RESUMO
BACKGROUND: Considerable evidence indicates that a signaling crosstalk between the brain and periphery plays important roles in neurological disorders, and that both acute and chronic peripheral inflammation can produce brain changes leading to cognitive impairments. Recent clinical and epidemiological studies have revealed an increased risk of cognitive impairment and dementia in individuals with impaired pulmonary function. However, the mechanistic underpinnings of this association remain unknown. Exposure to SiO2 (silica) particles triggers lung inflammation, including infiltration by peripheral immune cells and upregulation of pro-inflammatory cytokines. We here utilized a mouse model of lung silicosis to investigate the crosstalk between lung inflammation and memory. METHODS: Silicosis was induced by intratracheal administration of a single dose of 2.5 mg SiO2/kg in mice. Molecular and behavioral measurements were conducted 24 h and 15 days after silica administration. Lung and hippocampal inflammation were investigated by histological analysis and by determination of pro-inflammatory cytokines. Hippocampal synapse damage, amyloid-ß (Aß) peptide content and phosphorylation of Akt, a proxy of hippocampal insulin signaling, were investigated by Western blotting and ELISA. Memory was assessed using the open field and novel object recognition tests. RESULTS: Administration of silica induced alveolar collapse, lung infiltration by polymorphonuclear (PMN) cells, and increased lung pro-inflammatory cytokines. Lung inflammation was followed by upregulation of hippocampal pro-inflammatory cytokines, synapse damage, accumulation of the Aß peptide, and memory impairment in mice. CONCLUSION: The current study identified a crosstalk between lung and brain inflammatory responses leading to hippocampal synapse damage and memory impairment after exposure to a single low dose of silica in mice.
Assuntos
Pneumonia , Silicose , Animais , Camundongos , Dióxido de Silício/toxicidade , Camundongos Endogâmicos C57BL , Silicose/patologia , Pneumonia/induzido quimicamente , Pneumonia/patologia , Inflamação/induzido quimicamente , Inflamação/patologia , Pulmão/patologia , Sinapses/patologia , Peptídeos beta-Amiloides , Hipocampo/patologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/patologia , CitocinasRESUMO
Panic disorder (PD) pathophysiology is very heterogeneous, and the discrimination of distinct subtypes could be very useful. A subtype based on respiratory symptoms is known to constitute a specific subgroup. However, evidence to support the respiratory subtype (RS) as a distinct subgroup of PD with a well-defined phenotype remains controversial. Studies have focused on characterization of the RS based on symptoms and response to CO2. In this line, we described clinical and biological aspects focused on symptomatology and CO2 challenge tests in PD RS. The main symptoms that characterize RS are dyspnea (shortness of breath) and a choking sensation. Moreover, patients with the RS tended to be more responsive to CO2 challenge tests, which triggered more panic attacks in this subgroup. Future studies should focus on discriminating respiratory-related clusters and exploring psychophysiological and neuroimaging outcomes in order to provide robust evidence to confirm RS as a distinct subtype of PD.
Assuntos
Humanos , Dióxido de Carbono/sangue , Transtorno de Pânico/fisiopatologia , Ventilação Pulmonar/fisiologia , Hiperventilação/fisiopatologia , Psicopatologia , Psicofisiologia , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/psicologia , Dispneia/etiologia , Hiperventilação/diagnóstico , Hiperventilação/psicologiaRESUMO
Panic disorder (PD) pathophysiology is very heterogeneous, and the discrimination of distinct subtypes could be very useful. A subtype based on respiratory symptoms is known to constitute a specific subgroup. However, evidence to support the respiratory subtype (RS) as a distinct subgroup of PD with a well-defined phenotype remains controversial. Studies have focused on characterization of the RS based on symptoms and response to CO2. In this line, we described clinical and biological aspects focused on symptomatology and CO2 challenge tests in PD RS. The main symptoms that characterize RS are dyspnea (shortness of breath) and a choking sensation. Moreover, patients with the RS tended to be more responsive to CO2 challenge tests, which triggered more panic attacks in this subgroup. Future studies should focus on discriminating respiratory-related clusters and exploring psychophysiological and neuroimaging outcomes in order to provide robust evidence to confirm RS as a distinct subtype of PD.
