Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis.
OBJECTIVE
To evaluate the effect of low molecular weight heparin on plasma xanthine oxidase concentrations and lung inflammatory response during acute pancreatitis.


METHODS
Randomized, controlled trial.


METHODS
Experimental laboratory.


METHODS
Male Wistar rats.


METHODS
Acute pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Low molecular weight heparin (0, 30, 90, or 300 units/kg) was administered immediately after induction of pancreatitis.


RESULTS
Lipase and xanthine oxidase plasma concentrations were measured 3 hrs after pancreatitis induction. Expression of P-selectin messenger RNA and myeloperoxidase activity as a marker of neutrophil infiltration were determined in the lung. An increase in xanthine oxidase plasma concentrations was observed during pancreatitis. Administration of heparin also increased plasma xanthine oxidase activity in both control and pancreatitis animals. Measures of xanthine oxidase present in the endothelial surface indicate that during pancreatitis, the enzyme is released from the gastrointestinal endothelium. By contrast, heparin mobilizes xanthine oxidase from almost all organs evaluated. Neutrophil infiltration was increased in the lung during pancreatitis. Heparin administration further increased, in a dose-dependent manner, myeloperoxidase activity and P-selectin expression in the lung in animals with pancreatitis. By contrast, in control animals, heparin had no effect on myeloperoxidase activity and did not induce P-selectin up-regulation.


CONCLUSIONS
During acute pancreatitis, heparin administration might mobilize xanthine oxidase attached to endothelial cells, originating a free radical-generating system in the circulation that would trigger an inflammatory response in the lung.
Granell
S
S
Department of Experimental Pathology, Institut d' Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas, Spain.
Gironella
M
M
Bulbena
O
O
Panés
J
J
Mauri
M
M
Sabater
L
L
Aparisi
L
L
Gelpí
E
E
Closa
Daniel
D
D000208:Acute Disease; D000818:Animals; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D008297:Male; D010195:Pancreatitis / Q000097:blood / Q000150:complications*; D011014:Pneumonia / Q000209:etiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014969:Xanthine Oxidase / Q000097:blood / Q000187:drug effects*
D006495:Heparin, Low-Molecular-Weight; D014969:Xanthine Oxidase