PubMed Health⌕ Search

Biomedical subjects

K L Brigham

Publications and source records attributed to K L Brigham.

At least 73 records · Page 4Linked to original sources
PubMed1988

Continuous air embolization into sheep causes sustained pulmonary hypertension and increased pulmonary vasoreactivity.

Baseline pulmonary arterial, left atrial and systemic artery pressures, cardiac output, and lung lymph flow were measured in seven chronically catheterized sheep before continuous air embolization into the pulmonary artery, which caused a two-to-threefold increase in pulmonary vascular resistance (PVR) for 12 days. Air embolization was discontinued on days 4, 8, and 12 and hemodynamic measurements were repeated. Thromboxane B2, 6-keto-PGF1 alpha, and protein were measured in lung lymph and blood plasma on days 0, 4, 8 and 12. Air embolization caused an acute, sustained rise in pulmonary artery pressure and PVR (baseline, 3.68 +/- 0.21; air, 8.32 +/- 0.62, mean +/- SE). By day 4, PVR was increased significantly even when air flow was interrupted (5.97 +/- 0.72) and by day 12, it was almost twice baseline; pulmonary artery pressure also remained elevated (baseline, 19 +/- 1 cm H2O; day 12, 31 +/- 3). Pulmonary vasoreactivity to PGH2-A was significantly increased on days 4, 8, and 12 (day 12, 285 +/- 41% of baseline response). Lung lymph flow, protein, and thromboxane clearance were increased throughout the study while clearance of 6-keto-PGF1 alpha was increased at day 4 and falling by day 8. At autopsy, morphometric analysis of the barium-injected pulmonary arterial bed revealed striking structural remodeling, extension of muscle into smaller arteries than normal: decreased peripheral arterial filling, increased medial thickness, and dilated large pulmonary arteries. Continuous air embolization into sheep causes the structural and functional changes of chronic pulmonary hypertension accompanied by increased pulmonary vasoreactivity to a bolus of PGH2-A. The abrupt onset of the sustained elevation in PVR induced by air embolization may account for the severity of the structural remodelling, particularly for the increased medial thickness.

Animals↗
PubMed1987

Prevention of release of granulocyte aggregants into sheep lung lymph following endotoxemia by N-acetylcysteine.

Interactions of granulocytes with the lungs are altered by endotoxemia and may be critical in the pathogenesis of endotoxin-induced lung injury. In chronically instrumented unanesthetized sheep, we measured the ability of lung lymph to aggregate normal sheep neutrophils in vitro. We found a marked increase in lung lymph aggregating activity beginning within 1 hour after endotoxin infusion and persisting for several hours. When n-acetylcysteine was administered to the animals before endotoxin infusion, neutrophil aggregating activity in lung lymph after endotoxin infusion was markedly reduced. N-acetylcysteine did not affect neutrophil aggregation, adherence, or leukotriene B4 production in vitro and did not prevent complement activation at concentrations achieved in vivo. It is concluded that endotoxemia causes release from the lungs of substance(s) that activate granulocytes, and that this response is prevented by n-acetylcysteine, possibly as a result of the antioxidant properties of the drug.

Acetylcysteine↗
PubMed1987

Endotoxin increases superoxide dismutase in cultured bovine pulmonary endothelial cells.

Manganous (Mn) and copper zinc (CuZn) superoxide dismutase (SOD) concentrations and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured in cultured bovine pulmonary endothelial cells with and without exposure to Escherichia coli endotoxin (10(-1) micrograms/ml) over intervals of 0.5-24 h. The activities of two mitochondrial marker enzymes, fumarase and cytochrome-c oxidase, were also measured. Endotoxin exposure caused a marked increase (9-fold) in endothelial cell Mn SOD content without significant effects on GSH-Px, CAT, fumarase, or cytochrome-c oxidase activities. Endotoxin induced a slight decrease in CuZn SOD content over 24 h. This is the first report of a selective effect of endotoxin on Mn SOD in pulmonary endothelial cells. The response appears to be independent of an increase in mitochondrial activity (no change was observed in cytochrome-c oxidase or fumarase activities). These findings support the notion that endotoxin increases generation of toxic oxygen metabolites within pulmonary endothelial cells. An endotoxin-induced increase in Mn SOD could contribute to the reported protective effect of endotoxin against oxygen toxicity in these cells.

