorta. Treatment with the antioxidant TEMPOL or lung-specific overexpression of ecSOD prevented CAP-induced vascular insulin resistance and inflammation. Short-term exposure to PM2.5 induces vascular insulin resistance and inflammation triggered by a mechanism involving pulmonary oxidative stress. Suppression of vascular insulin signaling by PM2.5 may accelerate the progression to systemic insulin resistance, particularly in the context of diet-induced obesity. Citation: Haberzettl P, O'Toole TE, Bhatnagar A, Conklin DJ. 2016. Exposure to fine

  12. Non-invasive estimation of pulmonary vascular resistance in patients of pulmonary hypertension in congenital heart disease with unobstructed pulmonary flow

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    Arindam Pande

    2014-01-01

    Full Text Available Context: Pulmonary vascular resistance (PVR is a critical and essential parameter during the assessment and selection of modality of treatment in patients with congenital heart disease accompanied by pulmonary arterial hypertension. Aim: The present study was planned to evaluate non-invasive echocardiographic parameters to assess pulmonary vascular resistance. Settings and Design: This prospective observational study included 44 patients admitted in the cardiology and pediatric cardiology ward of our institution for diagnostic or pre-operative catheter based evaluation of pulmonary arterial pressure and PVR. Materials and Methods: Detailed echocardiographic evaluation was carried out including tricuspid regurgitation velocity (TRV and velocity time integral of the right-ventricular outflow tract (VTI RVOT . These parameters were correlated with catheter-based measurements of PVR. Results: The TRV/VTI RVOT ratio correlated well with PVR measured at catheterization (PVRcath (r = 0.896, 95% confidence interval [CI] 0.816 to 0.9423, P < 0.001. Using the Bland-Altman analysis, PVR measurements derived from Doppler data showed satisfactory limits of agreement with catheterization estimated PVR. For a PVR of 6 Wood units (WU, a TRV/VTI RVOT value of 0.14 provided a sensitivity of 96.67% and a specificity of 92.86% (area under the curve 0.963, 95% confidence interval 0.858 to 0.997 and for PVR of 8 WU a TRV/VTI RVOT value of 0.17 provided a sensitivity of 79.17% and a specificity of 95% (area under the curve 0. 0.923, 95% confidence interval 0.801 to 0.982. Conclusions: Doppler-derived ratio of TRV/VTI RVOT is a simple, non-invasive index, which can be used to estimate PVR.

  13. Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

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    Fabregat-Andrés, Óscar, E-mail: osfabregat@gmail.com [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Fundación para la Investigación - Hospital General Universitario de Valencia, Valencia (Spain); Estornell-Erill, Jordi [Unidad de Imagen Cardiaca - ERESA - Hospital General Universitario de Valencia, Valencia (Spain); Ridocci-Soriano, Francisco [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Medicina. Universitat de Valencia, Valencia (Spain); Pérez-Boscá, José Leandro [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); García-González, Pilar [Unidad de Imagen Cardiaca - ERESA - Hospital General Universitario de Valencia, Valencia (Spain); Payá-Serrano, Rafael [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Medicina. Universitat de Valencia, Valencia (Spain); Morell, Salvador [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Cortijo, Julio [Fundación para la Investigación - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Farmacologia. Universitat de Valencia, Valencia (Spain)

    2016-03-15

    Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF.

  14. A novel echocardiography formula for calculating predicted pulmonary vascular resistance in patients with mitral stenosis

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    Amiliana M. Soesanto

    2016-07-01

    Full Text Available Background: Pulmonary vascular resistance (PVR plays an important role in the natural history, prognosis, and outcome after valve intervention in patients with mitral stenosis (MS. The existing formula to estimate PVR by means of echocardiography is not readily applicable in the MS patient subset because it does not specifically calculate the risk of PVR in MS. The aim of this study was to find a new echocardiography formula to estimate PVR in MS.Methods: This diagnostic study was conducted in 2 stages. In the first stage, 58 consecutive subjects with MS were studied to find some model formulas for estimating PVR by multiple regression. Eight echo parameters were analyzed to seek their correlation with the invasive PVR value as a gold standard. The formula that had the best correlation and was easiest to use would be selected. In the second stage, those model formulas were validated by applying them to a further 34 consecutive MS subjects.Results: Four formulas which gave a discriminator coefficient of r2 0.62–0.68 were derived.  The best model formula was proposed for further application.  The new selected formula PVR=-7.465+3.566 TRvmax –(0.23 TVs’+6.799 (RV-MPI showed good correlation (r=0.71, p<0.001 to the invasive PVR value, with good reliability. TRvmax is maximal velocity of tricuspid regurgitation, TVs’ is systolic velocity of tricuspid annulus, and RV-MPI is right ventricle index myocardial performance. ROC curve showed that the cut off point 7.2 has good sensitivity and specificity (90% and 88%, respectively to predict PVR 7 WU.Conclusion: This study has shown that a novel echocardiography formula can estimate PVR with good correlation and reliability in subjects with mitral stenosis.

  15. A feasible method for non-invasive measurement of pulmonary vascular resistance in pulmonary arterial hypertension: Combined use of transthoracic Doppler-echocardiography and cardiac magnetic resonance. Non-invasive estimation of pulmonary vascular resistance.

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    Yan, Chaowu; Xu, Zhongying; Jin, Jinglin; Lv, Jianhua; Liu, Qiong; Zhu, Zhenhui; Pang, Kunjing; Shi, Yisheng; Fang, Wei; Wang, Yang

    2015-12-07

    Transthoracic Doppler-echocardiography (TTE) can estimate mean pulmonary arterial pressure (MPAP) and pulmonary capillary wedge pressure (PCWP) reliably, and cardiac magnetic resonance (CMR) is the best modality for non-invasive measurement of cardiac output (CO). We speculated that the combined use of TTE and CMR could provide a feasible method for non-invasive measurement of pulmonary vascular resistance (PVR) in pulmonary arterial hypertension (PAH). Right heart catheterization (RHC) was undertaken in 77 patients (17M/60F) with PAH, and simultaneous TTE was carried out to evaluate MPAP, PCWP and CO. Within 2 days, CO was measured again with CMR in similar physiological status. Then, PVR was calculated with the integrated non-invasive method: TTE-derived (MPAP-PCWP)/CMR-derived CO and the isolated TTE method: TTE-derived (MPAP-PCWP)/TTE-derived CO, respectively. The PVR calculated with integrated non-invasive method correlated well with RHC-calculated PVR (r = 0.931, 95% confidence interval 0.893 to 0.956). Between the integrated non-invasive PVR and RHC-calculated PVR, the Bland-Altman analysis showed the satisfactory limits of agreement (mean value: - 0.89 ± 2.59). In comparison, the limits of agreement were less satisfactory between TTE-calculated PVR and RHC-calculated PVR (mean value: - 1.80 ± 3.33). Furthermore, there were excellent intra- and inter-observer correlations for the measurements of TTE and CMR (P measurement of PVR is very important in clinical practice. Up to now, however, the widely accepted non-invasive method is still unavailable. Since TTE can estimate (MPAP-PCWP) reliably and CMR is the best image modality for the measurement of CO, the combined use of two modalities has the potential to determine PVR non-invasively. In this research, the integrated non-invasive method showed good diagnostic accuracy and repeatability compared with RHC. Therefore, it might be a feasible method for non-invasive measurement of PVR in patients

  16. Endothelin inhibitors lower pulmonary vascular resistance and improve functional capacity in patients with Fontan circulation.

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    Agnoletti, Gabriella; Gala, Simona; Ferroni, Francesca; Bordese, Roberto; Appendini, Lorenzo; Pace Napoleone, Carlo; Bergamasco, Laura

    2017-06-01

    To evaluate the effects of endothelin inhibitors (ERAs) on hemodynamic and functional parameters in patients post-Fontan procedure with high pulmonary vascular resistance (PVR). Among our cohort of patients with Fontan circulation, 8 children, 8 adolescents, and 8 adults had PVR ≥2 WU*m(2). These patients were treated with ERAs (minors with bosentan, adults with macitentan) and reevaluated after 6 months. Pre- and posttreatment hemodynamic variables were assessed by cardiac catheterization. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). Our primary endpoint was to obtain a reduction of PVR; the secondary endpoint was to obtain an improvement of functional capacity. Under treatment, New York Heart Association class improved for adolescents and adults. PVR decreased (P = .01) in all groups: in children from the median value 2.3 (interquartile range 2.0-3.1) to 1.9 (1.4-2.3) WU*m(2), in adolescents from 2.3 (2.1-2.4) to 1.7 (1.4-1.8) WU*m(2), and in adults from 2.8 (2.0-4.7) to 2.1 (1.8-2.8)WU*m(2). In 71% of patients, PVR fell to less than 2 WU*m(2). Cardiac index increased in adolescents from 2.6 (2.4-3.3) to 3.6 (3.4-4.3) L/min/m(2), P = .04, and in adults from 2.1 (2.0-2.3) to 2.8 (2.3-4.7) L/min/m(2), P = .03. CPET showed that only adolescents displayed a significant functional improvement. Anaerobic threshold improved from 17 (13-19) to 18 (13-20) mL/kg/min, P = .03; oxygen consumption and VO2 max increased from 1.3 (1.0-1.6) to 1.7 (1.1-1.9) L/min, P = .02 and from 25 (21-28) to 28 (26-31) L/min, P = .02, respectively. Oxygen pulse increased from 7.9 (5.7-10.4) to 11.2 (8.2-13.0) L/beat, P = .01. This is the first study that assesses by cardiac catheterization and CPET the effects of ERA in patients with Fontan circulation with increased PVR. These results suggest that ERAs might provide most pronounced hemodynamic and functional improvement in adults and adolescents. Copyright © 2017 The American Association for

  17. Estimation of cardiac output and pulmonary vascular resistance by contrast echocardiography transit time measurement: a prospective pilot study.

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    Choi, Brian G; Sanai, Reza; Yang, Benjamin; Young, Heather A; Mazhari, Ramesh; Reiner, Jonathan S; Lewis, Jannet F

    2014-10-31

    Studies with other imaging modalities have demonstrated a relationship between contrast transit and cardiac output (CO) and pulmonary vascular resistance (PVR). We tested the hypothesis that the transit time during contrast echocardiography could accurately estimate both CO and PVR compared to right heart catheterization (RHC). 27 patients scheduled for RHC had 2D-echocardiogram immediately prior to RHC. 3 ml of DEFINITY contrast followed by a 10 ml saline flush was injected, and a multi-cycle echo clip was acquired from the beginning of injection to opacification of the left ventricle. 2D-echo based calculations of CO and PVR along with the DEFINITY-based transit time calculations were subsequently correlated with the RHC-determined CO and PVR. The transit time from full opacification of the right ventricle to full opacification of the left ventricle inversely correlated with CO (r=-0.61, p<0.001). The transit time from peak opacification of the right ventricle to first appearance in the left ventricle moderately correlated with PVR (r=0.46, p<0.01). Previously described echocardiographic methods for the determination of CO (Huntsman method) and PVR (Abbas and Haddad methods) did not correlate with RHC-determined values (p = 0.20 for CO, p = 0.18 and p = 0.22 for PVR, respectively). The contrast transit time method demonstrated reliable intra- (p<0.0001) and inter-observer correlation (p<0.001). We describe a novel method for the quantification of CO and estimation of PVR using contrast echocardiography transit time. This technique adds to the methodologies used for noninvasive hemodynamic assessment, but requires further validation to determine overall applicability.

  18. Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension

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    S.M.K. Shehata; W.J. Mooi (Wolter); T. Okazaki (Tadaharu); I. El-Banna; H.S. Sharma (Hari); D. Tibboel (Dick)

    1999-01-01

    textabstractBACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the mo

  19. Time course of pulmonary vascular response to an acutely repetitive pulmonary microembolism in dogs--an analysis using pulmonary vascular impedance.

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    Tobise, K; Tosaka, S; Onodera, S

    1992-05-01

    To understand the mechanism leading to progressive pulmonary hypertension, we investigated the time course of vascular response to an acutely repetitive pulmonary microembolism in dogs by using pulmonary vascular impedance. In a normal state, the mean pulmonary arterial pressure (mPAP) was transiently increased by emboli, and the impedance moduli of 0 Hz (= Rin), 1.5 Hz and 3 Hz were slightly increased. A four-element electrical vascular model showed the transient increase in peripheral pulmonary vascular resistance (R2) and inertia, and reduction in compliance (C). In contrast, in a state of a slight pulmonary hypertension, mPAP was continuously increased by the same amount of emboli, and the impedance moduli of both 0 Hz and 3 Hz were significantly increased. By a four-element model, a severe increase in R2 and reduction in C were observed, and these changes continued. Therefore, although the vascular response to pulmonary microembolism basically depends on the degree of mechanical obstruction, this response is thought to be modulated by the responsiveness of pulmonary vessels at that time, which is involved in the alteration in the local characteristics of pulmonary vessels, and/or the recruitment of a new blood flow.

  20. Biventricular failure with low pulmonary vascular resistance was managed by left ventricular assist device alone without right-sided mechanical support.

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    Imamura, Teruhiko; Kinugawa, Koichiro; Nitta, Daisuke; Hatano, Masaru; Kinoshita, Osamu; Nawata, Kan; Ono, Minoru

    2015-09-01

    How to manage preoperative right ventricular dysfunction (RVD) in heart failure patients without cardiogenic shock remains as a matter to be debated because implantable biventricular assist device treatment has not been established thus far. We here presented a patient with significant RVD indicated by low RV stroke work index (0.3 g/m) and RV dilatation as well as low pulmonary vascular resistance (PVR, 0.8 Wood Unit), who was managed by the introduction of pimobendan and sildenafil after the implantation of DuraHeart and tricuspid annuloplasty without right VAD, although his New York Heart Association symptom remained class III. Preoperative low PVR may be a key for successful LVAD treatment alone without right VAD in patients with INTERMACS profile 3 suffering RVD.

  1. Novel echocardiographic approach to the accurate measurement of pulmonary vascular resistance based on a theoretical formula in patients with left heart failure -- pilot study.

    Science.gov (United States)

    Kanda, Takashi; Fujita, Masashi; Iida, Osamu; Masuda, Masaharu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Shiraki, Tatsuya; Takahara, Mitsuyoshi; Sakata, Yasushi; Uematsu, Masaaki

    2015-01-01

    Several non-invasive methods for measuring pulmonary vascular resistance (PVR) have been proposed to date, but they remain empirical, lacking sufficient accuracy to be used in clinical practice. The aims of this study were to propose a novel echocardiographic measurement of PVR based on a theoretical formula and investigate the feasibilty and accuracy of this method in patients with heart failure. Echocardiography was performed in 27 patients before right heart catheterization. Peak tricuspid regurgitation pressure gradient (TRPG), pulmonary regurgitation pressure gradient in end-diastole (PRPGed), and cardiac output derived from the time-velocity integral and the diameter in the left ventricular outflow tract (COLVOT) were measured. PVR based on a theoretical formula (PVRtheo) was calculated as (TRPG-PRPGed)/3COLVOTin Wood units (WU). The results were compared with PVR obtained by right heart catheterization (PVRcath) using linear regression and Bland-Altman analysis. Mean PVRcathwas 2.4±1.4 WU. PVRtheocorrelated well with PVRcath(r=0.83, P<0.001). On Bland-Altman analysis the mean difference was 0.1±0.7 WU. The limits of agreements were smaller than for other non-invasive estimations previously reported. The new echocardiographic approach based on a theoretical formula provides a non-invasive and accurate assessment of PVR in patients with heart failure.

  2. Initial Experience with Sildenafil, Bosentan, and Nitric Oxide for Pediatric Cardiomyopathy Patients with Elevated Pulmonary Vascular Resistance before and after Orthotopic Heart Transplantation

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    Babak Daftari

    2010-01-01

    Full Text Available Background. Although pulmonary hypertension complicating dilated cardiomyopathy has been shown to be a significant risk factor for graft failure after heart transplantation, the upper limits of pulmonary vascular resistance (PVR that would contraindicate pediatric heart transplantation are not known. Methods. A retrospective review of all pediatric orthotopic heart transplant (OHT performed at our institution from 2002 to 2007 was performed. Seven patients with PVR >6 Wood's units (WU prior to transplant were compared pre- and postoperatively with 20 matched controls with PVR <6 WU. All pulmonary vasodilator therapies used are described as well as outcomes during the first year posttransplant. Results. The mean PVR prior to transplantation in the 7 study cases was 11.0±4.6 (range 6–22 WU, compared to mean PVR of 3.07±0.9 WU (0.56–4.5 in the controls (=.27×10−6. All patients with elevated PVR were treated pre-OHT with either Sildenafil or Bosentan. Post-OHT, case patients received a combination of sildenafil, iloprost, and inhaled nitric oxide. All 7 case patients survived one year post-OHT, and there was no statistical difference between cases and controls for hospital stay, rejection/readmissions, or graft right ventricular failure. Mean PVR in the cases at one and three months post-OHT was not significantly different between the two groups. Only one of the cases required prolonged treatment with iloprost after OHT. Conclusions. A PVR above 6 WU should not be an absolute contraindication to heart transplantation in children.

  3. Reliability of Doppler-Based Measurement of Pulmonary Vascular Resistance in Congenital Heart Disease with Left-to-Right Shunt Lesions.

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    Bhyravavajhala, Srinivas; Velam, Vanajakshamma; Polapragada, Nishanth V; Pallempati, Pranav; Iragavarapu, Tammi Raju; Patnaik, Amar Narayan; Damera, Seshagiri Rao

    2015-06-01

    Pulmonary vascular resistance (PVR) is a crucial parameter in the management of patients with left-to-right shunt lesions. Cardiac catheterization (Cath) is the gold standard test to assess PVR (PVRcath ), but it is invasive and hence, risky in children with pulmonary arterial hypertension (PAH). A noninvasive tool to assess PVR is desirable. Ratio of tricuspid regurgitation velocity (TRV) and time-velocity integral of right ventricular outflow tract (TVIRVOT ) by Doppler was previously shown to be a reliable noninvasive method for estimation of PVR in acquired PAH. Peak TR velocity and TVIRVOT were recorded from 63 prospective patients with various congenital shunt lesions. Subsequently, the patients were subjected to cath in less than 2 hours. The patients were subdivided into four subsets based on age and pulmonary arterial mean pressure (PAMP). A regression equation was developed for calculation of PVR from TRV/TVIRVOT (PVREcho ) which was indexed for BSA (PVRIEcho ). Bland-Altman analysis was done for agreement between PVRIcath and PVRIEcho . Receiver operating characteristic (ROC) curves were plotted to test the identity of the two methods and also the applicability of PVRIEcho across a wide range of Wood units. Receiver operating characteristic curve plotted between the two methods showed good identity. Bland-Altman analysis showed excellent agreement between the two methods with negligible bias. ROC curves showed that PVRIEcho was accurate in distinguishing different cutoff values of PVR in each of the 4 groups. Noninvasive Doppler estimation of PVR is reliable in patients with shunt lesions over a wide range of PVR. © 2014, Wiley Periodicals, Inc.

  4. Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease.

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    Mariana Muñoz-Esquerre

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes.All consecutive subjects undergoing lung resection were included and divided into 3 groups: 1 COPD, 2 smokers, and 3 non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1 percentage of intimal area (%IA, 2 percentage of luminal narrowing, 3 intimal thickness index, and 4 intima-to-media ratio.In the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA than those of smokers (15.6±1.5% vs. 14.2±1.6%, p = 0.038. In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs. 29.3±2.3%, p = 0.016. Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman's rho = 0.46, p = 0.008.Greater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population.

  5. Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats

    Science.gov (United States)

    Zeidler-Erdely, Patti C.; Meighan, Terence G.; Erdely, Aaron; Fedan, Jeffrey S.; Thompson, Janet A.; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B.; Afshari, Aliakbar; McKinney, Walter; Frazer, David G.; Antonini, James M.

    2015-01-01

    Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (RL) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline RL was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased RL and result in endothelial dysfunction, but otherwise had minor effects on the lung. PMID:25140454

  6. Monitoring pulmonary vascular permeability using radiolabeled transferrin

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    Basran, G.S.; Hardy, J.G.

    1988-07-01

    A simple, noninvasive technique for monitoring pulmonary vascular permeability in patients in critical care units is discussed. High vascular permeability is observed in patients with clinically defined adult respiratory distress syndrome (ARDS) but not in patients with hydrostatic pulmonary edema or in patients with minor pulmonary insults who are considered to be at risk of developing ARDS. The technique has been used in the field of therapeutics and pharmacology to test the effects of the putative antipermeability agents methylprednisolone and terbutaline sulfate. There appears to be a good correlation between the acute inhibitory effect of either drug on transferrin exudation and patient prognosis. Thus, a byproduct of such drug studies may be an index of survival in patients with established ARDS.

  7. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance

  8. Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

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    Ronald W. Day

    2015-03-01

    Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

  9. Pulmonary manifestations of the collagen vascular diseases.

    Science.gov (United States)

    Wiedemann, H P; Matthay, R A

    1989-12-01

    The collagen vascular diseases are a heterogeneous group of immunologically mediated inflammatory disorders. The organs and tissues that compose the respiratory system are frequently affected by these diseases. Potential targets of the inflammation and injury include the lung parenchyma, tracheobronchial tree, pulmonary vasculature, pleura, larynx, and respiratory muscles. In this article, the spectrum of respiratory disease caused by systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, mixed connective tissue disease, ankylosing spondylitis, relapsing polychondritis, and Sjögren's syndrome is reviewed. Where appropriate, therapeutic options are discussed.

  10. Mitigation of Radiation Induced Pulmonary Vascular Injury by Delayed Treatment with Captopril

    Science.gov (United States)

    MOLTHEN, Robert C.; WU, Qingping; FISH, Brian L.; MOULDER, John E.; JACOBS, Elizabeth R.; MEDHORA, Meetha M.

    2013-01-01

    Background and objective A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2-months post-exposure. In this study we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Methods Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2-months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2-weeks after radiation exposure, with 2 doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary hemodynamics, lung ACE activity, pulmonary arterial distensibility, and peripheral vessel density. Results Captopril, given at a vasoactive but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly these beneficial effects were observed even if drug therapy was delayed for up to two weeks after exposure. Conclusions Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident. PMID:22882664

  11. Pulmonary vascular response to digoxin in newborn lambs.

    Science.gov (United States)

    Milstein, J M; Goetzman, B W

    1984-01-01

    The effects of digoxin on pulmonary vascular resistance (PVR) were evaluated in normoxic (N) and hypoxic (H) newborn lambs with normal and elevated PVR, respectively. Lambs were anesthetized and instrumented to enable continuous measurement of mean pulmonary arterial pressure (PPA), mean left atrial pressure (PLA), mean pulmonary blood flow (Qp), and mean aortic pressure (PAO). Digoxin (10-20 micrograms/kg) was injected via central venous catheters in 11 N lambs and 4 H lambs. Under N conditions, baseline PVR was equal to 0.12 mm Hg/ml/min/kg, PPA was 33 mm Hg, PLA was 6 mm Hg, Qp was 235 ml/min/kg, and PAO was 69 mm Hg. Following digoxin, mean PVR increased by 24% (P less than 0.001) and PPA increased by 23% (P less than 0.001) for an average duration of 199 sec while QP increased by 5% (P less than 0.02) and PLA was constant suggesting a direct vasoconstrictive effect. Under H conditions, baseline PVR was equal to 0.26 mm Hg/ml/min/kg, PPA was 58 mm Hg, PLA was 4 mm Hg, Qp was 208 ml/min/kg, and PAo was 65 mm Hg. Following digoxin, mean PVR, Qp, PLA, and PAo did not change appreciably although PPA had a uniform increase of 5% (P less than 0.001). The blunted response may suggest that either the pulmonary vascular bed was maximally constricted or that digoxin and hypoxia share a common mechanism. In conclusion, digoxin has a direct pulmonary vasoconstrictor action in newborn lambs. Because of its short duration, this action probably should not alter the clinical use of this drug in newborn humans.

  12. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    NARCIS (Netherlands)

    van Loon, Rosa Laura E; Bartelds, Beatrijs; Wagener, Frank A D T G; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W C; Takens, Janny; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progeni

  13. Pulmonary Vascular Capacitance as a Predictor of Vasoreactivity in Idiopathic Pulmonary Arterial Hypertension Tested by Adenosine

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    Shafie

    2015-09-01

    Full Text Available Background Acute pulmonary vasoreactivity testing has been recommended in the diagnostic work-up of patients with idiopathic pulmonary arterial hypertension (IPAH. Pulmonary arteriolar capacitance (Cp approximated by stroke volume divided by pulmonary pulse pressure (SV/PP is considered as an independent predictor of mortality in patients with IPAH. Objectives We sought to evaluate any differences in baseline and adenosine Cp between vasoreactive and non-vasoreactive IPAH patients tested with adenosine. Patients and Methods Fourteen patients with IPAH and a vasoreactive adenosine vasoreactivity testing according to the ESC guidelines were compared with 24 IPAH patients with nonreactive adenosine test results. Results There were no statistical significant differences between the two groups regarding NYHA class, body surface area, heart rate, and systemic blood pressure during right heart catheterization. Hemodynamic study showed no statistical significant differences in cardiac output/Index, mean pulmonary artery pressure, pulmonary vascular resistance, and baseline Cp between the two groups. There was a statistical significant but weak increase in adenosine Cp in vasoreactive group compared to non-reactive group (P = 0.04. Multivariable analysis showed an association between Cp and vasoreactivity (Beta = 2, P = 0.04, OR = 0.05 (95%CI = 0.003 - 0.9. Conclusions Cp could be considered as an index for the prediction of vasoreactivity in patients with IPAH. Prediction of long-term response to calcium channel blockers in patients with IPAH and a positive vasoreactive test by this index should be addressed in further studies.

  14. Cardiac catheterization in children with pulmonary hypertensive vascular disease.

    Science.gov (United States)

    Bobhate, Prashant; Guo, Long; Jain, Shreepal; Haugen, Richard; Coe, James Y; Cave, Dominic; Rutledge, Jennifer; Adatia, Ian

    2015-04-01

    The risks associated with cardiac catheterization in children with pulmonary hypertension (PH) are increased compared with adults. We reviewed retrospectively all clinical data in children with PH [mean pulmonary artery pressure (mean PAp) ≥25 mmHg and pulmonary vascular resistance index (PVRI) ≥3 Wood units m(2)] undergoing cardiac catheterization between 2009 and 2014. Our strategy included a team approach, minimal catheter manipulation and sildenafil administration prior to extubation. Adverse events occurring within 48 h were noted. Seventy-five patients (36 males), median age 4 years (0.3-17) and median weight 14.6 kg (2.6-77 kg), underwent 97 cardiac catheterizations. Diagnoses included idiopathic or heritable pulmonary arterial hypertension (PAH) (29 %), PAH associated with congenital heart disease (52 %), left heart disease (5 %) and lung disease (14 %). Mean PAp was 43 ± 19 mmHg; mean PVRI was 9.7 ± 6 Wood units m(2). There were no deaths or serious arrhythmias. No patient required cardiac massage. Three patients who suffered adverse events had suprasystemic PAp (3/3), heritable PAH (2/3), decreased right ventricular function (3/3), and pulmonary artery capacitance index <1 ml/mmHg/m(2) (3/3) and were treatment naïve (3/3). No patient undergoing follow-up cardiac catheterization suffered a complication. In 45 % of cases, the data acquired from the follow-up cardiac catheterization resulted in an alteration of therapy. Three percent of children with PH undergoing cardiac catheterization suffered adverse events. However, there were no intra or post procedural deaths and no one required cardiac massage or cardioversion. Follow-up cardiac catheterization in patients receiving pulmonary hypertensive targeted therapy is safe and provides useful information.

  15. CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls.

    Science.gov (United States)

    Taslakian, Bedros; Latson, Larry A; Truong, Mylene T; Aaltonen, Eric; Shiau, Maria C; Girvin, Francis; Alpert, Jeffrey B; Wickstrom, Maj; Ko, Jane P

    2016-11-01

    Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

  16. Hemodynamic evidence of vascular remodeling in combined post- and precapillary pulmonary hypertension

    Science.gov (United States)

    Brittain, Evan L.; Wells, Quinn S.; Farber-Eger, Eric H.; Halliday, Stephen J.; Doss, Laura N.; Xu, Meng; Wang, Li; Harrell, Frank E.; Yu, Chang; Robbins, Ivan M.; Newman, John H.; Hemnes, Anna R.

    2016-01-01

    Abstract Although commonly encountered, patients with combined postcapillary and precapillary pulmonary hypertension (Cpc-PH) have poorly understood pulmonary vascular properties. The product of pulmonary vascular resistance and compliance, resistance-compliance (RC) time, is a measure of pulmonary vascular physiology. While RC time is lower in postcapillary PH than in precapillary PH, the RC time in Cpc-PH and the effect of pulmonary wedge pressure (PWP) on RC time are unknown. We tested the hypothesis that Cpc-PH has an RC time that resembles that in pulmonary arterial hypertension (PAH) more than that in isolated postcapillary PH (Ipc-PH). We analyzed the hemodynamics of 282 consecutive patients with PH referred for right heart catheterization (RHC) with a fluid challenge from 2004 to 2013 (cohort A) and 4,382 patients who underwent RHC between 1998 and 2014 for validation (cohort B). Baseline RC time in Cpc-PH was higher than that in Ipc-PH and lower than that in PAH in both cohorts (P < 0.001). In cohort A, RC time decreased after fluid challenge in patients with Ipc-PH but not in those with PAH or Cpc-PH (P < 0.001). In cohort B, the inverse relationship of pulmonary vascular compliance and resistance, as well as that of RC time and PWP, in Cpc-PH was similar to that in PAH and distinct from that in Ipc-PH. Our findings demonstrate that patients with Cpc-PH have pulmonary vascular physiology that resembles that of patients with PAH more than that of Ipc-PH patients. Further study is warranted to identify determinants of vascular remodeling and assess therapeutic response in this subset of PH. PMID:27683608

  17. Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue

    Directory of Open Access Journals (Sweden)

    Weingartner R.

    1999-01-01

    Full Text Available To investigate the role of nitric oxide in human sepsis, ten patients with severe septic shock requiring vasoactive drug therapy and mechanical ventilation were enrolled in a prospective, open, non-randomized clinical trial to study the acute effects of methylene blue, an inhibitor of guanylate cyclase. Hemodynamic and metabolic variables were measured before and 20, 40, 60, and 120 min after the start of a 1-h intravenous infusion of 4 mg/kg of methylene blue. Methylene blue administration caused a progressive increase in mean arterial pressure (60 [55-70] to 70 [65-100] mmHg, median [25-75th percentiles]; P<0.05, systemic vascular resistance index (649 [479-1084] to 1066 [585-1356] dyne s-1 cm-5 m-2; P<0.05 and the left ventricular stroke work index (35 [27-47] to 38 [32-56] g m-1 m-2; P<0.05 from baseline to 60 min. The pulmonary vascular resistance index increased from 150 [83-207] to 186 [121-367] dyne s-1 cm-5 m-2 after 20 min (P<0.05. Mixed venous saturation decreased from 65 [56-76] to 63 [55-69]% (P<0.05 after 60 min. The PaO2/FiO2 ratio decreased from 168 [131-215] to 132 [109-156] mmHg (P<0.05 after 40 min. Arterial lactate concentration decreased from 5.1 ± 2.9 to 4.5 ± 2.1 mmol/l, mean ± SD (P<0.05 after 60 min. Heart rate, cardiac filling pressures, cardiac output, oxygen delivery and consumption did not change. Methylene blue administration was safe and no adverse effect was observed. In severe human septic shock, a short infusion of methylene blue increases systemic vascular resistance and may improve myocardial function. Although there was a reduction in blood lactate concentration, this was not explained by an improvement in tissue oxygenation, since overall oxygen availability did not change. However, there was a significant increase in pulmonary vascular tone and a deterioration in gas exchange. Further studies are needed to demonstrate if nitric oxide blockade with methylene blue can be safe for patients with septic shock

  18. Evaluation of direct effects of enoximone on systemic and pulmonary vascular bed in animals with a Jarvik total artificial heart.

    Science.gov (United States)

    Deleuze, P H; Rande, J L; Okude, J; Wan, F; Brunet, S; Thoraval, F R; Cachera, J P; Loisance, D Y

    1992-03-01

    Enoximone, a phosphodiesterase inhibitor, has positive inotropic and vasodilating actions. To evaluate specific effects of this drug on the systemic and pulmonary vascular bed, we administered enoximone as a 10-minute intravenous bolus at two different doses of 2 and 3 mg/kg of body weight, at different days, to five Holstein calves with a Jarvik 7-70 ml total artificial heart (Symbion, Inc., Salt Lake City, Utah). The calves were monitored for aortic pressure, right atrial pressure, pulmonary arterial pressure, and left atrial pressure. For each experiment cardiac output was maintained constant, and systemic and pulmonary vascular resistances were calculated at 0, 15, 30, and 60 minutes and every hour for 8 hours after infusion. Statistical analysis used analysis of variance and the paired t test with Bonferroni's correction. Data showed the following: (1) a marked systemic vasodilating action of enoximone at peak effect at 30 minutes with a 20% decrease in systemic vascular resistance from baseline value under constant cardiac output, returning progressively to normal values throughout the 8 hours; (2) a comparable effect for the two separate doses tested; (3) no specific action on the pulmonary vascular bed with "nonunidirectional" changes in pulmonary vascular resistance. This model was validated by the infusion of prostaglandin I2 in the same animals, at different days, which significantly decreased pulmonary vascular resistance of 50% at peak effect, under constant cardiac output. In summary, enoximone showed a proper systemic vasodilating effect with no specific action on the pulmonary vascular bed in an animal model of the total artificial heart. Decrease in pulmonary vascular resistances obtained with enoximone in clinical practice seems more related to the inotropic properties of the drug. Enoximone should not be administered in pulmonary hypertension, as suggested before.

  19. Effects of erythropoietin on advanced pulmonary vascular remodelling

    NARCIS (Netherlands)

    van Albada, M. E.; Sarvaas, G. J. du Marchie; Koster, J.; Houwertjes, M. C.; Berger, R. M. F.; Schoemaker, R. G.

    2008-01-01

    Erythropoietin (EPO) mobilises endothelial progenitor cells and promotes neovascularisation in heart failure. The present authors studied the effects of EPO on pulmonary vascular and cardiac remodelling in a model for flow-associated pulmonary arterial hypertension (PAH). PAH was induced in adult ma

  20. Pulmonary vascular response of dogs with heartworm disease.

    Science.gov (United States)

    Rawlings, C A

    1978-10-01

    Heartworm diseases in dogs is an infectious disease that produces pulmonary hypertension. Dogs with the early vascular changes of heartworm disease, but without the clinical cardiopulmonary signs and pulmonary hypertension, were studied. Dogs with early heartworm were identified that had an exaggerated hypertensive response to hypoxia and to postaglandin F2alpha as compared to those of normal dogs. The pulmonary hypertensive response of dogs with spontaneous heartworm disease varied widely between individuals.

  1. Lung biopsy diagnosis of operative indication in secundum atrial septal defect with severe pulmonary vascular disease.

    Science.gov (United States)

    Yamaki, Shigeo; Kumate, Munetaka; Yonesaka, Susumu; Maeda, Katsuhide; Endo, Masato; Tabayashi, Koichi

    2004-10-01

    Surgical indication was determined by lung biopsy in 91 patients with secundum atrial septal defect (ASD) and severe pulmonary hypertension > 70 mm Hg of pulmonary arterial peak pressure and/or pulmonary vascular resistance of > 8 U/m(2). Pulmonary vascular disease (PVD) in ASD was classified into four types: (1) Musculoelastosis consisting of longitudinal muscle bundles and elastic fibers; surgery is indicated no matter how severely the peripheral small pulmonary arteries are occluded. Surgery was performed in all of the 20 patients, and the postoperative course was uneventful. (2) Plexogenic pulmonary arteriopathy: surgery is indicated for a PVD index < or = 2.3. Surgery was performed in 25 of the 32 patients. The remaining seven patients for whom surgery was not indicated are under follow-up observation. No deaths have occurred among the 32 patients. (3) Thromboembolism of small pulmonary arteries: Surgery is indicated for all such cases. Surgery was indicated in all of the five patients. (4) Mixed type of plexogenic pulmonary arteriopathy and musculoelastosis: Surgery is indicated if the collateral is not observed. Surgery was performed in 15 of the 25 patients. The remaining 10 patients for whom surgery was not indicated are under follow-up observation. Nine of these 91 patients associated with primary pulmonary hypertension were eliminated from this study. No deaths due to PVD occurred among the 82 patients who underwent lung biopsy diagnosis. Lung biopsy diagnosis is concluded to be very effective.

  2. 应用Swan-Ganz导管测定肺动脉高压犬模型肺循环阻力及心输出量的实验研究%Application of Swan-Ganz catheter to measure pulmonary vascular resistance and cardiac output of canine model with pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    林约瑟; 李淑娟; 李轩狄; 李运泉; 王慧深

    2015-01-01

    ObjectiveTo explore the value of Swan-Ganz catheter to measure pulmonary vascular resistance (PVR) and cardiac output (CO) of canine model with pulmonary arterial hypertension (PAH).MethodsSixteen Beagle dogs were randomly divided into two groups, the control group(n=8) and the pulmonary arterial hypertension group (n=8). Arterial blood was obtained to test arterial oxygen saturation. A Swan-Ganz catheter was advanced through the the right jugular vein way to the pulmonary artery and the pulmonary arterial pressure (PAP) were measured. Blood was obtained to test the pulmonary arterial oxygen saturation and plasma concentration of brain natriuretic peptide (BNP). Cardiac output and pulmonary vascular resistance were then calculated according to formula. The pulmonary arterial hypertension group were injected dehydromonocrataline 2.5 mg/kgto set up pulmonary arterial hypertension model. Hemodynamic measure was repeated after eight weeks.ResultsEight weeks after injection of dehydromonocrotaline, the pulmonary arterial systolic pressure, mean pulmonary arterial pressure of the pulmonary arterial hypertension group were significantly increased from (20.33±1.86) mmHg to (50.10±3.72) mmHg, (10.42±1.48) mmHg to (34.30±2.35) mmHg, the pulmonary arterial resistance, pulmonary vascular resistance were significantly increased from (1.10±0.24) Wood to (12.60±0.29) Wood, (2.34±0.33) Wood to (15.68±0.68) Wood, respectively, cardiac output was significantly decreased from (4.60±0.64) L/min to (2.30±0.35) L/min (P<0.05).ConclusionIt is an accurate, stable and repeatable method to apply Swan-Ganz catheter for measuring pulmonary vascular resistance and cardiac output in Beagle models with pulmonary arterial hypertension.%目的:探讨Swan-Ganz导管在肺动脉高压犬模型肺循环阻力及心输出量测定中的应用价值。方法16只比格犬随机分为2组,正常对照组(n=8)、肺动脉高压组(n=8)。穿刺动脉取血检测血氧饱和度。

  3. The effects of sufentanil in the feline pulmonary vascular bed.

    Science.gov (United States)

    Kaye, Alan D; Phelps, James; Baluch, Amir; Ibrahim, Ikhlass N; Hoover, Jason M; Baber, Syed R; Zhang, Cuihua; Armstrong, Christopher; Huffman, Shane; Fields, Aaron

    2006-03-18

    The purpose of this prospective vehicle controlled study was to test the hypothesis that sufentanil induces a depressor response in the pulmonary vascular bed of the cat and identify the receptors involved in the mediation or modulation of these effects. In separate experiments, the effects of diphenydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase (COX)-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to sufentanil and other agonists in the feline pulmonary vascular bed. The lobar arterial perfusion pressures were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, sufentanil induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. However, the responses to sufentanil were significantly attenuated following administration of diphenhydramine and naloxone. The results of the present study suggest that sufentanil has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opioid receptor sensitive pathways.

  4. Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

    Science.gov (United States)

    Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

    1999-12-01

    Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

  5. Dysfunction of pulmonary vascular endothelium in chronic obstructive pulmonary disease: basic considerations for future drug development.

    Science.gov (United States)

    Yang, Qin; Underwood, Malcolm J; Hsin, Michael K Y; Liu, Xiao-Cheng; He, Guo-Wei

    2008-09-01

    Chronic obstructive pulmonary disease (COPD) is one of the leading health problems worldwide and continues to be a major cause of morbidity and mortality in developed countries. The clinical features of COPD are chronic obstructive bronchiolitis and emphysema. Pulmonary vascular endothelial dysfunction is a characteristic pathological finding of COPD at different stages of the disease. Functional changes of pulmonary endothelial cells in COPD include antiplatelet abnormalities, anticoagulant disturbances, endothelial activation, atherogenesis, and compromised regulation of vascular tone which may adversely affect the ventilation-perfusion match in COPD. As the most important risk factor of COPD, cigarette smoking may initiate pulmonary vascular impairment through direct injury of endothelial cells or release of inflammatory mediators. Morphological changes such as denudation of endothelium and endothelial cell apoptosis have been observed in the pulmonary vasculature in COPD patients as well as functional alterations. Changes in the expression of tissue factor pathway inhibitor (TFPI), thrombomodulin, selectins, and adhesion molecules in pulmonary endothelial cells as well as complex regulation and interaction of vasoactive substances and growth factors released from endothelium may underlie the mechanisms of pulmonary endothelial dysfunction in COPD. The mechanism of endothelial repair/regeneration in COPD, although not fully understood, may involve upregulation of vascular endothelial growth factors in the early stages along with an increased number of bone marrow-derived progenitor cells. These factors should be taken into account when developing new strategies for the pharmacological therapy of patients with COPD.

  6. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  7. Occlusion of pulmonary arteriovenous malformations by use of vascular plug

    DEFF Research Database (Denmark)

    Andersen, P E; Kjeldsen, A D

    2007-01-01

    Pulmonary arteriovenous malformations are commonly treated by embolization with coils or balloons to prevent cerebral complications and to raise the oxygenation of the blood. The Amplatzer vascular plug is a new occlusive device made of a self-expanding cylindrical nitinol mesh. It is fast and safe...

  8. Mast Cell Inhibition Improves Pulmonary Vascular Remodeling in Pulmonary Hypertension

    NARCIS (Netherlands)

    Bartelds, Beatrijs; van Loon, Rosa Laura E.; Mohaupt, Saffloer; Wijnberg, Hans; Dickinson, Michael G.; Takens, Janny; van Albada, Mirjam; Berger, Rolf M. F.; Boersma, B.

    2012-01-01

    Background: Pulmonary arterial hypertension (PAH) is a progressive angioproliferative disease with high morbidity and mortality. Although the histopathology is well described, its pathogenesis is largely unknown. We previously identified the increased presence of mast cells and their markers in a ra

  9. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension

    Science.gov (United States)

    Phan, Carole; Seferian, Andrei; Huertas, Alice; Thuillet, Raphaël; Sattler, Caroline; Le Hiress, Morane; Tamura, Yuichi; Jutant, Etienne-Marie; Chaumais, Marie-Camille; Bouchet, Stéphane; Manéglier, Benjamin; Molimard, Mathieu; Rousselot, Philippe; Sitbon, Olivier; Simonneau, Gérald; Montani, David; Humbert, Marc

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease that can be induced by dasatinib, a dual Src and BCR-ABL tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). Today, key questions remain regarding the mechanisms involved in the long-term development of dasatinib-induced PAH. Here, we demonstrated that chronic dasatinib therapy causes pulmonary endothelial damage in humans and rodents. We found that dasatinib treatment attenuated hypoxic pulmonary vasoconstriction responses and increased susceptibility to experimental pulmonary hypertension (PH) in rats, but these effects were absent in rats treated with imatinib, another BCR-ABL tyrosine kinase inhibitor. Furthermore, dasatinib treatment induced pulmonary endothelial cell apoptosis in a dose-dependent manner, while imatinib did not. Dasatinib treatment mediated endothelial cell dysfunction via increased production of ROS that was independent of Src family kinases. Consistent with these findings, we observed elevations in markers of endothelial dysfunction and vascular damage in the serum of CML patients who were treated with dasatinib, compared with CML patients treated with imatinib. Taken together, our findings indicate that dasatinib causes pulmonary vascular damage, induction of ER stress, and mitochondrial ROS production, which leads to increased susceptibility to PH development. PMID:27482885

  10. Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

    Science.gov (United States)

    Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

    2012-01-01

    Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening

  11. Pulmonary arterial dysfunction in insulin resistant obese Zucker rats

    Directory of Open Access Journals (Sweden)

    Cogolludo Angel

    2011-04-01

    Full Text Available Abstract Background Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat. Methods Large and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. KV currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique. Results Right ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, KV1.5 and 5-HT2A receptor mRNA and protein expression and KV current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W. Conclusions In contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.

  12. Vascular Stiffness in Insulin Resistance and Obesity

    Directory of Open Access Journals (Sweden)

    Guanghong eJia

    2015-08-01

    Full Text Available Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies.

  13. Measurement of pulmonary flow reserve and pulmonary index of microcirculatory resistance for detection of pulmonary microvascular obstruction.

    Directory of Open Access Journals (Sweden)

    Rahn Ilsar

    Full Text Available BACKGROUND: The pulmonary microcirculation is the chief regulatory site for resistance in the pulmonary circuit. Despite pulmonary microvascular dysfunction being implicated in the pathogenesis of several pulmonary vascular conditions, there are currently no techniques for the specific assessment of pulmonary microvascular integrity in humans. Peak hyperemic flow assessment using thermodilution-derived mean transit-time (T(mn facilitate accurate coronary microcirculatory evaluation, but remain unvalidated in the lung circulation. Using a high primate model, we aimed to explore the use of T(mn as a surrogate of pulmonary blood flow for the purpose of measuring the novel indices Pulmonary Flow Reserve [PFR = (maximum hyperemic/(basal flow] and Pulmonary Index of Microcirculatory Resistance [PIMR = (maximum hyperemic distal pulmonary artery pressurex(maximum hyperemic T(mn]. Ultimately, we aimed to investigate the effect of progressive pulmonary microvascular obstruction on PFR and PIMR. METHODS AND RESULTS: Temperature- and pressure-sensor guidewires (TPSG were placed in segmental pulmonary arteries (SPA of 13 baboons and intravascular temperature measured. T(mn and hemodynamics were recorded at rest and following intra-SPA administration of the vasodilator agents adenosine (10-400 microg/kg/min and papaverine (3-24 mg. Temperature did not vary with intra-SPA sensor position (0.010+/-0.009 v 0.010+/-0.009 degrees C; distal v proximal; p = 0.1, supporting T(mn use in lung for the purpose of hemodynamic indices derivation. Adenosine (to 200 microg/kg/min & papaverine (to 24 mg induced dose-dependent flow augmentations (40+/-7% & 35+/-13% T(mn reductions v baseline, respectively; p<0.0001. PFR and PIMR were then calculated before and after progressive administration of ceramic microspheres into the SPA. Cumulative microsphere doses progressively reduced PFR (1.41+/-0.06, 1.26+/-0.19, 1.17+/-0.07 & 1.01+/-0.03; for 0, 10(4, 10(5 & 10(6 microspheres; p

  14. Bile pigments in pulmonary and vascular disease

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter

    2012-03-01

    Full Text Available The bile pigments, biliverdin and bilirubin, are endogenously-derived substances generated during enzymatic heme degradation. These compounds have been shown to act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion. The excess production of bilirubin has been associated with neurotoxicity, in particular to the newborn. Nevertheless, clinical evidence suggests that mild states of hyperbilirubinemia may be beneficial in protecting against cardiovascular disease in adults. Pharmacological application of either bilirubin and/or its biological precursor biliverdin, can provide therapeutic benefit in several animal models of cardiovascular and pulmonary disease. Furthermore, biliverdin and bilirubin can confer protection against ischemia/reperfusion injury and graft rejection secondary to organ transplantation in animal models. Several possible mechanisms for these effects have been proposed, including direct antioxidant and scavenging effects, and modulation of signaling pathways regulating inflammation, apoptosis, cell proliferation, and immune responses. The practicality and therapeutic-effectiveness of bile pigment application to humans remains unclear.

  15. Bile pigments in pulmonary and vascular disease.

    Science.gov (United States)

    Ryter, Stefan W

    2012-01-01

    The bile pigments, biliverdin, and bilirubin, are endogenously derived substances generated during enzymatic heme degradation. These compounds have been shown to act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion. The excess production of bilirubin has been associated with neurotoxicity, in particular to the newborn. Nevertheless, clinical evidence suggests that mild states of hyperbilirubinemia may be beneficial in protecting against cardiovascular disease in adults. Pharmacological application of either bilirubin and/or its biological precursor biliverdin, can provide therapeutic benefit in several animal models of cardiovascular and pulmonary disease. Furthermore, biliverdin and bilirubin can confer protection against ischemia/reperfusion injury and graft rejection secondary to organ transplantation in animal models. Several possible mechanisms for these effects have been proposed, including direct antioxidant and scavenging effects, and modulation of signaling pathways regulating inflammation, apoptosis, cell proliferation, and immune responses. The practicality and therapeutic-effectiveness of bile pigment application to humans remains unclear.

  16. Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation.

    Science.gov (United States)

    Landsberg, Judd W; Yuan, Jason X-J

    2004-04-01

    Ca(2+) is a major trigger for pulmonary vasoconstriction and a stimulus for pulmonary vascular smooth muscle cell proliferation. The transient receptor potential cation channels participate in regulating intracellular Ca(2+) and thus vascular contractility and cell proliferation. Upregulation of genes encoding these channels is involved in the development of pulmonary hypertension.

  17. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling

    Directory of Open Access Journals (Sweden)

    Angelini Daniel J

    2013-01-01

    Full Text Available Abstract Background Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in explaining this differential response. Methods We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge. Mice were evaluated for markers of PH and pulmonary vascular remodeling throughout the lung vascular bed as well as HIMF expression and genomic analysis of whole lung. Results Chronic hypoxia increased both mean pulmonary artery pressure (mPAP and right ventricular (RV hypertrophy; these changes were associated with increased muscularization and thickening of small pulmonary vessels throughout the lung vascular bed. Allergic inflammation, by contrast, had minimal effect on mPAP and produced no RV hypertrophy. Only peribronchial vessels were significantly thickened, and vessels within the lung periphery did not become muscularized. Genomic analysis revealed that HIMF was the most consistently upregulated gene in the lungs following both chronic hypoxia and antigen challenge. HIMF was upregulated in the airway epithelial and inflammatory cells in both models, but only chronic hypoxia induced HIMF upregulation in vascular tissue. Conclusions The results show that pulmonary vascular remodeling in mice induced by chronic hypoxia or antigen challenge is associated with marked increases in HIMF expression. The lack of HIMF expression in the vasculature of the lung and no vascular remodeling in the peripheral resistance vessels of the lung is likely to account for the failure to develop PH in the allergic inflammation model.

  18. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance a

  19. Pulmonary hypertension in children with congenital heart disease (PAH-CHD, PPHVD-CHD). Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    Science.gov (United States)

    Kozlik-Feldmann, Rainer; Hansmann, Georg; Bonnet, Damien; Schranz, Dietmar; Apitz, Christian; Michel-Behnke, Ina

    2016-05-01

    Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a complex disease that presents with a broad spectrum of morphological and haemodynamic findings of varying severity. Recently, the aspect of paediatric pulmonary hypertensive vascular disease (PPHVD) has been introduced to expand the understanding of the full spectrum of pulmonary hypertension and increased pulmonary vascular resistance. Evaluation and treatment of PAH-CHD/PPHVD-CHD can be divided into in different topics. First, defining criteria for operability and initiation of advanced therapies preoperatively and postoperatively is an unresolved issue. Second, management of Eisenmenger syndrome is still an important question, with recent evidence on the severity of the disease and a more rapidly progressive course than previously described. Third, the Fontan circulation with no subpulmonary ventricle requires a distinct discussion, definition and classification since even a mild rise in pulmonary vascular resistance may lead to the so-called failing Fontan situation. Patients with CHD and single-ventricle physiology (Fontan/total cavopulmonary anastomosis) require a particularly stepwise and individualised approach. This consensus statement is on the current evidence for the most accurate evaluation and treatment of increased pulmonary artery pressure and resistance, as well as ventricular dysfunction, in children with congenital heart defects, and provides according practical recommendations. To optimise preoperative and postoperative management in patients with PAH-CHD, diagnostic and treatment algorithms are provided.

  20. Endotoxin increases pulmonary vascular protein permeability in the dog

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, C.H.; Dauber, I.M.; Weil, J.V.

    1986-10-01

    Endotoxin increases pulmonary vascular permeability consistently in some species but fails to reliably cause injury in the dog. We wondered whether this phenomenon depended on the method of injury assessment, as others have relied on edema measurement; we quantified injury by monitoring the rate of extravascular protein accumulation. /sup 113m/In-labeled protein and /sup 99m/Tc-labeled erythrocytes were injected into anesthetized dogs and monitored by an externally placed lung probe. A protein leak index, the rate of extravascular protein accumulation, was derived from the rate of increase in lung protein counts corrected for changes in intravascular protein activity. After administration of Salmonella enteriditis endotoxin (4 micrograms/kg), the protein leak index was elevated 2.5-fold (41.1 +/- 4.6 X 10(-4) min-1) compared with control (16.0 +/- 2.8 X 10(-4) min-1). In contrast, wet-to-dry weight ratios failed to increase after endotoxin (4.6 +/- 0.8 vs. control values of 4.2 +/- 0.5 g/g dry bloodless lung). However, we observed that endotoxin increased lung dry weight (per unit body weight), which may have attenuated the change in wet-to-dry weight ratios. To determine whether low microvascular pressures following endotoxin attenuated edema formation, we increased pulmonary arterial wedge pressures in five dogs by saline infusion, which caused an increase in wet-to-dry weight ratios following endotoxin but no change in the five controls. We conclude that low dose endotoxin causes pulmonary vascular protein leak in the dog while edema formation is minimal or absent.

  1. Effect of L-Arginine on Pulmonary Artery Smooth Muscle Cell Apoptosis in Rats with Hypoxic Pulmonary Vascular Structural Remodeling

    Institute of Scientific and Technical Information of China (English)

    Ingrid Karmane SUMOU; Jun-Bao DU; Bing WEI; Chun-Yu ZHANG; Jian-Guang QI; Chao-Shu TANG

    2006-01-01

    This study investigated the effect of L-arginine (L-Arg) on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in rats with hypoxic pulmonary vascular structural remodeling, and its mechanisms. Seventeen Wistar rats were randomly divided into a control group (n=5), a hypoxia group (n=7), and a hypoxia+L-Arg group (n=5). The morphologic changes of lung tissues were observed under optical microscope. Using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatebiotin nick end labeling assay, the apoptosis of PASMC was examined. Fas expression in PASMC was examined using immunohistochemistry. The results showed that the percentage of muscularized artery in small pulmonary vessels, and the relative medial thickness and relative medial area of the small and median pulmonary muscularized arteries in the hypoxic group were all significantly increased. Pulmonary vascular structural remodeling developed after hypoxia. Apoptotic smooth muscle cells of the small and median pulmonary arteries in the hypoxia group were significantly less than those in the control group. After 14 d of hypoxia, Fas expression by smooth muscle cells of median and small pulmonary arteries was significantly inhibited. L-Arg significantly inhibited hypoxic pulmonary vascular structural remodeling in association with an augmentation of apoptosis of smooth muscle cells as well as Fas expression in PASMC. These results showed that L-Arg could play an important role in attenuating hypoxic pulmonary vascular structural remodeling by upregulating Fas expression in PASMC, thus promoting the apoptosis of PASMC.

  2. Enhanced expression of fibroblast growth factors and receptor FGFR-1 during vascular remodeling in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    A.R. Kranenburg (Andor); W.I. de Boer (Pim); J.H.J.M. van Krieken (Han); W.J. Mooi (Wolter); J.E. Walters (Jane); P.R. Saxena (Pramod Ranjan); P.J. Sterk (Peter); H.S. Sharma (Hari)

    2002-01-01

    textabstractImportant characteristics of chronic obstructive pulmonary disease (COPD) include airway and vascular remodeling, the molecular mechanisms of which are poorly understood. We assessed the role of fibroblast growth factors (FGF) in pulmonary vascular remodeling by examini

  3. Pulmonary manifestations in collagen vascular diseases; Pulmonale Manifestationen bei Kollagenosen

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, M.N.A. [Thoraxklinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kreuter, M. [Thoraxklinik, Universitaetsklinikum Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kauczor, H.U. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Heussel, C.P. [Thoraxklinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Heidelberg (Germany); Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany)

    2016-10-15

    Pulmonary complications are frequent in patients with collagen vascular diseases (CVD). Frequent causes are a direct manifestation of the underlying disease, side effects of specific medications and lung infections. The standard radiological procedure for the work-up of pulmonary pathologies in patients with CVD is multidetector computed tomography (MDCT) with thin-slice high-resolution reconstruction. The accuracy of thin-slice CT for the identification of particular disease patterns is very high. The pattern of usual interstitial pneumonia (UIP) representing the direct pulmonary manifestation of rheumatoid arthritis (RA) can be identified with a sensitivity of 45 % and a specificity of 96 %. Both direct pulmonary manifestations, drug-induced toxicity and certain infections can have a similar appearance in thin-slice MDCT in various forms of CVD. Knowledge of the patterns and causes contributes to the diagnostic certainty. At first diagnosis of a CVD and associated pulmonary symptoms thin-slice MDCT is recommended. Clinical, lung function and imaging follow-up examinations should be performed every 6-12 months depending on the results of the MDCT. In every case the individual CT morphological patterns of pulmonary involvement must be identified. The combination of information on the anamnesis, clinical and imaging results is a prerequisite for an appropriate disease management. (orig.) [German] Pulmonale Komplikationen sind bei Patienten mit Kollagenosen keine Seltenheit. Haeufig sind eine direkte Manifestation der Grunderkrankung, eine Nebenwirkung der medikamentoesen Therapie oder eine Lungeninfektion die Ursachen. Das radiologische Standardverfahren zur Klaerung pulmonaler Pathologien bei Patienten mit Kollagenosen ist die Multidetektorcomputertomographie mit duennschichtigen Rekonstruktionen (Duennschicht-MDCT). Die Treffsicherheit der Duennschicht-MDCT ist fuer die Identifikation eines Erkrankungsmusters sehr hoch. So kann beispielsweise das Muster einer

  4. Erythropoietin attenuates pulmonary vascular remodeling in experimental pulmonary arterial hypertension through interplay between endothelial progenitor cells and heme-oxygenase

    Directory of Open Access Journals (Sweden)

    Rosa L.E. Loon

    2015-08-01

    Full Text Available BackgroundPulmonary arterial hypertension (PAH is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs and activation of the cytoprotective enzyme heme oxygenase-1 (HO1.MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity-inhibitor tin-mesoporphyrin (SnMP. HO-activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.ResultsIn PAH-rats, circulating EPCs were decreased and HO-activity was increased compared to control. EPO-treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO-activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.ConclusionsIn experimental PAH, EPO treatment restored the number of circulating EPC’s to control level, improved pulmonary vascular remodeling, and showed important interplay with HO-activity. Inhibition of increased HO-activity in PAH-rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored numbers of circulating EPC’s. We suggest that both EPO-induced HO1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.

  5. Plasticity of vascular progenitor cells: Implications in pulmonary vascular remodelling in COPD

    Directory of Open Access Journals (Sweden)

    M. Díez

    2006-12-01

    Full Text Available Vascular progenitor cells (VPC have shown in vitro and in vivo their ability to differentiate into endothelial cells (EC. Some evidence suggests that the plasticity of these cells to differentiate into other cell types might contribute not only to angiogenesis but also to perpetuate vascular lesions. Studies done in pulmonary arteries (PA of patients with COPD have demonstrated the presence of VPC infiltrating the intima. Since intimal thickening is mainly constituted by smooth muscle cells (SMC, we asked whether VPC could play a role in wall thickening. Accordingly, the objective was to evaluate in vitro the plasticity of VPC to differentiate into SMC and EC of human PA. G-CSF-mobilized peripheral blood CD133+ cells from a commercial primary line were expanded and labelled with acetylated-LDL-DiI for tracking cell purposes. Then, cells were co-cultured with commercial primary lines of human PA EC or SMC (n = 3. As control, CD133+ cells were cultured alone, with minimal medium with or without VEGF (50ng·ml–1. After 6 and 12 days of growth, the phenotype of cultures was characterized by immunofluorescence with: lectin, -actin and CD31. Cells were also evaluated morphologically. After 6 days, VPC acquired the morphology and the phenotype of the cells with which they were co-cultured, EC (lectin+, CD31+, alpha-actin- or SMC (alpha-actin+, lectin-, CD31-. VPC cultured 12 days alone or with VEGF did not acquire typical morphology and markers of mature EC or SMC of PA. We conclude that VPC have the potential to differentiate in vitro into SMC, and that this plasticity could contribute to perpetuate pulmonary vascular remodelling in COPD.

