The direct effect of tobacco smoke on the intrinsic mechanical properties of cardiac muscle.
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Biomedical subjects
Publications and source records attributed to G L Huber.
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Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge.
Polymorphonuclear leukocytes (PMN) and macrophages, harvested from the peritoneum and lung, release superoxide (O-.2) and hydrogen peroxide (H2O2) during phagocytosis. These two agents are thought to react with each other to produce a highly active oxidative substance known as hydroxyl radical (OH.). We present evidence suggesting that these radicals are generated by phagocytic cells of the rat. Our findings are based upon an assay where ethylene gas is generated from methional by the action of this radical. Ethylene generation was shown to be inhibited by superoxide dismutase, catalase, and scavengers of OH.. Of the cells examined, PMN generated the most ethylene from methional, exhibiting a fourfold increase during phagocytosis. Pulmonary and peritoneal macrophages caused smaller amounts of this gas to be formed. Regardless of cell type, an intact cell was required for ethylene generation. Zymosan appeared to be the most effective particle for all cells in ethylene formation from methional, although opsonization was critical only for PMN. Ethylene generation was dependent on cell concentration to an extent and increased with time.
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Quantitative morphologic analyses were performed by stereologic methods on the tracheal glands of male and female rats after exposure to tobacco smoke for 30 consecutive days. The female rats were evaluated at 2 stages of their estrous cycle. The upper segment of trachea from each animal was embedded in glycol methacrylate, sectioned, and stained with a combined Alcian blue and periodic acid-Schiff stain for glycoproteins. Exposure to tobacco smoke caused an increase in the relative proportion of gland cells in each sex when expressed in reference to the total tissue within the cartilage ring, and an increase in mucins in the gland by 50% in both sexes. Although the relative proportions of gland cells and lumina were equivalent between the sexes, male rats had a larger quantity of mucin. The volume proportion in the glands of Alcian blue-positive mucin was 80 to 84% greater in males, and periodic acid-Schiff-positive mucin was 18 to 19 per cent greater in males than in females, both in control animals and those exposed to tobacco smoke. This study demonstrated that sexual differences were present in the mucin composition of the tracheal glands of normal male and female rats, that the female glycoproteins varied during the estrous cycle, and that these differences were retained after exposure to tobacco smoke.
A case of pulmonary edema following reexpansion of a collapsed lung due to pneumothorax is described and illustrated. The importance of recognizing this relatively uncommon phenomenon is stressed. The development of such edema can be prevented by avoiding application of sudden and excessive negative pleural pressures during the evacuation of a pneumothorax or a pleural effusion. The edema generally occurs in a lung that has been collapsed for more than three days. The importance of the duration of pulmonary collapse in the causation of edema is demonstrated in this patient.
Male rats were exposed for 30 consecutive days to whole smoke from either marijuana or tobacco cigarettes. At the end of this period, anesthetized animals from the two smoke-exposed groups together with their age-matched, nonexposed controls underwent bronchopulmonary lavage, and the free lung cells obtained were fixed and collected for light and electron microscopy. Measurements made on 1-micrometer. sections indicated slight, but statistically nonsignificant, shifts in the frequency distributions of alveolar macrophage profile diameters after both exposure regimens. Stereologic techniques were used to study the subcellular morphology of alveolar macrophages from the three groups of animals. Statistically significant changes were found in cells from tobacco-exposed animals in the volume densities of mitochondria, lipid inclusions, lysosomes, remaining cytoplasm, and the surface to volume ratio of the cell. In contrast, only two parameters in the cells from marijuana-exposed animals were found to have changed significantly, with a 3-fold increase in the volume density of lipid inclusions and a slight reduction in the volume density of the remaining cytoplasm. Possible reasons for the differences in the response of the cells in the two smoke-exposed groups are discussed.
A combined biochemical and cytochemical study of catalase was performed on alveolar macrophages lavaged from the lungs of adult male rats. Biochemically, catalase activity was present in both a high-speed granule fraction and in the supernatant. The granule-associated activity exhibited latency. Two methods of cell breakage, sonication and homogenization, yielded similar levels and distributions of catalase activity. Catalase activity in whole cells was identified cytochemically by the alkaline diaminobenzidine method and was localized within membrane-lined cytoplasmic granules similar in size to microperoxisomes and associated with cisternae of smooth endoplasmic reticulum. Localization of the reaction product was inhibited by 0.04 M aminotriazole, by cyanide, and by boiling prior to incubation. The cytochemical reaction continued in the absence of exogenous peroxide, but could be prevented by addition of catalase or pyruvate to the peroxide-free medium. Enzyme activity was also localized within a portion of the membrane-bound granules present in the cell fractions used for the biochemical assays.
