Experimental lung research
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Recent clinical studies have suggested that peripheral airways dysfunction contributes to the pathogenesis of idiopathic pulmonary hypertension. To determine whether similar peripheral airways defects occur in a common animal model of pulmonary hypertension, pulmonary function tests were performed in adult male rats rendered pulmonary hypertensive with a single subcutaneous injection of monocrotaline. ⋯ The specific changes in pulmonary function observed in monocrotaline-treated rats were qualitatively similar to abnormalities reported in patients with idiopathic pulmonary hypertension. These results demonstrate that significant pulmonary mechanical, ventilatory, and gas exchange dysfunction is present in rats with monocrotaline-induced pulmonary hypertension and highlight the suitability of this model for investigating a potential contributory role of pulmonary function abnormalities in the pathogenesis of this disorder.
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Monocrotaline given to rats causes lung injury which is followed by pulmonary hypertension. A large, abnormal intraalveolar cell has been repeatedly observed. The purpose of the present study was to define the nature of the cell and to determine how it related to the lung injury. ⋯ When we reduced the number of circulating leukocytes by whole body radiation, monocrotaline administration was followed both by accelerated pulmonary hypertension and increased numbers of abnormal alveolar macrophages. The abnormal macrophage appeared to be a marker of the monocrotaline induced pulmonary hypertension. However, neither the abnormal macrophage nor the monocrotaline injury appeared to depend on circulating leukocytes.
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Comparative Study
Degradation of elastin in experimental elastase-induced emphysema measured by a radioimmunoassay for desmosine.
Experimental emphysema, produced by a single intratracheal injection of elastase in hamsters, progresses in severity over months. To investigate whether this progression is due to continuous elastolysis, we measured the urinary excretion of desmosine by radioimmunoassay (RIA) as a measure of elastin catabolism in vivo. Normal hamster excreted 1.6 microgram of desmosine, equivalent to a daily turnover of approximately 0.4 mg of elastin. ⋯ The method was sufficiently sensitive to detect 0.1 microgram of enzyme bound to elastin. Desmosine solubilized in vitro from lungs removed at intervals after elastase injection was 10-fold that of control at 1 hr and slightly elevated at 48 hr, but equaled control levels at 7 days. These results indicate that the late progression of elastase-induced emphysema is not accompanied by increased elastolysis.