  6. Adipokines: A Possible Contribution to Vascular and Bone Remodeling in Idiopathic Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Kochetkova, Evgenia A; Ugai, Ludmila G; Maistrovskaia, Yuliya V; Nevzorova, Vera A

    2017-04-01

    Osteoporosis is a major comorbidity of cardio-respiratory diseases, but the mechanistic links between pulmonary arterial hypertension and bone remain elusive. The purpose of the stud was to evaluate serum adipokines and endothelin-1 (ET-1) levels in the patients with idiopathic pulmonary arterial hypertension (IPAH) NYHA class III-IV and to determine its associations with bone mineral density (BMD). Pulmonary and hemodynamic parameters, BMD Z-scores at the lumbar spine (LS) and femoral neck (FN), serum leptin, adiponectin, visfatin and endothelin-1 (ET-1), were evaluated in 32 patients with IPAH NYHA class III-IV and 30 healthy volunteers. Leptin, adiponectin and ET-1 were higher in the patients with IPAH than in healthy subjects. Visfatin level showed a tendency to increase compared to that of healthy subjects (p = 0.076). The univariate analysis revealed a positive correlation between BMD Z-scores at both sites and 6-min walk test, and inverse relation with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP). Adiponectin and visfatin showed positive correlations with PVR (p = 0.009 and p = 0.006). Serum adiponectin, visfatin and leptin were inversely associated with Z-scores. After adjusting for BMI and FMI, such associations persisted between visfatin and adiponectin levels and Z-scores at both sites. ET-1 related to mPAP, cardiac index and PVR. Negative correlation was observed between ET-1 and FN BMD (p = 0.01). Positive correlations have revealed between ET-1 and adiponectin (p = 0.02), visfatin (p = 0.004) in IPAH patients. These results provide further evidence that adipokine and endothelial dysregulation may cause not only a decrease in BMD, but also an increase in hemodynamic disorders of IPAH.

  7. Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure

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    Alaeddin B. Abukabda

    2017-05-01

    . Femoral artery response was reduced by 18 ± 5%, while third-order mesenteric arterioles were negatively affected by 20 µg nano-TiO2 with a mean decrease in response of 38.37 ± 10%. This is the first study to directly compare the differential effect of ENM exposure on discrete anatomical segments of the vascular tree. Pulmonary ENM exposure produced macrovascular and microvascular dysfunction resulting in impaired responses to endothelium-dependent, endothelium-independent, and adrenergic agonists with a more robust dysfunction at the microvascular level. These results provide additional evidence of an endothelium-dependent and endothelium-independent impairment in vascular reactivity.

  8. Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-hui LI; Jun-bao DU; Ding-fang BU; Xiu-ying TANG; Chao-shu TANG

    2006-01-01

    Aim: To explore the possible role of endogenous hydrogen sulfide (H2S), a novel gasotransmitter, in the pathogenesis of pulmonary vascular structural remodeling (PVSR) induced by high pulmonary blood flow. Methods: Thirty-two Sprague-Dawley male rats were randomly divided into sham, shunt, sham+NaHS (a H2S donor) and shunt+NaHS groups. Rats in shunt and shunt+NaHS groups underwent an abdominal aorta-inferior vena cava shunt, and rats in shunt+NaHS and sham+NaHS groups were intraperitoneally injected with NaHS. PVSR was investigated using optical microscope and transmission electron microscope. Lung tissue H2S was evaluated by sulfide-sensitive electrodes. Nitric oxide synthase (NOS), heme oxygenase (HO-1), proliferative cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) activation were analyzed by Western blotting. Results: After 11 weeks of shunting, PVSR developed with a decrease in lung tissue H2S production and an increase in nitric oxide (NO). However, lung tissue carbon monoxide (CO) did not change. After the treatment with NaHS for 11 weeks, H2S donor ameliorated PVSR and downregulated PCNA expression and ERK activation with an increase in lung tissue CO production and HO-1 protein expression but a decrease in NO production, NOS activity and eNOS protein expression in shunted rats. Conclusions: H2S exerted a regulatory effect on PVSR induced by high pulmonary blood flow. Meanwhile, H2S down-regulated the ERK/MAPK signal pathway, inhibited the NO/NOS pathway and enhanced the CO/HO pathway in rats with high pulmonary blood flow.

  9. Clinical studies on the distribution of the pulmonary blood flow at rest and with exercise in mitral stenosis in connection with the reversibility of the pulmonary vascular lesion

    Energy Technology Data Exchange (ETDEWEB)

    Kohno, Tomio

    1988-09-01

    In order to determine the severity and reversibilty of pathologic changes in the pulmonary vascular bed in mitral stenosis (MS), a retrospective review was made of pulmonary perfusion scans obtained at rest and during exercise in a series of 60 subjects - 37 patients with MS, 8 with mitral regurgitation (MR), 7 with aortic regurgitation and stenosis (ARS), and 8 normal persons (N). As expressed by Q(U/L), an increased ratio of pulmonary blood flow in the upper part to that in the lower part of the lung was significantly associated with exercise in the MR and ARS groups, as well as the N group. In the MS group, Q(U/L) patterns associated with exercise fell into three categories: (I) an increase in Q(U/L) that was lower at rest than 1.1, (II) an increase in Q(U/L) that was higher at rest that 1.1, and (III) a decrease in Q(U/L). The MS group I had the worst preoperative parameters for cardiac and pulmonary function, followed by the group II and then the group III. For 23 patients receiving mitral valve replacement, postoperative parameters, including mean pulmonary arterial pressure, cardiac index, and pulmonary arterial resistance, were worse in the group II than the groups I and III. The results suggest that organic changes in the pulmonary vascular bed, as opposed to its reversible changes in the groups I and III, have occurred in the group II. Q(U/L) changes associated with exercise may be of value in determining the severity of MS. (Namekawa, K.).

  10. Contrasting effects of ascorbate and iron on the pulmonary vascular response to hypoxia in humans.

    Science.gov (United States)

    Talbot, Nick P; Croft, Quentin P; Curtis, M Kate; Turner, Brandon E; Dorrington, Keith L; Robbins, Peter A; Smith, Thomas G

    2014-12-01

    Hypoxia causes an increase in pulmonary artery pressure. Gene expression controlled by the hypoxia-inducible factor (HIF) family of transcription factors plays an important role in the underlying pulmonary vascular responses. The hydroxylase enzymes that regulate HIF are highly sensitive to varying iron availability, and iron status modifies the pulmonary vascular response to hypoxia, possibly through its effects on HIF. Ascorbate (vitamin C) affects HIF hydroxylation in a similar manner to iron and may therefore have similar pulmonary effects. This study investigated the possible contribution of ascorbate availability to hypoxic pulmonary vasoconstriction in humans. Seven healthy volunteers undertook a randomized, controlled, double-blind, crossover protocol which studied the effects of high-dose intravenous ascorbic acid (total 6 g) on the pulmonary vascular response to 5 h of sustained hypoxia. Systolic pulmonary artery pressure (SPAP) was assessed during hypoxia by Doppler echocardiography. Results were compared with corresponding data from a similar study investigating the effect of intravenous iron, in which SPAP was measured in seven healthy volunteers during 8 h of sustained hypoxia. Consistent with other studies, iron supplementation profoundly inhibited hypoxic pulmonary vasoconstriction (P ascorbate did not affect the increase in pulmonary artery pressure induced by several hours of hypoxia (P = 0.61). We conclude that ascorbate does not interact with hypoxia and the pulmonary circulation in the same manner as iron. Whether the effects of iron are HIF-mediated remains unknown, and the extent to which ascorbate contributes to HIF hydroxylation in vivo is also unclear.

  11. Mechanisms responsible for pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Pulmonary hypertension is a pathophysiologic process characterized by progressive elevation of pulmonary vascular resistance and right heart failure, which is a common complication of many diseases. Pulmonary hypertension with no apparent causes (unknown etiology) is termed primary pulmonary hypertension or, more recently, idiopathic pulmonary arterial hypertension (IPAH).

  12. Rate of angiotensin II generation within the human pulmonary vascular bed

    DEFF Research Database (Denmark)

    Giese, Jacob; Kappelgaard, A M; Tønnesen, K H

    1980-01-01

    Plasma angiotensin II concentration gradients across the pulmonary vascular bed were measured during diagnostic renal venous/right heart catheterization in twenty-seven hypertensive patients with renal or renovascular disease. There was a linear correlation between the plasma angiotensin II...... vascular bed varied from 0.7 to 1.71/min, i.e. within a fairly narrow range....

  13. Meandering right pulmonary vein associated with severe and progressive "idiopathic-like" pulmonary hypertensive vascular disease.

    Science.gov (United States)

    Cuenca, Sofia; Bret, Montserrat; del Cerro, Maria Jesus

    2016-03-01

    Congenital anomalies of the pulmonary veins are rare. Meandering right pulmonary vein, considered a part of the Scimitar syndrome spectrum, is often an incidental finding during chest imaging. We present the case of a 4-year-old girl diagnosed with meandering pulmonary vein, who developed pulmonary hypertensive disease with an aggressive course, in spite of absence of hypoxia or elevated pulmonary wedge pressure.

  14. Robust method for extracting the pulmonary vascular trees from 3D MDCT images

    Science.gov (United States)

    Taeprasartsit, Pinyo; Higgins, William E.

    2011-03-01

    Segmentation of pulmonary blood vessels from three-dimensional (3D) multi-detector CT (MDCT) images is important for pulmonary applications. This work presents a method for extracting the vascular trees of the pulmonary arteries and veins, applicable to both contrast-enhanced and unenhanced 3D MDCT image data. The method finds 2D elliptical cross-sections and evaluates agreement of these cross-sections in consecutive slices to find likely cross-sections. It next employs morphological multiscale analysis to separate vessels from adjoining airway walls. The method then tracks the center of the likely cross-sections to connect them to the pulmonary vessels in the mediastinum and forms connected vascular trees spanning both lungs. A ground-truth study indicates that the method was able to detect on the order of 98% of the vessel branches having diameter >= 3.0 mm. The extracted vascular trees can be utilized for the guidance of safe bronchoscopic biopsy.

  15. Pulmonary exposure to carbon black nanoparticles and vascular effects

    Directory of Open Access Journals (Sweden)

    Wallin Håkan

    2010-11-01

    Full Text Available Abstract Background Exposure to small size particulates is regarded as a risk factor for cardiovascular diseases. Methods We exposed young and aged apolipoprotein E knockout mice (apoE-/- to carbon black (Printex 90, 14 nm by intratracheal instillation, with different dosing and timing, and measured vasomotor function, progression of atherosclerotic plaques, and VCAM-1, ICAM-1, and 3-nitrotyrosine in blood vessels. The mRNA expression of VCAM-1, ICAM-1, HO-1, and MCP-1 was examined in lung tissue. Results Young apoE-/- mice exposed to two consecutive 0.5 mg/kg doses of carbon black exhibited lower acetylcholine-induced vasorelaxation in aorta segments mounted in myographs, whereas single doses of 0.05-2.7 mg/kg produced no such effects. The phenylephrine-dependent vasocontraction response was shifted toward a lower responsiveness in the mice exposed once to a low dose for 24 hours. No effects were seen on the progression of atherosclerotic plaques in the aged apoE-/- mice or on the expression of VCAM-1 and ICAM-1 and the presence of 3-nitrotyrosine in the vascular tissue of either young or aged apoE-/- mice. The expression of MCP-1 mRNA was increased in the lungs of young apoE-/- mice exposed to 0.9-2.7 mg/kg carbon black for 24 hours and of aged apoE-/- mice exposed to two consecutive 0.5 mg/kg doses of carbon black seven and five weeks prior to sacrifice. Conclusion Exposure to nano-sized carbon black particles is associated with modest vasomotor impairment, which is associated neither with nitrosative stress nor with any obvious increases in the expression of cell adhesion proteins on endothelial cells or in plaque progression. Evidence of pulmonary inflammation was observed, but only in animals exposed to higher doses.

  16. Pulmonary alveolar microlithiasis with cor pulmonale: an autopsy case demonstrating a marked decrease in pulmonary vascular beds.

    Science.gov (United States)

    Terada, Tadashi

    2009-11-01

    Pulmonary alveolar microlithiasis (PAM) is a very rare autosomal recessive disorder in which microliths are formed in the alveolar space. PAM is infrequently complicated by pulmonary hypertension, the cause of which is unclear. The author in this paper found that the pulmonary hypertension was caused by a marked decrease in pulmonary vascular beds. Here, an autopsy case of PAM with a marked cor pulmonale is reported. A 14-year-old woman was found to have an abnormal pulmonary shadow, but the cause was unclear. At 24 years, she was diagnosed with a diffuse pulmonary abnormal shadow. At 42 years, she was diagnosed with PAM by imaging techniques. Her condition gradually worsened and she had to be treated with oxygen. She died of respiratory failure at 54 years. An autopsy revealed severe PAM and marked cor pulmonale. The heart weighed 360 g and right ventricular thickness was 10 mm (normal, 2-3 mm). Microscopically, the alveolar space was diffusely filled with microliths, and heart failure cells were recognized. Bone formations were scattered. The alveolar walls showed fibrous thickening, and pulmonary arteries showed atherosclerosis. The right ventricle showed marked cardiac hypertrophy. Chronic severe liver congestion was noted. A morphometric analysis using CD34-stained specimens showed a marked decrease (one tenth) in pulmonary capillary beds (capillary number: 8.6 +/- 3.1 per image), compared with normal lungs obtained from two other autopsies (85.3 +/- 9.4 and 96.2 +/- 10,3). It was concluded that the cor pulmonale and pulmonary hypertension in the present case were caused by the marked decrease of the pulmonary arterial vascular beds. More research is required regarding the etiology and treatment of PAM.

  17. Pulmonary vascular complications in portal hypertension and liver disease: A concise review

    Directory of Open Access Journals (Sweden)

    M. Porres-Aguilar

    2013-01-01

    Full Text Available Chronic liver disease and/or portal hypertension may be associated with one of the two pulmonary vascular complications: portopulmonary hypertension and hepatopulmonary syndrome. These pulmonary vascular disorders are notoriously underdiagnosed; however, they have a substantial negative impact on survival and require special attention in order to understand their diagnostic approach and to select the best therapeutic options. Portopulmonary hypertension results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. On the other hand, abnormal intrapulmonary vascular dilations, profound hypoxemia, and a wide alveolar-arterial gradient are the hallmarks of the hepatopulmonary syndrome, resulting in difficult-to-treat hypoxemia. The aim of this review is to summarize the latest pathophysiologic concepts, diagnostic approach, therapy, and prognosis of portopulmonary hypertension and hepatopulmonary syndrome, as well as to discuss the role of liver transplantation as a definitive therapy in selected patients with these conditions.

  18. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension

    Science.gov (United States)

    Bertero, Thomas; Oldham, William M.; Cottrill, Katherine A.; Pisano, Sabrina; Vanderpool, Rebecca R.; Yu, Qiujun; Zhao, Jingsi; Tai, Yiyin; Tang, Ying; Zhang, Ying-Yi; Rehman, Sofiya; Sugahara, Masataka; Qi, Zhi; Gorcsan, John; Vargas, Sara O.; Saggar, Rajan; Saggar, Rajeev; Wallace, W. Dean; Ross, David J.; Haley, Kathleen J.; Parikh, Victoria N.; De Marco, Teresa; Hsue, Priscilla Y.; Morris, Alison; Simon, Marc A.; Norris, Karen A.; Gaggioli, Cedric; Loscalzo, Joseph; Fessel, Joshua; Chan, Stephen Y.

    2016-01-01

    Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP-dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus–infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ–GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH. PMID:27548520

  19. Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

    Energy Technology Data Exchange (ETDEWEB)

    Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

    2017-07-15

    The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

  20. Role of platelets in maintenance of pulmonary vascular permeability to protein

    Energy Technology Data Exchange (ETDEWEB)

    Lo, S.K.; Burhop, K.E.; Kaplan, J.E.; Malik, A.B. (Albany Medical College of Union Univ., NY (USA))

    1988-04-01

    The authors examined the role of platelets in maintenance of pulmonary vascular integrity by inducing thrombocytopenia in sheep using antiplatelet serum (APS). A causal relationship between thrombocytopenia and increase in pulmonary vascular permeability was established by platelet repletion using platelet-rich plasma (PRP). Sheep were chronically instrumented and lung lymph fistulas prepared to monitor pulmonary lymph flow (Q{sub lym}). A balloon catheter was positioned in the left atrium to assess pulmonary vascular permeability to protein after raising the left atrial pressure (P{sub la}). Thrombocytopenia was maintained for 3 days by daily intramuscular APS injections. In studies using cultured bovine pulmonary artery endothelial monolayers, transendothelia permeability of {sup 125}I-labeled albumin was reduced 50 and 95%, respectively, when 2.5 {times} 10{sup 7} or 5 {times} 10{sup 7} platelets were added onto endothelial monolayers. However, addition of 5 {times} 10{sup 6} platelets or 5 {times} 10{sup 7} red blood cells did not reduce endothelial monolayer albumin permeability. Results indicate that platelets are required for the maintenance of pulmonary vascular permeability. Reduction in permeability appears to involve an interaction of platelets with the endothelium.

  1. Pulmonary vascular effects of serotonin and selective serotonin reuptake inhibitors in the late-gestation ovine fetus.

    Science.gov (United States)

    Delaney, Cassidy; Gien, Jason; Grover, Theresa R; Roe, Gates; Abman, Steven H

    2011-12-01

    Maternal use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) is associated with an increased risk for persistent pulmonary hypertension of the newborn (PPHN), but little is known about 5-HT signaling in the developing lung. We hypothesize that 5-HT plays a key role in maintaining high pulmonary vascular resistance (PVR) in the fetus and that fetal exposure to SSRIs increases 5-HT activity and causes pulmonary hypertension. We studied the hemodynamic effects of 5-HT, 5-HT receptor antagonists, and SSRIs in chronically prepared fetal sheep. Brief infusions of 5-HT (3-20 μg) increased PVR in a dose-related fashion. Ketanserin, a 5-HT 2A receptor antagonist, caused pulmonary vasodilation and inhibited 5-HT-induced pulmonary vasoconstriction. In contrast, intrapulmonary infusions of GR127945 and SB206553, 5-HT 1B and 5-HT 2B receptor antagonists, respectively, had no effect on basal PVR or 5-HT-induced vasoconstriction. Pretreatment with fasudil, a Rho kinase inhibitor, blunted the effects of 5-HT infusion. Brief infusions of the SSRIs, sertraline and fluoxetine, caused potent and sustained elevations of PVR, which was sustained for over 60 min after the infusion. SSRI-induced pulmonary vasoconstriction was reversed by infusion of ketanserin and did not affect the acute vasodilator effects of acetylcholine. We conclude that 5-HT causes pulmonary vasoconstriction, contributes to maintenance of high PVR in the normal fetus through stimulation of 5-HT 2A receptors and Rho kinase activation, and mediates the hypertensive effects of SSRIs. We speculate that prolonged exposure to SSRIs can induce PPHN through direct effects on the fetal pulmonary circulation.

  2. Pulmonary hypertensive crisis following ethanol sclerotherapy for a complex vascular malformation.

    Science.gov (United States)

    Cordero-Schmidt, G; Wallenstein, M B; Ozen, M; Shah, N A; Jackson, E; Hovsepian, D M; Palma, J P

    2014-09-01

    Anhydrous ethanol is a commonly used sclerotic agent for treating vascular malformations. We describe the case of a full-term 15-day-old female with a complex venolymphatic malformation involving the face and orbit. During treatment of the lesion with ethanol sclerotherapy, she suffered acute pulmonary hypertensive crisis. We discuss the pathophysiology of pulmonary hypertension related to ethanol sclerotherapy, and propose that hemolysis plays a significant role. Recommendations for evaluation, monitoring and management of this complication are also discussed.

  3. Vascular endothelial-cadherin downregulation as a feature of endothelial transdifferentiation in monocrotaline-induced pulmonary hypertension.

    Science.gov (United States)

    Nikitopoulou, Ioanna; Orfanos, Stylianos E; Kotanidou, Anastasia; Maltabe, Violetta; Manitsopoulos, Nikolaos; Karras, Panagiotis; Kouklis, Panos; Armaganidis, Apostolos; Maniatis, Nikolaos A

    2016-08-01

    Increased pulmonary vascular resistance in pulmonary hypertension (PH) is caused by vasoconstriction and obstruction of small pulmonary arteries by proliferating vascular cells. In analogy to cancer, subsets of proliferating cells may be derived from endothelial cells transitioning into a mesenchymal phenotype. To understand phenotypic shifts transpiring within endothelial cells in PH, we injected rats with alkaloid monocrotaline to induce PH and measured lung tissue levels of endothelial-specific protein and critical differentiation marker vascular endothelial (VE)-cadherin. VE-cadherin expression by immonoblotting declined significantly 24 h and 15 days postinjection to rebound to baseline at 30 days. There was a concomitant increase in transcriptional repressors Snail and Slug, along with a reduction in VE-cadherin mRNA. Mesenchymal markers α-smooth muscle actin and vimentin were upregulated by immunohistochemistry and immunoblotting, and α-smooth muscle actin was colocalized with endothelial marker platelet endothelial cell adhesion molecule-1 by confocal microscopy. Apoptosis was limited in this model, especially in the 24-h time point. In addition, monocrotaline resulted in activation of protein kinase B/Akt, endothelial nitric oxide synthase (eNOS), nuclear factor (NF)-κB, and increased lung tissue nitrotyrosine staining. To understand the etiological relationship between nitrosative stress and VE-cadherin suppression, we incubated cultured rat lung endothelial cells with endothelin-1, a vasoconstrictor and pro-proliferative agent in pulmonary arterial hypertension. This resulted in activation of eNOS, NF-κB, and Akt, in addition to induction of Snail, downregulation of VE-cadherin, and synthesis of vimentin. These effects were blocked by eNOS inhibitor N(ω)-nitro-l-arginine methyl ester. We propose that transcriptional repression of VE-cadherin by nitrosative stress is involved in endothelial-mesenchymal transdifferentiation in experimental PH.

  4. Posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis

    NARCIS (Netherlands)

    Seyedmousavi, S.; Mouton, J.W.; Melchers, W.J.G.; Verweij, P.E.

    2015-01-01

    We investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant Aspergillus fumigatus isolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazo

  5. Pulmonary artery wave propagation and reservoir function in conscious man: impact of pulmonary vascular disease, respiration and dynamic stress tests.

    Science.gov (United States)

    Su, Junjing; Manisty, Charlotte; Simonsen, Ulf; Howard, Luke S; Parker, Kim H; Hughes, Alun D

    2017-08-17

    Wave travel plays an important role in cardiovascular physiology. However, many aspects of pulmonary arterial wave behaviour remain unclear. Wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery in subjects with and without pulmonary hypertension during spontaneous respiration and dynamic stress tests. Arterial wave energy decreased during expiration and Valsalva manoeuvre due to decreased ventricular preload. Wave energy also decreased during handgrip exercise due to increased heart rate. In pulmonary hypertension patients, the asymptotic pressure at which the microvascular flow ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by waves increased. The reservoir and excess pressures decreased during Valsalva manoeuvre but remained unchanged during handgrip exercise. This study provides insights into the influence of pulmonary vascular disease, spontaneous respiration and dynamic stress tests on pulmonary artery wave propagation and reservoir function. Detailed haemodynamic analysis may provide novel insights into the pulmonary circulation. Therefore, wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery to characterize changes in wave propagation and reservoir function during spontaneous respiration and dynamic stress tests. Right heart catheterization was performed using a pressure and Doppler flow sensor tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in control subjects and patients with pulmonary arterial hypertension (PAH) at rest. In controls, recordings were also obtained during Valsalva manoeuvre and handgrip exercise. The asymptotic pressure at which the flow through the microcirculation ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by arterial waves increased in PAH patients compared to controls. The systolic and diastolic rate constants

  6. Antagonism of Stem Cell Factor/c-kit Signaling Attenuates Neonatal Chronic Hypoxia-Induced Pulmonary Vascular Remodeling

    Science.gov (United States)

    Young, Karen C; Torres, Eneida; Hehre, Dorothy; Wu, Shu; Suguihara, Cleide; Hare, Joshua M.

    2015-01-01

    Background Accumulating evidence suggests that c-kit positive cells are present in the remodeled pulmonary vasculature bed of patients with pulmonary hypertension (PH). Whether stem cell factor (SCF)/ c-kit regulated pathways potentiate pulmonary vascular remodeling is unknown. Here, we tested the hypothesis that attenuated c-kit signaling would decrease chronic hypoxia-induced pulmonary vascular remodeling by decreasing pulmonary vascular cell mitogenesis. Methods Neonatal FVB/NJ mice treated with non-immune IgG (PL), or c-kit neutralizing antibody (ACK2) as well as c-kit mutant mice (WBB6F1- Kit W− v/ +) and their congenic controls, were exposed to normoxia (FiO2=0.21) or hypoxia (FiO2=0.12) for two weeks. Following this exposure, right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), pulmonary vascular cell proliferation and remodeling were evaluated. Results As compared to chronically hypoxic controls, c-kit mutant mice had decreased RVSP, RVH, pulmonary vascular remodeling and proliferation. Consistent with these findings, administration of ACK2 to neonatal mice with chronic hypoxia-induced PH decreased RVSP, RVH, pulmonary vascular cell proliferation and remodeling. This attenuation in PH was accompanied by decreased extracellular signal-regulated protein kinase (ERK) 1/2 activation. Conclusion SCF/c-kit signaling may potentiate chronic hypoxia-induced vascular remodeling by modulating ERK activation. Inhibition of c-kit activity may be a potential strategy to alleviate PH. PMID:26705118

  7. Three-Dimensions Segmentation of Pulmonary Vascular Trees for Low Dose CT Scans

    Science.gov (United States)

    Lai, Jun; Huang, Ying; Wang, Ying; Wang, Jun

    2016-12-01

    Due to the low contrast and the partial volume effects, providing an accurate and in vivo analysis for pulmonary vascular trees from low dose CT scans is a challenging task. This paper proposes an automatic integration segmentation approach for the vascular trees in low dose CT scans. It consists of the following steps: firstly, lung volumes are acquired by the knowledge based method from the CT scans, and then the data are smoothed by the 3D Gaussian filter; secondly, two or three seeds are gotten by the adaptive 2D segmentation and the maximum area selecting from different position scans; thirdly, each seed as the start voxel is inputted for a quick multi-seeds 3D region growing to get vascular trees; finally, the trees are refined by the smooth filter. Through skeleton analyzing for the vascular trees, the results show that the proposed method can provide much better and lower level vascular branches.

  8. Endovascular treatment of pulmonary sequestration in adults using Amplatzer® vascular plugs.

    Science.gov (United States)

    Leoncini, Giacomo; Rossi, Umberto G; Ferro, Carlo; Chessa, Leonardo

    2011-01-01

    Two adult patients were diagnosed with extralobar and intralobar pulmonary sequestration. One patient presented with haemoptysis. Both patients suffered from recurrent episodes of severe pulmonary infections. Both patients were treated by means of endovascular embolization using Amplatzer(®) vascular plugs (AVPs). They were discharged from hospital after 48 and 24 h and then followed up for 24 and six months, respectively. No recurrence of symptoms was observed. Computed tomography scans were obtained every six months. Persistent occlusion of vascular supply and moderate regression of the sequestered lung tissue are evident after 24 and six months in both patients. Just one case of an adult patient affected by pulmonary sequestration and treated by endovascular embolization has been reported to date. The present report is the first on the use of the AVPs in adults for this condition. The potential advantages and drawbacks of this treatment modality in adults are discussed, as well the specific benefit represented by the AVPs.

  9. Metabolic reprogramming and inflammation act in concert to control vascular remodeling in hypoxic pulmonary hypertension.

    Science.gov (United States)

    Stenmark, Kurt R; Tuder, Rubin M; El Kasmi, Karim C

    2015-11-15

    Pulmonary hypertension (PH) is a complex, multifactorial syndrome that remains poorly understood despite decades of research. PH is characterized by profound pulmonary artery (PA) remodeling that includes significant fibro-proliferative and inflammatory changes of the PA adventitia. In line with the emerging concept that PH shares key features with cancer, recent work centers on the idea that PH results from a multistep process driven by reprogramming of gene-expression patterns that govern changes in cell metabolism, inflammation, and proliferation. Data demonstrate that in addition to PA endothelial cells and smooth muscle cells, adventitial fibroblasts from animals with experimental hypoxic PH and from humans with PH (hereafter, termed PH-Fibs) exhibit proinflammatory activation, increased proliferation, and apoptosis resistance, all in the context of metabolic reprogramming to aerobic glycolysis. PH-Fibs can also recruit, retain, and activate naïve macrophages (Mϕ) toward a proinflammatory/proremodeling phenotype through secretion of chemokines, cytokines, and glycolytic metabolites, among which IL-6 and lactate play key roles. Furthermore, these fibroblast-activated Mϕ (hereafter, termed FAMϕ) exhibit aerobic glycolysis together with high expression of arginase 1, Vegfa, and I1lb, all of which require hypoxia-inducible factor 1α and STAT3 signaling. Strikingly, in situ, the adventitial Mϕ phenotype in the remodeled PA closely resembles the Mϕ phenotype induced by fibroblasts in vitro (FAMϕ), suggesting that FAMϕ crosstalk involving metabolic and inflammatory signals is a critical, pathogenetic component of vascular remodeling. This review discusses metabolic and inflammatory changes in fibroblasts and Mϕ in PH with the goal of raising ideas about new interventions to abrogate remodeling in hypoxic forms of PH.

  10. Pulmonary Vascular Tree Segmentation from Contrast-Enhanced CT Images

    CERN Document Server

    Helmberger, M; Pienn, M; Balint, Z; Olschewski, A; Bischof, H

    2013-01-01

    We present a pulmonary vessel segmentation algorithm, which is fast, fully automatic and robust. It uses a coarse segmentation of the airway tree and a left and right lung labeled volume to restrict a vessel enhancement filter, based on an offset medialness function, to the lungs. We show the application of our algorithm on contrast-enhanced CT images, where we derive a clinical parameter to detect pulmonary hypertension (PH) in patients. Results on a dataset of 24 patients show that quantitative indices derived from the segmentation are applicable to distinguish patients with and without PH. Further work-in-progress results are shown on the VESSEL12 challenge dataset, which is composed of non-contrast-enhanced scans, where we range in the midfield of participating contestants.

  11. Generating patient-specific pulmonary vascular models for surgical planning

    Science.gov (United States)

    Murff, Daniel; Co-Vu, Jennifer; O'Dell, Walter G.

    2015-03-01

    Each year in the U.S., 7.4 million surgical procedures involving the major vessels are performed. Many of our patients require multiple surgeries, and many of the procedures include "surgical exploration". Procedures of this kind come with a significant amount of risk, carrying up to a 17.4% predicted mortality rate. This is especially concerning for our target population of pediatric patients with congenital abnormalities of the heart and major pulmonary vessels. This paper offers a novel approach to surgical planning which includes studying virtual and physical models of pulmonary vasculature of an individual patient before operation obtained from conventional 3D X-ray computed tomography (CT) scans of the chest. These models would provide clinicians with a non-invasive, intricately detailed representation of patient anatomy, and could reduce the need for invasive planning procedures such as exploratory surgery. Researchers involved in the AirPROM project have already demonstrated the utility of virtual and physical models in treatment planning of the airways of the chest. Clinicians have acknowledged the potential benefit from such a technology. A method for creating patient-derived physical models is demonstrated on pulmonary vasculature extracted from a CT scan with contrast of an adult human. Using a modified version of the NIH ImageJ program, a series of image processing functions are used to extract and mathematically reconstruct the vasculature tree structures of interest. An auto-generated STL file is sent to a 3D printer to create a physical model of the major pulmonary vasculature generated from 3D CT scans of patients.

  12. Role of oxidized lipids in pulmonary arterial hypertension

    OpenAIRE

    Sharma, Salil; Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T.; Eghbali, Mansoureh

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pul...

  13. Insulin action and insulin resistance in vascular endothelium.

    Science.gov (United States)

    Muniyappa, Ranganath; Quon, Michael J

    2007-07-01

    Vasodilator actions of insulin are mediated by phosphatidylinositol 3-kinase dependent insulin signaling pathways in endothelium, which stimulate production of nitric oxide. Insulin-stimulated nitric oxide mediates capillary recruitment, vasodilation, increased blood flow, and subsequent augmentation of glucose disposal in skeletal muscle. Distinct mitogen-activated protein kinase dependent insulin signaling pathways regulate secretion of the vasoconstrictor endothelin-1 from endothelium. These vascular actions of insulin contribute to the coupling of metabolic and hemodynamic homeostasis that occurs under healthy conditions. Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase dependent signaling in both metabolic and vascular insulin target tissues. Here we discuss consequences of pathway-specific insulin resistance in endothelium and therapeutic interventions targeting this selective impairment. Shared causal factors such as glucotoxicity, lipotoxicity, and inflammation selectively impair phosphatidylinositol 3-kinase dependent insulin signaling pathways, creating reciprocal relationships between insulin resistance and endothelial dysfunction. Diet, exercise, cardiovascular drugs, and insulin sensitizers simultaneously modulate phosphatidylinositol 3-kinase and mitogen-activated protein kinase dependent pathways, improving metabolic and vascular actions of insulin. Pathway-specific impairment in insulin action contributes to reciprocal relationships between endothelial dysfunction and insulin resistance, fostering clustering of metabolic and cardiovascular diseases in insulin-resistant states. Therapeutic interventions that target this selective impairment often simultaneously improve both metabolic and vascular function.

  14. VASOACTIVE INTESTINAL POLYPEPTIDE PREVENTS INJURY OF PULMONARY VASCULAR PERMEABILITY DUE TO XANTHINE WITH XANTHINE OXIDASE

    Institute of Scientific and Technical Information of China (English)

    林耀广

    1995-01-01

    Hyperpermeability is a crux of pathogenesis of sudden lung edema in many pulmooary disorders,espe=cially in acute lung injury and adult respiratory distress syndrome(ARDS). Using our modified method for assessment of pulmonary vascular permeability,we observed the effects of xanthine with xanthine oxi-dase (X-XO) perfused in rat pulmonary artery and the protection of vasoactive intestinal polypeptide (VIP) against the injury of pulmonary vascular permesbility.After addition of xanthine oxidase in the perfusate reservoir containing xanthine,125I-albumin leak index (125IALI) was remarkably increased while peak airway pressure (Paw) was not significantly increased,and perfusion pressure of pulmonary artery (Ppa) and lung wet/dry weight ratio (W/D) were only slightly increased.Xanthine plus xanthine oxi-dase also increased thromboxane B2(TX B2) and 6-keto-prostaglandin F1α(6-keto-PGF1α) in the perfusat-e.Treatment with VIP obviously reduced or totally prevented all signs of injury.Simultaneously,VIP also diminished or abolished the associated generation of arachidonate products.The results indicated that VIP bas potent protective activity against injury of pulmonary vasculat permeability and may be a physiological modulator of inflammatory damage to vaseular eodothelium associated with toxic oxygen metabolites.

  15. Genetic Ablation of PDGF-Dependent Signaling Pathways Abolishes Vascular Remodeling and Experimental Pulmonary Hypertension.

    Science.gov (United States)

    Ten Freyhaus, Henrik; Berghausen, Eva M; Janssen, Wiebke; Leuchs, Maike; Zierden, Mario; Murmann, Kirsten; Klinke, Anna; Vantler, Marius; Caglayan, Evren; Kramer, Tilmann; Baldus, Stephan; Schermuly, Ralph T; Tallquist, Michelle D; Rosenkranz, Stephan

    2015-05-01

    Despite modern therapies, pulmonary arterial hypertension (PAH) harbors a high mortality. Vascular remodeling is a hallmark of the disease. Recent clinical studies revealed that antiremodeling approaches with tyrosine-kinase inhibitors such as imatinib are effective, but its applicability is limited by significant side effects. Although imatinib has multiple targets, expression analyses support a role for platelet-derived growth factor (PDGF) in the pathobiology of the disease. However, its precise role and downstream signaling events have not been established. Patients with PAH exhibit enhanced expression and phosphorylation of β PDGF receptor (βPDGFR) in remodeled pulmonary arterioles, particularly at the binding sites for phophatidyl-inositol-3-kinase and PLCγ at tyrosine residues 751 and 1021, respectively. These signaling molecules were identified as critical downstream mediators of βPDGFR-mediated proliferation and migration of pulmonary arterial smooth muscle cells. We, therefore, investigated mice expressing a mutated βPDGFR that is unable to recruit phophatidyl-inositol-3-kinase and PLCγ (βPDGFR(F3/F3)). PDGF-dependent Erk1/2 and Akt phosphorylation, cyclin D1 induction, and proliferation, migration, and protection against apoptosis were abolished in βPDGFR(F3/F3) pulmonary arterial smooth muscle cells. On exposure to chronic hypoxia, vascular remodeling of pulmonary arteries was blunted in βPDGFR(F3/F3) mice compared with wild-type littermates. These alterations led to protection from hypoxia-induced PAH and right ventricular hypertrophy. By means of a genetic approach, our data provide definite evidence that the activated βPDGFR is a key contributor to pulmonary vascular remodeling and PAH. Selective disruption of PDGF-dependent phophatidyl-inositol-3-kinase and PLCγ activity is sufficient to abolish these pathogenic responses in vivo, identifying these signaling events as valuable targets for antiremodeling strategies in PAH. © 2015 American

  16. [Treatment for pulmonary arterial hypertension under the new French hospital financing system. Recommendations of the Pulmonary Vascular Diseases Working Group of the French Society of Pulmonary Medicine].

    Science.gov (United States)

    Sitbon, O; Humbert, M; Simonneau, G

    2005-11-05

    Activity-based financing (that is, casemix-based hospital payments, known as T2A) is intended to harmonize and improve the fairness of remuneration of public and private hospitals. T2A will ultimately rely mainly on a flat rate per admission, set according to the diagnosis-related group (DRG). Although payment for drugs is usually included in the DRG price, some expensive drugs will be reimbursed on an additional cost basis after implementation of a "best practices" agreement. Four drugs used for treatment of pulmonary arterial hypertension are eligible for this additional reimbursement: 3 prostacyclin derivatives (intravenous epoprostenol, inhaled iloprost, and subcutaneous treprostinil), and oral bosentan, an endothelin receptor antagonist. The Pulmonary Vascular Diseases working group of the French Society of Pulmonary Medicine has developed guidelines for the best practices in use of these drugs.

  17. Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia

    NARCIS (Netherlands)

    S.B. Bender (Shawn ); V.J. de Beer (Vincent Jacob); D.L. Tharp (Darla); E.D. van Deel (Elza); D.K. Bowles; D.J.G.M. Duncker (Dirk); H. Laughlin (Harold); D. Merkus (Daphne)

    2014-01-01

    textabstractVascular dysfunction has been associated with familial hypercholesterolaemia (FH), a severe form of hyperlipidaemia. We recently demonstrated that swine with FH exhibit reduced exercise-induced systemic, but not pulmonary, vasodilatation involving reduced nitric oxide (NO) bioavailabilit

  18. Pulmonary arterial wall distensibility assessed by intravascular ultrasound in children with congenital heart disease : an indicator for pulmonary vascular disease?

    NARCIS (Netherlands)

    Berger, Rolf M F; Cromme-Dijkhuis, Adri H; Hop, Wim C J; Kruit, Marco N; Hess, John; Berger, Rudolphus

    2002-01-01

    BACKGROUND: Both pulmonary hypertension and pulmonary overflow are associated with functional and structural changes of the pulmonary arterial wall. Current techniques to evaluate the pulmonary vasculature neglect the pulsatile nature of pulmonary flow. STUDY OBJECTIVES: To determine whether the dyn

  19. Long-range enhancers modulate Foxf1 transcription in blood vessels of pulmonary vascular network.

    Science.gov (United States)

    Seo, Hyejin; Kim, Jinsun; Park, Gi-Hee; Kim, Yuri; Cho, Sung-Won

    2016-09-01

    Intimate crosstalk occurs between the pulmonary epithelium and the vascular network during lung development. The transcription factor forkhead box f1 (Foxf1) is expressed in the lung mesenchyme and plays an indispensable role in pulmonary angiogenesis. Sonic hedgehog (Shh), a signalling molecule, is expressed in lung epithelium and is required to establish proper angiogenesis. It has been suggested that Foxf1, a downstream target of the Shh signalling pathway, mediates interaction between angiogenesis and the epithelium in lung. However, there has been no clear evidence showing the mechanism how Foxf1 is regulated by Shh signalling pathway during lung development. In this study, we investigated the lung-specific enhancers of Foxf1 and the Gli binding on the enhancers. At first, we found three evolutionarily conserved Foxf1 enhancers, two of which were long-range enhancers. Of the long-range enhancers, one demonstrated tissue-specific activity in the proximal and distal pulmonary blood vessels, while the other one demonstrated activity only in distal blood vessels. At analogous positions in human, these long-range enhancers were included in a regulatory region that was reportedly repeatedly deleted in alveolar capillary dysplasia with misalignment of pulmonary vein patients, which indicates the importance of these enhancers in pulmonary blood vessel formation. We also determined that Gli increased the activity of one of these long-range enhancers, which was specific to distal blood vessel, suggesting that Shh regulates Foxf1 transcription in pulmonary distal blood vessel formation.

  20. Insulin resistance and adipose tissue in the development of vascular diseases in high-risk patients

    NARCIS (Netherlands)

    Gorter, P.M.

    2008-01-01

    The work in this thesis focused on the relationship between presence of insulin resistance and advanced vascular damage in patients with manifest atherosclerotic vascular disease, and on the occurrence of (new) vascular events in insulin resistant patients with and without evident vascular disease.

  1. Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

    Directory of Open Access Journals (Sweden)

    E.R. Parra

    2012-07-01

    Full Text Available In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1 and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF. Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci, severe (mural fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

  2. Effect of microgravity on forearm subcutaneous vascular resistance in humans

    DEFF Research Database (Denmark)

    Gabrielsen, A; Norsk, P; Videbæk, R;

    1995-01-01

    To test the hypothesis that the subcutaneous vascular constrictor response to an orthostatic stress in humans is augmented after exposure to microgravity, the following experiment was performed. Four male astronauts underwent a standardized stepwise lower body negative pressure (LBNP) profile 5 mo...... before and between 24 and 40 h after completion of the 10-day Spacelab D2 mission (STS-55). Forearm subcutaneous blood flow was continuously measured during LBNP by the 133Xe washout technique, and forearm subcutaneous vascular resistance (FSVR) was estimated by dividing mean arterial pressure by forearm...

  3. Nox4 Is Expressed In Pulmonary Artery Adventitia And Contributes To Hypertensive Vascular Remodeling

    Science.gov (United States)

    Barman, Scott A.; Chen, Feng; Su, Yunchao; Dimitropoulou, Christiana; Wang, Yusi; Catravas, John D.; Han, Weihong; Orfi, Laszlo; Szantai-Kis, Csaba; Keri, Gyorgy; Szabadkai, Istvan; Barabutis, Nektarios; Rafikova, Olga; Rafikov, Ruslan; Black, Stephen M.; Jonigk, Danny; Giannis, Athanassios; Asmis, Reto; Stepp, David W.; Ramesh, Ganesan; Fulton, David J.R.

    2014-01-01

    OBJECTIVE Pulmonary Hypertension (PH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) is associated with increased pressure in PH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PH remains poorly understood. Therefore, we sought to identify the vascular cells expressing Nox4 in PA and determine the functional relevance of Nox4 in PH. APPROACH AND RESULTS Elevated expression of Nox4 was detected in hypertensive PA from 3 rat PH models and human PH using qRT-PCR, Western blot, and immunofluorescence. In the vascular wall, Nox4 was detected in both endothelium and adventitia and perivascular staining was prominently increased in hypertensive lung sections, colocalizing with cells expressing fibroblast and monocyte markers and matching the adventitial location of ROS production. Small molecule inhibitors of Nox4 reduced adventitial ROS generation and vascular remodeling as well as ameliorating right ventricular hypertrophy and non-invasive indices of PA stiffness in monocrotaline (MCT)-treated rats as determined by morphometric analysis and high resolution digital ultrasound. Nox4 inhibitors improved PH in both prevention and reversal protocols and reduced the expression of fibroblast markers in isolated PA. In fibroblasts, Nox4 over-expression stimulated migration and proliferation and was necessary for matrix gene expression. CONCLUSIONS These findings indicate that Nox4 is prominently expressed in the adventitia and contributes to altered fibroblast behavior, hypertensive vascular remodeling and the development of PH. PMID:24947524

  4. Influence of vascular enhancement, age and gender on pulmonary perfused blood volume quantified by dual-energy-CTPA

    Energy Technology Data Exchange (ETDEWEB)

    Meinel, Felix G., E-mail: felix.meinel@med.uni-muenchen.de; Graef, Anita, E-mail: anita.graef@med.uni-muenchen.de; Sommer, Wieland H., E-mail: wieland.sommer@uni-muenchen.de; Thierfelder, Kolja M., E-mail: kolja.thierfelder@uni-muenchen.de; Reiser, Maximilian F., E-mail: maximilian.reiser@med.uni-muenchen.de; Johnson, Thorsten R.C., E-mail: thorsten.johnson@med.uni-muenchen.de

    2013-09-15

    Objectives: To determine the influence of technical and demographic parameters on quantification of pulmonary perfused blood volume (PBV) in dual energy computed tomography pulmonary angiography (DE-CTPA). Materials and methods: Pulmonary PBV was quantified in 142 patients who underwent DE-CTPA for suspected pulmonary embolism but in whom no thoracic pathologies were detected. Multivariate linear regression analysis was performed to calculate the influence of age, gender, enhancement of pulmonary trunk and enhancement difference between pulmonary trunk and left atrium (as a measure of timing) on PBV values. The resulting regression coefficients were used to calculate age-specific ranges of normal for PBV values adjusted for vascular enhancement and timing. Results: Enhancement of the pulmonary trunk (β = −0.29, p = 0.001) and enhancement difference between pulmonary trunk and left atrium (β = −0.24, p = 0.003) were found to significantly influence PBV values. Age (β = −0.33, p < 0.001) but not gender (β = 0.14, p = 0.05) had a significant negative influence on pulmonary PBV values. There was a 20% relative decrease of pulmonary PBV from patients aged <30 to patients over 80 years of age. Conclusions: DE-CTPA derived PBV values need to be corrected for age, vascular enhancement and timing but not for gender. The age-specific ranges of normal derived from this study can be used as a reference in future studies of PBV in pulmonary pathologies.

  5. Relationship Between Pulmonary Artery Smooth Muscle Cells and Mechanism of Hypoxia-induced Pulmonary Vascular Remodeling%肺动脉平滑肌细胞与低氧性肺血管重塑形成机制

    Institute of Scientific and Technical Information of China (English)

    张凌云

    2013-01-01

    低氧条件下肺血管收缩、重塑,继而导致肺血管的持续对抗,其中以中膜增厚为主的肺血管重塑是导致低氧性肺动脉高压持续不可逆性病理改变的重要因素.肺动脉平滑肌细胞是肺动脉中膜的主要构成部分,慢性缺氧条件下由于各种活性介质及细胞生长因子稳态的失衡,肺动脉平滑肌细胞聚集、增殖、肥大及分泌胞外基质;另外,肺动脉平滑肌细胞通过各种信号通路与内膜的内皮细胞及外膜的成纤维细胞相互作用,在低氧性肺血管重塑过程中起着至关重要的作用,本文将对肺动脉平滑肌细胞与低氧性肺血管重塑形成机制的最新研究概况作一综述.%Under conditions of hypoxia generalized vasoconstriction and remodeling of the pulmonary vascular leads to pulmonary vascular persistent resistance. The medial thickening is the main reason of pulmonary vascular remodeling and hypoxic pulmonary artery hypertension, pulmonary artery smooth muscle cells (PASMC) are the principal structure of media, and chronic hypoxia induces the imbalance of vasoactive substances and growth factors. Under this condition, the main medial thickening is believed to be attributable to proliferation, hypertrophy and increased accumulation of PASMC as well as expression of extracellular matrix proteins. Moreover, PASMC has an interaction with endothelial cell of intima and fibroblast of adventitia through multiple signal pathways and plays a crucial role in the development of pulmonary vascular remodeling. The article will make a summary of latest research on PASMC and mechanism of hypoxic pulmonary vascular remodeling.

  6. Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats

    Directory of Open Access Journals (Sweden)

    Hales Charles A

    2011-02-01

    Full Text Available Abstract Background CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood. Methods In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats. Results We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP, ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats. Conclusions The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment.

  7. Herpes virus infection is associated with vascular remodeling and pulmonary hypertension in idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Fiorella Calabrese

    Full Text Available BACKGROUND: Pulmonary hypertension (PH represents an important complication of idiopathic pulmonary fibrosis (IPF with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68 induced pulmonary fibrosis was also assessed. METHODS: Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice. RESULTS: A higher frequency of virus positive cases was found in IPF patients than in controls (p = 0.0003 and only herpes virus genomes were detected. Viral cases showed higher mPAP (p = 0.01, poorer performance in the six minute walking test (6MWT; p = 0.002 and higher frequency of primary graft (PGD dysfunction after lung transplant (p = 0.02. Increased arterial thickening, particularly of the intimal layer (p = 0.002 and p = 0.004 and higher TGF-β expression (p = 0.002 were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (p = 0.03, poorer performance in the 6MWT (p = 0.008 and PGD (p = 0.02 after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients

  8. Herpes Virus Infection Is Associated with Vascular Remodeling and Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Calabrese, Fiorella; Kipar, Anja; Lunardi, Francesca; Balestro, Elisabetta; Perissinotto, Egle; Rossi, Emanuela; Nannini, Nazarena; Marulli, Giuseppe; Stewart, James P.; Rea, Federico

    2013-01-01

    Background Pulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68) induced pulmonary fibrosis was also assessed. Methods Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP) and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice. Results A higher frequency of virus positive cases was found in IPF patients than in controls (p = 0.0003) and only herpes virus genomes were detected. Viral cases showed higher mPAP (p = 0.01), poorer performance in the six minute walking test (6MWT; p = 0.002) and higher frequency of primary graft (PGD) dysfunction after lung transplant (p = 0.02). Increased arterial thickening, particularly of the intimal layer (p = 0.002 and p = 0.004) and higher TGF-β expression (p = 0.002) were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells) in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (p = 0.03), poorer performance in the 6MWT (p = 0.008) and PGD (p = 0.02) after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients. Conclusion

  9. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    Science.gov (United States)

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  10. Experience with pulmonary resection for extensively drug-resistant tuberculosis.

    Science.gov (United States)

    Shiraishi, Yuji; Katsuragi, Naoya; Kita, Hidefumi; Toishi, Masayuki; Onda, Takahito

    2008-12-01

    Extensively drug-resistant tuberculosis is becoming a global threat. It is a relatively new phenomenon, and its optimal management remains undetermined. We report our experience in using pulmonary resection for treating patients with this disease. Records were reviewed of 54 consecutive patients undergoing a pulmonary resection for multidrug-resistant tuberculosis at Fukujuji Hospital between 2000 and 2006. These patients were identified using the definition approved by the World Health Organization Global Task Force on extensively drug-resistant tuberculosis in October 2006. Five (9%) patients (3 men and 2 women) aged 31-60 years met the definition. None of the patients was HIV-positive. Although the best available multidrug regimens were initiated, no patient could achieve sputum conversion. Adjuvant resectional surgery was considered because the patients had localized disease. Procedures performed included pneumonectomy (2) and upper lobectomy (3). There was no operative mortality or morbidity. All patients attained sputum-negative status after the operation, and they were maintained on multidrug regimens for 12-25 months postoperatively. All patients remained free from disease at the time of follow-up. Pulmonary resection under cover of state-of-the-art chemotherapy is safe and effective for patients with localized extensively drug-resistant tuberculosis.

  11. Long-term outcome of patients with persistent vascular obstruction on computed tomography pulmonary angiography 6 months after acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Golpe, Rafael; Llano, Luis A. Perez de; Olalla, Castro-Anon [The Respiratory Service, Hospital Lucus Augusti, Lugo (Spain)], e-mail: Rafael.golpe.gomez@sergas.es; Vazquez-Caruncho, Manuel [The Radiology Service, Hospital Lucus Augusti, Lugo (Spain); Gonzalez-Juanatey, Carlos [The Cardiology Service, Hospital Lucus Augusti, Lugo (Spain); Farinas, Maria Carmen [Internal Medicine Dept., Hospital Univ. Marques de Valdecilla, Santander (Spain)

    2012-09-15

    Background: The incidence and clinical significance of pulmonary residual thrombosis 6 months after an acute pulmonary embolism (PE) are still not well-known. Purpose: To evaluate the association between residual vascular obstruction and the risk of venous thromboembolism (VTE) recurrence or death. Material and Methods: Computed tomography pulmonary angiography (CTPA) was repeated in 97 consecutive patients 6 months after an acute episode of hemodynamically stable pulmonary embolism. We assessed the long-term consequences of residual thrombosis on vital status and incidence of recurrent VTE. Results: Six patients were lost for follow-up. The remaining 91 patients were classified according to the presence (Group 1: 18 cases) or absence (Group 2: 73 cases) of residual pulmonary vascular obstruction. After a mean {+-}SD of 2.91 {+-}0.99 years, there were eight (8.8%) deaths and 11 (12.1%) VTE recurrences. Groups 1 and 2 did not differ in the incidence of death or VTE recurrence. Conclusion: Persistent pulmonary vascular obstruction on 6-month CTPA did not predict long-term adverse outcome events.

  12. Transforming Growth Factor-β1 Induces Transdifferentiation of Fibroblasts into Myofibroblasts in Hypoxic Pulmonary Vascular Remodeling

    Institute of Scientific and Technical Information of China (English)

    Yong-Liang JIANG; Ai-Guo DAI; Qi-Fang LI; Rui-Cheng HU

    2006-01-01

    The muscularization of non-muscular pulmonary arterioles is animportant pathological feature of hypoxic pulmonary vascular remodeling. However, the origin of the cells involved in this process is still not well understood. The present study was undertaken to test the hypothesis that transforming growth factor-β 1 (TGF-β 1) can induce transdifferentiation of fibroblasts into myofibroblasts, which might play a key role in the muscularization of non-muscular pulmonary arterioles. It was found that mean pulmonary arterial pressure increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. The distribution of nonmuscular, partially muscular, and muscular vessels was significantly different after 7 d of hypoxia. Immunocytochemistry results demonstrated that the expression of α-smooth muscle actin was increased in intra-acinar pulmonary arteries with increasing hypoxic time. TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-β1 protein staining was poorly positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia. The myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments and a well-developed rough endoplasmic reticulum. Taken together, our results suggested that TGF-β1 induces transdifferentiation of fibroblasts into myofibroblasts, which is important in hypoxic pulmonary vascular remodeling.

  13. Genome wide expression analysis suggests perturbation of vascular homeostasis during high altitude pulmonary edema.

    Directory of Open Access Journals (Sweden)

    Manish Sharma

    Full Text Available BACKGROUND: High altitude pulmonary edema (HAPE is a life-threatening form of non-cardiogenic edema which occurs in unacclimatized but otherwise normal individuals within two to four days after rapid ascent to altitude beyond 3000 m. The precise pathoetiology and inciting mechanisms regulating HAPE remain unclear. METHODOLOGY/PRINCIPLE FINDINGS: We performed global gene expression profiling in individuals with established HAPE compared to acclimatized individuals. Our data suggests concurrent modulation of multiple pathways which regulate vascular homeostasis and consequently lung fluid dynamics. These pathways included those which regulate vasoconstriction through smooth muscle contraction, cellular actin cytoskeleton rearrangements and endothelial permeability/dysfunction. Some notable genes within these pathways included MYLK; rho family members ARGEF11, ARHGAP24; cell adhesion molecules such as CLDN6, CLDN23, PXN and VCAM1 besides other signaling intermediates. Further, several important regulators of systemic/pulmonary hypertension including ADRA1D, ECE1, and EDNRA were upregulated in HAPE. We also observed significant upregulation of genes involved in paracrine signaling through chemokines and lymphocyte activation pathways during HAPE represented by transcripts of TNF, JAK2, MAP2K2, MAP2K7, MAPK10, PLCB1, ARAF, SOS1, PAK3 and RELA amongst others. Perturbation of such pathways can potentially skew vascular homeostatic equilibrium towards altered vascular permeability. Additionally, differential regulation of hypoxia-sensing, hypoxia-response and OXPHOS pathway genes in individuals with HAPE were also observed. CONCLUSIONS/SIGNIFICANCE: Our data reveals specific components of the complex molecular circuitry underlying HAPE. We show concurrent perturbation of multiple pathways regulating vascular homeostasis and suggest multi-genic nature of regulation of HAPE.

  14. [Clinical and laboratory characteristics of patients with pulmonary hypertension and pulmonary vascular complications hospitalized at the Instituto Nacional de Salud del Niño].

    Science.gov (United States)

    Ormeño Julca, Alexis Jose; Alvarez Murillo, Carlos Melchor; Amoretti Alvino, Pedro Miguel; Florian Florian, Angel Aladino; Castro Johanson, Rosa Aurora; Celi Perez, Maria Danisa; Huamán Prado, Olga Rocío

    2017-01-01

    The hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHN) are distinct pulmonary vascular complications of portal hypertension (PHT) and are associated with increased morbidity and mortality. To describe the clinical and laboratory characteristics of patients with pulmonary hypertension and pulmonary vascular complications hospitalized at the Instituto Nacional de Salud del Niño. We included patients with HTP hospitalized from January 2012 to June 2013 and that during its evolution progressed with SHP or HTPP. For analysis, they were divided into a first group of patients with liver cirrhosis and a second group with extrahepatic portal vein obstruction. Of 22 patients with HPT 45.5% were male and the age range was between 1 month and 17 years. The etiology in the group of cirrhosis (n=14) was: autoimmune hepatitis (35.7%), cryptogenic cirrhosis (35.7%), inborn error of metabolism (14.3%), chronic viral hepatitis C (7.15%) virus and atresia extra-hepatic bile ducts (7.15%). Pulmonary vascular complications more frequently occurred in patients with liver cirrhosis (1 case of HPS and a case of PPHTN). They most often dyspnea, asthenia, edema, malnutrition, ascites, hypersplenism and gastrointestinal bleeding from esophageal varices was found. Also, they had elevated ALT values, alkaline phosphatase and serum albumin values decreased. In children with pulmonary hypertension, pulmonary vascular complications are rare. In the evaluation of these patients pulse oximetry should be included to detect hypoxemia and ubsequently a Doppler echocardiography and contrast echocardiography necessary. Dueto the finding of systolic pulmonary hypertension it is necessary to perform right heart catheterization.

  15. Increased pulmonary vascular permeability as a cause of re-expansion edema in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Pavlin, D.J.; Nessly, M.L.; Cheney, F.W.

    1981-01-01

    In order to study the mechanism(s) underlying re-expansion edema, we measured the concentration of labeled albumin (RISA) in the extravascular, extracellular water (EVECW) of the lung as a measure of pulmonary vascular permeability. Re-expansion edema was first induced by rapid re-expansion of rabbit lungs that had been collapsed for 1 wk by pneumothorax. The RISA in EVECW was expressed as a fraction of its plasma concentration: (RISA)L/(RISA)PL. The volume of EVECW (ml/gm dry lung) was measured using a /sup 24/Na indicator. Results in re-expansion edema were compared with normal control lungs and with oleic acid edema as a model of permeability edema. In re-expanded lungs, EVECW (3.41 +/- SD 1.24 ml/g) and (RISA)L/(RISA)PL 0.84 +/- SD 0.15) were significantly increased when compared with normal control lungs (2.25 +/- 0.41 ml/g and 0.51 +/- 0.20, respectively). Results in oleic acid edema (5.66 +/- 2.23 ml/g and 0.84 +/- 0.23) were similar to re-expansion edema. This suggested that re-expansion edema is due to increased pulmonary vascular permeability caused by mechanical stresses applied to the lung during re-expansion.

  16. Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat.

    Science.gov (United States)

    Badejo, Adeleke M; Hodnette, Chris; Dhaliwal, Jasdeep S; Casey, David B; Pankey, Edward; Murthy, Subramanyam N; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2010-09-01

    It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was approximately 1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat.

  17. Prevention of pulmonary vascular and myocardial remodeling by the combined tyrosine and serine-/threonine kinase inhibitor, sorafenib, in pulmonary hypertension and right heart failure

    Directory of Open Access Journals (Sweden)

    M. Klein

    2008-06-01

    Full Text Available Inhibition of tyrosine kinases can reverse pulmonary hypertension but little is known about the role of serine-/threonine kinases in vascular and myocardial remodeling. We investigated the effects of sorafenib, an inhibitor of the tyrosine kinases VEGFR, PDGFR and c-kit as well as the serine-/threonine kinase Raf-1, in pulmonary hypertension and right ventricular (RV pressure overload. In monocrotaline treated rats, sorafenib (10 mg·kg–1·d–1 p.o. reduced pulmonary arterial pressure, pulmonary artery muscularization and RV hypertrophy, and improved systemic hemodynamics (table 1. Sorafenib prevented phosphorylation of Raf-1 and suppressed activation of downstream signaling pathways (Erk 1/2. After pulmonary banding, sorafenib, but not the PDGFR/c-KIT/ABL-inhibitor imatinib reduced RV mass and RV filling pressure significantly. Congruent with these results, sorafenib only prevented ERK phosphorylation and vasopressin induced hypertrophy of the cardiomyocyte cell line H9c2 dose dependently (IC50 = 300 nM. Combined inhibition of tyrosine and serine-/threonine kinases by sorafenib prevents vascular and cardiac remodeling in pulmonary hypertension, which is partly mediated via inhibition of the Raf kinase pathway.

  18. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

  19. Measurement uncertainty in pulmonary vascular input impedance and characteristic impedance estimated from pulsed-wave Doppler ultrasound and pressure: clinical studies on 57 pediatric patients.

