Maria da Glória Rodrigues-Machado

Noninvasive Ventilation Coupled With Nebulization During Asthma Crises: A Randomized Controlled Trial

BACKGROUND: Despite the clinical improvements attributed to noninvasive ventilation (NIV) during asthma crises, and the well established effects of nebulization, there are few studies on the effects of these interventions together. We hypothesized that nebulization coupled to NIV should raise radio-aerosol pulmonary deposition in asthmatics. The aims of this study were to assess the effects of coupling β-agonist nebulization and NIV during asthma exacerbations on radio-aerosol pulmonary deposition, using scintigraphy and cardiopulmonary parameters, to correlate pulmonary function with radio-aerosol deposition index, radio-aerosol penetration index, and pulmonary clearance. METHODS: In this controlled trial, 21 adults with moderate to severe asthma attack were randomized to a control group (n = 11) or experimental group (NIV + nebulizer group, n = 10). All subjects inhaled bronchodilators for 9 minutes, and after particles were counted with a gamma camera to analyze regions of interest and pulmonary clearance at 0, 15, 30, 45, and 60 min. RESULTS: Breathing frequency (P = < .001) and minute ventilation (P = .01) were reduced, and tidal volume was increased (P = .01) in the NIV + nebulizer group, compared with the control group. The NIV + nebulizer group had improvement from baseline values, compared to the control group in the following parameters: FEV1 46.7 ± 0.5% of predicted vs 29.8 ± 8.9% of predicted, P = .02), FVC (41.2 ± 1.5% of predicted vs 23.2 ± 7.1% of predicted, P = .02), peak expiratory flow (67.3 ± 38.3% of predicted vs 26.9 ± 12.1% of predicted, P = .01), and inspiratory capacity (54.9 ± 28.8% of predicted vs 31.2 ± 9.1% of predicted, P = .01). No differences were observed between groups regarding radio-aerosol deposition index or pulmonary clearance. Negative correlations were found between FEV1, forced expiratory flow during the middle half of the FVC maneuver (FEF25–75%), inspiratory capacity, and radio-aerosol penetration index. CONCLUSIONS: Coupling nebulization and NIV during asthma exacerbation did not improve radio-aerosol pulmonary deposition, but we observed clinical improvement of pulmonary function in these subjects. (ClinicalTrials.gov registration NCT01012050)

Paraquat Poisoning Induces TNF-α-Dependent iNOS/NO Mediated Hyporesponsiveness of the Aorta to Vasoconstrictors in Rats

Paraquat is a toxic herbicide that may induce acute lung injury, circulatory failure and death. The present work aimed at investigating whether there is systemic inflammation and vascular dysfunction after paraquat exposure and whether these parameters were related. There was neutrophilia and accumulation of neutrophils in lung and bronchoalveolar lavage of animals given paraquat. This was associated with an increase in serum levels of TNF-α. In rats given paraquat, the relaxant response of aortic rings to acetylcholine was not modified but the contractile response to phenylephrine was greatly reduced. Endothelium removal or treatment with non-selective (L-NAME) or selective (L-NIL) inhibitors of inducible nitric oxide synthase (iNOS) restored contraction of aortas. There was greater production of nitric oxide (NO), which was restored to basal level by L-NIL, and greater expression of iNOS in endothelial cells, as seen by Western blot analyses and confocal microscopy. Blockade of TNF-α reduced pulmonary and systemic inflammation and vascular dysfunction. Together, our results clearly show that paraquat causes pulmonary and systemic inflammation, and vascular dysfunction in rats. Vascular dysfunction is TNF-α dependent, associated with enhanced expression of iNOS in aortic endothelial cells and greater NO production, which accounts for the decreased responsiveness of aortas to vasoconstrictors. Blockers of TNF-α may be useful in patients with paraquat poisoning.