Assuntos
Dióxido de Carbono/sangue , Hiperventilação/fisiopatologia , Transtorno de Pânico/fisiopatologia , Ventilação Pulmonar/fisiologia , Dispneia/etiologia , Humanos , Hiperventilação/diagnóstico , Hiperventilação/psicologia , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/psicologia , Psicopatologia , PsicofisiologiaRESUMO
Acute lung injury (ALI) remains a major cause of mortality. In lipopolysaccharide (LPS)-stimulated macrophages, eugenol reduces cyclooxygenase-2 expression, NF-κB activation, and inflammatory mediators. We examined the anti-inflammatory and anti-oxidative action of eugenol in an in vivo model of LPS-induced lung injury. Lung mechanics and histology were analyzed in mice 24â¯h after LPS exposure, with and without eugenol treatment at different doses. Additional animals, submited to the same protocol, were treated with eugenol at 150â¯mg/kg to determine its effect on inflammatory cytokines (ELISA) and oxidative markers. LPS-induced lung functional and histological changes were significantly improved by eugenol, in a dose-dependent way. Furthermore, eugenol (150â¯mg/kg) was able to inhibit the release of inflammatory cytokines (TNF-α, IL-1ß and IL-6), NADPH oxidase activity, as well as antioxidant enzymes activity (superoxide dismutase, catalase and glutathione peroxidase). Finally, eugenol reduced LPS-induced protein oxidation. In conclusion, eugenol improved in vivo LPS-induced ALI through both anti-inflammatory and anti-oxidative effects, avoiding damage to lung structure.
Assuntos
Anti-Inflamatórios/uso terapêutico , Eugenol/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Lesão Pulmonar/complicações , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NADPH Oxidases/metabolismo , Pneumologia/métodos , Estatísticas não ParamétricasRESUMO
Background: Laparoscopic surgery with pneumoperitoneum increases respiratory system elastance due to the augmented intra-abdominal pressure. We aim to evaluate to which extent positive end-expiratory pressure (PEEP) is able to counteract abdominal hypertension preventing progressive lung collapse and how rib cage elastance influences PEEP effect. Methods: Forty-four Wistar rats were mechanically ventilated and randomly assigned into three groups: control (CTRL), pneumoperitoneum (PPT) and pneumoperitoneum with restricted rib cage (PPT-RC). A pressure-volume (PV) curve followed by a recruitment maneuver and a decremental PEEP trial were performed in all groups. Thereafter, animals were ventilated using PEEP of 3 and 8 cmH2O divided into two subgroups used to evaluate respiratory mechanics or computed tomography (CT) images. In 26 rats, we compared respiratory system elastance (Ers) at the two PEEP levels. In 18 animals, CT images were acquired to calculate total lung volume (TLV), total volume and air volume in six anatomically delimited regions of interest (three along the cephalo-caudal and three along the ventro-dorsal axes). Results: PEEP of minimal Ers was similar in CTRL and PPT groups (3.8 ± 0.45 and 3.5 ± 3.89 cmH2O, respectively) and differed from PPT-RC group (9.8 ± 0.63 cmH2O). Chest restriction determined a right- and downward shift of the PV curve, increased Ers and diminished TLV and lung aeration. Increasing PEEP augmented TLV in CTRL group (11.8 ± 1.3 to 13.6 ± 2 ml, p < 0.05), and relative air content in the apex of PPT group (3.5 ± 1.4 to 4.6 ± 1.4% TLV, p < 0.03) and in the middle zones in PPT-RC group (21.4 ± 1.9 to 25.3 ± 2.1% TLV cephalo-caudally and 18.1 ± 4.3 to 22.0 ± 3.3% TLV ventro-dorsally, p < 0.005). Conclusion: Regional lung recruitment potential during pneumoperitoneum depends on rib cage elastance, reinforcing the concept of PEEP individualization according to the patient's condition.