    Science.gov (United States)

    Tian, Lian; Hunter, Kendall S; Kirby, K Scott; Ivy, D Dunbar; Shandas, Robin

    2010-06-01

    Pulmonary vascular input impedance better characterizes right ventricular (RV) afterload and disease outcomes in pulmonary hypertension compared to the standard clinical diagnostic, pulmonary vascular resistance (PVR). Early efforts to measure impedance were not routine, involving open-chest measurement. Recently, the use of pulsed-wave (PW) Doppler-measured velocity to non-invasively estimate instantaneous flow has made impedance measurement more practical. One critical concern remains with clinical use: the measurement uncertainty, especially since previous studies only incorporated random error. This study utilized data from a large pediatric patient population to comprehensively examine the systematic and random error contributions to the total impedance uncertainty and determined the least error prone methodology to compute impedance from among four different methods. We found that the systematic error contributes greatly to the total uncertainty and that one of the four methods had significantly smaller propagated uncertainty; however, even when this best method is used, the uncertainty can be large for input impedance at high harmonics and for the characteristic impedance modulus. Finally, we found that uncertainty in impedance between normotensive and hypertensive patient groups displays no significant difference. It is concluded that clinical impedance measurement would be most improved by advancements in instrumentation, and the best computation method is proposed for future clinical use of the input impedance.

  20. Socio Demographic Profile and Clinical Presentation of Collagen Vascular Disease with Pulmonary Symptoms: A Descriptive Cross Sectional Study

    Directory of Open Access Journals (Sweden)

    Parul Vadgama

    2013-02-01

    Full Text Available Introduction: Collagen Vascular Disease presented with varied systemic symptoms including pulmonary symptoms, commonly breathless on exertion; dry cough; cough with expectoration; chest pain; and hemoptysis. The current study was conducted to know socio demographic profile and clinical presentation of patient coming with Collagen Vascular Disease having pulmonary symptoms. Methodology: This was a descriptive cross sectional study conducted among Collagen Vascular Disease patient coming with pulmonary symptoms in outpatient department. Results: Among the 50 patients 40% patients were having SC followed by SLE (30%. Most common age group was 31 to 40 year of age followed by 21 to 30 year of age. Both these group contribute more than half of the cases. Eighty percent patients were female with female to male ratio was 4:1. The most common chest symptom in the patients was breathlessness (50% and fatigue (50%, followed by cough (46% and chest pain (18%. The most common sign was Crackles (32% followed by clubbing in 22% of patients. Conclusion: Female and young - middle age more commonly presented with Collagen Vascular Disease. Most of the patients when presented were having wide-ranging pulmonary symptoms-signs indicating extensive involvement of lung tissues which emphasis need for early diagnosis and treatment. [Natl J of Med Res 2013; 3(1.000: 27-29

  1. Posaconazole Prophylaxis in Experimental Azole-Resistant Invasive Pulmonary Aspergillosis

    OpenAIRE

    Seyedmousavi, Seyedmojtaba; Mouton, Johan W.; Melchers, Willem J. G.; Verweij, Paul E.

    2014-01-01

    We investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant Aspergillus fumigatus isolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazole MICs of 0.063 mg/liter (wild type), 0.5 mg/liter (F219I mutation), and 16 mg/liter. A fourth isolate harboring TR34/L98H (MIC of 0.5 mg/liter) was also tested. Posaconazole prophylaxis was effec...

  2. Human Multidrug Resistance 1 gene polymorphisms and Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Martinelli, Marcella; Scapoli, Luca; Pacilli, Angela Maria Grazia; Carbonara, Paolo; Girardi, Ambra; Mattei, Gabriella; Rodia, Maria Teresa; Solmi, Rossella

    2015-01-01

    Background: For the first time we tested an association between the human multidrug resistance gene 1 (MDR1) polymorphisms (SNPs) and idiopathic pulmonary fibrosis (IPF). Several MDR1 polymorphisms are associated with pathologies in which they modify the drug susceptibility and pharmacokinetics. Materials and Methods: We genotyped three MDR1 polymorphisms of 48 IPF patients and 100 control subjects with Italian origins. Results: No evidence of association was detected. Conclusion: There are 50 known MDR1 SNPs, and their role is explored in terms of the effectiveness of drug therapy. We consider our small-scale preliminary study as a starting point for further research. PMID:25767528

  3. Ameliorative Effect of Allopurinol on Vascular Complications of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hany M. El-Bassossy

    2015-01-01

    Full Text Available The aim of the current study was to evaluate the possible protective effect of allopurinol (Allo on experimentally induced insulin resistance (IR and vascular complications. Rats were divided into four groups: control, IR, allopurinol-treated IR (IR-Allo, and allopurinol-treated control (Allo. IR was induced by adding fructose and high fat, high salt diet for 12 weeks. The results showed that Allo has alleviated the increased level of TNF-α and the systolic, diastolic, mean, and notch pressure observed in IR with no change in pulse pressure. In addition, Allo decreased the heart rate in the treated group compared to IR rats. On the other hand, it has no effect on increased levels of insulin, glucose, fructosamine, or body weight gain compared to IR group, while it increased significantly the insulin level and body weight without hyperglycemia in the control group. Moreover, Allo treatment ameliorated increased level of 4HNE, Ang II, and Ang R1. In conclusion, the results of the current study show that Allo has a protective effect on vascular complications of IR which may be attributed to the effect of Allo on decreasing the TNF-α, 4HNE, Ang II, and Ang R1 as well as increasing the level of insulin secretion.

  4. Total peripheral vascular resistance in pediatric renal transplant patients.

    Science.gov (United States)

    Matteucci, Maria Chiara; Giordano, Ugo; Calzolari, Armando; Rizzoni, Gianfranco

    2002-11-01

    Abnormal cardiovascular reactivity at rest and during physical exercise may be a risk factor for left ventricular hypertrophy (LVH) in pediatric renal transplanted (Tx) patients. Data on total peripheral vascular resistance (TPR) are not available. Eleven renal Tx patients treated with cyclosporine (7 females and 4 males; mean age 14.6 +/- 3.3 years; mean time since transplantation 43 +/- 35 months) were evaluated for 24-hour blood pressure (BP), TPR and echocardiographic left ventricular mass (LVM). TPR values of patients were compared with data of a group of 11 healthy controls matched for sex and age. Twenty-four-hour ambulatory blood pressure monitoring showed that all but one patient had normal daytime BP values and six patients showed a reduced or inverse nocturnal dip. LVH was found in 72% of the patients. In comparison with healthy controls, patients showed significantly elevated TPR at rest and during exercise suggesting an increased vascular tone. The degree of LVH in these patients is severe and appears disproportionate to the BP values. The high incidence of LVH can reflect an augmented cardiovascular reactivity associated with a disturbed circadian pattern. The increase in TPR and the reduction of the nocturnal fall of BP also might contribute to the development of LVH in young renal Tx patients.

  5. Integration of complex data sources to provide biologic insight into pulmonary vascular disease (2015 Grover Conference Series)

    Science.gov (United States)

    Chan, Stephen Y.

    2016-01-01

    Abstract The application of complex data sources to pulmonary vascular diseases is an emerging and promising area of investigation. The use of -omics platforms, in silico modeling of gene networks, and linkage of large human cohorts with DNA biobanks are beginning to bear biologic insight into pulmonary hypertension. These approaches to high-throughput molecular phenotyping offer the possibility of discovering new therapeutic targets and identifying variability in response to therapy that can be leveraged to improve clinical care. Optimizing the methods for analyzing complex data sources and accruing large, well-phenotyped human cohorts linked to biologic data remain significant challenges. Here, we discuss two specific types of complex data sources—gene regulatory networks and DNA-linked electronic medical record cohorts—that illustrate the promise, challenges, and current limitations of these approaches to understanding and managing pulmonary vascular disease. PMID:27683602

  6. Regulation of Pulmonary Vascular Tone in Health and Disease: Special emphasis on exercise and pulmonary hypertension after myocardial infarction

    NARCIS (Netherlands)

    B. Houweling (Birgit)

    2007-01-01

    textabstractHigh bloodpressure in the pulmonary circulation is called pulmonary hypertension (PH). In patients with PH, the balance between vasodilators and vasoconstrictors is disturbed. PH is an important cause of death; it is characterized by elevated levels of pulmonary artery pressure a

  7. Pulmonary vascular response during phases of canine heartworm disease: scanning electron microscopic study.

    Science.gov (United States)

    Schaub, R G; Rawlings, C A

    1980-07-01

    Pulmonary arteries and veins of 14 dogs in phases of heartworm disease (Dirofilaria immitis infection) were examined by scanning electron microscopy. Two dogs were infected with D immitis microfilaria only, whereas 12 dogs were infected with adult D immitis. Seven of the dogs infected with adult worms were untreated. Two of these 7 dogs had natural infections of unknown duration introduced by mosquito bite, whereas 5 were experimentally infected for 30 days. The remaining five dogs were experimentally infected for 1 year and had worms removed by drug therapy. These five dogs were maintained 12 months after treatment. Arteries and veins from dogs infected with microfilaria had a continuous sheet of endothelial cells. Arterial endothelium from the seven nontreated dogs infected with adult heartworms exhibited swirling patterns, pore formation, and separation of intercellular junctions. Arteries from all dogs had numerous endothelialized villus protrusions; veins had similar, less extensive changes. Arteries and veins from experimentally infected dogs were similar to naturally infected dogs, indicating the infection procedure produced lesions similar to that normally seen in heartworm disease. The extent of vascular lesions was reduced in four of the five treated dogs that had been infected with adult worms. Adult worms, not microfilaria, may produce the vascular lesions seen in heartworm disease. Lesions will regress if worms are removed from the circulation. Lesions may be caused by generation of humoral factors initiated by the presence of adult worms.

  8. Nanotechnology and pulmonary delivery to overcome resistance in infectious diseases.

    Science.gov (United States)

    Andrade, Fernanda; Rafael, Diana; Videira, Mafalda; Ferreira, Domingos; Sosnik, Alejandro; Sarmento, Bruno

    2013-11-01

    Used since ancient times especially for the local treatment of pulmonary diseases, lungs and airways are a versatile target route for the administration of both local and systemic drugs. Despite the existence of different platforms and devices for the pulmonary administration of drugs, only a few formulations are marketed, partly due to physiological and technological limitations. Respiratory infections represent a significant burden to health systems worldwide mainly due to intrahospital infections that more easily affect immune-compromised patients. Moreover, tuberculosis (TB) is an endemic infectious disease in many developing nations and it has resurged in the developed world associated with the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. Currently, medicine faces the specter of antibiotic resistance. Besides the development of new anti-infectious drugs, the development of innovative and more efficient delivery systems for drugs that went off patent appears as a promising strategy pursued by the pharmaceutical industry to improve the therapeutic outcomes and to prolong the utilities of their intellectual property portfolio. In this context, nanotechnology-based drug delivery systems (nano-DDS) emerged as a promising approach to circumvent the limitations of conventional formulations and to treat drug resistance, opening the hypothesis for new developments in this area. © 2013.

  9. Transcription factors, transcriptional coregulators, and epigenetic modulation in the control of pulmonary vascular cell phenotype: therapeutic implications for pulmonary hypertension (2015 Grover Conference series).

    Science.gov (United States)

    Pullamsetti, Soni S; Perros, Frédéric; Chelladurai, Prakash; Yuan, Jason; Stenmark, Kurt

    2016-12-01

    Pulmonary hypertension (PH) is a complex and multifactorial disease involving genetic, epigenetic, and environmental factors. Numerous stimuli and pathological conditions facilitate severe vascular remodeling in PH by activation of a complex cascade of signaling pathways involving vascular cell proliferation, differentiation, and inflammation. Multiple signaling cascades modulate the activity of certain sequence-specific DNA-binding transcription factors (TFs) and coregulators that are critical for the transcriptional regulation of gene expression that facilitates PH-associated vascular cell phenotypes, as demonstrated by several studies summarized in this review. Past studies have largely focused on the role of the genetic component in the development of PH, while the presence of epigenetic alterations such as microRNAs, DNA methylation, histone levels, and histone deacetylases in PH is now also receiving increasing attention. Epigenetic regulation of chromatin structure is also recognized to influence gene expression in development or disease states. Therefore, a complete understanding of the mechanisms involved in altered gene expression in diseased cells is vital for the design of novel therapeutic strategies. Recent technological advances in DNA sequencing will provide a comprehensive improvement in our understanding of mechanisms involved in the development of PH. This review summarizes current concepts in TF and epigenetic control of cell phenotype in pulmonary vascular disease and discusses the current issues and possibilities in employing potential epigenetic or TF-based therapies for achieving complete reversal of PH.

  10. Posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis.

    Science.gov (United States)

    Seyedmousavi, Seyedmojtaba; Mouton, Johan W; Melchers, Willem J G; Verweij, Paul E

    2015-03-01

    We investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant Aspergillus fumigatus isolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazole MICs of 0.063 mg/liter (wild type), 0.5 mg/liter (F219I mutation), and 16 mg/liter. A fourth isolate harboring TR34/L98H (MIC of 0.5 mg/liter) was also tested. Posaconazole prophylaxis was effective in A. fumigatus with posaconazole MICs of ≤0.5 mg/liter, where 100% survival was reached. However, breakthrough infection was observed in mice infected with the isolate for which the posaconazole MIC was >16 mg/liter.

  11. The mast cell - B-cell axis in lung vascular remodeling and pulmonary hypertension.

    Science.gov (United States)

    Breitling, Siegfried; Hui, Zhang; Zabini, Diana; Hu, Yijie; Hoffmann, Julia; Goldenberg, Neil M; Tabuchi, Arata; Buelow, Roland; Dos Santos, Claudia; Kuebler, Wolfgang Michael

    2017-02-24

    Over the past years, a critical role for the immune system and in particular, for mast cells, in the pathogenesis of pulmonary hypertension (PH) has emerged. However, the way in which mast cells promote PH is still poorly understood. Here, we investigated the mechanisms by which mast cells may contribute to PH, specifically focusing on the interaction between the innate and adaptive immune response and the role of B-cells and autoimmunity. Experiments were performed in Sprague Dawley rats and B-cell deficient JH-KO rats in the monocrotaline, sugen-hypoxia and the aortic banding model of PH. Hemodynamics, cell infiltration, IL-6 expression, and vascular remodeling were analyzed. Gene array analyses revealed constituents of immunoglobulins as most prominently regulated mast cell dependent genes in the lung in experimental PH. IL-6 was shown to link mast cells to B-cells, as a) IL-6 was upregulated and colocalized with mast cells and was reduced by mast cell stabilizers, and b) IL-6 or mast cell blockade reduced B-cells in lungs of monocrotaline-treated rats. A functional role for B-cells in PH was demonstrated, in that either blocking B-cells by an anti-CD20 antibody or B-cell deficiency in JH-KO rats attenuated right ventricular systolic pressure and vascular remodeling in experimental PH. We here identify a mast cell - B-cell axis driven by IL-6 as critical immune pathway in the pathophysiology of PH. Our results provide novel insights into the role of the immune system in PH, which may be therapeutically exploited by targeted immunotherapy.

  12. Nicorandil attenuates monocrotaline-induced vascular endothelial damage and pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Makoto Sahara

    Full Text Available BACKGROUND: An antianginal K(ATP channel opener nicorandil has various beneficial effects on cardiovascular systems; however, its effects on pulmonary vasculature under pulmonary arterial hypertension (PAH have not yet been elucidated. Therefore, we attempted to determine whether nicorandil can attenuate monocrotaline (MCT-induced PAH in rats. MATERIALS AND METHODS: Sprague-Dawley rats injected intraperitoneally with 60 mg/kg MCT were randomized to receive either vehicle; nicorandil (5.0 mg·kg(-1·day(-1 alone; or nicorandil as well as either a K(ATP channel blocker glibenclamide or a nitric oxide synthase (NOS inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME, from immediately or 21 days after MCT injection. Four or five weeks later, right ventricular systolic pressure (RVSP was measured, and lung tissue was harvested. Also, we evaluated the nicorandil-induced anti-apoptotic effects and activation status of several molecules in cell survival signaling pathway in vitro using human umbilical vein endothelial cells (HUVECs. RESULTS: Four weeks after MCT injection, RVSP was significantly increased in the vehicle-treated group (51.0±4.7 mm Hg, whereas it was attenuated by nicorandil treatment (33.2±3.9 mm Hg; P<0.01. Nicorandil protected pulmonary endothelium from the MCT-induced thromboemboli formation and induction of apoptosis, accompanied with both upregulation of endothelial NOS (eNOS expression and downregulation of cleaved caspase-3 expression. Late treatment with nicorandil for the established PAH was also effective in suppressing the additional progression of PAH. These beneficial effects of nicorandil were blocked similarly by glibenclamide and l-NAME. Next, HUVECs were incubated in serum-free medium and then exhibited apoptotic morphology, while these changes were significantly attenuated by nicorandil administration. Nicorandil activated the phosphatidylinositol 3-kinase (PI3K/Akt and extracellular signal-regulated kinase (ERK

  13. Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    李启芳; 戴爱国

    2004-01-01

    Background Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry. Results mPAP values were significantly higher than the control values after 7days of hypoxia [(18.4±0.4) mmHg, P<0.05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1α protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1α protein was markedly increased by day 3 (0.20±0.02, P<0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1α mRNA increased significantly after day 14 of hypoxia (0.20±0.02, P<0.05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15±0.02, P<0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1α mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1α mRNA was positively correlated with VEGF mRNA and protein (P<0.01). Conclusion HIF-1α and VEGF are both involved in the

  14. Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia.

    Science.gov (United States)

    Bender, Shawn B; de Beer, Vincent J; Tharp, Darla L; van Deel, Elza D; Bowles, Douglas K; Duncker, Dirk J; Laughlin, M Harold; Merkus, Daphne

    2014-04-15

    Vascular dysfunction has been associated with familial hypercholesterolaemia (FH), a severe form of hyperlipidaemia. We recently demonstrated that swine with FH exhibit reduced exercise-induced systemic, but not pulmonary, vasodilatation involving reduced nitric oxide (NO) bioavailability. Since NO normally limits endothelin (ET) action, we examined the hypothesis that reduced systemic vasodilatation during exercise in FH swine results from increased ET-mediated vasoconstriction. Systemic and pulmonary vascular responses to exercise were examined in chronically instrumented normal and FH swine in the absence and presence of the ETA/B receptor antagonist tezosentan. Intrinsic reactivity to ET was further assessed in skeletal muscle arterioles. FH swine exhibited ∼9-fold elevation in total plasma cholesterol versus normal swine. Similar to our recent findings, systemic, not pulmonary, vasodilatation during exercise was reduced in FH swine. Blockade of ET receptors caused marked systemic vasodilatation at rest and during exercise in normal swine that was significantly reduced in FH swine. The reduced role of ET in FH swine in vivo was not the result of decreased arteriolar ET responsiveness, as responsiveness was increased in isolated arterioles. Smooth muscle ET receptor protein content was unaltered by FH. However, circulating plasma ET levels were reduced in FH swine. ET receptor antagonism caused pulmonary vasodilatation at rest and during exercise in normal, but not FH, swine. Therefore, contrary to our hypothesis, FH swine exhibit a generalised reduction in the role of ET in regulating vascular tone in vivo probably resulting from reduced ET production. This may represent a unique vascular consequence of severe familial hypercholesterolaemia.

  15. CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ARTERIAL HYPERTENSION: VASCULAR WALL AS THE TARGET ORGAN IN COMORBID PATIENTS

    Directory of Open Access Journals (Sweden)

    N. A. Karoli

    2017-01-01

    Full Text Available Studies of endothelial dysfunction in patients with respiratory diseases have become relevant in recent years. Perhaps endothelial dysfunction and high arterial stiffness bind bronchopulmonary and cardiovascular diseases.Aim. To reveal features of disturbances of arterial wall vasoregulatory function in patients with chronic obstructive pulmonary disease (COPD in the presence and absence of arterial hypertension (HT.Material and methods. The study included 50 patients with COPD with normal blood pressure (BP and 85 patients with COPD and HT. Control group was presented by 20 practically healthy men comparable in age with COPD patients. Tests with reactive hyperemia (endothelium-dependent dilation and nitroglycerin (endothelium-independent dilation were performed in order to evaluate endothelium function. The number of desquamated endotheliocytes in the blood was determined.Results. In patients with COPD and HT in comparison with COPD patients without HT and healthy individuals more pronounced damages of the vascular wall, endothelium vasoregulatory function disturbances and a tendency to the reduction in endothelium-dependent vasodilation were determined both during COPD exacerbation and remission. These differences were most pronounced during the COPD exacerbation. In patients with COPD and HT in comparison with COPD patients without HT the damage of the vascular wall was more pronounced during the remission and endothelium-dependent dilatation disorder – during the exacerbation. The revealed disorders in patients with COPD and HT were associated with smoking status (r=0.61, p<0.01, severity of bronchial obstruction (r=-0.49, p<0.05, and hypoxemia (r=-0.76, p<0.01. We noted relationships between the parameters of 24-hour BP monitoring and remodeling of the brachial artery (r=0.34, p<0.05, endothelium lesion (r=0.25, p<0.05, and impairment of its vasoregulating function (r=-0.58, p<0.05. At that, the following parameters were important: the

  16. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury.

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    Srabani Mitra

    Full Text Available Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1 induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury.

  17. Hereditary hemorrhagic telangiectasia with bilateral pulmonary vascular malformations: A case report

    Directory of Open Access Journals (Sweden)

    Lončarević Olivera

    2016-01-01

    Full Text Available Introduction. Hereditary hemorrhagic telangiectasia (HHT also known as Osler-Weber-Rendu syndrome is an autosomal dominant disease that occurs due to vascular dysplasia associated with the disorder in the signaling pathway of transforming growth factor β (TGF-β. The clinical consequence is a disorder of blood vessels in multiple organ systems with the existence of telangiectasia which causes dilation of capillaries and veins, are present from birth and are localized on the skin and mucosa of the mouth, respiratory, gastrointestinal and urinary tract. They can make a rupture with consequent serious bleeding that can end up with fatal outcome. Since there is a disruption of blood vessels of more than one organic system, the diagnosis is very complex and requires a multidisciplinary approach. Case report. We reported a 40-year-old female patient with a long-time evolution of problems, who was diagnosed and treated at the Clinic for Lung Diseases of the Military Medical Academy in Belgrade, Serbia, because of bilaterally pulmonary arteriovenous malformations associated with HHT. Embolization was performed in two acts, followed with normalization of clinical, radiological and functional findings with the cessation of hemoptysis, effort intolerance with a significant improvement of the quality of life. Conclusion. HHT is a rare dominant inherited multisystem disease that requires multidisciplinary approach to diagnosis and treatment. Embolization is the method of choice in the treatment of arteriovenous malformations with minor adverse effects and very satisfying therapeutic effect.

  18. Effect of C-myc Antisense Oligodeoxynucleotides on Hypoxia-induced Proliferation of Pulmonary Vascular Pericytes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the effect of c-myc antisense oligodeoxynucleotides (ODNs) on proliferation of pulmonary vascular pericytes (PC) induced by hypoxia, cell culture, dot hybridization using probe of digoxigenin-11-dUTP-labeled cDNA,3H-thymidine incorporation, immunocytochemical technique and image analysis methods were used to observe the effect of c-myc antisense ODNs on expression of c-myc gene and proliferating cell nuclear antigen (PCNA), and 3H-thymidine incorporation of PC induced by hypoxia. The results showed that hypoxia could significantly enhance the expression of c-myc and PCNA (P<0.01), and elevate 3H-thymidine incorporation of PC (P<0.01), but antisense ODNs could significantly inhibit the expression of c-myc and PCNA (P<0.05), and 3H-thymidine incorporation of PC (P<0.01). It was suggested that hypoxia could promote the proliferation of PC by up-regulating the expression of c-myc gene, but c-myc antisense ODNs could inhibit hypoxia-induced proliferation of PC by downregulating the expression of c-myc gene.

  19. Clearance of inhaled technetium-99m-DTPA as a clinical index of pulmonary vascular disease in systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Kon, O.M.; Daniil, Z.; Bois, R.M. du [Royal Brompton Hospital, Interstitial Lung Disease Unit, London (United Kingdom); Black, C.M. [Royal Free Hospital, Dept. of Rheumatology, London (United Kingdom)

    1999-01-01

    This study evaluated the utility of the clearance time of inhaled diethylenetriamine pentaacetate (DTPA) to distinguish pulmonary vascular disease from early fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) It was hypothesized that this would be preserved in patients with vascular disease compared with FA, despite similar gas-transfer deficits and matching lung volumes, because of the preservation of alveolar epithelial integrity. All patients had SSc and were categorized into a control group (C; n=9), pulmonary vascular group (VAS; n=14) or FA group (n=14) dependent on the appearance on a computed tomography (CT) scan and the transfer factor of the lung for carbon monoxide (TL,CO) (VAS and FA {<=}70%, C {>=}80%). All patients had a forced vital capacity (FVC) of >80%. The TL,CO (median) was similar in the VAS (57.5%) and FA (60%) groups. There was a significant difference in median DTPA clearance half-times between FA (21.25 min) and VAS (46.5 min) (p=0.014) and between FA and C (84.5 min) (p=0.0004). No difference was found between VAS and C (p=0.0778). Follow-up data from the VAS group showed no subsequent development of FA on the CT scan and no decrease in FVC (n=13, mean 42 months). These results suggest that clearance of diethylenetriamine pentaacetate is preserved in patients likely to have pulmonary vascular disease and may be useful in distinguishing fibrosing alveolitis from vascular disease in systemic sclerosis. (au) 22 refs.

  20. Intrauterine endotoxin-induced impairs pulmonary vascular function and right ventricular performance in infant rats and improvement with early vitamin D therapy.

    Science.gov (United States)

    Mandell, Erica; Powers, Kyle N; Harral, Julie W; Seedorf, Gregory J; Hunter, Kendall S; Abman, Steven H; Dodson, R Blair

    2015-12-15

    High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown. We hypothesized that intrauterine ETX impairs RV-PA coupling through sustained abnormalities of PA stiffening and RV performance that are attenuated with vit D therapy. Fetal rats were exposed to intra-amniotic injections of ETX, ETX+vit D, or saline at 20 days gestation (term = 22 days). At postnatal day 14, pups had pressure-volume measurements of the RV and isolated proximal PA, respectively. Lung homogenates were assayed for extracellular matrix (ECM) composition by Western blot. We found that ETX lungs contain decreased α-elastin, lysyl oxidase, collagen I, and collagen III proteins (P < 0.05) compared control and ETX+vit D lungs. ETX-exposed animals have increased RV mechanical stroke work (P < 0.05 vs. control and ETX+vit D) and elastic potential energy (P < 0.05 vs. control and ETX+vit D). Mechanical stiffness and ECM remodeling are increased in the PA (P < 0.05 vs. control and ETX+vit D). We conclude that intrauterine exposure of fetal rats to ETX during late gestation causes persistent impairment of RV-PA coupling throughout infancy that can be prevented with early vit D treatment.

  1. Treatment strategy for type 2 diabetes from the perspective of systemic vascular protection and insulin resistance

    Directory of Open Access Journals (Sweden)

    Utsunomiya K

    2012-07-01

    Full Text Available Kazunori UtsunomiyaDivision of Diabetes, Metabolism and Endocrinology, Jikei University School of Medicine, Tokyo, JapanAbstract: This paper provides an update on the mechanisms of vascular impairment associated with insulin resistance and the pathogenesis of diabetic nephropathy and peripheral artery disease (PAD. It also considers the optimal treatment strategies for systemic vascular protection in light of recent findings. This area is of major clinical importance given the ongoing global epidemic of type 2 diabetes and the pivotal role played by insulin resistance in the mechanism of vascular impairment that manifests as macroangiopathy and microangiopathy. Timely diagnosis and intervention is critical in patients with systemic arteriosclerotic disease. Therefore, treatment strategies are aimed not only at targeting the presenting pathology, but also at reducing the risk of cardiovascular events. These efforts can help reduce the risk of both cardiovascular events and mortality. Treatment for PAD includes pharmacotherapy, endovascular treatment, and vascular reconstruction, along with exercise therapy. Because PAD can cause ischemia in the lower extremities, typical drug approaches include use of vasodilators and antiplatelet agents. Beraprost sodium and cilostazol are common choices in Japan, and their risks and benefits are discussed. Of note, beraprost has several therapeutic properties, including vascular endothelial protection, and antiplatelet and anti-inflammatory effects, in addition to vasodilatory activity. In patients with PAD, these activities improve the pathological process in the lower extremities and reduce the incidence of systemic vascular events. Recent preclinical findings indicate that beraprost improves not only ischemic extremities through its vasodilatory properties, but also reduces the insulin resistance which affects vascular endothelium. In this way, beraprost may contribute to an overall systemic vascular

  2. A critical role for Egr-1 during vascular remodelling in pulmonary arterial hypertension

    NARCIS (Netherlands)

    Dickinson, Michael G.; Kowalski, Piotr S.; Bartelds, Beatrijs; Borgdorff, Marinus A. J.; van der Feen, Diederik; Sietsma, Hannie; Molema, Grietje; Kamps, Jan A. A. M.; Berger, Rolf M. F.

    2014-01-01

    Aims Pulmonary arterial hypertension (PAH) is characterized by the development of unique neointimal lesions in the small pulmonary arteries, leading to increased right ventricular (RV) afterload and failure. Novel therapeutic strategies are needed that target these neointimal lesions. Recently, the

  3. Relationship between Gastrointestinal Peptides, Intestinal Wall Compliance, and Vascular Resistance

    Science.gov (United States)

    1983-01-20

    elevations in pan - creatic secretions which were both enzyme and bicarbonate rich. These responses could be reproduced by Intravenous Infusions of low doses...Increases in blood flow to the duodenum, jejunum, and pan - creas (all three vascular beds are perfused by this artery). Yet, al- though the superior...Immunohisto- chemical localization of a vasodilatory polypeptide (VIP) in cerebro - vascular nerves. Brain Res. 113: 400-404, 1976, 135. Larsson, L,-I., J

  4. [Pathophysiology and classification of pulmonary hypertension].

    Science.gov (United States)

    Sládková, H; Jansa, P; Susa, Z; Aschermann, M

    2004-09-01

    Pulmonary hypertension is present when the mean pulmonary pressure is increased above 25 mm Hg in a rest or above 30 mm Hg during exercise. It is possible to divide it from different point of view. Well known is pathophysiologic classification and Venice classification suggested by WHO symposium 2003. The rise of arterial pulmonary pressure is caused by three essential abnormalities, these are elevated pulmonary vascular resistance, blood flow and pulmonary artery wedge pressure. Vasoconstriction, remodeling of vessels and in situ trombosis are pathogenetic mechanism which contribute to rise of pulmonary hypertension.

  5. Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury.

    Science.gov (United States)

    Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L; Connelly, Rhykka; Nakano, Yoshimitsu; Traber, Lillian D; Schmalstieg, Frank C; Herndon, David N; Enkhbaatar, Perenlei

    2012-11-01

    Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Sheep were randomized to a sham-injured control group (n=6) or ALI/sepsis group (n=7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24 h. Additional sheep (n=16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates. The injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (P<0.01 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (P<0.05 each). This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  6. Update in pulmonary arterial hypertension.

    Science.gov (United States)

    Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J

    2016-11-01

    Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations.

  7. Proteomic analysis of vascular smooth muscle cells in physiological condition and in pulmonary arterial hypertension: Toward contractile versus synthetic phenotypes.

    Science.gov (United States)

    Régent, Alexis; Ly, Kim Heang; Lofek, Sébastien; Clary, Guilhem; Tamby, Mathieu; Tamas, Nicolas; Federici, Christian; Broussard, Cédric; Chafey, Philippe; Liaudet-Coopman, Emmanuelle; Humbert, Marc; Perros, Frédéric; Mouthon, Luc

    2016-10-01

    Vascular smooth muscle cells (VSMCs) are highly specialized cells that regulate vascular tone and participate in vessel remodeling in physiological and pathological conditions. It is unclear why certain vascular pathologies involve one type of vessel and spare others. Our objective was to compare the proteomes of normal human VSMC from aorta (human aortic smooth muscle cells, HAoSMC), umbilical artery (human umbilical artery smooth muscle cells, HUASMC), pulmonary artery (HPASMC), or pulmonary artery VSMC from patients with pulmonary arterial hypertension (PAH-SMC). Proteomes of VSMC were compared by 2D DIGE and MS. Only 19 proteins were differentially expressed between HAoSMC and HPASMC while 132 and 124 were differentially expressed between HUASMC and HAoSMC or HPASMC, respectively (fold change 1.5≤ or -1.5≥, p < 0.05). As much as 336 proteins were differentially expressed between HPASMC and PAH-SMC (fold change 1.5≤ or -1.5≥, p < 0.05). HUASMC expressed increased amount of α-smooth muscle actin compared to either HPASMC or HAoSMC (although not statistically significant). In addition, PAH-SMC expressed decreased amount of smooth muscle myosin heavy chain and proliferation rate was increased compared to HPASMC thus supporting that PAH-SMC have a more synthetic phenotype. Analysis with Ingenuity identified paxillin and (embryonic lethal, abnormal vision, drosophila) like 1 (ELAVL1) as molecules linked with a lot of proteins differentially expressed between HPASMC and PAH-SMC. There was a trend toward reduced proliferation of PAH-SMC with paxillin-si-RNA and increased proliferation with ELAVL1-siRNA. Thus, VSMCs have very diverse protein content depending on their origin and this is in link with phenotypic differentiation. Paxillin targeting may be a promising treatment of PAH. ELAVL1 also participate in the regulation of PAH-SMC proliferation.

  8. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

    Science.gov (United States)

    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.

  9. An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo [Dept. of Radiology, Dong-A University Medicine Center, Dong-A University College of Medicine, Busan (Korea, Republic of); Ki, Chang Seok [Dept. of Radiology, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited disorder characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

  10. pulmonary performance in asymptomatic young nigerian population ...

    African Journals Online (AJOL)

    Bioline

    Ascorbic acid was given orally at a dose of 1.50 mg /kg body weight; and salbutamol at a dose of 70 ... vascular resistance in the pulmonary bed. The ... forces supporting and moving the lungs with ... Analysis of static pressure – volume data ... exercise (Aggarwal et al, 2000). ... effects of ascorbic acid on pulmonary function.

  11. Chronic allergic inflammation causes vascular remodeling and pulmonary hypertension in BMPR2 hypomorph and wild-type mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Mushaben

    Full Text Available Loss-of-function mutations in the bone morphogenetic protein receptor type 2 (BMPR2 gene have been identified in patients with heritable pulmonary arterial hypertension (PAH; however, disease penetrance is low, suggesting additional factors play a role. Inflammation is associated with PAH and vascular remodeling, but whether allergic inflammation triggers vascular remodeling in individuals with BMPR2 mutations is unknown. Our goal was to determine if chronic allergic inflammation would induce more severe vascular remodeling and PAH in mice with reduced BMPR-II signaling. Groups of Bmpr2 hypomorph and wild-type (WT Balb/c/Byj mice were exposed to house dust mite (HDM allergen, intranasally for 7 or 20 weeks to generate a model of chronic inflammation. HDM exposure induced similar inflammatory cell counts in all groups compared to controls. Muscularization of pulmonary arterioles and arterial wall thickness were increased after 7 weeks HDM, more severe at 20 weeks, but similar in both groups. Right ventricular systolic pressure (RVSP was measured by direct cardiac catheterization to assess PAH. RVSP was similarly increased in both HDM exposed groups after 20 weeks compared to controls, but not after 7 weeks. Airway hyperreactivity (AHR to methacholine was also assessed and interestingly, at 20 weeks, was more severe in HDM exposed Bmpr2 hypomorph mice versus WT. We conclude that chronic allergic inflammation caused PAH and while the severity was mild and similar between WT and Bmpr2 hypomorph mice, AHR was enhanced with reduced BMPR-II signaling. These data suggest that vascular remodeling and PAH resulting from chronic allergic inflammation occurs independently of BMPR-II pathway alterations.

  12. Additive effect of red blood cell rigidity and adherence to endothelial cells in inducing vascular resistance.

    Science.gov (United States)

    Kaul, D K; Koshkaryev, A; Artmann, G; Barshtein, G; Yedgar, S

    2008-10-01

    To explore the contribution of red blood cell (RBC) deformability and interaction with endothelial cells (ECs) to circulatory disorders, these RBC properties were modified by treatment with hydrogen peroxide (H(2)O(2)), and their effects on vascular resistance were monitored following their infusion into rat mesocecum vasculature. Treatment with 0.5 mM H(2)O(2) increased RBC/EC adherence without significant alteration of RBC deformability. At 5.0 mM H(2)O(2), RBC deformability was considerably reduced, inducing a threefold increase in the number of undeformable cells, whereas RBC/EC adherence was not further affected by the increased H(2)O(2) concentration. This enabled the selective manipulation of RBC adherence and deformability and the testing of their differential effect on vascular resistance. Perfusion of RBCs with enhanced adherence and unchanged deformability (treatment with 0.5 mM H(2)O(2)) increased vascular resistance by about 35% compared with untreated control RBCs. Perfusion of 5.0 mM H(2)O(2)-treated RBCs, with reduced deformability (without additional increase of adherence), further increased vascular resistance by about 60% compared with untreated control RBCs. These results demonstrate the specific effects of elevated adherence and reduced deformability of oxidized RBCs on vascular resistance. These effects can be additive, depending on the oxidation conditions. The oxidation-induced changes applied in this study are moderate compared with those observed in RBCs in pathological states. Yet, they caused a considerable increase in vascular resistance, thus demonstrating the potency of RBC/EC adherence and RBC deformability in determining resistance to blood flow in vivo.

  13. Combined effect of aerosolized iloprost and oxygen on assessment of pulmonary vasoreactivity in children with pulmonary hypertension.

    Science.gov (United States)

    Elkiran, Ozlem; Karakurt, Cemşit; Koçak, Gülendam

    2014-06-01

    The evaluation of pulmonary vascular reactivity plays a significant role in the management of patients with pulmonary hypertension. Inhaled nitric oxide in combination with oxygen (O2) has become widely used as an agent for pulmonary vasodilator testing. However, inhaled nitric oxide is not available in many developing countries. Recently, aerosolized iloprost was suggested as an alternative to nitric oxide for this purpose. In the present study, aerosolized iloprost was used together with O2 in the pulmonary vasoreactivity test of children with severe pulmonary hypertension. Thus, the synergistic effect of both vasodilators was utilized without extending the duration of cardiac catheterization. The prospective cohort study registered a total of 16 children with severe pulmonary hypertension whose median age was 4.5 years. Hemodynamic parameters were quantified before and after the vasoreactivity test. Increased left-to-right shunt, pulmonary vascular resistance of 10% in the pulmonary vascular resistance and pulmonary-systemic vascular resistance ratio after the vasoreactivity test were accepted as a positive response. The data were analyzed using Wilcoxon signed-rank and the Mann-Whitney U tests. Eleven children gave a positive response to the vasoreactivity test, while 5 children did not respond. Pulmonary vascular resistance dropped from 9.98 ± 1.39 WU/m(2) to 5.08 ± 1.05 WU/m(2) (p=0.013) and the pulmonary-systemic vascular resistance ratio fell from 0.68 ± 0.08 to 0.32 ± 0.05 (p=0.003) in the children who were responsive. No side effects were observed related to iloprost administration. Administration of inhaled iloprost in combination with O2 for pulmonary vasoreactivity testing can be useful for correctly identifying pulmonary vasoreactivity without extending the duration of cardiac catheterization.

  14. Brown Fat Lipoatrophy and Increased Visceral Adiposity through a Concerted Adipocytokines Overexpression Induces Vascular Insulin Resistance and Dysfunction

    National Research Council Canada - National Science Library

    Gómez-Hernández, Almudena; Otero, Yolanda F; de las Heras, Natalia; Escribano, Óscar; Cachofeiro, Victoria; Lahera, Vicente; Benito, Manuel

    2012-01-01

    In this study, we analyzed the role played by concerted expression of adipocytokines associated with brown fat lipoatrophy and increased visceral adiposity on triggering vascular insulin resistance...

  15. Contribution of perfusion pressure to vascular resistance response during head-up tilt

    Science.gov (United States)

    Imadojemu, V. A.; Lott, M. E.; Gleeson, K.; Hogeman, C. S.; Ray, C. A.; Sinoway, L. I.

    2001-01-01

    We measured brachial and femoral artery flow velocity in eight subjects and peroneal and median muscle sympathetic nerve activity (MSNA) in five subjects during tilt testing to 40 degrees. Tilt caused similar increases in MSNA in the peroneal and median nerves. Tilt caused a fall in femoral artery flow velocity, whereas no changes in flow velocity were seen in the brachial artery. Moreover, with tilt, the increase in the vascular resistance employed (blood pressure/flow velocity) was greater and more sustained in the leg than in the arm. The ratio of the percent increase in vascular resistance in leg to arm was 2.5:1. We suggest that the greater vascular resistance effects in the leg were due to an interaction between sympathetic nerve activity and the myogenic response.

  16. [Significance of extravascular lung water index, pulmonary vascular permeability index, and in- trathoracic blood volume index in the differential diagnosis of burn-induced pulmonary edema].

    Science.gov (United States)

    Lei, Li; Jiajun, Sheng; Guangyi, Wang; Kaiyang, Lyu; Jing, Qin; Gongcheng, Liu; Bing, Ma; Shichu, Xiao; Shihui, Zhu

    2015-06-01

    To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and

  17. Pulmonary vascular volume ratio measured by cardiac computed tomography in children and young adults with congenital heart disease: comparison with lung perfusion scintigraphy.

    Science.gov (United States)

    Goo, Hyun Woo; Park, Sang Hyub

    2017-06-23

    Lung perfusion scintigraphy is regarded as the gold standard for evaluating differential lung perfusion ratio in congenital heart disease. To compare cardiac CT with lung perfusion scintigraphy for estimated pulmonary vascular volume ratio in patients with congenital heart disease. We included 52 children and young adults (median age 4 years, range 2 months to 28 years; 31 males) with congenital heart disease who underwent cardiac CT and lung perfusion scintigraphy without an interim surgical or transcatheter intervention and within 1 year. We calculated the right and left pulmonary vascular volumes using threshold-based CT volumetry. Then we compared right pulmonary vascular volume percentages at cardiac CT with right lung perfusion percentages at lung perfusion scintigraphy by using paired t-test and Bland-Altman analysis. The right pulmonary vascular volume percentages at cardiac CT (66.3 ± 14.0%) were significantly smaller than the right lung perfusion percentages at lung perfusion scintigraphy (69.1 ± 15.0%; P=0.001). Bland-Altman analysis showed a mean difference of -2.8 ± 5.8% and 95% limits of agreement (-14.1%, 8.5%) between these two variables. Cardiac CT, in a single examination, can offer pulmonary vascular volume ratio in addition to pulmonary artery anatomy essential for evaluating peripheral pulmonary artery stenosis in patients with congenital heart disease. However there is a wide range of agreement between cardiac CT and lung perfusion scintigraphy.

  18. Hypoxia-inducible factor-1 α/platelet derived growth factor axis in HIV-associated pulmonary vascular remodeling

    Directory of Open Access Journals (Sweden)

    Bartolome Sonja

    2011-08-01

    Full Text Available Abstract Background Human immunodeficiency virus (HIV infected patients are at increased risk for the development of pulmonary arterial hypertension (PAH. Recent reports have demonstrated that HIV associated viral proteins induce reactive oxygen species (ROS with resultant endothelial cell dysfunction and related vascular injury. In this study, we explored the impact of HIV protein induced oxidative stress on production of hypoxia inducible factor (HIF-1α and platelet-derived growth factor (PDGF, critical mediators implicated in the pathogenesis of HIV-PAH. Methods The lungs from 4-5 months old HIV-1 transgenic (Tg rats were assessed for the presence of pulmonary vascular remodeling and HIF-1α/PDGF-BB expression in comparison with wild type controls. Human primary pulmonary arterial endothelial cells (HPAEC were treated with HIV-associated proteins in the presence or absence of pretreatment with antioxidants, for 24 hrs followed by estimation of ROS levels and western blot analysis of HIF-1α or PDGF-BB. Results HIV-Tg rats, a model with marked viral protein induced vascular oxidative stress in the absence of active HIV-1 replication demonstrated significant medial thickening of pulmonary vessels and increased right ventricular mass compared to wild-type controls, with increased expression of HIF-1α and PDGF-BB in HIV-Tg rats. The up-regulation of both HIF-1α and PDGF-B chain mRNA in each HIV-Tg rat was directly correlated with an increase in right ventricular/left ventricular+septum ratio. Supporting our in-vivo findings, HPAECs treated with HIV-proteins: Tat and gp120, demonstrated increased ROS and parallel increase of PDGF-BB expression with the maximum induction observed on treatment with R5 type gp-120CM. Pre-treatment of endothelial cells with antioxidants or transfection of cells with HIF-1α small interfering RNA resulted in abrogation of gp-120CM mediated induction of PDGF-BB, therefore, confirming that ROS generation and

  19. Experiência com transplante cardíaco heterotópico em pacientes com resistência pulmonar elevada: seguimento tardio Experiencia con trasplante cardíaco heterotópico en pacientes con resistencia pulmonar elevada: seguimiento tardío Experience with heterotopic heart transplantation in patients with elevated pulmonary vascular resistance: late follow-up

    Directory of Open Access Journals (Sweden)

    Jose Henrique Andrade Vila

    2010-02-01

    este tipo de alternativa, para pacientes seleccionados.BACKGROUND: Along the past few years the number of papers on heterotopic cardiac transplant has been very scarce in the medical literature, including at the international level; this is particularly true in reference to the long term follow-up of these patients and the reason which led to the presentation of our report. OBJECTIVE: To report the initial clinical experience and late evolution of 4 patients undergoing heterotopic heart transplantation, indications for this procedure and its major complications. METHODS: The surgeries were performed between 1992 and 2001, and all had as indication for heterotopic transplantation the PVR, which ranged from 4.8 WU to 6.5WU, with a transpulmonary gradient above 15mmHg. In the 3rd patient, a direct anastomosis between the pulmonary arteries was performed without the use of a prostetic tube, and a mitral valvuloplasty and a LV aneurysmectomy were performed in the native heart. The immediate immunosuppressive regimens were double, with cyclosporine and azathioprine in the first 3 patients, and cyclosporine and mycophenolate mofetil in the 4th patient. RESULTS: One immediate death occurred from graft failure, one death occurred after 2 ½ years, from endocarditis in an intraventricular thrombus in the native heart, and a third death occurred 6 years after transplantation, from post-operative complications of the aortic valve surgery in the native heart. The remaining patient is well, 15 years after the transplantation. This patient is in functional class II (NYHA, 6 years after a surgical occlusion of the native heart aortic valve. CONCLUSION: Heterotopic heart transplantation results are inferior to those of orthotopic heart transplantation because they present higher RVP. The intraventricular thrombi, in the native heart, which require prolonged anticoagulation, and aortic valve complications, also in the native heart, may require surgical treatment. However, a patient's 15

  20. Transforming growth factor-β plays divergent roles in modulating vascular remodeling, inflammation, and pulmonary fibrosis in a murine model of scleroderma.

    Science.gov (United States)

    Tsujino, Kazuyuki; Reed, Nilgun Isik; Atakilit, Amha; Ren, Xin; Sheppard, Dean

    2017-01-01

    The efficacy and feasibility of targeting transforming growth factor-β (TGFβ) in pulmonary fibrosis and lung vascular remodeling in systemic sclerosis (SSc) have not been well elucidated. In this study we analyzed how blocking TGFβ signaling affects pulmonary abnormalities in Fos-related antigen 2 (Fra-2) transgenic (Tg) mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling. To interrupt TGFβ signaling in the Fra-2 Tg mice, we used a pan-TGFβ-blocking antibody, 1D11, and Tg mice in which TGFβ receptor type 2 (Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (α-SMA-Cre(ER);Tgfbr2(flox/flox)). Global inhibition of TGFβ by 1D11 did not ameliorate lung fibrosis histologically or biochemically, whereas it resulted in a significant increase in the number of immune cells infiltrating the lungs. In contrast, 1D11 treatment ameliorated the severity of pulmonary vascular remodeling in Fra-2 Tg mice. Similarly, genetic deletion of Tgfbr2 from smooth muscle cells resulted in improvement of pulmonary vascular remodeling in the Fra-2 Tg mice, as well as a decrease in the number of Ki67-positive vascular smooth muscle cells, suggesting that TGFβ signaling contributes to development of pulmonary vascular remodeling by promoting the proliferation of vascular smooth muscle cells. Deletion of Tgfbr2 from α-smooth muscle actin-expressing cells had no effect on fibrosis or inflammation in this model. These results suggest that efforts to target TGFβ in SSc will likely require more precision than simply global inhibition of TGFβ function. Copyright © 2017 the American Physiological Society.

  1. Prediction of distribution volume of vancomycin in critically ill patients using extravascular lung water and pulmonary vascular permeability indices.

    Science.gov (United States)

    Imaura, Masaharu; Yokoyama, Haruko; Kohyama, Tomoki; Nagafuchi, Hiroyuki; Kohata, Yuji; Takahashi, Hiroyuki; Yamada, Yasuhiko

    2012-11-01

    Alterations in distribution volume affect the concentrations of hydrophilic drugs in plasma and tissues at the time of initial therapy. When the distribution volume of hydrophilic antimicrobials is increased in critically ill patients with a serious infection, antimicrobial concentrations are reduced, which may adversely affect the efficacy of antimicrobial therapy. A transpulmonary thermodilution technique system (PiCCO) enables measurements of pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), which are related to pulmonary edema and pulmonary vascular permeability, respectively. In addition, those indices may also be related to the distribution volume of hydrophilic antimicrobials. The aim of this study was to investigate the relationships of PVPI and EVLWI with the distribution volume of vancomycin (Vss), as well as to establish a method for estimating Vss for planning an appropriate initial dose for individual patients. Seven patients were administered vancomycin intravenously and underwent extended hemodynamic monitoring with the PiCCO system in the intensive care unit (ICU) from April 2009 to March 2011. Vss was calculated using the Bayesian method, and the relationships of PVPI and EVLWI with Vss were investigated. The relationship between Vss/actual body weight (ABW) and median EVLWI on days when blood levels were measured was significant (r = 0.900, p = 0.0057), whereas the relationship between Vss/ABW and PVPI was not significant (r = 0.649, p = 0.1112). EVLWI determined by the PiCCO system is useful to predict Vss and should lead to more effective vancomycin therapy for critically ill patients at the initial stage.

  2. Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

    Science.gov (United States)

    Steven, Sebastian; Oelze, Matthias; Brandt, Moritz; Ullmann, Elisabeth; Kröller-Schön, Swenja; Heeren, Tjebo; Tran, Lan P.; Daub, Steffen; Dib, Mobin; Stalleicken, Dirk; Wenzel, Philip; Münzel, Thomas

    2017-01-01

    Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

  3. Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Sebastian Steven

    2017-01-01

    Full Text Available Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH. The role of the nitrovasodilator pentaerythritol tetranitrate (PETN on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v. in Wistar rats. Low (30 mg/kg; MCT30, middle (40 mg/kg; MCT40, or high (60 mg/kg; MCT60 dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d and reduced by oral PETN (10 mg/kg, 24 d therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1. PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1 in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

  4. Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension.

    Science.gov (United States)

    Steven, Sebastian; Oelze, Matthias; Brandt, Moritz; Ullmann, Elisabeth; Kröller-Schön, Swenja; Heeren, Tjebo; Tran, Lan P; Daub, Steffen; Dib, Mobin; Stalleicken, Dirk; Wenzel, Philip; Münzel, Thomas; Daiber, Andreas

    2017-01-01

    Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

  5. Anesthetic Management of Pediatric Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Mediha Turktan

    2015-06-01

    Full Text Available Pulmonary arterial hypertension is the most important cause of morbidity and mortality associated with congenital heart disease. Patients in this group have a greater peroperative cardiovascular risks including cardiac arrest, pulmonary hypertensive crisis and death compared the normal population. The main purpose of anesthesia is to avoid increased pulmonary vascular resistance and myocardial depression. [Archives Medical Review Journal 2015; 24(2.000: 149-158

  6. Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    López Gude, María Jesús; Pérez de la Sota, Enrique; Pérez Vela, Jose Luís; Centeno Rodríguez, Jorge; Muñoz Guijosa, Christian; Velázquez, María Teresa; Alonso Chaterina, Sergio; Hernández González, Ignacio; Escribano Subías, Pilar; Cortina Romero, José María

    2017-07-07

    Pulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Since February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/sec/cm(-5), and group 2, which included the remaining 120 patients. Hospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (P=.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). Pulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  7. Rapamycin attenuates hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy in mice

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    Tillmanns Harald H

    2007-02-01

    Full Text Available Abstract Background Chronic hypoxia induces pulmonary arterial hypertension (PAH. Smooth muscle cell (SMC proliferation and hypertrophy are important contributors to the remodeling that occurs in chronic hypoxic pulmonary vasculature. We hypothesized that rapamycin (RAPA, a potent cell cycle inhibitor, prevents pulmonary hypertension in chronic hypoxic mice. Methods Mice were held either at normoxia (N; 21% O2 or at hypobaric hypoxia (H; 0.5 atm; ~10% O2. RAPA-treated animals (3 mg/kg*d, i.p. were compared to animals injected with vehicle alone. Proliferative activity within the pulmonary arteries was quantified by staining for Ki67 (positive nuclei/vessel and media area was quantified by computer-aided planimetry after immune-labeling for α-smooth muscle actin (pixel/vessel. The ratio of right ventricle to left ventricle plus septum (RV/[LV+S] was used to determine right ventricular hypertrophy. Results Proliferative activity increased by 34% at day 4 in mice held under H (median: 0.38 compared to N (median: 0.28, p = 0.028 which was completely blocked by RAPA (median HO+RAPA: 0.23, p = 0.003. H-induced proliferation had leveled off within 3 weeks. At this time point media area had, however, increased by 53% from 91 (N to 139 (H, p Conclusion Therapy with rapamycin may represent a new strategy for the treatment of pulmonary hypertension.

  8. High isoniazid resistance rates in rifampicin susceptible Mycobacterium tuberculosis pulmonary isolates from Pakistan.

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    Naima Fasih

    Full Text Available BACKGROUND: Rapid new diagnostic methods (including Xpert MTB/RIF assay use rifampicin resistance as a surrogate marker for multidrug resistant tuberculosis. Patients infected with rifampicin susceptible strains are prescribed first line anti-tuberculosis therapy. The roll out of such methods raises a concern that strains with resistance to other first line anti-tuberculosis drugs including isoniazid will be missed and inappropriate treatment given. To evaluate implications of using such methods review of resistance data from high burden settings such as ours is essential. OBJECTIVE: To determine resistance to first line anti-tuberculosis drugs amongst rifampicin susceptible pulmonary Mycobacterium tuberculosis (MTB isolates from Pakistan. MATERIALS AND METHODS: Data of pulmonary Mycobacterium tuberculosis strains isolated in Aga Khan University Hospital (AKUH laboratory (2009-2011 was retrospectively analyzed. Antimicrobial susceptibility profile of rifampicin susceptible isolates was evaluated for resistance to isoniazid, pyrazinamide, ethambutol, and streptomycin. RESULTS: Pulmonary specimens submitted to AKUH from 2009 to 2011 yielded 7738 strains of Mycobacterium tuberculosis. These included 54% (n 4183 rifampicin susceptible and 46% (n: 3555 rifampicin resistant strains. Analysis of rifampicin susceptible strains showed resistance to at least one of the first line drugs in 27% (n:1133 of isolates. Overall isoniazid resistance was 15.5% (n: 649, with an isoniazid mono-resistance rate of 4% (n: 174. Combined resistance to isoniazid, pyrazinamide, and ethambutol was noted in 1% (n: 40, while resistance to isoniazid, pyrazinamide, ethambutol, and streptomycin was observed in 1.7% (n: 70 of strains. CONCLUSIONS: Our data suggests that techniques (including Xpert MTB/RIF assay relying on rifampicin susceptibility as an indicator for initiating first line therapy will not detect patients infected with MTB strains resistant to other first line

  9. Differential effects of formoterol on thrombin- and PDGF-induced proliferation of human pulmonary arterial vascular smooth muscle cells

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    Goncharova Elena A

    2012-11-01

    Full Text Available Abstract Background Increased pulmonary arterial vascular smooth muscle (PAVSM cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH. The long-acting β2-adrenergic receptor (β2AR agonist formoterol, a racemate comprised of (R,R- and (S,S-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD. PH, a common complication of COPD, increases patients’ morbidity and reduces survival. Recent studies demonstrate that formoterol has anti-proliferative effects on airway smooth muscle cells and bronchial fibroblasts. The effects of formoterol and its enantiomers on PAVSM cell proliferation are not determined. The goals of this study were to examine effects of racemic formoterol and its enantiomers on PAVSM cell proliferation as it relates to COPD-associated PH. Methods Basal, thrombin-, PDGF- and chronic hypoxia-induced proliferation of primary human PAVSM cells was examined by DNA synthesis analysis using BrdU incorporation assay. ERK1/2, mTORC1 and mTORC2 activation were determined by phosphorylation levels of ERK1/2, ribosomal protein S6 and S473-Akt using immunoblot analysis. Results We found that (R,R and racemic formoterol inhibited basal, thrombin- and chronic hypoxia-induced proliferation of human PAVSM cells while (S,S formoterol had lesser inhibitory effect. The β2AR blocker propranolol abrogated the growth inhibitory effect of formoterol. (R,R, but not (S,S formoterol attenuated basal, thrombin- and chronic hypoxia-induced ERK1/2 phosphorylation, but had little effect on Akt and S6 phosphorylation levels. Formoterol and its enantiomers did not significantly affect PDGF-induced DNA synthesis and PDGF-dependent ERK1/2, S473-Akt and S6 phosphorylation in human PAVSM cells. Conclusions Formoterol inhibits basal, thrombin-, and chronic hypoxia-, but not PDGF-induced human PAVSM cell proliferation and ERK1/2, but has little effect on

  10. The effects of angiotensin II receptor antagonist (candesartan on rat renal vascular resistance

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    Supatraviwat, J

    2004-05-01

    Full Text Available The present study aimed to investigate the action of angiotensin II (AII on renal perfusion pressure and renal vascular resistance using noncompetitive AT1-receptor antagonist (candesartan or CV 11974. Experiments were performed in isolated kidney of adult male Wistar rats. Kreb's Henseleit solution was perfused into the renal artery at the rate of 3.5 ml/min. This flow rate was designed in order to maintain renal perfusion pressure between 80-120 mm Hg. Dose-response relationship between perfusion flow rate and AII concentration were studied. Renal perfusion pressure in response to 1, 10 and 100 nM AII were increased from basal perfusion pressure of 94±8 mm Hg to 127±6, 157±12 and 190±16 mm Hg, respectively. Administration of perfusate containing 11.4 μM candesartan for 30 min had no effect on the basal perfusion pressure. However, this significantly reduced renal perfusion pressure in the presence of AII (1, 10 and 100 nM by 39%, 47% and 61%, (n=7, P<0.05 respectively. At the basal perfusion pressure, calculated renal vascular resistance was 27±2 mm Hg · min · ml-1. However, the vascular resistance were found to be 41±1, 45±2 and 47±2 mm Hg · min · ml-1 when 1, 10 and 100 nM AII were added. Moreover, this dose of candesartan also showed a significant decrease in renal vascular resistance at the corresponding doses of AII by 38%, 48% and 43%, (n=7, P<0.05 respectively. The higher dose of candesartan (22.7 μM completely inhibited the action of 1, 10 and 100 nM AII on renal vasoconstriction. These results may indicate that the action of AII on renal vascular resistance is via AT1-receptor, at least in rat isolated perfusion kidney.

  11. Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Bojesen, Stig E; Nordestgaard, Børge G

    2012-01-01

    The aim of this review is to summarize present knowledge of genetic variation in cytochrome P450 1B1 (CYP1B1) and 2C9 (CYP2C9) genes and risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease. The CYP1B1 and CYP2C9 enzymes metabolize pol...

  12. Pulmonary artery haemodynamic properties in patients with pulmonary hypertension secondary to rheumatic mitral stenosis.

    Science.gov (United States)

    Yan, Tao; Zhang, Guan-xin; Li, Bai-lin; Zhong, Keng; Xu, Zhi-yun; Han, Lin

    2012-12-01

    We sought to explore the pulmonary haemodynamic changes in rheumatic mitral stenosis patients with secondary pulmonary hypertension. The pulmonary artery resistance and compliance of 35 patients with rheumatic mitral stenosis and 12 controls without cardiopulmonary vascular disease were evaluated by using an improved method, which is based on making calculations with parameters obtained from right heart catheterisation. The results are as follows: (1) pulmonary artery compliance in patients with secondary pulmonary hypertension was significantly lower than that of the control group (P0.05) The walls of pulmonary artery vessels in patients with pulmonary hypertension secondary to rheumatic mitral stenosis appeared to be remodelled by varying degrees as indicated by their haemodynamic properties. Structural remodelling may be a factor affecting preoperative pulmonary artery pressure. Mitral stenosis patients with severe pulmonary hypertension have significantly lower responses to sodium nitroprusside possibly due to aggradation and deposition of collagen in the artery walls, decreasing constriction and dilation, or atrophy of smooth muscle cells.