Animals↗
PubMed1987

Acute effects of thoracic irradiation on lung function and structure in awake sheep.

To investigate the acute physiological and structural changes after lung irradiation, the effects of whole-lung irradiation were investigated in fourteen sheep. Ten sheep were prepared with vascular and chronic lung lymph catheters, then a week later were given 1,500 rad whole-lung radiation and monitored for 2 days. Four sheep were given the same dose of radiation and were killed 4 h later for structural studies. Lung lymph flow increased at 3 h after radiation (14.6 +/- 2.1 ml/h) to twice the base-line flow rate (7.5 +/- 1.3), with a high lymph-to-plasma protein concentration. Pulmonary arterial pressure increased twofold from base line (18 +/- 1.6 cmH2O) at 2 h after radiation (33 +/- 3.8). Cardiac output and systemic pressure in the aorta did not change after lung radiation. Arterial O2 tension decreased from 85 +/- 3 to 59 +/- 4 Torr at 1 day after radiation. Lymphocyte counts in both blood and lung lymph decreased to a nadir by 4 h and remained low. Thromboxane B2 concentration in lung lymph increased from base line (0.07 +/- 0.03 ng/ml) to peak at 3 h after radiation (8.2 +/- 3.7 ng/ml). The structural studies showed numerous damaged lymphocytes in the peripheral lung and bronchial associated lymphoid tissue. Quantitative analysis of the number of granulocytes in peripheral lung showed no significant change (base line 6.2 +/- 0.8 granulocytes/100 alveoli, 4 h = 10.3 +/- 2.3). The most striking change involved lung airways. The epithelial lining of the majority of airways from intrapulmonary bronchus to respiratory bronchiolus revealed damage with the appearance of intracellular and intercellular cell fragments and granules. This new large animal model of acute radiation lung injury can be used to monitor physiological, biochemical, and morphological changes after lung radiation. It is relevant to the investigation of diffuse oxidant lung injury as well as to radiobiology per se.

Animals↗
PubMed1987

Antioxidants protect cultured bovine lung endothelial cells from injury by endotoxin.

Endotoxin injures bovine pulmonary endothelial cells in culture but the cytotoxicity is unaffected by a host of antiinflammatory drugs. We hypothesized that agents which could decrease intracellular concentrations of toxic metabolites of O2 would prevent endotoxin effects on cultured pulmonary artery endothelial cells. We measured endotoxin-induced release of lactate dehydrogenase (LDH) from and production of prostanoids by cultured bovine pulmonary endothelial cells in the presence and absence of dimethyl sulfoxide (DMSO) and the xanthine oxidase inhibitor allopurinol. Escherichia coli endotoxin (0.001-10 micrograms/ml) caused a dose-related release of LDH and stimulated production of both prostacyclin [measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha)] and prostaglandin E2 (PGE2). Both DMSO and allopurinol decreased endotoxin-induced LDH release; this effect was related to concentration of the drugs (0-2% for DMSO and 0-0.3 mg/ml for allopurinol). Both drugs also prevented endotoxin-induced changes in endothelial morphology. Endotoxin increased intracellular reduction of the redox dye nitro blue tetrazolium, caused intracellular oxidation of 2',7'-dichlorofluorescein diacetate and caused release of conjugated dienes from endothelial cells; both DMSO and allopurinol inhibited those responses. DMSO, but not allopurinol, prevented endotoxin-induced production of prostacyclin and PGE2 by endothelium. Direct injury of pulmonary endothelium by endotoxin is inhibited by two chemically dissimilar drugs which have a common potential for decreasing intracellular concentrations of toxic metabolites of O2; indirect evidence suggests that potential as a mechanism for the protective effects of the drugs.

