Effects of methylprednisolone on acute lung paraquat toxicity in sheep.
Infused into sheep, paraquat causes increased flow of protein-rich lung lymph, increased prostanoid production, and neutrophil accumulation in the lung. The effects of high-dose methylprednisolone on the response to paraquat infusion were studied in awake sheep with chronic lung lymph fistulas. Seven sheep were infused with paraquat (30 mg/kg) alone. Six sheep received methylprednisolone (1.0 g plus 0.5 g/h intravenously), beginning 30 min before paraquat (pretreatment), and 5 received methylprednisolone, beginning 4 h after paraquat (post-treatment). Neutrophil accumulation in the lung was measured in biopsy tissue taken at baseline and at postmortem. Methylprednisolone pretreatment significantly prevented the increase in lung lymph flow (paraquat, from 4.4 +/- 0.3 to 11.1 +/- 0.8 ml/h, p less than 0.05; pretreatment, from 4.8 +/- 0.9 to 3.7 +/- 0.3, NS), and the increase in lymph-to-plasma protein concentration ratio (paraquat, from 0.69 +/- 0.02 to 0.80 +/- 0.02, p less than 0.05; pretreatment, from 0.66 +/- 0.06 to 0.60 +/- 0.02, NS) during 8 h after paraquat infusion. Treatment with methylprednisolone after paraquat also reduced the changes in lung lymph flow and protein clearance. Methylprednisolone prior to paraquat significantly inhibited accumulation of 6-keto-PGF1 alpha in lymph and plasma, but did not significantly inhibit accumulation of TxB2 in lymph or plasma. The number of neutrophils in the paraquat lungs was 3 to 4 times that in the control lungs, with or without methylprednisolone. Methylprednisolone pretreatment prolonged the survival time, but did not prevent death within 48 h after paraquat infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000208:Acute Disease; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008196:Lymph / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008775:Methylprednisolone / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010269:Paraquat / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood
D011506:Proteins; D002245:Carbon Dioxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010269:Paraquat; D010100:Oxygen; D008775:Methylprednisolone