RESUMO
Vitamin D receptor-knockout mice fail to produce mature oocytes, indicating vitamin D is crucial for folliculogenesis in mice. However, the actions of vitamin D during folliculogenesis remain unknown. This prospective study aimed to assess whether follicular fluid (FF) vitamin D (25OHD3) concentrations are related to specific responses to ovarian stimulation. Women undergoing ovarian stimulation for IVF participated in the study. FF 25OHD3 concentrations were assessed in the first follicle aspirate on oocyte retrieval day. Oestradiol and progesterone concentrations were assessed on the trigger day. K-means grouping analysis showed that 25OHD3 FF concentrations clustered into a higher and lower group (mean ± SEM 17.4 ± 6.61 ng/ml and 35.5 ± 7.17 ng/ml, respectively, P < 0.001). The clusters were analysed according to the oestradiol and progesterone concentrations, follicle number and size and resulting oocyte number and maturity. The FF 25OHD3 concentrations were no different among the infertility diagnoses. The lower 25OHD3 group had more follicles (≥16.0 mm, P = 0.009) and higher serum oestradiol concentrations (P < 0.03) on the day of HCG administration. In this study, lower follicular 25OHD3 concentrations predicted a better response to ovarian stimulation shown by a greater production of larger follicles and higher serum oestradiol concentrations.
Assuntos
Estradiol/sangue , Líquido Folicular/metabolismo , Folículo Ovariano/citologia , Progesterona/sangue , Vitamina D/metabolismo , Adulto , Feminino , Fertilização in vitro , Humanos , Folículo Ovariano/metabolismo , Indução da Ovulação , Estudos ProspectivosRESUMO
OBJECTIVES: Lung-protective mechanical ventilation aims to prevent alveolar collapse and overdistension, but reliable bedside methods to quantify them are lacking. We propose a quantitative descriptor of the shape of local pressure-volume curves derived from electrical impedance tomography, for computing maps that highlight the presence and location of regions of presumed tidal recruitment (i.e., elastance decrease during inflation, pressure-volume curve with upward curvature) or overdistension (i.e., elastance increase during inflation, downward curvature). DESIGN: Secondary analysis of experimental cohort study. SETTING: University research facility. SUBJECTS: Twelve mechanically ventilated pigs. INTERVENTIONS: After induction of acute respiratory distress syndrome by hydrochloric acid instillation, animals underwent a decremental positive end-expiratory pressure titration (steps of 2 cm H2O starting from ≥ 26 cm H2O). MEASUREMENTS AND MAIN RESULTS: Electrical impedance tomography-derived maps were computed at each positive end-expiratory pressure-titration step, and whole-lung CT taken every second steps. Airway flow and pressure were recorded to compute driving pressure and elastance. Significant correlations between electrical impedance tomography-derived maps and positive end-expiratory pressure indicate that, expectedly, tidal recruitment increases in dependent regions with decreasing positive end-expiratory pressure (p < 0.001) and suggest that overdistension increases both at high and low positive end-expiratory pressures in nondependent regions (p < 0.027), supporting the idea of two different scenarios of overdistension occurrence. Significant correlations with CT measurements were observed: electrical impedance tomography-derived tidal recruitment with poorly aerated regions (r = 0.43; p < 0.001); electrical impedance tomography-derived overdistension with nonaerated regions at lower positive end-expiratory pressures and with hyperaerated regions at higher positive end-expiratory pressures (r ≥ 0.72; p < 0.003). Even for positive end-expiratory pressure levels minimizing global elastance and driving pressure, electrical impedance tomography-derived maps showed nonnegligible regions of presumed overdistension and tidal recruitment. CONCLUSIONS: Electrical impedance tomography-derived maps of pressure-volume curve shapes allow to detect regions in which elastance changes during inflation. This could promote individualized mechanical ventilation by minimizing the probability of local tidal recruitment and/or overdistension. Electrical impedance tomography-derived maps might become clinically feasible and relevant, being simpler than currently available alternative approaches.
Assuntos
Impedância Elétrica , Pulmão/diagnóstico por imagem , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Tomografia , Animais , Modelos Animais de Doenças , Elasticidade , Pulmão/fisiopatologia , Respiração com Pressão Positiva , Pressão , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , SuínosRESUMO
BACKGROUND: Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a potentially lethal complication of clinical malaria. Acute lung injury in MA-ARDS shares features with ARDS triggered by other causes, including alveolar inflammation and increased alveolar-capillary permeability, leading to leak of protein-rich pulmonary oedema fluid. Mechanisms and physiologic alterations in MA-ARDS can be examined in murine models of this syndrome. Integrin αDß2 is a member of the leukocyte, or ß2 (CD18), sub-family of integrins, and emerging observations indicate that it has important activities in leukocyte adhesion, accumulation and signalling. The goal was to perform analysis of the lungs of mice wild type C57Bl/6 (a D (+/+) ) and Knockout C57Bl/6 (a D (-/-) ) with malaria-associated acute lung injury to better determine the relevancy of the murine models and investigate the mechanism of disease. METHODS: C57BL/6 wild type (a D (+/+) ) and deficient for CD11d sub-unit (a D (-/-) ) mice were monitored after infection with 10(5) Plasmodium berghei ANKA. CD11d subunit expression RNA was measured by real-time polymerase chain reaction, vascular barrier integrity by Evans blue dye (EBD) exclusion and cytokines by ELISA. Protein and leukocytes were measured in bronchoalveolar lavage fluid (BALF) samples. Tissue cellularity was measured by the point-counting technique, F4/80 and VCAM-1 expression by immunohistochemistry. Respiratory function was analysed by non-invasive BUXCO and mechanical ventilation. RESULTS: Alveolar inflammation, vascular and interstitial accumulation of monocytes and macrophages, and disrupted alveolar-capillary barrier function with exudation of protein-rich pulmonary oedema fluid were present in P. berghei-infected wild type mice and were improved in αDß2-deficient animals. Key pro-inflammatory cytokines were also decreased in lung tissue from α D (-/-) mice, providing a mechanistic explanation for reduced alveolar-capillary inflammation and leak. CONCLUSIONS: The results indicate that αDß2 is an important inflammatory effector molecule in P. berghei-induced MA-ARDS, and that leukocyte integrins regulate critical inflammatory and pathophysiologic events in this model of complicated malaria. Genetic deletion of integrin subunit αD in mice, leading to deficiency of integrin αDß2, alters lung inflammation and acute lung injury in a mouse model of MA-ARDS caused by P. berghei.