  13. Determination of renal vascular resistance in dogs with diabetes mellitus and hyperadrenocorticism.

    Science.gov (United States)

    Novellas, R; de Gopegui, R Ruiz; Espada, Y

    2008-11-15

    In dogs, diabetes mellitus and hyperadrenocorticism are causes of hypertension associated with increases in vascular peripheral resistance. In human patients, the renal resistive index (ri) and pulsatility index (pi) are related to hypertension and diabetes and are used as indicators of disease severity. In this study the renal vascular resistance was measured in 12 dogs with hyperadrenocorticism, three with diabetes mellitus and four with both conditions, and the possible relationships between the two indices, blood pressure and biochemical parameters were investigated. Hypertension, defined as a systolic blood pressure more than 150 mmHg, was recorded in two of the dogs with hyperadrenocorticism and three of the dogs with hyperadrenocorticism and diabetes. The overall mean values for ri, pi and systolic blood pressure were higher in the diseased group of dogs than in 27 healthy dogs, and both indices were correlated with blood glucose concentration.

  14. Deletion of mineralocorticoid receptors in smooth muscle cells blunts renal vascular resistance following acute cyclosporine administration

    Science.gov (United States)

    Amador, Cristian A.; Bertocchio, Jean-Philippe; Andre-Gregoire, Gwennan; Placier, Sandrine; Van Huyen, Jean-Paul Duong; El Moghrabi, Soumaya; Berger, Stefan; Warnock, David G.; Chatziantoniou, Christos; Jaffe, Iris Z.; Rieu, Philippe; Jaisser, Frederic

    2016-01-01

    Calcineurin inhibitors such as cyclosporine A (CsA) are still commonly used after renal transplantation, despite CsA–induced nephrotoxicity (CIN), which is partly related to vasoactive mechanisms. The mineralocorticoid receptor (MR) is now recognized as a key player in the control of vascular tone, and both endothelial cell- and vascular smooth muscle cell (SMC)-MR modulate the vasoactive responses to vasodilators and vasoconstrictors. Here we tested whether vascular MR is involved in renal hemodynamic changes induced by CsA. The relative contribution of vascular MR in acute CsA treatment was evaluated using mouse models with targeted deletion of MR in endothelial cell or SMC. Results indicate that MR expressed in SMC, but not in endothelium, contributes to the increase of plasma urea and creatinine, the appearance of isometric tubular vacuolization, and overexpression of a kidney injury biomarker (neutrophil gelatinase–associated lipocalin) after CsA treatment. Inactivation of MR in SMC blunted CsA–induced phosphorylation of contractile proteins. Finally, the in vivo increase of renal vascular resistance induced by CsA was blunted when MR was deleted from SMC cells, and this was associated with decreased L-type Ca2+ channel activity. Thus, our study provides new insights into the role of vascular MR in renal hemodynamics during acute CIN, and provides rationale for clinical studies of MR antagonism to manage the side effects of calcineurin inhibitors. PMID:26422501

  15. The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans.

    Science.gov (United States)

    Ghimire, Anukul; Andersen, Mads J; Burrowes, Lindsay M; Bouwmeester, J Christopher; Grant, Andrew D; Belenkie, Israel; Fine, Nowell M; Borlaug, Barry A; Tyberg, John V

    2016-12-01

    Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies.

  16. Peroxynitrite-mediated pulmonary vascular injury induced by endotoxin and protective role of cholecystokinin

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this study we found: 1\\, There was endogenous ONOO- formation in lungs in the early stage of endotoxic shock. Exogenous ONOO- led to increase in microvascular permeability, severe lung pathological changes and enhanced MDA content. 2\\, It was, for the first time, found that responses of isolated pulmonary artery preincubated with ONOO- showed abnormal manifestations. (1) Low dose of ONOO- let to the inhibition of endothelial dependent relaxation, but enhacement of contractile response, both of which were similar to changes of reactivity in isolated pulmonary artery induced by LPS. (2) High dose of ONOO- reduced contractile response to PE and relaxation to SNP. 3\\, ONOO- had direct effect for relaxation of precontracted isolated pulmonary artery. The relaxing action of ONOO- was weak and was negtively regulated by endothelial cells, supporting the notion that ONOO- may be involved in pulmonary hypertension in the early stage of endotoxic shock. 4\\, It was, for the first time, found that LPS-induced increase in endogenous ONOO- generation in BPAEC and that endogenous ONOO- mediated injury to BPAEC induced by LPS, which may be a novel mechanism for endotoxin-elicited damage to endothelial cells. 5\\, Exposure of pulmonary artery to LPS led to reduction in endothelial dependent relaxation but enhancement in contractile response, both of which were reversed by concomitant exposure to CCK and LPS. 6\\, CCK protected cultured BPAEC against the detrimental effects of LPS such as lipoperoxide damages and cellular apoptosis as well as LPS-induced endogenous ONOO- formation. The underlying mechanism of CCK for cytoprotection may be mediated by its receptors and related to its reduced ability of endothelia to generate ONOO- induced by LPS.

  17. Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

    DEFF Research Database (Denmark)

    Oppermann, Mona; Hansen, Pernille B; Castrop, Hayo;

    2007-01-01

    Loop diuretics like furosemide have been shown to cause renal vasodilatation in dogs and humans, an effect thought to result from both a direct vascular dilator effect and from inhibition of tubuloglomerular feedback. In isolated perfused afferent arterioles preconstricted with angiotensin II or N...... that furosemide, despite its direct vasodilator potential in isolated afferent arterioles, causes a marked increase in flow resistance of the vascular bed of the intact mouse kidney. We suggest that generation of angiotensin II and/or a vasoconstrictor prostaglandin combined with compression of peritubular...

  18. Pulmonary Hypertension in Elderly Patients with Diastolic Dysfunction and Preserved Ejection Fraction

    Science.gov (United States)

    Afshar, Majid; Collado, Fareed; Doukky, Rami

    2012-01-01

    Purpose: Patients with diastolic dysfunction may have a disproportionate degree of elevation in pulmonary pressure, particularly in the elderly. Higher pulmonary vascular resistance in the elderly patients with heart failure but preserved ejection fraction suggests that beyond the post-capillary contribution of pulmonary venous congestion, a pre-capillary component of pulmonary arterial hypertension occurs. We aim to identify if pulmonary vascular resistance in elderly patients with diastolic dysfunction is disproportionately higher than patients with systolic dysfunction independent of filling pressures. Methods: 389 patients identified retrospectively between 2003- 2010; elderly with preserved ejection fraction, elderly with depressed ejection fraction, and primary arterial hypertension who underwent right-heart catheterization at Rush University. Results: No significant difference in pulmonary vascular resistance between systolic and diastolic dysfunction. The mean difference in pulmonary vascular resistance was not statistically significant at 0.40 mmHg·min/l (95% CI -3.03 to 3.83) with similar left ventricular filling pressures with mean difference of 3.38 mmHg (95% CI, -1.27 to 8.02). When adjusted for filling pressures, there remained no difference in pulmonary vascular resistance for systolic and diastolic dysfunction. The mean pulmonary vascular resistance is more elevated in systolic heart failure compared to diastolic heart failure with means 3.13 mmHg·min/l and 3.52 mmHg·min/l, respectively. Conclusion: There was no other association identified for secondary pulmonary hypertension other than diastolic dysfunction and chronic venous pulmonary hypertension. Our results argue against any significant arterial remodeling that would lead to disproportionate pre-capillary hypertension, and implies that treatment should focus on lowering filling pressure rather than treating the pulmonary vascular tree. PMID:22282715

  19. Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Bojesen, Stig E; Nordestgaard, Børge G

    2012-01-01

    The aim of this review is to summarize present knowledge of genetic variation in cytochrome P450 1B1 (CYP1B1) and 2C9 (CYP2C9) genes and risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease. The CYP1B1 and CYP2C9 enzymes metabolize...... between genetic variation in CYP1B1 and CYP2C9 and risk of disease with considerable statistical power rebutted the hypotheses that these genetic variants affect risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease....... of female cancer or ischemic vascular disease. Genetic variation in genes coding for CYP1B1 and CYP2C9 enzymes have shown altered enzyme activity affecting levels of metabolites and thus potentially risk of disease. So far, however, findings have been inconsistent. Recently, large studies on the association...

  20. Fundamentals of management of acute postoperative pulmonary hypertension.

    Science.gov (United States)

    Taylor, Mary B; Laussen, Peter C

    2010-03-01

    In the last several years, there have been numerous advancements in the field of pulmonary hypertension as a whole, but there have been few changes in the management of children with pulmonary hypertension after cardiac surgery. Patients at particular risk for postoperative pulmonary hypertension can be identified preoperatively based on their cardiac disease and can be grouped into four broad categories based on the mechanisms responsible for pulmonary hypertension: 1) increased pulmonary vascular resistance; 2) increased pulmonary blood flow with normal pulmonary vascular resistance; 3) a combination of increased pulmonary vascular resistance and increased blood flow; and 4) increased pulmonary venous pressure. In this review of the immediate postoperative management of pulmonary hypertension, various strategies are discussed including medical therapies, monitoring, ventilatory strategies, and weaning from these supports. With early recognition of patients at particular risk for severe pulmonary hypertension, management strategies can be directed at preventing or minimizing hemodynamic instability and thereby prevent the development of ventricular dysfunction and a low output state.

  1. Haemophilus influenzae induces a potentiated increase in guinea-pig pulmonary resistance to histamine

    NARCIS (Netherlands)

    Folkerts, G.; Nijkamp, F.P.

    1985-01-01

    The human respiratory pathogen Haemophilus influenzae (H.i.) induced bronchial hyperreactivity to histamine (1.0–8.0 μg/100 g b.w. i.v.) in vivo in anaesthetized spontaneously breathing guinea-pigs. This hyperreactivity was caused by a potentiated increase in pulmonary resistance. Decreases in dynam

  2. Capreomycin-induced optic neuritis in a case of multidrug resistant pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Magazine Rahul

    2010-01-01

    Full Text Available A patient of multidrug-resistant pulmonary tuberculosis was prescribed an anti-tubercular regimen containing capreomycin. Patient developed optic neuritis 3 months after starting treatment. Investigations did not reveal any specific cause for this ocular condition and on discontinuing capreomycin his vision recovered. We conclude that capreomycin is the cause of reversible optic neuritis in our case.

  3. Dual-energy CT based vascular iodine analysis improves sensitivity for peripheral pulmonary artery thrombus detection: An experimental study in canines

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chun Xiang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Zhang, Long Jiang, E-mail: kevinzhlj@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Han, Zong Hong; Zhou, Chang Sheng [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Krazinski, Aleksander W.; Silverman, Justin R. [Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China)

    2013-12-01

    Purpose: To evaluate the performance of dual-energy CT (DECT) based vascular iodine analysis for the detection of acute peripheral pulmonary thrombus (PE) in a canine model with histopathological findings as the reference standard. Materials and methods: The study protocol was approved by our institutional animal committee. Thrombi (n = 12) or saline (n = 4) were intravenously injected via right femoral vein in sixteen dogs, respectively. CT pulmonary angiography (CTPA) in DECT mode was performed and conventional CTPA images and DECT based vascular iodine studies using Lung Vessels application were reconstructed. Two radiologists visually evaluated the number and location of PEs using conventional CTPA and DECT series on a per-animal and a per-clot basis. Detailed histopathological examination of lung specimens and catheter angiography served as reference standard. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of DECT and CTPA were calculated on a segmental and subsegmental or more distal pulmonary artery basis. Weighted κ values were computed to evaluate inter-modality and inter-reader agreement. Results: Thirteen dogs were enrolled for final image analysis (experimental group = 9, control group = 4). Histopathological results revealed 237 emboli in 45 lung lobes in 9 experimental dogs, 11 emboli in segmental pulmonary arteries, 49 in subsegmental pulmonary arteries, 177 in fifth-order or more distal pulmonary arteries. Overall sensitivity, specificity, accuracy, PPV, and NPV for CTPA plus DECT were 93.1%, 76.9%, 87.8%, 89.4%, and 84.2% for the detection of pulmonary emboli. With CTPA versus DECT, sensitivities, specificities, accuracies, PPVs, and NPVs are all 100% for the detection of pulmonary emboli on a segmental pulmonary artery basis, 88.9%, 100%, 96.0%, 100%, and 94.1% for CTPA and 90.4%, 93.0%, 92.0%, 88.7%, and 94.1% for DECT on a subsegmental pulmonary artery basis; 23.8%, 96.4%, 50.4%, 93

  4. Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.

    Science.gov (United States)

    Bart, Nicole K; Curtis, M Kate; Cheng, Hung-Yuan; Hungerford, Sara L; McLaren, Ross; Petousi, Nayia; Dorrington, Keith L; Robbins, Peter A

    2016-08-01

    Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.

  5. HIF2α–arginase axis is essential for the development of pulmonary hypertension

    OpenAIRE

    Cowburn, Andrew S.; Crosby, Alexi; Macias, David; Branco, Cristina; Colaço, Renato D. D. R.; Southwood, Mark; Toshner, Mark; Crotty Alexander, Laura E.; Morrell, Nicholas W.; Chilvers, Edwin R.; Johnson, Randall S.

    2016-01-01

    The expression of hypoxia-inducible factor (HIF)-2α in pulmonary endothelium of mice influences pulmonary vascular resistance and development of hypoxic pulmonary hypertension (PH) via an arginase-1–dependent mechanism. The HIF-2α:arginase-1 axis influences the homeostatic regulation of nitric oxide synthesis in the lung. Impaired generation of this vasoactive agent contributes to the initial development and vascular remodeling process of PH.

  6. The effects of epinine on arterial blood pressure and regional vascular resistances in anesthetized rats.

    Science.gov (United States)

    Martínez-Mir, I; Palop, V; Morales-Olivas, F J; Estañ, L; Rubio, E

    1998-07-01

    1. We carried out experiments in anesthetized rats to study the hemodynamic effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg) produced a biphasic effect on mean arterial blood pressure (n = 30). At doses lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as 21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the hypotensive effect of epinine but did not change the hypertensive effect. In the presence of prazosin (1,000 micrograms/kg), arterial blood pressure remained significantly decreased at all doses of epinine. Neither sulpiride nor prazosin changed the bradycardic effect of epinine. 3. Prazosin produced a significant decrease in renal vascular resistance. Epinine (5 micrograms/kg) after prazosin reverted the effects of prazosin in renal vascular resistance, without any significant modification in the renal blood flows. However, 20 micrograms/kg epinine increased the renal vascular resistances and, moreover, produced a significant decrease in the blood flows of both kidneys. Neither prazosin nor epinine produced modifications in the intestinal vascular bed. 4. Although epinine possesses significant dopamine and alpha-adrenergic activities that are involved in the biphasic effect of the agent on mean arterial blood pressure in anesthetized rats, in the presence of prazosin, it is not possible to manifest dopaminergic activity involved in the increase in renal or mesenteric blood flow; this may be due to the low tone of the vascular wall induced by the alpha-adrenergic antagonist, though an alpha 2-activity cannot be discarded.

  7. [Physiopathology of pulmonary arterial hypertension. Cellular and molecular aspects].

    Science.gov (United States)

    Perros, Frédéric; Humbert, Marc

    2005-02-12

    The combined effects of vasoconstriction, remodelling of the pulmonary vessel walls and in situ thrombosis contribute to the increase in pulmonary vascular resistance during pulmonary arterial hypertension. Vascular remodelling involves all the sheaths of the vessel wall and all the cell types of which it is composed (endothelial cells, smooth muscle cells, fibroblasts, inflammatory cells and platelets). Excessive vasoconstriction has been related to a defect in the function of expression of the potassium channels and endothelial dysfunction. This leads to chronic insufficiency in the production of vasodilators, notably nitrogen monoxide and prostacyclin and the excessive production of vasoconstrictors such as endotheline-1. These defects contribute to the increase in vascular tonus and pulmonary vascular remodelling and represent pertinent pharmacological targets. Certain growth factors, including those of the super-family of transforming growth factor beta, angiopoietine-1 and serotonin, may play a part in the pathogenesis of pulmonary arterial hypertension.

  8. Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents

    Directory of Open Access Journals (Sweden)

    Natália Portela

    Full Text Available Abstract Background: A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. Objective: To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. Methods: The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years and 14 without (FH-; 27 ± 5 years a family history of hypertension. Blood pressure, heart rate (DIXTAL®, forearm blood flow (Hokanson®, and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®. Results: At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96, heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18, forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16, and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21, respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86, heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86, and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25, respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03. Conclusion: Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.

  9. Sildenafil in the treatment of pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Christopher F Barnett

    2006-12-01

    Full Text Available Christopher F Barnett1,2, Roberto F Machado1,21Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA; 2Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USAAbstract: The therapy of pulmonary hypertension has evolved rapidly in the last 10 years from the use of non-selective vasodilators to drugs that specifically target pulmonary vasodilation, endothelial function, and vascular remodeling. Sildenafil is a phosphodiesterase type 5 inhibitor that has an expanding role in the treatment of pulmonary hypertension. Case series and small studies, as well as the first large randomized controlled trial, have  demonstrated the safety and efficacy of sildenafil in improving mean pulmonary artery pressure, pulmonary vascular resistance, cardiac index, and exercise tolerance in pulmonary arterial hypertension. It may be useful in adults, children, and neonates after cardiac surgery, with left heart failure, in fibrotic pulmonary disease, high altitude exposure, and thromboembolic disease, and in combination with other therapies for pulmonary hypertension, such as inhaled iloprost. The oral formulation and favorable adverse effect profile make sildenafil an attractive alternative in the treatment of selected patients with pulmonary hypertension. Keywords: sildenafil, phosphodiesterase inhibitor, pulmonary hypertension, right heart failure

  10. Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia

    Directory of Open Access Journals (Sweden)

    Desiree Ji Re Lee

    2015-09-01

    Full Text Available AbstractWe observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure.

  11. Cultured rat vascular smooth muscle cells are resistant to methylamine toxicity: no correlation to semicarbazide-sensitive amine oxidase

    Science.gov (United States)

    Langford, S. D.; Trent, M. B.; Boor, P. J.

    2001-01-01

    Methylamine (MA), a component of serum and a metabolite of nicotine and certain insecticides and herbicides, is metabolized by semicarbazide-sensitive amine oxidase (SSAO). MA is toxic to cultured human umbilical vein and calf pulmonary artery endothelial cells. Endothelial cells, which do not exhibit endogenous SSAO activity, are exposed to SSAO circulating in serum. In contrast, vascular smooth muscle cells (VSMC) do exhibit innate SSAO activity both in vivo and in vitro. This property, together with the critical localization of VSMC within the arterial wall, led us to investigate the potential toxicity of MA to VSMC. Cultured rat VSMC were treated with MA (10-5 to 1 M). In some cultures, SSAO was selectively inhibited with semicarbazide or MDL-72145 [(E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine]. Cytotoxicity was measured via MTT, vital dye exclusion, and clonogenic assays. MA proved to be toxic to VSMC only at relatively high concentrations (LC(50) of 0.1 M). The inhibition of SSAO with semicarbazide or MDL-72145 did not increase MA toxicity, suggesting that the production of formaldehyde via tissue-bound, SSAO-mediated MA metabolism does not play a role in the minimal toxicity observed in isolated rat VSMC. The omission of fetal calf serum (FCS), which contains high SSAO activity, from media similarly showed little effect on cytotoxicity. We conclude that VSMC--in contrast to previous results in endothelial cells--are relatively resistant to MA toxicity, and SSAO does not play a role in VSMC injury by MA.

  12. Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

    Science.gov (United States)

    Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

    2017-06-15

    The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel

  13. WNT5A-JNK regulation of vascular insulin resistance in human obesity.

    Science.gov (United States)

    Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

    2016-12-01

    Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m(2)) and five metabolically normal non-obese (BMI 26±2 kg/m(2)) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (pobese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (pinsulin resistance and impaired eNOS phosphorylation (pinsulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. © The Author(s) 2016.

  14. Increased vascular resistance in vasodilated skin an indicator of diabetic microangiopathy?

    DEFF Research Database (Denmark)

    Faris, I B; Lassen, N A

    1982-01-01

    The method of isotope clearance has been used to investigate the vascular resistance in skin in severely atherosclerotic patients with and without diabetes. Dilatation of the skin vessels was achieved by the injection of histamine with a radioactive tracer (99mTc). The perfusion pressure...... of the skin was varied by applying graded external counter pressure over the injected area. The blood flow at any given perfusion pressure was lower (and thus the resistance higher) in the diabetic subjects (P = 0.01). These results could be explained if there was microangiopathy affecting the skin vessels....

  15. Identification of G-Protein-Coupled Receptors (GPCRs) in Pulmonary Artery Smooth Muscle Cells as Novel Therapeutic Targets

    Science.gov (United States)

    2015-10-01

    enhanced proliferation of pulmonary arterial smooth muscle cells (PASMCs). The underlying idea of this project is that the currently limited...Pulmonary arterial hypertension (PAH) is associated with increased vascular resistance, sustained contraction, and enhanced proliferation of pulmonary... CRISPR /Cas9) to knock down receptor expression in cells of interest and then to assess the impact of receptor knock down on functional activity

  16. Effect of chemoreceptor denervation on the pulmonary vascular response to atelectasis.

    Science.gov (United States)

    Levitzky, M G; Newell, J C; Dutton, R E

    1978-10-01

    Six dogs anesthetized with 30 mg/kg pentobarbital were ventilated after differential cannulation of the main stem bronchi. Following sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta (QT). Following 10 min of bilateral 100% O2, QL was 37.4 +/- 5.8% of QT. When left lung atelectasis was induced while the right lung remained on 100% O2, PaO2 remained above 75 mm Hg and QL fell to 26.1 +/- 5.0% of QT. However, when the right lung was ventilated with room air while the left lung remained atelectatic, PaO2 fell to 50.0 +/- 2.6 mm Hg and QL rose to 36.7 +/- 6.2% of QT. Six dogs which had undergone peripheral chemoreceptor denervation prior to these experiments showed a similar decrease in perfusion of the atelectatic left lung when the right lung was ventilated with 100% O2, but did not increase blood flow to the atelectatic lung during systemic hypoxemia. Thus, the increased blood flow to the atelectatic lung which occurs during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.

  17. Daptomycin Failure for Treatment of Pulmonary Septic Emboli in Native Tricuspid and Mitral Valve Methicillin-Resistant Staphylococcus aureus Endocarditis

    Directory of Open Access Journals (Sweden)

    Hadeel Zainah

    2013-01-01

    Full Text Available Daptomycin has been used with success for the treatment of right-sided methicillin-resistant Staphylococcus aureus (MRSA endocarditis. However, its efficacy has not been completely assessed for the treatment of MRSA endocarditis when it is associated with pulmonary septic emboli. Hereby, we present a case of MRSA mitral and tricuspid native valve endocarditis with pulmonary septic emboli, which was treated with daptomycin as a sole agent, resulting in worsening pulmonary infiltrates and treatment failure.

  18. Modulation of pulmonary vasomotor tone in the fetus and neonate

    OpenAIRE

    2001-01-01

    Abstract The high pulmonary vascular resistance (PVR) of atelectatic, hypoxic, fetal lungs limits intrauterine pulmonary blood flow (PBF) to less than 10% of combined right and left ventricular output. At birth, PVR decreases precipitously to accommodate the entire cardiac output. The present review focuses on the role of endothelium-derived nitric oxide (NO), prostacyclin, and vascular smooth muscle potassium channels in mediating the decrease in PVR that occurs at birth, and in maintaining ...

  19. Immunoglobulin E anaphylaxis in rabbits: mechanisms of pulmonary resistance and compliance changes.

    Science.gov (United States)

    Habib, M P; Dunn, A M; Sobonya, R E; Baumgartener, C C; Newell, J D; Halonen, M

    1988-03-01

    Factors causing changes in pulmonary resistance and dynamic compliance with immunoglobulin (Ig) E anaphylaxis in spontaneously breathing rabbits were assessed in ventilated rabbits using tantalum bronchography and wet-to-dry wt ratios. Ventilated rabbits demonstrated changes in resistance and compliance similar to spontaneously breathing rabbits. Chlorpheniramine pretreatment prevented increases in resistance but not decreases in compliance. Anaphylaxis constricted small (less than 1 mm) airways 20.9 +/- 16.0% (mean +/- SD) and intermediate (between 1 and 3 mm) airways 21.8 +/- 19.8%. Chlorpheniramine (10 mg/kg) prevented small airway changes and attenuated those in intermediate airways. Chlorpheniramine prevented histamine-induced constriction of small (23.6 +/- 15.7%) and intermediate (17.6 +/- 15.0%) airways. Lung wet-to-dry wt ratios were unchanged. Changes in resistance and compliance during rabbit IgE anaphylaxis are not due to changes in tidal volume or frequency. Histamine, via H1 receptors, is the principal mediator of pulmonary resistance increases but not dynamic compliance reductions. Chlorpheniramine-sensitive increases in resistance are caused by constrictions of intermediate and small airways, whereas the chlorpheniramine-resistant decrease in compliance is not caused directly by constriction of the smallest measurable airways (0.25 mm) or changes in lung water.

  20. Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents.

    Science.gov (United States)

    Portela, Natália; Amaral, Josária Ferraz; Mira, Pedro Augusto de Carvalho; Souza, Livia Victorino de; Martinez, Daniel Godoy; Laterza, Mateus Camaroti

    2017-07-10

    A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®). At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03). Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. O histórico familiar para hipertensão arterial está relacionado a anormalidades vasculares e autonômicas, bem como disfunções no comportamento neuro-hemodinâmico durante o exerc

  1. Pulmonary arterial hypertension: Basic knowledge for clinicians.

    Science.gov (United States)

    Santos-Ribeiro, Diana; Mendes-Ferreira, Pedro; Maia-Rocha, Carolina; Adão, Rui; Leite-Moreira, Adelino F; Brás-Silva, Carmen

    2016-10-01

    Pulmonary arterial hypertension is a progressive syndrome based on diverse aetiologies, which is characterized by a persistent increase in pulmonary vascular resistance and overload of the right ventricle, leading to heart failure and death. Currently, none of the available treatments is able to cure pulmonary arterial hypertension; additional research is therefore needed to unravel the associated pathophysiological mechanisms. This review summarizes current knowledge related to this disorder, and the several experimental animal models that can mimic pulmonary arterial hypertension and are available for translational research.

  2. White Paper of the Society of Computed Body Tomography and Magnetic Resonance on Dual-Energy CT, Part 3: Vascular, Cardiac, Pulmonary, and Musculoskeletal Applications.

    Science.gov (United States)

    De Cecco, Carlo N; Schoepf, U Joseph; Steinbach, Lynne; Boll, Daniel T; Foley, W Dennis; Kaza, Ravi K; Bolus, David N; Morgan, Desiree E; Sahani, Dushyant V; Shuman, William P; Siegel, Marilyn J; Vrtiska, Terri J; Yeh, Benjamin M; Berland, Lincoln L

    2017-01-01

    This is the third of a series of 4 white papers that represent Expert Consensus Documents developed by the Society of Computed Body Tomography and Magnetic Resonance through its Task Force on dual-energy computed tomography. This paper, part 3, describes computed tomography angiography and thoracic, cardiac, vascular, and musculoskeletal clinical applications. At the end of the discussion of each application category (vascular, cardiac, pulmonary, and musculoskeletal), we present our consensus opinions on the current clinical utility of the application and opportunities for further research.

  3. Effects of particulate matter on the pulmonary and vascular system: time course in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Salonen Raimo O

    2005-03-01

    Full Text Available Abstract Background This study was performed within the scope of two multi-center European Commission-funded projects (HEPMEAP and PAMCHAR concerning source-composition-toxicity relationship for particulate matter (PM sampled in Europe. The present study aimed to optimize the design for PM in vivo toxicity screening studies in terms of dose and time between a single exposure and the determination of the biological responses in a rat model mimicking human disease resulting in susceptibility to ambient PM. Dust in thoracic PM size-range (aerodynamic diameter Results The neutrophil numbers in bronchoalveolar lavage fluid increased tremendously after exposure to the highest RTD doses or EHC-93. Furthermore, PM exposure slightly affected blood coagulation since there was a small but significant increase in the plasma fibrinogen levels (factor 1.2. Pulmonary inflammation and oxidative stress as well as changes in blood coagulation factors and circulating blood cell populations were observed within the range of 3 to 10 mg PM/kg of body weight without significant pulmonary injury. Conclusion The optimal dose for determining the toxicity ranking of ambient derived PM samples in spontaneously hypertensive rats is suggested to be between 3 and 10 mg PM/kg of body weight under the conditions used in the present study. At a lower dose only some inflammatory effects were detected, which will probably be too few to be able to discriminate between PM samples while a completely different response pattern was observed with the highest dose. In addition to the dose, a 24-hr interval from exposure to sacrifice seemed appropriate to assess the relative toxic potency of PM since the majority of the health effects were observed one day after PM exposure compared to the other times examined. The aforementioned considerations provide a good basis for conducting PM toxicity screening studies in spontaneously hypertensive rats.

  4. Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    de Matthaeis A

    2014-05-01

    Full Text Available Angela de Matthaeis,1 Antonio Greco,2,* Mariangela Pia Dagostino,2 Giulia Paroni,2 Andrea Fontana,3 Manlio Vinciguerra,1,4,5 Gianluigi Mazzoccoli,1,* Davide Seripa,2 Gianluigi Vendemiale61Division of Internal Medicine and Chronobiology Unit, 2Geriatrics Unit and Gerontology, Geriatrics Research Laboratory, Department of Medical Sciences, 3Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, 4Euro-Mediterranean Institute of Sciences and Technology, Palermo, Italy; 5University College London, Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, London, UK; 6Geriatrics Unit, University of Foggia, Foggia, Italy*These authors contributed equally to this workAbstract: Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD, a common medical condition in the elderly. Flow-mediated dilation (FMD, a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1 and after (phase 2 standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001, pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001, pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001, FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001 and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001. FMD values were

  5. Macrophage Akt1 Kinase-Mediated Mitophagy Modulates Apoptosis Resistance and Pulmonary Fibrosis.

    Science.gov (United States)

    Larson-Casey, Jennifer L; Deshane, Jessy S; Ryan, Alan J; Thannickal, Victor J; Carter, A Brent

    2016-03-15

    Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder with increasing incidence. Mitochondrial oxidative stress in alveolar macrophages is directly linked to pulmonary fibrosis. Mitophagy, the selective engulfment of dysfunctional mitochondria by autophagasomes, is important for cellular homeostasis and can be induced by mitochondrial oxidative stress. Here, we show Akt1 induced macrophage mitochondrial reactive oxygen species (ROS) and mitophagy. Mice harboring a conditional deletion of Akt1 in macrophages (Akt1(-/-)Lyz2-cre) and Park2(-/-) mice had impaired mitophagy and reduced active transforming growth factor-β1 (TGF-β1). Although Akt1 increased TGF-β1 expression, mitophagy inhibition in Akt1-overexpressing macrophages abrogated TGF-β1 expression and fibroblast differentiation. Importantly, conditional Akt1(-/-)Lyz2-cre mice and Park2(-/-) mice had increased macrophage apoptosis and were protected from pulmonary fibrosis. Moreover, IPF alveolar macrophages had evidence of increased mitophagy and displayed apoptosis resistance. These observations suggest that Akt1-mediated mitophagy contributes to alveolar macrophage apoptosis resistance and is required for pulmonary fibrosis development.

  6. Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Tharciano Luiz Teixeira Braga da; Mota, Marcelo Mendonça; Fontes, Milene Tavares; Araújo, João Eliakim dos Santos; Carvalho, Vitor Oliveira; Bonjardim, Leonardo Rigoldi; Santos, Márcio Roberto Viana, E-mail: marciorvsantos@bol.com.br [Universidade Federal de Sergipe, Universidade de São Paulo (Brazil)

    2015-08-15

    Hypertension is a public health problem and increases the incidence of cardiovascular diseases. To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of N{sup G}-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H. One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

  7. Vascular reactivity of rabbit isolated renal and femoral resistance arteries in renal wrap hypertension.

    Science.gov (United States)

    Khammy, Makhala M; Angus, James A; Wright, Christine E

    2016-02-15

    In rabbits with cellophane renal wrap hypertension, hindquarter and total vascular resistance changes to pressor and depressor agents are amplified compared to those of normotensive rabbits. The aim of the present study was to evaluate the in vitro pharmacodynamics of hypertensive and normotensive rabbit small artery segments isolated from the renal and hindquarter vascular beds. Using wire myography, the full range (Emax) and sensitivity (EC50) to a range of agonists of segments of renal interlobar (≈ 600 µm i.d.), renal arcuate (≈ 250 µm i.d.) and deep femoral branch (≈ 250 µm i.d.) arteries were assessed under normalised conditions of passive tension. Interlobar arteries from hypertensive rabbits were more sensitive (EC50) than those from normotensive rabbits to noradrenaline (6-fold), methoxamine (3-fold) and angiotensin II (3-fold). Arcuate artery reactivity was largely unaffected by hypertension. Deep femoral arteries from hypertensive rabbits had enhanced sensitivity only to noradrenaline (2-fold) and methoxamine (4-fold). Sensitivity to relaxation by acetylcholine was unaffected by hypertension in all arteries. Deep femoral arteries from hypertensive rabbits were more sensitive to sodium nitroprusside than normotensive counterparts. Adenosine caused little relaxation in renal arteries, but full relaxation in deep femoral arteries, unaltered by hypertension. This study found substantial heterogeneity in the pharmacodynamic profile of vessels isolated from different vascular beds and between arterial segments within the kidney. These profiles were differentially affected by hypertension suggesting that hypertension per se is not a resultant of general vascular dysfunction.

  8. Effects of Puerarin on Pulmonary Vascular Remodeling and Protein Kinase C-α in Chronic Cigarette Smoke Exposure Smoke-exposed Rats

    Institute of Scientific and Technical Information of China (English)

    Zhaoxia ZHU; Yongjian XU; Hui ZOU; Zhenxiang ZHANG; Wang NI; Shixin CHEN

    2008-01-01

    In order to investigate the effects of puerarin on pulmonary vascular remodeling and protein kinase C-α (PKC-α) in chronic exposure smoke rats, 54 male Wistar rats were randomly di- vided into 7 groups: control group (C group), smoke exposure groups (S4w group, Saw group), puer- arin groups (P4w group, P8w group), propylene glycol control groups (PC4w group,PC8w group). Rats were exposed to cigarette smoke or air for 4 to 8 weeks. Rats in puerarin groups also received puer- arin. To evaluate vascular remodeling, alpha-smooth muscle actin (α-SM-actin) staining was used to count the percentage of completely muscularised vessels to intraacinar pulmonary arteries (CMA/IAPA) which was determined by morphometric analysis of histological sections. Pulmonary artery smooth muscle cell (PASMC) apoptosis was detected by in situ end labeling technique (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining. Reverse transcrip- tion-polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot analysis were done to detect the PKC-α mRNA and protein expression in pulmonary arteries. The results showed that in cigarette smoke-exposed rats the percentage of CMA/IAPA and α-SM-actin expres- sion were increased greatly, PASMC apoptosis was increased and proliferation was markedly in- creased; Apoptosis indices (AI) and proliferation indices (PI) were higher than in C group; AI and PI were correlated with vascular remodeling indices; The expression of PKC-ct mRNA and protein in pulmonary arteries was significantly higher than in C group. In rats treated with puerarin, the per- eentage of CMA/IAPA and cell proliferation was reduced, whereas PASMC apoptosis was increased; The expression levels of PKC-α mRNA and protein were lower than in smoke exposure rats. There was no difference among all these data between S groups and PC groups. These findings suggested that cigarette smoke-induced pulmonary vascular remodeling was most likely an

  9. Fetal and postnatal pulmonary circulation in the Alto Andino.

    Science.gov (United States)

    Llanos, A J; Ebensperger, G; Herrera, E A; Reyes, R V; Pulgar, V M; Serón-Ferré, M; Díaz, M; Parer, J T; Giussani, D A; Moraga, F A; Riquelme, R A

    2011-03-01

    Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the llama fetus compared to the sheep fetus. Altogether these data show that the fetal llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the llama. The llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.

  10. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery

    DEFF Research Database (Denmark)

    Storkebaum, Erik; Ruiz de Almodovar, Carmen; Meens, Merlijn;

    2010-01-01

    BACKGROUND: Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. METHODS AND RESULTS: Here, we report that VEGF( ...

  11. Idiopathic pulmonary fibrosis and collagen vascular diseases - high resolution CT findings; Pneumopatias intersticiais difusas idiopaticas e associadas a colagenoses - aspectos da tomografia computadorizada de alta resolucao

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira Neto, Armando Leao; Mogami, Roberto [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Centro Biomedico. Inst. de Radiologia; Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Inst. Biomedico. Dept. de Radiologia; Capone, Domenico [Universidade Estadual, Rio de Janeiro, RJ (Brazil). Dept. de Penumologia

    1996-09-01

    The aspects of the thorax high-resolution computed tomography of 15 patients with idiopathic pulmonary fibrosis and 11 patients with collagen vascular diseases are described and characterized mainly by the presence of reticular lesions with little cysts predominantly in the periphery and lower lobes. They may be associated with ground-glass lesions that, as usual, means areas of alveolitis. (author) 31 refs., 5 figs.

  12. Diverse contribution of bone marrow-derived late-outgrowth endothelial progenitor cells to vascular repair under pulmonary arterial hypertension and arterial neointimal formation.

    Science.gov (United States)

    Ikutomi, Masayasu; Sahara, Makoto; Nakajima, Toshiaki; Minami, Yoshiyasu; Morita, Toshihiro; Hirata, Yasunobu; Komuro, Issei; Nakamura, Fumitaka; Sata, Masataka

    2015-09-01

    It is still controversial whether bone marrow (BM)-derived endothelial progenitor cells (EPCs) can contribute to vascular repair and prevent the progression of vascular diseases. We aimed to characterize BM-derived EPC subpopulations and to evaluate their therapeutic efficacies to repair injured vascular endothelium of systemic and pulmonary arteries. BM mononuclear cells of Fisher-344 rats were cultured under endothelial cell-conditions. Early EPCs appeared on days 3-6. Late-outgrowth and very late-outgrowth EPCs (LOCs and VLOCs) were defined as cells forming cobblestone colonies on days 9-14 and 17-21, respectively. Among EPC subpopulations, LOCs showed the highest angiogenic capability with enhanced proliferation potential and secretion of proangiogenic proteins. To investigate the therapeutic effects of these EPCs, Fisher-344 rats underwent wire-mediated endovascular injury in femoral artery (FA) and were concurrently injected intraperitoneally with 60mg/kg monocrotaline (MCT). Injured rats were then treated with six injections of one of three EPCs (1×10(6) per time). After 4weeks, transplanted LOCs, but not early EPCs or VLOCs, significantly attenuated neointimal lesion formation in injured FAs. Some of CD31(+) LOCs directly replaced the injured FA endothelium (replacement ratio: 11.7±7.0%). In contrast, any EPC treatment could neither replace MCT-injured endothelium of pulmonary arterioles nor prevent the progression of pulmonary arterial hypertension (PAH). LOCs modified protectively the expression profile of angiogenic and inflammatory genes in injured FAs, but not in MCT-injured lungs. BM-derived LOCs can contribute to vascular repair of injured systemic artery; however, even they cannot rescue injured pulmonary vasculature under MCT-induced PAH. Copyright © 2015. Published by Elsevier Ltd.

  13. World Health Organization Group I Pulmonary Hypertension: Epidemiology and Pathophysiology.

    Science.gov (United States)

    Prins, Kurt W; Thenappan, Thenappan

    2016-08-01

    Pulmonary arterial hypertension (PAH) is a debilitating disease characterized by pathologic remodeling of the resistance pulmonary arteries, ultimately leading to right ventricular (RV) failure and death. In this article we discuss the definition of PAH, the initial epidemiology based on the National Institutes of Health Registry, and the updated epidemiology gleaned from contemporary registries, pathogenesis of pulmonary vascular dysfunction and proliferation, and RV failure in PAH. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Evaluation of drug resistance in pulmonary tuberculosis patients at Sureyyapasa Chest Diseases Hospital, Istanbul, Turkey.

    Science.gov (United States)

    Karagoz, T; Pazarli, P; Mocin, O Y; Duman, D; Duman, G; Salturk, C; Unal, O

    2008-06-01

    Sureyyapasa Chest Diseases and Thoracic Surgery Training Hospital, Istanbul, Turkey. To determine levels of Mycobacterium tuberculosis resistance to first-line drugs in patients with pulmonary tuberculosis (PTB). Between 1 January and 31 December 2005, all hospitalised PTB patients with culture-positive M. tuberculosis specimens and corresponding drug susceptibility tests (DST) for isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol, routinely performed for every tuberculosis (TB) case at our centre, were included. Of a total of 1513 cases, 1277 (84.4%) were new and 236 (15.6%) were previously treated cases. Of the 1513 isolates, 290 (19%) isolates were resistant to at least one of the drugs tested. Resistance among new and previously treated cases was respectively 16.3% (209 of 1277) and 34.3% (81/236). Any SM resistance and any INH resistance were the most common drug resistance in new cases, while any RMP resistance was the most common drug resistance in previously treated cases. Multidrug resistance was detected in 3.2% (n = 41) of new cases and in 13.5% (n = 32) of previously treated cases. Planning for TB control requires an assessment of the number and distribution of drug-resistant cases, with laboratories providing accurate and reliable results.

  15. Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

    Science.gov (United States)

    de Matthaeis, Angela; Greco, Antonio; Dagostino, Mariangela Pia; Paroni, Giulia; Fontana, Andrea; Vinciguerra, Manlio; Mazzoccoli, Gianluigi; Seripa, Davide; Vendemiale, Gianluigi

    2014-01-01

    Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium. PMID:24904207

  16. Functional high-resolution computed tomography of pulmonary vascular and airway reactions. Experimental results. Funktionelle HR-CT der Lunge. Experimentelle Untersuchungen pulmonaler Gefaess- und Atemwegsreaktionen

    Energy Technology Data Exchange (ETDEWEB)

    Herold, C.J. (Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria) Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology); Brown, R.H. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Physiology); Wetzel, R.C.; Herold, S.M. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine); Zeerhouni, E.A. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology)

    1993-03-01

    We describe the use of high-resolution computed tomography (HRCT) for assessment of the function of pulmonary vessels and airways. With its excellent spatial resolution, HRCT is able to demonstrate pulmonary structures as small as 300 [mu]m and can be used to monitor changes following various stimuli. HRCT also provides information about structures smaller than 300 [mu]m through measurement of parenchymal background density. To date, sequential, spiral and ultrafast HRCT techniques have been used in a variety of challenges to gather information about the anatomical correlates of traditional physiological measurements, thus making anatomical-physiological correlation possible. HRCT of bronchial reactivity can demonstrate the location and time course of aerosol-induced broncho-constriction and may show changes not apparent on spirometry. HRCT of the pulmonary vascular system visualized adaptations of vessels during hypoxia and intravascular volume loading and elucidates cardiorespiratory interactions. Experimental studies provide a basis for potential clinical applications of this method. (orig.).

  17. Alteration of Leukocyte Count Correlates With Increased Pulmonary Vascular Permeability and Decreased PaO2:FiO2 Ratio Early After Major Burns.

    Science.gov (United States)

    Johansson, Joakim; Steinvall, Ingrid; Herwald, Heiko; Lindbom, Lennart; Sjöberg, Folke

    2015-01-01

    Leukocytes are activated systemically and their numbers increase soon after a burn followed by a rapid decline to low normal or subnormal levels, possibly by increased extravasation. Experimental data support that an important target for such extravasation is the lungs and that leukocytes when they adhere to endothelial cells cause an increase in vascular permeability. The authors investigated a possible relation between early increased pulmonary vascular permeability or a decreased PaO2:FiO2 ratio and the dynamic change in concentration of blood leukocytes after a burn. This is a prospective, exploratory, single-center study. The authors measured the dynamic changes of leukocytes in blood starting early after the burn, pulmonary vascular permeability index by thermodilution, and PaO2:FiO2-ratios in 20 patients during the first 21 days after a major burn (>20% TBSA%). Median TBSA was 40% interquartile range (IQR, 25-52) and full thickness burn 28% (IQR, 2-39). There was a correlation between the early (PaO2:FiO2 < 27 kPa (P = .004). The authors have documented a correlation between dynamic change of blood leukocytes and pulmonary failure early after burns.

  18. Usual interstitial pneumonia preceding collagen vascular disease: a retrospective case control study of patients initially diagnosed with idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Masato Kono

    Full Text Available BACKGROUND: The aim of this study was to evaluate the cumulative incidence and the predictive factors for collagen vascular disease (CVD in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF, and to examine the features of patients who then developed CVD. METHODS: This was a retrospective review of 111 consecutive patients with IPF diagnosed at our institution. None of the patients fulfilled any of the CVD criteria from the American College of Rheumatology (ACR within 6 months or more after the diagnosis of IPF. RESULTS: Ten patients (9.0% developed CVD during the follow-up period: four had rheumatoid arthritis (RA; four had microscopic polyangiitis (MPA; one had systemic sclerosis (SSc; and one had SSc and Sjogren's syndrome (SjS. The mean time until CVD diagnosis was 3.9 years. The cumulative incidences of CVD at 1, 5, and 10 years were 0.91%, 9.85%, and 15.5%, respectively. Patients who developed CVD were significantly younger, more likely to be women and had a better prognosis than those with IPF. Cox proportional hazards regression analysis showed that female sex and the presence of lymphoid aggregates with germinal centers were significantly associated with the occurrence of CVD in patients initially diagnosed with IPF. CONCLUSIONS: CVD is an important underlying condition in IPF, and shows better prognosis. The possibility of the development of CVD should remain a consideration in the follow-up of IPF.

  19. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

    Science.gov (United States)

    Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

    2016-06-01

    Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Copyright © 2016 the American Physiological Society.

  20. Recurrence after treatment for pulmonary multidrug-resistant tuberculosis.

    Science.gov (United States)

    Becerra, Mercedes C; Appleton, Sasha C; Franke, Molly F; Chalco, Katiuska; Bayona, Jaime; Murray, Megan B; Mitnick, Carole D

    2010-09-15

    We estimated the proportion of recurrence within 2 years among adults cured by individualized multidrug-resistant tuberculosis regimens in Peru. Among 310 individuals with at least 24 months of follow-up, 16 experienced an episode of recurrent tuberculosis. If we assume the worst for treatment effectiveness-that all 16 episodes were caused by the original tuberculosis strain-then 5.2% (95% confidence interval, 3.0%-8.2%) experienced true relapse. This is an upper-bound estimate of relapse on which new regimens must improve.

  1. Body Size Predicts Cardiac and Vascular Resistance Effects on Men's and Women's Blood Pressure.

    Science.gov (United States)

    Evans, Joyce M; Wang, Siqi; Greb, Christopher; Kostas, Vladimir; Knapp, Charles F; Zhang, Qingguang; Roemmele, Eric S; Stenger, Michael B; Randall, David C

    2017-01-01

    Key Points Summary We report how blood pressure, cardiac output and vascular resistance are related to height, weight, body surface area (BSA), and body mass index (BMI) in healthy young adults at supine rest and standing.Much inter-subject variability in young adult's blood pressure, currently attributed to health status, may actually result from inter-individual body size differences.Each cardiovascular variable is linearly related to height, weight and/or BSA (more than to BMI).When supine, cardiac output is positively related, while vascular resistance is negatively related, to body size. Upon standing, the change in vascular resistance is positively related to size.The height/weight relationships of cardiac output and vascular resistance to body size are responsible for blood pressure relationships to body size.These basic components of blood pressure could help distinguish normal from abnormal blood pressures in young adults by providing a more effective scaling mechanism. Introduction: Effects of body size on inter-subject blood pressure (BP) variability are not well established in adults. We hypothesized that relationships linking stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) with body size would account for a significant fraction of inter-subject BP variability. Methods: Thirty-four young, healthy adults (19 men, 15 women) participated in 38 stand tests during which brachial artery BP, heart rate, SV, CO, TPR, and indexes of body size were measured/calculated. Results: Steady state diastolic arterial BP was not significantly correlated with any index of body size when subjects were supine. However, upon standing, the more the subject weighed, or the taller s/he was, the greater the increase in diastolic pressure. Systolic pressure strongly correlated with body weight and height both supine and standing. Diastolic and systolic BP were more strongly related to height, weight and body surface area than to body mass index. When

  2. Primary drug resistance among pulmonary treatment-naïve tuberculosis patients in Amazonas State, Brazil.

    Science.gov (United States)

    da Silva Garrido, M; Ramasawmy, R; Perez-Porcuna, T M; Zaranza, E; Chrusciak Talhari, A; Martinez-Espinosa, F E; Bührer-Sékula, S

    2014-05-01

    Multidrug-resistant tuberculosis (MDR-TB) is the main indicator of previous treatment in tuberculosis (TB) patients. MDR-TB among treatment-naïve patients indicates infection with drug-resistant Mycobacterium tuberculosis strains, and such cases are considered primary drug-resistant cases. To estimate the prevalence of drug resistance in pulmonary TB (PTB) treatment-naïve patients and to identify the socio-demographic and clinical characteristics of the resistant population. A total of 205 treatment-naïve PTB patients from Manaus, Amazonas State, Brazil, were enrolled. Drug susceptibility testing (DST) was performed on all positive mycobacterial cultures using the 1% proportion method. Positive M. tuberculosis cultures were obtained from only 175 patients for DST. The prevalence of primary MDR-TB was 1.7% (3/175); 14.3% (25/175) of the cultures presented resistance to at least one of the drugs. Resistance to streptomycin, isoniazid, rifampicin and ethambutol was respectively 8.6%, 6.9%, 3.4% and 2.3%. An association between TB patients with resistance to more than one drug and known previous household contact with a TB patient was observed (P= 0.008, OR 6.7, 95%CI 1.2-67.3). Although the prevalence of primary MDR-TB currently is relatively low, it may become a major public health problem if tailored treatment is not provided, as resistance to more than one drug is significantly associated with household contact.

  3. Vascular wall dysfunction in JCR:LA-cp rats: effects of age and insulin resistance.

    Science.gov (United States)

    O'brien, S F; Russell, J C; Davidge, S T

    1999-11-01

    We tested the hypothesis that aging and insulin resistance interact to increase vascular dysfunction by comparing the function of isolated mesenteric resistance arteries in obese, insulin-resistant JCR:LA-cp rats and lean, insulin-sensitive rats of the same strain at 3, 6, 9, and 12 mo of age. The peak constrictor responses to norepinephrine, phenylephrine, and high potassium were elevated in arteries from obese rats. Responses to these agents increased with age in both obese and lean rats. An eicosanoid constrictor contributed substantially to vasoconstriction in the arteries from both lean and obese animals. Inhibition of nitric oxide synthase increased the vasoconstrictor response to norepinephrine in both obese and lean rats. This effect increased with age in lean rats only. Vascular relaxation in response to acetylcholine and sodium nitroprusside was impaired in the obese rats and did not alter with age. The results suggest that obese JCR:LA-cp rats have enhanced maximal constriction, which originates in the arterial smooth muscle and increases with age. There is evidence that the ability of the arteries to compensate for the enhanced contractility is impaired in obese rats, particularly with advanced age.

  4. The control of vascular resistance in the southern rock lobster, Jasus edwardsii (Decapoda: Palinuridae).

    Science.gov (United States)

    Wilkens, J L; Taylor, H H

    2003-07-01

    In Jasus edwardsii (Hutton) the vascular resistance of each of the seven major arterial systems leaving the heart was increased in response to several of the following neurotransmitters and neurohormones: acetylcholine, adrenalin, serotonin, dopamine, octopamine and peptides proctolin and FLRFamide-related peptide F(1). The resistance to flow through the infrabranchial sinus (IBS), part of the venous system, was also sensitive to these drugs. Unexpectedly, the responses of the IBS continued after removal of the gills. Differences in the profiles of responses of the arteries to individual hormones and in the magnitudes and the time courses of back pressure changes, eliminate a common downstream location such as the venous sinuses or gills, as the source of the arterial responses. Vasoactive drugs were effective when applied either via the lumen or, with longer delay, to the basal side of an artery via the IBS. It is concluded that the resistance of each of these sections of the vascular system is independently controllable by hormones.

  5. Systemic vascular resistance during brief withdrawal of angiotensin converting enzyme inhibition in heart failure

    DEFF Research Database (Denmark)

    Gabrielsen, A; Bie, P; Christensen, N J

    2002-01-01

    We tested the hypothesis that moderate increases in endogenous angiotensin II (Ang II) concentrations, induced by withdrawal of angiotensin converting enzyme inhibition (ACE-I) in patients with compensated heart failure (HF) on chronic medical therapy, do not increase or impair control of systemic...... vascular resistance (SVR). SVR was determined in supine and seated positions in 12 HF patients [NYHA class II-III; ejection fraction=0.29 +/- 0.03 (mean +/- SE)] and 9 control subjects. HF patients were investigated during high (n=11; withdrawal of ACE-I treatment for 24 h) and low (n=9; sustained ACE...

  6. The role of inflammation in vascular insulin resistance with focus on IL-6

    DEFF Research Database (Denmark)

    Andersen, Kirsten; Pedersen, B.K.

    2008-01-01

    . It is likely that chronic low-level inflammation plays an important role in developing endothelial dysfunction mainly through proinflammatory actions of tumor necrosis factor alpha (TNF-alpha). TNF-alpha induces production of IL-6 and it has been suggested that a causal relationship exists between endothelial...... dysfunction and these cytokines. With regard to vascular insulin resistance, the available data point to a direct pathogenic role of TNF-alpha in mediating endothelial dysfunction, whereas with regard to IL-6 evidence is sparse and does not allow any firm conclusions Udgivelsesdato: 2008/9...

  7. Brown fat lipoatrophy and increased visceral adiposity through a concerted adipocytokines overexpression induces vascular insulin resistance and dysfunction.

    Science.gov (United States)

    Gómez-Hernández, Almudena; Otero, Yolanda F; de las Heras, Natalia; Escribano, Oscar; Cachofeiro, Victoria; Lahera, Vicente; Benito, Manuel

    2012-03-01

    In this study, we analyzed the role played by concerted expression of adipocytokines associated with brown fat lipoatrophy and increased visceral adiposity on triggering vascular insulin resistance and dysfunction in brown adipose tissue (BAT) insulin receptor knockout (BATIRKO) mice. In addition, we assessed whether vascular insulin resistance may aggravate vascular damage. The 52-wk-old, but not 33-wk-old, BATIRKO mice had a significant decrease of BAT mass associated with a significant increase of visceral white adipose tissue (WAT) mass, without changes in body weight. Brown fat lipoatrophy and increased visceral adiposity enhanced the concerted expression of adipocytokines (TNF-α, leptin, and plasminogen activator inhibitor 1) and nuclear factor-κB binding activity in BAT and visceral WAT, mainly in the gonadal depot, and aorta. Although those mice showed insulin sensitivity in the liver and skeletal muscle, insulin signaling in WAT (gonadal depot) and aorta was markedly impaired. Treatment with anti-TNF-α antibody impaired the inflammatory activity in visceral adipose tissue, attenuated insulin resistance in WAT and aorta and induced glucose tolerance. Finally, 52-wk-old BATIRKO mice showed vascular dysfunction, macrophage infiltration, oxidative stress, and a significant increase of gene markers of endothelial activation and inflammation, the latter effect being totally reverted by anti-TNF-α antibody treatment. Our results suggest that brown fat lipoatrophy and increased visceral adiposity through the concerted overexpression of cytoadipokines induces nuclear factor-κB-mediated inflammatory signaling, vascular insulin resistance, and vascular dysfunction. Inhibition of inflammatory activity by anti-TNF-α antibody treatment attenuates vascular insulin resistance and impairs gene expression of vascular dysfunction markers.

  8. Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention.

    Science.gov (United States)

    Cuthbertson, Leah; Rogers, Geraint B; Walker, Alan W; Oliver, Anna; Green, Laura E; Daniels, Thomas W V; Carroll, Mary P; Parkhill, Julian; Bruce, Kenneth D; van der Gast, Christopher J

    2016-05-01

    Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression. In this study multiple sputum samples were collected from adult CF patients over the course of CFPEs to better understand how changes in microbiota are associated with CFPE onset and management. Data were divided into five clinical periods: pre-CFPE baseline, CFPE, antibiotic treatment, recovery, and post-CFPE baseline. Samples were treated with propidium monoazide prior to DNA extraction, to remove the impact of bacterial cell death artefacts following antibiotic treatment, and then characterised by 16S rRNA gene-targeted high-throughput sequencing. Partitioning CF microbiota into core and rare groups revealed compositional resistance to CFPE and resilience to antibiotics interventions. Mixed effects modelling of core microbiota members revealed no significant negative impact on the relative abundance of Pseudomonas aeruginosa across the exacerbation cycle. Our findings have implications for current CFPE management strategies, supporting reassessment of existing antimicrobial treatment regimens, as antimicrobial resistance by pathogens and other members of the microbiota may be significant contributing factors.

  9. Effects of simulated obstructive sleep apnoea on the human carotid baroreceptor-vascular resistance reflex.

    Science.gov (United States)

    Cooper, V L; Bowker, C M; Pearson, S B; Elliott, M W; Hainsworth, R

    2004-06-15

    Obstructive sleep apnoea (OSA), which is characterized by periodic inspiratory obstruction, is associated with hypertension and possibly with changes in the baroreceptor reflex. In this investigation we induced changes in inspiratory resistance and in inspiratory oxygen and carbon dioxide content, which simulate some of the changes in OSA, to determine whether this caused changes in the gain or setting of the carotid baroreflex. In eight healthy subjects (aged 21-62 years) we changed the stimulus to carotid baroreceptors, using neck chambers and graded pressures of -40 to +60 mmHg, and assessed vascular resistance responses in the brachial artery from changes in blood pressure (Finapres) divided by brachial artery blood flow velocity (Doppler ultrasound). Stimulus-response curves were defined during (a) sham (no additional stimulus), (b) addition of an inspiratory resistance (inspiratory pressure -10 mmHg), (c) breathing asphyxic gas (12% O(2), 5% CO(2)), and (d) combined resistance and asphyxia. Sigmoid or polynomial functions were applied to the curves and maximum differentials (equivalent to peak gain) and the corresponding carotid pressures (equivalent to 'set point') were determined. The sham test had no effect on either gain or 'set point'. Inspiratory resistance alone had no effect on blood pressure and did not displace the curve. However, it reduced gain from -3.0 +/- 0.6 to -2.1 +/- 0.4 units (P sleep apnoea.

  10. Prevalence of multidrug resistance among retreatment pulmonary tuberculosis cases in a tertiary care hospital, Hyderabad, India

    Directory of Open Access Journals (Sweden)

    Subhakar Kandi

    2013-01-01

    Full Text Available Background: India is one of the high tuberculosis (TB burden countries in the world. India ranks second in harboring multi drug resistant (MDR-TB cases. About 50,000 of MDR cases are recorded in retreatment pulmonary TB cases. This study was conducted in a tertiary care facility (Government General and Chest Hospital in Hyderabad, India. Objectives: Toassess: Proportion of the TB patients having MDR-TB at the initiation of retreatment regimen; the prevalence of isoniazid (INH resistance in this geographical area. Materials and Methods: An analytical, observational, prospective cohort study of patients attending the out-patient department from December 2010 to March 2011. Results: Sputum samples from 100 patients were subjected to acid fast bacilli (AFB culture and drug sensitivity testing. Of these, 28 (28% were MDR-TB, 42 (42% were non-MDR-TB and 39% being INH resistance. Conclusions: In conclusion, one third of the retreatment pulmonary TB cases attending a tertiary care institute for TB will be MDR-TB at the initiation of treatment and there is a need to include ethambutol in the continuation phase of new TB case treatment in view of high INH resistance.

  11. Utility of line probe assay for the early detection of multidrug-resistant pulmonary tuberculosis

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    K Madhuri

    2015-01-01

    Full Text Available Background: Despite endorsement of the line probe assay (LPA for the diagnosis of drug-resistant pulmonary tuberculosis patients, there is limited data available on the performance of LPAs in India, especially from high burden states like Maharashtra, for the early diagnosis and detection of drug resistance, in order to initiate timely and appropriate treatment. Objective: To evaluate the utility of the line probe assay (LPA for the early diagnosis of drug-resistant pulmonary tuberculosis as compared to the ′Gold standard′ 1% proportion method (PM. Materials and Methods: A total of 687 patients suspected of pulmonary tuberculosis were screened. One hundred samples (95 sputum and 5 BAL, positive for Acid Fast Bacilli (AFB by Ziehl Neelson (ZN smears, were included in the study. Digested and decontaminated specimens were subjected directly to the LPA (Genotype MTBDR@ plus assay and were processed in parallel using the conventional culture on the Lowenstein-Jensen (LJ medium followed by drug susceptibility testing (DST using the PM. Results: All the 100 samples gave interpretable results on LPA with a turnaround time of 24-48 hours as opposed to six to eight weeks taken by the 1% proportion method. Sensitivity for the detection of rifampicin, isoniazid, and multidrug resistance (MDR was 98.1, 92.1, and 95%, respectively, with a specificity of 97.8% for rifampicin and 98.33% for MDR detection. It also had the additional advantage of allowing a study of mutation patterns. Conclusions: High performance characteristics and a short turnaround time makes LPA an excellent diagnostic tool, for an early and accurate diagnosis, in a high MDR- TB-prevalent region, as reflected from our data.

