RESUMO
Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 microg of DEP/10 microl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation.
Assuntos
Exposição por Inalação/efeitos adversos , Material Particulado/administração & dosagem , Material Particulado/efeitos adversos , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/patologia , Emissões de Veículos , Administração Intranasal , Poluentes Atmosféricos/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar , Inflamação/induzido quimicamente , Inflamação/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI). In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally (i.t.) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 microg i.t.). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v.) or methylprednisolone (2 mg x kg(-1) i.v.) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured. In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design. Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.
Assuntos
Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/patologia , Metilprednisolona/administração & dosagem , Doença Aguda , Animais , Anti-Inflamatórios/administração & dosagem , Colágeno/química , Citocinas/metabolismo , Escherichia coli/metabolismo , Inflamação , Lipopolissacarídeos/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fatores de TempoRESUMO
The impact of lung remodelling in respiratory mechanics has been widely studied in bleomycin-induced lung injury. However, little is known regarding the relationship between the amount of lung inflammation and pulmonary tissue mechanics. For this purpose, rats were intratracheally instilled with bleomycin (n=29) or saline (n=8) and sacrificed at 3, 7, or 15 days. Forced oscillatory mechanics as well as indices of remodelling (elastic fibre content and hydroxyproline) and inflammation (myeloperoxidase content, total cell count, alveolar wall thickness, and lung water content) were studied in lung tissue strips. Tissue resistance increased significantly at day 15, while hysteresivity was significantly higher in bleomycin group compared to control at all time points. Elastic fibres, hydroxyproline and myeloperoxidase contents augmented after bleomycin at days 7 and 15. Tissue resistance and hysteresivity were significantly correlated with myeloperoxidase, elastic fibre and lung water content. In conclusion, inflammatory structural changes and elastogenesis are the main determinants for hysteretic changes in this 2-week bleomycin-induced lung injury model.
Assuntos
Antibióticos Antineoplásicos/toxicidade , Bleomicina/toxicidade , Hidroxiprolina/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Animais , Elasticidade , Água Extravascular Pulmonar/efeitos dos fármacos , Água Extravascular Pulmonar/imunologia , Água Extravascular Pulmonar/fisiologia , Hidroxiprolina/metabolismo , Técnicas In Vitro , Inflamação/induzido quimicamente , Inflamação/imunologia , Masculino , Peroxidase/metabolismo , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance), histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber) were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9), mice were immunized with 10 microg ovalbumin (OVA, ip) on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 microg OVA at 3-day intervals. Control mice (N = 8) received saline under the same protocol. In the dexamethasone (N = 8) and LASSBio596 (N = 8) groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip) or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip) 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively) compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.
Assuntos
Asma/tratamento farmacológico , Inibidores de Fosfodiesterase/farmacologia , Ftalimidas/farmacologia , Mecânica Respiratória/efeitos dos fármacos , Animais , Asma/patologia , Doença Crônica , Dexametasona/farmacologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C , Ácidos Ftálicos , Distribuição Aleatória , Testes de Função Respiratória , SulfonamidasRESUMO
RATIONALE AND HYPOTHESIS: Previous studies evaluating the histoarchitecture of distal airspaces have been shown to be limited by the difficulty in adequately differentiating alveoli and alveolar ducts. This limitation has been specially noticed in studies addressing lung recruitment and in situations of diffuse alveolar damage (DAD), where generic nominations for distal airspaces had to be created, such as "peripheral airspaces" (PAS) and "large-volume gas-exchanging airspaces" (LVGEA). Elastic stains have been largely used to describe normal lung structures. Weigert's resorcin-fuchsin staining (WRF) demarcates the thickened free portions of the ductal septum facilitating its recognition. We hypothesized that this staining could help in differentiating alveoli from alveolar ducts in distorted lung parenchyma. MATERIAL AND METHODS: Samples of control lungs and of DAD lungs induced by mechanical ventilation (VILI) were stained with hematoxylin-eosin (HE) and with WRF. Using morphometry we assessed the volume proportion of alveoli, alveolar ducts and LVGEA in control and VILI lungs. RESULTS: WRF stained VILI lungs showed a significant decrease in the volume proportion of LVGEA and alveoli and a significant increase in the volume proportion of alveolar ducts when compared to HE stained samples. CONCLUSION: We conclude that WRF staining is useful to distinguish alveolar ducts from alveoli in a DAD model, and suggest that it should be routinely used when morphometric studies of lung parenchyma are performed.