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Murine papain-induced emphysema is a model that reproduces many of the features found in patients. Bone marrow-derived mononuclear cells (BMMC) have already been used to repair the alveolar epithelium in respiratory diseases, but not in the papain model. Thus, we hypothesized that BMMC could prevent the pathophysiological processes in papain-induced experimental emphysema. Female BALB/c mice received intratracheal instillation of 50 µL of saline (S groups) or papain (P groups, 10 IU/50 µl of saline) on days 1 and 7 of the experimental protocol. On the 14th day, 2 × 106 BMMC of male BALB/c mice (SC21 and PC21) or saline (SS21 and PS21) were injected by the jugular vein. Analyses were done on days 14 (S14 and P14) and 21 (SS21, PS21, SC21, and PC21) of the protocol. qPCR evaluated the presence of the Y chromosome in the lungs of BMMC recipient animals. Functional residual capacity (FRC), alveolar diameter, cellularity, elastic fiber content, concentrations of TNF-α, IL-1ß, IL-6, MIP-2, KC, IFN-γ, apoptosis, mRNA expression of the dual oxidase (DUOX1 and DUOX2), production of H2O2 and DUOX activity were evaluated in lung tissue. We did not detect the Y chromosome in recipients' lungs. FRC, alveolar diameter, polymorphonuclear cells (PMN) and levels of KC, MIP-2, and IFN-γ increased in P14 and PS21 groups; the changes in the latter were reverted by BMMC. TNF-α, IL-1ß e IL-6 were similar in all groups. The amount of elastic fibers was smaller in P14 and PS21 than in other groups, and BMMC did not increase it in PC21 mice. PS21 animals showed increased DUOX activity and mRNA expression for DUOX1 and 2. Cell therapy reverted the activity of DUOX and mRNA expression of DUOX1. BMMC reduced mRNA expression of DUOX2. Apoptosis index was elevated in PS21 mice, which was reduced by cell therapy in PC21. Static compliance, viscoelastic component of elastance and pressure to overcome viscoelasticity were increased in P14 and PS21 groups. These changes and the high resistive pressure found on day 21 were reverted by BMMC. In conclusion, BMMC showed potent anti-inflammatory, antiapoptotic, antioxidant, and restorative roles in papain-triggered pulmonary emphysema.
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Microcystins-LR (MC-LR) is a cyanotoxin produced by cyanobacteria. We evaluated the antioxidant potential of LASSBio-596 (LB-596, inhibitor of phosphodiesterases 4 and 5), per os, and biochemical markers involved in lung and liver injury induced by exposure to sublethal dose of MC-LR. Fifty male Swiss mice received an intraperitoneal injection of 60 µL of saline (CTRL group, n = 20) or a sublethal dose of MC-LR (40 µg/kg, TOX group, n = 20). After 6 h the animals received either saline (TOX and CTRL groups) or LB-596 (50 mg/kg, TOX + LASS group, n = 10) by gavage. At 6 h after exposure, respiratory mechanics was evaluated in 10 CTRL and 10 TOX mice: there was a significant increase of all lung mechanics parameters (static elastance, viscoelastic component of elastance and lung resistive and viscoelastic/inhomogeneous pressures) in TOX compared to CTRL. 8 h after saline or MC-LR administration, i.e., 2 h after treatment with LB-596, blood serum levels of alanine aminotransferase and aspartate aminotransferase, activity of superoxide dismutase, catalase, and content of malondialdehyde and carbonyl in lung and liver, NADPH oxidase 2 and 4 mRNA expressions, dual oxidase enzyme activity and H2O2 generation were analyzed in lung homogenates. All parameters were significantly higher in TOX than in the other groups. There was no significant difference between CTRL and TOX + LASS. MC-LR deteriorated lung and liver functions and induced redox imbalance in them, which was prevented by oral administration of LB-596.
Assuntos
Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Microcistinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ácidos Ftálicos/farmacologia , Sulfonamidas/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/metabolismo , Fígado/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Toxinas Marinhas , Camundongos , Oxirredução , Ácidos Ftálicos/administração & dosagem , Sulfonamidas/administração & dosagemRESUMO
Recently, several studies have reported that respiratory disease may be associated with an increased production of free radicals. In this context, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) is a free radical-generating compound widely used to mimic the oxidative stress state. We aimed to investigate whether AAPH can generate lung functional, inflammatory, histological and biochemical impairments in the lung. Wistar rats were divided into five groups and instilled with saline solution (714 µL/kg, CTRL group) or different amounts of AAPH (25, 50, 100, and 200 mg/kg, 714 µL/kg, AAPH groups). Seventy-two hours later the animals were anesthetized, paralyzed, intubated and static elastance (Est), viscoelastic component of elastance (ΔE), resistive (ΔP1) and viscoelastic (ΔP2) pressures were measured. Oxidative damage, inflammatory markers and lung morphometry were analyzed. ΔP1 and Est were significantly higher in AAPH100 and AAPH200 than in the other groups. The bronchoconstriction indexes were larger in AAPH groups than in CTRL. The area occupied by collagen and elastic fibers, polymorpho- and mononuclear cells, malondialdehyde and carbonyl groups levels were significantly higher in AAPH200 than in CTRL. In comparison to CTRL, AAPH200 showed significant decrease and increase in the activities of superoxide dismutase and catalase, respectively. AAPH augmented the release of pro-inflammatory cytokines IL-1ß, IL-6 e TNF-α. Hence, exposure to AAPH caused significant inflammatory alterations and redox imbalance accompanied by altered lung mechanics and histology. Furthermore, we disclosed that exposure to AAPH may represent a useful in vivo tool to trigger lung lesions.