Exercise attenuates pulmonary injury in mice with bleomycin-induced pulmonary fibrosis

Human idiopathic pulmonary fibrosis (IPF) is a disease with unknown etiology and poor prognosis in which patients present a decrease in functional exercise tolerance and quality of life. At present, no treatment which can improve the prognosis of this disease is available. Many biomarkers of pulmonary fibrosis have been studied, and surfactant protein A (SP-A) expression is considered a specific marker of lung disease. This study aimed to investigate the influence of exercise training on exercise endurance capacity and murine-lung lesions induced by bleomycin (BLM). Thirty-four male Balb/c mice were subdivided into four groups: control sedentary (C-SED), bleomycin-treated sedentary (BLM-SED), control exercised (C-EXE) and bleomycin-treated exercised (BLM-EXE). Mice received 6.25 U/kg of BLM or saline via intratracheal instillation. After adaptation in a swimming pool, the animals started training one hour per day, with 60% of maximum load obtained in exercise endurance capacity assessment, five days/week for four weeks. The lungs were collected 48 h after the second endurance capacity assessment, fixed in buffered formalin and embedded in paraffin. Sections were analyzed using histochemical and immunohistochemical reactions for digital morphometry of pulmonary fibrosis, type I collagen, SP-A and type II pneumocytes (PII). The exercise endurance capacity of groups C-EXE (9.20 ± 0.81 min) and BLM-EXE (8.40 ± 0.82 min) increased significantly when compared with groups C-SED (5.84 ± 0.4 min) and BLM-SED (5.67 ± 0.60 min). The amounts of connective tissue, type I collagen, PII and SP-A increased significantly in the BLM-SED group. Exercise training significantly attenuated this response as observed in the BLM-EXE group. The present study shows that exercise training can prevent the decline of exercise endurance capacity and attenuate the progression of IPF.

Increased expression of endothelial iNOS accounts for hyporesponsiveness of pulmonary artery to vasoconstrictors after paraquat poisoning.

Paraquat is a toxic herbicide that induces severe acute lung injury (ALI) and pulmonary hypertension in humans. Although vascular disorders are present and contribute to increased mortality in ALI patients, there is little data available on vascular responsiveness after toxic exposure to paraquat. We aimed to evaluate the vascular response of isolated pulmonary arteries from rats treated with a dose of paraquat that induces ALI. Paraquat treatment did not modify the relaxant response of pulmonary artery to acetylcholine, but greatly reduced phenylephrine-induced contraction. Removal of the endothelium, inhibition of nitric oxide synthase (NOS) with L-NAME or selective inhibition of inducible NOS (iNOS) with L-NIL, restored contraction of vessels from paraquat poisoned rats to the same level as those not exposed to paraquat. The basal production of NO and expression of iNOS were increased in endothelium-intact but not in endothelium-denuded vessels from paraquat-poisoned rats. Expression of endothelial NOS was not modified. Our findings suggest that paraquat poisoning increases endothelial iNOS expression and basal NO production decreasing responsiveness of pulmonary artery to vasoconstrictors. Thus, our results do not support the hypothesis that pulmonary hypertension in paraquat-induced ALI is mediated by a reduction in endothelial NO production or increased contractility of pulmonary artery.

Effects of sepsis-induced acute lung injury on glycogen content in different tissues

ABSTRACT The metabolic profile is very affected in sepsis, which is the most important cause of extrapulmonary acute lung injury (ALI-EX). The aim of the present study was to investigate whether sepsis-induced ALI-EX in mice affects the glycogen content in different tissues. This measurement could indicate performance limitations of tissues and constitute a novel biochemical aspect of ALI. ALI was induced by cecal ligation and puncture (CLP), which is a model that reproduces clinical and pathological alterations stemming from sepsis. Control group mice were sham-operated. Glycogen content (mg/g tissue) from different tissues was measured using the anthrone reagent. Glycogen content in the diaphragm (0.3 ± 0.1) and gastrocnemius muscle (0.4 ± 0.1) was lower in the sepsis group than the control group (0.9 ± 0.1 and 1.1 ± 0.2, respectively). However, there were no significant differences in glycogen content in the heart and kidney. Sepsis caused a greater thickening of the alveolar walls, more areas of atelectasis, and a greater abundance of inflammatory cells in comparison to the control group. These results demonstrate that glycogen content in sepsis-induced ALI-EX is altered in different tissues.

Glycogen content is affected differently in acute pulmonary and extra-pulmonary lung injury

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.

Clinimetric properties of breath-stacking technique for assessment of inspiratory capacity.