  12. Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

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    Tharciano Luiz Teixeira Braga da Silva

    2015-01-01

    Full Text Available Abstract Background: Hypertension is a public health problem and increases the incidence of cardiovascular diseases. Objective: To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME-induced hypertensive rats. Methods: Wistar rats were divided into three groups: control (C, hypertensive (H, and exercised hypertensive (EH. Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN, potassium chloride (KCl and sodium nitroprusside (SNP. Results: Rats treated with L-NAME showed an increase (p < 0.001 in systolic blood pressure (SBP, diastolic blood pressure (DBP and mean arterial pressure (MAP compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001 the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01 smooth muscle sensitivity to NPS was observed in group EH as compared to group H. Conclusion: One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

  13. Pulmonary Thromboendarterectomy for Pulmonary Hypertension Before Considering Transplant

    Science.gov (United States)

    Kooperkamp, Hannah; Mehta, Inder; Fary, David; Bates, Michael

    2017-01-01

    Background: In cases of chronic thromboembolic pulmonary hypertension (CTEPH), referral for possible surgical intervention is important because surgery can be curative. Surgery necessitates cardiopulmonary bypass and deep circulatory arrest with pulmonary thrombectomy and bilateral endarterectomy (PTE). If surgery fails, lung transplant is the next best surgical option. Medical treatment is also an important adjunct. Case Report: A 35-year-old female presented 3 months after a pulmonary embolus was found to be completely occluding her left pulmonary artery. She was found to have pulmonary hypertension with a pulmonary artery pressure of 81/33 mmHg, with a mean pressure of 52 mmHg. The right atrial pressure was also severely elevated at 29 mmHg, and her echocardiogram revealed severe tricuspid regurgitation and severe right ventricular dysfunction. She underwent PTE and postoperatively was followed by the heart failure team. Her 6-minute walk distance improved from 396 meters at 1 month to 670 meters at 7 months, and her pulmonary artery pressure improved significantly to 55/17 mmHg with a mean pressure of 31 mmHg. The patient's right atrial pressure also improved significantly from 29 mmHg to 13 mmHg. Conclusion: CTEPH is likely underrecognized, and patients with pulmonary hypertension or a history of pulmonary embolism should be screened for CTEPH. This case illustrates the surgical treatment for CTEPH and discusses alternative and adjunctive treatments. Residual pulmonary hypertension after PTE occurs in approximately 35% of patients. Overall, 4-year mortality rates after surgery appear to be approximately 15%, and mortality rates correlate with the postoperative pulmonary vascular resistance. Recognition of chronic pulmonary thromboembolic disease as the etiology of pulmonary hypertension warrants evaluation for surgery.

  14. Pregnancy in women with pulmonary hypertension

    NARCIS (Netherlands)

    Pieper, P. G.; Hoendermis, E. S.

    2011-01-01

    Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced

  15. Pregnancy in women with pulmonary hypertension

    NARCIS (Netherlands)

    Pieper, P. G.; Hoendermis, E. S.

    2011-01-01

    Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced

  16. A STUDY TO EVALUATE PATTERN OF RIFAMPICIN RESISTANCE IN CASES OF SPUTUM POSITIVE PULMONARY TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    Joydeep

    2015-04-01

    Full Text Available AIMS: The emergence of drug resistance and development of multidrug resistant tuberculosis (MDR TB has become a new but significant obstacle for TB control. As Rifampicin resistance is an important indicator for drug resistant TB , rapid diagnosis of tuberculosis and detection of Rifampicin (RIF resistance are essential for knowing the magnitude of problem & early management of drug resistance TB. The aim of this study is to determine the pattern of rifampicin resistance in the sputum positive MDR TB suspects by using GeneXpert MTB/RIF and thus to focus on magnitude of the problem on drug resistance tuberculosis. ST UDY DESIGN: A cross sectional observational study carried out over a period of 2 years in a tertiary care hospital. SUBJECTS & METHODS : In this study 428 sputum positive cases of pulmonary tuberculosis who were potential MDR suspect were included , there sp utum samples were collected and tested by GeneXpert MTB/RIF assay , which is an automated cartridge based nucleic acid amplification test to detect presence of mycobacterium tuberculosis and status of Rifampicin resistance. The results are statistically ana lyzed. RESULTS : Out of 428 patients , mycobacterium tuberculosis was detected in 328 patients (76.63% & out of these 328 patients , Rifampicin resistance was found in 98 cases (29.87%. Male and female ratio was 6:1 among Rifampicin resistant cases. Regardi ng age distribution , maximum no. of patients with Rifampicin resistance were in the age group of 21 - 30 yrs (26.53% followed by 31 - 40 yrs (22.44%. In this study among cases of Rifampicin resistance , 23.47% of cases were new smear positive failure patients , retreatment cases smear positive at 4 months were 8.16% , 22.44% of cases were retreatment cases smear positive at diagnosis , 41.83% of cases were retreatment failure cases , 1.03% patient had history of contact with MDR TB and 3.06% patient was HIV seropositive. CONCLUSIONS: Rifampicin resistance cases are found

  17. A Rare Cause of Persistent Pulmonary Hypertension Resistant to Therapy in The Newborn: Short-Rib Polydactyly Syndrome

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    Nihat Demir

    2015-01-01

    Full Text Available Short-rib polydactyly syndrome is an autosomal recessively inherited lethal skeletal dysplasia. The syndrome is characterized by marked narrow fetal thorax, short extremities, micromelia, cleft palate/lip, polydactyly, cardiac and renal abnormalities, and genital malformations. In cases with pulmonary hypoplasia, persistent pulmonary hypertension of the newborn can develop. In this paper, we present a term newborn with persistent pulmonary hypertension of the newborn, which has developed secondary to short-rib polydactyly syndrome and was resistant to therapy with inhaled nitric oxide and oral sildenafil.

  18. Clinical and haemodynamic evaluation of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy: Is schistosomiasis hypertension an important confounding factor?

    Directory of Open Access Journals (Sweden)

    Mario Terra-Filho

    2010-01-01

    Full Text Available INTRODUCTION: Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described. OBJECTIVES: To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil. METHODS: From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels. RESULTS: Thirty-five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male. The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR of 970.8 ± 494.36 dynas·s·cm-5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p=0.001. Brain natriuretic peptide serum levels were elevated in 19 of 27 patients. CONCLUSIONS: In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for

  19. Clinical and haemodynamic evaluation of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy. Is schistosomiasis hypertension an important confounding factor?

    Science.gov (United States)

    Terra‐Filho, Mario; Mello, Marcos Figueiredo; Lapa, Mônica Silveira; Teixeira, Ricardo Henrique Oliveira Braga; Jatene, Fábio Biscegli

    2010-01-01

    INTRODUCTION: Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described. OBJECTIVES: To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil. METHODS: From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels. RESULTS: Thirty‐five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male). The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR) of 970.8 ± 494.36 dynas·s·cm‐5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p = 0.001). Brain natriuretic peptide serum levels were elevated in 19 of 27 patients. CONCLUSIONS: In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for pulmonary

  20. 7A.03: TRANSGENERATIONAL INHERITANCE OF GENOME-WIDE DNA METHYLATION PROFILES IN PULMONARY VASCULAR ENDOTHELIAL DYSFUNCTION FOLLOWING EXTRAUTERINE GROWTH RESTRICTION.

    Science.gov (United States)

    Zhang, L; Du, L; Tang, L; Lao, L; Hu, Q

    2015-06-01

    Early postnatal life is considered as a critical time window for determination of long-term metabolic states and organ functions. Extrauterine growth restriction (EUGR) causes the development of adult onset chronic diseases, including pulmonary hypertension (PH). However, the mechanisms involved and the possibilities of transgenerational transmission on pulmonary vascular consequences in later life are still unclear. Epigenetic information can be inherited and represents a plausible transgenerational carrier of environmental information. Our study was designed to test whether epigenetics dysregulation mediates the cellular memory of this early postnatal event.(Figure is included in full-text article.) : To test this hypothesis, the EUGR pups were established by undernutritional until weaning. We isolated pulmonary vascular endothelial cells (PVEC) by magnetic-activated cell sorting (MACS) from EUGR and control rats. MeDIP-chip (Methyl-DNA immune precipitation chip), genome-scale mapping studies to search for differentially methylated loci. A postnatal insult, nutritional restriction-induced EUGR caused development of an increased PH at 9-week of age in male rats (First-generation of EUGR, F1-EUGR male). We intercrossed female adult control and F1-EUGR-male rats to obtain the second-generation (F2) offspring in two groups: C male-C female, EUGR-male -C-female. We found that significantly decreased pulmonary artery pressure in F2 female offspring in EUGR-male-C-female group (F2-EUGR-female), compared with controls to some degrees. we carried out genome-wide DNA methylation profiles screen for genes in rats between F1-EUGR-male and F2-EUGR-female. The EUGR and control group comparisons revealed consistently and distinctively methylated loci, with 74.8% F1-EUGR-male group and 84.5% F2-EUGR-female group changes in hyper-methylation loci enriched for highly significant group differences. Gene ontology (GO) analysis on no consistent differentially methylated genes

  1. Acute exercise improves endothelial function despite increasing vascular resistance during stress in smokers and nonsmokers.

    Science.gov (United States)

    Rooks, Cherie R; McCully, Kevin K; Dishman, Rod K

    2011-09-01

    The present study examined the effect of acute exercise on flow mediated dilation (FMD) and reactivity to neurovascular challenges among female smokers and nonsmokers. FMD was determined by arterial diameter, velocity, and blood flow measured by Doppler ultrasonography after forearm occlusion. Those measures and blood pressure and heart rate were also assessed in response to forehead cold and the Stroop Color-Word Conflict Test (CWT) before and after 30 min of rest or an acute bout of cycling exercise (∼50% VO₂ peak). Baseline FMD and stress responses were not different between smokers and nonsmokers. Compared to passive rest, exercise increased FMD and decreased arterial velocity and blood flow responses during the Stroop CWT and forehead cold in both groups. Overall, acute exercise improved endothelial function among smokers and nonsmokers despite increasing vascular resistance and reducing limb blood flow during neurovascular stress.

  2. Interactions among Vascular-Tone Modulators Contribute to High Altitude Pulmonary Edema and Augmented Vasoreactivity in Highlanders

    Science.gov (United States)

    Ali, Zahara; Mishra, Aastha; Kumar, Rahul; Alam, Perwez; Pandey, Priyanka; Ram, Rekhbala; Thinlas, Tashi; Mohammad, Ghulam; Pasha, M. A. Qadar

    2012-01-01

    Background The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) and adaptation in highland natives (HLs); both in comparison to HAPE-free sojourners (HAPE-f). Methodology/Principal Findings All the subjects were recruited at 3500 m. We measured clinical parameters, biochemical levels in plasma and gene expression using RNA from blood; analyzed various correlations between and among the clinical parameters, especially arterial oxygen saturation (SaO2) and mean arterial pressure (MAP) and biochemical parameters like, asymmetric dimethylarginine (ADMA), serotonin (5-HT), 8-iso-prostaglandin F2α (8-isoPGF2α), endothelin-1 (ET-1), plasma renin activity (PRA), plasma aldosterone concentration (PAC), superoxide dismutase (SOD) and nitric oxide (NO) in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8-isoPGF2α, ET-1 levels, and PAC were significantly higher (p0.05) lower in HLs than HAPE-f. The expression of respective genes differed in the three groups. In the correlations, SaO2 inversely correlated with ADMA, 5-HT and 8-isoPGF2α and positively with SOD in HAPE-p (p≤0.009). MAP correlated positively with 5-HT and 8-isoPGF2α in HAPE-p and HLs (p≤0.004). A strong positive correlation was observed between ADMA and 5-HT, 5-HT and 8-isoPGF2α (p≤0.001), whereas inverse correlation of SOD with ET-1 in HAPE-p and HLs (p≤0.004), with 5-HT and 8-isoPGF2α in HAPE-p (p = 0.01) and with 5-HT in HLs (p = 0.05). Conclusions/Significance The interactions among these markers confer enhanced vascular activity in HLs and HAPE in sojourners. PMID:22984459

  3. Interactions among vascular-tone modulators contribute to high altitude pulmonary edema and augmented vasoreactivity in highlanders.

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    Zahara Ali

    Full Text Available BACKGROUND: The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE in HAPE-patients (HAPE-p and adaptation in highland natives (HLs; both in comparison to HAPE-free sojourners (HAPE-f. METHODOLOGY/PRINCIPAL FINDINGS: All the subjects were recruited at 3500 m. We measured clinical parameters, biochemical levels in plasma and gene expression using RNA from blood; analyzed various correlations between and among the clinical parameters, especially arterial oxygen saturation (SaO(2 and mean arterial pressure (MAP and biochemical parameters like, asymmetric dimethylarginine (ADMA, serotonin (5-HT, 8-iso-prostaglandin F2α (8-isoPGF2α, endothelin-1 (ET-1, plasma renin activity (PRA, plasma aldosterone concentration (PAC, superoxide dismutase (SOD and nitric oxide (NO in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8-isoPGF2α, ET-1 levels, and PAC were significantly higher (p0.05 lower in HLs than HAPE-f. The expression of respective genes differed in the three groups. In the correlations, SaO(2 inversely correlated with ADMA, 5-HT and 8-isoPGF2α and positively with SOD in HAPE-p (p≤0.009. MAP correlated positively with 5-HT and 8-isoPGF2α in HAPE-p and HLs (p ≤ 0.004. A strong positive correlation was observed between ADMA and 5-HT, 5-HT and 8-isoPGF2α (p≤0.001, whereas inverse correlation of SOD with ET-1 in HAPE-p and HLs (p ≤ 0.004, with 5-HT and 8-isoPGF2α in HAPE-p (p = 0.01 and with 5-HT in HLs (p = 0.05. CONCLUSIONS/SIGNIFICANCE: The interactions among these markers confer enhanced vascular activity in HLs and HAPE in sojourners.

  4. Pulmonary Hypertension in Pregnancy: Critical Care Management

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    Adel M. Bassily-Marcus

    2012-01-01

    Full Text Available Pulmonary hypertension is common in critical care settings and in presence of right ventricular failure is challenging to manage. Pulmonary hypertension in pregnant patients carries a high mortality rates between 30–56%. In the past decade, new treatments for pulmonary hypertension have emerged. Their application in pregnant women with pulmonary hypertension may hold promise in reducing morbidity and mortality. Signs and symptoms of pulmonary hypertension are nonspecific in pregnant women. Imaging workup may have undesirable radiation exposure. Pulmonary artery catheter remains the gold standard for diagnosing pulmonary hypertension, although its use in the intensive care unit for other conditions has slowly fallen out of favor. Goal-directed bedside echocardiogram and lung ultrasonography provide attractive alternatives. Basic principles of managing pulmonary hypertension with right ventricular failure are maintaining right ventricular function and reducing pulmonary vascular resistance. Fluid resuscitation and various vasopressors are used with caution. Pulmonary-hypertension-targeted therapies have been utilized in pregnant women with understanding of their safety profile. Mainstay therapy for pulmonary embolism is anticoagulation, and the treatment for amniotic fluid embolism remains supportive care. Multidisciplinary team approach is crucial to achieving successful outcomes in these difficult cases.

  5. Leptin Resistance: A Possible Interface Between Obesity and Pulmonary-Related Disorders

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    Rehman Khan

    2016-02-01

    Full Text Available Context Under normal physiological conditions, leptin regulates body weight by creating a balance between food intake and energy expenditure. However, in obesity, serum leptin levels increase and become defective to retain energy balance. Evidence Acquisition Elevated serum leptin levels are regarded as an established marker of obesity. It is also reported that obese asthmatic patients have maximum serum leptin levels compared to other groups such as non-obese asthmatics, and normal obese and non obese subjects without asthma. In addition to having an appetite suppressing effect, leptin also regulates certain acute-phase protein expressions including α-1 antitrypsin (A1AT in the liver. Results A1AT is a protease inhibitor that counterbalances the activity of the neutrophil elastase (NE enzyme. A1AT reductions in obese-leptin resistant subjects lead to increased NE activity. The overactivity of NE degrades lung tissue proteins, which may lead to pulmonary disorders including asthma. Conclusions On the basis of prior studies, it could be hypothesized that, in obese asthmatic patients, the highest degree of leptin failure/resistance might lead to the creation of an imbalance between NE and its inhibitor A1AT. To ascertain this, large scale prospective studies are warranted to assess the comparative serum leptin and A1AT levels and NE activity in asthmatic non-obese and obese patients, simultaneously. Such studies might help to devise novel interventional therapies for the treatment of pulmonary-related problems including asthma, chronic obstructive pulmonary disorder (COPD, and other lung defects in susceptible obese subjects in the future.

  6. Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats

    OpenAIRE

    XU, DUNQUAN; Li, Yan; Zhang, Bo; Wang, Yanxia; Liu, Yi; Luo, Ying; Niu, Wen; Dong, Mingqing; Liu, Manling; Dong, Haiying; Zhao, Pengtao; Li, Zhichao

    2016-01-01

    Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The pres...

  7. Diagnosing chronic thromboembolic pulmonary hypertension: current perspectives

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    Hadinnapola C

    2014-09-01

    Full Text Available Charaka Hadinnapola, Deepa Gopalan, David P Jenkins Papworth Hospital National Health Service Foundation Trust, Papworth Everard, Cambridge, United Kingdom Abstract: Chronic thromboembolic pulmonary hypertension is a rare and relatively poorly understood disease. It remains underdiagnosed and is often not recognized in primary and secondary care, as its symptoms are nonspecific and there are few clinical signs until late in the disease process. However, pulmonary endarterectomy (PEA offers a potential cure for patients with this type of pulmonary hypertension; therefore, it is important that they are identified and diagnosed in a timely manner. PEA is associated with a 2.2%–5% risk of significant morbidity and mortality, even in experienced PEA centers. Therefore, once chronic thromboembolic pulmonary hypertension is diagnosed, further assessment of operability and patient selection is crucial. Assessment of operability involves determining the distribution and burden of chronic thromboembolic disease, assessing pulmonary hemodynamics, and assessing the functional impairment of the patient. Ventilation perfusion scintigraphy is of value in screening for the presence of chronic thromboembolic disease. However, computer tomography pulmonary angiography and magnetic resonance pulmonary angiography are now increasingly used to image the vascular occlusions directly. This allows assessment of the surgically accessible disease burden. Some centers still advocate conventional selective pulmonary angiography for the latter. Right-heart catheterization remains the gold standard for assessing pulmonary hemodynamics. Higher pulmonary vascular resistances are associated with poorer outcomes as well as increased risks at the time of surgery. This is in part because of the presence of more distal chronic thromboembolic material and distal pulmonary artery remodeling. However, in experienced centers, these patients are being operated on safely and with good

  8. The effect of ACE inhibition on the pulmonary vasculature in combined model of chronic hypoxia and pulmonary arterial banding in Sprague Dawley rats

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    Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

    2010-03-01

    Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular

  9. Treatment of pediatric pulmonary hypertension

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    Amy Hawkins

    2009-06-01

    Full Text Available Amy Hawkins, Robert TullohDepartment of Congenital Heart Disease, Bristol Royal Hospital for Children, Bristol UKAbstract: Pulmonary hypertension was once thought to be a rare condition and only managed in specialized centers. Now however, with the advent of echocardiography, it is found in many clinical scenarios, in the neonate with chronic lung disease, in the acute setting in the intensive care unit, in connective tissue disease and in cardiology pre- and postoperatively. We have a better understanding of the pathological process and have a range of medication which is starting to be able to palliate this previously fatal condition. This review describes the areas that are known in this condition and those that are less familiar. The basic physiology behind pulmonary hypertension and pulmonary vascular disease is explained. The histopathologic process and the various diagnostic tools are described and are followed by the current and future therapy at our disposal.Keywords: pulmonary hypertension, congenital heart disease, pulmonary vascular resistance, pulmonary vasodilators

  10. Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Hjerkinn, E; Wachtell, K;

    2003-01-01

    Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients...

  11. Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Hjerkinn, E; Wachtell, K;

    2003-01-01

    Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patien...

  12. Intra-arterial papaverine and leg vascular resistance during in situ bypass surgery with high or low epidural anaesthesia

    DEFF Research Database (Denmark)

    Rørdam, Peter; Jensen, Leif Panduro; Schroeder, T V;

    1993-01-01

    patients were operated during high epidural anaesthesia (> Th. 10). Flow increased and arterial pressure decreased after i.a. papaverine in all patients. When compared with patients operated during high epidural anaesthesia, flow increase and decrease in vascular resistance took place in patients operated...

  13. Increased Nitric Oxide Bioavailability and Decreased Sympathetic Modulation Are Involved in Vascular Adjustments Induced by Low-Intensity Resistance Training.

    Science.gov (United States)

    Macedo, Fabrício N; Mesquita, Thassio R R; Melo, Vitor U; Mota, Marcelo M; Silva, Tharciano L T B; Santana, Michael N; Oliveira, Larissa R; Santos, Robervan V; Miguel Dos Santos, Rodrigo; Lauton-Santos, Sandra; Santos, Marcio R V; Barreto, Andre S; Santana-Filho, Valter J

    2016-01-01

    Resistance training is one of the most common kind of exercise used nowadays. Long-term high-intensity resistance training are associated with deleterious effects on vascular adjustments. On the other hand, is unclear whether low-intensity resistance training (LI-RT) is able to induce systemic changes in vascular tone. Thus, we aimed to evaluate the effects of chronic LI-RT on endothelial nitric oxide (NO) bioavailability of mesenteric artery and cardiovascular autonomic modulation in healthy rats. Wistar animals were divided into two groups: exercised (Ex) and sedentary (SED) rats submitted to the resistance (40% of 1RM) or fictitious training for 8 weeks, respectively. After LI-RT, hemodynamic measurements and cardiovascular autonomic modulation by spectral analysis were evaluated. Vascular reactivity, NO production and protein expression of endothelial and neuronal nitric oxide synthase isoforms (eNOS and nNOS, respectively) were evaluated in mesenteric artery. In addition, cardiac superoxide anion production and ventricle morphological changes were also assessed. In vivo measurements revealed a reduction in mean arterial pressure and heart rate after 8 weeks of LI-RT. In vitro studies showed an increased acetylcholine (ACh)-induced vasorelaxation and greater NOS dependence in Ex than SED rats. Hence, decreased phenylephrine-induced vasoconstriction was found in Ex rats. Accordingly, LI-RT increased the NO bioavailability under basal and ACh stimulation conditions, associated with upregulation of eNOS and nNOS protein expression in mesenteric artery. Regarding autonomic control, LI-RT increased spontaneous baroreflex sensitivity, which was associated to reduction in both, cardiac and vascular sympathetic modulation. No changes in cardiac superoxide anion or left ventricle morphometric parameters after LI-RT were observed. In summary, these results suggest that RT promotes beneficial vascular adjustments favoring augmented endothelial NO bioavailability and

  14. Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration.

    Science.gov (United States)

    Goncharova, Elena A; Goncharov, Dmitry A; Krymskaya, Vera P

    2006-01-01

    Migration of human pulmonary vascular smooth muscle (VSM) cells contributes to vascular remodeling in pulmonary arterial hypertension and atherosclerosis. Evidence also indicates that, in part, migration of airway smooth muscle (ASM) cells may contribute to airway remodeling associated with asthma. Here we describe migration of VSM and ASM cells in vitro using Transwell or Boyden chamber assays. Because dissecting signaling mechanisms regulating cell migration requires molecular approaches, our protocol also describes how to assess migration of transfected VSM and ASM cells. Transwell or Boyden chamber assays can be completed in approximately 8 h and include plating of serum-deprived VSM or ASM cell suspension on membrane precoated with collagen, migration of cells toward chemotactic gradient and visual (Transwell) or digital (Boyden chamber) analysis of membrane. Although the Transwell assay is easy, the Boyden chamber assay requires hands-on experience; however, both assays are reliable cell-based approaches providing valuable information on how chemotactic and inflammatory factors modulate VSM and ASM migration.

  15. Endothelial and vascular dysfunctions and insulin resistance in rats fed a high-fat, high-sucrose diet.

    Science.gov (United States)

    Bourgoin, Frédéric; Bachelard, Hélène; Badeau, Mylène; Mélançon, Sébastien; Pitre, Maryse; Larivière, Richard; Nadeau, André

    2008-09-01

    This study was designed to examine the effects of a high-fat, high-sucrose (HFHS) diet on vascular and metabolic actions of insulin. Male rats were randomized to receive an HFHS or regular chow diet for 4 wk. In a first series of experiments, the rats had pulsed Doppler flow probes and intravascular catheters implanted to measure blood pressure, heart rate, and regional blood flows. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine skeletal muscle glucose transport activity and to determine in vitro vascular reactivity, endothelial nitric oxide synthase (eNOS) protein expression in muscle and vascular tissues and endothelin content, nitrotyrosine formation, and NAD(P)H oxidase protein expression in vascular tissues. The HFHS-fed rats displayed insulin resistance, hyperinsulinemia, hypertriglyceridemia, hyperlipidemia, elevated blood pressure, and impaired insulin-mediated renal and skeletal muscle vasodilator responses. A reduction in endothelium-dependent vasorelaxation, accompanied by a decreased eNOS protein expression in muscles and blood vessel endothelium, and increased vascular endothelin-1 protein content were also noted in HFHS-fed rats compared with control rats. Furthermore, the HFHS diet induced a reduced insulin-stimulated glucose transport activity in muscles and increased levels of NAD(P)H oxidase protein and nitrotyrosine formation in vascular tissues. These findings support the importance of eNOS protein in linking metabolic and vascular disease and indicate the ability of a Westernized diet to induce endothelial dysfunction and to alter metabolic and vascular homeostasis.

  16. Delayed Onset Vascular Stiffening Induced by Eccentric Resistance Exercise and Downhill Running.

    Science.gov (United States)

    Lin, Hsin-Fu; Chou, Chun-Chung; Cheng, Hao-Min; Tanaka, Hirofumi

    2017-07-01

    Eccentric exercise induces muscle stiffening and soreness as well as unfavorable changes in macrovascular function. We tested the hypothesis that systemic eccentric exercise could evoke greater arterial stiffening than local eccentric resistance exercise. Twenty healthy young men were randomly assigned into either the downhill running (DR) and the eccentric resistance exercise (RE) group followed by a crossover design with an exercise and sham control trial. Carotid-femoral pulse wave velocity (cfPWV), central hemodynamic measures, and biomarkers were obtained. Muscle soreness and plasma creatine kinase concentrations increased similarly after exercise in both groups. The cfPWV increased significantly at 48 hours post-exercise in both groups and remained elevated at 72 hours in DR. C-reactive protein (CRP) was elevated at 24 and 48 hours in DR, and 48 hours in RE. The increases in cfPWV were associated with the corresponding elevations in CRP in DR (r = 0.70, P < 0.05). There were no changes in arterial wave reflection measures. Both systemic and localized eccentric exercise modes induced delayed onset vascular stiffening with more prolonged changes observed in downhill running. The effect on arterial stiffening was associated, at least in part, with systemic inflammatory responses.

  17. 缺氧性肺动脉高压新生大鼠肺血管重塑的研究%Pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    桑葵; 周英; 李明霞

    2012-01-01

    Objective To study the changes of pulmonary vascular remodeling in the pathogenesis of hypoxia-induced pulmonary hypertension ( HPH) in neonatal rats. Methods Ninety-six newborn Wistar rats were randomly divided into an HPH group (hypoxia exposure) and a control group (room air exposure). The mean pulmonary arteria pressure (mPAP) , right ventricle hypertrophy index ( RVHI) , and vascular remodeling indexes MT% and MA% were measured 3, 5, 7, 10, 14 and 21 days after exposure (re =8 each time point). The ultrastructure of pulmonary vascular was observed under a transmission electron microscope. Results mPAP in the HPH group 3,5,7, 10, 14 and 21 days after hypoxia exposure increased compared with the control group ( P < 0. 05). With the prolonged hypoxia time, mPAP in the HPH group increased more significantly. MT% , MA% and RVHI increased significantly in the HPH group after 7 days of hypoxia exposure in a time-dependent manner compared with the control group (P<0. 05). The transmission electron microscopy demonstrated that small pulmonary arterials became thickened, endothelial cell hyperplasia and degeneration, and organelles increased in the HPH group after 7 days of hypoxia exposure. Besides, collagen deposition in the extracellular matrix and the changes of pulmonary vascular remodeling were observed. Conclusions mPAP increases between 3 and 5 days of hypoxia exposure, resulting from pulmonary vascular spasm caused by hypoxia. After hypoxia of 7 days, the mPAP increases more significantly, pulmonary vascular remodeling occurs, and right ventricle becomes irreversibly hypertrophic. These changes may be intensified as the prolonged hypoxia time.%目的 通过建立新生大鼠缺氧性肺动脉高压(hypoxia-induced pulmonary hypertension,HPH)模型,探讨HPH新生大鼠发病过程中肺血管重塑的变化.方法 将96只新生Wistar大鼠随机分为2组:缺氧组和常氧对照组,缺氧组建立新生大鼠HPH模型.分别于缺氧3、5、7、10、14、21

  18. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

    Science.gov (United States)

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). Conclusion

  19. Management of a child with pulmonary arterial hypertension presenting with systemic hypertension.

    Science.gov (United States)

    Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel

    2016-02-01

    We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.

  20. Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade

    Directory of Open Access Journals (Sweden)

    Julien Guihaire

    2015-01-01

    Full Text Available Background. The epidemiology of pulmonary hypertension (PH is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg. After 28 days, right ventricular (RV remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients.

  1. [Effects of feixin decoction on the contents of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in the rat model of hypoxic pulmonary hypertension].

    Science.gov (United States)

    He, Hong-Jun; Dai, Ai-Guo

    2012-05-01

    To explore the effects of Feixin Decoction (FXD) on the hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in the rat model of hypoxic pulmonary hypertension (HPH), and to study its mechanisms for treating HPH. Forty healthy male SD rats were randomly divided into four groups, i. e., the normal control group, the HPH model group, the FXD group, and the Nifedipine group, 10 rats in each group. The HPH rat model was prepared using normal pressure intermittent hypoxia method. Except the normal control group, rats in the rest groups were fed in a self-made hypoxic plexiglass cabin, with the poor oxygen condition for 8 h daily for 14 successive days. Then the distilled water (at 30 mL/kg) was given by gastrogavage to rats in the normal control group and the HPH model group. FXD (at 28 g/kg) and Nifedipine (at 20 mg/kg) were given by gastrogavage to rats in the FXD group and the Nifedipine group respectively, once daily, for 14 successive days. Besides, hypoxia was continued for 14 days while medicating. The mean pulmonary artery pressure (mPAP) was detected on the second day after the last medication. The morphology of the pulmonary arteriole was detected. The ratio of pulmonary artery wall area and tube area (WA%) was determined. The protein and mRNA expressions of HIF-1alpha and VEGF were detected using immunohistochemistry and in situ hybridization technique. Compared with the normal control group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly increased in the model group (P model group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly decreased in the FXD group (P < 0.01, P < 0.05). FXD down-regulated the expression of VEGF through decreasing the expression of HIF-1alpha. One of its mechanisms for treating HPH might be partially due to reversing the remodeling of pulmonary vascular smooth muscle.

  2. [The role of individual stress resistance in realization of immobilization and zoosocial stress effects on pulmonary surfactant system].

    Science.gov (United States)

    Vasil'eva, N N; Bryndina, I G

    2012-07-01

    The aim of the present study was to investigate the effect of chronic exposure to immobilization and psychosocial stress on surface activity, biochemical composition of pulmonary surfactant and lung fluid balance of rats with different stress-resistance. It is shown that both types of stress lead to elevation of lysophospholipids level and decrease of surface-active properties of pulmonary surfactant, more prominent in stress-vulnerable rats. Blood supply was decreased and extravascular fluid was increased under the psychosocial stress only in stress-vulnerable animals, in all rest cases the blood supply was increased and the content of extravascular fluid was not changed. Surfactant alteration was coupled on the level of 11-OCS in the blood and amount of fluid in the lungs. The obtained results indicate that different degree of impairment in the pulmonary surfactant system during immobilization and psychosocial conflicts depends on different resistance to emotional stress.

  3. Análise da remodelação vascular na isquemia pulmonar experimental, nas fases aguda e crônica Analysis of acute and chronic vascular remodeling in an experimental model of pulmonary ischemia

    Directory of Open Access Journals (Sweden)

    Wanderley M. Bernardo

    2005-02-01

    pulmonary circulation characterize the vascular remodeling process and are likely correlated with local variations in flow and ischemia. OBJECTIVE: To define the histological alterations to the pulmonary circulation seen after experimentally-induced ischemia of the pulmonary artery and to correlate those alterations with known patterns of blood redistribution and vascular remodeling. METHOD: Wistar rats (n = 48 were randomized into two groups with ligation of the pulmonary artery and without (controls and were sacrificed on post-ischemia days 1, 7, 30 and 60. Lungs were removed and inspected for signs of parenchymal injury. External diameters, as well as wall thicknesses in the pulmonary, alveolar and bronchial end arterioles, were measured. Internal diameter and wall thickness percentage were calculated. RESULTS: Infarction, necrosis and hemorrhage occurred only in ischemic lungs. In nonischemic lungs, there was a sustained increase in the internal and external arteriolar diameters, with an initial reduction in wall thickness on day 1, and day-60 values were similar to those seen in controls. In ischemic lungs, there was a transitory reduction in the internal and external diameters of the pulmonary and bronchial end arterioles, together with an initial, equally transitory, increase in their wall thickness. The alveolar arterioles presented sustained and progressive increases in external diameter and wall thickness, with concomitant reductions in internal diameter. CONCLUSION: This model mimics distal arterial disease in patients with chronic pulmonary thromboembolism. The vascular response in nonischemic lungs was consistent with a pattern of flow remodeling, whereas that seen in ischemic lungs was more consistent with flow and ischemia. In the pulmonary and bronchial end arterioles, the response was transitory, in contrast to the sustained and progressive response seen in the alveolar arterioles, which was probably caused by delayed local flow.

  4. Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats.

    Science.gov (United States)

    Babacanoglu, C; Yildirim, N; Sadi, G; Pektas, M B; Akar, F

    2013-10-01

    Dietary intake of fructose and sucrose can cause development of metabolic and cardiovascular disorders. The consequences of high-fructose corn syrup (HFCS), a commonly consumed form of fructose and glucose, have poorly been examined. Therefore, in this study, we investigated whether HFCS intake (10% and 20% beverages for 12 weeks) impacts vascular reactivity to insulin and endothelin-1 in conjunction with insulin receptor substrate-1(IRS-1), endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) mRNA/proteins levels in aorta of rats. At challenge, we tested the effectiveness of resveratrol (28-30 mg/kg body weight/day) on outcomes of HFCS feeding. HFCS (20%) diet feeding increased plasma triglyceride, VLDL, cholesterol, insulin and glucose levels, but not body weights of rats. Impaired nitric oxide-mediated relaxation to insulin (10⁻⁹ to 3×10⁻⁶ M), and enhanced contraction to endothelin-1 (10⁻¹¹ to 10⁻⁸ M) were associated with decreased expression of IRS-1 and eNOS mRNA and protein, but increased expression of iNOS, in aortas of rats fed with HFCS. Resveratrol supplementation restored many features of HFCS-induced disturbances, probably by regulating eNOS and iNOS production. In conclusion, dietary HFCS causes vascular insulin resistance and endothelial dysfunction through attenuating IRS-1 and eNOS expressions as well as increasing iNOS in rats. Resveratrol has capability to recover HFCS-induced disturbances.

  5. A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis

    DEFF Research Database (Denmark)

    Su, Junjing; Hilberg, Ole; Howard, Luke

    2016-01-01

    Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects...... reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used...

  6. Baroreflex-mediated heart rate and vascular resistance responses 24 h after maximal exercise

    Science.gov (United States)

    Convertino, Victor A.

    2003-01-01

    INTRODUCTION: Plasma volume, heart rate (HR) variability, and stimulus-response relationships for baroreflex control of forearm vascular resistance (FVR) and HR were studied in eight healthy men after and without performing a bout of maximal exercise to test the hypotheses that acute expansion of plasma volume is associated with 1) reduction in baroreflex-mediated HR response, and 2) altered operational range for central venous pressure (CVP). METHODS: The relationship between stimulus (DeltaCVP) and vasoconstrictive reflex response (DeltaFVR) during unloading of cardiopulmonary baroreceptors was assessed with lower-body negative pressure (LBNP, 0, -5, -10, -15, -20 mm Hg). The relationship between stimulus (Deltamean arterial pressure (MAP)) and cardiac reflex response (DeltaHR) during loading of arterial baroreceptors was assessed with steady-state infusion of phenylephrine (PE) designed to increase MAP by 15 mm Hg alone and during application of LBNP (PE+LBNP) and neck pressure (PE+LBNP+NP). Measurements of vascular volume and autonomic baroreflex responses were conducted on two different test days, each separated by at least 1 wk. On one day, baroreflex response was tested 24 h after graded cycle exercise to volitional exhaustion. On another day, measurement of baroreflex response was repeated with no exercise (control). The order of exercise and control treatments was counterbalanced. RESULTS: Baseline CVP was elevated (P = 0.04) from a control value of 10.5 +/- 0.4 to 12.3 +/- 0.4 mm Hg 24 h after exercise. Average DeltaFVR/DeltaCVP during LBNP was not different (P = 0.942) between the exercise (-1.35 +/- 0.32 pru x mm Hg-1) and control (-1.32 +/- 0.36 pru x mm Hg-1) conditions. However, maximal exercise caused a shift along the reflex response relationship to a higher CVP and lower FVR. HR baroreflex response (DeltaHR/DeltaMAP) to PE+LBNP+NP was lower (P = 0.015) after maximal exercise (-0.43 +/- 0.15 beats x min-1 x mm Hg-1) compared with the control

  7. Current insights on the pathogenesis of pulmonary arterial hypertension.

    Science.gov (United States)

    Perros, Frédéric; Dorfmüller, Peter; Humbert, Marc

    2005-08-01

    Regardless of the initial trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with pulmonary arterial hypertension are primarily caused by remodeling and thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well as sustained vasoconstriction. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by cellular heterogeneity within each compartment. Indeed, each cell type (endothelial cells, smooth muscle cells, and fibroblasts), as well as inflammatory cells and platelets, may play significant roles in this condition. Recent studies have emphasized the relevance of several mediators in this condition, including prostaglandin-I (2) (prostacyclin), nitric oxide, endothelin-1, angiopoietin-1, 5-hydroxytryptamine (serotonin), cytokines, chemokines, and members of the transforming growth factor beta (TGF-beta) superfamily. Targeting some of these dysfunctional pathways (prostacyclin, nitric oxide, and endothelin-1) has been beneficial in subjects displaying pulmonary arterial hypertension.

  8. Multidrug-Resistant Tuberculosis in Patients with Chronic Obstructive Pulmonary Disease in China.

    Directory of Open Access Journals (Sweden)

    Jiang-Nan Zhao

    Full Text Available Relatively little is known about the specific relationship and impact from chronic obstructive pulmonary disease (COPD on multidrug-resistant tuberculsosis (MDR-TB.We conducted a retrospective study included patients aged ≥40 years with a confirmed pulmonary TB at three tertiary hospitals (Shandong, China between January 2011 and October 2014. Univariable and multivariable analyses were performed to identify the relationship of MDR-TB and COPD.A total of 2164 patients aged ≥ 40 years with available results of drug susceptibility test (DST and medical records were screened for this study: 268 patients with discharge diagnosis of COPD and 1896 patients without COPD. Overall, 14.2% of patients with COPD and 8.5% patients without COPD were MDR-TB. The rate of MDR-TB were significantly higher in patients with COPD (P<0.05. Migrant (odds ratios (OR 1.32, 95% confidence interval (CI 1.02-1.72, previous anti-TB treatment (OR 4.58, 95% CI 1.69-12.42, cavity (OR 2.33, 95% CI 1.14-4.75, and GOLD stage (OR 1.86, 95% CI 1.01-2.93 were the independent predictors for MDR-TB among patients with COPD.MDR-TB occurs more frequently in patients with underlying COPD, especially those with being migrant, previous anti-TB therapy, cavity and severe airway obstruction.

  9. Terpene Profile, Leaf Anatomy, and Enzyme Activity of Resistant and Susceptible Cocoa Clonesto Vascular Streak Dieback Disease

    Directory of Open Access Journals (Sweden)

    Adi Prawoto

    2014-10-01

    Full Text Available Vascular-streak dieback (VSD, Oncobasidium theobromae is the most prevalent disease of Theobroma cacao L. in Indonesia. This study aims to analyze resistance mechanism to VSD based on terpene profile, leaf anatomy, chitinase, and peroxidase study. Resistant clones of Sulawesi 1 and Sca 6 and susceptible clones of ICS 60 and TSH 858 were used for terpene profile, leaf anatomy analysis, chitinase, peroxides, polyphenol, lignin, and cellulose analysis. Those clones and KEE 2, KKM 22 and ICS 13 were used for peroxides analysis. For trichome study, the resistant clones of Sulawesi 1, Sca 6, KEE 2, and KKM 22, and susceptible clones of ICS 60 and TSH 858 were used. GCMS analysis showed that chromatogram pattern of resistant and susceptible groups were quite similar, but resistant clones contained 22% more components than the susceptible ones. Resistant clones contained groups of pinene, decane, myrcene, and octadecanoic acid, while those substances on usceptible clones were absent. Trichome was thicker on younger leaf, and its density on the basal was higher than that on the middle and tip leaf parts. Trichome density of resistant clone was not always thicker than that of susceptible ones. On resistant clones, stomatal density was lower and width of stomate pits was narrower, while thickness of epidermis layer and pallisade parenchym were higher. Polyphenol content of resistant clones were higher but lignin and cellulose of both groups were similar. Chitinase activity which has a role in hydrolysis of mycelia cell wall was higher on the resistant clones, but peroxides which has a role in polymeration of lignin biosynthesis was similar between both groups. It is concluded that groups of terpene pinene, decane, myrcene, and octadecanoic acid, thickness of leaf epidermis, density and width of stomata pit, and chitinase activity plays important role in cocoa resistance to VSD. Key words: Theobroma cacaoL., clone, vascular-streak dieback, resistance, leaf

  10. Solitary pulmonary nodules: comparison of multi-slice computed tomography perfusion study with vascular endothelial growth factor and microvessel density

    Institute of Scientific and Technical Information of China (English)

    BAI Rong-jie; CHENG Xiao-guang; QU Hui; SHEN Bao-zhong; HAN Ming-jun; WU Zhen-hua

    2009-01-01

    Background The solitary pulmonary nodule (SPN) is one of the most common findings on chest radiographs. The objectives of clinical practice are to differentiate malignant nodules from benign nodules in the least invasive way and to make a specific diagnosis. This study was aimed to evaluate the correlation between perfusion imaging features and microvessel density (MVD) and vascular endothelial growth factors (VEGF) in SPNs using multi-slice computed tomography (MSCT); and to provide the theoretical basis for SPN blood flow pattern and blood flow quantitative features.Also, the study called for the discussion of the method's clinical application value in the differential diagnosis of benign and malignant SPNs.Methods Sixty-eight patients with SPN underwent multi-location dynamic contrast enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 ml/s) MSCT. Precontrast and postcontrast attenuations on every scan was studied. Perfusion, peak height, and the ratio of the peak height of the SPN to that of the aorta were analyzed. Perfusion was calculated using the maximum gradient of the time-density curves (TDC) and the peak height of the aorta. The quantitative parameters (perfusion, peak height, ratio of peak height of the SPN to that of the aorta) of the blood flow pattern were compared with MVD and the VEGF expression of immunohistochemistry.Results The perfusion peak heights of malignant ((96.15±11.55) HU) and inflammatory ((101.15±8.41) HU) SPNs were significantly higher than those of benign ((47.24±9.15) HU) SPNs (P<0.05, P<0.05). Ratios of SPN-to-aorta of malignant and inflammatory SPNs were significantly higher than those of benign SPNs (P<0.05, P<0.05). No significant differences were found between the peak height and SPN-to-aorta ratio of malignant SPNs and inflammatory SPNs (P>0.05, P>0.05). The precontrast densities of inflammatory SPNs were lower than those of malignant SPNs (P<0.05).Perfusion values

  11. Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming; Henriksen, Jens Henrik

    2001-01-01

    ) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P controls 1.01 ml/mmHg; P ... systemic vascular resistance increased substantially (1083 versus 1378 dyn x s x cm-5, +27%; P blood pressure (-6%; P blood flow (-22%; P ... with beta-blockers increases small vessel (arteriolar) vascular tone towards the normal level, but does not affect the elevated compliance of the larger arteries in patients with cirrhosis....

  12. The clinical application of pulmonary vascular permeability index on differential diagnosis of acute pulmonary edema%肺血管通透性指数对急性肺水肿鉴别诊断价值初探

    Institute of Scientific and Technical Information of China (English)

    杨从山; 谢剑锋; 莫敏; 刘松桥; 黄英姿; 邱海波; 杨毅

    2011-01-01

    目的 探讨肺血管通透性指数(PVPI)在急性肺水肿鉴别诊断中的价值.方法 选2004年5月至2008年9月收住东南大学附属中大医院重症医学科,留置脉搏指示连续心排血量(PiCCO)导管,氧合指数[PaO2/吸入氧浓度(FiO2)]<300 mm Hg(1 mm Hg=0.133 kPa)且血管外肺水指数(EVLWI)≥7 ml/kg的急性肺水肿患者,分为急性肺损伤(ALI)组和心源性肺水肿组,观察PVPI、胸腔内血容量指数(ITBVI)、肺血容量(PBV)、血管外肺水(EVLW)/胸腔内血容量(ITBV)在2组中的变化与差异.结果 (1)34例患者纳入研究,其中ALI 22例,心源性肺水肿12例;(2)ALI组PVPI为2.7±1.4,心源性肺水肿组为1.9±0.6,2组比较,P<0.05.EVLWI、ITBVI在2组间差异无统计学意义(P>0.05);(3)PVPI与EVLWI呈正相关(r=0.762,P=0.000),与PaO2/FiO2呈负相关(r=-0.478,P=0.012);(4)纳入患者中肺内原因ARDS 8例,肺外原因ARDS 5例,肺外原因ARDS患者PVPI、EVLW/ITBV和EVLWI显著高于肺内原因ARDS患者.结论 PVPI有助于对重症患者肺水肿类型的鉴别.%Objective To assess the value of pulmonary vascular permeability index in differentiating acute lung injury (ALI) from cardiac pulmonary edema. Methods Critically ill patients with acute pulmonary edema were included from May, 2004 to September, 2008. Patients were divided into two groups, the ALI group and the cardiac pulmonary edema group (C group). Pulmonary vascular permeability index (PVPI) , intrathoracic blood volume (ITBVI) were determined by pulse indicator continuous cardiac output(PiCCO) system. Results ( 1 ) Thirty-four patients were enrolled, 22 cases in ALI group and 12 cases in C group. (2) The PVPI in patients of ALI group (2.7 ± 1.4) was higher than that of C group (1.9 ±0.6 ;P<0.05). EVLWI and ITBVI did not have the significant difference between the two groups (P >0. 05). (3) PVPI was positively correlated with EVLWI(r = 0. 762) , negatively correlated with PaO2/ FiO2(r= -0.478). (4)ARDS was diagnosed

  13. Smooth muscle myosin inhibition: a novel therapeutic approach for pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    David Ho

    Full Text Available OBJECTIVE: Pulmonary hypertension remains a major clinical problem despite current therapies. In this study, we examine for the first time a novel pharmacological target, smooth muscle myosin, and determine if the smooth muscle myosin inhibitor, CK-2019165 (CK-165 ameliorates pulmonary hypertension. MATERIALS AND METHODS: Six domestic female pigs were surgically instrumented to measure pulmonary blood flow and systemic and pulmonary vascular dynamics. Pulmonary hypertension was induced by hypoxia, or infusion of the thromboxane analog (U-46619, 0.1 µg/kg/min, i.v.. In rats, chronic pulmonary hypertension was induced by monocrotaline. RESULTS: CK-165 (4 mg/kg, i.v. reduced pulmonary vascular resistance by 22±3 and 28±6% from baseline in hypoxia and thromboxane pig models, respectively (p<0.01 and 0.01, while mean arterial pressure also fell and heart rate rose slightly. When CK-165 was delivered via inhalation in the hypoxia model, pulmonary vascular resistance fell by 17±6% (p<0.05 while mean arterial pressure and heart rate were unchanged. In the monocrotaline model of chronic pulmonary hypertension, inhaled CK-165 resulted in a similar (18.0±3.8% reduction in right ventricular systolic pressure as compared with sildenafil (20.3±4.5%. CONCLUSION: Inhibition of smooth muscle myosin may be a novel therapeutic target for treatment of pulmonary hypertension.

  14. The Role of Endogenous Carbon Monoxide in the Hypoxic Vascular Remodeling of Rat Model of Hypoxic Pulmonary Hypertension

    Institute of Scientific and Technical Information of China (English)

    甄国华; 张珍祥; 徐永健

    2003-01-01

    We investigated the expression of heme oxygenase-1 (HO-l) gene and production of endogenous carbon monoxide (CO) in the rat lung tissue at different time points of chronic hypoxic pulmonary hypertension and the effect of hemin on the expression of HO-1 gene and pulmonary hypertension. A rat model of hypoxic pulmonary hypertension was recreated by exposure to intermittent normobaric hypoxic environment (10 % O2 ). Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the level of HO-1 mRNA in the rat lung tissue and double wave length spectrophotometry was used to evaluate the quantity of COHb in arterial blood. Cardiac catheterization was employed to measure the right ventricular systolic pressure (RVSP) and HE staining was performed in dissected lung tissue to observe the pathological changes of the intra-acinar pulmonary arteries (IAPA). It was found that (1) There was a low level of HO-1 mRNA in normal rat lung tissue, but the level of HO-1 mRNA increased by 2-4 times in the lung tissue of hypoxic rats (P<0.01). The quantity of COHb was 2-3 times those of control group (P<0.01or P<0. 05). These were accompanied by the increased of RVSP and the thickened IAPA; (2) Hemin could keep the HO-1 mRNA and COHb in the hypoxic rat lung tissue at a high level, and partially suppressed the increase of rat RVSP, thereby ameliorating the pathological changes of IAPA.In conclusion, the upregulation of the expression of HO-1 gene and production of CO in the rat lung of hypoxic pulmonary hypertension plays a role of inhibition in the development of hypoxic pulmonary hypertension. Hemin has a therapeutic effect on hypoxic pulmonary hypertension.

  15. Efficacy of losartan for improving insulin resistance and vascular remodeling in hemodialysis patients.

    Science.gov (United States)

    Sun, Fang; Song, Yan; Liu, Jing; Ma, Li-Jie; Shen, Yang; Huang, Jing; Zhou, Yi-Lun

    2016-01-01

    Insulin resistance and vascular remodeling are prevalent and predict cardiovascular mortality in hemodialysis patients. Angiotensin II (Ang II) may be involved in both pathogenesis. In the present study, we investigated the effects of the Ang II receptor blocker losartan on insulin resistance, arterial stiffness, and carotid artery structure in hemodialysis patients. Seventy-two hemodialysis patients were randomly assigned to receive either losartan 50 mg qd (n = 36) or β-blocker bisoprolol 5 mg qd (n = 36). At the start and at month 12, ambulatory blood pressure (BP) monitoring, aortic pulse wave velocity (PWV) measurements, and carotid artery ultrasound were performed, and homeostasis model assessment index of insulin resistance (HOMA-IR) was determined. During the study period, bioimpedance method was used to evaluate volume status every 3 months. Home-monitored BPs were measured at least monthly. Ambulatory BP decreased significantly and similarly by either losartan or bisoprolol. Decreases in PWVs in losartan group at the end of month 12 were significantly greater than changes in PWV in bisoprolol group (0.9 ± 0.3 vs. 0.4 ± 0.5 m/s, P = 0.021). Common carotid artery intima-media cross-sectional area decreased significantly only in patients treated with losartan (20.3 ± 4.9 vs. 19.1 ± 5.1 mm(2) , P = 0.001), and HOMA-IR was also reduced in losartan group only (1.9 ± 1.0 vs. 1.7 ± 0.8, P = 0.003). Multiple regression analysis showed significant correlations between changes in PWV and changes in HOMA-IR. With comparable BP-lowering efficacy, losartan achieved better improvement in insulin sensitivity, arterial stiffness, and carotid artery hypertrophy in hemodialysis patients. The regression of arterial stiffness may be in part through attenuation in insulin resistance.

  16. Managing chronic thromboembolic pulmonary hypertension: pharmacological treatment options

    Directory of Open Access Journals (Sweden)

    I. M. Lang

    2009-03-01

    Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH and right heart failure. The treatment of choice is pulmonary endarterectomy, which restores pulmonary haemodynamics with acceptable periprocedural mortality rates in the majority of suitable patients. However, CTEPH may be inoperable owing to surgically inaccessible thrombi or comorbid diseases that confer an unacceptably high risk. Pharmacotherapies, although not yet approved, may be useful in this situation or for treating residual or recurrent PH following surgery. Vasodilator drugs for PH are attracting growing interest as potential treatments for CTEPH because this disease has recently been labelled as a "dual" pulmonary vascular disorder: major vessel obstruction and remodelling is combined with a small vessel arteriopathy that is histologically indistinguishable from the classical pulmonary arteriopathy observed in pulmonary arterial hypertension. Of three completed randomised controlled trials in patients with CTEPH, only one was powered to detect a treatment effect. The BENEFIT trial employed the dual endothelin-receptor antagonist bosentan. Although haemodynamics improved significantly, the second component of the primary end-point, exercise capacity, was not met. More evidence is required to resolve whether vasodilator treatments are beneficial for inoperable chronic thromboembolic pulmonary hypertension.

  17. Effects of low-load resistance training with vascular occlusion on the mechanical properties of muscle and tendon.

    Science.gov (United States)

    Kubo, Keitaro; Komuro, Teruaki; Ishiguro, Noriko; Tsunoda, Naoya; Sato, Yoshiaki; Ishii, Naokata; Kanehisa, Hiroaki; Fukunaga, Tetsuo

    2006-05-01

    The present study aimed to investigate the effects of low-load resistance training with vascular occlusion on the specific tension and tendon properties by comparing with those of high-load training. Nine participants completed 12 weeks (3 days/week) of a unilateral isotonic training program on knee extensors. One leg was trained using low load (20% of 1 RM) with vascular occlusion (LLO) and other leg using high load (80% of 1 RM) without vascular occlusion (HL). Before and after training, maximal isometric knee extension torque (MVC) and muscle volume were measured. Specific tension of vastus lateralis muscle (VL) was calculated from MVC, muscle volume, and muscle architecture measurements. Stiffness of tendon-aponeurosis complex in VL was measured using ultrasonography during isometric knee extension. Both protocols significantly increased MVC and muscle volume of quadriceps femoris muscle. Specific tension of VL increased significantly 5.5% for HL, but not for LLO. The LLO protocol did not alter the stiffness of tendon-aponeurosis complex in knee extensors, while the HL protocol increased it significantly. The present study demonstrated that the specific tension and tendon properties were found to remain following low-load resistance training with vascular occlusion, whereas they increased significantly after high-load training.

  18. The Role of Hyperglycemia and Insulin Resistance in the Development and Progression of Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Daniel Grinnan

    2016-01-01

    Full Text Available Pulmonary hypertension is a progressive disorder which often leads to right ventricular failure and death. While the existing classification system for pulmonary hypertension does not account for the impact of diabetes mellitus, evidence is emerging that suggests that diabetes is associated with pulmonary hypertension and that diabetes modifies the course of pulmonary hypertension. There is also growing radiographic, hemodynamic, biochemical, and pathologic data supporting an association between diabetes and pulmonary hypertension. More robust epidemiologic studies are needed to confirm an association between diabetes and pulmonary hypertension and to show that diabetes is a disease modifier in pulmonary hypertension. In addition, evaluating the effects of glucose control in animals with pulmonary hypertension and diabetes (as well as in humans is warranted.

  19. Ozone-Induced Pulmonary Injury and Vascular Contractility are Differentially Impacted by Coconut, Fish, and Olive Oil-Rich Diets

    Science.gov (United States)

    Pulmonary and systemic effects of ozone (O3) are mediated by hypothalamus pituitary adrenal (HPA)-axis activation. Fish oil (FO) and olive oil (OO) dietary supplementation have several cardioprotective benefits, but it is not established if these supplements can protect against t...

  20. Ozone-Induced Pulmonary Injury and Vascular Contractility are Differentially Impacted by Coconut, Fish, and Olive Oil-Rich Diets

    Science.gov (United States)

    Pulmonary and systemic effects of ozone (O3) are mediated by hypothalamus pituitary adrenal (HPA)-axis activation. Fish oil (FO) and olive oil (OO) dietary supplementation have several cardioprotective benefits, but it is not established if these supplements can protect against t...

  1. Acquired resistance to innate immune clearance promotes Klebsiella pneumoniae ST258 pulmonary infection

    Science.gov (United States)

    Ahn, Danielle; Peñaloza, Hernán; Wang, Zheng; Wickersham, Matthew; Parker, Dane; Patel, Purvi; Koller, Antonius; Chen, Emily I.; Bueno, Susan M.; Uhlemann, Anne-Catrin; Prince, Alice

    2016-01-01

    Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant Klebsiella pneumoniae ST258 (KP35) were identified and help to explain the selection of this strain as a successful pulmonary pathogen. The acquisition of 4 new ortholog groups, including an arginine transporter, enabled KP35 to outcompete related ST258 strains lacking these genes. KP35 infection elicited a monocytic response, dominated by Ly6Chi monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers. In comparison with other K. pneumoniae strains, KP35 induced global changes in the phagocytic response identified with proteomics, including evasion of Ca2+ and calpain activation necessary for phagocytic killing, confirmed in functional studies with neutrophils. This comprehensive analysis of an ST258 K. pneumoniae isolate reveals ongoing genetic adaptation to host microenvironments and innate immune clearance mechanisms that complements its repertoire of antimicrobial resistance genes and facilitates persistence in the lung. PMID:27777978

  2. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    Energy Technology Data Exchange (ETDEWEB)

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. (Medical Univ. of South Carolina, Charleston (USA))

    1990-06-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  3. Radioimmunotherapy Using Vascular Targeted 213Bi: The Role of TNF-Alpha in the Development of Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Davis, I.A.; Kennel, S.J.

    1998-10-14

    A monoclonal antibody (201B) specific to murine thrombomodulin, covalently linked to CHX-b-DTPA, successfully delivers chelated 213Bi, an {alpha}-particle emitter, (213Bi-201B) rapidly to lungvascular endothelium. When injected at doses of l MBq/mouse, 213Bi-201B destroyed most of the 100 colonies of EMT-6 mammary carcinomas growing as lung tumors of up to 2000 cells/colony. Some mice were cured of lung tumors and others had extended life-spans compared to untreated control animals but eventually succumbed to tumor recurrence. At injected doses of 4-6 MBq/mouse, 100% of lung tumor colonies were eliminated; however, 3-4 months later these mice developed pulmonary fibrosis and died. The mechanisms leading to the fibrotic response in other pulmonary irradiation models strongly implicate tumor necrosis factor-alpha (TNF-{alpha}), released from damaged tissues, as the pivotal inflammatory cytokine in a cascade of events which culminate in fibrosis. Attempts to prevent the development of pulmonary fibrosis, by using antibodies or soluble receptor (Enbrel{trademark}) as inhibitors of TNF-{alpha}, were unsuccessful. Additionally, mice genetically deficient for TNF-{alpha} production developed pulmonary fibrosis following 213Bi-201B treatment. Interestingly, non-tumor bearing BALB/c mice receiving Enbrel{trademark} or mice genetically deficient in TNF-{alpha} production and treated with 213Bi-201B, had significantly reduced life spans compared to mice receiving no treatment or 213Bi-201B alone. We speculate that, in normal mice, while TNF-{alpha} may induce an inflammatory response following {alpha}-particle radiation mediated tumor clearance and pulmonary damage, its effects in the post-tumor clearance time period may actually retard the development of fibrosis.

  4. Effects of alpha-adrenoceptor and of combined sympathetic and parasympathetic blockade on cardiac performance and vascular resistance

    DEFF Research Database (Denmark)

    Kelbaek, H; Frandsen, Henrik Lund; Hilsted, J

    1992-01-01

    1. Cardiac performance and vascular resistance was studied in seven healthy men by radionuclide cardiography and venous plethysmography before and after alpha-adrenoceptor blockade with phentolamine and after combined alpha-adrenoceptor, beta-adrenoceptor (propranolol) and parasympathetic (atropine...... propranolol and atropine were added. 3. These results indicate that peripheral vasoconstriction especially that exerted by alpha-adrenoceptor nervous tone in skeletal muscle restricts left ventricular emptying of the intact heart. During pharmacologic blockade of the sympathetic and parasympathetic nervous...

  5. Impact of Resisted Exercise on Chronic Obstructive Pulmonary Disease (COPD in Elderly Patients in Alkharj, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Walid Kamal M. A

    2016-05-01

    Full Text Available Some studies have evaluated the effect of resisted exercise on COPD in adult but there is limited data on the effectiveness of resistance exercise on COPD in elderly patients. The effect of three months resisted exercise training on pulmonary functions for COPD in elderly patients has been studied. The aim of this study was to investigate the influences of resisted exercise on COPD in elderly patients at Alkharj, Saudi Arabia. Forty obese elderly patients with moderate COPD with age of 60-70 years were selected from the patients living in Alkharj, KSA for this study. Their body mass index (BMI ranged from 30 to > 40 kg/m2 .They were randomly divided into two groups, each group consisted of 20 patients, group A received a program of resisted exercise(RE 3 times/week with breathing exercise and group B received only breathing exercise without any program of resisted exercise. The pulmonary functions changes (FVC, FEV1, FEV1/FVC%, PEF, FEF25-75% and MVV were measured at the beginning of the study and after twelve weeks. Showed that resisted exercise had greater improvement in FVC, FEV1, FEV1/FVC%, PEF, FEF25-75% and MVV were respectively (+0.1, +0.19, +4.2, +0.44, +0.09 and +3.8 when compared to the second group, little changes were respectively (+0.04, +0.04, +0.5, +0.45, +.03 and +1.2. It was concluded that a program of resisted exercise showed significant improvement in pulmonary functions in elderly patients with COPD in a short term (up to twelve weeks.

