Multimodal management - of value in fulminant acute pancreatitis?
BACKGROUND
The multiple organ dysfunction syndrome (MODS) is the major cause of morbidity and mortality associated with acute pancreatitis. Presently, therapy is merely organ supportive as no effective therapy against underlying causative pathophysiological mechanisms exists.


OBJECTIVE
To evaluate the effect of treatment with a platelet-activating factor inhibitor (PAFI), a monoclonal antibody against platelet endothelial cell adhesion molecule 1 (PECAM-1-MAb) and an oxygen free radical scavenger (N-acetylcystein; NAC), alone or in combination, on systemic organ dysfunction in experimental acute pancreatitis.


METHODS
Severe acute pancreatitis was induced in rats by the intraductal administration of taurodeoxycholate. Treatment was given after 1 or 3 h, and evaluations were performed 6 h after induction. Organ dysfunction was evaluated by means of endothelial integrity impairment expressed as endothelial barrier leakage index.


RESULTS
Severe acute pancreatitis caused a significant impairment in endothelial integrity in all organs studied and decreased levels of protease inhibitors compared to controls. The endothelial barrier impairment was significantly ameliorated by all treatment modalities, either given early or later. Combinations of NAC and the PECAM-1-MAb or the PECAM-1-MAb and the PAFI were the only schedules to restore endothelial barrier integrity to normal levels in most of the organs studied.


CONCLUSIONS
Combination therapy with NAC and PECAM-1-MAb and/or PAFI may offer effective, causative-directed supplements to organ-supportive therapy of MODS in severe acute pancreatitis.
Haraldsen
P
P
Department of Surgery, University Hospital of Lund, Sweden.
Sun
Z W
ZW
Börjesson
A
A
Olanders
K
K
Lasson
A
A
Andersson
R
R
D000111:Acetylcysteine / Q000627:therapeutic use*; D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy* / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D016166:Free Radical Scavengers; D007093:Imidazoles; D010972:Platelet Activating Factor; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D007930:Leucine; C103289:lexipafant; D000111:Acetylcysteine