Treatment of experimental canine endotoxin shock with ibuprofen, a cyclooxygenase inhibitor.

The arachidonic acid derivative thromboxane A2, a very potent platelet aggregator, is increased in endotoxin shock. Ibuprofen blocks the formation of thromboxane A2 and has antiplatelet and antileukocyte aggregability properties. The effects of ibuprofen on pulmonary platelet trapping, platelet and leukocyte counts, platelet aggregability, hematocrit, and blood pressure were evaluated in endotoxin-shocked dogs. The initial decrease in blood pressure and in leukocyte and platelet counts seen in endotoxin shock was not altered by ibuprofen treatment. At 2 h the ibuprofen-treated dogs had less hypotension compared to endotoxin control. Platelet counts were also higher in the ibuprofen-treated dogs at 2 h. Significant recovery of leukocytes was seen only when pretreatment was used. Pulmonary platelet trapping was significantly lower in the ibuprofen-treated dogs compared to endotoxin controls and not significantly different from the sham dogs when ibuprofen was given before endotoxin injection. This study demonstrates the efficacy of ibuprofen not only in reducing pulmonary platelet trapping but also in obviating the late hypotension in experimental endotoxin shock.