RESUMO
Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1ß, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.
Assuntos
Acetaldeído/toxicidade , Poluentes Atmosféricos/toxicidade , Formaldeído/toxicidade , Pulmão/efeitos dos fármacos , Compostos Orgânicos Voláteis/toxicidade , Poluição do Ar , Animais , Fenômenos Biomecânicos , Feminino , Pulmão/patologia , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pressão , Ventilação Pulmonar , Fatores de TempoRESUMO
Microcystin-LR (MC-LR) is a harmful cyanotoxin able to induce adverse outcomes in the respiratory system. We aimed to examine the lungs and nasal epithelium of mice following a sub-chronic exposure to MC-LR. Swiss mice were intranasally instilled with 10 µL of distilled water (CTRL, n = 10) or 6.7 ng/kg of MC-LR diluted in 10 µL of distilled water (TOX, n = 8) during 30 consecutive days. Respiratory mechanics was measured in vivo and histology measurements (morphology and inflammation) were assessed in lungs and nasal epithelium samples 24 h after the last intranasal instillation. Despite the lack of changes in the nasal epithelium, TOX mice displayed an increased amount of PMN cells in the lungs (× 10(-3)/µm(2)), higher lung static elastance (cmH2O/mL), resistive and viscoelastic/inhomogeneous pressures (cmH2O) (7.87 ± 3.78, 33.96 ± 2.64, 1.03 ± 0.12, 1.01 ± 0.08, respectively) than CTRL (5.37 ± 4.02, 26.65 ± 1.24, 0.78 ± 0.06, 0.72 ± 0.05, respectively). Overall, our findings suggest that the nasal epithelium appears more resistant than lungs in this model of MC-LR intoxication.
Assuntos
Pulmão/efeitos dos fármacos , Microcistinas/toxicidade , Mucosa Nasal/efeitos dos fármacos , Administração Intranasal , Animais , Relação Dose-Resposta a Droga , Granulócitos/citologia , Granulócitos/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/patologia , Pulmão/metabolismo , Masculino , Toxinas Marinhas , Camundongos , Mucosa Nasal/metabolismoRESUMO
OBJECTIVES: Variable ventilation (VV) seems to improve respiratory function in acute lung injury and may be combined with positive end-expiratory pressure (PEEP) in order to protect the lungs even in healthy subjects. We hypothesized that VV in combination with moderate levels of PEEP reduce the deterioration of pulmonary function related to general anesthesia. Hence, we aimed at evaluating the alveolar stability and lung protection of the combination of VV at different PEEP levels. DESIGN: Randomized experimental study. SETTING: Animal research facility. SUBJECTS: Forty-nine male Wistar rats (200-270 g). INTERVENTIONS: Animals were ventilated during 2 hours with protective low tidal volume (VT) in volume control ventilation (VCV) or VV and PEEP adjusted at the level of minimum respiratory system elastance (Ers), obtained during a decremental PEEP trial subsequent to a recruitment maneuver, and 2 cmH2O above or below of this level. MEASUREMENTS AND MAIN RESULTS: Ers, gas exchange and hemodynamic variables were measured. Cytokines were determined in lung homogenate and plasma samples and left lung was used for histologic analysis and diffuse alveolar damage scoring. A progressive time-dependent increase in Ers was observed independent on ventilatory mode or PEEP level. Despite of that, the rate of increase of Ers and lung tissue IL-1 beta concentration were significantly lower in VV than in VCV at the level of the PEEP of minimum Ers. A significant increase in lung tissue cytokines (IL-6, IL-1 beta, CINC-1 and TNF-alpha) as well as a ventral to dorsal and cranial to caudal reduction in aeration was observed in all ventilated rats with no significant differences among groups. CONCLUSIONS: VV combined with PEEP adjusted at the level of the PEEP of minimal Ers seemed to better prevent anesthesia-induced atelectasis and might improve lung protection throughout general anesthesia.
