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Biomedical subjects

G L Snider

Publications and source records attributed to G L Snider.

At least 145 records · Page 8Linked to original sources
PubMed1982

Pulmonary ventilation and blood gas values in emphysematous hamsters.

Emphysema is known to progress in severity during the year after its induction by pancreatic elastase. A barometric chamber and indwelling aortic cannulas were used to evaluate the effects of worsening emphysema on pulmonary ventilation and arterial blood gases. Unanesthetized, unrestrained hamsters were studied 1, 5, and 13 months after panlobular emphysema was induced by intratracheal injection of porcine pancreatic elastase (0.2 mg in 0.5 ml of 0.15 M NaCl solution/100 g body weight). Lung volumes were subsequently measured in the anesthetized animals and the lungs were examined histologically and stereologically. The pattern of breathing in the 1-month emphysematous hamsters (n = 12) wsa the same as that of untreated control animals (n = 28) but the 5-month (n = 7) and 13-month (n = 6) animals breathed more deeply and slowly; there were no changes in mean inspiratory flow rate of proportion of time per breath occupied by inspiration. The PaO2 for all elastase-treated groups was significantly lower than the control but hypoxemia did not progress significantly with advancing age of the animals. The hematocrit was elevated for the 1-month and 5-month treated animals but not for the 13-month emphysematous animals. The arterial pH and PaCO2 values were not significantly different from control values in any of the three groups of emphysematous animals. We conclude that as hamsters with emphysema age their breathing becomes slower and deeper, that hypoxemia is present from 1 month onwards and does not progress and that hypercapnia is not found at any time.

Aging↗
PubMed1982

Modification of oxygen toxicity after lung injury by bleomycin in hamsters.

In order to explore the interactions between oxygen toxicity and a model of interstitial pulmonary fibrosis, we studied the effects of exposure to 100% O2 at 1 atmosphere and exposure to 60% O2 for 21 days on survival, lung statics, and lung weight in hamsters previously treated intratracheally with bleomycin sulfate for 8 days (BLEO-8) and for 21 days (BLEO-21). All 10 saline-treated control animals died between 5 and 7.5 days in 100% O2; 7 of 15 BLEO-8 hamsters died before Day 5 (Fisher's exact test, p = 0.01) and 7 BLEO-21 hamsters died after Day 7.5 (Fisher's exact test, p = 0.03). Five of 11 BLEO-8 hamsters died in 60% O2, but there were no deaths among 8 BLEO-21 hamsters so exposed (Fisher's exact test, p = 0.04). There were slight decreases in the volume of air in the lungs at 25 cm H2O transpulmonary pressure (TLC25), vital capacity (VC), and quasi-static lung compliance (Cst(L)) in the saline-treated hamsters breathing 60% O2, compared with air-breathing control animals. The BLEO-8 animals exposed to 60% O2 showed greater decreases in TLC25, VC, and Cst(L) than the air-breathing control animals, and the mean dry lung weight of the O2-breathing group was significantly greater than that of the control animals. The BLEO-21 hamsters exposed to 60% O2 showed only a 15 to 18% greater decrease in TLC25, VC, and Cst(L) than the air-breathing control animals; the mean dry lung weight of the O2-breathing group was similar to the air-breathing control group. We concluded that the breathing of either 100 or 60% O2 adds to the severity of the lung injury previously induced by bleomycin; the degree of worsening is greater at 8 days than at 21 days after bleomycin treatment. These findings suggest that concentrations of inhaled oxygen used in treating human interstitial lung diseases should be kept at the lowest levels compatible with adequate tissue oxygenation.

Animals↗
PubMed1982

Role of alpha-macroglobulin-elastase complexes in the pathogenesis of elastase-induced emphysema in hamsters.

Radiolabeled, enzymatically active or chloromethyl ketone-inactivated porcine pancreatic elastase was endotracheally instilled into hamsters. Gel filtration of the bronchopulmonary lavage fluid revealed two major radioactive fractions: one, eluting at 780,000 daltons, corresponding to an alpha-macroglobulin-pancreatic elastase complex, and another, at 68,000 daltons, corresponding to an alpha-1-protease inhibitor-pancreatic elastase complex. Elastolytic activity was recovered in the bronchopulmonary lavage fluid up to 4 d after elastase instillation and was associated with the alpha-macroglobulin-pancreatic elastase complex. Small amounts of this complex were recovered 14 d after instillation. When less than 1% (1.5--1.7 micrograms) of the usual dose of elastase was instilled into hamsters, the major radioactive complex was alpha-1-protease inhibitor-pancreatic elastase complex, and little or no elastolytic activity was found in the lavage fluid. In contrast to the instillation of 220 micrograms of elastase, no disease or hemorrhagic reaction was detected with this low dose, and without hemorrhage only insignificant amounts of alpha-macroglobulin-pancreatic elastase complexes were recovered from the lungs. To study the interaction of circulating antiproteases with elastase, hamster plasma was allowed to interact directly with the radiolabeled elastase; alpha-macroglobulin bound much more of the elastase than alpha-1-protease inhibitor, confirming the findings in the lung lavage experiments. The hamster's susceptibility to pancreatic elastase-induced emphysema may depend on the preferential binding of elastase to alpha-macroglobulin, which protects the elastolytic potential, rather than to alpha-1-protease inhibitor, which inactivates elastase. We speculate that if even a fraction of the residual radioactivity found in the hamster lungs as long as 144 d after instillation of elastase represents enzymatically active alpha-macroglobulin-pancreatic elastase complex, this could serve as a source of persistent elastolytic activity, which might explain the progressive nature of the pulmonary lesion.

