JOAO BATISTA BORGES SOBRINHO DORINI
Projetos de Pesquisa
Unidades Organizacionais
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
8 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.- Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities(2016) BORGES, J. B.; PORRA, L.; PELLEGRINI, M.; TANNOIA, A.; DEROSA, S.; LARSSON, A.; BAYAT, S.; PERCHIAZZI, G.; HEDENSTIERNA, G.BackgroundIt is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. MethodsIn a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV.). Heterogeneity of ventilation was calculated as the coefficient of variation in sV. (CVsV.). The coefficient of variation in lung densities (CVD) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FIO2 0.21; ZEEP and FIO2 1.0; PEEP 12 cmH(2)O and F(I)O(2)1.0 (Open Lung-PEEP = OLP). ResultsThe mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV. and poor aeration at ZEEP-0.21 than at OLP: 12.9 9.0 vs. 0.6 +/- 0.4% in the non-dependent level, and 17.5 +/- 8.2 vs. 0.4 +/- 0.1% in the dependent one (P = 0.041). The CVsV. of the total imaged lung at PEEP 12 cmH(2)O was significantly lower than on ZEEP, regardless of FIO2, indicating more heterogeneity of ventilation during ZEEP (0.23 +/- 0.03 vs. 0.54 +/- 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. ConclusionZEEP together with low FIO2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.
- How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography(2012) MATOS, Gustavo F. J. de; STANZANI, Fabiana; PASSOS, Rogerio H.; FONTANA, Mauricio F.; ALBALADEJO, Renata; CASERTA, Raquel E.; SANTOS, Durval C. B.; BORGES, Joao Batista; AMATO, Marcelo B. P.; BARBAS, Carmen S. V.Introduction: The benefits of higher positive end expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) have been modest, but few studies have fully tested the ""open-lung hypothesis"". This hypothesis states that most of the collapsed lung tissue observed in ARDS can be reversed at an acceptable clinical cost, potentially resulting in better lung protection, but requiring more intensive maneuvers. The short-/middle-term efficacy of a maximum recruitment strategy (MRS) was recently described in a small physiological study. The present study extends those results, describing a case-series of non-selected patients with early, severe ARDS submitted to MRS and followed until hospital discharge or death. Methods: MRS guided by thoracic computed tomography (CT) included two parts: a recruitment phase to calculate opening pressures (incremental steps under pressure-controlled ventilation up to maximum inspiratory pressures of 60 cmH(2)O, at constant driving-pressures of 15 cmH(2)O); and a PEEP titration phase (decremental PEEP steps from 25 to 10 cmH2O) used to estimate the minimum PEEP to keep lungs open. During all steps, we calculated the size of the non-aerated (-100 to +100 HU) compartment and the recruitability of the lungs (the percent mass of collapsed tissue re-aerated from baseline to maximum PEEP). Results: A total of 51 severe ARDS patients, with a mean age of 50.7 years (84% primary ARDS) was studied. The opening plateau-pressure was 59.6 (+/- 5.9 cmH(2)O), and the mean PEEP titrated after MRS was 24.6 (+/- 2.9 cmH(2)O). Mean PaO2/FiO(2) ratio increased from 125 (+/- 43) to 300 (+/- 103; P < 0.0001) after MRS and was sustained above 300 throughout seven days. Non-aerated parenchyma decreased significantly from 53.6% (interquartile range (IQR): 42.5 to 62.4) to 12.7% (IQR: 4.9 to 24.2) (P < 0.0001) after MRS. The potentially recruitable lung was estimated at 45% (IQR: 25 to 53). We did not observe major barotrauma or significant clinical complications associated with the maneuver. Conclusions: MRS could efficiently reverse hypoxemia and most of the collapsed lung tissue during the course of ARDS, compatible with a high lung recruitability in non-selected patients with early, severe ARDS. This strategy should be tested in a prospective randomized clinical trial.
- 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 in Lateral Decubitus With Differential Selective Positive End-Expiratory Pressure in an Experimental Model of Early Acute Respiratory Distress Syndrome(2015) BORGES, Joao Batista; SENTURK, Mert; AHLGREN, Oskar; HEDENSTIERNA, Goran; LARSSON, AndersObjective: After lung recruitment, lateral decubitus and differential lung ventilation may enable the titration and application of optimum-selective positive end-expiratory pressure values for the dependent and nondependent lungs. We aimed at compare the effects of optimum-selective positive end-expiratory pressure with optimum global positive end-expiratory pressure on regional collapse and aeration distribution in an experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Seven piglets. Interventions: A one-hit injury acute respiratory distress syndrome model was established by repeated lung lavages. After replacing the tracheal tube by a double-lumen one, we initiated lateral decubitus and differential ventilation. After maximum-recruitment maneuver, decremental positive end-expiratory pressure titration was performed. The positive end-expiratory pressure corresponding to maximum dynamic compliance was defined globally (optimum global positive end-expiratory pressure) and for each individual lung (optimum-selective positive end-expiratory pressure). After new maximum-recruitment maneuver, two steps were performed in randomized order (15 min each): ventilation applying the optimum global positive end-expiratory pressure and the optimum-selective positive end-expiratory pressure. CT scans were acquired at end expiration and end inspiration. Measurements and Main Results: Aeration homogeneity was evaluated as a nondependent/dependent ratio (percent of total gas content in upper lung/percent of total gas content in lower lung) and tidal recruitment as the difference in the percent mass of nonaerated tissue between expiration and inspiration. At the end of the 15-minute optimum-selective positive end-expiratory pressure, compared with the optimum global positive end-expiratory pressure, resulted in 1) decrease in the percent mass of collapse in the lower lung at expiratory CT (19% 15% vs 4% +/- 5%; p = 0.03); 2) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-expiratory-CT and optimum-selective positive end-expiratory pressure-expiratory-CT (3.7 +/- 1.2 vs 0.8 +/- 0.5; p = 0.01); 3) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-inspiratory-CT and optimum-selective positive end-expiratory pressure-inspiratory-CT (2.8 +/- 1.1 vs 0.6 +/- 0.3; p = 0.01); and 4) less tidal recruitment (p = 0.049). Conclusions: After maximum lung recruitment, lateral decubitus and differential lung ventilation enabled the titration of optimum-selective positive end-expiratory pressure values for the dependent and the nondependent lungs, made possible the application of an optimized regional open lung approach, promoted better aeration distribution, and minimized lung tissue inhomogeneities.