Assuntos
Anestesia Geral , Alvéolos Pulmonares/fisiologia , Atelectasia Pulmonar/prevenção & controle , Ventilação Pulmonar/fisiologia , Animais , Hemodinâmica , Masculino , Respiração com Pressão Positiva , Troca Gasosa Pulmonar , Ratos , Ratos WistarRESUMO
Silicosis is an occupational lung disease, characterized by irreversible and progressive fibrosis. Silica exposure leads to intense lung inflammation, reactive oxygen production, and extracellular ATP (eATP) release by macrophages. The P2X7 purinergic receptor is thought to be an important immunomodulator that responds to eATP in sites of inflammation and tissue damage. The present study investigates the role of P2X7 receptor in a murine model of silicosis. To that end wild-type (C57BL/6) and P2X7 receptor knockout mice received intratracheal injection of saline or silica particles. After 14 days, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage and flow cytometry analyzes were performed. Lungs were harvested for histological and immunochemistry analysis of fibers content, inflammatory infiltration, apoptosis, as well as cytokine and oxidative stress expression. Silica particle effects on lung alveolar macrophages and fibroblasts were also evaluated in cell line cultures. Phagocytosis assay was performed in peritoneal macrophages. Silica exposure increased lung mechanical parameters in wild-type but not in P2X7 knockout mice. Inflammatory cell infiltration and collagen deposition in lung parenchyma, apoptosis, TGF-ß and NF-κB activation, as well as nitric oxide, reactive oxygen species (ROS) and IL-1ß secretion were higher in wild-type than knockout silica-exposed mice. In vitro studies suggested that P2X7 receptor participates in silica particle phagocytosis, IL-1ß secretion, as well as reactive oxygen species and nitric oxide production. In conclusion, our data showed a significant role for P2X7 receptor in silica-induced lung changes, modulating lung inflammatory, fibrotic, and functional changes.
Assuntos
Inflamação/metabolismo , Inflamação/patologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Dióxido de Silício/toxicidade , Animais , Apoptose , Líquido da Lavagem Broncoalveolar , Colágeno/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Imunofenotipagem , Interleucina-1beta/metabolismo , Pulmão/patologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Células NIH 3T3 , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fagocitose/efeitos dos fármacos , Fibrose Pulmonar/patologia , Fibrose Pulmonar/fisiopatologia , Antagonistas do Receptor Purinérgico P2X/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Corantes de Rosanilina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
We compared the toxicity of subchronic exposure to equivalent masses of particles from sugar cane burning and traffic. BALB/c mice received 3 intranasal instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4) or particles (15µg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2, BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the last instillation. In all instances UP and BP groups presented worse pulmonary elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse bronchial and alveolar lesion scores than their controls; BP4 had greater bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4. In conclusion, biomass particles were more toxic than those from traffic after repeated exposures.
