Liver ischemia-reperfusion increases pulmonary permeability in rat: Role of circulating xanthine oxidase

A. Weinbroum, V. G. Nielsen, S. Tan, S. Gelman, S. Matalon, K. A. Skinner, E. Bradley, D. A. Parks

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Reactive oxygen species play an important role in pathogenesis of a variety of pathological processes, e.g., ischemia-reperfusion, acute vital infections, thermal injury, hepatic diseases, and acute lung injury. Xanthine oxidase (XO) may be a significant source of these cytotoxic oxygen species. We tested the hypothesis that hepatic ischemia-reperfusion releases xanthine dehydrogenase + XO (XDH + XO) into the circulation and that circulating XO damages isolated perfused lung. Isolated liver + lung preparation was perfused with Krebs-Henseleit buffer to minimize confounding effects of circulating neutrophils. In one group, livers were rendered globally ischemic for 2 h and then reperfused (I/R). In another group, livers were pretreated with allopurinol and perfused with buffer containing additional allopurinol (I/R + Allo). After 2 h of ischemia, an isolated lung was connected to liver, and liver + lung preparation was reperfused in series for 15 min. Liver reperfusion was terminated, and lung was recirculated with liver effluent for 45 min. Capillary filtration coefficient (ml · min-1 · cmH2O-1 · 100 g lung dry wt-1) was 2.0 ± 0.3 and 1.9 ± 0.4 in control and I/R + Allo lungs, respectively, and 9.0 ± 1.2 in I/R lungs (P < 0.001). Lung wet-to- dry weight ratio in control and I/R + Allo rungs was 8.6 ± 0.3 and 9.1 ± 0.5, respectively, and 14.9 ± 1.1 in I/R lungs (P < 0.01). Control and I/R + Allo bronchoalveolar lavage protein content was < 1.0 mg/ml compared with 32.6 ± 8.4 mg/ml in I/R group. XDH + XO activity in control and I/R + Allo liver effluent was 0.5-10 μU/ml throughout the experiments, whereas in I/R it increased to 2,303 ± 688 μU/ml upon reperfusion. XDH + XO activity in lung tissue was 28 ± 2 mU/g in control and increased 14-fold after perfusion with ischemic liver effluent. We conclude that ischemic-reperfused liver releases large amounts of XDH + XO into the circulation and that this circulating XDH + XO alters alveolar-capillary membrane integrity in the absence of circulating neutrophils.

Original languageEnglish (US)
Pages (from-to)G988-G996
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume268
Issue number6 31-6
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • bronchoalveolar lavage
  • lung

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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