TY - JOUR
T1 - Liver ischemia-reperfusion increases pulmonary permeability in rat
T2 - Role of circulating xanthine oxidase
AU - Weinbroum, A.
AU - Nielsen, V. G.
AU - Tan, S.
AU - Gelman, S.
AU - Matalon, S.
AU - Skinner, K. A.
AU - Bradley, E.
AU - Parks, D. A.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - bronchoalveolar lavage
KW - lung
UR - http://www.scopus.com/inward/record.url?scp=0028997168&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028997168&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.1995.268.6.g988
DO - 10.1152/ajpgi.1995.268.6.g988
M3 - Article
C2 - 7611420
AN - SCOPUS:0028997168
SN - 0193-1857
VL - 268
SP - G988-G996
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 6 31-6
ER -