Oxygen radicals promote ICAM-1 expression and microcirculatory disturbances in experimental acute pancreatitis.
OBJECTIVE
The course of pancreatitis is paralleled by a drastic reduction in organ perfusion and increased ICAM-1-mediated leukocyte-endothelial interaction. We aimed to evaluate the effect of oxygen radicals on ICAM-1 expression and the microcirculation in severe acute pancreatitis using the oxygen radical scavenger dimethylsulfoxide (DMSO).


METHODS
Severe pancreatitis was induced in rats (n = 32) who were randomly assigned to one of two groups: either 4 ml/kg 50% DMSO/saline (v/v) started 3 h after induction of pancreatitis or 4 ml/kg saline (control). Microcirculation was evaluated by intermittent intravital microscopy. Serum amylase and lipase, histomorphometric changes, immunohistochemistry for ICAM-1 expression and 24-hour survival were investigated.


RESULTS
Leukocyte adherence was significantly reduced (4.4 +/- 0.47 vs. 5.58 +/- 0.69 sticker/100 micro m, p < 0.05), and mean capillary (0.96 +/- 0.06 vs. 0.45 +/- 0.13 mm/s; p < 0.01) and venous erythrocyte velocity (1.16 +/- 0.12 vs. 0.58 +/- 0.16 mm/s, p < 0.01) were significantly increased by DMSO treatment. Microcirculatory disturbances were paralleled by an increase in endothelial ICAM-1 expression, whereas DMSO reduced ICAM-1 expression.


CONCLUSIONS
DMSO improves pancreatic microcirculation and reduces ICAM-1 expression and subsequent leukocyte adhesion, suggesting an important role of oxygen free radicals in the pathway of endothelial ICAM-1 expression and microcirculatory disturbances in acute pancreatitis.
Department of Surgery, University of Freiburg, Germany.
Tobias
T
Keck
Jens
J
Werner
Ramin
R
Banafsche
Anke
A
Stalmann
Lutz
L
Schneider
Martha-Maria
MM
Gebhard
Christian
C
Herfarth
Ernst
E
Klar
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001783:Blood Flow Velocity; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008049:Lipase / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; D008049:Lipase; D000681:Amylases; D004121:Dimethyl Sulfoxide