VERA LUIZA CAPELOZZI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
55 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 55
- A more gradual positive end-expiratory pressure increase reduces lung damage and improves cardiac function in experimental acute respiratory distress syndrome(2022) FERNANDES, Marcos V. S.; ROCHA, Nazareth N.; FELIX, Nathane S.; RODRIGUES, Gisele C.; SILVA, Luisa H. A.; COELHO, Mariana S.; FONSECA, Ana Carolina F.; TEIXEIRA, Ana Carolina G. M.; CAPELOZZI, Vera L.; PELOSI, Paolo; SILVA, Pedro L.; MARINI, John J.; ROCCO, Patricia R. M.Increases in positive end-expiratory pressure (PEEP) or recruitment maneuvers may increase stress in lung parenchyma, extracellular matrix, and lung vessels; however, adaptative responses may occur. We evaluated the effects of PEEP on lung damage and cardiac function when increased abruptly, gradually, or more gradually in experimental mild/moderate acute respiratory distress syndrome (ARDS) induced by Escherichia coli lipopolysaccharide intratracheally. After 24 h, Wistar rats (n = 48) were randomly assigned to four mechanical ventilation strategies according to PEEP levels: 1) 3 cmH(2)O for 2 h (control); 2) 3 cmH(2)O for 1 h followed by an abrupt increase to 9 cmH(2)O for 1 h (no adaptation time); 3) 3 cmH(2)O for 30 min followed by a gradual increase to 9 cmH(2)O over 30 min then kept constant for 1 h (shorter adaptation time); and 4) more gradual increase in PEEP from 3 cmH(2)O to 9 cmH(2)O over 1 h and kept constant thereafter (longer adaptation time). At the end of the experiment, oxygenation improved in the shorter and longer adaptation time groups compared with the no-adaptation and control groups. Diffuse alveolar damage and expressions of interleukin-6, club cell protein-16, vascular cell adhesion molecule-1, amphiregulin, decorin, and syndecan were higher in no adaptation time compared with other groups. Pulmonary arterial pressure was lower in longer adaptation time than in no adaptation (P = 0.002) and shorter adaptation time (P = 0.025) groups. In this model, gradually increasing PEEP limited lung damage and release of biomarkers associated with lung epithelial/endothelial cell and extracellular matrix damage, as well as the PEEP-associated increase in pulmonary arterial pressure. NEW & NOTEWORTHY In a rat model of Escherichia coli lipopolysaccharide-induced mild/moderate acute respiratory distress syndrome, a gradual PEEP increase (shorter adaptation time) effectively mitigated histological lung injury and biomarker release associated with lung inflammation, damage to epithelial cells, endothelial cells, and the extracellular matrix compared with an abrupt increase in PEEP. A more gradual PEEP increase (longer adaptation time) decreased lung damage, pulmonary vessel compression, and pulmonary arterial pressure.