Assuntos
Antígenos CD11/metabolismo , Cadeias alfa de Integrinas/metabolismo , Malária/complicações , Síndrome do Desconforto Respiratório/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/análise , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Azul Evans/metabolismo , Perfilação da Expressão Gênica , Imuno-Histoquímica , Contagem de Leucócitos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Permeabilidade , Plasmodium berghei/crescimento & desenvolvimento , Proteínas/análise , Reação em Cadeia da Polimerase em Tempo Real , Testes de Função RespiratóriaRESUMO
BACKGROUND: Uncertainty persists regarding the optimal ventilatory strategy in trauma patients developing acute respiratory distress syndrome (ARDS). This work aims to assess the effects of two mechanical ventilation strategies with high positive end-expiratory pressure (PEEP) in experimental ARDS following blunt chest trauma. METHODS: Twenty-six juvenile pigs were anesthetized, tracheotomized and mechanically ventilated. A contusion was applied to the right chest using a bolt-shot device. Ninety minutes after contusion, animals were randomized to two different ventilation modes, applied for 24 h: Twelve pigs received conventional pressure-controlled ventilation with moderately low tidal volumes (VT, 8 ml/kg) and empirically chosen high external PEEP (16 cmH2O) and are referred to as the HP-CMV-group. The other group (n = 14) underwent high-frequency inverse-ratio pressure-controlled ventilation (HFPPV) involving respiratory rate of 65 breaths · min(-1), inspiratory-to-expiratory-ratio 2:1, development of intrinsic PEEP and recruitment maneuvers, compatible with the rationale of the Open Lung Concept. Hemodynamics, gas exchange and respiratory mechanics were monitored during 24 h. Computed tomography and histology were analyzed in subgroups. RESULTS: Comparing changes which occurred from randomization (90 min after chest trauma) over the 24-h treatment period, groups differed statistically significantly (all P values for group effect <0.001, General Linear Model analysis) for the following parameters (values are mean ± SD for randomization vs. 24-h): PaO2 (100% O2) (HFPPV 186 ± 82 vs. 450 ± 59 mmHg; HP-CMV 249 ± 73 vs. 243 ± 81 mmHg), venous admixture (HFPPV 34 ± 9.8 vs. 11.2 ± 3.7%; HP-CMV 33.9 ± 10.5 vs. 21.8 ± 7.2%), PaCO2 (HFPPV 46.9 ± 6.8 vs. 33.1 ± 2.4 mmHg; HP-CMV 46.3 ± 11.9 vs. 59.7 ± 18.3 mmHg) and normally aerated lung mass (HFPPV 42.8 ± 11.8 vs. 74.6 ± 10.0 %; HP-CMV 40.7 ± 8.6 vs. 53.4 ± 11.6%). Improvements occurring after recruitment in the HFPPV-group persisted throughout the study. Peak airway pressure and VT did not differ significantly. HFPPV animals had lower atelectasis and inflammation scores in gravity-dependent lung areas. CONCLUSIONS: In this model of ARDS following unilateral blunt chest trauma, HFPPV ventilation improved respiratory function and fulfilled relevant ventilation endpoints for trauma patients, i.e. restoration of oxygenation and lung aeration while avoiding hypercapnia and respiratory acidosis.
