Liver ischemia-reperfusion increases pulmonary permeability in rat: role of circulating xanthine oxidase.
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.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 lungs 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Weinbroum
A
A
Department of Anesthesiology, University of Alabama at Birmingham 35233, USA.
Nielsen
V G
VG
Tan
S
S
Gelman
S
S
Matalon
S
S
Skinner
K A
KA
Bradley
E
E
Parks
D A
DA
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D007770:L-Lactate Dehydrogenase; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010477:Perfusion; D010539:Permeability; D011506:Proteins / Q000032:analysis; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015424:Reperfusion; D014968:Xanthine Dehydrogenase / Q000097:blood; D014969:Xanthine Oxidase / Q000097:blood*
D011506:Proteins; D017382:Reactive Oxygen Species; D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase