RESUMO
OBJECTIVE: To investigate the effect of bronchodilator on the respiratory mechanics and pulmonary function of children and adolescents with cystic fibrosis. METHODS: Cross-sectional study on clinically stable children and adolescents with cystic fibrosis aged from six to 15 years. Participants underwent impulse oscillometry and spirometry evaluations before and 15 minutes after bronchodilator inhalation. The Kolmogorov-Smirnov test was applied to verify the sample distribution, and the Student's t-test and Wilcoxon test were used to compare the data before and after bronchodilator inhalation. RESULTS: The study included 54 individuals with a mean age of 9.7±2.8 years. The analysis showed a statistically significant improvement in impulse oscillometry and spirometry parameters after bronchodilator inhalation. However, according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) recommendations (2020 and 2021), this improvement was not sufficient to classify it as a bronchodilator response. CONCLUSIONS: The use of bronchodilator medication improved respiratory mechanics and pulmonary function parameters of children and adolescents with cystic fibrosis; however, most patients did not show bronchodilator response according to ATS/ERS recommendations.
Assuntos
Broncodilatadores , Fibrose Cística , Oscilometria , Espirometria , Humanos , Fibrose Cística/fisiopatologia , Fibrose Cística/tratamento farmacológico , Criança , Adolescente , Estudos Transversais , Espirometria/métodos , Feminino , Masculino , Oscilometria/métodos , Broncodilatadores/uso terapêutico , Broncodilatadores/administração & dosagem , Mecânica Respiratória/efeitos dos fármacos , Mecânica Respiratória/fisiologia , Testes de Função Respiratória/métodosRESUMO
Acute intermittent hypoxia (AIH) modifies the functioning of the respiratory network, causing respiratory motor facilitation in anesthetized animals and a compensatory increase in pulmonary ventilation in freely behaving animals. However, it is still unclear whether the ventilatory facilitation induced by AIH in unanesthetized animals is associated with changes in the respiratory pattern. We found that Holtzman male rats (80-150 g) exposed to AIH (10 × 6% O2 for 30-40 s every 5 min, n = 9) exhibited a prolonged (30 min) increase in baseline minute ventilation (P < 0.05) compared to control animals (n = 13), combined with the occurrence of late expiratory peak flow events, suggesting the presence of active expiration. The increase in ventilation after AIH was also accompanied by reductions in arterial CO2 and body temperature (n = 5-6, P < 0.05). The systemic treatment with ketanserin (a 5-HT2 receptor antagonist) before AIH prevented the changes in ventilation and active expiration (n = 11) but potentiated the hypothermic response (n = 5, P < 0.05) when compared to appropriate control rats (n = 13). Our findings indicate that the ventilatory long-term facilitation elicited by AIH exposure in unanesthetized rats is linked to the generation of active expiration by mechanisms that may depend on the activation of serotonin receptors. In contrast, the decrease in body temperature induced by AIH may not require 5-HT2 receptor activation.
Assuntos
Hipóxia/fisiopatologia , Ketanserina/farmacologia , Ventilação Pulmonar/fisiologia , Mecânica Respiratória/fisiologia , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Ventilação Pulmonar/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Mecânica Respiratória/efeitos dos fármacos , Volume de Ventilação Pulmonar/fisiologiaRESUMO
We aimed at evaluating the anti-asthmatic effect of cis-[Ru(bpy)2(2-MIM)(NO)](PF6)3 (FOR811A), a nitrosyl-ruthenium compound, in a murine model of allergic asthma. The anti-asthmatic effects were analyzed by measuring the mechanical lung and morphometrical parameters in female Swiss mice allocated in the following groups: untreated control (Ctl+Sal) and control treated with FOR811A (Ctl+FOR), along asthmatic groups untreated (Ast+Sal) and treated with FOR811A (Ast+FOR). The drug-protein interaction was evaluated by in-silico assay using molecular docking. The results showed that the use of FOR811A in experimental asthma (Ast+FOR) decreased the pressure-volume curve, hysteresis, tissue elastance, tissue resistance, and airway resistance, similar to the control groups (Ctl+Sal; Ctl+FOR). However, it differed from the untreated asthmatic group (Ast+Sal, p<0.05), indicating that FOR811A corrected the lung parenchyma and relaxed the smooth muscles of the bronchi. Similar to control groups (Ctl+Sal; Ctl+FOR), FOR811A increased the inspiratory capacity and static compliance in asthmatic animals (Ast+Sal, p<0.05), showing that this metallodrug improved the capacity of inspiration during asthma. The morphometric parameters showed that FOR811A decreased the alveolar collapse and kept the bronchoconstriction during asthma. Beyond that, the molecular docking using FOR811A showed a strong interaction in the distal portion of the heme group of the soluble guanylate cyclase, particularly with cysteine residue (Cys141). In summary, FOR811A relaxed bronchial smooth muscles and improved respiratory mechanics during asthma, providing a protective effect and promising use for the development of an anti-asthmatic drug.