Assuntos
Barreira Alveolocapilar/patologia , Lesão Pulmonar , Pulmão/patologia , Alvéolos Pulmonares/patologia , Animais , Ratos , Resorcinóis , Corantes de Rosanilina , Coloração e Rotulagem/métodosRESUMO
The increasing coexistence of cancer and diabetes within the elderly population requires specific palliative care skills on diabetes treatment. We report our experience of diabetes management in a palliative care setting. In our retrospective 3-year activity sample (n = 563), 27.2% of patients have a diagnosis of diabetes mellitus: 80% have cancer whereas 20% have a main diagnosis of other severe chronic diseases. As to the presence/absence of diabetes, no differences emerge in the examined clinical indicators and global survival, with the exception of body mass index and days of hospitalization. At lifetime analysis, Barthel index and palliative prognostic index are the only parameters significantly related to death. Even if diabetes seems not to modify the prognosis, it significantly influences the health care burden and the team engagement.
Assuntos
Diabetes Mellitus/terapia , Neoplasias/complicações , Neoplasias/terapia , Assistência Terminal/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Pneumonia is responsible for 50% of antibiotics prescribed in ICUs. Treatment failure, ie, absence of improvement or clinical deterioration under antibiotic therapy, presents a dilemma to physicians. BAL is an invasive method validated for etiologic diagnosis in pneumonia. STUDY OBJECTIVE: To evaluate in ICU patients the impact of BAL in the etiologic diagnosis, treatment, and outcome of pneumonia with treatment failure. DESIGN: Prospective clinical study. SETTING: Nonsurgical, medical ICU of a university hospital in Brazil. PATIENTS AND PARTICIPANTS: Sixty-two episodes of pneumonia treated for at least 72 h without clinical improvement in 53 patients hospitalized for diverse clinical emergencies. Mean duration of hospitalization was 14.2 days. Mean duration of previous antibiotic therapy was 11.4 days. INTERVENTIONS: Bronchoscopy and BAL were performed in each episode. BAL fluid was cultivated for aerobic and anaerobic bacteria; the cutoff considered positive was 10(4) cfu/mL; 10(3) cfu/mL was also analyzed if under treatment. Pneumocystis carinii, fungi, Legionella spp, and Mycobacterium spp were also researched. MEASUREMENTS AND RESULTS: Fifty-eight of 62 BAL were performed under antibiotics. The results showed positivity in 45 of 62 (72.6%); 42 of the 45 positive episodes (93.3%) had > 10(4) cfu/mL. The three cases with between 10(3) and 10(4) cfu/mL were considered positive and were treated according to BAL cultures. The main agents were Acinetobacter baumannii (37.1%), Pseudomonas aeruginosa (17.7%), and methicillin-resistant Staphylococcus aureus (MRSA; 16.1%); 46.7% of the episodes (21 of 45) were polymicrobial. BAL results directed a change of therapy in 34 episodes (54.8%). Overall mortality was 43.5%. There was no difference in mortality among positives, negatives, and patients who changed therapy guided by BAL culture. CONCLUSIONS: (1) BAL fluid examination was positive in 45 of 62 episodes (72.6%), with 58 of 62 BAL performed under antibiotics. This suggests that BAL may be a sensitive diagnostic method for treatment failures of clinically diagnosed pneumonias, even if performed under antibiotics; (2) the main pathogens in our study were A baumannii, P aeruginosa, and MRSA, and approximately 45% of infections were polymicrobial; (3) BAL culture results directed a change of therapy in 75.6% of positive episodes (34 of 45) and in 54.8% of all episodes of treatment failure (34 of 62); and (4) there was no difference in mortality among positives, negatives, and patients who changed therapy guided by BAL culture.