Allopurinol↗
PubMed1987

Effects of endotoxemia on pulmonary vascular resistances in unanesthetized sheep.

Ten experiments were conducted on nine sheep to determine the effects of endotoxemia (1.0 microgram/kg iv over 15 min) on the vascular resistances of two segments of the pulmonary circulation. The first segment (S1) was from the main pulmonary artery to the site in the pulmonary veins corresponding to the pressure measured with a deflated and wedged 7-Fr Swan-Ganz catheter. The second segment (S2) was from the wedge pressure measurement site to the left atrium. Endotoxemia caused both pulmonary arterial pressure and pulmonary arterial wedge pressure to increase significantly during early (phase 1) and late (phase 2) periods of response; left atrial pressure was significantly decreased during both phases. Normalized cardiac output decreased significantly at 35 and 180 min but not at 240 min after starting endotoxin infusion. The calculated resistance of S1 significantly increased from a base-line value of 3.03 +/- 0.31 (cmH2O.1-1.min) to 7.60 +/- 0.71, 6.34 +/- 1.22, and 6.66 +/- 1.35 at 35, 180, and 240 min, respectively. Calculated resistance of S2 was 1.32 +/- 0.14 at base line and increased significantly to 11.43 +/- 1.66 at 35 min, 4.45 +/- 0.47 at 180 min, and 3.32 +/- 0.61 at 240 min. The calculated percent of total pulmonary resistance in S2 increased significantly from approximately 31 to 59% during phase 1 and remained significantly increased at 41% from 90 to 180 min after endotoxin. Hematocrit increased by 40% at 35 min, whereas plasma total protein concentration increased by only 8% at 35 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep.

The direct and indirect actions of two active components of slow-reacting substance of anaphylaxis, leukotrienes C4 (LTC4) and D4 (LTD4), were studied in chronically instrumented unanesthetized sheep. Intravenous injection of 3 micrograms of LTD4 caused immediate marked pulmonary arterial hypertension which returned to baseline in 6.5 +/- 1.0 min. Dynamic compliance of the lungs (Cdyn) and left atrial (PLA) and aortic (Paorta) blood pressure fell concomitantly with the increases in pulmonary artery pressure (PPA). PLA and Paorta then increased above baseline and heart rate deceased significantly. LTD4 caused only small increases in lung lymph flow but did increase lung lymph concentrations of thromboxane B2. Lung lymph concentrations of 6-keto-prostaglandin F1 alpha did not increase following LTD4 infusion. The increase in PPA after 3-micrograms injections of LTD4 was greater than that caused by 10-micrograms injections of prostaglandin H2-analog. Injections of 10-30 micrograms of LTC4 caused only minor increases in PPA but did cause bradycardia and delayed increases in PLA and Paorta. The cyclooxygenase inhibitors meclofenamate and ibuprofen inhibited the increases in PPA caused by LTD4 but not the later bradycardia or increases in PLA and Paorta. The thromboxane synthetase inhibitor UK-38485 attenuated the early increase in PPA and moderated the later increases in PLA and Paorta and bradycardia caused by LTD4 injection. The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Lung water and vascular permeability-surface area in premature newborn lambs with hyaline membrane disease.

Extravascular lung water and vascular permeability-surface area products were measured with a multiple indicator dilution method in 6 premature lambs with hyaline membrane disease 1-5 hours following delivery by cesarean section. The indicators used were 51Cr-labelled erythrocytes, 125I-albumin, 3H-water, and 14C-urea. Results were compared with previously obtained data in newborn lambs without hyaline membrane disease also delivered by cesarean section. Extravascular lung water was significantly higher in lambs with hyaline membrane disease [23.2 +/- 1.0 (SEM) vs. 10.7 +/- 1.4 ml/kg body wt]. Vascular permeability-surface area products for 14C-urea were significantly lower in lambs with hyaline membrane disease (0.30 +/- 0.10 vs 0.78 +/- 0.11 ml/s per kg). It is concluded that extravascular lung water is high in lambs with hyaline membrane disease. Permeability-surface area products for 14C-urea is low in lambs with hyaline membrane disease, which probably indicates a decrease in detectable surface area for exchange due to derecruitment or hypoperfusion of pulmonary exchange vessels in edematous and hypoxic areas of the lungs.

