Effects of two different inhibitors of the arachidonic acid metabolism on platelet sequestration in endotoxic shock.
Metabolites of arachidonic acid are known to play an important part in the pathogenesis of organ injury in endotoxic shock. We compared the effects of the classical cyclooxygenase inhibitor aspirin with that of the dual cyclooxygenase and lipoxygenase inhibitor ketoprofen on the behavior of platelets tagged with 111In-labeled oxine in multiple organs during endotoxin shock. Three groups of sheep (n = 7 in each) were anesthetized before being subjected to endotoxin shock. Group E had no drug treatment (shock controls), group KET received ketoprofen and group ASP received aspirin treatment. In the lungs and in the liver of group E there was a marked sequestration of platelets, which started in both organs immediately after administration of endotoxin and continued throughout the study. In the treated groups, however, the response to endotoxin was both delayed and reduced compared with the untreated shock controls. The first changes in platelet activity were noted after more than 1 h in the treated groups. Four hours after administration of endotoxin, platelet activity (sequestration) had increased in the lungs by 102 +/- 14% in group E, 53 +/- 11% in group ASP and 20 +/- 13% in group KET (P < 0.01, P < 0.01 and P < 0.05 respectively compared to baseline). Corresponding values for the liver were 52 +/- 16% in group E, 22 +/- 19% in group ASP and -2 +/- 12% in group KET (P < 0.01, P < 0.01 and P > 0.05 respectively compared with baseline).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anesthesia and Intensive Care Medicine, University of Berne, Inselspital, Switzerland.
G H
GH
Sigurdsson
H A
HA
Youssef
A
A
Owunnwanne
D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004731:Endotoxins / Q000633:toxicity; D006439:Hemodynamics / Q000502:physiology; D007205:Indium Radioisotopes; D007660:Ketoprofen / Q000494:pharmacology*; D008099:Liver / Q000502:physiology; D008168:Lung / Q000502:physiology; D012756:Sheep; D012757:Sheep Diseases / Q000503:physiopathology*; D012772:Shock, Septic / Q000503:physiopathology / Q000662:veterinary*
D001095:Arachidonic Acids; D004731:Endotoxins; D007205:Indium Radioisotopes; C044101:endotoxin, Escherichia coli; D007660:Ketoprofen; D001241:Aspirin