Assuntos
Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Mecânica Respiratória/fisiologia , Traumatismos Torácicos/terapia , Ferimentos não Penetrantes/terapia , Animais , Respiração com Pressão Positiva/métodos , Distribuição Aleatória , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Suínos , Traumatismos Torácicos/complicações , Traumatismos Torácicos/fisiopatologia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/fisiopatologiaRESUMO
INTRODUCTION: When alveoli collapse the traction forces exerted on their walls by adjacent expanded units may increase and concentrate. These forces may promote its re-expansion at the expense of potentially injurious stresses at the interface between the collapsed and the expanded units. We developed an experimental model to test the hypothesis that a local non-lobar atelectasis can act as a stress concentrator, contributing to inflammation and structural alveolar injury in the surrounding healthy lung tissue during mechanical ventilation. METHODS: A total of 35 rats were anesthetized, paralyzed and mechanically ventilated. Atelectasis was induced by bronchial blocking: after five minutes of stabilization and pre-oxygenation with FIO2 = 1.0, a silicon cylinder blocker was wedged in the terminal bronchial tree. Afterwards, the animals were randomized between two groups: 1) Tidal volume (VT) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH2O (VT10/PEEP3); and 2) VT = 20 ml/kg and PEEP = 0 cmH2O (VT20/zero end-expiratory pressure (ZEEP)). The animals were then ventilated during 180 minutes. Three series of experiments were performed: histological (n = 12); tissue cytokines (n = 12); and micro-computed tomography (microCT; n = 2). An additional six, non-ventilated, healthy animals were used as controls. RESULTS: Atelectasis was successfully induced in the basal region of the lung of 26 out of 29 animals. The microCT of two animals revealed that the volume of the atelectasis was 0.12 and 0.21 cm3. There were more alveolar disruption and neutrophilic infiltration in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. Edema was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in the VT20/ZEEP than VT10/PEEP3 group. The volume-to-surface ratio was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. We did not find statistical difference in tissue interleukin-1ß and cytokine-induced neutrophil chemoattractant-1 between regions. CONCLUSIONS: The present findings suggest that a local non-lobar atelectasis acts as a stress concentrator, generating structural alveolar injury and inflammation in the surrounding lung tissue.
Assuntos
Inflamação/etiologia , Alvéolos Pulmonares/patologia , Atelectasia Pulmonar/complicações , Animais , Interleucina-1beta , Pulmão/patologia , Masculino , Respiração com Pressão Positiva/métodos , Atelectasia Pulmonar/patologia , Ratos , Mecânica Respiratória/fisiologia , Volume de Ventilação Pulmonar , Microtomografia por Raio-XRESUMO
PURPOSE: To compare texture-based analysis using convolutional neural networks (CNNs) against lung densitometry in detecting chest computed tomography (CT) image abnormalities. MATERIAL AND METHODS: A U-NET was used for lung segmentation, and an ensemble of 7 CNN architectures was trained for the classification of low-attenuation areas (LAAs; emphysema, cysts), normal-attenuation areas (NAAs; normal parenchyma), and high-attenuation areas (HAAs; ground-glass opacities, crazy paving/linear opacity, consolidation). Lung densitometry also computes (LAAs, ≤-950 HU), NAAs (-949 to -700 HU), and HAAs (-699 to -250 HU). CNN-based and densitometry-based severity indices (CNN and Dens, respectively) were calculated as (LAA+HAA)/(LAA+NAA+HAA) in 812 CT scans from 176 normal subjects, 343 patients with emphysema, and 293 patients with interstitial lung disease (ILD). The correlation between CNN-derived and densitometry-derived indices was analyzed, alongside a comparison of severity indices among patient subgroups with emphysema and ILD, using the Spearman correlation and ANOVA with Bonferroni correction. RESULTS: CNN-derived and densitometry-derived severity indices (SIs) showed a strong correlation (ρ=0.90) and increased with disease severity. CNN-SIs differed from densitometry SIs, being lower for emphysema and higher for moderate to severe ILD cases. CNN estimations for normal attenuation areas were higher than those from densitometry across all groups, indicating a potential for more accurate characterization of lung abnormalities. CONCLUSIONS: CNN outputs align closely with densitometry in assessing lung abnormalities on CT scans, offering improved estimates of normal areas and better distinguishing similar abnormalities. However, this requires higher computing power.
RESUMO
OBJECTIVES: To explore whether 1) conventional pressure support ventilation improves lung function and attenuates the pulmonary inflammatory response compared to pressure-controlled ventilation and 2) random variation of pressure support levels (noisy pressure support ventilation) adds further beneficial effects to pressure support ventilation. DESIGN: Three-arm, randomized, experimental study. SETTING: University hospital research facility. SUBJECTS: Twenty-four juvenile pigs. INTERVENTIONS: Acute lung injury was induced by surfactant depletion. Animals were randomly assigned to 6 hrs of mechanical ventilation (n = 8 per group) with either 1) pressure-controlled ventilation, 2) pressure support ventilation, or 3) noisy pressure support ventilation. During noisy pressure support ventilation, the pressure support varied randomly, with values following a normal distribution. In all groups, the driving pressures were set to achieve a mean tidal volume of 6 mL/kg. At the end of experiments, animals were killed and lungs extracted for histologic and biochemical analysis. MEASUREMENTS AND MAIN RESULTS: Respiratory, gas-exchange, and hemodynamics variables were assessed hourly. The diffuse alveolar damage and the inflammatory response of lungs were quantified. Pressure support ventilation and noisy pressure support ventilation improved gas exchange and were associated with reduced histologic damage and interleukin-6 concentrations in lung tissue compared to pressure-controlled ventilation. Noisy pressure support ventilation further improved gas exchange and decreased the inspiratory effort while reducing alveolar edema and inflammatory infiltration compared to pressure support ventilation. CONCLUSIONS: In this model of acute lung injury, pressure support ventilation and noisy pressure support ventilation attenuated pulmonary inflammatory response and improved gas exchange as compared to pressure-controlled ventilation. Noisy pressure support ventilation further improved gas exchange, reduced the inspiratory effort, and attenuated alveolar edema and inflammatory infiltration as compared to conventional pressure support ventilation.