Assuntos
Antiasmáticos , Asma , Doadores de Óxido Nítrico , Compostos Organometálicos , Mecânica Respiratória/efeitos dos fármacos , Rutênio , Animais , Antiasmáticos/química , Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Asma/fisiopatologia , Feminino , Camundongos , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Rutênio/química , Rutênio/farmacologiaRESUMO
Assessment of respiratory mechanics extends from basic research and animal modeling to clinical applications in humans. However, to employ the applications in human models, it is desirable and sometimes mandatory to study non-human animals first. To acquire further precise and controlled signals and parameters, the animals studied must be further distant from their spontaneous ventilation. The majority of respiratory mechanics studies use positive pressure ventilation to model the respiratory system. In this scenario, a few drug categories become relevant: anesthetics, muscle blockers, bronchoconstrictors, and bronchodilators. Hence, the main objective of this study is to briefly review and discuss each drug category, and the impact of a drug on the assessment of respiratory mechanics. Before and during the positive pressure ventilation, the experimental animal must be appropriately sedated and anesthetized. The sedation will lower the pain and distress of the studied animal and the plane of anesthesia will prevent the pain. With those drugs, a more controlled procedure is carried out; further, because many anesthetics depress the respiratory system activity, a minimum interference of the animal's respiration efforts are achieved. The latter phenomenon is related to muscle blockers, which aim to minimize respiratory artifacts that may interfere with forced oscillation techniques. Generally, the respiratory mechanics are studied under appropriate anesthesia and muscle blockage. The application of bronchoconstrictors is prevalent in respiratory mechanics studies. To verify the differences among studied groups, it is often necessary to challenge the respiratory system, for example, by pharmacologically inducing bronchoconstriction. However, the selected bronchoconstrictor, doses, and administration can affect the evaluation of respiratory mechanics. Although not prevalent, studies have applied bronchodilators to return (airway resistance) to the basal state after bronchoconstriction. The drug categories can influence the mathematical modeling of the respiratory system, systemic conditions, and respiratory mechanics outcomes.
Assuntos
Modelos Animais , Mecânica Respiratória/efeitos dos fármacos , Anestésicos/farmacologia , Animais , Broncoconstritores/farmacologia , Broncodilatadores/farmacologia , Bloqueadores Neuromusculares/farmacologiaRESUMO
One of the possible causes of death in epilepsy is breathing disorders, especially apneas, which lead to an increase in CO2 levels (hypercapnia) and/or a decrease in O2 levels in arterial blood (hypoxemia). The respiratory neurons located in the ventral brainstem respiratory column are the main groups responsible for controlling breathing. Recent data from our group demonstrated respiratory changes in two experimental models of epilepsy, i.e. audiogenic epilepsy, and amygdala rapid kindling. Here, we aimed to evaluate respiratory changes in the classic model of temporal lobe epilepsy induced by intra-hippocampal injection of pilocarpine. Adult Wistar rats with stainless-steel cannulas implanted in the hippocampus region were used. The animals were submitted to pilocarpine injection (2.4 mg/µL, N = 12-15) or saline (N = 9) into the hippocampus. The respiratory parameters analyzed by whole-body plethysmography were respiratory rate (fR), tidal volume (VT) and ventilation (VE). Respiratory mechanics such as Newtonian airway resistance (Rn), viscance of the pulmonary parenchyma (G) and the elastance of the pulmonary parenchyma (H) were also investigated. No changes in baseline breathing were detected 15 or 30 days after pilocarpine-induced status epilepticus (SE). However, 30 days after pilocarpine-induced SE, a significant reduction in VE was observed during hypercapnic (7% CO2) stimulation, without affecting the hypoxia (8% O2) ventilatory response. We also did not observe changes in respiratory mechanics. The present results suggest that the impairment of the hypercapnia ventilatory response in pilocarpine-induced SE could be related to a presumable degeneration of brainstem respiratory neurons but not to peripheral mechanisms.
