Inhibition of cyclooxygenase metabolite production attenuates ischemia-reperfusion lung injury.

Abstract

We investigated if cyclooxygenase metabolites of arachidonic acid were involved in ischemia-reperfusion lung injury by determining if inhibition of their production attenuated the injury. Isolated rat lungs were perfused with physiologic salt solution osmotically stabilized with Ficoll until circulating blood elements were not detected in lung effluent. Ischemia was induced by stopping ventilation and perfusion for 90 min. Lung ventilation and perfusion were then resumed. Ischemia-reperfusion resulted in the production of prostacyclin and thromboxane assessed by lung effluent and tissue measurements of their respective stable metabolites, 6-keto-PGF1 alpha thromboxane B2 (TxB2). In contrast, prostaglandin F2 alpha did not increase. Ischemia-reperfusion also caused lung injury as assessed by increased lung 125I-BSA accumulation compared with nonischemic control lungs. Addition of the cyclooxygenase inhibitors, indomethacin, or flubiprofen to the lung perfusate before and after ischemia inhibited lung injury as well as the production of 6-keto-PGF1 alpha and TxB2. Addition of a thromboxane synthetase inhibitor (U 63557A) reduced lung injury as well as TxB2 formation without affecting the production of 6-keto-PGF1 alpha. The attenuation of lung injury was not explained by direct H2O2 removal by indomethacin, flubiprofen, or U 63557A because the concentrations of the inhibitors used in the isolated lung experiments did not remove exogenously added H2O2 from buffer in vitro. We conclude that cyclooxygenase metabolites of arachidonic acid are involved in ischemia-reperfusion injury to isolated rat lungs.

• Authors: A G Ljungman, C M Grum, G M Deeb, S F Bolling, M L Morganroth
• Journal: The American review of respiratory disease (Am Rev Respir Dis) Vol. 143 Issue 3 Pg. 610-7 (Mar 1991) ISSN: 0003-0805 [Print] United States
• PMID: 1900402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzofurans
• Cyclooxygenase Inhibitors
• Thromboxane B2
• 6-Ketoprostaglandin F1 alpha
• Flurbiprofen
• Dinoprost
• Hydrogen Peroxide
• Prostaglandin-Endoperoxide Synthases
• Thromboxane-A Synthase
• furegrelate
• Indomethacin

Topics

• 6-Ketoprostaglandin F1 alpha (metabolism)
• Animals
• Benzofurans (pharmacology)
• Blood Pressure (drug effects)
• Cyclooxygenase Inhibitors
• Dinoprost (metabolism)
• Flurbiprofen (pharmacology)
• Hydrogen Peroxide (metabolism)
• Indomethacin (pharmacology)
• Lung (blood supply, metabolism, pathology, physiopathology)
• Male
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Pulmonary Artery (physiopathology)
• Rats
• Rats, Inbred Strains
• Reperfusion Injury (metabolism, pathology, physiopathology)
• Thromboxane B2 (metabolism)
• Thromboxane-A Synthase (antagonists & inhibitors)