Assuntos
Antibacterianos/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Pneumonia Bacteriana/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Broncoscopia , Contagem de Colônia Microbiana , Resistência Microbiana a Medicamentos , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Estudos Prospectivos , Taxa de Sobrevida , Falha de TratamentoRESUMO
The dynamic mechanical properties of lung tissue and its contents of collagen and elastic fibers were studied in strips prepared from mice instilled intratracheally with saline (C) or silica [15 (S15) and 30 days (S30) after instillation]. Resistance, elastance, and hysteresivity were studied during oscillations at different frequencies on S15 and S30. Elastance increased from C to silica groups but was similar between S15 and S30. Resistance was augmented from C to S15 and S30 and was greater in S30 than in S15 at higher frequencies. Hysteresivity was higher in S30 than in C and S15. Silica groups presented a greater amount of collagen than did C. Elastic fiber content increased progressively along time. This increment was related to the higher amount of oxytalan fibers at 15 and 30 days, whereas elaunin and fully developed elastic fibers were augmented only at 30 days. Silicosis led not only to pulmonary fibrosis but also to fibroelastosis, thus assigning a major role to the elastic system in the silicotic lung.
Assuntos
Matriz Extracelular/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Mecânica Respiratória , Silicose/metabolismo , Silicose/fisiopatologia , Algoritmos , Animais , Fenômenos Biomecânicos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Contração Muscular , Circulação Pulmonar , Resistência VascularRESUMO
The aim of this study was to determine whether an intrapleural injection of barium sulphate would produce pleurodesis in rats. Additionally, respiratory mechanics and pleural remodelling were analysed. Single intrapleural injection of barium sulphate (100%) or saline was given to Wistar rats. Respiratory system, lung, and chest wall elastic, resistive and viscoelastic/inhomogeneous pressures were measured by the end-inflation occlusion method at 2 and 30 days after injection. The pleura were examined for gross and histopathological evidence of pleural inflammation and fibrosis, and the underlying lungs were also studied by morphometry. All pulmonary mechanical parameters increased at day 2, but were not different from control at 30 days after injection. Chest wall mechanical parameters did not change. Macroscopic evaluation demonstrated pleural adherence without haemothorax. Histopathologic analysis showed pleural inflammation and fibrosis. There was no alveolar inflammation or fibrosis in both groups. In conclusion, barium sulphate induced pleurodesis with either no changes in respiratory mechanics or lung lesion at day 30.
Assuntos
Sulfato de Bário/farmacologia , Pleura/efeitos dos fármacos , Pleurodese , Mecânica Respiratória/efeitos dos fármacos , Animais , Fibrose/etiologia , Capacidade Residual Funcional/efeitos dos fármacos , Histologia , Inflamação/etiologia , Complacência Pulmonar/efeitos dos fármacos , Masculino , Pleura/patologia , Pleura/fisiologia , Ratos , Ratos Wistar , Mecânica Respiratória/fisiologia , Sistema Respiratório/efeitos dos fármacos , Tórax/efeitos dos fármacos , Tórax/patologia , Fatores de TempoRESUMO
The present study was undertaken in order to describe the morphological differences between pulmonary lesions in acute respiratory distress syndrome originating from direct pulmonary injury (ARDSp) and those originating from extrapulmonary injury (ARDSexp). We investigated a total of 38 ARDS-patients (27 males) ranging in age from 19 to 75 years, classified according to underlying disease in pulmonary (ARDSp) and extrapulmonary disease (ARDSexp). The extent of acute diffuse alveolar damage was assessed morphometrically on histologic gross sections in the upper and lower lobes of one lung. The lesions showed quantitative differences in extent and distribution according to underlying disease (primary pulmonary or secondary involvement). In pulmonary ARDS, a predominance of alveolar collapse (16.6%+/-12.3% versus 10.3%+/-11.9%, p = 0,03), fibrinous exudate (1.7%+/-3.2% versus 0.4%+/-1.1%, p = 0.01) and alveolar wall edema (11.2%+/-7.4% versus 6.6%+/-4.4%, p = 0,05) were found compared to extrapulmonary ARDS. We conclude that the morphology of acute diffuse alveolar damage (DAD) is mainly determined by underlying disease (pulmonary ARDS or extrapulmonary ARDS) differing in quantitative terms within the lung. Physiological, radiographic and respiratory system mechanics differences described in ARDSp and ARDSexp may therefore be due to morphometric differences in pulmonary lesions.