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Alveolar macrophages harvested by bronchopulmonary lavage from rats exposed to tobacco smoke for 30 days ("smokers") showed alterations in oxidative metabolism, lactate production and phagocytosis of inert starch particles when compared with control macrophages. Phagocytosis of viable Staphylococcus aureus was unaffected by tobacco smoke. Glucose oxidation measured by conversion of glucose-1-14C to 14CO2 moderately affected while oxidation of glucose-6-14C to 14CO2 was not. Smokers routinely yielded fewer cells than controls, though these cells contained approximately 17% more protein than did controls. Opsonization of particles was not necessary for macrophages from either smoker or control animals to manifest a respiratory burst and increased superoxide and hydrogen peroxide release during phagocytosis. The glycolytic inhibitors, sodium fluoride and iodoacetamide, while effectively blocking glycolysis, did not inhibit phagocytosis by macrophages from either group. The results reported clearly distinguish alveolar macrophages from other phagocytic cells (peritoneal macrophages and polymorphonuclear leukocytes) and suggest a state of non-specific activation caused by exposure to tobacco smoke.
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Histochemical quantification of goblet cells and measurements of the epithelial thickness were made in the trachea of male and female rats exposed to fresh whole tobacco smoke for 30 consecutive days. Exposure to tobacco smoke resulted in an increase in the total goblet cell count in both sexes, with the female rats differentially responding to a greater degree than the male rats. There was a shift from PAS-positive to alcian blue-positive goblet cells, an increase in the number of both "large" and "small" goblet cells, and an increase in the epithelial thickness. PAS-positive "small" cells, the major glycoprotein-reactive cell in the rat tracheal epithelium, increased in the female rats but showed no increase in the male rats. On the other hand, male rats contained a substantially higher proportion of alcian blue-positive cells than did female rats, both before and after exposure to the smoke. The significance of these observations in relation to the prevalence of chronic bronchitis in human smokers is discussed.
Nineteen fiberoptic bronchoscopic procedures were performed on ten patients for the treatment of pulmonary collapse. All but two patients were being treated for severe, life-threatening nonpulmonary diseases. Thick, tenacious, and, at times, purulent mucous plugs were successfully aspirated from the bronchial passages. Complete to partial radiologic reexpansion of the collapsed pulmonary region was observed following all but one procedure. Significant improvement in blood gas levels was also noticed immediately after the procedure. Bronchoscopic examination in these seriously ill patients did not cause any complications. The therapeutic value of fiberoptic bronchoscopic procedures in patients developing pulmonary collapse due to thick secretions and mucous plugs was demonstrated.
The in vitro antibacterial activity of rat alveolar macrophages against a challenge of radiolabeled Staphylococcus epidermidis was studied following 30 and 60 consecutive days of in vivo tobacco smoke inhalation in a dose equivalent to approximately 1 1/2 packs of unfiltered cigarettes per day in man. Macrophages harvested by bronchopulmonary lavage, were cultured, infected, and assayed hourly for 3 hr to determine the relative percentage of surviving radiolabeled intracellular bacteria. Macrophages harvested from smoke-treated rats for 30 days had an impaired capacity to kill bacteria when compared to macrophages from control and sham-smoked animals (63.5% +/- 3.3, 80.8% +/- 3.8, and 86.2% %/- 1.2 killed in 3 hr, respectively). Alveolar macrophages harvested from rats exposed to cigarette smoke for 60 days, however, did not have an impairment in their bactericidal activity relative to matched controls (73.3% +/- 3.9 vs 69.8% +/- 6.9 killed in 3 hr). These data imply that doses of cigarette smoke commonly consumed by man impair the in vitro bactericidal function of the rat alveolar macrophages following 30 consecutive days of experimental smoke treatment. The disappearance of this effect after 60 days of exposure to tobacco smoke suggests that an adaptation to the initial impairment has developed.
The cause of higher morbidity rates among men than women from diseases of the respiratory tract may be complex and involve several factors, one of which may be structural differences within airways. In an attempt to determine whether such differences exist, 13 male rats and 45 female rats (15 each in proestrous, estrous, and diestrous) were evaluated. Tracheas were fixed in situ by injection of a mixture of formaldehyde and glutaraldehyde. Longitudinal sections cut from paraffin blocks were stained and combined alcian blue (pH 2.5) and periodic acid-Schiff stain to count goblet cells, or with Weigert's hematoxylin and eosin stain to determine epithelial thickness. In the normal rat trachea, cells containing periodic acid-Schiff-positive granules at their apices constituted a major population of goblet cells. The number of these goblet cells present in the trachea was greater in female than in male rats at each stage of the estrous cycle, with the values in the diestrous females closest to the value in the males. Among females, estrous and proestrous rats contained significantly more of these goblet cells than did diestrous animals. The tracheal epithelium of male rats was significantly thicker than that of female rats. These studies demonstrate that the tracheal epithelium differs in male and female rats and varies in the female rat as a function of hormonal cycles. These results raise the question of whether similar differences might be important in the pathogenesis of human disease, and they deserve further clarification in man.
A method is described for the collection and fixation for microscopy of samples of alveolar macrophages harvested by bronchopulmonary lavage. The cell pellicles thus obtained were analyzed by light microscopy by measurement of cell profile diameters. Statistical comparison indicated that no gradient in profile size was present across individual pellicles; they were therefore suitable for random sampling. Mean profile diameters and size distributions were compared for the individual populations of alveolar macrophages.