| 931. |
- Retamal, Jaime, et al.
(författare)
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High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS
- 2016
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 60:1, s. 79-92
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-β) in the lung epithelium.METHODS: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-β pathway markers, regional histology, and cytokines were evaluated.RESULTS: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-β pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR.CONCLUSION: HRR was associated with more pulmonary edema and higher activation of the TGF-β pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.
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| 932. |
- Retamal, Jaime, et al.
(författare)
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Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation
- 2014
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 18:5, s. 505-
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionWhen alveoli collapse the traction forces exerted on their walls by adjacent expanded units may increase and concentrate. These forces may promote its re-expansion at the expense of potentially injurious stresses at the interface between the collapsed and the expanded units. We developed an experimental model to test the hypothesis that a local non-lobar atelectasis can act as a stress concentrator, contributing to inflammation and structural alveolar injury in the surrounding healthy lung tissue during mechanical ventilation.MethodsA total of 35 rats were anesthetized, paralyzed and mechanically ventilated. Atelectasis was induced by bronchial blocking: after five minutes of stabilization and pre-oxygenation with FIO2 = 1.0, a silicon cylinder blocker was wedged in the terminal bronchial tree. Afterwards, the animals were randomized between two groups: 1) Tidal volume (VT) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH2O (VT10/PEEP3); and 2) VT = 20 ml/kg and PEEP = 0 cmH2O (VT20/zero end-expiratory pressure (ZEEP)). The animals were then ventilated during 180 minutes. Three series of experiments were performed: histological (n = 12); tissue cytokines (n = 12); and micro-computed tomography (microCT; n = 2). An additional six, non-ventilated, healthy animals were used as controls.ResultsAtelectasis was successfully induced in the basal region of the lung of 26 out of 29 animals. The microCT of two animals revealed that the volume of the atelectasis was 0.12 and 0.21 cm3. There were more alveolar disruption and neutrophilic infiltration in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. Edema was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in the VT20/ZEEP than VT10/PEEP3 group. The volume-to-surface ratio was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. We did not find statistical difference in tissue interleukin-1β and cytokine-induced neutrophil chemoattractant-1 between regions.ConclusionsThe present findings suggest that a local non-lobar atelectasis acts as a stress concentrator, generating structural alveolar injury and inflammation in the surrounding lung tissue.
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| 933. |
- Retamal, Jaime, et al.
(författare)
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Physiological and inflammatory consequences of high and low respiratory rate in acute respiratory distress syndrome
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 65:8, s. 1013-1022
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Forskningsöversikt (refereegranskat)abstract
- Using protective mechanical ventilation strategies with low tidal volume is usually accompanied by an increment of respiratory rate to maintain adequate alveolar ventilation. However, there is no robust data that support the safety of a high respiratory rate concerning ventilator-induced lung injury. Several experimental animal studies have explored the effects of respiratory rate over lung physiology, using a wide range of frequencies and different models. Clinical evidence is scarce and restricted to the physiological impact of increased respiratory rate. Undoubtedly, the respiratory rate can influence respiratory mechanics in various ways as a factor of multiplication of the power of ventilation, and gas exchange, and also on alveolar dynamics. In this narrative review, we present our point of view over the main experimental and clinical evidence available regarding the effect of respiratory rate on ventilator-induced lung injury development.
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| 934. |
- Retamal, Jaime, et al.
(författare)
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Regional pulmonary deformation is positively correlated with regional lung inflammation assessed by 18F-FDG positron emission tomography / computed tomography
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Lung deformation beyond of physiological capacity is associated with cell death and inflammation. Lung strain has been estimated as a global strain, but uneven strain distribution may lead to regional stress concentrations and lung damage. Local lung inflammation can be estimated using PET imaging of [18F]fluoro-2-deoxy-D-glucose. We hypothesized that local lung deformation correlates well with local inflammation. The aim of this study was to assess local tidal deformations by using a new mathematical model of finite-elements to analyze CT images, and to correlate them with local inflammation in a porcine experimental model of early acute respiratory distress syndrome.Design: Retrospective images analysis, laboratory investigation.Setting: University animal research laboratory.Subjects: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy ventilated controls.Intervention: Lung injury was induced by repeated lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [18F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration. Then maps of deformation were constructed and regional deformation was estimated. We divided the lung parenchyma in 10 horizontal ROIs, and correlations of local volumetric strain and [18F]fluoro-2-deoxy-D-glucose uptake were analyzed in each ROI.Measurements and Main Results: The deformation maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions. We found a strong correlation between local strain and inflammation (R2 > 0.5) for the whole lung, when we eliminate the 3/10 dorsal ROIs R2 increased until>0.8.Conclusion: the present findings suggest that the greater local stretches were mainly concentrated in the intermediate gravitational zones of injured heterogeneous lungs. Additionally, local lung deformations correlated well with local inflammation in this experimental model of VILI. And the new proposed image-based estimation of regional volumetric strain based on finite element interpolations has the potential to give new insights of local pathogenic mechanisms of VILI and how best design protective-ventilations strategies.