Assuntos
Poluentes Atmosféricos/toxicidade , Exposição por Inalação , Pulmão/patologia , Material Particulado/toxicidade , Transtornos Respiratórios/induzido quimicamente , Saccharum/química , Animais , Brônquios/patologia , Líquido da Lavagem Broncoalveolar , Catalase/metabolismo , Feminino , Galectina 3/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Estatísticas não Paramétricas , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de TempoRESUMO
RATIONALE: In normal lungs, local changes in pleural pressure (P(pl)) are generalized over the whole pleural surface. However, in a patient with injured lungs, we observed (using electrical impedance tomography) a pendelluft phenomenon (movement of air within the lung from nondependent to dependent regions without change in tidal volume) that was caused by spontaneous breathing during mechanical ventilation. OBJECTIVES: To test the hypotheses that in injured lungs negative P(pl) generated by diaphragm contraction has localized effects (in dependent regions) that are not uniformly transmitted, and that such localized changes in P(pl) cause pendelluft. METHODS: We used electrical impedance tomography and dynamic computed tomography (CT) to analyze regional inflation in anesthetized pigs with lung injury. Changes in local P(pl) were measured in nondependent versus dependent regions using intrabronchial balloon catheters. The airway pressure needed to achieve comparable dependent lung inflation during paralysis versus spontaneous breathing was estimated. MEASUREMENTS AND MAIN RESULTS: In all animals, spontaneous breathing caused pendelluft during early inflation, which was associated with more negative local P(pl) in dependent regions versus nondependent regions (-13.0 ± 4.0 vs. -6.4 ± 3.8 cm H2O; P < 0.05). Dynamic CT confirmed pendelluft, which occurred despite limitation of tidal volume to less than 6 ml/kg. Comparable inflation of dependent lung during paralysis required almost threefold greater driving pressure (and tidal volume) versus spontaneous breathing (28.0 ± 0.5 vs. 10.3 ± 0.6 cm H2O, P < 0.01; 14.8 ± 4.6 vs. 5.8 ± 1.6 ml/kg, P < 0.05). CONCLUSIONS: Spontaneous breathing effort during mechanical ventilation causes unsuspected overstretch of dependent lung during early inflation (associated with reciprocal deflation of nondependent lung). Even when not increasing tidal volume, strong spontaneous effort may potentially enhance lung damage.
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Pulmão/fisiopatologia , Pleura/fisiopatologia , Respiração com Pressão Positiva , Pressão , Respiração , Síndrome do Desconforto Respiratório/fisiopatologia , Adulto , Animais , Humanos , Masculino , Pletismografia de Impedância , Síndrome do Desconforto Respiratório/terapia , Suínos , Volume de Ventilação Pulmonar , TomografiaRESUMO
BACKGROUND: A decremental positive end-expiratory pressure (PEEP) trial after full lung recruitment allows for the adjustment of the lowest PEEP that prevents end-expiratory collapse (open-lung PEEP). For a tidal volume (Vt) approaching zero, the PEEP of minimum respiratory system elastance (PEEP(minErs)) is theoretically equal to the pressure at the mathematical inflection point (MIP) of the pressure-volume curve, and seems to correspond to the open-lung PEEP in a decremental PEEP trial. Nevertheless, the PEEP(minErs) is dependent on Vt and decreases as Vt increases. To circumvent this dependency, we proposed the use of a second-order model in which the volume-independent elastance (E1) is used to set open-lung PEEP. METHODS: Pressure-volume curves and a recruitment maneuver followed by decremental PEEP trials, with a Vt of 6 and 12 mL/kg, were performed in 24 Wistar rats with acute lung injury induced by intraperitoneally injected (n = 8) or intratracheally instilled (n = 8) Escherichia coli lipopolysaccharide. In 8 control animals, the anterior chest wall was surgically removed after PEEP trials, and the protocol was repeated. Airway pressure (Paw) and flow (F) were continuously acquired and fitted by the linear single-compartment model (Paw = Rrs·F + Ers·V + PEEP, where Rrs is the resistance of the respiratory system, and V is volume) and the volume-dependent elastance model (Paw = Rrs·F + E1 + E2·V·V + PEEP, where E2·V is the volume-dependent elastance). From each model, PEEPs of minimum Ers and E1 (PEEP(minE1)) were identified and compared with each respective MIP. The accuracy of PEEPminE1 and PEEPminErs in estimating MIP was assessed by bias and precision plots. Comparisons among groups were performed with the unpaired t test whereas a paired t test was used between the control group before and after chest wall removal and within groups at different Vts. All P values were then corrected for multiple comparisons by the Bonferroni procedure. RESULTS: In all experimental groups, PEEPminErs, but not PEEPminE1, tended to decrease as Vt increased. The difference between MIP and PEEPminE1 exhibited a lower bias compared with the difference between MIP and PEEPminErs (P < 0.001). The PEEPminE1 was always significantly higher than the PEEPminErs (7.7 vs 3.8, P < 0.001) and better approached MIP (7.7 vs 7.3 cm H2O with P = 0.04 at low Vt, and 7.8 vs 7.1 cm H2O with P < 0.001 at high Vt). CONCLUSIONS: PEEPminE1 better identifies the open-lung PEEP independently of the adjusted Vt, and may be a practical, more individualized approach for PEEP titration.