Assuntos
Células Quimiorreceptoras/efeitos dos fármacos , Pilocarpina/toxicidade , Respiração/efeitos dos fármacos , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/fisiopatologia , Volume de Ventilação Pulmonar/efeitos dos fármacos , Animais , Células Quimiorreceptoras/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Hipercapnia/induzido quimicamente , Hipercapnia/fisiopatologia , Injeções Intraventriculares , Masculino , Agonistas Muscarínicos/administração & dosagem , Agonistas Muscarínicos/toxicidade , Pilocarpina/administração & dosagem , Ratos , Ratos Wistar , Mecânica Respiratória/efeitos dos fármacos , Mecânica Respiratória/fisiologia , Volume de Ventilação Pulmonar/fisiologiaRESUMO
Aim: This study aimed to analyze the Constant Phase Model (CPM) Coefficient of Determination (COD) and an index of harmonic distortion ([Formula: see text]) behavior in intravenous methacholine dose response curve. We studied the COD and [Formula: see text] behavior of Control and Lung Inflammation (OVA) groups of mice and we proposed an alternative for moments when the CPM should not be applied. Methods: 9-week female BALB/c mice were studied, 8 of the control group (23.11 ± 1.27 g) and 11 of the lung inflammation group (OVA) (21.45 ± 2.16 g). The COD values were obtained during the respiratory mechanics assessment via Forced Oscillation Technique (FOT) and the [Formula: see text] was estimated a posteriori. Both control and OVA groups were submitted to 4 doses of Methacholine (MCh) protocol. Results: A strong correlation between COD and [Formula: see text] was present at the last two doses (0.3 mg/kg: r = -0.75, p = 0.0013 and 1 mg/kg: r = -0.91; p < 0.0001) in the OVA group. Differences were found in doses of 0.3 mg/kg between control and OVA for the maximum values of Rn (Newtonian Resistance) and G (tissue viscous); and between groups at PBS and doses of 0.03, 0.1 and 0.3 mg/kg for H (Elastance). A similar behavior was observed for the analysis of Area Under the Curve with the exclusion of the 3 first measurements of each dose. However, in this scenario, the comparison with the maximum value presented a higher discriminatory capacity of the parameters associated with the parenchyma. Conclusions: During severe bronchoconstriction there is a strong negative correlation between model goodness of fit and nonlinearities levels, reinforcing that COD is a robust acceptance criterion, whether still simple and easily obtained from the ventilator. We also pointed out the area under the CPM parameters dose response curve is a useful and can be used as a complementary analysis to peak comparison following bolus injections of methacholine.
Assuntos
Cloreto de Metacolina/administração & dosagem , Cloreto de Metacolina/farmacologia , Mecânica Respiratória/efeitos dos fármacos , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Broncoconstrição/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Pneumonia/tratamento farmacológico , Testes de Função Respiratória/métodosRESUMO
Mammals airways are extensively innervated by the vagus nerve, which controls the airway diameter and bronchial tone. However, very few studies described the respiratory function and lung morphology after vagal section. In the present study, we evaluated the respiratory mechanics after aerosolization of vehicle (to obtain control values), a muscarinic agonist (methacholine), a ß2-adrenergic agonist (salbutamol) or a muscarinic antagonist (ipratropium bromide) in intact (Vi) and bilaterally vagotomized (Vx) Swiss male mice. Different group was established for morphometric analyze. The total lung resistance, airway resistance, elastance, compliance, lung tissue damping, lung tissue elastance, and morphological parameters (collagen and elastic fibers) were significantly different in the Vx group compared to the Vi group. Bronchoconstrictor and bronchodilators change the respiratory function of the Vx group. In conclusion, the vagus nerve modulates the lung function in response to bronchoconstriction and bronchodilation, as well as lung architecture of mice.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Broncoconstritores/farmacologia , Broncodilatadores/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Antagonistas Muscarínicos/farmacologia , Mecânica Respiratória/efeitos dos fármacos , Mecânica Respiratória/fisiologia , Vagotomia , Nervo Vago/fisiologia , Albuterol/farmacologia , Animais , Colágeno , Tecido Elástico , Ipratrópio/farmacologia , Pulmão/ultraestrutura , Masculino , Cloreto de Metacolina/farmacologia , Camundongos , Agonistas Muscarínicos/farmacologiaRESUMO
To evaluate whether a recombinant serine protease inhibitor (rBmTI-A) modulates inflammation in an experimental model of chronic allergic lung inflammation. Balb/c mice were divided into four groups: SAL (saline), OVA (sensitized with ovalbumin), SAL + rBmTI-A (control treated with rBmTI-A) and OVA + rBmTI-A (sensitized with ovalbumin and treated with rBmTI-A). The animals received an intraperitoneal injection of saline or ovalbumin, according to the group. The groups received inhalation with saline or ovalbumin and were treated with rBmTI-A or saline by nasal instillation. After 29 days, we evaluated the respiratory mechanics; bronchoalveolar lavage fluid (BALF); cytokines; MMP-9, TIMP-1; eosinophils; collagen and elastic fibre expression in the airways; and the trypsin-like, MMP-1, and MMP-9 lung tissue proteolytic activity. Treatment with rBmTI-A reduced the trypsin-like proteolytic activity, the elastance and resistance maximum response, the polymorphonuclear cells, IL-5, IL-10, IL-13 and IL-17A in the BALF, the expression of IL-5, IL-13, IL-17, CD4+, MMP-9, TIMP-1, eosinophils, collagen and elastic fibres in the airways of the OVA + rBmTI-A group compared to the OVA group (p < 0.05). rBmTI-A attenuated bronchial hyperresponsiveness, inflammation and remodelling in this experimental model of chronic allergic pulmonary inflammation. This inhibitor may serve as a potential therapeutic tool for asthma treatment.