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| 935. |
- Retamal Montes, Jaime, 1978-
(författare)
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Aspects on ventilation induced stress and strain on regional and global inflammation in experimental acute respiratory distress syndrome
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mechanical ventilation (MV) is a life-saving therapy in acute respiratory distress syndrome (ARDS), a condition that affects 3000 patients/year in Sweden with a mortality rate of about 40%. However, MV may induce or worsen lung injury causing “ventilator-induced lung injury (VILI)”. From a mechanical perspective strain (deformation, or relative change in lung volume) and stress (tension) have been postulated as main determinants of VILI. High respiratory rate is potentially another factor that may exacerbate VILI by amplifying the total energy transmitted to the lungs during MV. In this thesis in animal ARDS models the hypotheses were that 1) lung parenchyma inhomogeneities concentrate stress and amplify lung damage and inflammation, 2) higher respiratory rates increase lung inflammation and lung edema in heterogeneous ARDS, and 3) local lung deformation is related to local inflammation.First, in a rat model the effect on inflammation and structural damage of regional lung collapse on the healthy surrounding lung tissue was assessed. Second, in porcine models the effect of respiratory rate on lung edema and inflammation was studied during two ventilatory modes; a) a permissive collapse mode and b) a homogenized lung parenchyma mode. Finally, lung deformation was correlated with lung inflammation assessed by positron emission tomography using 18F-FDG uptake.It was found that; 1) local inhomogeneities can act as stress amplifiers, increasing lung tissue inflammation and damage in the healthy surrounded lung. 2) high respiratory rate increases lung edema but decreases lung inflammation when permissive lung collapse is used and that these effects are prevented with lung parenchyma homogenization; 3) local lung deformation and inflammation are well correlated.In conclusion, lung inhomogeneities may aggravate VILI, respiratory rate may affect in different ways VILI progression depending on the ventilatory strategy, and finally, lung deformation is closely related to lung inflammation. With the caveat that the studies are performed in animal models, the results suggest that using ventilator strategies that homogenize the lungs, i.e., open collapsed lung regions and prevent re-collapse in ARDS will reduce VILI and in the end may decrease morbidity and the high mortality in this condition.
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| 936. |
- Retamal Montes, Jaime, 1978-, et al.
(författare)
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Open lung approach ventilation abolishes the negative effects of respiratory rate in experimental lung injury
- 2016
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 60:8, s. 1131-1141
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We recently reported that a high respiratory rate was associated with less inflammation than a low respiratory rate, but caused more pulmonary edema in a model of ARDS when an ARDSNet ventilatory strategy was used. We hypothesized that an open lung approach (OLA) strategy would neutralize the independent effects of respiratory rate on lung inflammation and edema. This hypothesis was tested in an ARDS model using two clinically relevant respiratory rates during OLA strategy.METHODS: Twelve piglets were subjected to an experimental model of ARDS and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated for 6 h according to an OLA strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, wet/dry ratio, regional histology, and cytokines were evaluated.RESULTS: After the ARDS model was established, Cdyn,rs decreased from 21 ± 3.3 to 9.0 ± 1.8 ml/cmH2 O (P < 0.0001). After the lung recruitment maneuver, Cdyn,rs increased to the pre-injury value. During OLA ventilation, no differences in respiratory mechanics, hemodynamics, or EVLW were observed between groups. Wet/dry ratio and histological scores were not different between groups. Cytokine quantification was similar and showed a homogeneous distribution throughout the lung in both groups.CONCLUSION: Contrary to previous findings with the ARDSNet strategy, respiratory rate did not influence lung inflammatory response or pulmonary edema during OLA ventilation in experimental ARDS. This indicates that changing the respiratory rate when OLA ventilation is used will not exacerbate lung injury.
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| 937. |
- Ribom, Dan, et al.
(författare)
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Growth factor analysis of low-grade glioma CSF : PDGF and VEGF are not detectable
- 2003
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Ingår i: Neurological Sciences. - 1590-1874 .- 1590-3478. ; 24:2, s. 70-73
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) are involved in the development of grade 2 gliomas. The aim of the present study was to determine the presence of these growth factors in the cerebrospinal fluid (CSF) and to assess their usefulness as biological markers. CSF was collected from 7 adult patients with newly diagnosed supratentorial low-grade gliomas by lumbar puncture and was analysed together with matched serum samples using radioreceptor and enzyme-linked immunosorbant assays. Neither PDGF nor VEGF were detected in the CSF, and FGF-2 was measurable at extremely low concentrations in only 2 of 7 patients. Serum levels were within normal limits. We conclude that these growth factors are not released into the CSF in any significant amounts and are therefore not suitable as biological markers in grade 2 gliomas.
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| 938. |
- Ricci, Fabrizio, et al.
