Beneficial effects of ibuprofen in oleic acid induced lung injury.
Metabolites of arachidonic acid, particularly thromboxanes, have been implicated as mediators of lung injury. The formation of thromboxane A2 can be decreased by glucocorticoid steroids by inhibiting the enzyme phospholipase A2 or by ibuprofen which inhibits fatty acid cyclooxygenase. This study was performed to determine if ibuprofen, methylprednisolone, or a combination of both could improve the pulmonary injury induced by oleic acid. Five groups of dogs were instrumented with pulmonary artery and extravascular lung water (EVLW) catheters and ventilated with 100% O2. Serial determinations of hemodynamic and pulmonary parameters were performed before and after oleic acid infusion. Plasma immunoreactive thromboxane B2 (iTxB2) and ibuprofen levels were also determined. Oleic acid rapidly induced a significant pulmonary injury as evidenced by hypoxemia and increases in extravascular lung water. Plasma iTxB2 rose significantly in the control group receiving only oleic acid. Pulmonary function and hemodynamic parameters were not changed by ibuprofen infusion alone. Ibuprofen attenuated the oleic acid induced hypoxemia and increased EVLW but did not significantly reduce plasma iTxB2. Methylprednisolone did not prevent the increase in plasma iTxB2 and was less effective than ibuprofen in preventing hypoxemia and increases in EVLW. The combination of ibuprofen and methylprednisolone did significantly inhibit the production of iTxB2, however in combination they protected less against the hypoxemia and increased EVLW than either agent alone. These results indicate that ibuprofen may have a protective effect in oleic acid induced lung injury that is not mediated through the inhibition of fatty acid cyclooxygenase. The results are also further evidence that thromboxane is probably not a pathogenetic factor in oleic acid induced lung injury.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004285:Dogs; D005110:Extracellular Space / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008775:Methylprednisolone / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000633:toxicity; D014655:Vascular Resistance / Q000187:drug effects
D001095:Arachidonic Acids; D009829:Oleic Acids; D016718:Arachidonic Acid; D019301:Oleic Acid; D007052:Ibuprofen; D008775:Methylprednisolone