Assuntos
Pulmão/patologia , Síndrome do Desconforto Respiratório/patologia , Adulto , Idoso , Edema/etiologia , Edema/patologia , Exsudatos e Transudatos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/patologia , Síndrome do Desconforto Respiratório/complicações , Estudos RetrospectivosRESUMO
Hypomagnesemia is the most common electrolyte disturbance seen upon admission to the intensive care unit (ICU). Reliable predictors of its occurrence are not described. The objective of this prospective study was to determine factors predictive of hypomagnesemia upon admission to the ICU. In a single tertiary cancer center, 226 patients with different diagnoses upon entering were studied. Hypomagnesemia was defined by serum levels <1.5 mg/dl. Demographic data, type of cancer, cause of admission, previous history of arrhythmia, cardiovascular disease, renal failure, drug administration (particularly diuretics, antiarrhythmics, chemotherapy and platinum compounds), previous nutrition intake and presence of hypovolemia were recorded for each patient. Blood was collected for determination of serum magnesium, potassium, sodium, calcium, phosphorus, blood urea nitrogen and creatinine levels. Upon admission, 103 (45.6%) patients had hypomagnesemia and 123 (54.4%) had normomagnesemia. A normal dietary habit prior to ICU admission was associated with normal Mg levels (P = 0.007) and higher average levels of serum Mg (P = 0.002). Postoperative patients (N = 182) had lower levels of serum Mg (0.60 +/- 0.14 mmol/l compared with 0.66 +/- 0.17 mmol/l, P = 0.006). A stepwise multiple linear regression disclosed that only normal dietary habits (OR = 0.45; CI = 0.26-0.79) and the fact of being a postoperative patient (OR = 2.42; CI = 1. 17-4.98) were significantly correlated with serum Mg levels (overall model probability = 0.001). These findings should be used to identify patients at risk for such disturbance, even in other critically ill populations.
Assuntos
Estado Terminal , Magnésio/sangue , Neoplasias/complicações , Idoso , Análise de Variância , Nitrogênio da Ureia Sanguínea , Cálcio/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Fósforo/sangue , Período Pós-Operatório , Potássio/sangue , Estudos Prospectivos , Sódio/sangueRESUMO
Shock and resuscitation render patients more susceptible to acute lung injury due to an exacerbated immune response to subsequent inflammatory stimuli. To study the role of innate immunity in this situation, we investigated acute lung injury in an experimental model of ischemia-reperfusion (I-R) followed by an early challenge with live bacteria. Conscious rats (N = 8 in each group) were submitted to controlled hemorrhage and resuscitated with isotonic saline (SS, 0.9% NaCl) or hypertonic saline (HS, 7.5% NaCl) solution, followed by intratracheal or intraperitoneal inoculation of Escherichia coli. After infection, toll-like receptor (TLR) 2 and 4 mRNA expression was monitored by RT-PCR in infected tissues. Plasma levels of tumor necrosis factor alpha and interleukins 6 and 10 were determined by ELISA. All animals showed similar hemodynamic variables, with mean arterial pressure decreasing to nearly 40 mmHg after bleeding. HS or SS used as resuscitation fluid yielded equal hemodynamic results. Intratracheal E. coli inoculation per se induced a marked neutrophil infiltration in septa and inside the alveoli, while intraperitoneal inoculation-associated neutrophils and edema were restricted to the interseptal space. Previous I-R enhanced lung neutrophil infiltration upon bacterial challenge when SS was used as reperfusion fluid, whereas neutrophil influx was unchanged in HS-treated animals. No difference in TLR expression or cytokine secretion was detected between groups receiving HS or SS. We conclude that HS is effective in reducing the early inflammatory response to infection after I-R, and that this phenomenon is achieved by modulation of factors other than expression of innate immunity components.