Assuntos
Lesão Pulmonar Aguda/terapia , Ventilação com Pressão Positiva Intermitente/métodos , Respiração com Pressão Positiva/métodos , Respiração Artificial/métodos , Lesão Pulmonar Aguda/prevenção & controle , Animais , Pressão Sanguínea , Débito Cardíaco , Feminino , Hemodinâmica , Pulmão/fisiopatologia , Troca Gasosa Pulmonar , Surfactantes Pulmonares/metabolismo , SuínosRESUMO
BACKGROUND: We studied the occurrence of intraoperative tidal alveolar recruitment/derecruitment, exhaled nitric oxide (eNO), and lung dysfunction in patients with and without chronic obstructive pulmonary disease (COPD) undergoing coronary artery bypass grafting (CABG). METHODS: We performed a prospective observational physiological study at a university hospital. Respiratory mechanics, shunt, and eNO were assessed in moderate COPD patients undergoing on-pump (n = 12) and off-pump (n = 8) CABG and on-pump controls (n = 8) before sternotomy (baseline), after sternotomy and before cardiopulmonary bypass (CPB), and following CPB before and after chest closure. Respiratory system resistance (R (rs)), elastance (E (rs)), and stress index (to quantify tidal recruitment) were estimated using regression analysis. eNO was measured with chemiluminescence. RESULTS: Mechanical evidence of tidal recruitment/derecruitment (stress index <1.0) was observed in all patients, with stress index <0.8 in 29% of measurements. Rrs in on-pump COPD was larger than in controls (p < 0.05). Ers increased in controls from baseline to end of surgery (19.4 ± 5.5 to 27.0 ± 8.5 ml cm H(2)O(-1), p < 0.01), associated with increased shunt (p < 0.05). Neither Ers nor shunt increased significantly in the COPD on-pump group. eNO was comparable in the control (11.7 ± 7.0 ppb) and COPD on-pump (9.9 ± 6.8 ppb) groups at baseline, and decreased similarly by 29% at end of surgery(p < 0.05). Changes in eNO were not correlated to changes in lung function. CONCLUSIONS: Tidal recruitment/derecruitment occurs frequently during CABG and represents a risk for ventilator-associated lung injury. eNO changes are consistent with small airway injury, including that from tidal recruitment injury. However, those changes are not correlated with respiratory dysfunction. Controls have higher susceptibility to develop complete lung derecruitment.
Assuntos
Ponte de Artéria Coronária , Expiração/fisiologia , Óxido Nítrico/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Mecânica Respiratória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Testes Respiratórios , Estudos de Casos e Controles , Feminino , Cardiopatias/cirurgia , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Troca Gasosa Pulmonar/fisiologia , Análise de Regressão , Estudos Retrospectivos , Estresse Fisiológico/fisiologia , Volume de Ventilação Pulmonar/fisiologiaRESUMO
INTRODUCTION: There is an increasing interest in biphasic positive airway pressure with spontaneous breathing (BIPAP+SBmean), which is a combination of time-cycled controlled breaths at two levels of continuous positive airway pressure (BIPAP+SBcontrolled) and non-assisted spontaneous breathing (BIPAP+SBspont), in the early phase of acute lung injury (ALI). However, pressure support ventilation (PSV) remains the most commonly used mode of assisted ventilation. To date, the effects of BIPAP+SBmean and PSV on regional lung aeration and ventilation during ALI are only poorly defined. METHODS: In 10 anesthetized juvenile pigs, ALI was induced by surfactant depletion. BIPAP+SBmean and PSV were performed in a random sequence (1 h each) at comparable mean airway pressures and minute volumes. Gas exchange, hemodynamics, and inspiratory effort were determined and dynamic computed tomography scans obtained. Aeration and ventilation were calculated in four zones along the ventral-dorsal axis at lung apex, hilum and base. RESULTS: Compared to PSV, BIPAP+SBmean resulted in: 1) lower mean tidal volume, comparable oxygenation and hemodynamics, and increased PaCO2 and inspiratory effort; 2) less nonaerated areas at end-expiration; 3) decreased tidal hyperaeration and re-aeration; 4) similar distributions of ventilation. During BIPAP+SBmean: i) BIPAP+SBspont had lower tidal volumes and higher rates than BIPAP+SBcontrolled; ii) BIPAP+SBspont and BIPAP+SBcontrolled had similar distributions of ventilation and aeration; iii) BIPAP+SBcontrolled resulted in increased tidal re-aeration and hyperareation, compared to PSV. BIPAP+SBspont showed an opposite pattern. CONCLUSIONS: In this model of ALI, the reduction of tidal re-aeration and hyperaeration during BIPAP+SBmean compared to PSV is not due to decreased nonaerated areas at end-expiration or different distribution of ventilation, but to lower tidal volumes during BIPAP+SBspont. The ratio between spontaneous to controlled breaths seems to play a pivotal role in reducing tidal re-aeration and hyperaeration during BIPAP+SBmean.
