Adult respiratory distress syndrome.
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Biomedical subjects
Publications and source records attributed to D F Tierney.
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Pathogen-free rats were given either hydrocortisone (4 mg) or saline by intraperitoneal injection twice daily for 7 consecutive days. Lung weight, body weight, DNA, and total phosphatidylcholine content in lungs were equal in the saline and hydrocortisone groups. Lungs of rats receiving hydrocortisone had 23% more saturated phosphatidylcholine (P less than 0.001) and 7% less unsaturated phosphatidylcholine (P greater than 0.05). When tissue slices of these lungs were incubated with radioactive glycerol and palmitate, the incorporation of radioactivity into saturated phosphatidylcholine from animals given hydrocortisone was significantly higher (P less than 0.001 and P less than 0.05, respectively). Incorporation of radioactivity from lysophosphatidylcholine into phosphatidylcholine was 10 times greater than from glycerol or palmitate, but hydrocortisone had no effect. These results suggest that lysophosphatidylcholine may be an important precursor for phosphatidylcholine synthesis, especially saturated phosphatidylcholine, and hydrocortisone may lead to increased de novo synthesis of phosphatidylcholine.
Although air embolism is known to occur in humans and animals when the lung is overdistended, very few cases have been reported to be associated with positive-pressure ventilation. We have observed that air embolism occurs in rats ventilated with high inspiratory pressures (70 cmH2O) associated with high end-expiratory pressures (10 cmH2O). However, it does not occur in normal rats if the end-expiratory pressure is less than 5 cmH2O or the peak inspiratory pressure is below 60 cmH2O when the frequency of ventilation is 30. Hemorrhagic shock predisposes to air embolism, whereas conditions with pulmonary edema (fluid overloading, lung injury from ventilation with high inspiratory and low expiratory pressures, or oxygen toxicity) decrease the probability of its occurrence.
We compared several sets of conditions used to estimate metabolism in rat lung slices. 14CO2 production from [14C]glucose, oxygen consumption, lactate production, and glucose consumption were used as measures of metabolic activity. The calculated results differed when we used 1) different techniques for estimating tissue weight, 2) tissue slices of 0.3-, 0.5-, 0.7-, and 1.0-mm thickness, 3) 95% air or 95% oxygen with 5% CO2 4) a delay after slice preparation and 4 degrees C and room temperature or periods of anoxia before incubation, 5) shaking rates of 60, 90, 120, or 150/min, 6) phosphate or bicarbonate buffers. Conditions of maximal activity were found using 95% O2 with 1.0-mm tissue slices, shaking at 120/min in phosphate buffer without periods of hypoxia or undue delays before incubation. Tissue weight should be obtained without exposure to aqueous solutions or dehydration by contact with cotton gauze or filter paper.
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Twenty pregnant rabbits were studied in pairs. Half were given cortisol subcutaneously on days 24, 25, and 26 of gestation in dosage of 2 mg/kg/day. Half served as controls and received saline. The fetal lungs were studied on the 27th day of gestation by incubating lung slices in the presence of [6-14C]glucose. Glucose consumption significantly increased in the tissue from animals treated with cortisol, 17.61 "/- 5.56 (SD) mumol/g in the controls (P less than 0.05). The glycogen content of tissue treated with cortisol was significantly reduced compared to the controls, 2.42 +/- 0.97 (SD) mg/g wet lung versus 3.81 +/- 1.05 (SD) mg/g (P less than 0.05). Treatment with cortisol resulted in significantly enhanced incorporation of the 14C label into glycogen and phosphatidyl choline (Tables 3 and 4). These data suggest that glucocorticoids affect fetal lung phosphatidyl choline production by promoting glycogenolysis and increasing glucose incorporation into phosphatidyl choline.
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Lung metabolism has been extremely difficult to determine in vivo primarily because the lung is overwhelmed by a great blood flow that generally makes the Fick principle inadequate. Largely for reasons such as this, investigators have had to rely on in vitro preparations. The isolated perfused lung has the apparent advantage of being similar to the lung in vivo when compared with other preparations. For instance, there is evidence that the capillary bed of the lung may alter substrates and influence their subsequent metabolism. Substrates have contact with the capillary endothelium in isolated perfused lungs but not to tissue slices, homogenates, or isolated cells. Our studies indicate that precursors of saturated phosphatidylcholine may include lipids, which are hydrolyzed in the capillary of the isolated perfused lung and thus become substrates such as free fatty acids, etc. However, tissue slices do not use the esterified lipids to the same extent, presumably because in this preparation the enzymes in the capillary endothelium do not have contact with the esterified lipids. Substrate utilization of the isolated perfused lung may be considerably altered by inflation of the lung or by pulmonary edema. Although glucose utilization and palmitate oxidation by the isolated perfused lung and by tissue slices of the rat lung are very similar, if the isolated perfused lung develops pulmonary edema, glucose utilization increases by nearly 100%. This phenomenon is apparently not due solely to fluid in the airspaces because in control studies with fluid added into the airways the glucose utilization did not increase to the degree observed with edematous lungs. Lung distention is associated with increased glucose consumption but marked distention is also associated with pulmonary edema. The effect of lung distension may be a direct effect or it may be secondary to the pulmonary edema.
Using conventional concepts, it is possible that a single pathologic entity, pulmonary telangiectases, can produce hypoxia by 3 physiologic mechanisms; shunt, diffusion defect, and ventilation-perfusion abnormalities. The estimation of shunt or shunt-like effect is traditionally calculated by measuring the Po2 of arterial blood during the breathing of 100 per cent 02. This method, however, did not determine blood flow through large alveolar vessels in a patient with familial hemorrhagic telangiectasis who was severely hypoxemic while breathing air. This case served to test the concept that blood flowing through large vessels in the airspaces may be hypoxemic when the patient breathes air, but not 02. Blood flow through these vessles can be estimated by use of radionuclide lung perfusion techniques and estimation of the quantity of radioactive particles that pass through an abnormal pulmonary vascular bed and lodge in kidney and brain. Conventional approaches to estimating blood flow through these fistulas underestimated their effect.
To learn whether surface force changes precede the appearance of lung edema during experimental intoxication due to paraquat, we studied rats for 1 day following injection of 27 mg/kg iv. By 24 h, surface-active material recovered by lung lavage was decreased 32 percent, and changes in lung microsections and recoil pressure at half-deflation suggested decreased alveolar stability. Despite a 25 percent loss in overall body weight, lung weight increased more than 7 percent and protein concentration in lung lavage fluid increased by 158 percent. Lung edema was demonstrated morphologically as early as we could detect changes in surfactant or lung mechanical properties. Metabolic studies with lung tissue slices incubated with 4.5 times 10-4 M paraquat showed a fourfold increase in 14CO2 formed from (1-14C) glucose, but no significant change in 14CO2 form (6-14C) glucose, suggesting increased utilization of the pentose pathway for oxidation of glucose. (1-14C) Acetate oxidation was impaired slightly, but incorporation into lipid was decreased by 70 percent. we conclude that paraquat intoxication in the rat is not a suitable model for studying uncomplicated perturbation of the surfactant system.
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