Assuntos
Lesão Pulmonar Aguda/imunologia , Infecções por Escherichia coli/imunologia , Inflamação/imunologia , Traumatismo por Reperfusão/imunologia , Solução Salina Hipertônica/uso terapêutico , Choque Hemorrágico/tratamento farmacológico , Doença Aguda , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/microbiologia , Animais , Citocinas/sangue , Modelos Animais de Doenças , Imunidade Inata , Inflamação/sangue , Inflamação/tratamento farmacológico , Masculino , RNA Mensageiro/sangue , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Choque Hemorrágico/imunologia , Receptor 2 Toll-Like/sangueRESUMO
AIMS: Pulmonary fibrosis in acute and chronic lung disease has been much investigated, but little attention has been directed at the elastic tissue in these situations. Our aim was to verify whether elastic deposition accompanies collagen deposition in the repairing process of acute and chronic lung injury. METHODS AND RESULTS: We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides sampled from autopsied lungs, using the picrosirius-polarization method and Weigert's resorcin-fuchsin stain, respectively. Five groups were studied: I, 10 normal patients; II, 10 patients with cardiogenic pulmonary oedema; III, 23 adult respiratory distress syndrome (ARDS) patients in the early phase; IV, 14 ARDS patients in the late fibroproliferative phase; and V, 10 idiopathic pulmonary fibrosis patients. The first two groups were used as controls. The content of fibres of the collagenous and elastic systems was significantly increased in groups IV and V as compared to the other groups. CONCLUSIONS: Our results indicate that deposition of elastic system fibres is present in the fibroproliferative phase of ARDS and in usual interstitial pneumonia and suggest that this event may contribute to the alveolar mechanical dysfunction and remodelling that occur in acute and chronic interstitial lung disease.
Assuntos
Tecido Elástico/patologia , Doenças Pulmonares Intersticiais/patologia , Fibrose Pulmonar/patologia , Síndrome do Desconforto Respiratório/patologia , Doença Aguda , Adolescente , Adulto , Idoso , Doença Crônica , Colágeno/metabolismo , Tecido Elástico/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Doenças Pulmonares Intersticiais/metabolismo , Pessoa de Meia-Idade , Edema Pulmonar/metabolismo , Edema Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Estudos RetrospectivosRESUMO
Seven control subjects and seven patients with adult respiratory distress syndrome (ARDS) were artificially ventilated and flow, volume, and tracheal pressure were monitored. Respiratory system resistance (Rrs,max) was partitioned into its homogeneous (Rrs,min) and uneven (Rrs,u) components. Respiratory system elastance (Ers) was also measured. In both groups Ers did not vary with different inspiratory flows and volumes, but was significantly higher in ARDS. With increasing volume (isoflow maneuvers), Rrs,max and Rrs,u increased but Rrs,min remained unaltered in ARDS. In control patients, however, resistances did not vary but Rrs,max and Rrs,u were smaller and Rrs,min equaled their corresponding values in ARDS. Hence, stress relaxation seems to be increased in ARDS. During isovolume maneuvers Rrs,max and Rrs,u decreased with increasing flows (both groups), although they were significantly higher in ARDS. Rrs,min was not modified by different flows and was similar in both groups. Thus, pendelluft is also increased in ARDS. In conclusion, the mechanical profile of ARDS is characterized by increased Ers and Rrs,max, the latter being secondary to augmented mechanical unevenness within the system.
Assuntos
Resistência das Vias Respiratórias , Complacência Pulmonar , Ventilação Pulmonar , Respiração Artificial , Síndrome do Desconforto Respiratório/fisiopatologia , Mecânica Respiratória , Adolescente , Adulto , Idoso , Feminino , Humanos , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Troca Gasosa Pulmonar , Espaço Morto Respiratório , Síndrome do Desconforto Respiratório/terapiaRESUMO
The infusion of the hypertonic 7.5% NaCl solution stimulates the afferent vagal innervation of the lungs. In order to verify if this reflex elicits any respiratory mechanical alterations, normovolemic (n = 18) and hypovolemic (n = 18) (20 ml of shed blood/kg) guinea pigs were studied. The animals were assigned to groups of nine receiving either isotonic 0.9% NaCl or hypertonic 7.5% NaCl solutions (4 ml/kg body weight). Passive respiratory system elastance (Ers) and the maximal value of the resistance (Rrsmax) were measured. The latter was further partitioned into its minimal value (Rrsu) using the constant flow inflation method. Ers, Rrsmax, Rrsmin, and Rrsu were measured before and at 0, 2, 5, 10, and 15 minutes following the infusion. The results showed that both isotonic and hypertonic solutions, at the given volume rate, caused no significant alterations of respiratory mechanics in normovolemic and hypovolemic animals.
