RESUMEN
Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.
Asunto(s)
Compuestos Epoxi/toxicidad , Grafito/toxicidad , Neumonía/fisiopatología , Síndrome de Dificultad Respiratoria/fisiopatología , Lesión por Inhalación de Humo/fisiopatología , Animales , Líquido del Lavado Bronquioalveolar/química , Quimiocina CXCL2 , Modelos Animales de Enfermedad , Herbicidas/toxicidad , Histocitoquímica , Interferón gamma/biosíntesis , Masculino , Monocinas/biosíntesis , Paraquat/toxicidad , Neumonía/etiología , Neumonía/metabolismo , Distribución Aleatoria , Ratas , Ratas Endogámicas F344 , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/metabolismo , Pruebas de Función Respiratoria , Humo/efectos adversos , Lesión por Inhalación de Humo/etiología , Lesión por Inhalación de Humo/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
The physical and chemical properties of the particulate fraction of carbon-graphite/epoxy advanced composite material (cgeACM) smoke were measured to address concerns regarding potential health hazards posed by the release of fibers during pyrolysis of this material. Filter, low-pressure cascade impactor, and electrostatic precipitator samples were collected from cgeACM smoke in which the aerosol concentration ranged from 0.20 to 5.39 g/m3. Fibers were found in the smoke among individual, spherical, or nearly spherical particles and chain aggregates. The fibers had a mean count diameter of 0.54 micron and an average length of 2.84 microns. However, fibers accounted for approximately 0.3% of the particles counted. The smoke aerosols (including fibers) had mass median aerodynamic diameters (MMAD) ranging from 1.4 to 1.9 microns with standard geometric deviations ranging from 1.6 to 1.8, and hence more than 88% of the particles were in the thoracic size range (MMAD < or = 4.0 microns). All particles were composed primarily of carbon, silicon, sulfur, and oxygen with traces of other metals. By comparison fibers were composed almost exclusively of silicon.
Asunto(s)
Contaminantes Atmosféricos/análisis , Resinas Compuestas/análisis , Humo/análisis , Carbono/análisis , Resinas Compuestas/efectos adversos , Resinas Compuestas/química , Compuestos Epoxi/análisis , Grafito/análisis , Humanos , Fibras Minerales/análisis , Tamaño de la Partícula , Lesión por Inhalación de Humo/prevención & controlRESUMEN
Barometric (whole body) plethysmography is used to examine changes in ventilation and breathing pattern in unrestrained animals during exposure to therapeutic or toxic aerosols. Whole body plethysmographs (WBP) may be operated with a bias flow in order to maintain an adequate supply of oxygen and remove expired CO(2). However, some aerosol generation and delivery methods may require operation of the WBP without bias flow, which would artificially deplete aerosol concentration. Under these conditions, expired CO(2) accumulates in the plethysmograph and stimulates ventilation, increasing total aerosol deposition, shifting regional deposition, and significantly altering some airway function indices. We characterized these effects in guinea pigs using a commercially available 4.5-L WBP, with and without a 1 L/min bias flow. CO(2)-induced changes in breathing frequency (f), tidal volume (Vt), minute ventilation (Ve), and indices of airway function -- including enhanced pause (penh), flow derived parameter (FDP), and respiratory duty cycle -- were measured. Without bias flow, CO(2) in the plethysmograph increased steadily to 5.4% after 30 min compared to a steady state 0.9% with bias flow. This resulted in a moderate suppression of f, and significant increases in Vt and Ve by factors of 1.5 and 1.4, respectively. Changes in regional deposition were stimulated for 300 mg/m(3) polydisperse aerosols with mass median aerodynamic diameters of 0.3, 1, 3, or 7 microm and geometric standard deviations of 1.7. Percent increase in aerosol deposition from CO(2) inhalation ranged from 24% to 90%, by mass, depending on aerosol size distribution and respiratory tract region. In addition, fractional deposition shifted toward the pulmonary region. Empirical indices of airway constriction, penh and FDP, also were increased significantly to 1.7 and 1.3 times their respective baseline values. The study quantifies the effect of inadvertent coexposure to CO(2) on ventilation, aerosol deposition, and airway function in WBP evaluation of aerosol effects in airway function.
Asunto(s)
Dióxido de Carbono/metabolismo , Pletismografía Total , Administración por Inhalación , Aerosoles , Resistencia de las Vías Respiratorias , Animales , Cobayas , Pulmón/fisiología , Masculino , Oxígeno/metabolismo , Tamaño de la Partícula , Pruebas de Función RespiratoriaRESUMEN
Exposure of naïve guinea pigs for a total of 30 min to aged smoke from pyrolysis of 5, 10 and 100 g of carbon-graphite/epoxy-advanced composite material (cgeCM) elicited changes in the ventilation and breathing pattern reminiscent of an acute, asthmatic episode. The severity of these responses was dose related. Although breathing pattern changes were not definitive of stimulation by a single type of respiratory irritant, non-dimensional indices derived from breath structure appeared to be characteristic of bronchoconstriction possibly complicated by CO(2)-stimulated ventilation. The highest exposure concentration also elicited convulsions in the animals, which may or may not be related to the airway reactivity (AR) response. Upon treatment with fresh air, breathing returned to normal. However, this recovery was transient with some respiratory parameters returning to abnormal levels, possibly indicating a rebound or delayed component of the response. Filtration of particulate material from the smoke moderated but did not eliminate the AR response. Animals exposed to diluted smoke from the pyrolysis of 2 g of cgeCM showed no remarkable changes in breathing or ventilation, suggesting that there may be a threshold for aged cgeCM smoke-elicited AR response.