  6. [Thrombo-embolic pulmonary hypertension--do not spoil a chance for effective surgery!].

    Science.gov (United States)

    Kurzyna, Marcin; Torbicki, Adam; Poloński, Lech; Skoczylas, Ilona; Przybylski, Roman; Wieteska, Maria; Dyk, Wojciech; Biederman, Andrzej; Zembala, Marian

    2011-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as pulmonary hypertension with persistent pulmonary perfusion defects causes by unresolved thrombi. All symptomatic CTEPH patients with documented pulmonary vascular resistance > 300 dyn*sec*cm(-5) and proximal lesions should be considered for surgical treatment--pulmonary endarterectomy. The role of pharmacological treatment remains controversial and should be restricted to inoperable cases and persistent pulmonary hypertension after pulmonary endarterectomy. Every year about 30 procedures is performed in two specialised centers in Poland with 1 year mortality at 8-9%. Number of procedures done gives the frequency of pulmonary endarterectomy at 0.7/million of population/year. Current data from UK indicate the actual ratio of surgical treatment of CTPH at 2/million/year. The article discusses reasons for CTEPH is underdiagnosed and why rate of surgical therapy in Poland is too low.

  7. Effect of stellate block on vasomotor factor, vascular endothelial nitricoxide synthase and pulmonary arterial pressure in rabbits with hypoxic pulmonary artery hypertension

    Institute of Scientific and Technical Information of China (English)

    Shunhou He; Qing Li; Sen Chen; Qingxiu Wang

    2007-01-01

    BACKGROUND: At present, inhalation of nitrogen monoxidum (NO) or other angiotenic is widely used to cure hypoxic pulmonary artery hypertension. In addition, recent researches demonstrate that postganglionic fiber of stellate ganglion can regulate contents of blood vessel endothelium-calcitonin gene-related peptide (BE-CGRP) and nitricoxide synthase (NOS) in lung tissue. Therefore, stellate ganglion which is blocked with the local anesthetic may cause therapeutic effects on hypoxic pulmonary artery hypertension.OBJECTIVE: To observe the effects of stellate block on calcitonin gene-related peptide (CGRP) of vasodilation factors, prostacyclin, endothelin-1 of vasoconstriction factors, thromboxan, blood vessel endothelium-nitricoxide synthase (BE-NOS) and mean arterial pressure of lung tissue in rabbits with hypoxic pulmonary artery hypertension.DESIGN: Randomly controlled animal study.SETTING: Neurological Institute of Taihe Hospital Affiliated to Yunyang Medical College.MATERIALS: A total of 24 adult Japanese rabbits of both genders and weighing 2.3 - 2.6 kg were provided by Animal Experimental Center of Hubei Academy of Medical Science. SP kit was provided by Beijing Zhongshan Biotechnology Co., Ltd.; moreover, kits of endothelin-1, CGRP, prostacyclin and thromboxan were provided by Radioimmunity Institute, Scientific and Technological Developing Center, General Hospital of Chinese PLA, and color image analytical system (Leica-Q500IW) was made in Germany.METHODS: The experiment was carried out in the Neurological Institute of Taihe Hospital affiliated to Yunyang Medical College from February to December 2002, ① Rabbits were performed with aseptic manipulation to exposure left stellate ganglion and then it was put in epidural catheter for 1 week. In addition,one end of epidural catheter was fixed near by stellate ganglion and the other end was fixed through dorsal neck. All rabbits were randomly divided into 4 groups, including normal control group, stellate block

  8. Serum angiopoietin-like protein 3 levels: possible correlation with progressive skin sclerosis, digital ulcers and pulmonary vascular involvement in patients with systemic sclerosis.

    Science.gov (United States)

    Ichimura, Yohei; Asano, Yoshihide; Akamata, Kaname; Aozasa, Naohiko; Noda, Shinji; Taniguchi, Takashi; Takahashi, Takehiro; Toyama, Tetsuo; Sumida, Hayakazu; Kuwano, Yosihiro; Yanaba, Koichi; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

    2014-03-01

    Angiopoietin-like protein 3 (ANGPTL3), which is part of a family of secreted glycoproteins that are structurally similar to angiopoietins, is principally expressed in the liver and is involved in lipid metabolism and angiogenesis. The aim of this study was to determine the clinical significance of serum ANGPTL3 levels, measured with a specific enzyme-linked immunosorbent assay, in patients with systemic sclerosis. Serum ANGPTL3 levels correlated positively with skin score in diffuse cutaneous systemic sclerosis with a disease duration ≤ 6 years. Furthermore, the prevalence of digital ulcers was significantly higher in patients with elevated serum ANGPTL3 levels than in other patients. Moreover, among patients excluding diffuse cutaneous systemic sclerosis with disease duration ≤ 6 years, serum ANGPTL3 levels correlated positively with estimated right ventricular systolic pressure. In conclusion, ANGPTL3 may contribute to the development of progressive skin sclerosis and proliferative obliterative vasculopathy, such as digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, in systemic sclerosis.

  9. Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Jalpa Kotecha

    2016-09-01

    Full Text Available Background: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF. Vascular endothelial growth factor (VEGF concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. Methods: 27 IPF patients were studied (maximum follow-up 65 months. Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB % predicted. Results: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. Conclusion: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF.

  10. Prevalence of Pre-Extensively Drug-Resistant Tuberculosis (Pre XDR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) among Pulmonary Multidrug Resistant Tuberculosis (MDR-TB) at a Tertiary Care Center in Mumbai

    OpenAIRE

    Unnati D. Desai; Joshi, Jyotsna M

    2016-01-01

    Background: India is a high burden country for Tuberculosis (TB). As per the World Health Organization (WHO) statistics, 24000 cases of Multi Drug Resistant (MDR) TB were diagnosed in India in 2014. MDR-TB patients consist of a heterogeneous cohort and management has its challenges. Aims and objectives: We studied the prevalence of PreExtensively Drug Resistant TB (Pre XDR-TB) and Extensively Drug Resistant TB (XDR-TB) among patients of pulmonary MDR-TB not previous...

  11. Soluble receptor for advanced glycation end products as an indicator of pulmonary vascular injury after cardiac surgery

    NARCIS (Netherlands)

    S. Tuinman (Sietske); A.D. Cornet (Alexander); M.T. Kuipers (Maria); A.P.J. Vlaar (Alexander); M.J. Schultz (Marcus); A. Beishuizen (Auke); A.B.J. Groeneveld (Johan); N.P. Juffermans (Nicole)

    2013-01-01

    textabstractBackground: Cardiac surgery is frequently complicated by an acute vascular lung injury and this may be mediated, at least in part, by the (soluble) receptor for advanced glycation end products (sRAGE).Methods: In two university hospital intensive care units, circulating sRAGE was measure

  12. Proximal pulmonary arterial obstruction decreases the time constant of the pulmonary circulation and increases right ventricular afterload.

    Science.gov (United States)

    Pagnamenta, Alberto; Vanderpool, Rebecca; Brimioulle, Serge; Naeije, Robert

    2013-06-01

    The time constant of the pulmonary circulation, or product of pulmonary vascular resistance (PVR) and compliance (Ca), called the RC-time, has been reported to remain constant over a wide range of pressures, etiologies of pulmonary hypertension, and treatments. We wondered if increased wave reflection on proximal pulmonary vascular obstruction, like in operable chronic thromboembolic pulmonary hypertension, might also decrease the RC-time and thereby increase pulse pressure and right ventricular afterload. Pulmonary hypertension of variable severity was induced either by proximal obstruction (pulmonary arterial ensnarement) or distal obstruction (microembolism) eight anesthetized dogs. Pulmonary arterial pressures (Ppa) were measured with high-fidelity micromanometer-tipped catheters, and pulmonary flow with transonic technology. Pulmonary ensnarement increased mean Ppa, PVR, and characteristic impedance, decreased Ca and the RC-time (from 0.46 ± 0.07 to 0.30 ± 0.03 s), and increased the oscillatory component of hydraulic load (Wosc/Wtot) from 25 ± 2 to 29 ± 2%. Pulmonary microembolism increased mean Ppa and PVR, with no significant change in Ca and characteristic impedance, increased RC-time from 0.53 ± 0.09 to 0.74 ± 0.05 s, and decreased Wosc/Wtot from 26 ± 2 to 13 ± 2%. Pulse pressure increased more after pulmonary ensnarement than after microembolism. Concomitant measurements with fluid-filled catheters showed the same functional differences between the two types of pulmonary hypertension, with, however, an underestimation of Wosc. We conclude that pulmonary hypertension caused by proximal vs. distal obstruction is associated with a decreased RC-time and increased pulsatile component of right ventricular hydraulic load.

  13. Vascular rings.

    Science.gov (United States)

    Backer, Carl L; Mongé, Michael C; Popescu, Andrada R; Eltayeb, Osama M; Rastatter, Jeffrey C; Rigsby, Cynthia K

    2016-06-01

    The term vascular ring refers to congenital vascular anomalies of the aortic arch system that compress the esophagus and trachea, causing symptoms related to those two structures. The most common vascular rings are double aortic arch and right aortic arch with left ligamentum. Pulmonary artery sling is rare and these patients need to be carefully evaluated for frequently associated tracheal stenosis. Another cause of tracheal compression occurring only in infants is the innominate artery compression syndrome. In the current era, the diagnosis of a vascular ring is best established by CT imaging that can accurately delineate the anatomy of the vascular ring and associated tracheal pathology. For patients with a right aortic arch there recently has been an increased recognition of a structure called a Kommerell diverticulum which may require resection and transfer of the left subclavian artery to the left carotid artery. A very rare vascular ring is the circumflex aorta that is now treated with the aortic uncrossing operation. Patients with vascular rings should all have an echocardiogram because of the incidence of associated congenital heart disease. We also recommend bronchoscopy to assess for additional tracheal pathology and provide an assessment of the degree of tracheomalacia and bronchomalacia. The outcomes of surgical intervention are excellent and most patients have complete resolution of symptoms over a period of time. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Enlarged pulmonary artery is predicted by vascular injury biomarkers and is associated with WTC-Lung Injury in exposed fire fighters: a case–control study

    Science.gov (United States)

    Schenck, Edward J; Echevarria, Ghislaine C; Girvin, Francis G; Kwon, Sophia; Comfort, Ashley L; Rom, William N; Prezant, David J; Weiden, Michael D; Nolan, Anna

    2014-01-01

    Objectives We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Design Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Setting Urban tertiary care centre and occupational healthcare centre. Participants Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1) ≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/AWTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. Results PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Conclusions Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of vascular disease found in serum drawn within 6 months of WTC exposure. Increased PA/A is a potentially useful non-invasive biomarker of WTC-LI and warrants further study. PMID:25270856

  15. Enlarged pulmonary artery is predicted by vascular injury biomarkers and is associated with WTC-Lung Injury in exposed fire fighters: a case-control study.

    Science.gov (United States)

    Schenck, Edward J; Echevarria, Ghislaine C; Girvin, Francis G; Kwon, Sophia; Comfort, Ashley L; Rom, William N; Prezant, David J; Weiden, Michael D; Nolan, Anna

    2014-09-29

    We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Urban tertiary care centre and occupational healthcare centre. Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1)≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/AWTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of vascular disease found in serum drawn within 6 months of WTC exposure. Increased PA/A is a potentially useful non-invasive biomarker of WTC-LI and warrants further study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

  16. A feasible method for non-invasive measurement of pulmonary vascular resistance in pulmonary arterial hypertension: Combined use of transthoracic Doppler-echocardiography and cardiac magnetic resonance. Non-invasive estimation of pulmonary vascular resistance

    Directory of Open Access Journals (Sweden)

    Yan Chaowu

    2015-12-01

    Translational perspective: In PAH, the non-invasive measurement of PVR is very important in clinical practice. Up to now, however, the widely accepted non-invasive method is still unavailable. Since TTE can estimate (MPAP–PCWP reliably and CMR is the best image modality for the measurement of CO, the combined use of two modalities has the potential to determine PVR non-invasively. In this research, the integrated non-invasive method showed good diagnostic accuracy and repeatability compared with RHC. Therefore, it might be a feasible method for non-invasive measurement of PVR in patients with PAH.

  17. Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010

    OpenAIRE

    Báez-Saldaña, Renata; Delgado-Sánchez, Guadalupe; García-García, Lourdes; Cruz-Hervert, Luis Pablo; Montesinos-Castillo, Marlene; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Yanes-Lane, Mercedes; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José

    2016-01-01

    Background Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. Objective To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. Materials and Methods We conducted a prospective cohort study of pulmonary TB patients...

  18. Mechanisms of corticosteroid resistance in severe asthma and chronic obstructive pulmonary disease (COPD).

    Science.gov (United States)

    Adcock, Ian M; Marwick, John; Casolari, Paolo; Contoli, Marco; Chung, Kian Fan; Kirkham, Paul; Papi, Alberto; Caramori, Gaetano

    2010-01-01

    Inhaled glucocorticoids, also know as corticosteroids (ICS), revolutionized the treatment of asthma by suppressing airways inflammation and ICS therapy now forms the basis of treatment of asthma of all severities. More recently and usually in combination with a long-acting β-agonist (LABA), ICS use has been established in the treatment of chronic obstructive pulmonary disease (COPD). In asthma, ICS improves asthma control, lung function and prevents exacerbations, including hospital admissions and probably decreases mortality. Similar effects are seen in COPD but to a much lesser degree, however, an improvement in symptoms such as breathlessness and reduction in exacerbations occur particularly in more advanced disease with ICS. Chronic inflammation is a feature of both asthma and COPD, although there are differences in the site and characteristics of the inflammatory response. ICS have proven to be less effective in patients with severe asthma, smoking asthmatics and in patients with COPD. ICS act by binding to and activating specific cytosolic receptors (GR), which then translocate to the nucleus where they regulate gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. GR is able to selective repress specific inflammatory genes by differing actions on specific intracellular signalling pathways and transcription factors such as nuclear factor κB and on kinases pathways. Abnormal activation of these pathways may result in glucocorticoid resistance. Although, ICS/LABA combinations will remain the main focus of treatment of airways diseases in the near future; other combinations that improve the efficacy of ICS by reducing the abnormal activation of pathways that cause glucocorticoid resistance will be developed.

  19. Clinical prediction rule for stratifying risk of pulmonary multidrug-resistant tuberculosis.

    Science.gov (United States)

    Martínez, Dalila; Heudebert, Gustavo; Seas, Carlos; Henostroza, German; Rodriguez, Martin; Zamudio, Carlos; Centor, Robert M; Herrera, Cesar; Gotuzzo, Eduardo; Estrada, Carlos

    2010-08-11

    Multidrug-resistant tuberculosis (MDR-TB), resistance to at least isoniazid and rifampin, is a worldwide problem. To develop a clinical prediction rule to stratify risk for MDR-TB among patients with pulmonary tuberculosis. Derivation and internal validation of the rule among adult patients prospectively recruited from 37 health centers (Perú), either a) presenting with a positive acid-fast bacillus smear, or b) had failed therapy or had a relapse within the first 12 months. Among 964 patients, 82 had MDR-TB (prevalence, 8.5%). Variables included were MDR-TB contact within the family, previous tuberculosis, cavitary radiologic pattern, and abnormal lung exam. The area under the receiver-operating curve (AUROC) was 0.76. Selecting a cut-off score of one or greater resulted in a sensitivity of 72.6%, specificity of 62.8%, likelihood ratio (LR) positive of 1.95, and LR negative of 0.44. Similarly, selecting a cut-off score of two or greater resulted in a sensitivity of 60.8%, specificity of 87.5%, LR positive of 4.85, and LR negative of 0.45. Finally, selecting a cut-off score of three or greater resulted in a sensitivity of 45.1%, specificity of 95.3%, LR positive of 9.56, and LR negative of 0.58. A simple clinical prediction rule at presentation can stratify risk for MDR-TB. If further validated, the rule could be used for management decisions in resource-limited areas.

  20. Clinical prediction rule for stratifying risk of pulmonary multidrug-resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Dalila Martínez

    Full Text Available BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB, resistance to at least isoniazid and rifampin, is a worldwide problem. OBJECTIVE: To develop a clinical prediction rule to stratify risk for MDR-TB among patients with pulmonary tuberculosis. METHODS: Derivation and internal validation of the rule among adult patients prospectively recruited from 37 health centers (Perú, either a presenting with a positive acid-fast bacillus smear, or b had failed therapy or had a relapse within the first 12 months. RESULTS: Among 964 patients, 82 had MDR-TB (prevalence, 8.5%. Variables included were MDR-TB contact within the family, previous tuberculosis, cavitary radiologic pattern, and abnormal lung exam. The area under the receiver-operating curve (AUROC was 0.76. Selecting a cut-off score of one or greater resulted in a sensitivity of 72.6%, specificity of 62.8%, likelihood ratio (LR positive of 1.95, and LR negative of 0.44. Similarly, selecting a cut-off score of two or greater resulted in a sensitivity of 60.8%, specificity of 87.5%, LR positive of 4.85, and LR negative of 0.45. Finally, selecting a cut-off score of three or greater resulted in a sensitivity of 45.1%, specificity of 95.3%, LR positive of 9.56, and LR negative of 0.58. CONCLUSION: A simple clinical prediction rule at presentation can stratify risk for MDR-TB. If further validated, the rule could be used for management decisions in resource-limited areas.

  1. Adjuvant interferon gamma in patients with drug – resistant pulmonary tuberculosis: a pilot study

    Directory of Open Access Journals (Sweden)

    Carbonell Dalia

    2004-10-01

    Full Text Available Abstract Background Tuberculosis (TB is increasing in the world and drug-resistant (DR disease beckons new treatments. Methods To evaluate the action of interferon (IFN gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 × 106 IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. Results Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. Conclusions These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged.

  2. Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study.

    Science.gov (United States)

    Siehr, Stephanie L; Feinstein, Jeffrey A; Yang, Weiguang; Peng, Lynn F; Ogawa, Michelle T; Ramamoorthy, Chandra

    2016-05-01

    During a pulmonary hypertensive crisis, the marked increase in pulmonary vascular resistance can result in acute right ventricular failure and death. Currently, there are no therapeutic guidelines for managing an acute crisis. This pilot study examined the hemodynamic effects of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertension. In this prospective, open-label, nonrandomized pilot study, we enrolled pediatric patients previously diagnosed with pulmonary hypertensive who were scheduled electively for cardiac catheterization. Primary outcome was a change in the ratio of pulmonary-to-systemic vascular resistance. Baseline hemodynamic data were collected before and after the study drug was administered. Eleven of 15 participants were women, median age was 9.2 years (range, 1.7-14.9 yr), and median weight was 26.8 kg (range, 8.5-55.2 kg). Baseline mean pulmonary artery pressure was 49 ± 19 mm Hg, and mean indexed pulmonary vascular resistance was 10 ± 5.4 Wood units. Etiology of pulmonary hypertensive varied, and all were on systemic pulmonary hypertensive medications. Patients 1-5 received phenylephrine 1 μg/kg; patients 6-10 received arginine vasopressin 0.03 U/kg; and patients 11-15 received epinephrine 1 μg/kg. Hemodynamics was measured continuously for up to 10 minutes following study drug administration. After study drug administration, the ratio of pulmonary-to-systemic vascular resistance decreased in three of five patients receiving phenylephrine, five of five patients receiving arginine vasopressin, and three of five patients receiving epinephrine. Although all three medications resulted in an increase in aortic pressure, only arginine vasopressin consistently resulted in a decrease in the ratio of systolic pulmonary artery-to-aortic pressure. This prospective pilot study of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertensive showed an increase in aortic

  3. Arterial pulmonary hypertension in noncardiac intensive care unit

    Directory of Open Access Journals (Sweden)

    Mykola V Tsapenko

    2008-10-01

    Full Text Available Mykola V Tsapenko1,5, Arseniy V Tsapenko2, Thomas BO Comfere3,5, Girish K Mour1,5, Sunil V Mankad4, Ognjen Gajic1,51Division of Pulmonary and Critical Care Medicine; 3Division of Critical Care Medicine; 4Division of Cardiovascular Diseases, Mayo Epidemiology and Translational Research in Intensive Care (M.E.T.R.I.C, Mayo Clinic, Rochester, MN, USA; 2Division of Pulmonary and Critical Care Medicine, Brown University, Miriam Hospital, Providence, RI, USAAbstract: Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in

  4. Chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Schölzel, B E; Snijder, R J; Mager, J J; van Es, H W; Plokker, H W M; Reesink, H J; Morshuis, W J; Post, M C

    2014-12-01

    Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

  5. Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs

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    Shimodaira Kayoko

    2012-11-01

    Full Text Available Abstract Background Idiopathic pulmonary arterial hypertension (IPAH continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our envelopment. Methods Microarray assays with ontology and pathway analyses were performed with the lungs of mice. A comparison was made of the expression patterns of biological pathways between our model and those published for IPAH. Results Some pathways in our model showed the same expression patterns in IPAH, which included bone morphogenetic protein (BMP signaling with down-regulation of BMP receptor type 2, activin-like kinase type 1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP signaling and its downstream Rho/ROCK signaling were found alone to be activated in IPAH and not in our model. Conclusions Activation of Wnt/PCP signaling, in upstream positions of the pathway, found alone in lungs from end stage IPAH may play essential roles in the pathogenesis of the disease.

  6. Ion channels and transporters as therapeutic targets in the pulmonary circulation.

    Science.gov (United States)

    Olschewski, Andrea; Papp, Rita; Nagaraj, Chandran; Olschewski, Horst

    2014-12-01

    Pulmonary circulation is a low pressure, low resistance, high flow system. The low resting vascular tone is maintained by the concerted action of ion channels, exchangers and pumps. Under physiological as well as pathophysiological conditions, they are targets of locally secreted or circulating vasodilators and/or vasoconstrictors, leading to changes in expression or to posttranslational modifications. Both structural changes in the pulmonary arteries and a sustained increase in pulmonary vascular tone result in pulmonary vascular remodeling contributing to morbidity and mortality in pediatric and adult patients. There is increasing evidence demonstrating the pivotal role of ion channels such as K(+) and Cl(-) or transient receptor potential channels in different cell types which are thought to play a key role in vasoconstrictive remodeling. This review focuses on ion channels, exchangers and pumps in the pulmonary circulation and summarizes their putative pathophysiological as well as therapeutic role in pulmonary vascular remodeling. A better understanding of the mechanisms of their actions may allow for the development of new options for attenuating acute and chronic pulmonary vasoconstriction and remodeling treating the devastating disease pulmonary hypertension.

  7. Dramatic response of a patient with pregnancy induced idiopathic pulmonary arterial hypertension to sildenafil treatment.

    Science.gov (United States)

    Taçoy, Gülten; Ekim, Numan Nadir; Cengel, Atiye

    2010-04-01

    Idiopathic pulmonary arterial hypertension (IPAH) is characterized by a progressive increase in pulmonary vascular resistance, which may lead to right ventricular failure and death. Major cardiovascular and pulmonary alterations occur during pregnancy and therefore worsen or increase the complications of pulmonary arterial hypertension (PAH). A patient diagnosed with IPAH after a successful full-term pregnancy and cesarean section with epidural anesthesia is presented. The postoperative course was complicated by progressive dyspnea, and lower limb edema. The outcome of treatment with sildenafil during puerperium was favorable in this patient. The clinical course was complicated by an unexpected spontaneous pregnancy after primary infertility.

  8. Interstitial Pulmonary Edema Following Bromocarbamide Intoxication

    Science.gov (United States)

    Sugihara, H.; Hagedorn, M.; Bōttcher, D.; Neuhof, H.; Mittermayer, Ch.

    1974-01-01

    Bromocarbamides are sleep-inducing drugs which can lead, in man, to intoxication and death due to respiratory failure. To prove whether hemodynamic factors or the changed endothelial permeability induce pulmonary edema, animal experiments were performed. The fine structural changes in pulmonary edema in rabbits were observed at 60, 90 and 120 minutes after oral administration. The major findings were a) large blebs between capillary endothelium and alveolar epithelium and b) interstitial edema of the vessel wall. The bleb contents were much less electron dense than the blood contents in the capillary. Colloidal carbon did not enter the bleb or the edematous interstitial tissue. Exogenous peroxidase uptake in pinocytotie vesicles increased in pathologic cases. The hemodynamic measurements in animal receiving artificial respiration which maintained the blood pO2 at a steady state showed similar blebs in the pulmonary vessels, indicating that anoxia is not the major cause of the vascular lesion. Moreover, pulmonary arterial pressure and pulmonary vascular resistance could be held in the normal range in artificially respirated animals under bromocarbamide intoxication. Thus, hemodynamic factors are not likely to play a pathogenetic role in bringing about pulmonary edema. The chief, early factor is the increased endothelial permeability due to increased cytoplasmic transport. From this a practical suggestion for treating patients with bromocarbamide intoxication is derived: the usual fluid replacement in shock patients should be handled with great care to avoid fluid overload of the lung. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:4835993

  9. Store-operated channels in the pulmonary circulation of high- and low-altitude neonatal lambs.

    Science.gov (United States)

    Parrau, Daniela; Ebensperger, Germán; Herrera, Emilio A; Moraga, Fernando; Riquelme, Raquel A; Ulloa, César E; Rojas, Rodrigo T; Silva, Pablo; Hernandez, Ismael; Ferrada, Javiera; Diaz, Marcela; Parer, Julian T; Cabello, Gertrudis; Llanos, Aníbal J; Reyes, Roberto V

    2013-04-15

    We determined whether store-operated channels (SOC) are involved in neonatal pulmonary artery function under conditions of acute and chronic hypoxia, using newborn sheep gestated and born either at high altitude (HA, 3,600 m) or low altitude (LA, 520 m). Cardiopulmonary variables were recorded in vivo, with and without SOC blockade by 2-aminoethyldiphenylborinate (2-APB), during basal or acute hypoxic conditions. 2-APB did not have effects on basal mean pulmonary arterial pressure (mPAP), cardiac output, systemic arterial blood pressure, or systemic vascular resistance in both groups of neonates. During acute hypoxia 2-APB reduced mPAP and pulmonary vascular resistance in LA and HA, but this reduction was greater in HA. In addition, isolated pulmonary arteries mounted in a wire myograph were assessed for vascular reactivity. HA arteries showed a greater relaxation and sensitivity to SOC blockers than LA arteries. The pulmonary expression of two SOC-forming subunits, TRPC4 and STIM1, was upregulated in HA. Taken together, our results show that SOC contribute to hypoxic pulmonary vasoconstriction in newborn sheep and that SOC are upregulated by chronic hypoxia. Therefore, SOC may contribute to the development of neonatal pulmonary hypertension. We propose SOC channels could be potential targets to treat neonatal pulmonary hypertension.

  10. Cardiac output and systemic vascular resistance: Clinical assessment compared with a noninvasive objective measurement in children with shock.

    Science.gov (United States)

    Razavi, Asma; Newth, Christopher J L; Khemani, Robinder G; Beltramo, Fernando; Ross, Patrick A

    2017-06-01

    To evaluate physician assessment of cardiac output and systemic vascular resistance in patients with shock compared with an ultrasonic cardiac output monitor (USCOM). To explore potential changes in therapy decisions if USCOM data were available using physician intervention answers. Double-blinded, prospective, observational study in a tertiary hospital pediatric intensive care unit. Forty children (resistance, categorizing them as high, normal, or low. An investigator simultaneously measured cardiac index (CI) and systemic vascular resistance index (SVRI) with USCOM categorized as high, normal, or low. Overall agreement between physician and USCOM for CI (48.5% [κ = 0.18]) and SVRI (45.9% [κ = 0.16]) was poor. Interobserver agreement was also poor for CI (58.7% [κ = 0.33]) and SVRI (52.3% [κ = 0.28]). Comparing theoretical physician interventions to "acceptable" or "unacceptable" clinical interventions, based on USCOM measurement, 56 (21%) physician interventions were found to be "unacceptable." There is poor agreement between physician-assessed CI and SVRI and USCOM, with significant interobserver variability among physicians. Objective measurement of CI and SVRI may reduce variability and improve diagnostic accuracy. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation.

    Science.gov (United States)

    Ogbozor, Uchenna D; Opene, Michael; Renteria, Lissette S; McBride, Shaemion; Ibe, Basil O

    2015-09-01

    Platelet activating factor (PAF) modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR) in pulmonary vascular smooth muscle cells (PVSMC) to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a) PAF induces NF-kB p65 DNA binding and (b) NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

  12. Mechanism by which nuclear factor-kappa beta (NF-kB regulates ovine fetal pulmonary vascular smooth muscle cell proliferation

    Directory of Open Access Journals (Sweden)

    Uchenna D. Ogbozor

    2015-09-01

    Full Text Available Platelet activating factor (PAF modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR in pulmonary vascular smooth muscle cells (PVSMC to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a PAF induces NF-kB p65 DNA binding and (b NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

  13. Insulin resistance impairs endothelial function but not adrenergic reactivity or vascular structure in fructose-fed rats.

    Science.gov (United States)

    Romanko, Olga P; Ali, M Irfan; Mintz, James D; Stepp, David W

    2009-07-01

    Obesity and diabetes are major risk factors for the development of vascular disease in the lower limbs. Previous studies have demonstrated reduced nitric oxide (NO)-mediated vasodilation, increased adrenergic constriction, and inward, atrophic remodeling in the limb circulation of obese Zucker rats, but the component of the "metabolic syndrome" driving these changes is unclear. Because insulin resistance precedes the state of frank diabetes, the current study hypothesized that insulin resistance independent of obesity induced by fructose feeding would impair microvascular function in the skeletal muscle circulation in lean Zucker rats (LZR). A 66% fructose diet impaired glucose tolerance and induced moderate insulin resistance with no changes in whole-body hemodynamics of anesthetized rats (FF-LZR), compared to control LZR. NO-mediated vasodilation of isolated gracilis arteries, assessed in vitro with acetylcholine and sodium nitroprusside, was reduced approximately 20% in FF-LZR vs. LZR. NO-independent cGMP-mediated vasodilation was unimpaired. Pretreatment of isolated vessels with the superoxide scavenger, tempol, improved responses to both vasodilators. Reactivity to adrenergic stimulation was unaltered in FF-LZR vs. LZR, although constriction to endothelin was increased. Structural and passive mechanical characteristics of isolated gracilis arteries were similar in both LZR and FF-LZR. Taken together, these findings indicate that moderate insulin resistance is sufficient to impair endothelial function in an oxidant-dependent manner in the rat hindlimb circulation. Other aspects of skeletal muscle vascular function documented in obese models, specifically adrenergic tone and inward remodeling, must reflect either severe insulin resistance or other aspects of obesity. The factors accounting for nonendothelial vasculopathies remain unknown.

  14. Peculiarities of Blood Flow Changes in Venae Cavae during Experimental Pulmonary Embolism.

    Science.gov (United States)

    Evlakhov, V I; Poyassov, I Z; Shaidakov, E V

    2016-10-01

    The model of acute pulmonary embolism in rabbits demonstrated reduced pulmonary blood flow, cardiac output, left atrial pressure, and blood flow in venae cavae against the background of elevated left pulmonary artery pressure and increased pulmonary vascular resistance. Simultaneously, the blood flow in the superior vena cava decreased to a lesser extent than that in the inferior vena cava, which was a characteristic feature of the model of pulmonary pathology. In contrast, when histamine was infused into the left jugular vein to equally elevate pressure in pulmonary artery as in the above model, the blood flow in the superior vena cava decreased to a greater extent than that in inferior vena cava. During stenosis of inferior vena cava that decreased the cardiac output to the level observed during modeled pulmonary embolism, the blood flows in both venae cavae dropped equally.

  15. Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension%肾去交感神经对肺动脉高压模型犬肺血管重构的影响

    Institute of Scientific and Technical Information of China (English)

    张淑娟; 赵庆彦; 蒋学俊; 杨波; 代子玄; 王晓占; 王徐乐; 郭宗文; 于胜波

    2015-01-01

    目的 探讨肾去交感神经(RSD)对肺动脉高压(PAH)模型犬肺血管重构的影响.方法 24只比格犬按随机数字表法随机均分为对照组、PAH组、PAH+ RSD组各8只.检测各组犬实验前血清神经激素水平、心脏超声和血流动力学参数后,对照组右心房注入二甲基甲酰胺(0.1 ml/kg),PAH组右心房注入脱氢野百合碱(2 ml/kg),PAH+ RSD组先行肾去交感神经术,后右心房注入脱氢野百合碱(2 ml/kg).喂养8周,检测各组犬实验后的血清神经激素水平、心脏超声和血流动力学参数后,开胸取肺组织检测肺血管形态学.结果 实验后PAH组、PAH+ RSD组右心室收缩压(RVSP)和肺动脉收缩压(PASP)均显著高于对照组[(42.8±8.7)、(30.8±6.8)比(23.2±5.7) mmHg(1mmHg =0.133 kPa)和(45.1±11.2)、(32.6±7.9)比(24.7 ±7.1)mmHg],且PAH组RVSP和PASP显著高于PAH+ RSD组[均P<0.01].实验后PAH组血清血管紧张素Ⅱ(AngⅡ)和内皮素1水平均显著高于实验前[(228 ±41)比(113±34) pg/ml和(135 ±15)比(77±7)pg/ml,均P<0.01],且肺组织中AngⅡ和内皮素1水平[(65±10)和(96±10)pg/ml]均显著高于对照组[(38±7)和(54±6)pg/ml]和PAH+ RSD组[(46±8)和(67±9)pg/ml](均P<0.01).与对照组相比,PAH组肺泡2型细胞破坏严重,组织纤维化明显,而PAH+ RSD组肺泡2型细胞破坏及组织纤维化较PAH组轻.结论 RSD可降低PAH模型犬肺动脉高压并抑制肺血管重构,此作用可能与其降低神经激素水平有关.%Objective To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH).Methods According to the random number table,24 beagles were randomized into control,PAH and PAH + RSD groups (n =8 each).The levels of neurohormone,echocardiogram and dynamics parameters were measured.Then 0.1 ml/kg dimethylformamide (control group) or 2 mg/kg dehydromonocrotaline (PAH and PAH + RSD groups) were injected.The PAH + RSD group

  16. Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension

    Science.gov (United States)

    Rex, Steffen; Missant, Carlo; Claus, Piet; Buhre, Wolfgang; Wouters, Patrick F

    2008-01-01

    Introduction Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension. Methods In this prospective, randomized, placebo-controlled animal study, twenty-six pigs (mean weight 35 ± 2 kg) were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary artery pressure catheter. The effects of inhaled iloprost (50 μg) were studied in the following groups: animals with acute hypoxia-induced pulmonary hypertension, and healthy animals with and without blockade of the autonomic nervous system. Results During pulmonary hypertension, inhalation of iloprost resulted in a 51% increase in cardiac output compared with placebo (5.6 ± 0.7 versus 3.7 ± 0.8 l/minute; P = 0.0013), a selective reduction in right ventricular afterload (effective pulmonary arterial elastance: 0.6 ± 0.3 versus 1.2 ± 0.5 mmHg/ml; P = 0.0005) and a significant increase in left ventricular end-diastolic volume (91 ± 12 versus 70 ± 20 ml; P = 0.006). Interestingly, right ventricular contractility was reduced after iloprost-treatment (slope of preload recruitable stroke work: 2.2 ± 0.5 versus 3.4 ± 0.8 mWatt·s/ml; P = 0.0002), whereas ventriculo-vascular coupling remained essentially preserved (ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance: 0.97 ± 0.33 versus 1.03 ± 0.15). In healthy animals, inhaled iloprost had only minimal haemodynamic effects and produced no direct effects on myocardial contractility, even after pharmacological blockade of the autonomic

  17. Role of Renin-Angiotensin System and Oxidative Stress on Vascular Inflammation in Insulin Resistence Model

    Directory of Open Access Journals (Sweden)

    N. F. Renna

    2013-01-01

    Full Text Available (1 This study aims to demonstrate the causal involvement of renin angiotensin system (RAS and oxidative stress (OS on vascular inflammation in an experimental model of metabolic syndrome (MS achieved by fructose administration to spontaneously hypertensive rats (FFHR during 12 weeks. (2 Chronic treatment with candesartan (C (10 mg/kg per day for the last 6 weeks or 4OH-Tempol (T (10−3 mmol/L in drinking water for the last 6 weeks reversed the increment in metabolic variables and systolic blood pressure. In addition, chronic C treatment reverted cardiovascular remodeling but not T. (3 Furthermore, chronic treatment with C was able to completely reverse the expression of NF-κB and VCAM-1, but T only reduced the expression. C reduced the expression of proatherogenic cytokines as CINC2, CINC3, VEGF, Leptin, TNF-alpha, and MCP-1 and also significantly reduced MIP-3, beta-NGF, and INF-gamma in vascular tissue in this experimental model. T was not able to substantially modify the expression of these cytokines. (4 The data suggest the involvement of RAS in the expression of inflammatory proteins at different vascular levels, allowing the creation of a microenvironment suitable for the creation, perpetuation, growth, and destabilization of vascular injury.

  18. Beneficial insulin-sensitizing and vascular effects of S15261 in the insulin-resistant JCR:LA-cp rat.

    Science.gov (United States)

    Russell, J C; Ravel, D; Pégorier, J P; Delrat, P; Jochemsen, R; O'Brien, S F; Kelly, S E; Davidge, S T; Brindley, D N

    2000-11-01

    S15261, a compound developed for the oral treatment of type II diabetes, is cleaved by esterases to the fragments Y415 and S15511. The aim was to define the insulin-sensitizing effects of S15261, the cleavage products, and troglitazone and metformin in the JCR:LA-cp rat, an animal model of the obesity/insulin resistance syndrome that exhibits an associated vasculopathy and cardiovascular disease. Treatment of the animals from 8 to 12 weeks of age with S15261 or S15511 resulted in reductions in food intake and body weights, whereas Y415 had no effect. Troglitazone caused a small increase in food intake (P JCR:LA-cp rat. S15261 may thus offer effective treatment for the insulin resistance syndrome and its associated vascular complications.

  19. Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension

    Science.gov (United States)

    Galambos, Csaba; Minic, Angela D.; Bush, Douglas; Nguyen, Dominique; Dodson, Blair; Seedorf, Gregory; Abman, Steven H.

    2016-01-01

    Background and Aims Infants with Down syndrome (DS) or Trisomy 21, are at high risk for developing pulmonary arterial hypertension (PAH), but mechanisms that increase susceptibility are poorly understood. Laboratory studies have shown that early disruption of angiogenesis during development impairs vascular and alveolar growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors, including collagen18a1 (endostatin, ES), ß-amyloid peptide (BAP) and Down Syndrome Critical Region 1 (DSCR-1). Therefore, we hypothesized that fetal lungs from subjects with DS are characterized by early over-expression of anti-angiogenic factors and have abnormal lung vascular growth in utero. Methods Human fetal lung tissue from DS and non-DS subjects were obtained from a biorepository. Quantitative reverse transcriptase PCR (qRT-PCR) was performed to assay 84 angiogenesis-associated genes and individual qRT-PCR was performed for ES, amyloid protein precursor (APP) and DSCR1. Western blot analysis (WBA) was used to assay lung ES, APP and DSCR-1 protein contents. Lung vessel density and wall thickness were determined by morphometric analysis. Results The angiogenesis array identified up-regulation of three anti-angiogenic genes: COL18A1 (ES), COL4A3 (tumstatin) and TIMP3 (tissue inhibitor of metallopeptidase 3) in DS lungs. Single qRT-PCR and WBA showed striking elevations of ES and APP mRNA (p = 0.022 and p = 0.001) and protein (p = 0.040 and p = 0.002; respectively). Vessel density was reduced (p = 0.041) and vessel wall thickness was increased in DS lung tissue (p = 0.033) when compared to non-DS subjects. Conclusions We conclude that lung anti-angiogenic factors, including COL18A1 (ES), COL4A3, TIMP3 and APP are over-expressed and fetal lung vessel growth is decreased in subjects with DS. We speculate that increased fetal lung anti-angiogenic factor expression due to trisomy 21 impairs lung vascular growth and signaling, which impairs alveolarization and

  20. Upregulated copper transporters in hypoxia-induced pulmonary hypertension.

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    Adriana M Zimnicka

    Full Text Available Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX, a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2 also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC. In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness.

  1. Pulmonary oligemia maneuver can alleviate pulmonary artery injury during pulmonary thromboendarterectomy procedure

    Institute of Scientific and Technical Information of China (English)

    GAN Hui-li; ZHANG Jian-qun; LU Jia-kai; DONG Xiu-hua; HOU Xiao-tong; GAO Yuan-ming; ZHU Guang-fa

    2013-01-01

    Background Pulmonary thromboendarterectomy (PTE) has evolved as a treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH).This study aimed to characterize if pulmonary oligemia maneuver (POM) can alleviate pulmonary artery injury during PTE procedure.Methods A total of 112 cases of CTEPH admitted to Beijing Anzhen Hospital from March 2002 to August 2011 received PTE procedure.They were retrospectively classified as non-POM group (group A,n=55) or POM group (group B,n=57).Members from group B received POM during rewarming period,whereas members from group A did not.Results There were three (5.45%) early deaths in group A,no death in group B (0) (Fisher's exact test,P=-0.118).Six patients in group A needed extracorporeal membrane oxygenation (ECMO) as life support after the PTE procedure,no patients in group B needed ECMO (Fisher's exact test,P=0.013).The patients in group B had a shorter intubation and ICU stay,lower mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR),higher partial pressure of oxygen in artery (PaO2) and arterial oxygen saturation (SaO2) and less medical expenditure than patients in group A.With a mean follow-up time of (58.3 ± 30.6) months,two patients in group A and one patient in group B died.The difference of the actuarial survival after the procedure between the two groups did not reach statistical significance.Three months post the PTE procedure,the difference of residual occluded pulmonary segment between the two groups did not reach statistical significance (P=-0.393).Conclusion POM can alleviate pulmonary artery injury,shorten ICU stay and intubation time,and lower down the rate of ECMO after PTE procedure.

  2. Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India

    Science.gov (United States)

    Sara, Chandy; Elsa, Heylen; Baijayanti, Mishra; Lennartsdotter, Ekstrand Maria

    2016-01-01

    Objectives To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline. PMID:27708985

  3. [Vasodilator therapy in pulmonary hypertension and chronic obstructive lung disease (COPD). Hemodynamic studies exemplified by nifedipine and nitroglycerin].

    Science.gov (United States)

    Gassner, A; Fridrich, L; Magometschnigg, D; Sommer, G; Klicpera, M

    1986-08-01

    In 41 patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension, the effects of sublingual administration of 20 mg nifedipine and 0.8 mg nitroglycerin on the hemodynamics were assessed at rest and during bicycle ergometry. Additionally, in six patients, the effects of nifedipine during longterm treatment were analyzed. On acute testing, at rest and during exercise nifedipine led to decreases in mean pulmonary artery pressure of 16% and 23% and pulmonary arteriolar resistance of 23 and 35%, respectively, in 81% (17/21) of the patients. The reduction in the pulmonary vascular resistance was greater than that of the systemic resistance. In all patients, cardiac output increased. There was a similar number of responders to nitroglycerin (16/20). The reductions in mean pulmonary artery pressure and pulmonary arteriolar resistance ranging between 20 and 25% at rest and during exercise were comparable to those affected by nifedipine. In addition to the right ventricular afterload reduction, there was a decrease in cardiac output of 17%. During longterm treatment with nifedipine (average 18 months), the reduction in mean pulmonary artery pressure and pulmonary arteriolar resistance was not of the same magnitude as seen on acute testing. This may be due primarily to progression of the underlying disease since pulmonary function studies demonstrated an increase in the obstructive component. With the intention of circumventing or postponing the onset of right ventricular failure, the individual patient should undergo hemodynamic studies to delineate the optimal medication.

  4. Targeted delivery of genes to endothelial cells and cell- and gene-based therapy in pulmonary vascular diseases.

    Science.gov (United States)

    Suen, Colin M; Mei, Shirley H J; Kugathasan, Lakshmi; Stewart, Duncan J

    2013-10-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that, despite significant advances in medical therapies over the last several decades, continues to have an extremely poor prognosis. Gene therapy is a method to deliver therapeutic genes to replace defective or mutant genes or supplement existing cellular processes to modify disease. Over the last few decades, several viral and nonviral methods of gene therapy have been developed for preclinical PAH studies with varying degrees of efficacy. However, these gene delivery methods face challenges of immunogenicity, low transduction rates, and nonspecific targeting which have limited their translation to clinical studies. More recently, the emergence of regenerative approaches using stem and progenitor cells such as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have offered a new approach to gene therapy. Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. These new regenerative approaches have shown tremendous potential in preclinical studies; however, large, rigorously designed clinical studies will be necessary to evaluate clinical efficacy and safety.

  5. Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Muller H Konrad

    2010-07-01

    Full Text Available Abstract Background Little is known about airway remodelling in bronchial biopsies (BB in smokers and chronic obstructive pulmonary disease (COPD. We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm fragmentation and altered vessel distribution in COPD. Methods To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects. Results Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p Conclusions Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.

  6. Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems.

    Science.gov (United States)

    Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com

  7. Hipertensão arterial pulmonar e acidente vascular encefálico em paciente com Arterite de Takayasu Pulmonary arterial hypertension and cerebrovascular disease in patient with Takayasu Arteritis

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    Carlos Frederico Rodrigues Parchen

    2006-12-01

    Full Text Available Arterite de Takayasu (AT é uma doença rara caracterizada por vasculite dos grandes vasos, principalmente aorta e seus ramos. A inflamação vascular leva a irregularidades na parede do vaso, causando estenoses e aneurismas. O envolvimento da artéria pulmonar (AP é freqüente na AT. Apesar disso, o desenvolvimento de hipertensão arterial pulmonar (HAP é menos comum, alterando o tratamento e o prognóstico dos pacientes. Descrevemos um caso de uma paciente com AT com estenoses múltiplas em artérias pulmonares, HAP e doença cerebrovascular, além de revisão de literatura sobre o assunto.Takayasu arteritis (TA is a rare illness characterized by vasculitis of great vessels, mainly of aorta and its branches. The vascular inflammation leads to irregularities of the vessel wall causing stenosis and aneurysms. The pulmonary artery (PA involvement is frequent in TA. Despite this, the development of pulmonary arterial hypertension is less common, modifying the treatment and the prognosis of the patients. We describe a case of a patient with TA with multiple stenosis in pulmonary arteries, pulmonary arterial hypertension and cerebrovascular disease, as well as review of the literature on the subject.

  8. Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and female sex.

    Science.gov (United States)

    O'Brien, S F; Russell, J C; Dolphin, P J; Davidge, S T

    2000-08-01

    Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats showed enhanced maximum contractility in response to norepinephrine; impaired smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and impaired relaxation in response to acetylcholine (ACh), compared with their lean counterparts. The abnormalities were similar in male and female cp/cp rats. The NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no reduction in maximal relaxation, and was absent in cp/cp females. These effects suggest that the relative importance of NO in the endothelial modulation of smooth muscle contractility is greater in male rats. The results are consistent with a decreased role for endothelial NO in the cp/cp rats of both sexes and a reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO-independent mechanism is not affected in the female cp/cp rats. The relatively small differences between males and females in smooth muscle cell and vascular function may contribute to sex-related differences in the atherogenesis, vasospasm, and ischemic damage associated with the obese insulin-resistant state.

  9. Prevalence, Risk Factors, and Treatment Outcomes of Isoniazid- and Rifampicin-Mono-Resistant Pulmonary Tuberculosis in Lima, Peru.

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    Leonela Villegas

    Full Text Available Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes.A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment.Of 1292 patients enrolled, 1039 (80% were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8% patients and rifampicin mono-resistance was present in 24 (2% patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR = 2.10; 95% confidence interval (CI: 1.1-4.1, and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9-47.8. Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01 and death (4/85, 5%, p<0.02. Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01.A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes.

  10. The effects of oxygen induced pulmonary vasoconstriction on bedside measurement of pulmonary gas exchange.

    Science.gov (United States)

    Weinreich, Ulla M; Thomsen, Lars P; Rees, Stephen E; Rasmussen, Bodil S

    2016-04-01

    In patients with respiratory failure measurements of pulmonary gas exchange are of importance. The bedside automatic lung parameter estimator (ALPE) of pulmonary gas exchange is based on changes in inspired oxygen (FiO2) assuming that these changes do not affect pulmonary circulation. This assumption is investigated in this study. Forty-two out of 65 patients undergoing coronary artery bypass grafting (CABG) had measurements of mean pulmonary arterial pressure (MPAP), cardiac output and pulmonary capillary wedge pressure thus enabling the calculation of pulmonary vascular resistance (PVR) at each FiO2 level. The research version of ALPE was used and FiO2 was step-wise reduced a median of 0.20 and ultimately returned towards baseline values, allowing 6-8 min' steady state period at each of 4-6 levels before recording the oxygen saturation (SpO2). FiO2 reduction led to median decrease in SpO2 from 99 to 92 %, an increase in MPAP of 4 mmHg and an increase in PVR of 36 dyn s cm(-5). Changes were immediately reversed on returning FiO2 towards baseline. In this study changes in MPAP and PVR are small and immediately reversible consistent with small changes in pulmonary gas exchange. This indicates that mild deoxygenation induced pulmonary vasoconstriction does not have significant influences on the ALPE parameters in patients after CABG.

  11. Pulmonary hemodynamics in obstructive sleep apnea: frequency and causes of pulmonary hypertension.

    Science.gov (United States)

    Hetzel, M; Kochs, M; Marx, N; Woehrle, H; Mobarak, I; Hombach, V; Hetzel, J

    2003-01-01

    The association between nocturnal apneas and transient pulmonary hypertension (PHT) has been well documented. However, there is controversy over the frequency and pathophysiological mechanisms of daytime pulmonary hypertension in patients with obstructive sleep apnea (OSAS). The present study sought to evaluate frequency and mechanisms of pulmonary hypertension in patients with OSAS. It included 49 consecutive patients with polysomnographically proven OSAS without pathological lung function testing. All patients performed daytime measurements of pulmonary hemodynamics at rest and during exercise (50-75W). Six patients (12%) had resting PHT mean pulmonary of artery pressure (PAPM) of >20 mmHg), whereas 39 patients (80%) showed PHT during exercise (PAPM >30 mmHg). Multiple regression analysis revealed 3 independent contributing factors for mean pulmonary artery pressure during exercise (PAPMmax): body mass index, age and total lung capacity % of predicted. Twenty-five of the 39 patients with pathologically high PAPMmax (64%) showed elevated pulmonary capillary wedge pressures (PCWPmax > 20 mmHg), whereas no patient had elevated pulmonary vascular resistance (PVRmax > 120 dynes x s x cm(-5)). In conclusion, daytime PHT during exercise is frequently seen in patients with OSAS and normal lung function testing and is mainly caused by abnormally high PCWP, whereas PVR seems to play a minor role.

  12. Molecular detection of multidrug-resistant tuberculosis among smear-positive pulmonary tuberculosis patients in Jigjiga town, Ethiopia

    Science.gov (United States)

    Brhane, Mussie; Kebede, Ameha; Petros, Yohannes

    2017-01-01

    Background Molecular methods that target drug resistance mutations are suitable approaches for rapid drug susceptibility testing to detect multidrug-resistant tuberculosis (MDR-TB). The aim of the study was to determine MDR-TB cases and to analyze the frequency of gene mutations associated with rifampicin (RIF) and/or isoniazid (INH) resistance of Mycobacterium tuberculosis among smear-positive pulmonary tuberculosis patients. Methods Institution-based cross-sectional study design was employed. Sputum specimens were collected, and using a pretested questionnaire, data for associated risk factors for drug resistance were collected from 105 consecutive smear-positive pulmonary tuberculosis patients in Karamara General Hospital. Specimens were transported to Harar Health Research and Regional Laboratory, Harar, where molecular drug susceptibility testing was performed using GenoType® MTBDRplus assay. Results Of the total 105 sputum specimens, 98 (93.3%) gave interpretable results, in which 67 (68.4%) were new cases and 31 (31.6%) were previously treated cases. Of these, 80 (81.6%) were sensitive to both drugs and 18 (18.4%) were resistant to RIF and/or INH. The prevalences of MDR-TB in total cases, new, and previously treated cases were 10 (10.2%), 3 (4.5%), and 7 (22.6%), respectively. Among the ten total RIF-resistant specimens, eight (80%) had resulted because of absence of rpoB WT8 and presence of MUT3 and in all specimens, the amino acids changed were Ser531Lue. Of the 18 total INH-resistant specimens, 15 (83.3%) had mutations in the katG gene (katG MUT1, Ser315Thr1), indicating high-level resistance, while 3 (14.7%) had mutations in the inhA promoter gene (Cys15Thr), indicating low-level resistance. Conclusion Among the mutations associated with resistance to RIF and INH, the majority were in codon 531 of the rpoB gene and codon 315 of the katG gene. Relatively high prevalence of MDR-TB was observed in the study.

  13. Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.

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    Chuanyu Wei

    Full Text Available Pulmonary hypertension (PH is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC dysfunction and pulmonary arterial smooth muscle cell (PASMC proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4 is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH.

  14. Treatment of Vasodilator-resistant Mixed Connective Tissue Disease-associated Pulmonary Arterial Hypertension with Glucocorticoid and Cyclophosphamide.

    Science.gov (United States)

    Sugawara, Eri; Kato, Masaru; Hisada, Ryo; Oku, Kenji; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Atsumi, Tatsuya

    2017-01-01

    Pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MTCD), in contrast to other types of PAH, may respond to immunosuppressive therapy. Most PAH cases with an immunosuppressant response were in the early stages of the disease (WHO functional class III or less). The present case was a 34-year-old woman with MCTD-associated PAH (WHO functional class IV) who was resistant to a combination of three vasodilators. Afterwards, she was treated with glucocorticoid and cyclophosphamide. This case suggested the potential benefit of immunosuppressants in patients with severe MCTD-associated PAH.

  15. TNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice.

    Science.gov (United States)

    da Costa, Rafael Menezes; Neves, Karla Bianca; Mestriner, Fabíola Leslie; Louzada-Junior, Paulo; Bruder-Nascimento, Thiago; Tostes, Rita C

    2016-08-25

    High fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-α, a cytokine that contributes to insulin resistance and vascular dysfunction. Considering that the enzyme phosphatase and tension homologue (PTEN), whose expression is increased by TNF-α, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-α-mediated vascular resistance to insulin induced by HFD. Mechanisms underlying PTEN effects were determined. Mesenteric vascular beds were isolated from C57Bl/6J and TNF-α KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-α and PTEN contribute to vascular dysfunction. Vasodilation in response to insulin was decreased in HFD-fed mice and in ex vivo control arteries incubated with TNF-α. TNF-α receptors deficiency and TNF-α blockade with infliximab abolished the effects of HFD and TNF-α on insulin-induced vasodilation. PTEN vascular expression (total and phosphorylated isoforms) was increased in HFD-fed mice. Treatment with a PTEN inhibitor improved insulin-induced vasodilation in HFD-fed mice. TNF-α receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice. TNF-α induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-α and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity-related conditions.

  16. Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet.

    Science.gov (United States)

    Noly, Pierre-Emmanuel; Guihaire, Julien; Coblence, Matthieu; Dorfmüller, Peter; Fadel, Elie; Mercier, Olaf

    2015-11-04

    An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. Pulmonary Hypertension (PH) was induced in 3-week-old piglets by a progressive obstruction of the pulmonary vascular bed. A ligation of the left Pulmonary Artery (PA) was performed first through a mini-thoracotomy. Second, weekly embolizations of the right lower pulmonary lobe were done under fluoroscopic guidance with n-butyl-2-cyanoacrylate during 5 weeks. Mean Pulmonary Arterial Pressure (mPAP) measured by ritght heart catheterism, increased progressively, as well as Right Atrial pressure and Pulmonary Vascular Resistances (PVR) after 5 weeks compared to sham animals. Right Ventricular (RV) structural and functional remodeling were assessed by transthoracic echocardiography (RV diameters, RV wall thickness, RV systolic function). RV elastance and RV-pulmonary coupling were assessed by Pressure-Volume Loops (PVL) analysis with conductance method. Histologic study of the lung and the right ventricle were also performed. Molecular analyses on RV fresh tissues could be performed through repeated transcutaneous endomyocardial biopsies. Pulmonary microvascular disease in obstructed and unobstructed territories was studied from lung biopsies using molecular analyses and pathology. Furthermore, the reliability and the reproducibility was associated with a range of PH severity in animals. Most aspects of the human CTEPH disease were reproduced in this model, which allows new perspectives for the understanding of the underlying mechanisms (mitochondria, inflammation) and new therapeutic approaches (targeted, cellular or gene therapies) of the overloaded right ventricle but also pulmonary microvascular disease.

  17. A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis.

    Science.gov (United States)

    Su, J; Hilberg, O; Howard, L; Simonsen, U; Hughes, A D

    2016-12-01

    Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness, and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery.

  18. Fibrinogen Aα Thr312Ala polymorphism specifically contributes to chronic thromboembolic pulmonary hypertension by increasing fibrin resistance.

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    Ji-Feng Li

    Full Text Available BACKGROUND: Polymorphisms are associated with chronic thromboembolic pulmonary hypertension (CTEPH and pulmonary thromboembolism (PTE, but no polymorphism specific to CTEPH but not PTE has yet been reported. Fibrin resistance is associated with CTEPH, but the mechanism has not been elucidated. METHODS: Polymorphisms were analyzed in 101 CTEPH subjects, 102 PTE subjects and 108 healthy controls by Massarray or restriction fragment length polymorphism (RFLP. Plasmin-mediated cleavage of fibrin was characterized in 69 subjects (29 with CTEPH, 21 with PTE and 19 controls. RESULTS: Genotype frequencies and allele frequencies of fibrinogen Aα Thr312Ala were significantly higher in CTEPH subjects than in controls and PTE subjects, while there was no difference between PTE subjects and controls. The odd ratio (OR 2.037 and 95% confidence interval (95% CI, 1.262-3.289 showed that Thr312Ala polymorphism was a risk factor for CTEPH but not PTE. Fibrin from CTEPH subjects was more resistant to lysis than that from PTE subjects and controls. Fibrin resistance was significantly different between Aα Thr312Ala (A/G genotypes within CTEPH subjects, and the fibrin with GG genotype was more resistant than that with AA and AG genotype. CONCLUSIONS: Fibrinogen Aα Thr312Ala (A/G polymorphism was associated with CTEPH, but not PTE, suggesting that the fibrinogen Aα Thr312Ala polymorphism may act as a potential biomarker in identifying CTEPH from PTE. GG genotype polymorphism contributes to CTEPH through increasing fibrin resistance, implying that PTE subjects with fibrinogen Aα GG genotype may need long-term anticoagulation therapy.

  19. Systemic vascular resistance is increased and associated with accelerated arterial stiffening change in patients with chronic cervical spinal cord injury.

    Science.gov (United States)

    Huang, S C; May-Kuen Wong, A; Lien, H Y; Fuk-Tan Tang, S; Fu, T C; Lin, Y; Wang, J S

    2013-02-01

    Despite of stiffening change of conduit arteries, how total peripheral resistance (TPR) is adapted to chronic spinal cord injury (SCI) remains unclear. To investigate how chronic cervical SCI influences hemodynamic characteristics Cross-sectional, case-control study. Rehabilitation department in the tertiary medical center. Twenty-one male patients with traumatic SCI resulting from cervical spine fracture were recruited. The injury occurred three to 289 months (46 months in average) previously. Twenty-one healthy male participants with matched age and body mass index were enrolled as control group. The subjects were asked to maintain supine rest (SR) and then head-up tilt (HUT) at 60 degree for five minutes, respectively. A novel noninvasive bio-reactance device was employed to measure cardiac hemodynamics, whereas heart rate variability was used to determine cardiac autonomic activity. Additionally, the digital volume pulse analysis was applied to calculate arterial stiffness index (SI) and arteriolar reflection index (RI). SCI patients revealed less stroke volume and cardiac output (CO), as well as, greater total peripheral resistance (TPR) and SI during SR than normal subjects did. Moreover, the positive correlation between TPR and SI was observed in SCI patients rather than normal subjects. In SCI patients, HUT (1) markedly decreased TPR while CO and cardio-acceleration responses remained intact and (2) decreased HF power value but failed to change LF/HF ratio. Furthermore, the degree of orthostatic hypotension was correlated with the TPRHUT/TPRSR ratio but not the COHUT/COSR ratio. Chronic cervical SCI leads to a progressively accelerated increase in vascular stiffness, which is associated with increase in systemic vascular resistance. Furthermore, the cervical SCI-related orthostatic hypotension lies in the impairment of vasoconstriction without cardiac dysfunction. Clinical Rehabilitation Impact. SI, rather than blood pressure, reflects not only

  20. Inflammation marker, damage marker and anabolic hormone responses to resistance training with vascular restriction in older males.

