Liver ischemia-reperfusion increases pulmonary permeability in the
rat: role of circulating xanthine oxidase.
Weinbroum, Abraham, Vance G. Nielsen, Sidhartha Tan, Simon Gelman,
Sadis Matalon, Kelly A. Skinner, E. Bradley, Jr, and Dale A. Parks.
Departments of Anesthesiology, Pediatrics, Physiology and
Biophysics and Biostatistics, University of Alabama at Birmingham,
Birmingham, AL 35233
APStracts 2:0022G, 1995.
Reactive oxygen species play an important role in the pathogenesis of
a variety of pathologic processes, including ischemia-reperfusion,
acute viral infections, thermal injury, hepatic diseases and acute
lung injury. Although reactive oxygen metabolites can arise from a
number of sources, xanthine oxidase may be a significant source of
these toxic oxygen species. We tested the hypothesis that hepatic
ischemia and subsequent reperfusion releases xanthine
dehyrogenase+oxidase (XDH+XO) into the circulation and that
circulating xanthine oxidase (XO) damages the isolated perfused lung.
The isolated liver and lung were perfused with Krebs-Henseleit buffer
to minimize the possible confounding effects of circulating
neutrophils. Control livers underwent oxygenated perfusion for 2h
whereas ischemic (I/R) livers were rendered globally ischemic for 2h
and then reperfused. Another group of ischemic livers was isolated
from rats pretreated with allopurinol (50 mg.kg-1) and perfused with
buffer containing 25 [mu]M allopurinol (I/R+Allo). After the 2h ischemic
period, an isolated lung was perfused with liver effluent and both
liver+lung reperfused in series for 15 min. Liver reperfusion was
terminated and lung continually recirculated with accumulated liver
effluent for 45 min. Capillary filtration coefficient (Kf,c) was
2.00.3 and 1.90.4 ml.min-1.cmH2O-1.100 g lung dry weight-1 in Control
and I/R+Allo lungs, respectively, compared to 9.01.2 ml.min-1.cmH2O
-1.100 g lung dry weight -1 in the I/R lungs (p<0.001). Lung wet/dry
ratio in the control and I/R+Allo was 8.60.3 and 9.10.5, respectively
whereas I/R lung ratio was 14.91.1 (p<0.01). Control and I/R+Allo BAL
protein content was <1.0 mg.ml-1 and LDH activity were measured
8.33.4 and 472147 U.l-1compared to 32.68.4 mg. ml-1 of protein and
1875461 U.[lambda]-1 in I/R BAL. XDH+XO activity in the control
and I/R+Allo liver effluent ranged 0.5-10 U.ml-1 throughout the
experiments whereas the activity in I/R increased to 2303688 U.ml-1
upon reperfusion. XDH+XO activity in the lung tissue was 282 mU.g-1
in control group and increased 14-fold following perfusion with
ischemic liver effluent. We conclude that the 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.
Received 1 June 1993; accepted in final form 30 January 1995.
APS Manuscript Number G203-3.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.