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 with¹¹¹In-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). The platelet activity was significantly higher in group ASP than in group KET at the end of the study both in the lungs and in the liver (P<0.01 and P<0.05 respectively). No significant changes were measured in the intestine or kidneys in any of the groups and the changes in the spleen were inconsistent. It is concluded that the dual cyclooxygenase and lipoxygenase inhibitor ketoprofen offered significantly more effective protection against endotoxin-induced platelet sequestration in the lungs and the liver than the cyclooxygenase inhibitor aspirin.