Assuntos
Lesão Pulmonar Aguda , Respiração com Pressão Positiva/métodos , Respiração Artificial/métodos , Respiração , Lesão Pulmonar Aguda/diagnóstico por imagem , Animais , Alemanha , Hemodinâmica/fisiologia , Modelos Animais , Radiografia , Suínos , Volume de Ventilação Pulmonar/fisiologiaRESUMO
RATIONALE: Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. OBJECTIVES: To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. METHODS: In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). MEASUREMENTS AND MAIN RESULTS: Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. CONCLUSIONS: Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.
Assuntos
Lesão Pulmonar Aguda/terapia , Respiração Artificial/métodos , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/fisiopatologia , Animais , Modelos Animais de Doenças , Hemodinâmica , Pulmão/irrigação sanguínea , Oxigênio/metabolismo , Consumo de Oxigênio/fisiologia , Pressão Parcial , Alvéolos Pulmonares/patologia , Troca Gasosa Pulmonar/fisiologia , Distribuição Aleatória , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , Mecânica Respiratória/fisiologia , Estatísticas não Paramétricas , Suínos , Volume de Ventilação Pulmonar/fisiologiaRESUMO
RATIONALE AND OBJECTIVES: Pulmonary atelectasis presumably promotes and facilitates lung injury. However, data are limited on its direct and remote relation to inflammation. We aimed to assess regional 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) kinetics representative of inflammation in atelectatic and normally aerated regions in models of early lung injury. MATERIALS AND METHODS: We studied supine sheep in four groups: Permissive Atelectasis (nâ¯=â¯6)-16 hours protective tidal volume (VT) and zero positive end-expiratory pressure; Mild (nâ¯=â¯5) and Moderate Endotoxemia (nâ¯=â¯6)- 20-24 hours protective ventilation and intravenous lipopolysaccharide (Mildâ¯=â¯2.5 and Moderateâ¯=â¯10.0 ng/kg/min), and Surfactant Depletion (nâ¯=â¯6)-saline lung lavage and 4 hours high VT. Measurements performed immediately after anesthesia induction served as controls (nâ¯=â¯8). Atelectasis was defined as regions of gas fraction <0.1 in transmission or computed tomography scans. 18F-FDG kinetics measured with positron emission tomography were analyzed with a three-compartment model. RESULTS: 18F-FDG net uptake rate in atelectatic tissue was larger during Moderate Endotoxemia (0.0092 ± 0.0019/min) than controls (0.0051 ± 0.0014/min, p = 0.01). 18F-FDG phosphorylation rate in atelectatic tissue was larger in both endotoxemia groups (0.0287 ± 0.0075/min) than controls (0.0198 ± 0.0039/min, p = 0.05) while the 18F-FDG volume of distribution was not significantly different among groups. Additionally, normally aerated regions showed larger 18F-FDG uptake during Permissive Atelectasis (0.0031 ± 0.0005/min, p < 0.01), Mild (0.0028 ± 0.0006/min, p = 0.04), and Moderate Endotoxemia (0.0039 ± 0.0005/min, p < 0.01) than controls (0.0020 ± 0.0003/min). CONCLUSION: Atelectatic regions present increased metabolic activation during moderate endotoxemia mostly due to increased 18F-FDG phosphorylation, indicative of increased cellular metabolic activation. Increased 18F-FDG uptake in normally aerated regions during permissive atelectasis suggests an injurious remote effect of atelectasis even with protective tidal volumes.
Assuntos
Lesão Pulmonar Aguda , Respiração Artificial , Lesão Pulmonar Aguda/diagnóstico por imagem , Animais , Fluordesoxiglucose F18 , Pulmão , Tomografia por Emissão de Pósitrons , OvinosRESUMO
BACKGROUND: Noisy pressure support ventilation has been reported to improve respiratory function compared to conventional assisted mechanical ventilation. We aimed at determining the optimal level of pressure support variability during noisy pressure support ventilation. METHODS: Twelve pigs were anesthetized and mechanically ventilated. Acute lung injury was induced by surfactant depletion. At four levels of pressure support variability (coefficients of variation of pressure support equal to 7.5, 15, 30, and 45%, 30 min each, crossover design, special Latin squares sequence), we measured respiratory variables, gas exchange, hemodynamics, inspiratory effort, and comfort of breathing. The mean level of tidal volume was constant among variability levels. RESULTS: Compared to conventional pressure support ventilation, different levels of variability in pressure support improved the elastance of the respiratory system, peak airway pressure, oxygenation, and intrapulmonary shunt. Oxygenation and venous admixture benefited more from intermediate (30%) levels of variability, whereas elastance and peak airway pressure improved linearly with increasing variability. Heart rate as well as mean arterial and pulmonary arterial pressures decreased slightly at intermediate to high (30-45%) levels of variability in pressure support. Inspiratory effort and comfort of breathing were not importantly influenced by increased variability in pressure support. CONCLUSION: In a surfactant depletion model of acute lung injury, variability of pressure support improves lung function. The variability level of 30% seems to represent a reasonable compromise to improve lung functional variables during noisy pressure support ventilation.
