Effect of a selective thromboxane A2 synthetase inhibitor on the systemic changes induced by circulating pancreatic phospholipase A2.
BACKGROUND
In acute pancreatitis, pancreatic phospholipase A(2) (PLA2) in the circulating blood hydrolyzes phospholipids contained in plasma lipoproteins, liberating eicosanoid precursors that are subsequently converted to various eicosanoids. The pathophysiological significance of eicosanoid synthesis via this pathway is unknown. The aim of this study was to clarify the role of thromboxane A(2) (TXA(2)) synthesis by circulating pancreatic PLA(2) in the pathogenesis of the systemic complications of acute pancreatitis.


METHODS
Guinea pigs were divided into two groups: a control group and an ozagrel group, which received intravenous administration of ozagrel, a selective TXA(2) synthetase inhibitor. Pancreatic PLA(2) was infused intravenously in both groups for 30 min, and systemic changes during the infusion were examined.


RESULTS
In the control group, there was an increase in plasma thromboxane B(2) (TXB(2)) concentration, a decrease in mean arterial pressure and heart rate, a decrease in arterial base excess (BE), bicarbonate concentration (HCO(3) (-)), and pH, a decrease in platelet count and plasma fibrinogen concentration, and a shortened prothrombin time during the infusion of pancreatic PLA(2). In the ozagrel-treated group, changes in plasma TXB(2) concentration, BE, HCO(3) (-), and platelet count were significantly inhibited.


CONCLUSIONS
TXA(2) synthesis by circulating pancreatic PLA(2) contributes to metabolic acidosis and thrombocytopenia during acute pancreatitis.
Motoyoshi
Makoto
M
Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Sugiyama
Masanori
M
Atomi
Yutaka
Y
Kimura
Wataru
W
Nagawa
Hirokazu
H
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000627:therapeutic use*; D010195:Pancreatitis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D010741:Phospholipases A / Q000097:blood* / Q000187:drug effects; D054467:Phospholipases A2; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D008689:Methacrylates; D010741:Phospholipases A; D054467:Phospholipases A2; D013930:Thromboxane-A Synthase; C034364:ozagrel