RESUMO
BACKGROUND: Recruitment maneuver and positive end-expiratory pressure (PEEP) can be used to counteract intraoperative anesthesia-induced atelectasis. Variable ventilation can stabilize lung mechanics by avoiding the monotonic tidal volume and protect lung parenchyma as tidal recruitment is encompassed within the tidal volume variability. METHODS: Forty-nine (7 per group) male Wistar rats were anesthetized, paralyzed, and mechanically ventilated. A recruitment maneuver followed by stepwise decremental PEEP titration was performed while continuously estimating respiratory system mechanics using recursive least squares. After a new recruitment, animals were ventilated for 2 hours in volume-control with monotonic (VCV) or variable (VV) tidal volumes. PEEP was adjusted at a level corresponding to the minimum elastance or 2 cm H2O above or below this level. Lungs were harvested for histologic analysis (left lung) and cytokines measurement (right lung). Seven animals were euthanized before the first recruitment as controls. RESULTS: A time-dependent increase in respiratory system elastance was observed and significantly minimized by PEEP (P < .001). Variable ventilation attenuated the amount of concentrations of proinflammatory mediators in lung homogenate: neutrophil cytokine-induced neutrophil chemoattractant 1 (VV = 40 ± 5 and VCV = 57 ± 8 pg/mg; P < .0001) and interleukin-1ß (VV = 59 ± 25 and VCV = 261 ± 113 pg/mg; P < .0001). Variable ventilation was also associated with lower structural lung parenchyma damage. Significant reductions in air fraction at dorsal and caudal lung regions were observed in all ventilated animals (P < .001). CONCLUSIONS: Variable ventilation was more protective than conventional ventilation within the applied PEEP levels.
Assuntos
Anestésicos Dissociativos/administração & dosagem , Pneumonia/metabolismo , Pneumonia/patologia , Respiração com Pressão Positiva/métodos , Mecânica Respiratória/fisiologia , Animais , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pneumonia/etiologia , Respiração com Pressão Positiva/efeitos adversos , Respiração com Pressão Positiva/tendências , Ratos , Ratos Wistar , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Respiração Artificial/tendências , Volume de Ventilação Pulmonar/fisiologiaRESUMO
Ovalbumin-induced allergic lung inflammation (ALI) is a condition believed to be mediated by cytokines, extracellular matrix remodeling, and redox imbalance. In this study, we evaluated pulmonary function together with inflammatory markers as interleukin-4 (IL-4), myeloperoxidase (MPO), eosinophil cells, and redox markers in the lungs of BALB/c mice after ovalbumin (OVA) sensitization and challenge. Our results showed an increase in bronchial hyperresponsiveness stimulated by methacholine (Mch), inflammatory cell influx, especially eosinophils together with an increase of high mobility group box 1 (HMGB1) and altered lipid peroxidation (LP) and antioxidant defenses in the OVA group compared to the control group (p ≤ 0.5). Thus, we demonstrated that OVA-induced ALI altered redox status concomitantly with impaired lung function, which was associated with HMGB1 expression and proteolytic remodeling. Taken together all results found here, we may suggest HMGB1 is an important therapeutic target for asthma, once orchestrates the redox signaling, inflammation, and remodeling that contribute to the disease development.
Assuntos
Asma/metabolismo , Asma/patologia , Proteína HMGB1/metabolismo , Inflamação , Estresse Oxidativo , Animais , Biomarcadores/análise , Hiper-Reatividade Brônquica , Eosinófilos , Inflamação/diagnóstico , Inflamação/imunologia , Peroxidação de Lipídeos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , ProteóliseRESUMO
The cyanotoxin cylindrospermopsin (CYN) has lately been reported with a notorious toxicity to mammals. LASSBio-596 is a compound with anti-inflammatory actions. We aimed at evaluating the therapeutic effects of LASSBio-596 in a model of CYN-induced lung injury. Protocol #1: BALB/c mice received intratracheally (i.t.) 50-µL of saline or semi-purified extract of CYN (70 µg/kg). 18 h later, animals that received saline were gavaged with saline (SALSAL) or 50 mg/kg of LASSBio-596 (SALLAS), and mice that received CYN were gavaged with either saline (TOXSAL) or 50 mg/kg of LASSBio-596 (TOXLAS). Pulmonary mechanics was measured 6 h after gavage. Lungs were prepared for histology and inflammatory mediators determination. Protocol #2: Mice received 50-µL of CYN (70 µg/kg, i.t.) and 18 h later were gavaged with saline (NOT TREATED), or 50 mg/kg of LASSBio-596 (TREATED). Survival rates and pulmonary mechanics of the survivors were assessed. CYN exposure increased mechanical components, alveolar collapse, PMN cells and fiber deposition in the lungs, as well as the production of IL-1ß, IL-6 and KC in Protocol #1. LASSBio-596 attenuated those changes. TREATED mice in Protocol #2 presented significantly higher survival rates and tended to improve lung mechanics. Briefly, LASSBio-596 showed positive effects in mice exposed to CYN.
Assuntos
Anti-Inflamatórios/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Ácidos Ftálicos/uso terapêutico , Sulfonamidas/uso terapêutico , Uracila/análogos & derivados , Alcaloides , Animais , Anti-Inflamatórios/efeitos adversos , Toxinas Bacterianas , Toxinas de Cianobactérias , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Camundongos Endogâmicos BALB C , Ácidos Ftálicos/efeitos adversos , Sulfonamidas/efeitos adversos , Análise de Sobrevida , Uracila/toxicidadeRESUMO
BALB/c mice received saline (SAL groups) or ovalbumin (OVA groups) intraperitoneally (days 1, 3, 5, 7, 9, 11 and 13). After 27 days, a burst of intratracheal OVA or SAL (days 40, 43 and 46) was performed. Animals were then divided into four groups (N=8, each) and intranasally instilled with saline (SAL-SAL and OVA-SAL) or residual oil fly ash (SAL-ROFA and OVA-ROFA). 24h later, total, initial and difference resistances (Rtot, Rinit, Rdiff) and static elastance (Est) were measured. Lung responsiveness to methacholine was assessed as slope and sensitivity of Est, Rtot, Rinit, and Rdiff. Lung morphometry (collapsed and normal areas and bronchoconstriction index) and cellularity (polymorphonuclear, mononuclear and mast cells) were determined. OVA or ROFA similarly impaired lung mechanics and increased the amount of polymorphonuclear cells and collapsed areas. OVA-ROFA showed even higher hyperresponsiveness, bronchoconstriction and mast cell infiltration. Thus, we concluded that ROFA exposure may add an extra burden to hyperresponsive lungs.