Assuntos
Pneumopatias/terapia , Respiração Artificial/métodos , Pressão do Ar , Animais , Gasometria , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Elasticidade , Feminino , Frequência Cardíaca/fisiologia , Pneumopatias/induzido quimicamente , Pico do Fluxo Expiratório/fisiologia , Respiração com Pressão Positiva , Artéria Pulmonar/fisiologia , Surfactantes Pulmonares , Respiração Artificial/estatística & dados numéricos , Testes de Função Respiratória , Mecânica Respiratória/fisiologia , Suínos , Irrigação Terapêutica , Volume de Ventilação Pulmonar/fisiologiaRESUMO
BACKGROUND: Spontaneous breathing (SB) activity may improve gas exchange during mechanical ventilation mainly by the recruitment of previously collapsed regions. Pressure support ventilation (PSV) and biphasic positive airway pressure (BIPAP) are frequently used modes of SB, but little is known about the mechanisms of improvement of lung function during these modes of assisted mechanical ventilation. We evaluated the mechanisms behind the improvement of gas exchange with PSV and BIPAP. METHODS: Five pigs (25-29.3 kg) were mechanically ventilated in supine position, and acute lung injury (ALI) was induced by surfactant depletion. After stabilization, BIPAP was initiated with lower continuous positive airway pressure equal to 5 cm H2O and the higher continuous positive airway pressure titrated to achieve a tidal volume between 6 and 8 mL/kg. The depth of anesthesia was reduced, and when SB represented > or = 20% of total minute ventilation, PSV and BIPAP + SB were each performed for 1 h (random sequence). Whole chest helical computed tomography was performed during end-expiratory pauses and functional variables were obtained. Pulmonary blood flow (PBF) was marked with IV administered fluorescent microspheres, and spatial cluster analysis was used to determine the effects of each ventilatory mode on the distribution of PBF. RESULTS: ALI led to impairment of lung function and increase of poorly and nonaerated areas in dependent lung regions (P < 0.05). PSV and BIPAP + SB similarly improved oxygenation and reduced venous admixture compared with controlled mechanical ventilation (P < 0.05). Despite that, a significant increase of nonaerated areas in dependent regions with a concomitant decrease of normally aerated areas was observed during SB. In five of six lung clusters, redistribution of PBF from dependent to nondependent, better aerated lung regions were observed during PSV and BIPAP + SB. CONCLUSIONS: In this model of ALI, the improvements of oxygenation and venous admixture obtained during assisted mechanical ventilation with PSV and BIPAP + SB were explained by the redistribution of PBF toward nondependent lung regions rather than recruitment of dependent zones.
Assuntos
Pulmão/irrigação sanguínea , Oxigênio/metabolismo , Respiração com Pressão Positiva/métodos , Lesão Pulmonar Aguda , Animais , Análise por Conglomerados , Feminino , Corantes Fluorescentes/química , Microesferas , Pressão , Respiração , Mecânica Respiratória , Suínos , Volume de Ventilação Pulmonar , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: To describe and evaluate the effects of the new noisy pressure support ventilation (noisy PSV) on lung physiologic variables. DESIGN: Crossover design with four modes of mechanical ventilation. SETTING: Experimental research facility of a university hospital. SUBJECTS: A total of 12 pigs weighing 25.0-36.5 kg. INTERVENTIONS: Animals were anesthetized, the trachea was intubated, and lungs were ventilated with a mechanical ventilator (volume-controlled mode). Acute lung injury was then induced by surfactant depletion. Biphasic intermittent airway pressure/airway pressure release ventilation (BIPAP/APRV) was initiated, and anesthesia depth was decreased to allow spontaneous breathing. After that, each animal was ventilated with four different modes of assisted mechanical ventilation (1 hr each, Latin squares sequence): 1) PSV, 2) PSV combined with intermittent sighs (PSV + Sighs), 3) BIPAP/APRV + spontaneous breathing, and 4) noisy PSV with random variation of pressure support (normal distribution). The mean level of pressure support was set identical in all PSV forms. MEASUREMENTS AND MAIN RESULTS: We found that noisy PSV increased tidal volume variability compared with PSV and PSV + Sighs (19% vs. 5% and 7%, respectively, p < .05) independently from the inspiratory effort; improved oxygenation and reduced venous admixture but did not affect the amount of nonaerated lung tissue as compared with other assisted ventilation modes; reduced mean airway pressure at comparable minute ventilation; redistributed pulmonary blood flow toward nondependent lung regions similar to other PSV forms, whereas BIPAP/APRV + spontaneous breathing did not; and reduced the inspiratory effort and cardiac output in comparison with BIPAP/APRV + spontaneous breathing. CONCLUSIONS: In the surfactant depletion model of acute lung injury, the new noisy PSV increased the variability of the respiratory pattern and improved oxygenation by a redistribution of perfusion toward the ventilated nondependent lung regions with simultaneous lower mean airway pressure, comparable minute ventilation, and no increase in the inspiratory effort or cardiac output.