Animals↗
PubMed1982

Influence of asbestos fibers on collagen and prostaglandin production in fibroblast and macrophage co-cultures.

The interaction of fibroblasts, macrophages, and crocidolite asbestos fibers was studied in cell culture. We determined the effects of co-cultivation and asbestos fibers on collagen, total protein, and PG production. The co-cultivation of guinea pig alveolar macrophages and fetal lung fibroblasts resulted in a 155% increase in protein and a 31% increase in collagen production above fibroblast controls. The collagen was derived exclusively from the fibroblasts. Although total protein production was derived predominantly from the fibroblasts, the macrophages in co-culture also contributed to the protein levels. The addition of asbestos fibers to fibroblast cultures resulted in a decrease in collagen and total protein production. The addition of asbestos fibers to fibroblast and macrophage co-cultures prevented the enhancement of collagen production and limited the increase in protein production above fibroblast controls. PGE2, PGI2, and TXA2 were measured in macrophage and fibroblast cultures. Very low, almost undetectable PG production was observed under basal conditions by either cell type alone or in co-culture. Bradykinin induced release of these PGs in fibroblast but not macrophage cultures. This release was enhanced in co-cultures. Asbestos fibers, when added to the co-cultures caused a significant increase in the release of PGs, particularly PGE2. PGE2 is known to inhibit collagen and total protein production by fibroblasts. The increased release of PGs in asbestos-treated co-cultures may have contributed to the described asbestos suppression of collagen production

Animals↗
PubMed1981

Partial purification and characterization of a gelatin-specific protease from the culture media of human pulmonary alveolar macrophages.

A gelatin-specific protease from the culture media of human pulmonary alveolar macrophages has been partial purified by gel filtration and characterized. The macrophages were obtained by bronchopulmonary lavage from the lungs of disease-free smoking volunteers. The gelatin-specific protease initially requires trypsin activation. After chromatographing the culture media on a Sephadex G-200 column, trypsin is no longer required for activation. The gelatin-specific protease reported here shares many properties of previously reported gelatinases. It is inhibited by EDTA, cysteine, dithiothreitol and serum. It is unaffected by other protease inhibitors: phenylmethylsulfonyl fluoride, tosyllysine chloromethyl ketone and p-chloromercuribenzoate. Of all substrates tested activity was observed only with gelatin. It was inactive toward collagen, elastin and methemoglobin. This enzyme may have a role in the digestion of collagen which has been cleaved by a mammalian collagenase.

Animals↗
PubMed1981

Ultrastructural changes in hamster lung four hours to twenty-four days after exposure to elastase.

A single endotracheal instillation of elastase initiates a series of changes in animal lungs that results in a condition resembling human panlobular emphysema. An ultrastructural examination of this series of changes was conducted on the lungs of male golden hamsters exposed to 3H-methylated pancreatic elastase and sacrificed at intervals between 4 hour and 24 days after exposure to enzyme. Lung tissue between 4 and 48 hours showed evidence of hemorrhage and progressive degradation of elastic fibers. Very little indication of epithelial cell damage accompanied these changes. Four days after exposure to elastase, synthesis of new elastic fibers began with the appearance of small clumps of microfibrils in close association with interstitial cells, fibroblasts, and smooth muscle cells. There was also evidence of alterations in alveolar type II cells at this time. Small fibrillar elastic fibers continued to be present in the lung through twenty-four days and may represent a slow repair process or may indicate a structural difference in elastic fibers synthesized after exposure to elastase. Evidence of the continued degradation of elastic fiber could be found up to 16 days after exposure to elastase, revealing that repair processes were occurring in some areas of the lung while destructive process still predominated in other areas.

Animals↗
PubMed1981

The moderation of elastase-induced emphysema in the hamster by intratracheal pretreatment or post-treatment with succinyl alanyl alanyl prolyl valine chloromethyl ketone.