- Biologic Impact of Mechanical Power at High and Low Tidal Volumes in Experimental Mild Acute Respiratory Distress Syndrome(2018) SANTOS, Raquel S.; MAIA, Ligia de A.; OLIVEIRA, Milena V.; SANTOS, Cintia L.; MORAES, Lillian; PINTO, Eliete F.; SAMARY, Cynthia dos S.; MACHADO, Joana A.; CARVALHO, Anna Carolinna; FERNANDES, Marcos Vinicius de S.; MARTINS, Vanessa; CAPELOZZI, Vera L.; MORALES, Marcelo M.; KOCH, Thea; ABREU, Marcelo Gama de; PELOSI, Paolo; SILVA, Pedro L.; ROCCO, Patricia R. M.Background: The authors hypothesized that low tidal volume (V-T) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of V-T and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS). Methods: Forty Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24h, 32 rats were randomly assigned to be mechanically ventilated (2 h) with a combination of different V-T (6 ml/kg and 11 ml/kg) and RR that resulted in low and high power. Power was calculated as energy (Delta P,(2)(L)/E,(L)) x RR (Delta P,(L) = transpulmonary driving pressure; E,(L) = lung elastance), and was three-fold higher in high than in low power groups. Eight rats were not mechanically ventilated and used for molecular biology analysis. Results: Diffuse alveolar damage score, which represents the severity of edema, atelectasis, and overdistension, was increased in high V-T compared to low V-T, in both low (low V-T: 11 [9 to 14], high V-T: 18 [15 to 20]) and high (low V-T: 19 [16 to 25], high V-T: 29 [27 to 30]) power groups. At high V-T, interleukin-6 and amphiregulin expressions were higher in high-power than in low-power groups. At high power, amphiregulin and club cell protein 16 expressions were higher in high V-T than in low V-T. Mechanical energy and power correlated well with diffuse alveolar damage score and interleukin-6, amphiregulin, and club cell protein 16 expression. Conclusions: In experimental mild ARDS, even at low V-T, high mechanical power promoted ventilator-induced lung injury. To minimize ventilator-induced lung injury, low V-T should be combined with low power.
- Gradually Increasing Tidal Volume May Mitigate Experimental Lung Injury in Rats(2019) FELIX, Nathane S.; SAMARY, Cynthia S.; CRUZ, Fernanda F.; ROCHA, Nazareth N.; FERNANDES, Marcos V. S.; MACHADO, Joana A.; BOSE-MADUREIRA, Rebecca L.; CAPELOZZI, Vera L.; PELOSI, Paolo; SILVA, Pedro L.; MARINI, John J.; ROCCO, Patricia R. M.Background: This study hypothesized that, in experimental mild acute respiratory distress syndrome, lung damage caused by high tidal volume (V T) could be attenuated if V T increased slowly enough to progressively reduce mechanical heterogeneity and to allow the epithelial and endothelial cells, as well as the extracellular matrix of the lung to adapt. For this purpose, different strategies of approaching maximal V T were tested. Methods: Sixty-four Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, animals were randomly assigned to receive mechanical ventilation with V T = 6 ml/kg for 2 h (control); V T = 6 ml/kg during hour 1 followed by an abrupt increase to V T = 22 ml/kg during hour 2 (no adaptation time); V T = 6 ml/kg during the first 30 min followed by a gradual V T increase up to 22 ml/kg for 30 min, then constant V T = 22 ml/kg during hour 2 (shorter adaptation time); and a more gradual V T increase, from 6 to 22 ml/ kg during hour 1 followed by V T = 22 ml/kg during hour 2 (longer adaptation time). All animals were ventilated with positive end-expiratory pressure of 3 cm H 2 O. Nonventilated animals were used for molecular biology analysis. Results: At 2 h, diffuse alveolar damage score and heterogeneity index were greater in the longer adaptation time group than in the control and shorter adaptation time animals. Gene expression of interleukin-6 favored the shorter (median [interquartile range], 12.4 [9.1-17.8]) adaptation time compared with longer (76.7 [20.8 to 95.4]; P = 0.02) and no adaptation (65.5 [18.1 to 129.4]) time (P = 0.02) strategies. Amphiregulin, metalloproteinase-9, club cell secretory protein-16, and syndecan showed similar behavior. Conclusions: In experimental mild acute respiratory distress syndrome, lung damage in the shorter adaptation time group compared with the no adaptation time group was attenuated in a time-dependent fashion by preemptive adaptation of the alveolar epithelial cells and extracellular matrix. Extending the adaptation period increased cumulative power and did not prevent lung damage, because it may have exposed animals to injurious strain earlier and for a longer time, thereby negating any adaptive benefit.
