Effects of methylprednisolone on acute lung paraquat toxicity in sheep.

Abstract

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)