(författare)
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Increased levels of circulating endostatin are linked to orthostatic hypotension
- 2023
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Ingår i: European Heart Journal. - 1522-9645 .- 0195-668X. ; 44:Supplement_2
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Konferensbidrag (refereegranskat)abstract
- BackgroundOrthostatic hypotension (OH) occurs when blood pressure regulation fails. The underlying molecular mechanism of OH remain largely unexplored. Endostatin is a biologically active molecule cleaved by matrix metalloproteinases, elastases and cathepsins from collagen XVIII in the extracellular matrix and inhibits angiogenesis. Circulating levels of endostatin have been proposed to be involved in blood pressure (BP) regulation, by inducing nitric oxide release. To date, the relationship between endostatin and OH have not been examined.PurposeWe aimed to investigate circulating levels of endostatin in patients with verified OH by tilt test at a tertiary syncope unit compared with healthy age- and sex-matched controls from the same geographical region.MethodsWe performed an age- and sex-matched case-control study in 150 patients with OH verified by positive head-up tilt-testing and other cardiovascular autonomic tests at a tertiary syncope unit, and 150 healthy controls with negative active standing tests and no history of syncope, orthostatic intolerance, and endocrine disease. High-sensitivity chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin in a blinded fashion. Receiver operating characteristic curves were constructed to analyze the discriminative ability of endostatin in OH compared with healthy controls. Multivariate logistic regression was used to assess the association between endostatin, OH and hemodynamic variables adjusting for age and sex.ResultsStudy characteristics are displayed in the Table. Patients with OH had significantly higher absolute levels of circulating endostatin compared with healthy controls (59,024 ± 2513 vs. 44,090 ± 1978 pg/mL, p<0.001). Multivariate-adjusted logistic regression analysis controlling for age, sex, minimum systolic and minimum diastolic BP during tilt, identified endostatin as an independent determinant for OH (beta-coefficient 0.80, p=0.025). The obtained area under the curve was 0.70, P<0.001, Figure).ConclusionsOur findings indicate that patients with orthostatic hypotension have increased circulating levels of endostatin, independent of age, sex, and hemodynamic variables. Our results highlight the relevance of investigating the molecular pathways related to orthostatic hypotension. Further studies are warranted to assess the prognostic and therapeutic role of endostatin assessment in individuals with orthostatic hypotension.
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| 939. |
- Ridefelt, Peter, et al.
(författare)
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Age- and sex-specific reference values for non-HDL cholesterol and remnant cholesterol derived from the Nordic Reference Interval Project (NORIP)
- 2019
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis Group. - 0036-5513 .- 1502-7686. ; 79:1-2, s. 39-42
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Non-HDL-cholesterol (non-HDL-C) has been reported to be a better marker of cardiovascular risk than LDL-cholesterol (LDL-C) especially in individuals with high triglyceride values. Further, levels of remnant cholesterol have been suggested to in part explain residual risk not captured with LDL-C. The aim of the present study was to define reference values for non-HDL-C and remnant cholesterol based on data from the Nordic Reference Interval Project (NORIP).METHODS: We analyzed the test results for total cholesterol, HDL-cholesterol and triglycerides from 1392 healthy females and 1236 healthy males. Non-HDL-C was calculated as measured total cholesterol minus measured HDL-cholesterol. Remnant cholesterol was calculated using the Friedewald equation for LDL-C: measured total cholesterol minus measured HDL-cholesterol and minus calculated LDL-cholesterol. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.RESULTS: Age (18-<30, 30-49 and ≥50 years) and sex-specific reference intervals were calculated for non-HDL-cholesterol and remnant-cholesterol. Levels of non-HDL-C and remnant cholesterol differed between sex and age strata.CONCLUSIONS: Age- and sex-specific reference intervals should be used for the triglyceride rich lipid variables non-HDL-C and remnant cholesterol. Since these markers may add information on risk burden beyond LDL-C, our hope is that these reference intervals will aid the introduction of automatic reporting of non-HDL-C by hospital laboratories.
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| 940. |
- Ridefelt, Peter, et al.
(författare)
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Diurnal variability of total calcium during normal sleep and after an acute shift of sleep
- 2012
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 50:1, s. 147-151
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum total calcium is becoming a widely used test when screening for hyperparathyroidism (HPT) and other causes of hypercalcemia, even if serum calcium is tightly regulated in the body it is unclear whether the reference values are correct for tests taken at different times of the day or for individuals with altered sleep patterns. Thus, the aim was to investigate how timing of testing and sleep affects serum calcium. Methods: The diurnal variation of total calcium in serum during night-time and day-time conditions was studied in seven healthy volunteers. Serum samples for calcium measurements were collected every hour (48 samples per individual) to evaluate the effect of sampling times, sleep and food intake on the test results. Results: The median intra-individual coefficients of variations for calcium were 3.3% during night-time sleep and 2.8% during day-time sleep conditions. There was a clear diurnal variation in serum calcium, with a trough at 08.00 h in the morning after night-time sleep and a difference of approximately 0.07 mmol/L between trough and peak. Calcium was lower around the end of the sleep periods, for both night-time and day-time sleep. Food intake did not affect calcium concentrations. Conclusions: Evaluation of serum calcium results should take diurnal variation into account and allow slightly higher calcium values in the afternoon in comparison with samples collected in the morning.
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