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/sup 0/C. After the ischemic interval, the lungs were reperfused with whole blood and lung injury was determined by measuring the accumulation of /sup 125/I-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.
- Research Organization:
- Univ. of Michigan Hospitals, Ann Arbor (USA)
- OSTI ID:
- 6971780
- Journal Information:
- J. Surg. Res.; (United States), Vol. 44:5
- Country of Publication:
- United States
- Language:
- English
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BLOOD FLOW
ENZYME INHIBITORS
INHIBITION
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LIQUID COLUMN CHROMATOGRAPHY
OXYGEN
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ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
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550901* - Pathology- Tracer Techniques