Assuntos
Respiração/efeitos dos fármacos , Ressuscitação , Solução Salina Hipertônica/farmacologia , Choque/fisiopatologia , Cloreto de Sódio/farmacologia , Animais , Feminino , Cobaias , Choque/terapia , Nervo Vago/fisiopatologiaRESUMO
BACKGROUND: Propofol is able to reduce airway resistance in lungs with previous airway constriction. The aim of this study was to evaluate the effects of propofol on respiratory mechanics in normal rats and to correlate these parameters with lung histology, to define the sites of action of propofol. METHODS: Sixteen Wistar rats were divided into two groups of eight animals. Rats were sedated (diazepam) and anaesthetized with pentobarbital sodium (C) or propofol (P), and paralysed. Respiratory system, lung, and chest wall resistive, elastic, and viscoelastic/inhomogeneous pressures were computed using the end-inflation occlusion method. RESULTS: Lung resistive pressure was smaller in group P (0.29 kPa (0.05)) than group C (0.37 kPa (0.04)) (P=0.007). The internal diameter of the central airways was greater in group P than C (P=0.01). CONCLUSION: Propofol acts at the airway level decreasing respiratory system and lung impedances as a result of central airway dilation.
Assuntos
Anestésicos Intravenosos/farmacologia , Pulmão/efeitos dos fármacos , Propofol/farmacologia , Mecânica Respiratória/efeitos dos fármacos , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Feminino , Pulmão/patologia , Pentobarbital/farmacologia , Ratos , Ratos WistarRESUMO
UNLABELLED: This study was undertaken to test whether there is structural remodeling of lung parenchyma that could lead to tissue mechanical changes at an early phase of varying degrees of acute lung injury (ALI). Tissue resistance (R), dynamic elastance (E), and hysteresivity (eta) were analyzed during sinusoidal oscillations of rat lung parenchymal strips 24 h after intraperitoneal injection of saline (C) or paraquat (P [10, 15, 25, and 30 mg/kg]). These strips were also stained in order to quantify the amount of collagen and of three types of elastic fibers (elaunin, oxytalan, and fully developed elastic fibers) in the alveolar septa. E augmented progressively from C to P25, but the data from the P25 and P30 groups were not different (p < 0.0001). R and eta increased from C to P10 and from P15 to P25 (p < 0.001). Collagen fiber content increased exponentially with the severity of the injury. Elaunin and fully developed elastic fibers remained unchanged in the five groups, while oxytalan fibers increased only in the P25 and P30 groups. In conclusion, the pronounced mechanical changes at the tissue level and fibroelastogenesis happened at an early phase of the disease and even in mildly abnormal lung parenchyma. KEYWORDS: elastance; collagen fibers; elastin; paraquat
Assuntos
Colágeno/fisiologia , Tecido Elástico/lesões , Elastina/fisiologia , Matriz Extracelular , Lesão Pulmonar , Doença Aguda , Análise de Variância , Animais , Fenômenos Biomecânicos , Colágeno/metabolismo , Proteínas Contráteis/fisiologia , Tecido Elástico/patologia , Tecido Elástico/fisiologia , Tecido Elástico/fisiopatologia , Elastina/metabolismo , Herbicidas/administração & dosagem , Herbicidas/toxicidade , Técnicas Histológicas , Injeções Intraperitoneais , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Complacência Pulmonar , Paraquat/administração & dosagem , Paraquat/toxicidade , Alvéolos Pulmonares/lesões , Alvéolos Pulmonares/fisiopatologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
We evaluated the effects of acute blood loss on the respiratory mechanics of guinea pigs. We measured respiratory system elastance (Ers) and resistance (Rrsmax) using the end-inflation occlusion method. Rrsmax was partitioned into its homogeneous component (Rrsmin) and that due to the unevenness within the respiratory system (Rrsu). Respiratory mechanics were studied both before and immediately after bleeding in eight animals. Another eight guinea pigs had received propranolol previously and were also submitted to hemorrhage. Propranolol-treated animals showed higher control values of Rrsmax (p less than .02) and Rrsmin (p less than .0001). Animals not treated with propranolol exhibited a decrease (p less than 0.001) in Rrsmax after hemorrhagic hypovolemia (from 0.375 +/- 0.051 to 0.323 +/- 0.042 cm H2O/ml.sec), due to a decrease (p less than 0.005) in Rrsmin (from 0.140 +/- 0.031 to 0.094 +/- 0.032 cm H2O/ml.sec), whereas Ers and Rrsu did not change. Propranolol-treated animals showed an increase (p less than .001) in Rrsmax (from 0.512 +/- 0.133 to 0.664 +/- 0.144 cm H2O/ml.sec), Rrsu (p less than 0.01) from 0.252 +/- 0.09 to 0.345 +/- 0.139 cm H2O/ml.sec, and Ers (p less than 0.001) (from 4.565 +/- 0.933 to 5.402 +/- 1.24 cm H2O/ml) after bleeding. The results indicate that the immediate effects of acute bleeding on respiratory mechanics are significantly influenced by catecholamines.
