Biomedical subjects

R C Lindenschmidt

Publications and source records attributed to R C Lindenschmidt.

24 records · Page 2Linked to original sources

PubMed1985

Progressive pulmonary fibrosis in rats: a biochemical, cell kinetic, and morphologic analysis.

The concomitant treatment of rats with bleomycin and hyperoxia results in synergistic development of pulmonary injury. We exposed rats to 70% oxygen for 72 hr following an intratracheal instillation of bleomycin (0.2 U/kg body wt). Animals were killed 15, 30, 60 and 90 days after treatment for hydroxyproline, cell kinetics, and histopathologic analysis. A 16% increase in hydroxyproline over controls was seen 15 days after treatment which was manifested by the proliferation phase of diffuse alveolar damage and an increase in cell labeling by tritiated thymidine. Thirty days after treatment the hydroxyproline remained elevated while lung injury appeared to be healing with a residual focal interstitial pneumonitis and a drop in cell labeling. Between 60 and 90 days, there was an additional significant increase in hydroxyproline to 44% over controls. Diffuse interstitial pneumonitis with fibrosis was observed. Cell labeling remained constant between 60 and 90 days. We conclude that the treatment of rats with bleomycin and hyperoxia results in slowly progressive pulmonary fibrosis. The increase in hydroxyproline in the chronic phase was not accompanied by an increase in cell proliferation, and therefore may have resulted from an increase in cellular production of hydroxyproline rather than increased number of cells producing collagen.

Animals↗

PubMed1985

The many faces of an increase in lung collagen.

Many toxic chemicals have been shown to produce an increase in lung collagen. Biochemical measurements of total lung hydroxyproline are a convenient method to quantitate and to follow disease processes associated with such an increase. However, biochemical measurements alone do not distinguish various pathological lesions and histology is needed to provide additional important information. Cell kinetic studies enhance histopathology in showing the dynamics of cell proliferation and tissue renewal. When these methods of studying lung collagen are applied to different toxic agents, such as butylated hydroxytoluene, methylcyclopentadienyl manganese tricarbonyl, CdCl2, or anticancer drugs, different patterns of hydroxyproline accumulation and cellular kinetics are revealed. It is speculated that the development of fibrotic lung disease may be at least partially determined by the initial lesion and that quantitative analyses of cell kinetic patterns help to understand and to predict the nature and evolution of disease processes.

Animals↗

PubMed1985

The effect of cyclosporin A on pulmonary fibrosis induced by butylated hydroxytoluene, bleomycin and beryllium sulfate.

Interstitial pulmonary fibrosis is characterized by an abnormal accumulation of fibroblasts with a resultant increase in lung collagen content. Previous research has implied a possible involvement of the T-lymphocyte in this process. We used cyclosporin A (Cy A), a known immunosuppressant, to deplete T-lymphocyte-dependent responses in animals following treatment with agents known to produce fibrosis; butylated hydroxytoluene (BHT), bleomycin and beryllium (Be). BHT-treated mice and bleomycin-treated rats showed significant reduction in total lung hydroxyproline content with Cy A (P less than 0.05). These results suggest a contribution of the T-lymphocyte in the overall process of fibrosis, but do not indicate its role as the sole causative agent.

Animals↗

PubMed1985

Propranolol-induced elevation of pulmonary collagen.

Current concepts of collagen metabolism suggest that fibroblasts tightly control collagen production. One of the possible mechanisms of control is via the cyclic nucleotides, cyclic AMP (cAMP) and cyclic GMP (cGMP). Beta adrenergic agonists, by elevating intracellular cAMP levels, have been shown in vitro to suppress fibroblast collagen production; whereas beta adrenergic antagonists were effective in removing this suppression by blocking the rise in cAMP. In the present study with mice, we showed that administration of the beta adrenergic antagonist, propranolol, at a dose demonstrated to decrease the ratio of cAMP to cGMP, resulted in an elevation in total lung collagen in vivo. The increase in collagen was evident only when propranolol was administered before and during acute lung damage induced by either butylated hydroxytoluene, bleomycin or high concentrations of oxygen. There was no increase in lung collagen when propranolol administration was delayed after injury or when given to an undamaged lung. We propose that via beta adrenergic blockade by propranolol, fibroblasts involved in the normal reparative process may have lost a mechanism for regulatory control, resulting in excessive deposition of collagen.

Animals↗

PubMed1985

Pathogenesis of acute and chronic lung injury induced by foreign compounds.

The lung may become damaged by both airborne or bloodborne agents. Mechanisms implicated in the pathogenesis of lung injury include formation of highly reactive metabolites formed by pulmonary mixed function oxidases or formation of free oxygen radicals. Acute and chronic damage can be evaluated by several methods, such as histology and quantitative morphometry, non-invasive and non-destructive respiratory function tests, and with biochemical techniques that include measuring lavage enzyme levels or quantitating the presence of macromolecules such as collagen. In addition, cell kinetics provide an additional method to explore events following lung damage.

Acute Disease↗

PubMed1983

Selective action of prostaglandin F2 alpha during paraquat-induced pulmonary edema in the perfused lung.

Lung prostaglandins (PGs) play a key role in normal pulmonary vascular regulation. We investigated PG metabolism during edema formation following paraquat-induced damage with an isolated perfused rat lung preparation. Lungs perfused with paraquat (PQ), 1 X 10(-7) M to 1 X 10(-2) M, showed significant increases in PGF2 alpha prior to detectable functional and pathological changes (increases in airway resistance, vascular resistance, and edema). No changes in PGE were observed. PGF2 alpha in perfused lungs showed a dose-related response following PQ exposure (up to 300% increase over control values). Lungs perfused with PQ and ventilated with high oxygen (95% O2-5% CO2) instead of air-5% CO2 showed a dramatic potentiation in the selective increase of PGF2 alpha, with levels reaching over 1 ng/ml (a 2600% increase over control values). The addition of exogenous PGF2 alpha to the perfusate without PQ initiated edema in a dose-related fashion, indicating the potential of PGF2 alpha as a causative agent in lung edema formation from PQ injury. The addition of ibuprofen (a nonsteroidal anti-inflammatory agent) to the perfusion medium blocked endogenous release of PGF2 alpha in lungs linked to oxidant-induced edema. These data show that in the perfused lung: (1) PQ caused a selective increase of PGF2 alpha; (2) this selective increase occurred prior to the onset of edema; (3) exogenous PGF2 alpha alone induced pulmonary edema; and (4) ibuprofen, in doses which blocked PGF2 alpha, also prevented edema formation.

Animals↗