- Comparison of different degrees of variability in tidal volume to prevent deterioration of respiratory system elastance in experimental acute lung inflammation(2016) KISS, T.; SILVA, P. L.; HUHLE, R.; MORAES, L.; SANTOS, R. S.; FELIX, N. S.; SANTOS, C. L.; MORALES, M. M.; CAPELOZZI, V. L.; KASPER, M.; PELOSI, P.; ABREU, M. Gama de; ROCCO, P. R. M.Background: Variable ventilation improves respiratory function, but it is not known whether the amount of variability in tidal volume (VT) can be reduced in recruited lungs without a deterioration of respiratory system elastance. Methods: Acute lung inflammation was induced by intratracheal instillation of lipopolysaccharide in 35 Wistar rats. Twenty-eight animals were anaesthetized and ventilated in volume-controlled mode. Lungs were recruited by random variation of VT (mean 6 ml kg(-1), coefficient of variation 30%, normal distribution) for 30 min. Animals were randomly assigned to different amounts of VT variability (n=7 for 90 min per group): 30, 15, 7.5, or 0%. Lung function, diffuse alveolar damage, and gene expression of biological markers associated with cell mechanical stress, inflammation, and fibrogenesis were assessed. Seven animals were not ventilated and served as controls for post-mortem analyses. Results: AV(T) variability of 30%, but not 15, 7.5, or 0%, prevented deterioration of respiratory system elastance [Mean (SD) -7.5 (8.7%), P<0.05; 21.1 (9.6%), P<0.05; 43.3 (25.9), P<0.05; and 41.2 (16.4), P<0.05, respectively]. Diffuse alveolar damagewas lower with a VT variability of 30% than with 0% and without ventilation, because of reduced oedema and haemorrhage. AVT variability of 30, 15, or 7.5% reduced the gene expression of amphiregulin, cytokine-induced neutrophil chemoattractant-1, and tumour necrosis factor a compared with a VT variability of 0%. Conclusions: In this model of acute lung inflammation, a VT variability of 30%, compared with 15 and 7.5%, was necessary to avoid deterioration of respiratory system elastance and was not associated with lung histological damage.
- Static and Dynamic Transpulmonary Driving Pressures Affect Lung and Diaphragm Injury during Pressure-controlled versus Pressure-support Ventilation in Experimental Mild Lung Injury in Rats(2020) PINTO, Eliete F.; SANTOS, Raquel S.; ANTUNES, Mariana A.; MAIA, Ligia A.; PADILHA, Gisele A.; MACHADO, Joana de A.; CARVALHO, Anna C. F.; FERNANDES, Marcos V. S.; CAPELOZZI, Vera L.; ABREU, Marcelo Gama de; PELOSI, Paolo; ROCCO, Patricia R. M.; SILVA, Pedro L.Background: Pressure-support ventilation may worsen lung damage due to increased dynamic transpulmonary driving pressure. The authors hypothesized that, at the same tidal volume (V-T) and dynamic transpulmonary driving pressure, pressure-support and pressure-controlled ventilation would yield comparable lung damage in mild lung injury. Methods: Male Wistar rats received endotoxin intratracheally and, after 24 h, were ventilated in pressure-support mode. Rats were then randomized to 2 h of pressure-controlled ventilation with V-T, dynamic transpulmonary driving pressure, dynamic transpulmonary driving pressure, and inspiratory time similar to those of pressure-support ventilation. The primary outcome was the difference in dynamic transpulmonary driving pressure between pressure-support and pressure-controlled ventilation at similar V-T; secondary outcomes were lung and diaphragm damage. Results: At V-T = 6 ml/kg, dynamic transpulmonary driving pressure was higher in pressure-support than pressure-controlled ventilation (12.0 +/- 2.2 vs. 8.0 +/- 1.8 cm H2O), whereas static transpulmonary driving pressure did not differ (6.7 +/- 0.6 vs. 7.0 +/- 0.3 cm H2O). Diffuse alveolar damage score and gene expression of markers associated with lung inflammation (interleukin-6), alveolar-stretch (amphiregulin), epithelial cell damage (club cell protein 16), and fibrogenesis (metalloproteinase-9 and type III procollagen), as well as diaphragm inflammation (tumor necrosis factor-alpha) and proteolysis (muscle RING-finger-1) were comparable between groups. At similar dynamic transpulmonary driving pressure, as well as dynamic transpulmonary driving pressure and inspiratory time, pressure-controlled ventilation increased V-T, static transpulmonary driving pressure, diffuse alveolar damage score, and gene expression of markers of lung inflammation, alveolar stretch, fibrogenesis, diaphragm inflammation, and proteolysis compared to pressure-support ventilation. Conclusions: In the mild lung injury model use herein, at the same V-T, pressure-support compared to pressure-controlled ventilation did not affect biologic markers. However, pressure-support ventilation was associated with a major difference between static and dynamic transpulmonary driving pressure; when the same dynamic transpulmonary driving pressure and inspiratory time were used for pressure-controlled ventilation, greater lung and diaphragm injury occurred compared to pressure-support ventilation.
