Liver ischemia-reperfusion increases pulmonary permeability in rat: role of circulating xanthine oxidase
Weinbroum, A.; Nielsen, V.G.; Tan, S.; Gelman, S.; Matalon, S.; Skinner, K.A.; Bradley, E.; Parks, D.A.
American Journal of Physiology 268(6 Pt 1): G988-G996
1995
ISSN/ISBN: 0002-9513 PMID: 7611420 Document Number: 451174
Reactive oxygen species play an important role in pathogenesis of a variety of pathological processes, e.g., ischemia-reperfusion, acute viral 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 cntdot min-1 cntdot cmH-2O-1 cntdot 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 lt 0.001). Lung wet-to-dry weight ratio in control and I/R + Allo lungs was 8.6 +- 0.3 and 9.1 +- 0.5, respectively, and 14.9 +- 1.1 in I/R lungs (P lt 0.01). Control and I/R + Allo bronchoalveolar lavage protein content was lt 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 mu-U/ml throughout the experiments, whereas in I/R it increased to 2,303 +- 688 mu-U/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.