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.- THAM reduces CO2-associated increase in pulmonary vascular resistance - an experimental study in lung-injured piglets(2015) HOSTMAN, Staffan; BORGES, Joao Batista; SUAREZ-SIPMANN, Fernando; AHLGREN, Kerstin M.; ENGSTROM, Joakim; HEDENSTIERNA, Goran; LARSSON, AndersIntroduction: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl) aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR. Methods: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with V-T of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment. Results: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0 +/- 0.5 to 13.8 +/- 1.5 kPa and lowered pH from 7.40 +/- 0.01 to 7.12 +/- 0.06, whereas base excess (BE) remained stable at 2.7 +/- 2.3 mEq/L to 3.4 +/- 3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2 +/- 1.7 kPa and 22.6 +/- 3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8 +/- 3.5 and 31.2 +/- 2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329 +/- 77 dyn.s/m(5) and 255 +/- 43 dyn.s/m(5) in the 1-h and 3-h groups, respectively, compared with 450 +/- 141 dyn.s/m(5) in the controls), as were pulmonary arterial pressures. Conclusions: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.
- Early Inflammation Mainly Affects Normally and Poorly Aerated Lung in Experimental Ventilator-Induced Lung Injury*(2014) BORGES, Joao Batista; COSTA, Eduardo L. V.; SUAREZ-SIPMANN, Fernando; WIDSTROM, Charles; LARSSON, Anders; AMATO, Marcelo; HEDENSTIERNA, GoranObjective: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F-18]fluoro-2-deoxy-d-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [F-18]fluoro-2-deoxy-d-glucose in a porcine experimental model of early acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: A university animal research laboratory. Subjects: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls. Interventions: Lung injury was induced by 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 [F-18]fluoro-2-deoxy-d-glucose. CT scans were acquired at end expiration and end inspiration. Measurements and Main Results: [F-18]fluoro-2-deoxy-d-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [F-18]fluoro-2-deoxy-d-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [F-18]fluoro-2-deoxy-d-glucose uptakes similar to controls. Conclusions: The present findings suggest that normally and poorly aerated regionscorresponding to intermediate gravitational zonesare the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.
- 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.
- Comment on Borges et al. ""Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse"" Reply(2012) BORGES, Joao Batista; SUAREZ-SIPMANN, Fernando; COSTA, Eduardo L. V.; HEDENSTIERNA, Goran; AMATO, Marcelo
- 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.
- Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse(2012) BORGES, Joao Batista; SUAREZ-SIPMANN, Fernando; BOHM, Stephan H.; TUSMAN, Gerardo; MELO, Alexandre; MARIPUU, Enn; SANDSTROM, Mattias; PARK, Marcelo; COSTA, Eduardo L. V.; HEDENSTIERNA, Goran; AMATO, MarceloBorges JB, Suarez-Sipmann F, Bohm SH, Tusman G, Melo A, Maripuu E, Sandstrom M, Park M, Costa EL, Hedenstierna G, Amato M. Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse. J Appl Physiol 112: 225-236, 2012. First published September 29, 2011; doi: 10.1152/japplphysiol.01090.2010.-The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology that provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT)-based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6%, with a SD of 2.9%. This method outperformed the estimates of lung perfusion based on impedance pulsatility. In conclusion, we describe a novel method based on EIT for estimating regional lung perfusion at the bedside. In both healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this study has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.
- Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung(2015) BORGES, Joao Batista; COSTA, Eduardo L. V.; BERGQUIST, Maria; LUCCHETTA, Luca; WIDSTROM, Charles; MARIPUU, Enn; SUAREZ-SIPMANN, Fernando; LARSSON, Anders; AMATO, Marcelo B. P.; HEDENSTIERNA, GoranObjective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.