Effect of platelet-activating factor antagonist WEB 2086 on microcirculatory disorders in acute experimental pancreatitis of graded severity.
OBJECTIVE
Platelet-activating factor (PAF) is an important mediator of inflammation and postulated to be involved in the pathogenesis of acute pancreatitis. In this study, we evaluated the therapeutic effect of PAF antagonist WEB 2086 in acute experimental pancreatitis of graded severity in rats.


METHODS
According to a block design, 64 animals were randomly allocated to 8 groups. Severe necrotizing pancreatitis was induced by intraductal infusion of taurocholic acid (4%, 0.4 mL), and the combination of glycodeoxycholic acid (10 mmol/L, 1.0 mL/kg, intraductal infusion) and cerulein (5 microg/kg per hour, intravenous) was applied to induce intermediate pancreatitis, or cerulein alone (5 microg/kg per hour, intravenous) to establish edematous pancreatitis. WEB 2086 was given 15 minutes after beginning the induction of pancreatitis. Pancreatic microcirculation was analyzed in vivo with an epiluminescent microscope. Histopathology was evaluated by a validated score. Trypsinogen-activating peptide and serum amylase were analyzed sequentially.


RESULTS
WEB 2086 had no significant influence on the breakdown of microcirculation, leukocyte adherence, histopathological damage, and amylase levels in severe necrotizing pancreatitis, intermediate pancreatitis, and edematous pancreatitis. Only in intermediate pancreatitis was there a significant reduction of trypsinogen-activating peptide levels.


CONCLUSIONS
In our study, PAF antagonist WEB 2086 had no beneficial effect on microcirculation in acute experimental pancreatitis.
Mann
Oliver
O
Departments of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. omann@uke.uni-hamburg.de
Tiefenbacher
Wolf-Jonas
WJ
Kaifi
Jussuf
J
Schneider
Claus
C
Kluth
Dirk
D
Bloechle
Christian
C
Yekebas
Emre
E
Izbicki
Jakob R
JR
Strate
Tim
T
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D002108:Ceruletide; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006002:Glycodeoxycholic Acid; D007962:Leukocytes / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects*; D009842:Oligopeptides / Q000378:metabolism; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D009842:Oligopeptides; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C080396:trypsinogen activation peptide; C052518:WEB 2086; D006002:Glycodeoxycholic Acid; D013656:Taurocholic Acid; D002108:Ceruletide; D000681:Amylases