acid-phosphatase and Respiratory-Distress-Syndrome

The early acute pulmonary response of Wistar rats exposed nose-only to respirable polymeric diphenylmethane 4,4'-diisocyanate (MDI) aerosol was examined. This study investigated the time course of the relationship between acute pulmonary irritation and ensuing disturbances of the air/blood barrier in rats exposed to concentrations of 0.7, 2.4, 8, or 20 mg MDI/m3. The duration of exposure was 6 h. The time-response relationship of MDI-induced acute lung injury was examined 0 h (directly after cessation of exposure), 3 h, 1 day, 3 days, and 7 days after exposure. Bronchoalveolar lavage (BAL) fluid was analyzed for markers indicative of injury of the bronchoalveolar region, i.e., angiotensin-converting enzyme, protein, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, and sialic acid. Phosphatidylcholine and acid phosphatase were determined in BAL fluid and cells. Glutathione was determined in BAL fluid and lung tissue. This analysis revealed no latent period of effects except a transiently delayed influx of cells and increased lung weights on postexposure days 1 and 3. Markedly loaded BAL cells with phosphatidylcholine were observed on day 1 only. In most instances, changes returned to the level of the air exposed control on day 7, except increased glutathione in lung tissue. The findings suggest that the most sensitive markers of dysfunction of the air/blood barrier are angiotensin-converting enzyme and protein, including alkaline phosphatase. The statistically significant increase in intracellular phosphatidylcholine and decreased intracellular acid phosphatase on the exposure day suggest that increased amounts of phospholipids are phagocytized by alveolar macrophages, associated with protracted lysosomal catabolism. Partially glutathione-depleted rats exposed to 20 mg/m3 experienced a more pronounced increase in BAL protein than normal rats. In summary, this study suggests that respirable polymeric MDI aerosol interacts directly with the air/blood barrier causing increased extravasation of plasma constituents as a result of increased permeability of capillary endothelial cells. Overall, a transient dysfunction of the pulmonary epithelial barrier occurred at level as low as 0.7 mg/m3 and appears to be related a dysfunction of pulmonary surfactant. Nonprotein sulfhydryl constituents appear to play a role as portal-of-entry specific modifying factors.

Topics: Acid Phosphatase; Aerosols; Alkaline Phosphatase; Animals; Bronchoalveolar Lavage Fluid; Buthionine Sulfoximine; Capillary Permeability; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; gamma-Glutamyltransferase; Glutathione; Inhalation Exposure; Isocyanates; L-Lactate Dehydrogenase; Lung; Lysosomes; Peptidyl-Dipeptidase A; Phosphatidylcholines; Polyurethanes; Pulmonary Edema; Pulmonary Surfactants; Rats; Rats, Wistar; Respiratory Distress Syndrome

An experimental model of haemorrhagic hypotension was standardized using rabbits to investigate the shock lung syndrome over a period of 120 minutes. Acute hypovolaemia was induced by withdrawal of blood under anaesthesia to a mean arterial pressure of 30 +/- 5 mmHg within 10 minutes. The mean leucocyte counts and the release of lysosomal enzymes (acid phosphatase and beta-glucuronidase) in the blood and in lung tissue, as well as the metabolic capacities of lung tissue in terms of protein and lipid biosynthesis, were investigated at set intervals after 30, 60, 90 and 120 minutes. The results indicate a progressive decline in leucocyte numbers over 120 minutes to about 40% of the original. An immediate granulocytopenia was observed with a relative lymphocytosis within 30 minutes. The beta-glucuronidase and acid phosphatase contents of the plasma increased with time; beta-glucuronidase activity increased progressively as leucocytes disappeared from the circulation. Concomitantly, the capacity of the lung tissue to synthesize protein and lipids was retarded with time, becoming significantly lower than baseline values after 60 minutes of hypovolaemia. The decline in leucocyte numbers in the circulation correlated well with the increase in beta-glucuronidase activity and the retarded metabolic capacity of the lung tissue.

Topics: Acid Phosphatase; Animals; Glucuronidase; Hematocrit; Leukocyte Count; Lipids; Lung; Proteins; Rabbits; Respiratory Distress Syndrome; Shock; Time Factors

The cause of the posttraumatic respiratory distress syndrome is not yet well known and cannot be proved with certainty. The early stage of posttraumatic lung failure has been examined both from a morphological and biochemical aspect. Lung biopsies taken during hypovolemic-traumatic shock show besides endothelial damage an accumulation of leucocytes with free granules, similar to lysosomes. Based on these results further tests have been carried out to achieve a similar reaction in the hypovolemic-traumatic shock model in the dog, enabling us to undertake more extensive examinations and to use new methods of treatment. The lung biopsies taken at the beginning and after finishing the test were observed by light-transmission and scanning electron-microscope. Similar to the results obtained from humans, we found a massive leucostasis with degranulated cells. A parallel increase of lysosomal enzyme activity and a peripheral leucocytosis was seen while after reinfusion a distinct decrease was found. The massive occurence of leucocytes in the lung may be caused either by chemotaxis or by the sieve function of the lung after peripheral leucocytes aggregation. Both could have an immunological cause, especially due to involvement of the complement system. Septic reasons in the early stage of shock can be disregarded. More likely the complex effects of the interactions complement--fibrinolysis--kallikrein system are involved. Presumably the leucocytes caused direct damage to the endothelial cells. Lysosomal enzymes as reason for producing the damage would be one possibility; an other is the recently discovered effect of oxygen radicals produced during the close contact between leucocytes and endothelium and the simultaneously activated complement system.

Topics: Acid Phosphatase; Animals; Chemotaxis; Complement Activation; Dogs; Glucuronidase; Humans; Leukocytes; Lung; Lysosomes; Respiratory Distress Syndrome; Shock