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| 2. |
- Scaramuzzo, Gaetano, et al.
(författare)
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Influence of Positive End-Expiratory Pressure Titration on the Effects of Pronation in Acute Respiratory Distress Syndrome : A Comprehensive Experimental Study
- 2020
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Ingår i: Frontiers in Physiology. - : FRONTIERS MEDIA SA. - 1664-042X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Prone position can reduce mortality in acute respiratory distress syndrome (ARDS), but several studies found variable effects on oxygenation and lung mechanics. It is unclear whether different positive end-expiratory pressure (PEEP) titration techniques modify the effect of prone position. We tested, in an animal model of ARDS, if the PEEP titration method may influence the effect of prone position on oxygenation and lung protection. In a crossover study in 10 piglets with a two-hit injury ARDS model, we set the "best PEEP" according to the ARDS Network low-PEEP table (BPARDS) or targeting the lowest transpulmonary driving pressure (BPDPL). We measured gas exchange, lung mechanics, aeration, ventilation, and perfusion with computed tomography (CT) and electrical impedance tomography in each position with both PEEP titration techniques. The primary endpoint was the PaO2/FiO(2) ratio. Secondary outcomes were lung mechanics, regional distribution of ventilation, regional distribution of perfusion, and homogeneity of strain derived by CT scan. The PaO2/FiO(2) ratio increased in prone position when PEEP was set with BPARDS [difference 54 (19-106) mmHg, p = 0.04] but not with BPDPL [difference 17 (-24 to 68) mmHg, p = 0.99]. The transpulmonary driving pressure significantly decreased during prone position with both BPARDS [difference -0.9 (-1.5 to -0.9) cmH(2)O, p = 0.009] and BPDPL [difference -0.55 (-1.6 to -0.4) cmH(2)O, p = 0.04]. Pronation homogenized lung regional strain and ventilation and redistributed the ventilation/perfusion ratio along the sternal-to-vertebral gradient. The PEEP titration technique influences the oxygenation response to prone position. However, the lung-protective effects of prone position could be independent of the PEEP titration strategy.
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| 3. |
- Scaramuzzo, Gaetano, et al.
(författare)
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Regional Behavior of Airspaces During Positive Pressure Reduction Assessed by Synchrotron Radiation Computed Tomography
- 2019
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The mechanisms of lung inflation and deflation are only partially known. Ventilatory strategies to support lung function rely upon the idea that lung alveoli are isotropic balloons that progressively inflate or deflate and that lung pressure/volume curves derive only by the interplay of critical opening pressures, critical closing pressures, lung history, and position of alveoli inside the lung. This notion has been recently challenged by subpleural microscopy, magnetic resonance, and computed tomography (CT). Phase-contrast synchrotron radiation CT (PC-SRCT) can yield in vivo images at resolutions higher than conventional CT.Objectives: We aimed to assess the numerosity (ASden) and the extension of the surface of airspaces (ASext) in healthy conditions at different volumes, during stepwise lung deflation, in concentric regions of the lung. Methods: The study was conducted in seven anesthetized New Zealand rabbits. They underwent PC-SRCT scans (resolution of 47.7 mu m) of the lung at five decreasing positive end expiratory pressure (PEEP) levels of 12, 9, 6, 3, and 0 cmH(2)O during end-expiratory holds. Three concentric regions of interest (ROIs) of the lung were studied: subpleural, mantellar, and core. The images were enhanced by phase contrast algorithms. ASden and ASext were computed by using the Image Processing Toolbox for MatLab. Statistical tests were used to assess any significant difference determined by PEEP or ROI on ASden and ASext.Results: When reducing PEEP, in each ROI the ASden significantly decreased. Conversely, ASext variation was not significant except for the core ROI. In the latter, the angular coefficient of the regression line was significantly low.Conclusion: The main mechanism behind the decrease in lung volume at PEEP reduction is derecruitment. In our study involving lung regions laying on isogravitational planes and thus equally influenced by gravitational forces, airspace numerosity and extension of surface depend on the local mechanical properties of the lung.
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| 4. |
- Scaramuzzo, Gaetano, et al.
