Constraint and innovation in the traditional fiddle repertoire of Cape Breton

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Time-dependent effects of maternal continuous propranolol on fetal lung development in rats

Previous studies have demonstrated a role for the beta-adrenergic system in the maturation of the fetal alveolar epithelium. Chronic blockade of beta-adrenergic binding sites has been shown to adversely ef f e c t p hysiologic and biochemical indices of fetal lung maturation. In the present study timed-pregnant female Sprague-Dawley rats were treated with a continuous 0.5 mg/hr dose of propranolol HCl, or saline, via an osmotic pump. The treatment periods were days 18-21, or 20-23 of gestation. Fetal body weights were obtained, and the morphology of the fetal lungs studied by light and electron microscopy. Cytoplasmic volume densities of lamellar inclusion bodies and glycogen within d eveloping type II alveolar epithelial cells were also determined. In addition, total phospholipids (as phosphorus) and glycogen content were determined b i o c h e m i c a l l y. The fetuses from females treated from day 20-23 demonstrated no differences between salinetreated and propranolol-treated groups, in either fetal weight or the morphologic appearance of the developing lung. In contrast, the fetuses from mothers treated from day 18-21 with propranolol were significantly smaller, and their lungs appeared less mature than saline-treated counterparts. The glycogen content of developing type II alveolar epithelial cells was significantly more abundant (as judged by stereologic and biochemical analyses) in the propranolol-treated fetuses. In addition, total phospholipids were decreased in the propranolol-treated 21-day fetuses. The results of the present study suggest that the development of the alveolar epithelium is s e n s i t ive to continuous beta-adrenergic blockade by propranolol during a critical time late in gestation

The fibrogenic response of adult rat lung to continuous propranolol treatment

Fibrogenesis is a common pulmonary response to injury, which is usually preceded by other severe reactions, including inflammation, fluid exudation, and alveolar epithelial damage and proliferation. The purpose of this study was to examine the morphologic effects on the distal lung of a continuous propranolol treatment. Adult male rats were treated, via a subcutaneous osmotic pump, with a continuous (approximately 0.5 mglhour) dose of propranolol HCl, a potent wide range beta-adrenergic blocking agent, in saline, or saline alone. The animals were killed after one week or three weeks. Electron microscopy of the lungs of the propranolol-treated animals revealed a dramatic increase in the prominence of interstitial cells and fibers of the alveolar septa, along with focal thickening of endothelial cells and some morphologic changes in type I1 alveolar epithelial cells. In some animals an analysis of total protein content, as well as 3H-proline incorporation into total protein and collagen was undertaken. The results of this study indicated a significant increase in total protein content and proline incorporation into collagen in the lungs of animals treated for seven days with continuous propranolol. There was no evidence of stimulated blood cells, macrophages, edema or severe epithelial damage. This study provides morphologic evidence that continuous treatment with moderate levels of propranolol results in a fibrogenic response in the peripheral lung, in the absence of typical hallmarks of severe pulmonary damage

Ultrastructural changes in the synthetic and secretory patterns of pulmonary surfactant following pilocarpine in vivo

Previous studies have demonstrated that the muscarinic agonist pilocarpine stimulates the secretion of pulmonary surfactant from mammalian alveolar type 11 cells. The results of the present study quantify, via ultrastructural stereologic analysis, this response through 24 hours. The cytoplasmic volume density of lamellar bodies decreases significantly at 0.5 and 4 hours postinjection. This value is increased significantly at 12 hours post-injection. Elements of the secretory apparatus increase significantly at many of the post-injection times. At 12 hours post-injection many of the type 11 cells are quite laden with lamellar bodies, with some appearing surprisingly large. This may be a useful model for continued study of the relationship between synthesis and secretion of pulmonary surfactant