We describe a guinea pig model of asthma in which animals were sensitized and challenged by inhalation of aerosolized ovalbumin. Challenge was performed under cover of mepyramine (10 mg/kg) to allow a high enough concentration of ovalbumin to elicit consistent late responses. Airway resistance and thoracic gas volume of conscious guinea pigs was assessed by whole body plethysmography before and at regular intervals for as long as 72 h after challenge. At the same time points, cellular changes in the lung were assessed by both examination of cells recovered by bronchoalveolar lavage (BAL) and lung histology. There were no significant changes in specific airway conductance (SGaw), BAL cell content or lung histology in animals challenged with saline control. Challenge with 2% ovalbumin caused an early fall in SGaw, which peaked at 2 h and amounted to a 43.7 +/- 4.1% fall from baseline. This was followed by 2 late responses, the first reaching maximum at 17 h with a 46.9 +/- 4.5% decrease in SGaw from baseline and the second at 72 h with a 39.0 +/- 3.5% fall in SGaw. Examination of BAL fluid revealed a 7-fold increase in neutrophils at 6 h and a 17-fold increase at 17 h, after which numbers decreased to baseline. Eosinophilia developed more slowly, being insignificant at 6 h and 6-fold at 17 h; by 72 h, eosinophils constituted 48.9 +/- 6.9% of the total cells recovered. No changes in mononuclear cells or lymphocytes were observed. Histologic examination of the lung revealed a progressive eosinophil infiltration of the airways, but not alveoli or vascular bed. Electron microscopy showed degranulation of eosinophils recovered by BAL and discharge of mucus from goblet cells in the trachea. Because these changes are similar to those that occur after allergen challenge in human asthma, we suggest that this represents a useful animal model in which to study the mechanism of early and late bronchoconstriction responses.
SUMMARY1. Intrapulmonary bronchi in excised dog lungs were outlined with tantalum dust and stereoscopic radiographs taken during deflation and inflation of the lung after rinsing with solutions of saline, histamine, isoprenaline or EDTA. Dimensions of airways were calculated from measurements of the stereoscopic X-ray images.2. After treatment with EDTA to minimize bronchial smooth muscle activity, airway diameters increased at all transpulmonary pressures (Ptp) and lung volumes relative to their diameter after treatment with histamine; airway hysteresis in relation to Ptp decreased.3. At low lung volumes, the per cent increase from histamine to EDTA for airways of different sizes was the same (24-30 %) but at high volumes (30 cm H20 distending pressure) the dilatation induced by EDTA was 30 % for airways less than 3-0 mm diameter and 13 % for those greater than 5-0 mm diameter. 4. Even at high lung volumes, intrapulmonary airways are free to constrict or dilate in spite of the stiffness of the supporting parenchyma.
SUMMARY1. Respiratory resistance was measured by a forced oscillation technique in vagotomized guinea-pigs before and after pulmonary micro-embolism produced by i.v. injection of 0 5 ml./kg of 10 % w/v BaSO4. Changes in quasi-static inspiratory compliance and arterial platelet count were also measured.2. Micro-embolic challenge with BaSO4 increased respiratory resistance by 27 %; this was abolished by prior treatment with indomethacin; no change in the control resistance occurred after indomethacin.3. No change in respiratory compliance or arterial platelet numbers were observed following low dose BaSO4 micro-embolism. This suggests that pulmonary microembolism produced a decrease in medium or large airway calibre, which was mediated by a prostaglandin-like substance from lung tissue, and did not require the presence of the vagus nerves.
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