The capacity of the synthetic elastase inhibitor, succinyl alanyl alanyl prolyl valine chloromethyl ketone (CMK), to moderate elastase-induced emphysema in hamsters was examined using morphometric and physiologic measurements. When 0.5 mg of CMK in saline was injected intratracheally 1 h before the intratracheal injection of 0.1 mg of porcine pancreatic elastase, the hamsters did not develop emphysema. When CMK was injected intratracheally 1 h after elastase, the severity of emphysema was reduced by approximately 50% compared with control animals receiving saline 1 h after elastase. The CMK was ineffective when administered intratracheally 4 h after elastase.

Amino Acid Chloromethyl Ketones↗
PubMed1981

Computed tomographic scanning of the mediastinum in the staging of bronchogenic carcinoma.

We investigated the efficacy of 2-s breath-holding computed tomographic (CT) scans and standard posteroanterior and lateral chest roentgenograms in staging the mediastinum and pulmonary hill in lung cancer. Fifty-one comparisons were made in 49 patients thought to have non-small-cell carcinoma, consecutively chosen to be free of disseminated tumor, and to be suitable candidates for thoracotomy. The CT scans accurately predicted mediastinal neoplastic lymphadenopathy in 15 or 17 instances of proved mediastinal lymph node metastasis for a sensitivity of 88%; specificity was also high (94%) with a true-negative scan in 32 of 34 instances. Standard chest roentgenograms were much less sensitive (47%) than rapid CT scanning in mediastinal staging; there were false-negative interpretations in 9 of 17 instances. Specificity of the methods was the same. both CT scans and standard chest roentgenograms had a sensitivity of only 67% in detecting neoplastic hilar adenopathy; enlarged hilar nodes were noted in only 10 of 15 patients with proved hilar node metastasis. We concluded from this preliminary study that rapid CT scanning shows promise of being useful in the noninvasive staging of the mediastinum of patients with otherwise operable non-small-cell bronchogenic carcinoma; the technique also provides useful guidance during mediastinoscopy and may detect lymphadenopathy not so visualized, but CT scanning appears to have little advantage over standard posteroanterior and lateral chest roentgenograms in staging the pulmonary hill.

Adult↗
PubMed1980

Lung statics and connective tissues after penicillamine in bleomycin-treated hamsters.

Penicillamine was administered intraperitoneally to male golden hamsters for 30 days following a single intratracheal dose of bleomycin. Penicillamine treatment increased soluble collagen and decreased glycosaminoglycans in both normal and fibrotic lungs; total collagen and elastin were not significantly changed in normals but were lower in fibrotic animals. The proportions of the different glycosaminoglycans were not affected by penicillamine treatment. When related to body weight, the total lung capacity, vital capacity, and compliance both at low and high lung volumes were increased in animals that received only penicillamine when compared with animals that did not, but interpretation of these results is difficult because penicillamine-treated animals had low body weights. Lung statics were the same in animals that received penicillamine after bleomycin as in those that received bleomycin only, though penicillamine partially reversed the connective tissue expression of the bleomycin lung injury. We conclude that factors other than connective tissue levels are important in determining the mechanical behavior of fibrotic lungs.

Animals↗
PubMed1980

Oxygen therapy, oxygen therapy in medical patients hospitalized outside of the intensive care unit.

The administration of O2-enriched breathing mixtures to acutely ill patients is based on the premise that this form of treatment can overcome the known deleterious effects of tissue hypoxia. Therapeutic practices are founded on a knowledge of the physiology of oxygenation in normal and diseased persons and on knowledge of pulmonary O2 toxicity rather than on demonstrated alterations in disease outcome. The arterial PO2 (Pao2), when markedly diminished, indicates O2 deprivation of tissues, especially in unstable or acute states. However, th Pao2 may show little or no abnormality in states with sharply diminished generalized or regional systemic blood flow. Despite these shortcomings, the Pao2 remains a useful guide for initiating and monitoring O2 therapy in many circumstances. To minimize pulmonary O2 toxicity, the concentration of O2 chosen should be the lowest dose that will correct hypoxemia; 40% O2 is not known to be clinically toxic even after prolonged administration, but toxicity increases progressively above this value. In hypoxemic eucapnic patients, Pao2 of 60 mm Hg represents a reasonable value for treatable hypoxemia, but it is often rational to treat unstable patients with higher Pao2 values, especially if the alveolar-arterial Po2 difference is abnormally wide; 40% O2 represents a reasonable initial dose, with adjustments made on the basis of serial Pao2 measurements. When hypercapnia accompanies hypoxemia, O2 is often not given for Pao2 values greater than 50 mm Hg, and controlled low-dose O2 (24 to 30%) should be used to correct hypoxemia partially while preserving an element of hypoxemic ventilatory drive. In states of low blood flow, high O2 concentrations should be used to maximize the amount of O2 dissolved in plasma, and the duration of therapy should be as brief as possible to minimize O2 toxicity.

Carbon Dioxide↗