    Science.gov (United States)

    Karabulut, Murat; Sherk, Vanessa D; Bemben, Debra A; Bemben, Michael G

    2013-09-01

    The goal of this study was to examine anabolic hormone, muscle damage marker and inflammation marker responses to two types of resistance training protocols in older men. Thirty-six healthy older males (mean age = 56.6 ± 0.6 years) completed 6 weeks of high-intensity resistance training (HI-RT), low-intensity resistance training with vascular restriction (LI-BFR) or no exercise control group (CON) three times per week. Three upper body exercises were performed by both exercise groups at the same intensity (at 80% 1-RM), but lower body exercises were performed by the HI-RT group at 80% 1-RM and by the LI-BFR group at 20% 1-RM with vascular restriction. Resting serum creatine kinase (CK), interleukin 6 (IL-6), insulin-like growth factor-I (IGF-I), IGF binding protein 3 (IGFBP-3) and testosterone (T) were measured before and after training. No significant group differences in resting CK, IL-6, IGF-I, IGFBP-3 and T were detected following training (P>0.05). In addition, there were no significant changes in muscle cross-sectional area (CSA), but a trend for significant decreases in the percent changes in thigh subcutaneous fat (P = 0.051). Although training-induced anabolic hormone response did not reach statistical significance, our findings on CK and IL-6 indicated that the LI-BFR training protocol was safe and well tolerated for older men to perform to improve muscular strength. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  1. The Role of Anion Exchanger on Pulmonary Vascular Response to Sustained Alveolar Hypoxia in the Isolated Perfused Rabbit Lung

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    Farzaneh Ketabchi

    2015-05-01

    Full Text Available Background: Some respiratory diseases may induce alveolar hypoxia thereby hypoxic pulmonary vasoconstriction (HPV. However, the mechanisms of this physiologic phenomenon are not fully understood. This study was the first to investigate the role of anion exchanger in sustained HPV. Methods: Experiments were performed in the isolated perfused rabbit lung. After preparation, the lungs were divided into six groups: two DIDS (4,4-diisothiocyanostilbene 2,2-disulfonic acid, anion exchanger inhibitor-treated [200 µM (n=5 or 400 µM (n=3] hypoxic groups, two HCO3- free hypoxic groups, one control hypoxic group (n=7 and one control normoxic group (n=4. DIDS were added to the perfusate at 10 minutes before starting the experiments. In the HCO3- free groups, HEPES (4-(2-Hydroxyethylpiperazine-1-ethanesulfonic acid were added to the perfusate instead of bicarbonate. Furthermore, in the HEPES1 (n=4 and HEPES2 (n=4 groups, the lungs were ventilated with hypoxic gas with or without CO2, respectively. Results: Ventilation of the lungs with hypoxic gas resulted in biphasic HPV, the acute (0-20 minutes and sustained (20-60 minutes phases. No alteration in both phases of HPV was detected by DIDS (200 µM. However, DIDS (400 µM, extended the ascending part of acute HPV until min 24. Both phases of HPV were decreased in the HEPES1 group. However, in the HEPES 2 group, HPV tended to increase during the rising part of the acute phase of HPV. Conclusions: Since DIDS (400 µM extended acute phase of HPV, and HCO3- free perfusate buffer enhanced rising phase of it, therefore it can be suggested that anion exchanger may modulate HPV especially during the acute phase. The abstract of this article was presented as a poster in the congress of European Respiratory Society (ERS on Monday, 08 September 2014, Munich, Germany and was published in the ERJ September 1, 2014 vol. 44 no. Suppl 58 P2343.

  2. [From acute pulmonary embolism to chronic thromboembolic pulmonary hypertension: Pathobiology and pathophysiology].

    Science.gov (United States)

    Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

    Chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique subtype of pulmonary hypertension characterized by the presence of mechanical obstruction of the major pulmonary vessels caused by venous thromboembolism. CTEPH is a progressive and devastating disease if not treated, and is the only subset of PH potentially curable by a surgical procedure known as pulmonary endarterectomy. The clot burden and pulmonary embolism recurrence may contribute to the development of CTEPH however only few thrombophilic factors have been found to be associated. A current hypothesis is that CTEPH results from the incomplete resolution and organization of thrombus modified by inflammatory, immunologic and genetic mechanisms, leading to the development of fibrotic stenosis and adaptive vascular remodeling of resistance vessels. The causes of thrombus non-resolution have yet to be fully clarified. CTEPH patients often display severe PH that cannot be fully explained by the degree of pulmonary vascular obstruction apparent on imaging studies. In such cases, the small vessel disease and distal obstructive thrombotic lesions beyond the sub-segmental level may contribute for out of proportion elevated PVR. The processes implicated in the development of arteriopathy and micro-vascular changes might explain the progressive nature of PH and gradual clinical deterioration with poor prognosis, as well as lack of correlation between measurable hemodynamic parameters and vascular obstruction even in the absence of recurrent venous thromboembolism. This review summarizes the most relevant up-to-date aspects on pathobiology and pathophysiology of CTEPH. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  3. STRUCTURE OF PULMONARY HYPERTENSION IN PATIENTS AWAITING HEART TRANSPLANTATION

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    A. A. Piontek

    2009-01-01

    Full Text Available The selection of recipients for the orthotopic heart transplantation is of great importance. In 2006–2009 we examined 25 tests on reversibility of pulmonary hypertension, i.e. in 14 patients with dilated cardiomyopathy (DCM (11 males and 3 females aged 41,1 ± 9,3 and in 11 patients with coronary artery disease (CAD (all males aged 50 ± 4.9. Initial pulmonary vascular resistance (PVR was 3,61 ± 1,02 and 3,59 ± 0,98 respectively. Alprostadil was infused to all the patients. Pulmonary hypertension was irreversible in 4 (28,5% DCM patients and in 2 (18% CAD patients. Initial PVR in those patients was 6,27 ± 3,2 and 5,7 ± 2,4 respectively. The average alprostadil dose necessary for the reverse of pulmonary hypertension was 0,054 ± 0,027 μg/kg/min in DCM patients, and 0,047 ± 0,022 μg/kg/min in CAD patients. Thus, the application of alprostadil for the pharmacological correction of pulmonary vascular resistance is most effective in patients with moderate pulmonary hypertension according to Rich classification. 

  4. [Pulmonary hypertension in pediatric heart surgery].

    Science.gov (United States)

    Falcone, N

    2001-12-01

    Congenital heart disease can increase or decrease pulmonary blood flow, pulmonary vascular resistance (PVR) or pulmonary artery pressure (PAP). PAP is the product of PVR and pulmonary minute volume (Qp), such that pulmonary hypertension (PHT) may develop as a result of an increase in either PVR or Qp or both. Given that the pulmonary vascular bed is a low pressure system with high flow, any increase in resistance would generate PHT. The normal value of PVR is 2 Woods units (mm Hg/l/min). Increased PAP is due to hypoxic lesions of the endothelium, which release proteolytic enzymes that alter the balance of metabolites of arachidonic acid, regulators of pulmonary vasomotor tone. Hypoxia and acidosis cause intense pulmonary vasoconstriction (hypoxic vasoconstrictor reflex). An increase of PVR is due to a combination of vasoconstrictive processes and remodeling, with hypertrophy of the pulmonary artery. Structural lesions are related to hypertrophy of the endothelium, the transformation of fibroblasts to myocytes and the decrease of the alveolar/arteriolar ratio with the formation of new vessels.PHT may be primary or secondary to another disease. Primary PHT is a rare genetic disease. The most common secondary forms of PHT in pediatrics are due to persistence of neonatal anatomy (neonatal PHT), to heart diseases with left-right shunt (CIV, DAP, etc.), to diseases of the pulmonary parenchyma (interstitial viral infection, mucoviscidosis), and complications of heart surgery. All congenital heart diseases can lead to PHT if not treated promptly. Clinical signs of PHT are highly non-specific: dyspnea, fatigue, syncopes, exercise intolerance, precordialgia, cyanosis and edema. The best approaches to diagnosis and prognosis are echocardiography and cardiac catheterization with vasodilators. Anesthetics that do not alter PVR should be used in such patients, who are sensitive to changes in pulmonary ventilation, to changes in cardiac output and to anesthetics. The treatment of

  5. [Pulmonary hypertension associated with congenital heart disease and Eisenmenger syndrome].

    Science.gov (United States)

    Calderón-Colmenero, Juan; Sandoval Zárate, Julio; Beltrán Gámez, Miguel

    2015-01-01

    Pulmonary arterial hypertension is a common complication of congenital heart disease (CHD). Congenital cardiopathies are the most frequent congenital malformations. The prevalence in our country remains unknown, based on birthrate, it is calculated that 12,000 to 16,000 infants in our country have some cardiac malformation. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodeling and endothelial dysfunction secondary to an imbalance in vasoactive mediators which promotes vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apotosis and fibrosis. The progressive rise in pulmonary vascular resistance and increased pressures in the right heart provocated reversal of the shunt may arise with the development of Eisenmenger' syndrome the most advanced form de Pulmonary arterial hypertension associated with congenital heart disease. The prevalence of Pulmonary arterial hypertension associated with CHD has fallen in developed countries in recent years that is not yet achieved in developing countries therefore diagnosed late as lack of hospital infrastructure and human resources for the care of patients with CHD. With the development of targeted medical treatments for pulmonary arterial hypertension, the concept of a combined medical and interventional/surgical approach for patients with Pulmonary arterial hypertension associated with CHD is a reality. We need to know the pathophysiological factors involved as well as a careful evaluation to determine the best therapeutic strategy. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  6. Increased minimal vascular resistance and arteriolar hyalinosis in skin on the leg in insulin-dependent diabetic patients

    DEFF Research Database (Denmark)

    Kastrup, J; Nørgaard, T; Parving, H H

    1987-01-01

    Minimal vascular resistance (MVR) was determined in a paralysed cutaneous vascular bed at the dorsum of the foot in diabetic patients. Twelve long-term insulin-dependent diabetic (IDDM) patients with and nine short-term IDDM patients without nephropathy and retinopathy and eight control subjects......-wise increases of external counter pressure. The MVR was calculated from the reciprocal of the slope of the relationship between blood flow and applied pressure. The MVR was significantly increased in diabetic patients with (mean: 9.3 mmHg ml-1.100 g.min) and without nephropathy and retinopathy (8.5 mmHg ml-1.......100 g.min) compared with non-diabetic subjects (5.2 mmHg ml-1.100 g.min) (p less than 0.001 and p less than 0.005, respectively). Diabetic microangiopathy (increased hyalinosis of the basement membranes in the terminal arterioles) was found in skin biopsies in nine of the 12 long-term IDDM patients...

  7. Effect of Nuclear Factor-kappa B on Vascular Endothelial Growth Factor mRNA Expression of Human Pulmonary Artery Smooth Muscle Cells in Hypoxia

    Institute of Scientific and Technical Information of China (English)

    张焕萍; 徐永健; 张珍祥; 许淑云; 倪望; 陈士新

    2004-01-01

    Summary: In order to investigate the effect of nuclear factor-kappa B (NF-κB) on vascular endothelial growth factor (VEGF) mRNA expression of human pulmonary artery smooth muscle cells (HPASMCs) in hypoxia, the cultured HPASMCs in vitro were stimulated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. The NF-κB p65 nuclei positive expression was detected by immunocytochemical technique. The IκBa protein expression was measured by Western blot.RT-PCR was used to detect the VEGF mRNA expression of HPASMCs. The results showed that no significant change was observed in the NF-κB p65 nuclei positive expression of cultured HPASMCs during 6 h-24 h in normoxia, but the levels of NF-κB p65 nuclei positive expression of cultured HPASMCs were significantly increased in hypoxia groups as compared with those in all normoxia groups (P<0.05). The IκBα protein expression of cultured HPASMCs showed no significant change during 6 h-24 h in normoxia, but significantly decreased in hypoxia as comapred with that in normoxia groups (P<0.05). PDTC (1 to 100 μmol/L) could inhibit the VEGF mRNA expression of HPASMCs in a concentration-dependent manner in hypoxia. In conclusion, NF-κB can be partly translocation activated from cytoplasm into nuclei in the cultured HPASMCs under hypoxia. The inhibition of NF-κB activation can decrease the VEGF mRNA expression. h is suggested that the activation of NF-κB is involved in the VEGFmRNA expression of HPASMCs under hypoxia.

  8. Hypoxic pulmonary hypertension and novel ATP-sensitive potassium channel opener: the new hope on the horizon

    Institute of Scientific and Technical Information of China (English)

    Yu JIN; Wei-ping XIE; Hong WANG

    2012-01-01

    Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries.The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance,reverse pulmonary vascular remodeling,and thereby improving right ventricular function.Iptakalim,a lipophilic para-amino compound with a low molecular weight,has been demonstrated to be a new selective ATP-sensitive potassium (KATP) channel opener via pharmacological,electrophysiological,biochemical studies,and receptor binding tests.In hypoxia-induced animal models,iptakalim decreases the elevated mean pressure in pulmonary arteries,and attenuates remodeling in the right ventricle,pulmonary arteries and airways.Furthermore,iptakalim has selective antihypertensive effects,selective vasorelaxation effects on smaller arteries,and protective effects on endothelial cells,but no effects on the central nervous,respiratory,digestive or endocrine systems at therapeutic dose.Our previous studies demonstrated that iptakalim inhibited the effects of endothelin-1,reduced the intracellular calcium concentration and inhibited the proliferation of pulmonary artery smooth muscle cells.Since iptakalim has been shown safe and effective in both experimental animal models and phase I clinical trials,it can be a potential candidate of HPH in the future.

  9. Hemodynamic effects of combination therapy with inhaled nitric oxide and iloprost in patients with pulmonary hypertension and right ventricular dysfunction after high-risk cardiac surgery.

    Science.gov (United States)

    Antoniou, Theofani; Koletsis, Efstratios N; Prokakis, Christos; Rellia, Panagiota; Thanopoulos, Apostolos; Theodoraki, Kassiani; Zarkalis, Dimitrios; Sfyrakis, Petros

    2013-06-01

    The purpose of this study was to evaluate the hemodynamic effects of inhaled nitric oxide (NO) plus aerosolized iloprost in patients with pulmonary hypertension/right ventricular dysfunction after cardiac surgery. A retrospective study. A single center. Eight consecutive patients with valve disease and postextracorporeal circulation (ECC) pulmonary hypertension/right ventricular dysfunction. The continuous inhalation of nitric oxide (10 ppm) and iloprost, 10 μg, in repeated doses. The hemodynamic profile was obtained before inhalation, during the administration of inhaled NO alone (prior and after iloprost), and after the first 2 doses of iloprost. Tricuspid annular velocity and tricuspid annular plane systolic excursion were estimated at baseline and before and after adding iloprost. At the end of the protocol, there were significant decreases in pulmonary vascular resistance (p iloprost dose was associated with further decreases in pulmonary vascular resistances/pressure. By comparing data at the beginning of inhaled NO with those after the second dose of iloprost, the authors noticed decreases in pulmonary vascular resistances (p = 0.004) and the mean pulmonary artery pressure (p = 0.017) and rises in tricuspid annular velocity (p iloprost significantly reduced pulmonary hypertension and contributed to the improvement in right ventricular function. Inhaled NO and iloprost have additive effects on pulmonary vasculature. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

    Science.gov (United States)

    Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

    2016-03-01

    Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.

  11. [Successful pregnancy in a patient with idiopathic pulmonary arterial hypertension. Case report].

    Science.gov (United States)

    Szenczi, Orsolya; Karlócai, Kristóf; Bucsek, László; Rigó, János

    2016-04-10

    Idiopathic pulmonary arterial hypertension is characterized by progressive increase in pulmonary arterial pressure and pulmonary vascular resistance which lead to right ventricular failure and death. Pregnancy in patients with idiopathic pulmonary arterial hypertension is contraindicated because of the high maternal and fetal mortality. The authors present a case of successful pregnancy and delivery of a patient with idiopathic pulmonary arterial hypertension in Hungary for the first time. The aim of the report was to demonstrate that management and treatment of idiopathic pulmonary arterial hypertension in a pregnant woman is a complex and multidisciplinary task that should involve obstetrician, cardiologist and anesthesiologist. Those patients who become pregnant and do not wish to terminate the pregnancy must be referred to obstetric centers where a multidiciplinary approach is taken.

  12. Pathogenic Mechanisms of Pulmonary Arterial Hypertension

    Science.gov (United States)

    Chan, Stephen Y.; Loscalzo, Joseph

    2008-01-01

    Pulmonary arterial hypertension (PAH)1 is a complex disease that causes significant morbidity and mortality and is clinically characterized by an increase in pulmonary vascular resistance. The histopathology is marked by vascular proliferation/fibrosis, remodeling, and vessel obstruction. Development of PAH involves the complex interaction of multiple vascular effectors at all anatomic levels of the arterial wall. Subsequent vasoconstriction, thrombosis, and inflammation ensue, leading to vessel wall remodeling and cellular hyperproliferation as the hallmarks of severe disease. These processes are influenced by genetic predisposition as well as diverse endogenous and exogenous stimuli. Recent studies have provided a glimpse at certain molecular pathways that contribute to pathogenesis; these have led to the identification of attractive targets for therapeutic intervention. We will review our current understanding of the mechanistic underpinnings of the genetic and exogenous/acquired triggers of PAH. The resulting imbalance of vascular effectors provoking pathogenic vascular changes will also be discussed, with an emphasis on common and overarching regulatory pathways that may relate to the primary triggers of disease. The current conceptual framework should allow for future studies to refine our understanding of the molecular pathogenesis of PAH and improve the therapeutic regimen for this disease. PMID:17950310

  13. Pulmonary Edema: Classification, Mechanisms of Development, Diagnosis

    Directory of Open Access Journals (Sweden)

    V. V. Moroz

    2009-01-01

    Full Text Available Pulmonary edema remains a topical problem of modern reanimatology. In clinical practice, there is a need for continuous monitoring of the content of extravascular water in the lung and the pulmonary vascular permeability index for the timely detection and treatment of pulmonary edema. This literature review considers the minor mechanisms of pulmonary extravas-cular water exchange in health and in different types of pulmonary edema (acute lung injury, pneumonia, sepsis, postoperative period, burns, injuries etc., as well as the most accessible current (irradiation and dilution studies permitting an estimate of the level of pulmonary extravascular water and the pulmonary vascular permeability index in clinical practice. Key words: pulmonary edema, acute lung injury, pulmonary extravascular water, pulmonary vascular permeability index.

  14. Expression of tissue factor and forkhead box transcription factor O-1 in a rat model for chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Deng, Chaosheng; Wu, Dawen; Yang, Minxia; Chen, Yunfei; Wang, Caiyun; Zhong, Zhanghua; Lian, Ningfang; Chen, Hua; Wu, Shuang

    2016-11-01

    Few reports have examined tissue factor (TF) and forkhead box transcription factor O-1 (FoxO1) expression in chronic thromboembolic pulmonary hypertension (CTEPH) animal models. To investigate the role of TF and FoxO1 and their interactions during CTEPH pathogenesis in a rat model. Autologous blood clots were repeatedly injected into the pulmonary arteries through right jugular vein to induce a rat model of CTEPH. Hemodynamic parameters, histopathology, and TF and FoxO1expression levels were detected. The mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance and vessel wall area/total area (WA/TA) ratio in the experiment group increased significantly than sham group (P model of CTEPH can be successfully established by the injection of autologous blood clots into the pulmonary artery. TF and FoxO1 may play a key role in vascular remodeling during CTEPH pathogenesis.

  15. Acute effects of riociguat in borderline or manifest pulmonary hypertension associated with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ghofrani, Hossein A; Staehler, Gerd; Grünig, Ekkehard; Halank, Michael; Mitrovic, Veselin; Unger, Sigrun; Mueck, Wolfgang; Frey, Reiner; Grimminger, Friedrich; Schermuly, Ralph T; Behr, Juergen

    2015-06-01

    Riociguat is the first oral soluble guanylate cyclase stimulator shown to improve pulmonary hemodynamics in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH). This pilot study assessed the impact of a single dose of riociguat on hemodynamics, gas exchange, and lung function in patients with PH associated with chronic obstructive pulmonary disease (COPD). Adults with COPD-associated borderline or manifest PH (pulmonary vascular resistance > 270 dyn·s·cm(-5), mean pulmonary artery pressure ≥ 23 mmHg, ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity 70%, and partial pressure of oxygen and carbon dioxide in arterial blood > 50 and ≤ 55 mmHg, respectively) received riociguat 1 or 2.5 mg during right heart catheterization. Twenty-two patients completed the study (11 men, 11 women, aged 56-82 years; 1-mg group: n = 10 [mean FEV1: 43.1%]; 2.5-mg group: n = 12 [mean FEV1: 41.2%]). Riociguat caused significant improvements (P mmHg [-11.44%]; 2.5 mg: -4.83 mmHg [-14.76%]) and pulmonary vascular resistance (1 mg: -58.32 dyn·s·cm(-5) [-15.35%]; 2.5 mg: -123.8 dyn·s·cm(-5) [-32.96%]). No relevant changes in lung function or gas exchange were observed. Single doses of riociguat were well tolerated and showed promising hemodynamic effects without untoward effects on gas exchange or lung function in patients with COPD-associated PH. Placebo-controlled studies of chronic treatment with riociguat are warranted.

  16. Suction/Inspiration against resistance or standardized Mueller maneuver : a new breathing technique to improve contrast density within the pulmonary artery: a pilot CT study.

    Science.gov (United States)

    Gutzeit, Andreas; Froehlich, Johannes M; Wälti, Stephan; Roos, Justus E; Meissnitzer, Matthias; Hergan, Klaus; von Weymarn, Constantin; Czell, David; Goyen, Matthias; Reischauer, Carolin

    2015-11-01

    Our aim was to prospectively investigate whether the recently introduced suction/inspiration against resistance breathing method leads to higher computed tomography (CT) contrast density in the pulmonary artery compared to standard breathing. The present study was approved by the Medical Ethics committee and all subjects gave written informed consent. Fifteen patients, each without suspicious lung emboli, were randomly assigned to four different groups with different breathing maneuvers (suction against resistance, Valsalva, inspiration, expiration) during routine CT. Contrast enhancement in the central and peripheral sections of the pulmonary artery were measured and compared with one another. Peripheral enhancement during suction yielded increased mean densities of 138.14 Hounsfield units (HU) (p = 0.001), compared to Valsalva and a mean density of 67.97 HU superior to inspiration (p = 0.075). Finally, suction in comparison to expiration resulted in a mean increase of 30.51 HU (p = 0.42). Central parts of pulmonary arteries presented significantly increased enhancement values (95.74 HU) for suction versus the Valsalva technique (p = 0.020), while all other mean densities were in favour of suction (versus inspiration: p = 0.201; versus expiration: p = 0.790) without reaching significance. Suction/Inspiration against resistance is a promising technique to improve contrast density within pulmonary vessels, especially in the peripheral parts, in comparison to other breathing maneuvers. • Suction/Inspiration against resistance is promising to improve contrast density within the pulmonary artery. • Patients potentially suffering pulmonary embolism are able to follow suction/inspiration against resistance. • Contrast density after suction is superior in comparison to other breathing maneuvers.

  17. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice.

    Science.gov (United States)

    Sartori, Claudio; Dessen, Pierre; Mathieu, Caroline; Monney, Anita; Bloch, Jonathan; Nicod, Pascal; Scherrer, Urs; Duplain, Hervé

    2009-12-01

    Obesity and insulin resistance represent a problem of utmost clinical significance worldwide. Insulin-resistant states are characterized by the inability of insulin to induce proper signal transduction leading to defective glucose uptake in skeletal muscle tissue and impaired insulin-induced vasodilation. In various pathophysiological models, melatonin interacts with crucial molecules of the insulin signaling pathway, but its effects on glucose homeostasis are not known. In a diet-induced mouse model of insulin resistance and normal chow-fed control mice, we sought to assess the effects of an 8-wk oral treatment with melatonin on insulin and glucose tolerance and to understand underlying mechanisms. In high-fat diet-fed mice, but not in normal chow-fed control mice, melatonin significantly improved insulin sensitivity and glucose tolerance, as evidenced by a higher rate of glucose infusion to maintain euglycemia during hyperinsulinemic clamp studies and an attenuated hyperglycemic response to an ip glucose challenge. Regarding underlying mechanisms, we found that melatonin restored insulin-induced vasodilation to skeletal muscle, a major site of glucose utilization. This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin-induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin-treated high-fat diet-fed mice. In contrast, melatonin had no effect on the ability of insulin to promote glucose uptake in skeletal muscle tissue in vitro. These data demonstrate for the first time that in a diet-induced rodent model of insulin resistance, melatonin improves glucose homeostasis by restoring the vascular action of insulin.

  18. Avaliação do suprimento sangüíneo vascular pulmonar nos portadores de atresia pulmonar com comunicação interventricular e artérias colaterais sistêmico-pulmonares Assessment of the pulmonary vascular blood supply in patients with pulmonary atresia, ventricular septal defect, and aortopulmonary collateral arteries

    Directory of Open Access Journals (Sweden)

    Ulisses Alexandre Croti

    2005-01-01

    Full Text Available OBJETIVO: Analisar as características morfométricas das artérias pulmonares centrais e artérias colaterais sistêmico-pulmonares, avaliando a morfologia do suprimento sangüíneo vascular pulmonar, procurando estabelecer suas implicações no tratamento cirúrgico. MÉTODO: Entre janeiro/1990 e junho/2001, foram estudados 40 pacientes, incluíndo-se os que apresentavam estudo cineangiocardiográfico completo e prévio à primeira intervenção cirúrgica. Analisaram-se as características morfométricas das artérias pulmonares centrais e artérias colaterais sistêmico-pulmonares, assim como a distribuição da irrigação sangüínea nos pulmões. Calcularam-se os índices arterial pulmonar (IAAPP, arterial colateral sistêmico-pulmonar (IACSP e arterial neopulmonar total (IANPT = IAAPP + IACSP. O tratamento cirúrgico foi considerado paliativo (TP, paliativo definitivo (TPD e definitivo (TD. RESULTADOS: O TP foi predominante. Não houve diferenças estatisticamente significantes entre os pacientes com TP, TPD e TD, em relação ao IAAPP, IACSP e IANPT. Comparando o IAAPP e o IACSP, não houve diferença entre os índices para o TD (p=0,4309, o IACSP foi maior que o IAAPP para o TP (p=0,0176 e descritivamente também maior para o TPD. O IANPT dos pacientes em TD foi maior que os em TP (p=0,0959. Foram identificados cinco subgrupos morfologicamente semelhantes, denominados: B1, B2, B3, B4 e B5. A mortalidade total foi de 17,5%. CONCLUSÃO: A morfologia do suprimento sangüíneo vascular pulmonar das artérias pulmonares centrais e artérias colaterais sistêmico-pulmonares mostrou-se soberana na orientação do tratamento cirúrgico. Independentemente da divisão didática em subgrupos, o TP foi predominante. A mortalidade não apresentou correlação com as características morfométricas.OBJECTIVE: To study the morphometric characteristics of the central pulmonary arteries and aortopulmonary collateral arteries by assessing the morphology

  19. Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Pettigrew, Melinda M; Tsuji, Brian T; Gent, Janneane F; Kong, Yong; Holden, Patricia N; Sethi, Sanjay; Murphy, Timothy F

    2016-07-01

    Little is known about the effect of antibiotics on eradication of carriage and development of resistance in Haemophilus influenzae in individuals with chronic obstructive pulmonary disease (COPD). Our goals were to assess antibiotic susceptibilities, prevalence of resistance genes, and development of resistance in H. influenzae and to evaluate the effect of macrolide and fluoroquinolone administration on H. influenzae eradication. Data were from a 15-year longitudinal study of COPD. Genome sequence data were used to determine genotype and identify resistance genes. MICs of antibiotics were determined by reference broth microdilution. Generalized linear mixed models were used to evaluate associations between antibiotic use and H. influenzae eradication. We examined 267 H. influenzae isolates from 77 individuals. All newly acquired H. influenzae isolates were susceptible to azithromycin. Five of 27 (19%) strains developed 4-fold increases in azithromycin MICs and reached or exceeded the susceptibility breakpoint (≤4 μg/ml) during exposure. H. influenzae isolates were uniformly susceptible to ciprofloxacin, levofloxacin, and moxifloxacin (MIC90s of 0.015, 0.015, and 0.06, respectively); there were no mutations in quinolone resistance-determining regions. Fluoroquinolone administration was associated with increased H. influenzae eradication compared to macrolides (odds ratio [OR], 16.67; 95% confidence interval [CI], 2.67 to 104.09). There was no difference in H. influenzae eradication when comparing macrolide administration to no antibiotic (OR, 1.89; 95% CI, 0.43 to 8.30). Fluoroquinolones are effective in eradicating H. influenzae in individuals with COPD. Macrolides are ineffective in eradicating H. influenzae, and their use in COPD patients may lead to decreased macrolide susceptibility and resistance.

  20. Prevalence, Risk Factors, and Treatment Outcomes of Isoniazid- and Rifampicin- Mono-Resistant Pulmonary Tuberculosis in Lima, Peru

    Science.gov (United States)

    Villegas, Leonela; Huaman, Moises A.; Van der Stuyft, Patrick; Gotuzzo, Eduardo; Seas, Carlos

    2016-01-01

    Background Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes. Methods A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment. Results Of 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1–4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9–47.8). Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01). Conclusion A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes. PMID:27045684

  1. HIPPO-Integrin-linked Kinase Cross-Talk Controls Self-Sustaining Proliferation and Survival in Pulmonary Hypertension

    NARCIS (Netherlands)

    Kudryashova, Tatiana V.; Goncharov, Dmitry A.; Pena, Andressa; Kelly, Neil; Vanderpool, Rebecca; Baust, Jeff; Kobir, Ahasanul; Shufesky, William; Mora, Ana L.; Morelli, Adrian E.; Zhao, Jing; Ihida-Stansbury, Kaori; Chang, Baojun; DeLisser, Horace; Tuder, Rubin M.; Kawut, Steven M.; Sillje, Herman H. W.; Shapiro, Steven; Zhao, Yutong; Goncharova, Elena A.

    2016-01-01

    Rationale: Enhanced proliferation and impaired apoptosis of pulmonary arterial vascular smooth muscle cells (PAVSMCs) are key pathophysiologic components of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Objectives: To determine the role and therapeutic relevance of HIPPO si

  2. Postoperative management of pulmonary endarterectomy and outcome

    Directory of Open Access Journals (Sweden)

    Narayana Iyengar Ramakrishna

    2010-01-01

    Full Text Available Pulmonary artery thromboendarterectomy (PTE has been regarded as a promising, potentially curative surgical procedure. However, PTE is associated with specific postoperative complications, such as reperfusion pulmonary edema and right heart failure leading to a considerable mortality of 7-24%. Despite its limitations PTE is a better surgical alternative to lung transplantation which carries high morbidity and mortality. The aim of the study is to analyze the efficacy, safety, morbidity and survival associated in the postoperative period and quality of life after six months of PTE in Indian patients. Forty-one patients with surgically correctable chronic thromboembolic pulmonary hypertension underwent pulmonary endarterectomy. All patients were in New York Heart Association (NYHA Class II, III or IV. Preoperative mean pulmonary artery pressure was 40.98 ± 9.29 mmHg and mean pulmonary vascular resistance was 418.39 ± 95.88 dynes/sec/cm -5 . All patients were followed up to six months and a telephonic survey was conducted using a standard questionnaire. They were assessed and classified as per NYHA grading. There was a significant reduction in the mean pulmonary artery pressure (from 40.98 ± 9.29 mmHg to 24.13 ± 7.36 mmHg, P < 0.001 and pulmonary vascular resistance (from 418.39 ± 95.88 dynes/sec/cm -5 to 142.45 ± 36.27 dynes/sec/cm -5 , P < 0.001 with a concomitant increase in the cardiac index (from 1.99 ± 0.20 L/min/m 2 to 3.28 ± 0.56 L/min/m 2 , P < 0.001 during the postoperative period. The mortality rate in our study was 12.19% (five patients. Ninety per cent of the patients reported a significant improvement in the quality of life and exercise tolerance after surgery compared to the preoperative state. Pulmonary endarterectomy is an effective and potentially curative surgical treatment for patients with severe chronic thromboembolic pulmonary hypertension. The current techniques of operation make the procedure relatively safe and

  3. 内皮抑制素对慢性阻塞性肺疾病肺血管重塑的影响%Effect of Endostar on pulmonary vascular remodeling in animal model of chronic obstructive pulmonarv disease

    Institute of Scientific and Technical Information of China (English)

    王昌明; 蒋明; 吕倩; 梁荣感; 李运千

    2011-01-01

    Objective To investigate the effect of Endostar on pulmonary vascular remodeling in chronic obstructive pulmonary disease (COPD). Methods 64 male SD rats were divided into healthy control, group A, chronic bronchitis group B, COPD group C,low oxygen with COPD group D. Intervention group included; Al (normal group) , Bl (chronic bronchitis intervented group) , Cl (COPD inter-vented group) , Dl (low oxygen with COPD intervented group). Animal models wwere made in the above intervention groups as the same as that in corresponding groups. Endostar 7. 5 mg ? M~ ? D ' ( 1. 25 mg/kg) was injected into the rats in each drug group from the third week. The saline water same dose of Endosta r was injected into the rat in Al group from the third week. The airway resistance and pulmonary he-modynamics were detected. HE staining was used to observe lung tissue pathological changes and VG + Victoria blue triple staining was used to observe the airway inflammation and pulmonary vascular remodeling in pathological changes. Immunohistochemistry was used to detect VEGF expression in rat lung tissue. ELISA was detected of VEGF expression in serum and RT-PCR was used to detect VEGF mRNA in lung tissue. Results Compared to the group A, the airway resistance, mean pulmonary arterial pressure (mPAP) in group C and D were higher than those of group A (P <0. 05) ; After Endostar intervention, the airway resistance, mPAP in group Cl , Dl were decreased than those of group C, D ( P < 0. 05). WT% , WA% value in group C, D were higher than those of group A, and WT% , WA% value were declined in these two groups after using Endostar. Serum VEGF level in group C and D were significantly higher than that of group A, and the VEGF concentration was significantly decreased in C, D groups than that of corresponding experimental group after using Endostar. VEGF mRNA of group B, C, D was gradually increased. The VEGF mRNA was gradually decreased in these three groups after using Endostar. Expression of

  4. Is pulmonary resistance constant, within the range of tidal volume ventilation, in patients with ARDS?

    Science.gov (United States)

    Mols, G; Kessler, V; Benzing, A; Lichtwarck-Aschoff, M; Geiger, K; Guttmann, J

    2001-02-01

    When managing patients with acute respiratory distress syndrome (ARDS), respiratory system compliance is usually considered first and changes in resistance, although recognized, are neglected. Resistance can change considerably between minimum and maximum lung volume, but is generally assumed to be constant in the tidal volume range (V(T)). We measured resistance during tidal ventilation in 16 patients with ARDS or acute lung injury by the slice method and multiple linear regression analysis. Resistance was constant within V(T) in only six of 16 patients. In the remaining patients, resistance decreased, increased or showed complex changes. We conclude that resistance within V(T) varies considerably from patient to patient and that constant resistance within V(T) is not always likely.

  5. Clinical worsening after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Schölzel, B; Snijder, R; Morshuis, W; Saouti, N; Plokker, T; Post, M

    2011-12-01

    Pulmonary endarterectomy (PEA) is the most effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study is to evaluate long-term survival and freedom from clinical worsening after PEA. All patients who underwent PEA in our hospital between May 2000 and August 2009 were included. Follow-up parameters were all-cause mortality and time to clinical worsening, defined as a combination of death, need for pulmonary hypertension-specific medication or 15% decrease in six-minute walk distance without improvement in functional class. The Cox proportional hazard regression was used to identify predictors. Seventy-four consecutive patients (mean age 55.9 ± 13.8 years, 51% female) underwent PEA. Prior to surgery, 55 patients were in NYHA functional class III or higher. The mean pulmonary artery pressure was 41.3 ± 11.9 mmHg with a mean pulmonary vascular resistance of 521 ± 264 dyn·s·cm(-5) (range 279-1331 dyn·s·cm(-5)). Five patients (6.8%) died in-hospital. Out of hospital, 5 out of 69 patients (7.2%) died during a median follow-up of 3.7 ± 2.2 years [range 0.1-8.5 years]). The one- and five-year survival rates were 93% and 89%, respectively. During follow-up, clinical worsening occurred in 13 out of 69 patients (18.8%). The one- and five-year rates of freedom from clinical worsening were 94% and 72%, respectively. The baseline NT-pro BNP level tended to be a predictor for occurrence of clinical worsening. Pulmonary endarterectomy is associated with good long-term survival in patients with CTEPH. However, clinical worsening occurred in a substantial number of patients at long-term follow-up.

  6. Effects of leukotriene receptor antagonist on chronic obstractive pulmonary disease induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    卜小宁; 王辰; 庞宝森

    2003-01-01

    Objectives To assess the hemodynamic, oxygen-dynamic and ventilative effects of Zafirlukast in chronic obstructive pulmonary disease (COPD) induced chronic cor pulmonale at acute exacerbation stage and the mechanisms of Zafirlukast efficacy.Methods Eleven cases of chronic cor pulmonale at acute exacerbation were examinted using Swan-Ganz catheter and peripheral intra-artery catheter. The hemodynamic, oxygen-dynamic parameters and respiratory rate, plasma endothelium-1 (ET-1) level, and urea leukotriene E4 (LTE4) level were measured before and at the 1st, 3rd, 5th, 7th, 9th, 12th hour after taking 40 mg Zafirlukast orally. Artarial and mixed venous blood gas analyses were done correspondingly.Results The average pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRI) were lowered at the 3rd hour after taking Zafirlukast by 23% and 36.5%, respectively. They returned to the baseline around 12th hour. Respiratory rate decreased significantly within the 3rd-7th hour after taking Zafirlukast. LTE4 and ET-1 levels lowered at the 3rd hour and showed a positive correlation with change of mPAP. Conclusions Zafirlukast can reduce mPAP, pulmonary vascular resistance (PVR) and does not affect the ambulatory blood pressure monitoring (ABPM) and oxygenation in cases of chronic cor pulmonale at acute exacerbation stage. Zafirlukast may play a role as an alternative to decrease PAP in COPD patients.

  7. Decreased time constant of the pulmonary circulation in chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    MacKenzie Ross, Robert V; Toshner, Mark R; Soon, Elaine; Naeije, Robert; Pepke-Zaba, Joanna

    2013-07-15

    This study analyzed the relationship between pulmonary vascular resistance (PVR) and pulmonary arterial compliance (Ca) in patients with idiopathic pulmonary arterial hypertension (IPAH) and proximal chronic thromboembolic pulmonary hypertension (CTEPH). It has recently been shown that the time constant of the pulmonary circulation (RC time constant), or PVR × Ca, remains unaltered in various forms and severities of pulmonary hypertension, with the exception of left heart failure. We reasoned that increased wave reflection in proximal CTEPH would be another cause of the decreased RC time constant. We conducted a retrospective analysis of invasive pulmonary hemodynamic measurements in IPAH (n = 78), proximal CTEPH (n = 91) before (pre) and after (post) pulmonary endarterectomy (PEA), and distal CTEPH (n = 53). Proximal CTEPH was defined by a postoperative mean pulmonary artery pressure (PAP) of ≤25 mmHg. Outcome measures were the RC time constant, PVR, Ca, and relationship between systolic and mean PAPs. The RC time constant for pre-PEA CTEPH was 0.49 ± 0.11 s compared with post-PEA-CTEPH (0.37 ± 0.11 s, P time constant was associated with a disproportionate decrease in systolic PAP with respect to mean PAP. We concluded that the pulmonary RC time constant is decreased in proximal CTEPH compared with IPAH, pre- and post-PEA, which may be explained by increased wave reflection but also, importantly, by persistent structural changes after the removal of proximal obstructions. A reduced RC time constant in CTEPH is in accord with a wider pulse pressure and hence greater right ventricular work for a given mean PAP.

  8. Teaching the effects of gravity and intravascular and alveolar pressures on the distribution of pulmonary blood flow using a classic paper by West et al.

    Science.gov (United States)

    Levitzky, Michael G

    2006-03-01

    "Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures" by J. B. West, C. T. Dollery, and A. Naimark (J Appl Physiol 19: 713-724, 1964) is a classic paper, although it has not yet been included in the Essays on the American Physiological Society Classic Papers Project (http://www.the-aps.org/publications/classics/). This is the paper that originally described the "zones of the lung." The final figure in the paper, which synthesizes the results and discussion, is now seen in most textbooks of physiology or respiratory physiology. The paper is also a model of clear, concise writing. The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow.

  9. Management of Sepsis in Patients with Pulmonary Arterial Hypertension in the Intensive Care Unit.

    Science.gov (United States)

    Tartavoulle, Todd M

    2017-03-01

    Pulmonary arterial hypertension is a lethal condition, and the management of sepsis in patients with pulmonary arterial hypertension is challenging. As the disease progresses, the right ventricle is susceptible to failure due to a high pulmonary vascular resistance. The limited ability of the right ventricle to increase cardiac output in septic shock makes it difficult to deliver oxygen to the organ and tissues. Intravascular volume replacement and vasoactive drugs should only be considered after a thorough assessment. Priorities of care include improving cardiac output and oxygen delivery by optimizing preload, reducing afterload, and improving contractility.

  10. Pulmonary manifestations of heartworm disease.

    Science.gov (United States)

    Calvert, C A; Rawlings, C A

    1985-09-01

    The clinical signs associated with heartworm disease are the result of changes in the pulmonary arterial system. These clinical signs are the result of either pulmonary hypertension or lung parenchymal disease associated with vascular changes. An increase in pulmonary arterial pressure produces an increase in right ventricular afterload, which may lead to exercise intolerance, syncope, and right-sided congestive heart failure. Coughing, dyspnea, and hemoptysis are the results of pulmonary parenchymal disease.

  11. Antibiotic resistance profiles of Pseudomonas aeruginosa strains isolated from patients with acute exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Nagihan Demir

    2014-12-01

    For typing and antibiotic susceptibility of isolates the Phoenix bacterial identification system (Becton Dickinson, USA was used.[¤]RESULTS[|]The antibiotic resistance rates of P. aeruginosa were 42.3% for cefepime, 41% for levofloxacin, 38.7% for ciprofloxacin, 29.4% for ceftazidime, 21.7% for cefoperazone / sulbactam, 17.9% for gentamicin, 17.9% for piperacillin / tazobactam, 8.9% for imipenem, 5.1% for amikacin and 2.5% for meropenem. Twenty eight (35.9% of the isolates were found to be sensitive to all of these antibiotics. Forty six (58.9% of the patients had steroid and 56 (71.8% of the patients had broad-spectrum antibiotic use.[¤]CONCLUSION[|]In acute exacerbations of chronic obstructive pulmonary disease, the inspection of antibiotic susceptibility of Pseudomonas infection would be beneficial for patient's health and the country's economy.[¤

  12. PP097. Cardiac output and systemic vascular resistance in normal pregnancy and in control non-pregnant women.

    Science.gov (United States)

    Khalil, A; Goodyear, Gemma; Joseph, Ehizele; Khalil, Asma

    2012-07-01

    Changes in cardiac output (CO) and systemic vascular resistance (SVR) have been shown to precede the clinical onset of pregnancy complications, such as pre-eclampsia and fetal growth restriction. CO and SVR undergo major changes during normal pregnancy. However, assessment of these vascular parameters requires intensive training and expensive techniques, so currently can be performed only in specialised centres. The aim of this study was to investigate maternal cardiovascular function measured using an ultrasonic cardiac output monitor (USCOM), a simple non-invasive continuous wave Doppler device, in a cohort of pregnant women and non-pregnant controls. This was a cross sectional study including 185 women with normal singleton pregnancies at 11-40weeks of gestation and 49 non-pregnant controls. Stroke volume (SV), CO and SVR were measured using the USCOM device. All measurements were performed with the patients in supine position. All women with a gestational age of >20weeks were in a left lateral position by placing a wedge-shaped pillow under their right side to prevent vena cava compression. In a group of 25 pregnant women, each measurement was repeated three times to evaluate the reproducibility of this technique. Cardiac index (CI), SV index (SVI) and SVR index (SVRI) relate CO, SV and SVR to the body surface area. The data were normally distributed after logarithmic transformation. Comparisons between pregnant and non-pregnant women were performed using Studentt-test, Chi-Square test or multiple regression analysis, when adjustment for potential confounders was necessary. Data analysis was performed using SPSS 16.0. In the first trimester, all of the following vascular parameters were higher in pregnant women compared to non-pregnant controls: CO [median (IQR): 4.86 (4.45-5.57) vs 5.57 (4.76-6.52)L/min, PPregnant women had significantly lower SVR [median (IQR): 1458 (1261-1649) vs 1165 (1023-1406)sec/cm(-5), P<0.001] and SVRI [median (IQR): 2646 (2307

  13. HIF-1α和VEGF在大鼠COPD中的表达及与肺血管重构的关系研究%Correlation between the expression of HIF-1α,VEGF and the pulmonary vascular remodeling in rats with COPD

    Institute of Scientific and Technical Information of China (English)

    吕倩; 王昌明; 蒋明; 梁荣感; 李运千

    2012-01-01

    ): 200 μg LPS was installed intratracheally once at Dayl and Dayl4 in all rats. Then these rats were exposed to cigarette smoke lh/d for 4 weeks. Airway resistance and pulmonary hemodynamic changes were studied. HE staining and VG + Victoria blue triple staining were used to observe the pathological changes of lung tissue and the index of pulmonary vascular remodeling. The positive expression of HIF-1α, VEGF in lung tissue was examined by RT-PCR and Western blot. Results ①Compared to group A, the airway resistance, mean pulmonary arterial pressure(mPAP) in group C were significantly increased (P < 0.05). ②The results of VG + Victoria blue triple staining was that WT% , WA% value in group C was higher than that in group A. ③ RT-PCR and Western blot showed that, compared with group A, the expression of HIF-la mRNA and protein in group C was higher, the expression of VEGF mRNA in group B&C was significantly increased and the expression of VEGF protein in group C was higher. The expression of HIF-1 α, VEGF was positively correlated to the index of pulmonary vascular remodeling (P < 0. 05). Conclusions HIF-1α & VEGF are closely related to the pathogen-esis of COPD, which aggravates COPD illness by promoting pulmonary vascular remodeling. Improving oxygen and antagonising the expression of HIF-1α, VEGF, especially in the early stage of VEGF, can reduce the pulmonary vascular remodeling of COPD and slow down the process to pulmonary arterial hypertension.

  14. Relationship between Pulmonary Airflow and Resistance in Patients with Airway Narrowing Using An 1-D Network Resistance and Compliance Model

    Science.gov (United States)

    Choi, Sanghun; Choi, Jiwoong; Hoffman, Eric; Lin, Ching-Long

    2016-11-01

    To predict the proper relationship between airway resistance and regional airflow, we proposed a novel 1-D network model for airway resistance and acinar compliance. First, we extracted 1-D skeletons at inspiration images, and generated 1-D trees of CT unresolved airways with a volume filling method. We used Horsfield order with random heterogeneity to create diameters of the generated 1-D trees. We employed a resistance model that accounts for kinetic energy and viscous dissipation (Model A). The resistance model is further coupled with a regional compliance model estimated from two static images (Model B). For validation, we applied both models to a healthy subject. The results showed that Model A failed to provide airflows consistent with air volume change, whereas Model B provided airflows consistent with air volume change. Since airflows shall be regionally consistent with air volume change in patients with normal airways, Model B was validated. Then, we applied Model B to severe asthmatic subjects. The results showed that regional airflows were significantly deviated from air volume change due to airway narrowing. This implies that airway resistance plays a major role in determining regional airflows of patients with airway narrowing. Support for this study was provided, in part, by NIH Grants U01 HL114494, R01 HL094315, R01 HL112986, and S10 RR022421.

  15. D-BMAP18 Antimicrobial Peptide Is Active In vitro, Resists to Pulmonary Proteases but Loses Its Activity in a Murine Model of Pseudomonas aeruginosa Lung Infection

    Science.gov (United States)

    Mardirossian, Mario; Pompilio, Arianna; Degasperi, Margherita; Runti, Giulia; Pacor, Sabrina; Di Bonaventura, Giovanni; Scocchi, Marco

    2017-01-01

    The spread of antibiotic resistant-pathogens is driving the search for new antimicrobial compounds. Pulmonary infections experienced by cystic fibrosis (CF) patients are a dramatic example of this health-care emergency. Antimicrobial peptides could answer the need for new antibiotics but translating them from basic research to the clinic is a challenge. We have previously evaluated the potential of the small membranolytic peptide BMAP-18 to treat CF-related infections, discovering that while this molecule had a good activity in vitro it was not active in vivo because of its rapid degradation by pulmonary proteases. In this study, we synthesized and tested the proteases-resistant all-D enantiomer. In spite of a good antimicrobial activity against Pseudomonas aeruginosa and Stenotrophomonas maltophilia clinical isolates and of a tolerable cytotoxicity in vitro, D-BMAP18 was ineffective to treat P. aeruginosa pulmonary infection in mice, in comparison to tobramycin. We observed that different factors other than peptide degradation hampered its efficacy for pulmonary application. These results indicate that D-BMAP18 needs further optimization before being suitable for clinical application and this approach may represent a guide for optimization of other anti-infective peptides eligible for the treatment of pulmonary infections. PMID:28674688

  16. D-BMAP18 Antimicrobial Peptide Is Active In vitro, Resists to Pulmonary Proteases but Loses Its Activity in a Murine Model of Pseudomonas aeruginosa Lung Infection

    Directory of Open Access Journals (Sweden)

    Mario Mardirossian

    2017-06-01

    Full Text Available The spread of antibiotic resistant-pathogens is driving the search for new antimicrobial compounds. Pulmonary infections experienced by cystic fibrosis (CF patients are a dramatic example of this health-care emergency. Antimicrobial peptides could answer the need for new antibiotics but translating them from basic research to the clinic is a challenge. We have previously evaluated the potential of the small membranolytic peptide BMAP-18 to treat CF-related infections, discovering that while this molecule had a good activity in vitro it was not active in vivo because of its rapid degradation by pulmonary proteases. In this study, we synthesized and tested the proteases-resistant all-D enantiomer. In spite of a good antimicrobial activity against Pseudomonas aeruginosa and Stenotrophomonas maltophilia clinical isolates and of a tolerable cytotoxicity in vitro, D-BMAP18 was ineffective to treat P. aeruginosa pulmonary infection in mice, in comparison to tobramycin. We observed that different factors other than peptide degradation hampered its efficacy for pulmonary application. These results indicate that D-BMAP18 needs further optimization before being suitable for clinical application and this approach may represent a guide for optimization of other anti-infective peptides eligible for the treatment of pulmonary infections.

  17. Role of Peripheral Vascular Resistance for the Association Between Major Depression and Cardiovascular Disease

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian

    2015-01-01

    Major depression and cardiovascular diseases are 2 of the most prevalent health problems in Western society, and an association between them is generally accepted. Although the specific mechanism behind this comorbidity remains to be elucidated, it is clear that it has a complex multifactorial....... The changes in arterial structure, contractile and relaxing functions associated with depression symptoms are discussed, and the role of these abnormalities for the pathology of major depression and cardiovascular diseases are suggested....... character including a number of neuronal, humoral, immune, and circulatory pathways. Depression-associated cardiovascular abnormalities associate with cardiac dysfunctions and with changes in peripheral resistance. Although cardiac dysfunction in association with depression has been studied in detail...

  18. Age does not affect uterine resistance to vascular flow in patients undergoing oocyte donation.

    Science.gov (United States)

    Guanes, P P; Remohí, J; Gallardo, E; Valbuena, D; Simón, C; Pellicer, A

    1996-08-01

    To determine whether uterine vasculature is affected by age using oocyte donation as an in vivo model. Prospective longitudinal study in which recipients were grouped according to age. They underwent a successful oocyte donation cycle, and single pregnancies were followed during the first trimester by color Doppler ultrasound in uterine arteries. Oocyte donation and IVF program at the Instituto Valenciano de Infertilidad. Serum E2, P, and hCG levels in single ovum donation pregnancies; pulsatility and resistance indexes in uterine arteries during initial pregnancy. Similar serum levels of E2, P, and hCG in both groups of patients were observed. There was no difference between groups regarding the flow indexes analyzed. The increased incidence of early pregnancy losses observed in patients > 40 years cannot be attributed to defective response of uterine vasculature to exogenous hormone replacement. Thus, uterine aging does not appear to be a factor influencing the poor reproductive performance of women with advancing age.

  19. Progression of chronic pulmonary tuberculosis in mice intravenously infected with ethambutol resistant Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Srivastava S

    2008-01-01

    Full Text Available Purpose: Ethambutol (EMB is an important first line drug, however little information on its molecular mechanism of resistance and pathogenicity of resistant isolates is available. Present work was designed to study virulence of the EMB resistant M. tuberculosis strains and the host responses in-vivo on infection of EMB resistant M. tuberculosis using Balb/c mouse model of infection. Methods: Three groups of Balb/c mice (female, age 4-6 wk; 21 mice in each group were infected intravenously with 106 CFU of M. tuberculosis H37Rv and two EMB resistant clinical isolates. Age and sex matched control animals were mock inoculated with Middlebrook 7H9 broth alone. At 10, 20, 30, 40, 50, 60, and 70 days post-infection three animals from each group were sacrificed by cervical dislocation and lung tissue was collected for further analysis. Results: Infection with EMB resistant M. tuberculosis led to progressive and chronic disease with significantly high bacillary load (p=0.02. Massive infiltration and exacerbated lung pathology with increased expression of IFN-γ and TNF-α was observed in lungs of mice infected with EMB resistant strains. The present study suggests that infection with EMB resistant M. tuberculosis leads to chronic infection with subsequent loss of lung function, bacterial persistence with elevated expression of TNF-α resulting in increased lung pathology. Conclusion: These findings highlight that EMB resistant M. tuberculosis regulates host immune response differentially and its pathogenicity is different from drug sensitive strains of M. tuberculosis.

  20. Pulmonary arterial hypertension associated with bronchopulmonary dysplasia and congenital heart disease in preterm infants. A case report of a preterm infant with recurrent pulmonary hypertension after corrective cardiac surgery and review of the literature.

    Science.gov (United States)

    Muneuchi, Jun; Kuraoka, Ayako; Watanabe, Mamie; Ochiai, Yoshie; Joo, Kunitaka

    2015-01-01

    In preterm infants with congenital heart disease, concomitant bronchopulmonary dysplasia (BPD) is associated with relatively poor clinical outcomes because of the increased pulmonary vascular resistance and adverse effects of inflammation on the damaged lungs, even after surgery. We present herein a 1-year-old female who developed recurrent pulmonary arterial hypertension 6 months after closure of a ventricular septal defect. She was born at 26 weeks of gestation (birth weight, 470 g), and developed BPD requiring oxygen supplementation. Her systemic-to-pulmonary blood flow ratio was 2.1 preoperatively and 1.0 postoperatively, pulmonary arterial pressure was 61/15 (mean 39) mmHg preoperatively and 41/17 (mean 24) mmHg postoperatively, and pulmonary vascular resistance was 4.2 mmHg/L·minute·m(2) preoperatively and 3.6 mmHg/L·minute·m(2) postoperatively. At 1 year of age, echocardiography showed an increase in her estimated right ventricular pressure, indicating worsening pulmonary hypertension. After 3 years of treatment with oxygen supplementation, prostacyclin, and bosentan, her pulmonary arterial pressure improved to the normal range. The pathophysiology of pulmonary arterial hypertension is heterogeneous in preterm infants with congenital heart disease and concomitant BPD. Careful management of these patients is warranted even after corrective cardiac surgery.

  1. Polyvinylpyrrolidone-Capped Silver Nanoparticle Inhibits Infection of Carbapenem-Resistant Strain of Acinetobacter baumannii in the Human Pulmonary Epithelial Cell

    Directory of Open Access Journals (Sweden)

    Vishvanath Tiwari

    2017-08-01

    Full Text Available Acinetobacter baumannii, an opportunistic ESKAPE pathogen, causes respiratory and urinary tract infections. Its prevalence increases gradually in the clinical setup. Pathogenicity of Acinetobacter is significantly influenced by its ability to infect and survive in human pulmonary cells. Therefore, it is important to study the infection of A. baumannii in human pulmonary host cell (A-549, monitoring surface interacting and internalized bacteria. It was found that during infection of A. baumannii, about 40% bacteria adhered to A-549, whereas 20% got internalized inside pulmonary cell and induces threefold increase in the reactive oxygen species production. We have synthesized polyvinylpyrrolidone (PVP-capped AgNPs using chemical methods and tested its efficacy against carbapenem-resistant strain of A. baumannii. PVP-capped silver nanoparticles (PVP-AgNPs (30 µM have shown antibacterial activity against carbapenem-resistant strain of A. baumannii and this concentration does not have any cytotoxic effect on the human pulmonary cell line (IC50 is 130 µM. Similarly, PVP-AgNPs treatment decreases 80% viability of intracellular bacteria, decreases adherence of A. baumannii to A-549 (40 to 2.2%, and decreases intracellular concentration (20 to 1.3% of A. baumannii. This concludes that PVP-AgNPs can be developed as a substitute for carbapenem to control the infection caused by carbapenem-resistant A. baumannii.

  2. Suction/inspiration against resistance or standardized Mueller maneuver: a new breathing technique to improve contrast density within the pulmonary artery: a pilot CT study

    Energy Technology Data Exchange (ETDEWEB)

    Gutzeit, Andreas [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Hospital St. Anna, Institute of Radiology and Nuclear Medicine, Clinical Research Unit, Lucerne (Switzerland); Kantonsspital Winterthur, Department of Radiology, Winterthur (Switzerland); Froehlich, Johannes M.; Weymarn, Constantin von; Goyen, Matthias [Hirslanden Hospital St. Anna, Institute of Radiology and Nuclear Medicine, Clinical Research Unit, Lucerne (Switzerland); Waelti, Stephan [Cantonal Hospital St. Gallen, Department of Radiology and Nuclear Medicine, St. Gallen (Switzerland); Roos, Justus E. [Duke University Medical Center, Department of Radiology, Durham, NC (United States); Meissnitzer, Matthias; Hergan, Klaus [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Czell, David [Cantonal Hospital Winterthur, Department of Neurology, Winterthur (Switzerland); Reischauer, Carolin [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Hospital St. Anna, Institute of Radiology and Nuclear Medicine, Clinical Research Unit, Lucerne (Switzerland)

    2015-11-15

    Our aim was to prospectively investigate whether the recently introduced suction/inspiration against resistance breathing method leads to higher computed tomography (CT) contrast density in the pulmonary artery compared to standard breathing. The present study was approved by the Medical Ethics committee and all subjects gave written informed consent. Fifteen patients, each without suspicious lung emboli, were randomly assigned to four different groups with different breathing maneuvers (suction against resistance, Valsalva, inspiration, expiration) during routine CT. Contrast enhancement in the central and peripheral sections of the pulmonary artery were measured and compared with one another. Peripheral enhancement during suction yielded increased mean densities of 138.14 Hounsfield units (HU) (p = 0.001), compared to Valsalva and a mean density of 67.97 HU superior to inspiration (p = 0.075). Finally, suction in comparison to expiration resulted in a mean increase of 30.51 HU (p = 0.42). Central parts of pulmonary arteries presented significantly increased enhancement values (95.74 HU) for suction versus the Valsalva technique (p = 0.020), while all other mean densities were in favour of suction (versus inspiration: p = 0.201; versus expiration: p = 0.790) without reaching significance. Suction/Inspiration against resistance is a promising technique to improve contrast density within pulmonary vessels, especially in the peripheral parts, in comparison to other breathing maneuvers. (orig.)

  3. Antimicrobial resistance and composition of algogen pathogeny in pulmonary infection%肺部感染病原体的构成谱及耐药现状

    Institute of Scientific and Technical Information of China (English)

    程知音; 吴斌

    2011-01-01

    肺部感染发病率、病死率高,其病原体多种多样,细菌是最常见的致病原.近年来,由于抗生素的广泛滥用,导致肺部感染的常见致病原发生了变化,细菌的耐药率在不断攀升,新的耐药菌株不断出现,多药耐药菌较为常见,全球细菌耐药形势十分严峻.为防治耐药菌感染,应积极采取科学、有效的措施.%The morbidity and mortality rate of pulmonary infection is high.There is a variety of pathogens in pulmonary infection,in which bacterium is the most common one.In recent years,with the widespread abuse of antibiotics,the common pathogens resulting in pulmonary infection have changed,bacterial resistance rate is continuing to rise,the new resistant strains are emerging continuously and multidrug-resistance bacteria are common.Antimicrobial resistance of bacteria is a serious problem worldwide.Scientific and effective measures should be actively taken to combat antibiotic-resistant bacteria infection.

  4. Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer.

