Xanthine oxidase inhibition attenuates ischemic-reperfusion lung injury

https://doi.org/10.1016/0022-4804(88)90159-XGet rights and content

Abstract

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°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.

References (22)

  • K.J. Johns et al.

    Acute lung injury in rat caused by immunoglobulin A immune complexes

    J. Clin. Invest.

    (1984)
  • Cited by (60)

    • Inhibition of nitric oxide synthesis augments pulmonary oedema in isolated perfused rabbit lung

      2000, British Journal of Anaesthesia
      Citation Excerpt :

      Other studies have used mast cell protease activity14 or tryptase release35 to demonstrate inhibition of mast cells by lodoxamide. Other actions of lodoxamide in the lung that may contribute to its anti-inflammatory behaviour include inhibition of xanthine oxidase36 and prevention of neutrophil accumulation.37 Of considerable clinical interest, in the context of lung transplantation, has been the finding that lodoxamide reduces lung injury after ischaemia and reperfusion38 and after re-expansion from a state of atelectasis.37

    • Current strategies in lung preservation

      2000, Journal of Laboratory and Clinical Medicine
      Citation Excerpt :

      These oxygen metabolites can then be further metabolized into other species, including the highly toxic hydroxyl radical. Lodoxamide and allopurinol have been used to inhibit xanthine oxidase and attenuate ischemic lung injury.95 Other additives have included superoxide dismutase, vasoactive intestinal peptide,96 and lazaroids.97

    View all citing articles on Scopus
    View full text