Experimental lung research
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Ventilator-induced lung injury in children and adults is characterized by an initial inflammatory phase. To investigate whether the inflammatory cytokine, IL-1, plays a role in this process, a rabbit model of ventilator-induced injury was created. Animals maintained under pentobarbital anesthesia were primed for injury by undergoing lung lavage with 22 mL/kg of saline and then ventilated for 8 h with either FIO2 0.21 and normal pressures or FIO2 1.0 and high ventilator pressures. ⋯ These animals had significantly lower concentrations of albumin and elastase and lower neutrophil counts in their lungs after the 8-h ventilatory period compared to hyperoxia/hyperventilation rabbits. IL-1 blockade had no effect on the decline in dynamic compliance and oxygenation seen in saline-treated hyperoxic/hyperventilated rabbits. IL-1 is a mediator of acute inflammation due to ventilator-induced lung injury.
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Immunocytochemical studies have shown that gel-forming glycoproteins (mucins) and the bacteriolytic protein lysozyme are selectively expressed in airway mucous and serous cells, respectively. The mechanisms mediating this selectivity are unknown. In this study, we localized mucin and lysozyme mRNA by in situ hybridization to investigate the possibility that phenotype-specific expression of these proteins is controlled at the level of mRNA. ⋯ Frozen sections of human bronchus were hybridized with these probes and washed under routine conditions. Autoradiography showed that although lysozyme mRNA was strictly limited to cells expressing lysozyme, mucin mRNA was present both in mucin-expressing and mucin-non-expressing epithelial cells. This suggests that the restriction of lysozyme to serous cells is controlled at the level of mRNA (synthesis and/or degradation), whereas the restriction of mucin to mucous cells is controlled at the level of translation.
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Hormonal regulation of compensatory lung growth is not well understood, but it may be similar to that during compensatory growth of other organs. Liver regeneration is blocked by hypocalcemia in thyroparathyroidectomized (TPX) animals. Although calcium status is an important regulator of growth in many biological systems, the effect of TPX on compensatory lung growth is unknown. ⋯ Similarly, TPX had no effect on the postpneumonectomy increase in right lung mass, which reached 118% (p < .01) of that in TPX controls. Analysis of right lung DNA, RNA, and protein concentrations on day 9 revealed that tissue macromolecule content increased postoperatively in both PNX and TPX/PNX rats in proportion to lung growth. These results demonstrate that postpneumonectomy compensatory growth of the lung is not blocked in the thyroparathyroprivic hypocalcemic rat.
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To study the effect of chronic hyperoxia and hypoxia on pneumonectomy-induced compensatory lung growth, 4-week-old male rats were randomly divided into 4 groups: pneumonectomy controls, pneumonectomy hyperoxic group (fraction of ambient oxygen [FO2] 0.35), pneumonectomy hypoxic group (FO2 0.14), and unoperated controls. After 2 weeks, somatic growth of pneumonectomy hypoxic rats was diminished. Compared to unoperated controls, lung weight increased in all pneumonectomy groups but lung volume increased only in pneumonectomy control and pneumonectomy hypoxic rats. ⋯ The results suggest that 2 weeks after left pneumonectomy, compensatory lung response is incomplete. Chronic hypoxia enhances, whereas hyperoxia inhibits compensatory lung growth. The post-caval and upper lobes respond more and the lower lobe responds less following left pneumonectomy in both hypoxia and hyperoxia.
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To study the effects of hyperoxia and beta-adrenergic stimulation on pulmonary surfactant in the neonatal lung, we measured disaturated phosphatidylcholine (DSPC) and [14C]choline incorporation into DSPC, obtained from alveolar lavage and lung tissue. We used an isolated salt-perfused rabbit lung preparation from neonatal rabbits exposed to room air or greater than 95% oxygen for 3 days. There were four experimental groups: room air, basal condition; room air, beta-adrenergic stimulation; hyperoxia, basal conditions; and hyperoxia, beta-adrenergic stimulation. ⋯ It appears that prolonged exposure to hyperoxia is manifested primarily by a decrease in [14C]DSPC specific activity suggesting alterations in surfactant synthesis, though DSPC in the lavage is not altered. Beta-adrenergic stimulation may enhance release of newly synthesized surfactant into the alveoli, and possibly enhances uptake for reutilization. The enhancement of surfactant release seems to be preserved after prolonged hyperoxia.