Assuntos
Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Animais , Estudos Cross-Over , Modelos Animais de Doenças , Projetos Piloto , SuínosRESUMO
OBJECTIVE: To evaluate the ability of three indices derived from the airway pressure curve for titrating positive end-expiratory pressure (PEEP) to minimize mechanical stress while improving lung aeration assessed by computed tomography (CT). DESIGN: Prospective, experimental study. SETTING: University research facilities. SUBJECTS: Twelve pigs. INTERVENTIONS: Animals were anesthetized and mechanically ventilated with tidal volume of 7 ml kg(-1). In non-injured lungs (n = 6), PEEP was set at 16 cmH(2)O and stepwise decreased until zero. Acute lung injury was then induced either with oleic acid (n = 6) or surfactant depletion (n = 6). A recruitment maneuver was performed, the PEEP set at 26 cmH(2)O and decreased stepwise until zero. CT scans were obtained at end-expiratory and end-inspiratory pauses. The elastance of the respiratory system (Ers), the stress index and the percentage of volume-dependent elastance (%E (2)) were estimated. MEASUREMENTS AND MAIN RESULTS: In non-injured and injured lungs, the PEEP at which Ers was lowest (8-4 and 16-12 cmH(2)O, respectively) corresponded to the best compromise between recruitment/hyperinflation. In non-injured lungs, stress index and %E (2) correlated with tidal recruitment and hyperinflation. In injured lungs, stress index and %E (2) suggested overdistension at all PEEP levels, whereas the CT scans evidenced tidal recruitment and hyperinflation simultaneously. CONCLUSION: During ventilation with low tidal volumes, Ers seems to be useful for guiding PEEP titration in non-injured and injured lungs, while stress index and %E (2) are useful in non-injured lungs only. Our results suggest that Ers can be superior to the stress index and %E (2) to guide PEEP titration in focal loss of lung aeration.
Assuntos
Lesão Pulmonar Aguda/fisiopatologia , Respiração com Pressão Positiva/efeitos adversos , Lesão Pulmonar Aguda/prevenção & controle , Animais , Gasometria , Modelos Animais de Doenças , Feminino , Modelos Biológicos , Testes de Função Respiratória , Sus scrofaRESUMO
Background: Laparoscopic surgery with pneumoperitoneum increases respiratory system elastance due to the augmented intra-abdominal pressure. We aim to evaluate to which extent positive end-expiratory pressure (PEEP) is able to counteract abdominal hypertension preventing progressive lung collapse and how rib cage elastance influences PEEP effect. Methods: Forty-four Wistar rats were mechanically ventilated and randomly assigned into three groups: control (CTRL), pneumoperitoneum (PPT) and pneumoperitoneum with restricted rib cage (PPT-RC). A pressure-volume (PV) curve followed by a recruitment maneuver and a decremental PEEP trial were performed in all groups. Thereafter, animals were ventilated using PEEP of 3 and 8 cmH2O divided into two subgroups used to evaluate respiratory mechanics or computed tomography (CT) images. In 26 rats, we compared respiratory system elastance (Ers) at the two PEEP levels. In 18 animals, CT images were acquired to calculate total lung volume (TLV), total volume and air volume in six anatomically delimited regions of interest (three along the cephalo-caudal and three along the ventro-dorsal axes). Results: PEEP of minimal Ers was similar in CTRL and PPT groups (3.8 ± 0.45 and 3.5 ± 3.89 cmH2O, respectively) and differed from PPT-RC group (9.8 ± 0.63 cmH2O). Chest restriction determined a right- and downward shift of the PV curve, increased Ers and diminished TLV and lung aeration. Increasing PEEP augmented TLV in CTRL group (11.8 ± 1.3 to 13.6 ± 2 ml, p < 0.05), and relative air content in the apex of PPT group (3.5 ± 1.4 to 4.6 ± 1.4% TLV, p < 0.03) and in the middle zones in PPT-RC group (21.4 ± 1.9 to 25.3 ± 2.1% TLV cephalo-caudally and 18.1 ± 4.3 to 22.0 ± 3.3% TLV ventro-dorsally, p < 0.005). Conclusion: Regional lung recruitment potential during pneumoperitoneum depends on rib cage elastance, reinforcing the concept of PEEP individualization according to the patient's condition.
RESUMO
BACKGROUND: With increased survival rates and the consequent emergence of an adult population with cystic fibrosis (CF), developing novel tools for periodic evaluations of these patients has become a new challenge. Thus, we sought to determine the contribution of lung-volume quantification using multidetector computed tomography (CT) in adults with CF and to investigate the association between structural changes and functional abnormalities. METHODS: This was a cross-sectional study in which 21 adults with CF and 22 control subjects underwent lung-volume quantification using multidetector CT. Voxel densities were divided into 4 bands: -1,000 to -900 Hounsfield units (HU) (hyperaerated region), -900 to -500 HU (normally aerated region), -500 to -100 HU (poorly aerated region), and -100 to 100 HU (non-aerated region). In addition, all participants performed pulmonary function tests including spirometry, body plethysmography, diffusion capacity for carbon monoxide, and the forced oscillation technique. RESULTS: Adults with CF had more non-aerated regions and poorly aerated regions with lung-volume quantification using multidetector CT than controls. Despite these abnormalities, total lung volume measured by lung-volume quantification using multidetector CT did not differ between subjects and controls. Total lung capacity (TLC) measured by body plethysmography correlated with both total lung volume (rs = 0.71, P < .001) and total air volume (rs = 0.71, P < .001) as measured with lung-volume quantification using multidetector CT. While the hyperaerated regions correlated with the functional markers of gas retention in the lungs (increased residual volume (RV) and RV/TLC ratio), the poorly aerated regions correlated with the resistive parameters measured by the forced oscillation technique (increased intercept resistance and mean resistance). We also observed a correlation between normally aerated regions and highest pulmonary diffusion values (rs = 0.68, P < .001). CONCLUSIONS: In adults with CF, lung-volume quantification using multidetector CT can destimate the lung volumes of compartments with different densities and determine the aerated and non-aerated contents of the lungs; furthermore, lung-volume quantification using multidetector CT is clearly related to pulmonary function parameters.
