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)
J H
JH
Newman
W J
WJ
Fulkerson
T
T
Kobayashi
D
D
English
B
B
Meyrick
K L
KL
Brigham
D000818:Animals; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D055370:Lung Injury; D008196:Lymph / Q000187:drug effects / Q000502:physiology; D008775:Methylprednisolone / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects
D010100:Oxygen; D008775:Methylprednisolone