Normobaric Pulmonary Oxygen Toxicity

This study investigated the involvement of substances derived from arachidonic acid in the mechanism of endotoxin's protective action against pulmonary oxygen toxicity. Eighty-three percent of rats treated with a small dose of endotoxin (1 mgjkg) survived exposure to over 95% oxygen for 7 days. In contrast, all control rats exposed to the same oxygen concentration died within 3 days. When the endotoxin-treated rats were a/so treated with the soluble lysine salt of acetylsalicylic acid (100 mgjkg), 7-day survival decreased to 25%. This suggests that prostaglandin metabolism may play an important role in the protective action of endotoxin during hyperoxia. INTRODUCTION Despite the potential dangers of hyperoxia on the lung, administration of aboveambient oxygen tensions is necessary for treatment of severe hypoxemia caused by respiratory failure or acute lung injury. Small doses of bacterial endotoxin markedly increase the survival rate of adult rats exposed to 98% oxygen for periods that are normally lethal (60-72 h) [1 ,2]. Details concerning the mechanism and even the cellular site(s) of endotoxin's action are not yet known, but there is evidence that the pulmonary responses after bacterial endotoxin administration are due to release of substances derived from arachidonic acid [3] and that these responses can be prevented by concurrent treatment with various cyclooxygenase inhibitors [4]. We investigated the involvement of arachidonic acid derivatives in the mechanism of endotoxin's protective action against pulmonary toxicity, by combined treatment with endotoxin and the soluble lysine salt of acetylsalicylic acid (L-ASA).