Assuntos
Oscilação da Parede Torácica/métodos , Fibrose Cística/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Adulto , Estudos Transversais , Fibrose Cística/fisiopatologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Medidas de Volume Pulmonar/métodos , Masculino , Pletismografia Total , Volume Residual , Testes de Função Respiratória/métodos , Espirometria , Capacidade Pulmonar Total , Adulto JovemRESUMO
INTRODUCTION: Atelectasis and distal airway closure are common clinical entities of general anaesthesia. These two phenomena are expected to reduce the ventilation of dependent lung regions and represent major causes of arterial oxygenation impairment in anaesthetic conditions. In the present study, the behavior of the elastance of the respiratory system (Ers), as well as the lung aeration assessed by CT-scan, was evaluated during a descendent positive end-expiratory pressure (PEEP) titration. This work sought to evaluate the potential usefulness of the Ers monitoring to set the PEEP in order to prevent tidal recruitment and hyperinflation of healthy lungs under general anaesthesia. METHODS: PEEP titration (from 16 to 0 cmH2O, with a tidal volume of 8 ml/kg) was performed, and at each PEEP, helical CT-scans were obtained during end-expiratory and end-inspiratory pauses in six healthy, anaesthetized and paralyzed piglets. The distribution of lung compartments (hyperinflated (HA), normally- (NA), poorly- (PA), and non-aerated areas (N)) was determined and the tidal re-aeration was calculated as the difference between end-expiratory and end-inspiratory PA and NA areas. Similarly, the tidal hyperinflation was obtained as the difference between end-inspiratory and end-expiratory HA. The Ers was estimated on a breath-by-breath basis from the equation of motion of the respiratory system during all PEEP titration with the least squares method. RESULTS: HA decreased throughout PEEP descent from PEEP 16 cmH2O to ZEEP (ranges from 24-62% to 1-7% at end-expiratory and from 44-73% to 4-17% at end-inspiratory pauses) whereas NA areas increased (30-66% to 72-83% at end-expiratory and from 19-48% to 73-77% at end-inspiratory pauses). From 16 to 8 cmH2O, Ers decreased with a correspondent reduction in tidal hyperinflation. A flat minimum of Ers was observed from 8 to 4 cmH2O. For PEEP below 4 cmH2O, Ers increased associated with a rise in tidal re-aeration and a flat maximum of the NA areas. CONCLUSION: In healthy piglets under a descending PEEP protocol, the PEEP at minimum Ers presented a compromise between maximizing NA areas and minimizing tidal re-aeration and hyperinflation. High levels of PEEP, greater than 8 cmH2O, reduced tidal re-aeration but enlarged hyperinflation with a concomitant decrease in normally aerated areas.
Assuntos
Anestesia Geral , Pulmão/fisiologia , Respiração com Pressão Positiva/métodos , Troca Gasosa Pulmonar/fisiologia , Mecânica Respiratória/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Complacência Pulmonar/fisiologia , SuínosRESUMO
Parenchymal strain is a key determinant of lung injury produced by mechanical ventilation. However, imaging estimates of volumetric tidal strain (ε = regional tidal volume/reference volume) present substantial conceptual differences in reference volume computation and consideration of tidally recruited lung. We compared current and new methods to estimate tidal volumetric strains with computed tomography, and quantified the effect of tidal volume (VT) and positive end-expiratory pressure (PEEP) on strain estimates. Eight supine pigs were ventilated with VT = 6 and 12 ml/kg and PEEP = 0, 6, and 12 cmH2O. End-expiratory and end-inspiratory scans were analyzed in eight regions of interest along the ventral-dorsal axis. Regional reference volumes were computed at end-expiration (with/without correction of regional VT for intratidal recruitment) and at resting lung volume (PEEP = 0) corrected for intratidal and PEEP-derived recruitment. All strain estimates demonstrated vertical heterogeneity with the largest tidal strains in middependent regions (P < 0.01). Maximal strains for distinct estimates occurred at different lung regions and were differently affected by VT-PEEP conditions. Values consistent with lung injury and inflammation were reached regionally, even when global measurements were below critical levels. Strains increased with VT and were larger in middependent than in nondependent lung regions. PEEP reduced tidal-strain estimates referenced to end-expiratory lung volumes, although it did not affect strains referenced to resting lung volume. These estimates of tidal strains in normal lungs point to middependent lung regions as those at risk for ventilator-induced lung injury. The different conditions and topography at which maximal strain estimates occur allow for testing the importance of each estimate for lung injury.
Assuntos
Pulmão/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Animais , Inflamação/fisiopatologia , Respiração com Pressão Positiva/métodos , Respiração Artificial/métodos , Suínos , Tomografia Computadorizada por Raios X/métodos , Lesão Pulmonar Induzida por Ventilação Mecânica/fisiopatologiaRESUMO
Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1ß, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.