Acute lung injury following pancreas ischaemia-reperfusion: role of xanthine oxidase.
BACKGROUND
Acute pancreatitis can lead to increased pulmonary vascular permeability and respiratory failure. Oxidants (and their generator, xanthine oxidase (XO)) play an important role in injuring the structural integrity of the pulmonary epithelium and endothelium, but their importance in the induction of acute lung injury following pancreas ischaemia-reperfusion (IR) has not been defined.


METHODS
Rats (n = 48) received a regular or a tungsten (oxidoreductase inhibitor)-enriched diet for 14 days. Their isolated pancreases were then either perfused (controls) or made ischaemic (IR) for 40 min (12 replicates/group). This was followed by in-series pancreas plus normal isolated lung reperfusion for 15 min. Lungs only were subsequently perfused with the 15-min accumulated pancreas effluents for 45 min.


RESULTS
Injury was induced in all IR pancreases as expressed by reperfusion pressure, wet-to-dry ratio and amylase and lipase concentrations. Tissue XO activity was high and reduced glutathione pool was low in the tungsten-free IR pancreases. Pulmonary plateau pressure increased by 46% and final PO(2)/FiO(2) decreased by 24%. Capillary pressure and weight rose two- to fourfold in lungs paired with IR non-treated pancreases. Twofold increases in bronchoalveolar lavage volume and contents, including XO, were also recorded in this group of lungs. Lungs exposed to tungsten-treated ischaemic pancreas effluents were minimally damaged and tissue XO content was low compared to controls.


CONCLUSIONS
Ex-vivo acute pancreatitis induces acute lung injury via oxidants/antioxidants misbalance, which may be prevented by attenuating pancreas oxidative stress.
Flaishon
R
R
Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
Szold
O
O
Weinbroum
A A
AA
D000208:Acute Disease; D000818:Animals; D008171:Lung Diseases / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress; D010179:Pancreas / Q000098:blood supply; D010195:Pancreatitis / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications*; D014969:Xanthine Oxidase / Q000378:metabolism
D014969:Xanthine Oxidase