BACKGROUND AND PURPOSE Breath stacking (BS) is used as an alternative method for lung expansion therapy and the assessment of inspiratory capacity in uncooperative patients. The aims of the present study were to identify the reproducibility of the BS technique in healthy volunteers and to compare BS with conventional spirometry with regard to inspiratory capacity. METHODS A cross-sectional study was carried out. Eighty-five healthy volunteers (21.78 ± 2.79 years; 41 men, 44 women) underwent spirometry and BS. Lung function, anthropometric and cardiopulmonary parameters were evaluated prior to the intervention. BS was performed with a unidirectional inspiratory valve by two different examiners. The order of each examiner was randomized. Spirometric tests were performed three times, and the BS manoeuvre was evaluated three times by each examiner. Respiratory rate, heart rate and peripheral arterial oxygen saturation were determined before, during and following the manoeuvre. RESULTS There were no statistically significant differences in the intra-examiner and inter-examiner analyses for the volume mobilized during BS, respiratory rate, duration of BS manoeuvre or perceived effort index (p > 0.05). The intra-class correlation coefficient was greater than 0.7 for all variables analysed. Maximal volumes achieved using the BS technique were significantly higher than those achieved with conventional spirometry (p < 0.0001). CONCLUSION Data from both the intra-examiner and inter-examiner analyses suggest that the BS technique is reproducible. This technique mobilizes greater lung volumes than conventional spirometry.

Evidence that central action of paraquat interferes in the dipsogenic effect of Ang II.

Paraquat is a widely used herbicide that may have central neurotoxic actions. In this study we investigated whether administration of paraquat in the central nervous system interferes with the physiological role of angiotensin II in regulating blood pressure, water intake and thermogenesis. Under tribromoethanol anesthesia (250 mg/kg, i.p.) guide canulas were implanted into the cerebral ventricle of male Wistar rats ( congruent with 300g) for microinjections of drugs. Four days later, a catheter was placed into the femoral artery to enable recording of cardiovascular parameters. After 24h, paraquat (38 or 44 nmol/2 microl), angiotensin II (Ang II, 1 nmol/2 microl) or the cholinergic agonist, carbachol (4 nmol/2 microl) were administered intracerebroventricular (icv) and physiological effects were measured. We observed that the dipsogenic action evoked by Ang II (8+/-2 ml) was markedly attenuated by previous icv injection of either 38 or 44 nmol paraquat (3+/-1 ml; P<0.05). However, the dipsogenic effect evoked by carbachol was not altered by pretreatment with paraquat (before 8+/-1 vs. after 6+/-2; P>0.05). Cardiovascular and thermogenic responses evoked by Ang II were not altered by paraquat. These results suggest that paraquat might selectively interfere with the drinking behavior mediated by the renin-angiotensin system in the central nervous system.

A influência de duas frações inspiradas de oxigênio no padrão respiratório de pacientes sob desmame ventilatório

INTRODUCAO E OBJETIVOS: Fracoes inspiradas de oxigenio (FiO2) 150-200 mmHg, O objetivo desse estudo foi comparar as variaveis respiratorias e os dados vitais coletados durante a utilizacao de uma FiO2 suficiente para manter a saturacao periferica de oxigenio em 92% (ideal) com aquelas coletadas durante uma FiO2 rotineiramente ajustada em 40% (basal) em pacientes sob desmame ventilatorio. METODOS: Estudo prospectivo cruzado. As variaveis frequencia respiratoria, volume corrente, pressao de oclusao, relacao tempo inspiratorio/tempo total, pressao arterial e frequencia cardiaca foram coletados, sequencialmente, aos 30 e 60 minutos sob FiO2 basal (40%) e, em seguida sob FiO2 ideal. Essas foram comparadas pelo modelo linear generalizado para medidas repetidas. Para comparar os valores basal e ideal da FiO2 e da PaO2 foram utilizados os testes t Student ou Wilcoxon. RESULTADOS: Em 30 pacientes adultos a mediana da FiO2 ideal foi 25% (IQ25%-75% 23-28), significativamente menor que a basal (40%) (p 92% nao alteraram o padrao respiratorio ou provocaram alteracoes clinicas em pacientes sob desmame ventilatorio.

CHANGES IN AORTIC PULSE WAVE COMPONENTS, PULSE PRESSURE AMPLIFICATION, AND HEMODYNAMIC PARAMETERS OF CHILDREN AND ADOLESCENTS WITH TYPE 1 DIABETES

Type 1 diabetes mellitus (DM1) presents important risk factors for cardiovascular events.