- There is no cephalocaudal gradient of computed tomography densities or lung behavior in supine patients with acute respiratory distress syndrome(2016) EL-DASH, S. A.; BORGES, J. B.; COSTA, E. L. V.; TUCCI, M. R.; RANZANI, O. T.; CARAMEZ, M. P.; CARVALHO, C. R. R.; AMATO, M. B. P.Background: There is debate whether pressure transmission within the lungs and alveolar collapse follow a hydrostatic pattern or the compression exerted by the weight of the heart and the diaphragm causes collapse localized in the areas adjacent to these structures. The second hypothesis proposes the existence of a cephalocaudal gradient in alveolar collapse. We aimed to define whether or not lung density and collapse follow a 'liquid-like' pattern with homogeneous isogravitational layers along the cephalocaudal axis in acute respiratory distress syndrome lungs. Methods: Acute respiratory distress syndrome patients were submitted to full lung computed tomography scans at positive end-expiratory pressure (PEEP) zero (before) and 25 cmH(2)O after a maximum-recruitment maneuver. PEEP was then decreased by 2 cmH2O every 4 min, and a semi-complete scan performed at the end of each PEEP step. Results: Lung densities were homogeneous within each lung layer. Lung density increased along the ventrodorsal axis toward the dorsal region (beta = 0.49, P < 0.001), while there was no increase, but rather a slight decrease, toward the diaphragm along the cephalocaudal axis and toward the heart. Higher PEEP attenuated density gradients. At PEEP 18 cmH2O, dependent lung regions started to collapse massively, while best compliance was only reached at a lower PEEP. Conclusions: We could not detect cephalocaudal gradients in lung densities or in alveolar collapse. Likely, external pressures applied on the lung by the chest wall, organs, and effusions are transmitted throughout the lung in a hydrostatic pattern with homogeneous consequences at each isogravitational layer. A single cross-sectional image of the lung could fully represent the heterogeneous mechanical properties of dependent and non-dependent lung regions.
- 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.
- Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial(2016) KACMAREK, Robert M.; VILLAR, Jesus; SULEMANJI, Demet; MONTIEL, Raquel; FERRANDO, Carlos; BLANCO, Jesus; KOH, Younsuck; SOLER, Juan Alfonso; MARTINEZ, Domingo; HERNANDEZ, Marianela; TUCCI, Mauro; BORGES, Joao Batista; LUBILLO, Santiago; SANTOS, Arnoldo; ARAUJO, Juan B.; AMATO, Marcelo B. P.; SUAREZ-SIPMANN, FernandoObjective: The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial. We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach resulting in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome. Design: A prospective, multicenter, pilot, randomized controlled trial. Setting: A network of 20 multidisciplinary ICUs. Patients: Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study. Interventions: At 12-36 hours after acute respiratory distress syndrome onset, patients were assessed under standardized ventilator settings (Fio(2)0.5, positive end-expiratory pressure 10 cm H2O). If Pao(2)/Fio(2) ratio remained less than or equal to 200 mm Hg, patients were randomized to open lung approach or Acute Respiratory Distress Syndrome network protocol. All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight. Measurements and Main Results: From 1,874 screened patients with acute respiratory distress syndrome, 200 were randomized: 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol. Main outcome measures were 60-day and ICU mortalities, and ventilator-free days. Mortality at day-60 (29% open lung approach vs. 33% Acute Respiratory Distress Syndrome Network protocol, p = 0.18, log rank test), ICU mortality (25% open lung approach vs. 30% Acute Respiratory Distress Syndrome network protocol, p = 0.53 Fisher's exact test), and ventilator-free days (8 [0-20] open lung approach vs. 7 [0-20] d Acute Respiratory Distress Syndrome network protocol, p = 0.53 Wilcoxon rank test) were not significantly different. Airway driving pressure (plateau pressure - positive end-expiratory pressure) and Pao(2)/Fio(2) improved significantly at 24, 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol. Barotrauma rate was similar in both groups. Conclusions: In patients with established acute respiratory distress syndrome, open lung approach improved oxygenation and driving pressure, without detrimental effects on mortality, ventilator-free days, or barotrauma. This pilot study supports the need for a large, multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome.