Generation of 5-lipoxygenase metabolites following pulmonary reperfusion in isolated rabbit lungs.
We characterized the release of arachidonic acid (AA) metabolites in lung effluent following lung ischemia-reperfusion since they may contribute to the pathophysiology of reperfusion lung injury. The left pulmonary artery of rabbits (N = 5) was occluded for 24 hrs with a surgically implanted vascular clip. At 24 hrs, the heart and lungs were removed en bloc and perfused with Ringers-albumin (0.5 gm%) at 60 ml/min while statically inflated with 95% O2-5% CO2. The lipid fraction of the lung effluent was concentrated using the Bligh-Dyer extraction and analyzed by gradient RP-HPLC. Samples obtained in the first minute of reperfusion showed significant increases in LTB4 (+180%), LTC4 (+3600%), 15-HETE (+370%), 5-HPETE (+270%), PGE2 (+140%), 6-keto-PGF1 alpha (+110%) and 12-HHT (+160%) compared to the effluent from the right control lung. The reperfusion-induced increases in LTB4, LTC4, LTD4 and 15-HETE were inhibited greater than or equal to 70% by pretreatment with the 5-LO inhibitors L663,536 or L651,392. The increases in lipid concentrations corresponded to significantly increased pulmonary arterial pressure from a baseline value of 9.5 +/- 0.3 to 29.3 +/- 2.9 (cmH2O) during the first min of reperfusion. The pulmonary arterial pressure remained elevated for at least 20 min of reperfusion. Reperfusion also resulted in PMN uptake (assessed by lung tissue myeloperoxidase content) in the reperfused lung versus control lung (25.0 +/- 2.4 vs. 10.5 +/- 2.5 units). The generation of lipoxygenase metabolites during the initial phase of reperfusion may contribute to post-reperfusion PMN uptake and pulmonary vasoconstriction.
Palace
G P
GP
Department of Physiology and Cell Biology, The Albany Medical College, New York 12208.
Horgan
M J
MJ
Malik
A B
AB
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D011651:Pulmonary Artery; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism*
D001094:Arachidonate 5-Lipoxygenase