RESUMO
UNLABELLED: Inspiratory muscles training in COPD is controversial not only in relation to the load level required to produce muscular conditioning effects but also in relation to the group of patients benefiting from the training. Consequently, inspiratory muscular response assessment during Threshold therapy may help optimizing training strategy. The objective of this study was to evaluate the participation of the diaphragm and the sternocleidomastoid (SMM) muscle to overcome with a 30% Threshold load using surface electromyography (sEMG) and to analyze the correlation between SMM activation, maximum strength level of inspiratory muscles (MIP) and obstruction degree in COPD patients (FEV1). We studied seven healthy elderly subjects, mean age of 68+/-4 years and seven COPD patients, FEV1 45+/-17% of the predicted value, with mean age 66+/-8 years. sEMG analysis of SMM muscles and diaphragm were obtained through RMS (root-mean-square) during three stages: pre-loading, loading and post-loading. RESULTS: In the COPD group, the RMS of the SMM increased 28% during load (p<0.05) while the RMS of the diaphragm remained constant. In the elderly there was a trend of a 11% increase in diaphragm activity and of 7% in SMM activity but, without reaching significance levels. SMM activity demonstrated good correlation with the obstruction level (r=-0.537). CONCLUSION: To overcome the load required by Threshold therapy, COPD patients demonstrated an increase of accessory muscles activity, represented by SMM. For the same relative load this increase seems to be proportional to the degree of pulmonary obstruction.
Assuntos
Exercícios Respiratórios , Terapia por Exercício/métodos , Inalação , Contração Muscular , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Músculos Respiratórios/fisiopatologia , Idoso , Eletromiografia , Terapia por Exercício/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica/fisiologia , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: A long-term imbalance between pro- and anti-inflammatory mediators leads to airway remodelling, which is strongly correlated to most of the symptoms, severity and progression of chronic lung inflammation. The Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis of the renin-angiotensin system is associated with attenuation of acute and chronic inflammatory processes. In this study, we investigated the effects of Ang-(1-7) treatment in a model of chronic allergic lung inflammation. EXPERIMENTAL APPROACH: Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged three times per week (days 21-46). These mice received Ang-(1-7) (1 µg·h(-1) , s.c.) by osmotic mini-pumps, for the last 28 days. Histology and morphometric analysis were performed in left lung and right ventricle. Airway responsiveness to methacholine, analysis of Ang-(1-7) levels (RIA), collagen I and III (qRT-PCR), ERK1/2 and JNK (Western blotting), IgE (elisa), cytokines and chemokines (elisa multiplex), and immunohistochemistry for Mas receptors were performed. KEY RESULTS: Infusion of Ang-(1-7) in OVA-sensitized and challenged mice decreased inflammatory cell infiltration and collagen deposition in the airways and lung parenchyma, and prevented bronchial hyperresponsiveness. These effects were accompanied by decreased IgE and ERK1/2 phosphorylation, and decreased pro-inflammatory cytokines. Mas receptors were detected in the epithelium and bronchial smooth muscle, suggesting a site in the lung for the beneficial actions of Ang-(1-7). CONCLUSIONS AND IMPLICATIONS: Ang-(1-7) exerted beneficial attenuation of three major features of chronic asthma: lung inflammation, airway remodelling and hyperresponsiveness. Our results support an important protective role of Ang-(1-7) in lung inflammation.
Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Angiotensina I/farmacologia , Anti-Inflamatórios/farmacologia , Hiper-Reatividade Brônquica/prevenção & controle , Broncoconstrição/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Pneumonia/prevenção & controle , Hipersensibilidade Respiratória/prevenção & controle , Animais , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/fisiopatologia , Colágeno/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Imunoglobulina E/sangue , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Camundongos Endogâmicos BALB C , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Ovalbumina , Fosforilação , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Pneumonia/fisiopatologia , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/agonistas , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/fisiopatologia , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: AVE 0991 (AVE) is a non-peptide compound, mimic of the angiotensin (Ang)-(1-7) actions in many tissues and pathophysiological states. Here, we have investigated the effect of AVE on pulmonary remodelling in a murine model of ovalbumin (OVA)-induced chronic allergic lung inflammation. EXPERIMENTAL APPROACH: We used BALB/c mice (6-8 weeks old) and induced chronic allergic lung inflammation by OVA sensitization (20 µg·mouse(-1) , i.p., four times, 14 days apart) and OVA challenge (1%, nebulised during 30 min, three times per·week, for 4 weeks). Control and AVE groups were given saline i.p and challenged with saline. AVE treatment (1 mg·kg(-1) ·per day, s.c.) or saline (100 µL·kg(-1) ·per day, s.c.) was given during the challenge period. Mice were anaesthetized 72 h after the last challenge and blood and lungs collected. In some animals, primary bronchi were isolated to test contractile responses. Cytokines were evaluated in bronchoalveolar lavage (BAL) and lung homogenates. KEY RESULTS: Treatment with AVE of OVA sensitised and challenged mice attenuated the altered contractile response to carbachol in bronchial rings and reversed the increased airway wall and pulmonary vasculature thickness and right ventricular hypertrophy. Furthermore, AVE reduced IL-5 and increased IL-10 levels in the BAL, accompanied by decreased Ang II levels in lungs. CONCLUSIONS AND IMPLICATIONS: AVE treatment prevented pulmonary remodelling, inflammation and right ventricular hypertrophy in OVA mice, suggesting that Ang-(1-7) receptor agonists are a new possibility for the treatment of pulmonary remodelling induced by chronic asthma.
Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Angiotensina I/farmacologia , Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Imidazóis/farmacologia , Pulmão/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Veias Pulmonares/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Asma/induzido quimicamente , Asma/imunologia , Asma/metabolismo , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/imunologia , Broncoconstrição/efeitos dos fármacos , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/prevenção & controle , Pulmão/irrigação sanguínea , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mimetismo Molecular , Ovalbumina , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Artéria Pulmonar/imunologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Veias Pulmonares/imunologia , Veias Pulmonares/metabolismo , Veias Pulmonares/fisiopatologia , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Fatores de TempoRESUMO
Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury (ALI). The aim of the present study was to investigate whether paraquat-induced acute pulmonary and extra-pulmonary lung injury (ALI-P and ALI-EX, respectively), in rats, affects glycogen content in different tissues. This measurement could indicate performance limitations of tissues, a new biochemical aspect of ARDS. ALI-P and ALI-EX were induced by injection into the trachea (0.5 mg/kg) and intraperitoneally (20 mg/kg) 24 hours prior to tissue collection. The control groups (CTRL) received the same volume of saline. Glycogen content (mg/g tissue) from different tissues was measured using the anthrone reagent. Glycogen content in the heart and kidney was higher in the ALI-EX group than the CTRL-EX group. Glycogen content in the gastrocnemius muscle was lower in the ALI-EX group than the CTRL-EX group. However, there were no significant differences in glycogen content in the diaphragm in the ALI-EX and ALI-P groups or in the gastrocnemius, heart and kidney in the ALI-P group when compared to the respective controls. ALI-EX caused a greater thickening of the alveolar walls, more areas of atelectasis and a greater abundance of inflammatory cells in comparison to ALI-P. These results demonstrate that glycogen content in ALI, induced by an herbicide that is highly toxic to humans and animals, is altered in different tissues depending on the location of the injury.