Animals↗
PubMed1987

Conference summary: lipid mediators in the pulmonary circulation.

Material presented and discussed at this conference is evidence of intense interest in the roles of lipid mediators in lung pathophysiology. This interest derives from the fact that these mediators are manufactured in abundance in response to many stimuli and from the fact that lipid mediators can effect structure and function of lungs and their component cells; whether these chemicals do effect dysfunction of the lungs in humans or act to preserve normal lung function is not yet resolved. However, major advances are being made and, even now, clinical trials of therapies based on experimental rationales suggested by the data discussed at this conference appear justified.

Animals↗
PubMed1987

Distribution of proteins in pulmonary edema. The value of fractional concentrations.

Pulmonary edema fluid (PEF) and serum (S) were obtained from 14 patients with cardiac pulmonary edema (CPE) and 25 noncardiac pulmonary edema (NCPE) patients. The type of pulmonary edema was based on a clinical classification. The protein content of PEF was not significantly different between CPE (3.89 +/- 0.25 g/dl, mean +/- SEM) and NCPE (4.35 +/- 0.34 g/dl) patients, but the protein content of serum was different (7.18 +/- 0.27 versus 5.13 +/- 0.23, respectively, p less than 0.001). As expected then, the PEF/S ratio was greater in NCPE than in CPE (0.85 +/- 0.06 versus 0.54 +/- 0.03, respectively, p less than 0.05). Thus, differences in the PEF/S ratios in CPE as compared with those in NCPE are independent of mean edema fluid protein content and dependent on differences in serum protein content. PEF and S proteins were separated into 9 fractions of increasing molecular radius by electrophoresis, and fractional concentrations (percent of total protein content) were calculated. The fractional concentrations of these combined fractions of serum proteins were not different between CPE and NCPE. Fractional PEF/S ratios were significantly greater for combined fractions I-III (p less than 0.01) in CPE than in NCPE and significantly less in fractions VII-IX (p less than 0.01). In CPE, a higher percentage of proteins with smaller molecular radii (45 A) enter the airway compartment in part because of higher hydrostatic pressures, whereas in NCPE, larger proteins enter the airways consequent to increased permeability to proteins with molecular radii greater than 72 A.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Correlation of permeability with the structure of the endothelial layer of pulmonary artery intimal explants.

Changes in vascular permeability are associated with structural damage to endothelial cells. These functional and structural changes can be produced experimentally and examined by using intimal explants from bovine pulmonary artery. Correlation of functional with structural changes allows us to dissect the mechanisms responsible for endothelial damage. We have shown that incubation of intimal explants with histamine causes transient formation of interendothelial dilatations and an increased rate of equilibration of tritiated water and [14C]sucrose across the intimal explant. Exposure to endotoxin also causes interendothelial dilatations but the endothelial damage is more severe than that with histamine, and in vivo experiments show a more prolonged increase in pulmonary vascular permeability. Leukocyte migration has also been suggested to result in a decreased barrier function of the endothelial layer. Experiments with the endothelial layer of intimal explants and separated bovine leukocytes suggest that transendothelial migration may depend on the chemotactic stimulus. Neither granulocyte migration toward zymosan-activated plasma nor lymphocyte migration toward lymphocyte-conditioned medium (RPMI in which lymphocytes were incubated with concanavalin A) leads to detectable increases in explant permeability, but granulocyte migration toward lymphocyte-conditioned medium does result in increased equilibration of [14C]sucrose. Finally, a theoretical model has been used to examine the permeability changes seen for the intimal explants exposed to histamine. The model consists of two compartments with radioactive tracers diffusing across a filter of known permeability. Such a model gives good agreement with data obtained in intact sheep, indicating that mathematical models allow quantitative estimates of barrier function in intimal explants that compare favorably with in vivo data.

Animals↗
PubMed1986

Pulmonary edema.

