Hyperoxic lung injury in mice: A possible protective role for prostacyclin

Lewis J Smith*, Eric Sommers, Carl E. Hunt, Lauren M Pachman

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Arachidonic acid metabolites have biologic properties that can mimic the pulmonary changes produced by hyperoxic exposure, but little information is available regarding their importance in this setting. The role of prostacyclin (PGI2) and thromboxane (Tx) A2 in oxygen-induced lung injury was evaluated by exposing mice to 100% oxygen for up to 4 days and measuring plasma and bronchoalveolar lavage (BAL) fluid concentrations of 6-keto-prostaglandin F (6-keto-PGF), a metabolite of PGI2, and TXB2, a metabolite of TXA2. To determine whether a relationship exists between changes in these arachidonlc acid metabolites and the severity of the lung injury, we also measured mortality, BAL protein concentration, BAL angiotensin-converting enzyme (ACE) activity, and plasma lactate dehydrogenase activity, and we examined lung sections by light and electron microscopy. After 3 days of exposure to 100% oxygen, microscopic and biochemical changes consistent with mild lung damage were found, but there was no increase in either plasma or BAL 6-keto-PGF concentration. On day 4, severe lung damage was present, and BAL 6-keto-PGF level increased threefold (P < 0.001). The level of TXB2 in BAL fluid did not change on any day. Twice-daily administration of either a high (5 mg/kg) or a low (1 mg/ kg) dose of indomethacin reduced BAL concentrations of 6-keto-PGF, and it resulted in increased mortality and higher BAL protein concentration and BAL ACE activity. These data suggest that TxA2 has little if any role in the pathogenesis of oxygen-induced lung injury, whereas prostacyclin may play a protective role.

Original languageEnglish (US)
Pages (from-to)473-478
Number of pages6
JournalThe Journal of Laboratory and Clinical Medicine
Volume108
Issue number5
StatePublished - Jan 1 1986

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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