Assuntos
Hipersensibilidade/complicações , Hipersensibilidade/tratamento farmacológico , Pneumonia/complicações , Pneumonia/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Inibidores de Serina Proteinase/uso terapêutico , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar , Doença Crônica , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Matriz Extracelular/metabolismo , Hipersensibilidade/fisiopatologia , Pulmão/patologia , Pulmão/fisiopatologia , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Pneumonia/fisiopatologia , Proteólise , Proteínas Recombinantes/farmacologia , Mecânica Respiratória/efeitos dos fármacosRESUMO
OBJECTIVE: Croton zehntneri Pax et Hoffm. is a Euphorbiaceae species, popularly known as "canela de cunhã," a native plant of northeastern Brazil, whose essential oil (EOCZ) shows relatively specific myorelaxant action for the smooth muscle of the airways and in the respiratory tract. Based on this information, EOCZ figures as a candidate for testing in the treatment of asthma, and the present study investigated the benefits of using EOCZ in an ovalbumin-induced asthma model. METHODS: 48 male BALB/c mice were divided into six groups (n = 8). In the ST, SO100, and SO300 groups, mice were sensitized and challenged with saline, and then treated with 200 µL of 0.1% Tween 80, 100 mg/kg EOCZ and 300 mg/kg EOCZ, respectively. In the OT, OO100, and OO300 groups, mice were sensitized and challenged with OVA, and then treated with 200 µL of 0.1% Tween 80, 100 mg/kg EOCZ and 300 mg/kg EOCZ, respectively. RESULTS: Our results demonstrated significant changes in all respiratory mechanics variables analyzed between the OO300 and OT groups demonstrating the effectiveness of EOCZ to attenuate the OVA-induced lung injury. In addition, the use of EOCZ at a dose of 300 mg/kg showed an antioxidant effect and decreased inflammatory cells in the pulmonary parenchyma. In conclusion, our results demonstrated that EOCZ was able to improve the lesion in the respiratory system of mice subjected to OVA-induced asthma. CONCLUSIONS: The antioxidant action of EOCZ was likely the main mechanism of action in the reversal of this lesion, so more tests should be performed for its confirmation.
Assuntos
Asma/tratamento farmacológico , Croton , Lesão Pulmonar/tratamento farmacológico , Óleos Voláteis/farmacologia , Mecânica Respiratória/efeitos dos fármacos , Animais , Asma/induzido quimicamente , Asma/patologia , Brasil , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Masculino , Cloreto de Metacolina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Fitoterapia , Folhas de PlantaRESUMO
INTRODUCTION: Hemodialysis (HD) is one treatment for acute kidney injury (AKI) patients. Studies have shown that this dialysis modality may lead to changes in pulmonary function with an impact on prognosis. The aim of our study was to evaluate changes in respiratory mechanics and oxygenation of AKI patients admitted to an intensive care unit who were undergoing intermittent mechanical ventilation (IMV) and daily HD. METHODS: This prospective cohort study evaluated 94 AKI patients and 234 HD sessions. Pulmonary static compliance (Pcs), resistance (Rsr), and arterial partial pressure of oxygen and the fraction of inspired oxygen (PaO2 /FiO2 ) ratio were assessed during the initial three-day period of daily HD therapy. FINDINGS: Psc increased progressively during HD sessions, from 39.4 ± 21.4 mL/cm H2 O prior to the initial dialysis to 55.5 ± 25.2 at the end of the last dialysis during the study period (P = 0.04). Similarly, Rsr and PaO2 /FiO2 ratio also improved, from 11.1 ± 6.3 cm H2 O/L/s prior to the initial dialysis to 8.8 ± 4.2 at the end of the last dialysis (P =0.0027) and from 228 ± 85 prior to the initial dialysis to 312.1 ± 111.5, P < 0.001, to the end of the last dialysis, respectively. CONCLUSION: This study showed that AKI patients undergoing IMV and daily HD improve their respiratory mechanics and oxygenation.