- Variable Ventilation Improved Respiratory System mechanics and Ameliorated pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion(2017) SOLURI-MARTINS, Andre; MORAES, Lillian; SANTOS, Raquel S.; SANTOS, Cintia L.; HUHLE, Robert; CAPELOZZI, Vera L.; PELOSI, Paolo; SILVA, Pedro L.; ABREU, Marcelo Gama de; ROCCO, Patricia R. M.Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV (n = 6/group) [tidal volume (V-T) = 6 mL/kg, positive endexpiratory pressure (PEEP) = 2 cmH(2)O, fraction of inspired oxygen (FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated V-T values (n = 1200; mean V-T = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory systemmechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean +/- SD, VCV 3.6 +/- 1.3 cmH20/ml and 2.0 +/- 0.8 cmH(2)O/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.
- Endotoxin-Induced Emphysema Exacerbation: A Novel Model of Chronic Obstructive Pulmonary Disease Exacerbations Causing Cardiopulmonary Impairment and Diaphragm Dysfunction(2019) OLIVEIRA, Milena Vasconcellos de; ROCHA, Nazareth de Novaes; SANTOS, Raquel Souza; ROCCO, Marcella Rieken Macedo; MAGALHAES, Raquel Ferreira de; SILVA, Johnatas Dutra; SOUZA, Sergio Augusto Lopes; CAPELOZZI, Vera Luiza; PELOSI, Paolo; SILVA, Pedro Leme; ROCCO, Patricia Rieken MacedoChronic obstructive pulmonary disease (COPD) is a progressive disorder of the lung parenchyma which also involves extrapulmonary manifestations, such as cardiovascular impairment, diaphragm dysfunction, and frequent exacerbations. The development of animal models is important to elucidate the pathophysiology of COPD exacerbations and enable analysis of possible therapeutic approaches. We aimed to characterize a model of acute emphysema exacerbation and evaluate its consequences on the lung, heart, and diaphragm. Twenty-four Wistar rats were randomly assigned into one of two groups: control (C) or emphysema (ELA). In ELA group, animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. The C group received saline under the same protocol. Five weeks after the last instillation, C and ELA animals received saline (SAL) or E. coil lipopolysaccharide (LPS) (200 mu g in 200 mu l) intratracheally. Twenty-four hours after saline or endotoxin administration, arterial blood gases, lung inflammation and morphometry, collagen fiber content, and lung mechanics were analyzed. Echocardiography, diaphragm ultrasonography (US), and computed tomography (CT) of the chest were done. ELA-LPS animals, compared to ELA-SAL, exhibited decreased arterial oxygenation; increases in alveolar collapse (p < 0.0001), relative neutrophil counts (p = 0.007), levels of cytokine-induced neutrophil chemoattractant-1, interleukin (IL)-1 beta, tumor necrosis factor-alpha, IL-6, and vascular endothelial growth factor in lung tissue, collagen fiber deposition in alveolar septa, airways, and pulmonary vessel walls, and dynamic lung elastance (p < 0.0001); reduced pulmonary acceleration time/ejection time ratio, (an indirect index of pulmonary arterial hypertension); decreased diaphragm thickening fraction and excursion; and areas of emphysema associated with heterogeneous alveolar opacities on chest CT. In conclusion, we developed a model of endotoxin-induced emphysema exacerbation that affected not only the lungs but also the heart and diaphragm, thus resembling several features of human disease. This model of emphysema should allow preclinical testing of novel therapies with potential for translation into clinical practice.
