Xanthine oxidase inhibition attenuates ischemic-reperfusion lung injury.
Ischemic-reperfusion lung injury is a factor potentially limiting the usefulness of distant organ procurement for heart-lung transplantation. Toxic oxygen metabolites are considered a major etiologic factor in reperfusion injury. Although oxygen-free radicals may be generated by many mechanisms, we investigated the role of xanthine oxidase in this injury process by using lodoxamide, a xanthine oxidase inhibitor, to inhibit ischemic-reperfusion injury in an isolated rat lung model. Isolated rat lungs were perfused with physiologic salt solution (PSS) osmotically stabilized with Ficoll until circulating blood elements were nondetectable in the pulmonary venous effluent. Lungs were rendered ischemic by interrupting ventilation and perfusion for 2 hr at 37 degrees C. After the ischemic interval, the lungs were reperfused with whole blood and lung injury was determined by measuring the accumulation of 125I-bovine serum albumin in lung parenchyma and alveolar lavage fluid as well as by gravimetric measurements. Lung effluent was collected immediately pre- and postischemia for analysis of uric acid by high-pressure liquid chromatography. Lodoxamide (1 mM) caused significant attenuation of postischemic lung injury. Uric acid levels in the lung effluent confirmed inhibition of xanthine oxidase. Protection from injury was not complete, however, implying that additional mechanisms may contribute to ischemic-reperfusion injury in the lung.
Lynch
M J
MJ
Department of Internal Medicine, University of Michigan Hospitals, Ann Arbor 48109.
Grum
C M
CM
Gallagher
K P
KP
Bolling
S F
SF
Deeb
G M
GM
Morganroth
M L
ML
D000818:Animals; D007457:Iodine Radioisotopes; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008854:Microscopy, Electron; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D012039:Regional Blood Flow; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D007457:Iodine Radioisotopes; D014527:Uric Acid; D012710:Serum Albumin, Bovine; D014969:Xanthine Oxidase; D010072:Oxamic Acid; C021702:lodoxamide ethyl