The pathophysiology of pulmonary edema formation has been discussed under normal conditions and when pulmonary capillary endothelial (and possibly alveolar epithelial) permeability are increased. The potential anatomic sites for pulmonary edema formation and the clinical relevance of the various sites were discussed. The role of potential "safety factors"--including increased lung lymph flow, increased interstitial hydrostatic pressure, and decreased interstitial protein osmotic pressure--in cardiogenic and fluid overload versus increased permeability pulmonary edema, were addressed. The clinical usefulness of quantitating various variables including pulmonary vascular pressures and lung water were also briefly discussed. Pulmonary edema fluid contains potential mediators that may contribute to the severity and chronicity of the lung injury. It is hoped that the concepts explored here should eventually provide clinically relevant information to guide in the management of critically ill patients with pulmonary edema.

Body Water↗
PubMed1986

Lymphocyte and granulocyte migration across the endothelial layer of bovine pulmonary artery intimal explants towards lymphocyte conditioned medium.

An intravenous infusion of endotoxin into sheep results in accumulation of equal numbers of lymphocytes and granulocytes in the pulmonary microcirculation. The role of the sequestered lymphocytes in acute lung injury is not known. The present study examines whether lymphocyte migration through pulmonary endothelium contributes to endothelial damage and also examines the effect of lymphokines on granulocyte migration. Bovine pulmonary artery intimal explants were mounted in Boyden chambers and conditioned media, prepared from bovine peripheral blood lymphocytes, was used as the chemoattractant. The rate of 51Cr labelled bovine granulocyte lymphocyte migration into intimal explants was determined over a 3 hr incubation period. Permeability changes were assessed by adding trace amounts of 14C-sucrose and 3H-water to the upper well and following their rate of equilibration with the lower well. 6-Keto-PGF1 alpha was measured in the upper well. Lymphocyte conditioned media was found to be chemotactic for both lymphocytes and granulocytes (lymphocyte migration at 60 min: lymphocyte conditioned media = 18.5 +/- 2.3%, mean +/- s.e. RPMI control = 12.5 +/- 1.5; granulocyte migration at 120 min: conditioned media = 36.1 +/- 5.7, RPMI control = 18.2 +/- 3.0). Ultrastructural examination revealed leukocyte migration followed an orderly sequence during which the leukocytes maintained close contact with the adjacent endothelial cells. No structural evidence of endothelial cell damage was seen at any time examined. Granulocyte migration was associated with an increased rate of 14C-sucrose equilibration after 2 hr of incubation (lower well counts/upper well counts at 2 hr, RPMI control = 0.18 +/- 0.02; lymphocyte conditioned medium = 0.30 +/- 0.04) indicating alteration in the endothelial barrier function. Leukocyte migration, particularly lymphocyte migration, was accompanied by a marked increase in prostacyclin accumulation (3 hr: no leukocytes, 188 +/- 17 ng/ml; lymphocytes, 560 +/- 104). These in vitro findings suggest that lymphocytes and lymphokines may be involved in acute lung injury and also that permeability changes associated with granulocyte migration may depend on the chemoattractant.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effects of inspiratory resistance loading on lung fluid balance in awake sheep.

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.

Airway Obstruction↗
PubMed1986

Effects of hypoproteinemia on lung microvascular protein sieving and lung lymph flow.

Experiments were conducted on five chronically instrumented unanesthetized sheep to determine the effects of sustained hypoproteinemia on lung fluid balance. Plasma total protein concentration was decreased from a control value of 6.17 +/- 0.019 to 3.97 +/- 0.17 g/dl (mean +/- SE) by acute plasmapheresis and maintained at this level by chronic thoracic lymph duct drainage. We measured pulmonary arterial pressure, left atrial pressure, aortic pressure, central venous pressure, cardiac output, oncotic pressures of both plasma and lung lymph, lung lymph flow rate, and lung lymph-to-plasma ratio of total proteins and six protein fractions for both control base-line conditions and hypoproteinemia base-line conditions. Moreover, we estimated the average osmotic reflection coefficient for total proteins and the solvent drag reflection coefficients for the six protein fractions during hypoproteinemia. Hypoproteinemia caused significant decreases in lung lymph total protein concentration, lung lymph-to-plasma total protein concentration ratio, and oncotic pressures of plasma and lung lymph. There were no significant alterations in the vascular pressures, lung lymph flow rate, cardiac output, or oncotic pressure gradient. The osmotic reflection coefficient for total proteins was found to be 0.900 +/- 0.004 for hypoproteinemia conditions, which is equal to that found in a previous investigation for sheep with a normal plasma protein concentration. Our results suggest that hypoproteinemia does not alter the lung filtration coefficient nor the reflection coefficients for plasma proteins. Possible explanations for the reported increase in the lung filtration coefficient during hypoproteinemia by other investigators are also made.