Assuntos
Pulmão/fisiologia , Respiração com Pressão Positiva/métodos , Mecânica Respiratória/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Animais , Masculino , Respiração com Pressão Positiva/instrumentação , Ratos , Ratos WistarRESUMO
Environmentally relevant doses of inhaled diesel particles elicit pulmonary inflammation and impair lung mechanics. Eugenol, a methoxyphenol component of clove oil, presents in vitro and in vivo anti-inflammatory and antioxidant properties. Our aim was to examine a possible protective role of eugenol against lung injuries induced by diesel particles. Male BALB/c mice were divided into four groups. Mice received saline (10 µl in; CTRL group) or 15 µg of diesel particles DEP (15 µg in; DIE and DEUG groups). After 1 h, mice received saline (10 µl; CTRL and DIE groups) or eugenol (164 mg/kg; EUG and DEUG group) by gavage. Twenty-four hours after gavage, pulmonary resistive (ΔP1), viscoelastic (ΔP2) and total (ΔPtot) pressures, static elastance (Est), and viscoelastic component of elastance (ΔE) were measured. We also determined the fraction areas of normal and collapsed alveoli, amounts of polymorpho- (PMN) and mononuclear cells in lung parenchyma, apoptosis, and oxidative stress. Est, ΔP2, ΔPtot, and ΔE were significantly higher in the DIE than in the other groups. DIE also showed significantly more PMN, airspace collapse, and apoptosis than the other groups. However, no beneficial effect on lipid peroxidation was observed in DEUG group. In conclusion, eugenol avoided changes in lung mechanics, pulmonary inflammation, and alveolar collapse elicited by diesel particles. It attenuated the activation signal of caspase-3 by DEP, but apoptosis evaluated by TUNEL was avoided. Finally, it could not avoid oxidative stress as indicated by malondialdehyde.
Assuntos
Eugenol/farmacologia , Pulmão/efeitos dos fármacos , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Alvéolos Pulmonares/efeitos dos fármacos , Emissões de Veículos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Marcação In Situ das Extremidades Cortadas/métodos , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Pneumonia/metabolismo , Pneumonia/patologia , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia , Mecânica Respiratória/efeitos dos fármacosRESUMO
BACKGROUND: Hypoxemia in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients represents a common finding in the intensive care unit (ICU) and frequently does not respond to standard ventilatory techniques. OBJECTIVE: To study whether the early short-term application of high-frequency percussive ventilation (HFPV) can improve gas exchange in hypoxemic patients with ALI/ARDS or many other conditions in comparison to conventional ventilation (CV) using the same mean airway pressure (P(aw)), representing the main determinant of oxygenation and hemodynamics, irrespective of the mode of ventilation. METHODS: Thirty-five patients not responding to CV were studied. During the first 12 h after admission to the ICU the patients underwent CV. Thereafter HFPV was applied for 12 h with P(aw) kept constant. They were then returned to CV. Gas exchange was measured at: 12 h after admission, every 4 h during the HFPV trial, 1 h after the end of HFPV, and 12 h after HFPV. Thirty-five matched patients ventilated with CV served as the control group (CTRL). RESULTS: PaO(2)/FiO(2) and the arterial alveolar ratio (a/A PO(2)) increased during HFPV treatment and a PaO(2)/FiO(2) steady state was reached during the last 12 h of CV, whereas both did not change in CTRL. PaCO(2) decreased during the first 4 h of HFPV, but thereafter it remained unaltered; PaCO(2) did not vary in CTRL. Respiratory system compliance increased after HFPV. CONCLUSIONS: HFPV improved gas exchange in patients who did not respond to conventional treatment. This improvement remained unaltered until 12 h after the end of HFPV.