    Science.gov (United States)

    Wagner, Anna Dorothea; Thomssen, Christoph; Haerting, Johannes; Unverzagt, Susanne

    2012-07-11

    Vascular-endothelial-growth-factor (VEGF) is a key mediator of angiogenesis. VEGF-targeting therapies have shown significant benefits and been successfully integrated in routine clinical practice for other types of cancer, such as metastatic colorectal cancer. By contrast, individual trial results in metastatic breast cancer (MBC) are highly variable and their value is controversial. To evaluate the benefits (in progression-free survival (PFS) and overall survival (OS)) and harms (toxicity) of VEGF-targeting therapies in patients with hormone-refractory or hormone-receptor negative metastatic breast cancer. Searches of CENTRAL, MEDLINE, EMBASE, the Cochrane Breast Cancer Group's Specialised Register, registers of ongoing trials and proceedings of conferences were conducted in January and September 2011, starting in 2000. Reference lists were scanned and members of the Cochrane Breast Cancer Group, experts and manufacturers of relevant drug were contacted to obtain further information. No language restrictions were applied. Randomised controlled trials (RCTs) to evaluate treatment benefit and non-randomised studies in the routine oncology practice setting to evaluate treatment harms. We performed data collection and analysis according to the published protocol. Individual patient data was sought but not provided. Therefore, the meta-analysis had to be based on published data. Summary statistics for the primary endpoint (PFS) were hazard ratios (HRs). We identified seven RCTs, one register, and five ongoing trials from a total of 347 references. The published trials for VEGF-targeting drugs in MBC were limited to bevacizumab. Four trials, including a total of 2886 patients, were available for the comparison of first-line chemotherapy, with versus without bevacizumab. PFS (HR 0.67; 95% confidence interval (CI) 0.61 to 0.73) and response rate were significantly better for patients treated with bevacizumab, with moderate heterogeneity regarding the magnitude of the

  5. Mechanisms of adreno- and cholinoreceptors in isolated pulmonary and systemic vasculature of the cane toad (Rhinella marina)

    DEFF Research Database (Denmark)

    Pedersen, Pil Birkefeldt Møller; Wang, Tobias; Brøndum, Emil Toft

    site of regulation of resistance and therefore holds the capacity to control blood flow and pressure. This vascular control allows amphibians to regulate their shunt, i.e. partially bypassing either the pulmonary or systemic circuit. Shunting in amphibians has been studied due to their multiple...

  6. Gap junction protein connexin43 exacerbates lung vascular permeability.

    Directory of Open Access Journals (Sweden)

    James J O'Donnell

    Full Text Available Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins. Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43. Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.

  7. Diagnosis and management of cardiogenic pulmonary edema.

    Science.gov (United States)

    Alwi, Idrus

    2010-07-01

    Acute cardiogenic pulmonary edema (ACPE) is a common cardiogenic emergency with a quite high in-hospital mortality rate. ACPE is defined as pulmonary edema with increased secondary hydrostatic capillary pressure due to elevated pulmonary venous pressure. Increased hydrostatic pressure may result from various causes including excessive administration of intravascular volume, obstruction of pulmonary venous outflow or secondary left ventricular failure due to left ventricular systolic or diastolic dysfunction. ACPE must be distinguished from pulmonary edema associated with injury of alveolar capillary membrane caused by various etiologies, i.e. direct pulmonary injury such as pneumonia and indirect pulmonary injury such as sepsis. Numerous clinical manifestations may differentiate ACPE and Non-ACPE. ACPE usually presents with a history of acute cardiac catastrophe. Physical examination reveals a low-flow state, S3 gallop, jugular venous distention and fine crepitant rales with auscultation. The diagnosis of pulmonary edema is made based on symptoms and clinical signs are found through history taking, physical examination, ECG, chest X-ray, echocardiography and laboratory tests including blood gas analysis and specific biomarkers. Medical treatment of ACPE has 3 main objectives, i.e.: (1) reduced venous return (preload reduction); (2) reduced resistance of systemic vascular (afterload reduction); and (3) inotropic support in some cases. Treatment that can be administered includes: vasodilator when there is normal or high BP, diuretics when there is volume overload or fluid retention, and inotropic drugs when there is hypotension or signs of organ hypoperfusion. Intubation and mechanical ventilation may be necessary to achieve adequate oxygenation.

  8. Comparison of acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide in adult congenital heart disease with severe pulmonary arterial hypertension.

    Science.gov (United States)

    Caojin, Zhang; Yigao, Huang; Tao, Huang; Wenhui, Huang; Chunli, Xia; Xinsheng, Huang

    2012-01-01

    To compare the acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide (NO) in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH). One hundred and eighty five adult CHDs with severe PAH were nonrandomized into two groups (iloprost, n=127; NO, n=58). Various hemodynamic parameters were measured before and after iloprost or NO inhalation. Iloprost and NO inhalation resulted in significant reductions in pulmonary arterial pressure (from 110.6±21.8 mmHg to 105.5±22.3 mmHg, piloprost and NO were compared, similar reductions in pulmonary arterial pressure and pulmonary vascular resistance were observed. Aerosolized iloprost and inhaled nitric oxide (iNO) were generally well tolerated and no patient experienced any side effects during inhalation. Aerosolized iloprost can be effectively and safely used and might be an alternative to NO for testing pulmonary vascular reactivity and treating severe PAH in adult CHD patients.

  9. Endothelial HIF signaling regulates pulmonary fibrosis-associated pulmonary hypertension.

    Science.gov (United States)

    Bryant, Andrew J; Carrick, Ryan P; McConaha, Melinda E; Jones, Brittany R; Shay, Sheila D; Moore, Christy S; Blackwell, Thomas R; Gladson, Santhi; Penner, Niki L; Burman, Ankita; Tanjore, Harikrishna; Hemnes, Anna R; Karwandyar, Ayub K; Polosukhin, Vasiliy V; Talati, Megha A; Dong, Hui-Jia; Gleaves, Linda A; Carrier, Erica J; Gaskill, Christa; Scott, Edward W; Majka, Susan M; Fessel, Joshua P; Haase, Volker H; West, James D; Blackwell, Timothy S; Lawson, William E

    2016-02-01

    Pulmonary hypertension (PH) complicating chronic parenchymal lung disease, such as idiopathic pulmonary fibrosis, results in significant morbidity and mortality. Since the hypoxia-inducible factor (HIF) signaling pathway is important for development of pulmonary hypertension in chronic hypoxia, we investigated whether HIF signaling in vascular endothelium regulates development of PH related to pulmonary fibrosis. We generated a transgenic model in which HIF is deleted within vascular endothelial cells and then exposed these mice to chronic intraperitoneal bleomycin to induce PH associated with lung fibrosis. Although no differences in the degree of fibrotic remodeling were observed, we found that endothelial HIF-deficient mice were protected against development of PH, including right ventricle and pulmonary vessel remodeling. Similarly, endothelial HIF-deficient mice were protected from PH after a 4-wk exposure to normobaric hypoxia. In vitro studies of pulmonary vascular endothelial cells isolated from the HIF-targeted mice and controls revealed that endothelial HIF signaling increases endothelial cell expression of connective tissue growth factor, enhances vascular permeability, and promotes pulmonary artery smooth muscle cell proliferation and wound healing ability, all of which have the potential to impact the development of PH in vivo. Taken together, these studies demonstrate that vascular endothelial cell HIF signaling is necessary for development of hypoxia and pulmonary fibrosis associated PH. As such, HIF and HIF-regulated targets represent a therapeutic target in these conditions.

  10. Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent

    Directory of Open Access Journals (Sweden)

    Brian Casserly

    2009-11-01

    Full Text Available Brian Casserly, James R KlingerDivision of Pulmonary and Critical Care Medicine, The Memorial Hospital of Rhode Island, Pawtucket, RI, Rhode Island Hospital, Providence, RI, Alpert Medical School of Brown University, Providence, RI, USAAbstract: B-type natriuretic peptide (BNP is a member of the natriuretic peptide family, a group of widely distributed, but evolutionarily conserved, polypeptide mediators that exert myriad cardiovascular effects. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. Circulating levels of BNP correlate with mean pulmonary arterial pressure (mPAP and pulmonary vascular resistance (PVR in patients with pulmonary arterial hypertension (PAH. Elevated plasma BNP levels are associated with increased mortality in patients with PAH and a fall in BNP levels after therapy is associated with improved survival. These findings have important clinical implications in that a noninvasive blood test may be used to identify PAH patients at high-risk of decompensation and to guide pulmonary vasodilator therapy. BNP also has several biologic effects that could be beneficial to patients with PAH. However, lack of a convenient method for achieving sustained increases in circulating BNP levels has impeded the development of BNP as a therapy for treating pulmonary hypertension. New technologies that allow transdermal or oral administration of the natriuretic peptides have the potential to greatly accelerate research into therapeutic use of BNP for cor pulmonale and pulmonary vascular diseases. This review will examine the basic science and clinical research that has led to our understanding of the role of BNP in cardiovascular physiology, its use as a biomarker of right ventricular function and its therapeutic potential for managing patients with pulmonary vascular disease.Keywords: brain natriuretic peptide, pulmonary artery hypertension

  11. Low-dose ouabain constricts small arteries from ouabain-hypertensive rats: implications for sustained elevation of vascular resistance

    Science.gov (United States)

    Zhang, Jin; Hamlyn, John M.; Karashima, Eiji; Raina, Hema; Mauban, Joseph R. H.; Izuka, Michelle; Berra-Romani, Roberto; Zulian, Alessandra; Wier, W. Gil; Blaustein, Mordecai P.

    2009-01-01

    Prolonged ouabain administration to normal rats causes sustained blood pressure (BP) elevation. This ouabain-induced hypertension (OH) has been attributed, in part, to the narrowing of third-order resistance arteries (∼320 μm internal diameter) as a result of collagen deposition in the artery media (see Ref. 6). Here we describe the structural and functional properties of fourth-order mesenteric small arteries from control and OH rats, including the effect of low-dose ouabain on myogenic tone in these arteries. Systolic BP in OH rats was 138 ± 3 versus 124 ± 4 mmHg in controls (P < 0.01). Pressurized (70 mmHg) control and OH arteries, with only a single layer of myocytes, both had ∼165-μm internal diameters and ∼20-μm wall thicknesses. Even after fixation, despite vasoconstriction, the diameters and wall thicknesses did not differ between control and OH fourth-order arteries, whereas in third-order arteries, both parameters were significantly smaller in OH than in controls. Myogenic reactivity was significantly augmented in OH fourth-order arteries. Nevertheless, phenylephrine- (1 μM) and high K+-induced vasoconstrictions and acetylcholine-induced vasodilation were comparable in control and OH arteries. Vasoconstrictions induced by 5 μM phenylephrine and by 10 mM caffeine in Ca2+-free media indicated that releasable sarcoplasmic reticulum Ca2+ stores were normal in OH arteries. Importantly, 100 nM ouabain constricted both control and OH arteries by ∼26 μm, indicating that this response was not downregulated in OH rats. This maximal ouabain-induced constriction corresponds to a ∼90% increase in resistance to flow in these small arteries; thus ouabain at EC50 of ∼0.66 nM should raise resistance by ∼35%. We conclude that dynamic constriction in response to circulating nanomolar ouabain in small arteries likely makes a major contribution to the increased vascular tone and BP in OH rats. PMID:19617413

  12. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide.

    Science.gov (United States)

    Vardavas, Constantine I; Anagnostopoulos, Nektarios; Kougias, Marios; Evangelopoulou, Vassiliki; Connolly, Gregory N; Behrakis, Panagiotis K

    2012-06-01

    Debate exists over the scientific evidence for claims that electronic cigarettes (e-cigarettes) have no health-related ramifications. This study aimed to assess whether using an e-cigarette for 5 min has an impact on the pulmonary function tests and fraction of exhaled nitric oxide (Feno) of healthy adult smokers. Thirty healthy smokers (aged 19-56 years, 14 men) participated in this laboratory-based experimental vs control group study. Ab lib use of an e-cigarette for 5 min with the cartridge included (experimental group, n = 30) or removed from the device (control group, n = 10) was assessed. Using an e-cigarette for 5 min led to an immediate decrease in Feno within the experimental group by 2.14 ppb (P = .005) but not in the control group (P = .859). Total respiratory impedance at 5 Hz in the experimental group was found to also increase by 0.033 kPa/(L/s) (P respiratory resistance at 5 Hz, 10 Hz, and 20 Hz also statistically increased. Regression analyses controlling for baseline measurements indicated a statistically significant decrease in Feno and an increase in impedance by 0.04 kPa/(L/s) (P = .003), respiratory resistance at 5 Hz by 0.04 kPa/(L/s) (P = .003), at 10 Hz by 0.034 kPa/(L/s) (P = .008), at 20 Hz by 0.043 kPa/(L/s) (P = .007), and overall peripheral airway resistance (β, 0.042 kPa/[L/s]; P = .024), after using an e-cigarette. e-Cigarettes assessed in the context of this study were found to have immediate adverse physiologic effects after short-term use that are similar to some of the effects seen with tobacco smoking; however, the long-term health effects of e-cigarette use are unknown but potentially adverse and worthy of further investigation.

  13. Vascular Cures

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  14. [The right ventricle and pulmonary circulation in hypertensive patients].

    Science.gov (United States)

    Guazzi, M D; Riva, S; Guazzi, M; Dardani, M; Berti, M; Tosi, E; Alimento, M

    1990-04-01

    Elevated blood pressure and vascular resistance in patients with systemic hypertension are paralleled by a proportional rise in pressure and resistance in the lesser circulation. It was hypothesized that increased systemic reaction to adrenergic stimulation is shared by the pulmonary vessels. Thus normotensive subjects and patients with primary hypertension were investigated during mental arithmetic and the cold pressor test. Both groups responded to both stimuli; during arithmetic pressure reaction was mediated through an increase of cardiac output, and during the cold pressor test through a predominant rise in systemic vascular resistance. The pressure changes were emphasized in the hypertensive population. Pressure in the pulmonary artery in normotensive subjects was not affected by cold and was slightly raised (systolic) during arithmetic. In hypertensive patients, on the other hand, systolic and diastolic pressures were consistently augmented by both tests, and pulmonary arteriolar resistance rose by 42% and 29% of control during the cold pressor test and arithmetic, respectively. Changes in resistance reflected neurally-mediated vasoconstriction but not variations in the passive relationship between pressure and flow, since during arithmetic, for a similar rise in flow the driving pressure across the lungs was steady in normotensive subjects and rose significantly in hypertensive patients. In these same patients pressure was augmented by cold test in the absence of substantial changes in flow. At baseline and during tests pulmonary wedge pressure, pleural pressure, arterial blood gases, and pH were similar in the two populations. The intravenous infusion of similar scalar doses of norepinephrine (the same mediator released during cold test) was not effective on the pulmonary vessels of normotensives and caused an obvious vasoconstriction in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Reversal of experimental pulmonary hypertension by PDGF inhibition

    OpenAIRE

    Schermuly, Ralph Theo; Dony, Eva; Ghofrani, Hossein Ardeschir; Pullamsetti, Soni; Savai, Rajkumar; Roth, Markus; Sydykov, Akylbek; Lai, Ying Ju; Weissmann, Norbert; Seeger, Werner; Grimminger, Friedrich

    2005-01-01

    Progression of pulmonary hypertension is associated with increased proliferation and migration of pulmonary vascular smooth muscle cells. PDGF is a potent mitogen and involved in this process. We now report that the PDGF receptor antagonist STI571 (imatinib) reversed advanced pulmonary vascular disease in 2 animal models of pulmonary hypertension. In rats with monocrotaline-induced pulmonary hypertension, therapy with daily administration of STI571 was started 28 days after induction of the d...

  16. Can geometric indices of heart rate variability predict improvement in autonomic modulation after resistance training in chronic obstructive pulmonary disease?

    Science.gov (United States)

    Santos, Ana Alice Soares Dos; Ricci-Vitor, Ana Laura; Bragatto, Vanessa Santa Rosa; Santos, Ana Paula Soares Dos; Ramos, Ercy Mara Cipulo; Vanderlei, Luiz Carlos Marques

    2017-03-01

    Chronic obstructive pulmonary disease (COPD) is associated with autonomic dysfunctions that can be evaluated through heart rate variability (HRV). Resistance training promotes improvement in autonomic modulation; however, studies that evaluate this scenario using geometric indices, which include nonlinear evaluation, thus providing more accurate information for physiological interpretation of HRV, are unknown. This study aimed to investigate the influence of resistance training on autonomic modulation, using geometric indices of HRV, and peripheral muscle strength in individuals with COPD. Fourteen volunteers with COPD were submitted to resistance training consisting of 24 sessions lasting 60 min each, with a frequency of three times a week. The intensity was determined as 60% of one maximum repetition and was progressively increased until 80% for the upper and lower limbs. The HRV and dynamometry were performed at two moments, the beginning and the end of the experimental protocol. Significant increases were observed in the RRtri (4·81 ± 1·60 versus 6·55 ± 2·69, P = 0·033), TINN (65·36 ± 35·49 versus 101·07 ± 63·34, P = 0·028), SD1 (7·48 ± 3·17 versus 11·04 ± 6·45, P = 0·038) and SD2 (22·30 ± 8·56 versus 32·92 ± 18·78, P = 0·022) indices after the resistance training. Visual analysis of the Poincare plot demonstrated greater dispersion beat-to-beat and in the long-term interval between consecutive heart beats. Regarding muscle strength, there was a significant increase in the shoulder abduction and knee flexion. In conclusion, geometric indices of HRV can predict improvement in autonomic modulation after resistance training in individuals with COPD; improvement in peripheral muscle strength in patients with COPD was also observed. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  17. Long-term treatment of pulmonary hypertension with aerosolized iloprost.

    Science.gov (United States)

    Machherndl, S; Kneussl, M; Baumgartner, H; Schneider, B; Petkov, V; Schenk, P; Lang, I M

    2001-01-01

    Pulmonary arterial hypertension (PAH), defined as elevated pulmonary arterial pressure and pulmonary vascular resistance, is an end-point of a variety of conditions. The only therapy that has been shown to improve both quality of life and survival is intravenous prostacyclin (prostaglandin I2 (PGI2), epoprostenol). The effect of long-term aerosolized iloprost (Ilomedin, Schering, Berlin, Germany and Vienna, Austria), a stable prostacyclin analogue and potent vasodilator, on haemodynamics and functional status was investigated in 12 patients with severe pulmonary hypertension. Haemodynamic measurements and vasodilator testing by right heart catheterization were performed prior to and after long-term iloprost inhalation therapy. Haemodynamic improvement or increased exercise tolerance was not observed in any of the patients. After a mean+/-SD treatment period of 10+/-5 months, mean+/-SD pulmonary vascular resistance had increased from 11+/-3 Wood Units (mmHg.L(-1).min) to 13+/-4 Wood Units, with unchanged arterial oxygen saturation (92+/-4%, versus 91+/-4%). Within the study period, three patients went into right heart failure and had to be placed on intravenous epoprostenol. The authors conclude that inhaled iloprost in addition to conventional therapy in the presently recommended dose of 100 microg.day(-1) delivered in 8-10 2 h portions, is not an efficient vasodilator therapy in severe pulmonary hypertension. It remains to be shown whether dose increases and/or combination protocols will be effective, or whether inhalation of iloprost may be safe for selected cases of pulmonary hypertension.

  18. Relationships between respiratory and airway resistances and activity-related dyspnea in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Plantier L

    2012-03-01

    Full Text Available Bruno Mahut1,2, Aurore Caumont-Prim3,4, Laurent Plantier1,5, Karine Gillet-Juvin1,6, Etienne Callens1, Olivier Sanchez5,6, Brigitte Chevalier-Bidaud3, Plamen Bokov1, Christophe Delclaux1,5,71Assistance Publique – Hôpitaux de Paris (AP-HP, Hôpital Européen Georges Pompidou, Service de Physiologie – Clinique de la Dyspnée, F-75015 Paris, France; 2Cabinet La Berma, 4 avenue de la Providence; F-92160 Antony, France; 3AP-HP, Hôpital Européen Georges Pompidou, Unité d'Épidémiologie et de Recherche Clinique, F-75015 Paris, France; 4INSERM, Centre d'Investigation Épidémiologique 4, F-75015 Paris, France; 5Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, F-75015 Paris, France; 6AP-HP, Hôpital Européen Georges Pompidou, Service de Pneumologie; F-75015 Paris, France; 7CIC 9201 Plurithématique, Hôpital Européen Georges Pompidou, F-75015 Paris, FranceBackground: The aims of the study were: (1 to compare numerical parameters of specific airway resistance (total, sRawtot, effective, sRaweff and at 0.5 L • s-1, sRaw0.5 and indices obtained from the forced oscillation technique (FOT: resistance extrapolated at 0 Hz [Rrs0 Hz], mean resistance [Rrsmean], and resistance/frequency slope [Rrsslope] and (2 to assess their relationships with dyspnea in chronic obstructive pulmonary disease (COPD.Methods: A specific statistical approach, principal component analysis that also allows graphic representation of all correlations between functional parameters was used. A total of 108 patients (mean ± SD age: 65 ± 9 years, 31 women; GOLD stages: I, 14; II, 47; III, 39 and IV, 8 underwent spirometry, body plethysmography, FOT, and Medical Research Council (MRC scale assessments.Results: Principal component analysis determined that the functional parameters were described by three independent dimensions (airway caliber, lung volumes and their combination, specific resistance and that resistance parameters of the two techniques

  19. Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism

    Science.gov (United States)

    Stubblefield, William B.; Alves, Nathan J.; Rondina, Matthew T.; Kline, Jeffrey A.

    2016-01-01

    Background We examine the clinical significance and biomarkers of tissue plasminogen activator (tPA)-catalyzed clot lysis time (CLT) in patients with intermediate-risk pulmonary embolism (PE). Methods Platelet-poor, citrated plasma was obtained from patients with PE. Healthy age- and sex-matched patients served as disease-negative controls. Fibrinogen, α2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator Inhibitor 1 (PAI-1), thrombin time and D-dimer were quantified. Clotting was induced using CaCl2, tissue factor, and phospholipid. Lysis was induced using 60 ng/mL tPA. Time to 50% clot lysis (CLT) was assessed by both thromboelastography (TEG) and turbidimetry (A405). Results Compared with disease-negative controls, patients with PE exhibited significantly longer mean CLT on TEG (+2,580 seconds, 95% CI 1,380 to 3,720 sec). Patients with PE and a short CLT who were treated with tenecteplase had increased risk of bleeding, whereas those with long CLT had significantly worse exercise tolerance and psychometric testing for quality of life at 3 months. A multivariate stepwise removal regression model selected PAI-1 and TAFI as predictive biomarkers of CLT. Conclusion The CLT from TEG predicted increased risk of bleeding and clinical failure with tenecteplase treatment for intermediate-risk PE. Plasmatic PAI-1 and TAFI were independent predictors of CLT. PMID:26866684

  20. Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism.

    Directory of Open Access Journals (Sweden)

    William B Stubblefield

    Full Text Available We examine the clinical significance and biomarkers of tissue plasminogen activator (tPA-catalyzed clot lysis time (CLT in patients with intermediate-risk pulmonary embolism (PE.Platelet-poor, citrated plasma was obtained from patients with PE. Healthy age- and sex-matched patients served as disease-negative controls. Fibrinogen, α2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI, plasminogen activator Inhibitor 1 (PAI-1, thrombin time and D-dimer were quantified. Clotting was induced using CaCl2, tissue factor, and phospholipid. Lysis was induced using 60 ng/mL tPA. Time to 50% clot lysis (CLT was assessed by both thromboelastography (TEG and turbidimetry (A405.Compared with disease-negative controls, patients with PE exhibited significantly longer mean CLT on TEG (+2,580 seconds, 95% CI 1,380 to 3,720 sec. Patients with PE and a short CLT who were treated with tenecteplase had increased risk of bleeding, whereas those with long CLT had significantly worse exercise tolerance and psychometric testing for quality of life at 3 months. A multivariate stepwise removal regression model selected PAI-1 and TAFI as predictive biomarkers of CLT.The CLT from TEG predicted increased risk of bleeding and clinical failure with tenecteplase treatment for intermediate-risk PE. Plasmatic PAI-1 and TAFI were independent predictors of CLT.

  1. Regulation of the pulmonary circulation in the fetus and newborn.

    Science.gov (United States)

    Gao, Yuansheng; Raj, J Usha

    2010-10-01

    During the development of the pulmonary vasculature in the fetus, many structural and functional changes occur to prepare the lung for the transition to air breathing. The development of the pulmonary circulation is genetically controlled by an array of mitogenic factors in a temporo-spatial order. With advancing gestation, pulmonary vessels acquire increased vasoreactivity. The fetal pulmonary vasculature is exposed to a low oxygen tension environment that promotes high intrinsic myogenic tone and high vasocontractility. At birth, a dramatic reduction in pulmonary arterial pressure and resistance occurs with an increase in oxygen tension and blood flow. The striking hemodynamic differences in the pulmonary circulation of the fetus and newborn are regulated by various factors and vasoactive agents. Among them, nitric oxide, endothelin-1, and prostaglandin I(2) are mainly derived from endothelial cells and exert their effects via cGMP, cAMP, and Rho kinase signaling pathways. Alterations in these signaling pathways may lead to vascular remodeling, high vasocontractility, and persistent pulmonary hypertension of the newborn.

  2. Prevalence of Pre-Extensively Drug-Resistant Tuberculosis (Pre XDR-TB and Extensively Drug-Resistant Tuberculosis (XDR-TB among Pulmonary Multidrug Resistant Tuberculosis (MDR-TB at a Tertiary Care Center in Mumbai

    Directory of Open Access Journals (Sweden)

    Unnati D. Desai

    2016-07-01

    Full Text Available Background: India is a high burden country for Tuberculosis (TB. As per the World Health Organization (WHO statistics, 24000 cases of Multi Drug Resistant (MDR TB were diagnosed in India in 2014. MDR-TB patients consist of a heterogeneous cohort and management has its challenges. Aims and objectives: We studied the prevalence of PreExtensively Drug Resistant TB (Pre XDR-TB and Extensively Drug Resistant TB (XDR-TB among patients of pulmonary MDR-TB not previously exposed to second-line anti-tuberculous drugs and having baseline second-line Drug Susceptibility Testing (DST against Fluoroquinolones (FQ and Aminoglycosides (AM. Results: We included 227 patients. On the basis of the DST, patients were grouped into- 1 MDR-TB, 2 MDR-TB with FQ resistance {Pre XDR-TB (FQ}, 3 MDR-TB with AM resistance {Pre XDR-TB (AM} 4 XDR-TB. Of the 227 patients, 89 (39.2% had MDR-TB, 127 (55.94% had Pre XDR-TB (FQ, none had Pre XDR-TB (AM and 11 (4.86% had XDR-TB. Nine (4% patients were human immunodeficiency (HIV infected and 25(11% had Diabetes Mellitus (DM. Conclusion: This study highlights the importance of baseline DST to FQ and AM in patients of diagnosed or suspected MDR-TB. We encountered a higher prevalence of Pre XDR-TB (FQ which of concern in management of MDR-TB.

  3. Endothelial injury in a transforming growth factor β-dependent mouse model of scleroderma induces pulmonary arterial hypertension.

    Science.gov (United States)

    Derrett-Smith, Emma C; Dooley, Audrey; Gilbane, Adrian J; Trinder, Sarah L; Khan, Korsa; Baliga, Reshma; Holmes, Alan M; Hobbs, Adrian J; Abraham, David; Denton, Christopher P

    2013-11-01

    To delineate the constitutive pulmonary vascular phenotype of the TβRIIΔk-fib mouse model of scleroderma, and to selectively induce pulmonary endothelial cell injury using vascular endothelial growth factor (VEGF) inhibition to develop a model with features characteristic of pulmonary arterial hypertension (PAH). The TβRIIΔk-fib mouse strain expresses a kinase-deficient transforming growth factor β (TGFβ) receptor type II driven by a fibroblast-specific promoter, leading to ligand-dependent up-regulation of TGFβ signaling, and replicates key fibrotic features of scleroderma. Structural, biochemical, and functional assessments of pulmonary vessels, including in vivo hemodynamic studies, were performed before and following VEGF inhibition, which induced pulmonary endothelial cell apoptosis. These assessments included biochemical analysis of the TGFβ and VEGF signaling axes in tissue sections and explanted smooth muscle cells. In the TβRIIΔk-fib mouse strain, a constitutive pulmonary vasculopathy with medial thickening, a perivascular proliferating chronic inflammatory cell infiltrate, and mildly elevated pulmonary artery pressure resembled the well-described chronic hypoxia model of pulmonary hypertension. Following administration of SU5416, the pulmonary vascular phenotype was more florid, with pulmonary arteriolar luminal obliteration by apoptosis-resistant proliferating endothelial cells. These changes resulted in right ventricular hypertrophy, confirming hemodynamically significant PAH. Altered expression of TGFβ and VEGF ligand and receptor was consistent with a scleroderma phenotype. In this study, we replicated key features of systemic sclerosis-related PAH in a mouse model. Our results suggest that pulmonary endothelial cell injury in a genetically susceptible mouse strain triggers this complication and support the underlying role of functional interplay between TGFβ and VEGF, which provides insight into the pathogenesis of this disease. Copyright

  4. Ultrasound -- Vascular

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate ... the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces pictures ...

  5. Ultrasound -- Vascular

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate the ... are the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces ...

  6. Prostanoid therapies in the management of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    LeVarge BL

    2015-03-01

    Full Text Available Barbara L LeVarge Department of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated with PAH; this pathway has thus become a therapeutic target. Epoprostenol, the synthetic equivalent of prostacyclin, was first utilized as short-term or bridging therapy in the 1980s. Further refinement of its long-term use via continuous intravenous infusion followed. A randomized controlled trial by Barst et al in 1996 demonstrated functional, hemodynamic, and mortality benefits of epoprostenol use. This work was a groundbreaking achievement in the management of PAH and initiated a wave of research that markedly altered the dismal prognosis previously associated with PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit increased stability and allow for an extended array of parenteral and non-parenteral (inhaled and oral therapeutic options. This review further examines the pharmacology and clinical use of epoprostenol and its analogs in PAH. Keywords: pulmonary arterial hypertension, prostacyclin analogs, epoprostenol, treprostinil, iloprost

  7. Role of oxidized lipids in pulmonary arterial hypertension

    Science.gov (United States)

    Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T.; Eghbali, Mansoureh

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH. PMID:27683603

  8. A novel mouse model of high flow-induced pulmonary hypertension-surgically induced by right pulmonary artery ligation.

    Science.gov (United States)

    Zhang, Anchen; Wang, Hongfei; Wang, Shengwei; Huang, Xiaofan; Ye, Ping; Du, Xinling; Xia, Jiahong

    2017-02-01

    This study sought to establish a new model of high-flow pulmonary hypertension (PH) in mice. This model may be useful for studies seeking to reduce the pulmonary vascular resistance and delay the development of PH caused by congenital heart disease. The right pulmonary artery was ligated via a right posterolateral thoracotomy. Pulmonary hemodynamics was evaluated by right heart catheterization immediately after ligation and at 2, 4, 8, and 12 wk postoperatively. The right ventricle (RV) and the left ventricle (LV) with septum (S) were weighed to calculate the RV/(LV + S) ratio as an index of right ventricular hypertrophy. Morphologic changes in the left lungs were analyzed, and percentages of muscularized pulmonary vessels were assessed by hematoxylin and eosin, elastica van Gieson and alpha-smooth muscle actin staining. All the study data were compared with data from a model of PH generated by hypoxic stimulation. A pulmonary hypertensive state was successfully induced by 2 wk after surgery. However, the morphologic analysis demonstrated that pulmonary vascular muscularization, as evaluated using right ventricular systolic pressure and RV/(LV + S), was not significantly increased until 4 wk postoperatively. When mice from the new model and the hypoxic model were compared, no significant differences were observed in any of the evaluated indices. High-flow PH can be induced within 4 wk after ligation of the right pulmonary artery, which is easily performed in mice. Such mice can be used as a model of high-flow PH. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Pulmonary circulatory changes after bilateral total knee arthroplasty during regional anesthesia

    Science.gov (United States)

    Bombardieri, Anna Maria; Memtsoudis, Stavros G.; Go, George; Ma, Yan; Sculco, Thomas; Sharrock, Nigel

    2014-01-01

    Study Objective To monitor the pulmonary hemodynamics of patients undergoing bilateral total knee arthroplasty (BTKA) intraoperatively and up to 24 hours following surgery. Design Prospective observational study. Setting University-affiliated teaching hospital. Patients 30 ASA physical status 2 and 3 patients scheduled for single-stage, cemented, BTKA during epidural anesthesia. Interventions Pulmonary artery catheters attached to all patients. Measurements Systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), the ratio of PVR to SVR at baseline, at the beginning of surgery, and after each knee implantation were recorded and compared with measurements taken one day postoperatively (POD 1). Main Results On POD 1, PVR/SVR was increased by 30% compared with baseline (P < 0.0001) and by 20% versus the end of surgery (P < 0.0001). Systemic vascular resistance decreased during surgery and was significantly lower than baseline at 24 hours after surgery (P < 0.0001). No significant change in PVR was noted during surgery. Conclusion The PVR/SVR ratio on the day following BTKA was increased. This change may represent the different effects of inflammatory perioperative stresses on the pulmonary and systemic vasculature. PMID:23391339

  10. Treatment of Hantavirus Pulmonary Syndrome

    Science.gov (United States)

    2007-10-14

    Clinical syndrome Hantaviruses cause a spectrum of vascular-leak syndromes n humans ranging from proteinuria to pulmonary edema and rank hemorrhage...of fatal illness. The illness is haracterized by fever and vascular leakage resulting in noncar- iogenic pulmonary edema followed in severe cases by...cardiopulmonary syndrome (HCPS) o emphasize the important role of cardiogenic shock; among ospitalized patients, death almost invariably results from

  11. miR-223 reverses experimental pulmonary arterial hypertension.

    Science.gov (United States)

    Meloche, Jolyane; Le Guen, Marie; Potus, François; Vinck, Jérôme; Ranchoux, Benoit; Johnson, Ian; Antigny, Fabrice; Tremblay, Eve; Breuils-Bonnet, Sandra; Perros, Frederic; Provencher, Steeve; Bonnet, Sébastien

    2015-09-15

    Pulmonary arterial hypertension (PAH) is a devastating disease affecting lung vasculature. The pulmonary arteries become occluded due to increased proliferation and suppressed apoptosis of the pulmonary artery smooth muscle cells (PASMCs) within the vascular wall. It was recently shown that DNA damage could trigger this phenotype by upregulating poly(ADP-ribose)polymerase 1 (PARP-1) expression, although the exact mechanism remains unclear. In silico analyses and studies in cancer demonstrated that microRNA miR-223 targets PARP-1. We thus hypothesized that miR-223 downregulation triggers PARP-1 overexpression, as well as the proliferation/apoptosis imbalance observed in PAH. We provide evidence that miR-223 is downregulated in human PAH lungs, distal PAs, and isolated PASMCs. Furthermore, using a gain and loss of function approach, we showed that increased hypoxia-inducible factor 1α, which is observed in PAH, triggers this decrease in miR-223 expression and subsequent overexpression of PARP-1 allowing PAH-PASMC proliferation and resistance to apoptosis. Finally, we demonstrated that restoring the expression of miR-223 in lungs of rats with monocrotaline-induced PAH reversed established PAH and provided beneficial effects on vascular remodeling, pulmonary resistance, right ventricle hypertrophy, and survival. We provide evidence that miR-223 downregulation in PAH plays an important role in numerous pathways implicated in the disease and restoring its expression is able to reverse PAH.

  12. Serum-resistant complex nanoparticles functionalized with imidazole-rich polypeptide for gene delivery to pulmonary metastatic melanoma.

    Science.gov (United States)

    Gu, Jijin; Chen, Xinyi; Xin, Hongliang; Fang, Xiaoling; Sha, Xianyi

    2014-01-30

    To enhance serum-resistance and overcome the lysosomal barrier are effective and feasible strategies to increase the transfection efficiency of non-viral gene delivery system. For the systemic delivery of therapeutic gene, we previously developed self-assemble carboxymethyl poly(l-histidine) (CM-PLH)/poly(β-amino ester) (PbAE)/pDNA ternary complex nanoparticles based on electrostatic coating as an effective pDNA carrier. Recharging cationic PbAE/pDNA polyplexes with CM-PLH was a promising method to reduce the cytotoxicity and enhance the stability in vivo of positive charged polyplexes. In the present study, the transfection activities of ternary complex nanoparticles were further evaluated in vitro and in vivo. The transfection efficiency of ternary complex nanoparticles showed significant serum-resistance (CM-PLH-containing (51.9±4.35)% in 50% FBS>CM-PLH-free (14.7±5.66)% in 50% FBS), cell line dependent (HEK293>MCF-7>COS7>B16F10>A549>Hela>SPC-A1>CHO>SKOV3) and incubation period dependent (24 h, 20 h, 16 h>12 h>8 h>4 h>2 h>1 h>0.5 h). After transfected with ternary complex nanoparticles loading pGV240-MDA-7/IL-24, the B16F10 cells exhibited significant apoptosis and proliferation inhibition due to the expression of IL-24. Moreover, in the pulmonary metastatic melanoma model, ternary complex nanoparticles loading pGV240-MDA-7/IL-24 showed significant antitumor therapeutic efficacy in vivo. These results suggested that CM-PLH/PbAE/pDNA ternary complex nanoparticles were promising and challenging gene vector for practical application.

  13. Phenotypic evaluation of the resistance in F1 carnation populations to vascular wilt caused by Fusarium oxysporum f.sp. dianthi

    Directory of Open Access Journals (Sweden)

    Johana Carolina Soto-Sedano

    2012-08-01

    Full Text Available One of the most important phytosanitary problems of the carnation crops in Colombia and in the entire world is vascular wilting produced by Fusarium oxysporum f.sp. dianthi. Currently, an effective treatment against the pathogen does not exist; the search for resistant varieties has been the most successful method for control of this disease. Breeding programs are vital to solving the problem of the carnation fusariosis. The objective of this research was the phenotypic evaluation of carnation F1 populations, products of contrasting crossing, resistant per susceptible to F. oxysporum f.sp. dianthi, in order to determine if the resistance is inherited in the lines. This information will contribute to the selection of material and to the successful introduction of the resistant characteristic, whose expression is commercially acceptable, to the gene pool. The methodology adopted was a phenotypic evaluation of the response to the parasite in the population (450 individuals and in the parental. This evaluation estimated the area under the curve (AU DPC, using a scale of symptoms reported for carnation vascular wilt. Three different phenotypes were established with this evaluation. The moderately susceptible one is the predominant phenotype and an analysis of phenotypic frequencies was carried out on it. The results show that the individuals of the evaluated F1 population were distributed between two extreme ranges, resistant and susceptible; this shows that there is segregation for the trait resistant to F. oxysporum f.sp dianthi. We did not observe clearly differentiated classes, i.e. with complete absence or presence of the disease, indicating a possible control of the resistance in the evaluated carnation material, governed by more than one gene and with a possible additive genetic action

  14. Genitourinary and pulmonary multidrug resistant Mycobacterium tuberculosis infection in an Asian elephant (Elephas maximus).

    Science.gov (United States)

    Dumonceaux, Genevieve A; St Leger, Judy; Olsen, John H; Burton, Michael S; Ashkin, David; Maslow, Joel N

    2011-12-01

    A female Asian elephant (Elephas maximus) developed vaginal and trunk discharge. Cultures were positive for pan-susceptible Mycobacterium tuberculosis. Isoniazid and pyrazinamide were given rectally and monitored by serum levels. After being trained at 10 mo to accept oral dosing, treatment was changed and rifampin was added. Oral medications were administered for another 10 mo. A year after completion of therapy, the vaginal discharge increased and cultures yielded M. tuberculosis, resistant to isoniazid and rifampin. Treatment with oral ethambutol, pyrazinamide, and enrofloxacin and intramuscular amikacin was initiated. Although followup cultures became negative, adverse reactions to medications precluded treatment completion. Due to public health concerns related to multidrug resistant M. tuberculosis (MDR-TB), the elephant was euthanized. Postmortem smears from the lung, peribronchial, and abdominal lymph nodes yielded acid-fast bacteria, although cultures were negative. This case highlights important considerations in the treatment of M. tuberculosis in animals and the need for a consistent approach to diagnosis, treatment, and follow-up.

  15. Diagnostic performance of state-of-the-art imaging techniques for morphological assessment of vascular abnormalities in patients with chronic thromboembolic pulmonary hypertension (CTEPH)

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Sebastian [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Ley-Zaporozhan, Julia [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Johannes Gutenberg University, Department of Diagnostic and Interventional Radiology; Universitaetsmedizin, Mainz (Germany); Pitton, Michael B.; Schneider, Jens; Wirth, Gesine M.; Dueber, Christoph; Kreitner, Karl-Friedrich [Johannes Gutenberg University, Department of Diagnostic and Interventional Radiology; Universitaetsmedizin, Mainz (Germany); Mayer, Eckhard [Kerckhoff-Hospital Bad Nauheim, Department of Thoracic Surgery, Bad Nauheim (Germany)

    2012-03-15

    To determine the most comprehensive imaging technique for the assessment of pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension (CTEPH). 24 patients with CTEPH were examined by ECG-gated multi-detector CT angiography (MD-CTA), contrast-enhanced MR angiography (ce-MRA) and selective digital subtraction angiography (DSA) within 3 days. Two readers in consensus separately evaluated each imaging technique (48 main, 144 lobar and 449 segmental arteries) for typical changes like complete obstructions, vessel cut-offs, intimal irregularities, incorporated thrombus formations, and bands and webs. A joint interpretation of all three techniques served as a reference standard. Based on image quality, there was no non-diagnostic examination by either imaging technique. DSA did not sufficiently display 1 main, 3 lobar and 4 segmental arteries. The pulmonary trunk was not assessable by DSA. One patient showed thrombotic material at this level only by MD-CTA and MRA. Sensitivity and specificity of MD-CTA regarding CTEPH-related changes at the main/lobar and at the segmental levels were 100%/100% and 100%/99%, of ce-MRA 83.1%/98.6% and 87.7%/98.1%, and of DSA 65.7%/100% and 75.8%/100%, respectively. ECG-gated MD-CTA proved the most adequate technique for assessment of the pulmonary arteries in the diagnostic work-up of CTEPH patients. (orig.)

  16. Effect of Adrenomedullin on Pulmonary Vascular Structural Remodeling Induced by High Pulmonary Blood Flow in Rats%肾上腺髓质素对大鼠高肺血流性肺血管结构重构的干预作用

    Institute of Scientific and Technical Information of China (English)

    高扬; 齐建光; 李晓惠; 庞璐璐; 金红芳; 杜军保

    2012-01-01

    Objective To explore the effect of adrenomedullin ( ADM) on the pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by high pulmonary blood flow. Methods Twenty - one male 6 - week - old SD rats were randomly divided into control group (n = 7 ) , shunt group ( n = 7 ) and shunt with ADM group (n = 7). Aortocaval shunting was produced in rats of shunt group and shunt with ADM group. In control group,the inferior vena cava and abdominal aorta were only exposed,but shunting procedure was not performed. After 8 weeks,ADM (1. 5 μg · kg-1 · h-1) was subcutaneously administered into rats of shunt with ADM group by mini - osmotic pump for 2 weeks. Pulmonary artery pressures of each rat were evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass.[ RV/( LV + SP) ] was calculated after weighting. The pulmonary artery micro - and ultra - morphologic changes of rats were observed. Results Compared with the rats of control group,pulmonary artery systolic pressure,pulmonary artery diastolic pressure,pulmonary artery mean pressure and RV/( LV + SP) in rats of shunt group were significantly increased (Pa <0.01) ,the muscularization of small pulmonary vessels, relative medial thickness and relative medial area of the pulmonary arteries were also significantly increased (Pa <0. 01 ). Ultrastructural changes, including swelling of endothelial cells, irregularity of inner elastic lamina, and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells,were found in pulmonary arteries of shunting rats. Pulmonary artery pressure and RV/(LV +SP) in rats of shunt with ADM group were significantly decreased compared with those of shunt group (Pa <0.01) ,with the alleviation of pulmonary artery micro - and ultra - morphologic changes. Conclusions ADM subcutaneously administered by mimi - osmotic pump alleviated the development of pulmonary hypertension and

  17. Pulmonary edema

    Science.gov (United States)

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  18. Nutritional status in multi-drug resistance-pulmonary tuberculosis patients

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2014-12-01

    Full Text Available Introduction: Malnutrition and tuberculosis are the major concerns of underdeveloped regions of the world. Undernutrition increases the risk of tuberculosis (TB and in turn TB can lead to Malnutrition. Undernutrition is therefore highly prevalent among people with TB. It has been demonstrated that undernutrition is a risk factor for progression from TB infection to active TB disease and severe form viz. MDR-TB. Undernutrition is a predictor of increased risk of death and TB relapse. Objectives: To study the effect of nutrition in MDR-TB patients at DR-TB centre, Dehradun. Methodology: The Observational cross sectional study was conducted at Drug Resistant Tuberculosis (DR-TB Centre of HIMS, Dehradun over a   period of 12 months to include all the cases reported from 1st October, 2011 (start of DR-TB Centre at HIMS, Dehradun to 30th April, 2014. 376 Subjects were recruited from 1598 suspected MDR TB subjects who were screened by Drug Susceptibility Testing (DST results. Results: Out of 376 MDR-TB patients, 258 (68.6% subjects were found to be undernourished. The mean body mass index (BMI was 17.33+1.99 kg/m2. Though undernutrition was more common among Males (61.2% but female’s BMI was more affected by MDR in comparison to males. Treatment success was better amongst males between 21- 60 year age group with normal BMI having mono drug resistance with no adverse reaction. The majority 47 (18.2% of adverse effect was found in undernourished patients. Treatment outcome was also poor among undernourished (76.9% MDR-TB patients. Conclusion: Prevalence of undernutrition was high (68.6% among subjects and the mean BMI was lower in female. Adverse drug reaction, poor treatment outcome are attributes of Undernutrition.

  19. A case of left main pulmonary artery aneurysm associated with valvular pulmonary stenosis in a child.

    Science.gov (United States)

    Lee, Ran; Son, Jae Sung; Park, Yong Mean

    2011-10-01

    Aneurysm of the main pulmonary artery is a rare clinical entity that can be congenital or acquired. Most cases occur in association with other congenital malformations, severe pulmonary hypertension, vasculitides, infectious agents, or collagen vascular disorders. We report here a pediatric case of left pulmonary artery aneurysm associated with valvular pulmonary stenosis and a hypoplastic right pulmonary artery, which we confirmed via multidetector computed tomography angiography.

  20. 重叠综合征患者肺动脉压力与血管内皮功能的研究%Pulmonary arterial pressure and vascular endothelial function in patients with overlap syndrome

    Institute of Scientific and Technical Information of China (English)

    陈文晖; 郝晴虹; 张海

    2012-01-01

    目的:探讨重叠综合征(OS)患者肺功能、睡眠呼吸参数和肺动脉压力的变化以及肺动脉压力与血管内皮功能的相关性.方法:收集2009年2月至2012年1月我院呼吸科诊断的慢性阻塞性肺疾病(COPD)、阻塞性睡眠呼吸暂停低通气综合征(OSAHS)和OS患者各60例,分别测定患者肺功能、睡眠呼吸参数、平均肺动脉压力(mPAP)、血清内皮素1(ET-1)、一氧化氮(NO)和血管内皮生长因子(VEGF)水平.结果:OS组与单纯COPD组和OSAHS组相比,第1秒用力呼气容积(FEV1)(%预测值)、FEV1/用力肺活量(FVC)和快速眼动相睡眠(REM)占总睡眠时间百分比(%)均明显降低(P<0.05);而睡眠呼吸暂停低通气指数(AHI、Epworth嗜睡量表(ESS)评分和mPAP明显增高(P<0.05); OS患者血清中ET-1和VEGF浓度明显高于单纯COPD和单纯OSAHS患者(P<0.05),并与其mPAP呈正相关,而NO浓度显著降低,与mPAP呈负相关.结论:OS患者较单纯的COPD和OSAHS患者更易合并肺动脉高压,外周血ET-1、VEGF和NO的浓度与肺动脉压力有一定的相关性.%Objective To explore the changes of pulmonary function and sleep respiratory parameters, and to analyze the correlation between mean pulmonary arterial pressure (mPAP) and vascular endothelial function in patients with overlap syndrome (OS). Methods Sixty OS patients, 60 chronic obstructive pulmonary disease (COPD) patients and 60 obstructive sleep apnea and hyperpnoea syndrome (OSAHS) patients from Feb 2009 to Jan 2012 were enrolled in this study. Pulmonary function, sleep respiratory parameter, mPAP, endothelin-1 (ET-1), nitric oxide (NO) and vascular endothelial growth factor (VECF) were assessed and analyzed. Results Forced expiaratory volume in 1 s (FEV,)(% predicted value), FEW forced vital capacity (FVC) and rapid eye movement sleep (REM) % were significantly lower in OS patients than those in COPD and OSAHS patients(P<0.05) .while apnea hypopnea index (AM), Epworth sleepiness scale

  1. Abrogation of IL-4 receptor-α-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response.

    Science.gov (United States)

    Müller, Uwe; Stenzel, Werner; Piehler, Daniel; Grahnert, Andreas; Protschka, Martina; Köhler, Gabriele; Frey, Oliver; Held, Josephin; Richter, Tina; Eschke, Maria; Kamradt, Thomas; Brombacher, Frank; Alber, Gottfried

    2013-08-01

    In the murine model of pulmonary infection with Cryptococcus neoformans, IL-4 receptor α (IL-4Rα)-dependent polyfunctional T(h)2 cells induce disease progression associated with alternative activation of lung macrophages. To characterize the effector role of IL-4Rα-dependent alternatively activated macrophages (aaMph), we intra-nasally infected mice with genetically ablated IL-4Rα expression on macrophages (LysM(Cre)IL-4Rα(-/lox) mice) and IL-4Rα(-/lox) littermates. LysM(Cre)IL-4Rα(-/lox) mice were significantly more resistant to pulmonary cryptococcosis with higher survival rates and lower lung burden than non-deficient heterozygous littermates. Infected LysM(Cre)IL-4Rα(-/lox) mice had reduced but detectable numbers of aaMph expressing arginase-1, chitinase-like enzyme (YM1) and CD206. Similar pulmonary expression of inducible nitric oxide synthase was found in LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) control mice, but macrophages from LysM(Cre)IL-4Rα(-/lox) mice showed a higher potential to produce nitric oxide. In contrast to the differences in the macrophage phenotype, pulmonary T(h)2 responses were similar in infected LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) mice with each mouse strain harboring polyfunctional T(h)2 cells. Consistently, type 2 pulmonary allergic inflammation associated with eosinophil recruitment and epithelial mucus production was present in lungs of both LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) mice. Our results demonstrate that, despite residual IL-4Rα-independent alternative macrophage activation and ongoing T(h)2-dependent allergic inflammation, abrogation of IL-4Rα-dependent aaMph is sufficient to confer resistance in pulmonary cryptococcosis. This is even evident on a relatively resistant heterozygous IL-4Rα(+/-) background indicating a key contribution of macrophage IL-4Rα expression to susceptibility in allergic bronchopulmonary mycosis.

  2. Assessment of perfusion pattern and extent of perfusion defect on dual-energy CT angiography: Correlation between the causes of pulmonary hypertension and vascular parameters

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Young [Dept. of Radiology, Chonbuk National University Medical School and Hospital, Research Institute of Clinical Medicine, Jeonju (Korea, Republic of); Seo, Joon Beom; Oh, Sang Young; Lee, Choong Wook; Lee, Sang Min [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Hwang, Hye Jeon [Dept. of Radiology, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of); Lee, Young Kyung [Dept. of Radiology, Seoul Medical Center, Seoul (Korea, Republic of)

    2014-04-15

    To assess perfusion patterns on a dual-energy pulmonary CT angiography (DECTA) of pulmonary hypertension (PHT) with variable causes and to assess whether the extent of perfusion defect can be used in the severity assessment of PHT. Between March 2007 and February 2011, DECTA scans of 62 consecutive patients (24 men, 38 women; mean age, 58.5 ± 17.3 [standard deviation] years; range, 19-87 years) with PHT were retrospectively included with following inclusion criteria; 1) absence of acute pulmonary thromboembolism, 2) maximal velocity of tricuspid regurgitation jet (TR Vmax) above 3 m/s on echocardiography performed within one week of the DECTA study. Perfusion patterns of iodine map were divided into normal (NL), diffuse heterogeneously decreased (DH), multifocal geographic and multiple peripheral wedging patterns. The extent of perfusion defects (PD), the diameter of main pulmonary artery (MPA) and the ratio of ascending aorta diameter/MPA (aortopulmonary ratio, APR) were measured. Pearson correlation analysis was performed between TR Vmax on echocardiography and CT imaging parameters. Common perfusion patterns of primary PHT were DH (n = 15) and NL (n = 12). The perfusion patterns of secondary PHT were variable. On the correlation analysis, in primary PHT, TR Vmax significantly correlated with PD, MPA and APR (r = 0.52, r = 0.40, r = -0.50, respectively, all p < 0.05). In secondary PHT, TR Vmax significantly correlated with PD and MPA (r = 0.38, r = 0.53, respectively, all p < 0.05). Different perfusion patterns are observed on DECTA of PHT according to the causes. PD and MPA are significantly correlated with the TR Vmax.

  3. Differential Sensitivities of Pulmonary and Coronary Arteries to Hemoglobin-Based Oxygen Carriers and Nitrovasodilators: Study in a Bovine Ex Vivo Model of Vascular Strips

    Science.gov (United States)

    2010-01-01

    lsev ier.c omflocate/ vph Differential sensitivities of pulmonary and coronary arteries to hemoglobin-based oxygen carriers and nitrovasodilators...preparation has been used extensively in multiple studies that led to the discovery of NO as endothelium-derived relaxing factor (lgnarro et al., 1984...G.M .• Wood, K.S., Chaudhuri, G., 1988a. Pharmacological evidence that endothelium-derived relaxing factor is nitric oxide: use or pyrogallol and

  4. Role of endogenous nitric oxide on PAF-induced vascular and respiratory effects

    Directory of Open Access Journals (Sweden)

    M. Clement

    1995-01-01

    Full Text Available The role of endogenous nitric oxide (NO on vascular and respiratory smooth muscle basal tone was evaluated in six anaesthetized, paralysed, mechanically ventilated pigs. The involvement of endogenous NO in PAF-induced shock and airway hyperresponsiveness was also studied. PAF (50 ng/kg, i.v. was administered before and after pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v., an NO synthesis inhibitor. PAF was also administered to three of these pigs after indomethacin infusion (3 mg/kg, i.v.. In normal pigs, L-NAME increased systemic and pulmonary vascular resistances, caused pulmonary hypertension and reduced cardiac output and stroke volume. The pulmonary vascular responses were correlated with the increase in static and dynamic lung elastances, without changing lung resistance. Inhibition of NO synthesis enhanced the PAF-dependent increase in total, intrinsic and viscoelastic lung resistances, without affecting lung elastances or cardiac activity. The systemic hypotensive effect of PAF was not abolished by pretreatment with L-NAME or indomethacin. This indicates that systemic hypotension is not correlated with the release of endogenous NO or prostacyclines. Indomethacin completely abolished the PAF-dependent respiratory effects.

  5. Inhaled iloprost for the control of pulmonary hypertension

    Science.gov (United States)

    Krug, Sabine; Sablotzki, Armin; Hammerschmidt, Stefan; Wirtz, Hubert; Seyfarth, Hans-Juergen

    2009-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an elevated pulmonary arterial pressure and vascular resistance with a poor prognosis. Various pulmonary and extrapulmonary causes are now recognized to exist separately from the idiopathic form of pulmonary hypertension. An imbalance in the presence of vasoconstrictors and vasodilators plays an important role in the pathophysiology of the disease, one example being the lack of prostacyclin. Prostacyclin and its analogues are potent vasodilators with antithrombotic, antiproliferative and anti-inflammatory qualities, all of which are important factors in the pathogenesis of precapillary pulmonary hypertension. Iloprost is a stable prostacyclin analogue available for intravenous and aerosolized application. Due to the severe side effects of intravenous administration, the use of inhaled iloprost has become a mainstay in PAH therapy. However, owing to the necessity for 6 to 9 inhalations a day, oral treatment is often preferred as a first-line therapy. Numerous studies proving the efficacy and safety of inhaled iloprost have been performed. It is therefore available for a first-line therapy for PAH. The combination with endothelin-receptor antagonists or sildenafil has shown encouraging effects. Further studies with larger patient populations will have to demonstrate the use of combination therapy for long-term treatment of pulmonary hypertension. PMID:19475782

  6. The pulmonary vascular blood supply in the pulmonary atresia with ventricular septal defect and its implications in surgical treatment O suprimento sangüíneo vascular pulmonar na atresia pulmonar com comunicação interventricular e suas implicações no tratamento cirúrgico

    Directory of Open Access Journals (Sweden)

    Ulisses Alexandre Croti

    2003-10-01

    Full Text Available OBJECTIVE: With base in the studies cineangiocardiography of pacients with pulmonary atresia (PA with ventricular septal defect (VSD, to identify in the groups proposed by BARBERO MARCIAL, subgroups with similar morphological characteristics, to measure their central pulmonary arteries (CPA and major aortopulmonary collateral arteries (MAPCA, thereby establishing their implications in surgical treatment. METHOD: Sixty three patients were classified in groups A (15, B (40 and C (8 between january 1990 and june 2001. Patients with complete cineangiocardiograms prior to the first surgical intervention were included in this study, being calculated the pulmonary arterial index (PAI, the major aortopulmonary collateral arterial index (MAPCAI and the total neopulmonary arterial index (TNPAI = PAI + MAPCAI. Surgical treatment was considered palliative (PT, definitively palliative (DPT and definitive (DT. RESULTS: Nine subgroups were identified, A (A1 and A2, B (B1, B2, B3, B4 and B5 and C (C1 and C2. In group A, the PAI of patients for DT was higher than for PT patients (p=0,0092. In group B, the TNPAI of DT patients was greater than for PT patients (p=0,0959. In group C, the MAPCAI in DPT patients was lower than in PT and DT patients. In the group A was not mortality, in the group B was of 17,5% and in the group C was of 12,5%. CONCLUSIONS:Among the groups A, B e C was possible to identifiy nine subgroups, the morphologic and morphometric characteristics allowed to suggest the surgical treatment in the patients of the group A had larger chance of TD, the group B of TP and the group C of TPD. The mortality presented larger correlation with the morphologic characteristics that with the morphometric.OBJETIVO: Com base nos estudos cineangiocardiográficos de pacientes portadores de atresia pulmonar (AP com comunicação interventricular (CIV, identificar nos grupos propostos pela classificação de BARBERO MARCIAL, subgrupos com suprimento sang

  7. Aldosterone and vascular damage.

    Science.gov (United States)

    Duprez, D; De Buyzere, M; Rietzschel, E R; Clement, D L

    2000-06-01

    Although the aldosterone escape mechanism is well known, aldosterone has often been neglected in the pathophysiologic consequences of the activated renin-angiotensin-aldosterone system in arterial hypertension and chronic heart failure. There is now evidence for vascular synthesis of aldosterone aside from its secretion by the adrenal cortex. Moreover, aldosterone is involved in vascular smooth muscle cell hypertrophy and hyperplasia, as well as in vascular matrix impairment and endothelial dysfunction. The mechanisms of action of aldosterone may be either delayed (genomic) or rapid (nongenomic). Deleterious effects of aldosterone leading to vascular target-organ damage include (besides salt and water retention) decreased arterial and venous compliance, increased peripheral vascular resistance, and impaired autonomic vascular control due to baroreflex dysfunction.

  8. Radiological Findings of Extensively Drug-Resistant Pulmonary Tuberculosis in Non-AIDS Adults: Comparisons with Findings of Multidrug-Resistant and Drug-Sensitive Tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Ji Hoon; Lee, Ho Yun; Lee, Kyung Soo; Koh, Won Jung; Kwon, O Jung; Yi, Chin A; Kim, Tae Sung; Chung, Myung Jin [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2009-06-15

    This study was designed to describe the radiological findings of extensively drug-resistant (XDR) pulmonary tuberculosis (TB) and to compare the observed findings with findings of drug-sensitive (DS) and non-XDR multidrug- resistant (MDR) TB in non-AIDS patients. From September 1994 to December 2007, 53 MDR TB patients (M:F = 32:21; mean age, 38 years) and 15 XDR TB non-AIDS patients (M:F = 8:7; mean age, 36 years) were enrolled in the study. All of the MDR TB patients had received no treatment or less than one month of anti-TB treatment. In addition, all XDR TB patients received either no anti-TB treatment or only first-line anti-TB drugs. In addition, 141 consecutive DS TB patients (M:F = 79:62; mean age, 51 years) were also enrolled in the study for comparison. Chest radiograph, CT and demographic findings were reviewed and were compared among the three patient groups. For patients with XDR TB, the most frequent radiographic abnormalities were nodules (15 of 15 patients, 100%), reticulo-nodular densities (11 of 15, 73%), consolidation (9 of 15, 60%) and cavities (7 of 15, 47%) that were located mainly in the upper and middle lung zones. As seen on radiographs, significant differences were found for the frequency of nodules and ground-glass opacity lesions (all p < 0.001) (more frequent in DS TB patients than in MDR and XDR TB patients). For the use of CT, significant differences (more frequent in MDR and XDR TB patients) were found for the frequency of multiple cavities, nodules and bronchial dilatation (p = 0.001 or p < 0.001). Patients with MDR TB and XDR TB were younger as compared to patients with DS TB (p < 0.001). Imaging findings were not different between patients with MDR TB and XDR TB. By observation of multiple cavities, nodules and bronchial dilatation as depicted on CT in young patients with acid-fast bacilli (AFB) positive sputum, the presence of MDR TB or XDR TB rather than DS TB can be suggested. There is no significant difference in imaging

  9. Vascular Cures

    Science.gov (United States)

    ... is Possible EVERY DOLLAR SAVES LIVES. Donate Now Vascular Cures innovates patient-centered research, catalyzes breakthrough collaborations and empowers people in their vascular health journey. what is vascular disease PATIENTS see ...

  10. Vascular ring

    Science.gov (United States)

    ... subclavian and left ligamentum ateriosus; Congenital heart defect