(författare)
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The Effect of Positive End-Expiratory Pressure on Lung Micromechanics Assessed by Synchrotron Radiation Computed Tomography in an Animal Model of ARDS
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Modern ventilatory strategies are based on the assumption that lung terminal airspaces act as isotropic balloons that progressively accommodate gas. Phase contrast synchrotron radiation computed tomography (PCSRCT) has recently challenged this concept, showing that in healthy lungs, deflation mechanisms are based on the sequential de-recruitment of airspaces. Using PCSRCT scans in an animal model of acute respiratory distress syndrome (ARDS), this study examined whether the numerosity (ASnum) and dimension (ASdim) of lung airspaces change during a deflation maneuver at decreasing levels of positive end-expiratory pressure (PEEP) at 12, 9, 6, 3, and 0 cmH(2)O. Deflation was associated with significant reduction of ASdim both in the whole lung section (passing from from 13.1 +/- 2.0 at PEEP 12 to 7.6 +/- 4.2 voxels at PEEP 0) and in single concentric regions of interest (ROIs). However, the regression between applied PEEP and ASnum was significant in the whole slice (ranging from 188 +/- 52 at PEEP 12 to 146.4 +/- 96.7 at PEEP 0) but not in the single ROIs. This mechanism of deflation in which reduction of ASdim is predominant, differs from the one observed in healthy conditions, suggesting that the peculiar alveolar micromechanics of ARDS might play a role in the deflation process.
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| 5. |
- Tricase, Angelo, et al.
(författare)
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Water-Based Conductive Ink Formulations for Enzyme-Based Wearable Biosensors
- 2024
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Ingår i: Advanced Sensor Research. - : Wiley-VCH Verlagsgesellschaft. - 2751-1219. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- Herein, this work reports the first example of second-generation wearable biosensor arrays based on a printed electrode technology involving a water-based graphite ink, for the simultaneous detection of l-lactate and d-glucose. The water-based graphite ink is deposited onto a flexible polyethylene terephthalate sheet, namely stencil-printed graphite (SPG) electrodes, and further modified with [Os(bpy)2(Cl)(PVI)10] as an osmium redox polymer to shuttle the electrons from the redox center of lactate oxidase from Aerococcus viridans (LOx) and gluocose oxidase from Aspergillus niger (GOx). The proposed biosensor array exhibits a limit of detection as low as (9.0 ± 1.0) × 10−6 m for LOx/SPG-[Os(bpy)2(Cl)(PVI)10] and (3.0 ± 0.5) × 10−6 m for GOx/SPG-[Os(bpy)2(Cl)(PVI)10], a sensitivity as high as 1.32 μA mm−1 for LOx/SPG-[Os(bpy)2(Cl)(PVI)10] and 28.4 μA mm−1 for GOx/SPG-[Os(bpy)2(Cl)(PVI)10]. The technology is also selective when tested in buffer and artificial sweat and is endowed with an operational/storage stability of ≈80% of the initial signal retained after 20 days. Finally, the proposed array is integrated in a wristband and successfully tested for the continuous monitoring of l-lactate and d-glucose in a healthy volunteer during daily activity. This is foreseen as a real-time wearable device for sport-medicine and healthcare applications.
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| 6. |
- Ahlström, J. Zebialowicz, et al.
(författare)
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Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits
- 2019
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Ingår i: Respiratory Research. - : BMC. - 1465-9921 .- 1465-993X. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.
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| 7. |
- Auckburally, Adam, et al.
(författare)
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Development of a method to measure regional perfusion of the lung in anesthetized ponies using computed tomography angiography and the maximum slope model
- 2022
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Ingår i: American Journal of Veterinary Research. - : AMER VETERINARY MEDICAL ASSOC. - 0002-9645 .- 1943-5681. ; 83:2, s. 162-170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To develop a method based on CT angiography and the maximum slope model (MSM) to measure regional lung perfusion in anesthetized ponies. ANIMALS 6 ponies. PROCEDURES Anesthetized ponies were positioned in dorsal recumbency in the CT gantry. Contrast was injected, and the lungs were imaged while ponies were breathing spontaneously and while they were mechanically ventilated. Two observers delineated regions of interest in aerated and atelectatic lung, and perfusion in those regions was calculated with the MSM. Measurements obtained with a computerized method were compared with manual measurements, and computerized measurements were compared with previously reported measurements obtained with microspheres. RESULTS Perfusion measurements obtained with the MSM were similar to previously reported values obtained with the microsphere method. While ponies were spontaneously breathing, mean +/- SD perfusion for aerated and atelectatic lung regions were 4.0 +/- 1.9 and 5.0 +/- 1.2 mL/min/g of lung tissue, respectively. During mechanical ventilation, values were 4.6 +/- 1.2 and 2.7 +/- 0.7 mL/min/g of lung tissue at end expiration and 4.1 +/- 0.5 and 2.7 +/- 0.6 mL/min/g of lung tissue at peak inspiration. Intraobserver agreement was acceptable, but interobserver agreement was lower. Computerized measurements compared well with manual measurements.
