JOAO BATISTA BORGES SOBRINHO DORINI
Projetos de Pesquisa
Unidades Organizacionais
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
7 resultados
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article Feasibility of Ga-68-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome(2016) RETAMAL, Jaime; SORENSEN, Jens; LUBBERINK, Mark; SUAREZ-SIPMANN, Fernando; BORGES, Joao Batista; FEINSTEIN, Ricardo; JALKANEN, Sirpa; ANTONI, Gunnar; HEDENSTIERNA, Goran; ROIVAINEN, Anne; LARSSON, Anders; VELIKYAN, IrinaThere is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [O-15]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting Ga-68-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([Ga-68]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [Ga-68]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (K-i) for the tissue perfusion resulted in 4-fold higher uptake rate of [Ga-68]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [Ga-68]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion.- Electrical impedance tomography in acute respiratory distress syndrome(2018) BACHMANN, M. Consuelo; MORAIS, Caio; BUGEDO, Guillermo; BRUHN, Alejandro; MORALES, Arturo; BORGES, Joao B.; COSTA, Eduardo; RETAMAL, JaimeAcute respiratory distress syndrome (ARDS) is a clinical entity that acutely affects the lung parenchyma, and is characterized by diffuse alveolar damage and increased pulmonary vascular permeability. Currently, computed tomography (CT) is commonly used for classifying and prognosticating ARDS. However, performing this examination in critically ill patients is complex, due to the need to transfer these patients to the CT room. Fortunately, new technologies have been developed that allow the monitoring of patients at the bedside. Electrical impedance tomography (EIT) is a monitoring tool that allows one to evaluate at the bedside the distribution of pulmonary ventilation continuously, in real time, and which has proven to be useful in optimizing mechanical ventilation parameters in critically ill patients. Several clinical applications of EIT have been developed during the last years and the technique has been generating increasing interest among researchers. However, among clinicians, there is still a lack of knowledge regarding the technical principles of EIT and potential applications in ARDS patients. The aim of this review is to present the characteristics, technical concepts, and clinical applications of EIT, which may allow better monitoring of lung function during ARDS.
- Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study(2018) RETAMAL, Jaime; HURTADO, Daniel; VILLARROEL, Nicolas; BRUHN, Alejandro; BUGEDO, Guillermo; AMATO, Marcelo Britto Passos; COSTA, Eduardo Leite Vieira; HEDENSTIERNA, Goeran; LARSSON, Anders; BORGES, Joao BatistaObjective: It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. Design: Retrospective analysis of CT images and positron emission tomography images using [F-18]fluoro-2-deoxy-D-glucose. Setting: University animal research laboratory. Subjects: Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. Interventions: Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4cm H2O) and high inspiratory pressures (mean plateau pressure, 45cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. Measurements and Main Results: The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.33.4 to 14.0 +/- 4.9mL/cm H2O; p < 0.05) and oxygenation (Pao(2)/Fio(2), 489 +/- 80 to 92 +/- 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F-18]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R-2 = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals. Conclusion: In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.
- Open lung approach ventilation abolishes the negative effects of respiratory rate in experimental lung injury(2016) RETAMAL, J.; BORGES, J. B.; BRUHN, A.; FEINSTEIN, R.; HEDENSTIERNA, G.; SUAREZ-SIPMANN, F.; LARSSON, A.BackgroundWe 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. MethodsTwelve 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. ResultsAfter the ARDS model was established, Cdyn,rs decreased from 21 3.3 to 9.0 +/- 1.8 ml/cmH(2)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. ConclusionContrary 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.
- High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS(2016) RETAMAL, J.; BORGES, J. B.; BRUHN, A.; CAO, X.; FEINSTEIN, R.; HEDENSTIERNA, G.; JOHANSSON, S.; SUAREZ-SIPMANN, F.; LARSSON, A.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-beta) 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-beta 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-beta 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-beta pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.
- Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation(2014) RETAMAL, Jaime; BERGAMINI, Bruno Curty; CARVALHO, Alysson R.; BOZZA, Fernando A.; BORZONE, Gisella; BORGES, Joao Batista; LARSSON, Anders; HEDENSTIERNA, Goeran; BUGEDO, Guillermo; BRUHN, AlejandroIntroduction: When 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. Methods: A 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 (V-T) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH(2)O (V(T)10/PEEP3); and 2) V-T=20 ml/kg and PEEP = 0 cmH2O (V(T)20/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. Results: Atelectasis 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 cm(3). 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 V(T)20/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-1 beta and cytokine-induced neutrophil chemoattractant-1 between regions. Conclusions: The 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.
- Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome(2017) SANTOS, Arnoldo; GOMEZ-PENALVER, Eva; MONGE-GARCIA, M. Ignacio; RETAMAL, Jaime; BORGES, Joao Batista; TUSMAN, Gerardo; HEDENSTIERNA, Goran; LARSSON, Anders; SUAREZ-SIPMANN, FernandoObjectives: To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Design: Experimental study. Setting: University animal research laboratory. Subjects: Twelve pigs (30.8 +/- 2.5 kg). Interventions: Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Measurements and Main Results: Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 +/- 252 vs 626 +/- 153 dyn. s/cm(5); p = 0.714), effective elastance, (0.63 +/- 0.22 vs 0.58 +/- 0.17 mm Hg/mL; p = 0.710), compliance (1.19 +/- 0.8 vs 1.50 +/- 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 +/- 0.04 vs 0.34 +/- 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 +/- 2.6 vs 10.5 +/- 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 +/- 1.3 vs 19.3 +/- 2.7 cm H2O; p < 0.001), and venous admixture (0.05 +/- 0.01 vs 0.22 +/- 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 +/- 3 vs 34 +/- 7 mm Hg; p = 0.045) despite of using a higher positive endexpiratory pressure (17.4 +/- 0.7 vs 9.5 +/- 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 +/- 0.16 vs 2.27 +/- 0.48 L/min; p = 0.005). Conclusions: In this experimental model, Acute Respiratory Distress Syndrome Network and open lung approach affected pulmonary vascular mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.