Animals↗
PubMed1986

Diethylcarbamazine on pulmonary vascular response to endotoxin in awake sheep.

Diethylcarbamazine (DEC) is an inhibitor of lipoxygenase, with protective effects in several experimental models of anaphylaxis and lung dysfunction. The hypothesis of this study was that DEC would alter the pulmonary response to endotoxin infusion, especially the prolonged pulmonary hypertension, leukopenia, hypoxemia, and high flow of protein-rich lung lymph. We prepared sheep for chronic measurements of hemodynamics and collection of lung lymph. In paired studies we gave six sheep endotoxin (0.5 micrograms/kg iv) either with or without DEC. DEC was given (80-100 mg/kg iv) over 30 min followed by a continuous infusion at 1 mg X kg-1 X min-1. Endotoxin was given after the loading infusion of DEC, and variables were monitored for 4 h. The response to endotoxin was characterized by pulmonary hypertension, leukopenia, hypoxemia, and elevations of thromboxane B2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha). Lymph flow and protein content reflected hemodynamic and permeability changes in the pulmonary circulation. DEC did not significantly modify the response to endotoxin by any measured variable, including pulmonary arterial and left atrial pressures, cardiac output, lymph flow and protein content, alveolar-to-arterial PO2 difference, blood leukocyte count, and lymph thromboxane B2 and 6-keto-PGF1 alpha. We could not find evidence of release of leukotriene C4/D4 by radioimmunoassay in lung lymph after endotoxin infusion with or without DEC treatment. We conclude that lipoxygenase products of arachidonic acid may not be a major component of the pulmonary vascular response to endotoxin.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effects of methylprednisolone on lung oxygen toxicity in awake sheep.

The purpose of this study was to measure the effects of high doses of corticosteroids on the response to breathing 100% O2 in sheep. Sheep were prepared for chronic measurement of vascular pressures, cardiac output, gas exchange, and for collection of lung lymph. Tracheostomies were made for accurate delivery of gas mixtures. Eight sheep received methylprednisolone 30 mg/kg body wt every 6 h for eight doses, four for the first 48 h, and four for the final 24-48 h of 100% O2 breathing. Eight control sheep breathed 100% O2 without methylprednisolone, four sheep breathed compressed air without methylprednisolone, and two breathed compressed air and received methylprednisolone. Sheep had daily measurements of hypoxic vasoconstriction (fractional concentration of O2 in inspired gas = 0.12), gas exchange, lymph flow, and lymph and plasma protein concentration. Polymorphonuclear leukocyte (granulocyte) function in experimental and control sheep was assessed ex vivo by tests of chemotaxis, aggregation, and superoxide production. The number of granulocytes in peripheral lung was measured in biopsy tissue taken at the time of original surgery and postmortem. Methylprednisolone did not affect the time course nor magnitude of gas exchange abnormality, lymph flow and composition, loss of hypoxic vasoconstriction, lung granulocyte accumulation, nor postmortem lung water caused by 100% O2 breathing. Sheep receiving methylprednisolone had a shorter survival by several h, independent of the timing of the drug. Granulocytes from methylprednisolone-treated sheep showed normal function ex vivo by all three assays. We conclude that high doses of methylprednisolone unfavorably affect the rate and progression of lung injury in sheep breathing 100% O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