conferenceObject Variable Ventilation Reduces Lung Damage Without Increasing Bacterial Translocation From The Lung Into The Systemic Circulation In A Rat Model Of Pneumonia(2016) MAGALHAES, R. F.; SAMARY, C. S.; SANTOS, R. S.; VASCONCELLOS, M. D. O.; ROCHA, N. N.; KITOKO, J. Z.; SILVA, C. A.; HILDEBRANDT, C.; ALBUQUERQUE, C. F.; SANTOS, C. L.; HUHLE, R.; FARIA-NETO, H. C.; CAPELOZZI, V. L.; MORALES, M. M.; OLSEN, P.; PELOSI, P.; ABREU, M. Gama De; ROCCO, P. R. M.; SILVA, P. L.- Rapid On-Site Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspirations for the Diagnosis of Lung Cancer A Perspective From Members of the Pulmonary Pathology Society(2018) JAIN, Deepali; ALLEN, Timothy Craig; AISNER, Dara L.; BEASLEY, Mary Beth; CAGLE, Philip T.; CAPELOZZI, Vera Luiza; HARIRI, Lida P.; LANTUEJOUL, Sylvie; MILLER, Ross; MINO-KENUDSON, Mari; MONACO, Sara E.; MOREIRA, Andre; RAPARIA, Kirtee; REKHTMAN, Natasha; RODEN, Anja Christiane; ROY-CHOWDHURI, Sinchita; SANTOS, Gilda da Cunha; THUNNISSEN, Erik; TRONCONE, Giancarlo; VIVERO, MarinaContext.-Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer. Objective.-To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer. Data Sources.-An electronic literature search in PubMed and Google databases was performed using the following key words: cytology, lung cancer, on-site evaluation, rapid on-site evaluation, and ROSE EBUS-TBNA. Only articles published in English were included in this review. Conclusions.-Rapid on-site evaluation can ensure that the targeted lesion is being sampled and can enable appropriate specimen triage. If available, it should be used with EBUS-TBNA in the diagnosis of lung cancer because it can minimize repeat procedures for additional desired testing (ie, molecular studies). Some studies have shown that ROSE does not adversely affect the number of aspirations, total procedure time of EBUS-TBNA, or the rate of postprocedure complications; it is also helpful in providing a preliminary diagnosis that can reduce the number of additional invasive procedures, such as mediastinoscopy. As EBUS technology continues to evolve, our knowledge of the role of ROSE in EBUS-TBNA for the diagnosis of lung cancer will also continue to grow and evolve.
- Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats(2018) SAMARY, Cynthia S.; RAMOS, Alane B.; MAIA, Ligia A.; ROCHA, Nazareth N.; SANTOS, Cintia L.; MAGALHAES, Raquel F.; CLEVELARIO, Amanda L.; PIMENTEL-COELHO, Pedro M.; MENDEZ-OTERO, Rosalia; CRUZ, Fernanda F.; CAPELOZZI, Vera L.; FERREIRA, Tatiana P. T.; KOCH, Thea; ABREU, Marcelo Gama de; SANTOS, Claudia C. dos; PELOSI, Paolo; SILVA, Pedro L.; ROCCO, Patricia R. M.Background: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. Methods: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naive rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Results: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-alpha and IL-6) and in BALF (TNF-alpha). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naive rats only upregulated expression of TNF-alpha and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-alpha and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. Conclusions: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.