Assuntos
Lesão Pulmonar Aguda/complicações , Ventilação de Alta Frequência/métodos , Hipóxia/terapia , Troca Gasosa Pulmonar , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/complicações , Adulto , Idoso , Gasometria , Intervenção Médica Precoce , Feminino , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Although the application of airway clearance techniques is considered an important component in the treatment of several obstructive pulmonary diseases, there is no scientific evidence supporting the use of Flutter Valve™ in the management of patients with bronchiectasis. Moreover, the consequences of respiratory physiotherapy techniques on respiratory mechanics have not been fully studied. Therefore, we investigated the acute, short-term effects of Flutter Valve™ on respiratory mechanics and sputum production in bronchiectatic patients. METHODS: EIGHT patients were evaluated in a randomized, blinded, cross-over trial. Impedance at 5 Hz (R5), resistance as a function of oscillation frequency (dR/dF), reactance at 5 Hz (X5), resonant frequency (f(0) ) and integral of reactance between 5 Hz and resonant frequency (AX) were recorded. RESULTS: Flutter Valve™ cleared 8.4 mL more secretions than the Sham Flutter intervention (95% confidence interval [95% CI], 3.4-13.4). There was a higher percentage decrease in R5 (-11.2%; 95% CI, -4.4 to -18.2), dR/dF (-20.8%; 95% CI, -32.4 to -9) and AX (-7.8%; 95% CI, -11.9 to -3.7) under Flutter Valve™. X5 and f(0) variation did not differ between interventions. CONCLUSIONS: Flutter Valve™ increases sputum removal during treatment and diminishes total and peripheral airway resistance in hypersecretive patients with bronchiectasis. Impulse oscillometry is a user-friendly tool to evaluate the effects of airway clearance techniques on respiratory mechanics.
Assuntos
Bronquiectasia/terapia , Mecânica Respiratória/fisiologia , Terapia Respiratória/instrumentação , Escarro/metabolismo , Adulto , Bronquiectasia/fisiopatologia , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oscilometria/instrumentação , Oscilometria/métodosRESUMO
RATIONALE: P2X7 receptors have been involved in inflammatory and immunological responses, and their activation modulates pro-inflammatory cytokines production by LPS-challenged macrophages. OBJECTIVES: To determine the role of P2X7R in LPS-induced acute lung injury in mice. METHODS: Wild-type (C57BL/6) and P2X7 knockout mice received intratracheal injection of saline or Escherichia coli LPS (60 µg). After 24h, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage was performed, and lungs were harvested for measurement of morphometry, fibers content, inflammatory cells and cytokine expression by histochemistry and immunohistochemistry. RESULTS: Compared with saline, LPS increased lung mechanical parameters, mast cell, collagen and fibronectin deposition in lung parenchyma, as well as nitric oxide and lactate dehydrogenase release into bronchoalveolar fluid in wild-type, but not in P2X7R knockout mice. Alveolar collapse, lung influx of polymorphonuclear and CD14(+) cells, as well as TGF-ß, MMP-2, and IL-1ß release were higher in wild-type than knockout LPS-challenged mice, while MMP-9 release where similar between the two genotypes. LPS increased macrophage immunoreactivity in lung tissue in both genotypes, but macrophages were not activated in the P2X7R knockout mice. Furthermore, LPS administration increased P2X7R immunoexpression in lung parenchyma in wild-type mice, and TLR4 in both wild-type and P2X7R knockout mice. CONCLUSION: P2X7 receptors are implicated in the pathophysiology of LPS-induced lung injury, modulating lung inflammatory and functional changes.
Assuntos
Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Imuno-Histoquímica , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/patologia , Mecânica Respiratória/fisiologiaRESUMO
Lung mechanics, histology, oxygenation and type-III procollagen (PCIII) mRNA were studied aiming to evaluate the need to readjust ventilatory pattern when going from two- to one-lung ventilation (OLV). Wistar rats were assigned to three groups: the left lung was not ventilated while the right lung received: (1) tidal volume (V(T))=5 ml/kg and positive end-expiratory pressure (PEEP)=2 cm H(2)O (V5P2), (2) V(T)=10 ml/kg and PEEP=2 cm H(2)O (V10P2), and (3) V(T)=5 ml/kg and PEEP=5 cm H(2)O (V5P5). At 1-h ventilation, V5P2 showed hypoxemia, alveolar collapse and impaired lung function. Higher PEEP minimized these changes and prevented hypoxemia. Although high V(T) prevented hypoxemia and maintained a higher specific compliance than V5P2, a morphologically inhomogeneous parenchyma and higher PCIII expression resulted. In conclusion, the association of low V(T) and an adequate PEEP level could be useful to maintain arterial oxygenation without inducing a possible inflammatory/remodeling response.