Assuntos
Resistência das Vias Respiratórias/efeitos dos fármacos , Complacência Pulmonar/efeitos dos fármacos , Propranolol/farmacologia , Choque Hemorrágico/fisiopatologia , Resistência das Vias Respiratórias/fisiologia , Animais , Fenômenos Biomecânicos , Catecolaminas/sangue , Catecolaminas/fisiologia , Feminino , Cobaias , Complacência Pulmonar/fisiologia , Medidas de Volume Pulmonar , Propranolol/administração & dosagem , Propranolol/uso terapêutico , Choque Hemorrágico/sangue , Choque Hemorrágico/tratamento farmacológicoRESUMO
Twenty-one patients who underwent elective surgery for coronary artery bypass were studied right after chest wall closure. They were anesthetized, paralyzed, and artificially ventilated with a constant-flow ventilator. Airflow, changes in lung volume, and tracheal pressure were measured. Respiratory system resistance (Rrs,max) was partitioned into its homogeneous (Rrs,min) and uneven (Rrs,u) components. Respiratory system elastance (Ers) was also measured. The subjects were randomly divided into two groups injected with test solutions just after chest wall closure: eleven patients received isotonic saline (0.9% NaCl solution), whereas the remaining ten were injected with hypertonic saline (7.5% NaCl solution). In all patients, mechanical parameters were measured at six different times: just before infusion, at 5 and 10 min (end of infusion); and at 15, 20, and 25 min after beginning of injection. No statistically significant differences were observed in respiratory system mechanical parameters between groups or between different times within each group. Our data suggest that hypertonic saline infusion does not result in significant changes in respiratory system mechanics in patients submitted to coronary artery bypass.
Assuntos
Mecânica Respiratória/efeitos dos fármacos , Solução Salina Hipertônica/farmacologia , Cloreto de Sódio/farmacologia , Adulto , Ponte de Artéria Coronária , Feminino , Humanos , Soluções Isotônicas , Masculino , Pessoa de Meia-Idade , Cloreto de Sódio/administração & dosagemRESUMO
Shock and resuscitation render patients more susceptible to acute lung injury due to an exacerbated immune response to subsequent inflammatory stimuli. To study the role of innate immunity in this situation, we investigated acute lung injury in an experimental model of ischemia-reperfusion (I-R) followed by an early challenge with live bacteria. Conscious rats (N = 8 in each group) were submitted to controlled hemorrhage and resuscitated with isotonic saline (SS, 0.9 percent NaCl) or hypertonic saline (HS, 7.5 percent NaCl) solution, followed by intratracheal or intraperitoneal inoculation of Escherichia coli. After infection, toll-like receptor (TLR) 2 and 4 mRNA expression was monitored by RT-PCR in infected tissues. Plasma levels of tumor necrosis factor α and interleukins 6 and 10 were determined by ELISA. All animals showed similar hemodynamic variables, with mean arterial pressure decreasing to nearly 40 mmHg after bleeding. HS or SS used as resuscitation fluid yielded equal hemodynamic results. Intratracheal E. coli inoculation per se induced a marked neutrophil infiltration in septa and inside the alveoli, while intraperitoneal inoculation-associated neutrophils and edema were restricted to the interseptal space. Previous I-R enhanced lung neutrophil infiltration upon bacterial challenge when SS was used as reperfusion fluid, whereas neutrophil influx was unchanged in HS-treated animals. No difference in TLR expression or cytokine secretion was detected between groups receiving HS or SS. We conclude that HS is effective in reducing the early inflammatory response to infection after I-R, and that this phenomenon is achieved by modulation of factors other than expression of innate immunity components.