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| 8. |
- Barrueta Tenhunen, Annelie
(författare)
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Adjuvant therapies to fluid resuscitation in experimental sepsis : Intervention studies in models of ARDS and peritonitis
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fluid resuscitation is essential to antagonize the deleterious effects of tissue hypo-perfusion in sepsis. If not thoroughly monitored and individually tailored, fluid therapy increases the risk of volume overload. Volume overload is associated with higher mortality in sepsis. Although considerable progress has been made to understand the complex nature of the cardiovascular derangements in sepsis and septic shock, the optimal fluid resuscitation strategy is yet to be defined. Current guidelines recommend balanced crystalloids and albumin for resuscitation; synthetic colloids are harmful and no longer in use. In search of adjuvant therapies to fluid resuscitation in sepsis and sepsis related complications with a volume sparing potential, this doctoral thesis aimed at exploring the effects of two endogenous molecules involved in fluid homeostasis.In Study I, the peptide containing the active site of the endogenous protein antisecreterory factor (AF-16) reduced lung edema formation, as reflected in a reduction in extra vascular lung water (EVLW), in a model of ventilator induced lung injury (VILI). The aim of Study I was to test the intervention AF-16 in a well-established porcine model of lung edema and capillary leak.In Study II, the intervention AF-16 was tested in a model of fecal peritonitis sepsis. The first aim of Study II was to elaborate a clinically relevant porcine model of fecal peritonitis-sepsis, including a standardized resuscitation protocol. Second aim was to test the effect of the intervention on volume status and inflammation. Wet-to-dry ratio was lower in liver samples of the intervention group, indicating less edema formation. No other differences were detected between intervention and control groups.In Study III, the intervention high molecular weight hyaluronan (HMW-HA) was tested in our model of fecal peritonitis as adjuvant to standardized fluid resuscitation. Fluid balance and the inflammatory response were comparable throughout the experiment in the intervention and control groups. The intervention counteracted the increase in proportion of fragmented hyaluronan associated with peritonitis-sepsis and was associated with lower modified shock index (MSI) than placebo.In Study IV, we administered an increased dose of HMW-HA directly after induction of peritonitis. The aim of Study IV was to study the effects of the intervention in a fluid restrictive model, to reduce a potentially negative effect of crystalloid infusion per se on the endothelial glycocalyx layer. In Study IV, hemodynamics and surrogate markers of endothelial damage were comparable in the intervention and control groups. The intervention was associated with an increase in cardiac output and diastolic blood pressure during the infusion, these effects disappeared as the experiment proceeded. Lactate was higher in the intervention group as a function of time.
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| 9. |
- Barrueta Tenhunen, Annelie, et al.
(författare)
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Does the antisecretory peptide AF-16 reduce lung oedema in experimental ARDS?
- 2019
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 124:4, s. 246-253
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with pulmonary capillary leakage and lung oedema formation. There is currently no pharmacologic treatment for the condition. The antisecretory peptide AF-16 reduces oedema in experimental traumatic brain injury. In this study, we tested AF-16 in an experimental porcine model of ARDS. Methods: Under surgical anaesthesia 12 piglets were subjected to lung lavage followed by 2 hours of injurious ventilation. Every hour for 4 hours, measurements of extravascular lung water (EVLW), mechanics of the respiratory system, and hemodynamics were obtained. Results: There was a statistically significant (p = 0.006, two-way ANOVA) reduction of EVLW in the AF-16 group compared with controls. However, this was not mirrored in any improvement in the wet-to-dry ratio of lung tissue samples, histology, inflammatory markers, lung mechanics, or gas exchange. Conclusions: This pilot study suggests that AF-16 might improve oedema resolution as indicated by a reduction in EVLW in experimental ARDS.
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| 10. |
- Barrueta Tenhunen, Annelie, et al.
(författare)
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Fluid restrictive resuscitation with high molecular weight hyaluronan infusion in early peritonitis sepsis
- 2023
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Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would counteract intravascular volume depletion and contribute to endothelial glycocalyx integrity in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with hyaluronan (n = 8) or 0.9% saline (n = 8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first 2 h of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output was higher in the intervention group during the infusion of hyaluronan (3.2 ± 0.5 l/min in intervention group vs 2.7 ± 0.2 l/min in the control group) (p = 0.039). The increase in lactate was more pronounced in the intervention group (3.2 ± 1.0 mmol/l in the intervention group and 1.7 ± 0.7 mmol/l in the control group) at the end of the experiment (p < 0.001). Concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 ± 0.2 ng/ml vs 0.5 ± 0.2 ng/ml, p = 0.292), heparan sulphate (1.23 ± 0.2 vs 1.4 ± 0.3 ng/ml, p = 0.211) and vascular adhesion protein 1 (7.0 ± 4.1 vs 8.2 ± 2.3 ng/ml, p = 0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. However, this finding is hampered by the short observation period and a beneficial effect of HMW-HA in peritonitis sepsis cannot be discarded based on the results of the present study.
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