Effect of ticlopidine and prostaglandin E on endotoxin-induced pulmonary platelet sequestration in vivo.

Prostaglandin E1 has earlier been shown to decrease pulmonary platelet trapping (PPT) following shock. This experiment was performed to evaluate a new method to study PPT in vivo, and to study the effect of prostaglandin E1 and a new antiplatelet drug (ticlopidine) on PPT in rabbits after i.v. administration of endotoxin. Following platelet labeling with In-111, the rabbits were placed under a scintillation camera for continuous measuring of the activity distribution for 40 minutes. The first five minutes represented reference values, whereafter endotoxin E. coli was injected i.v. The following 2-4 minutes showed a sudden increase of radioactivity over the lungs and a simultaneous decrease over the heart, indicating PPT in the nontreated animals, followed by a slow decrease to almost preshock values during the following 30 minutes. Animals receiving prostaglandin E1 showed a significantly lower activity peak in the lungs after the administration of endotoxin, while the corresponding peak in ticlopidine-treated animals did not differ from that seen in the nontreated animals. In all groups, endotoxin caused a decrease in platelet count, but it was significantly lower in the PGE1-treated animals. The results have shown that this diagnostic model for PPT is reliable and may be used for evaluation of the effect on platelet aggregation in vivo of different drugs.

Effects of acetylsalicylic acid and prostaglandin on endotoxin-induced pulmonary platelet sequestration.

Previous experimental studies have shown that soft tissue trauma and endotoxin shock cause pulmonary platelet trapping. In the soft tissue trauma model it has been found that this event can be obviated by pretreatment with aspirin and prostaglandin E1 in combination. This study was made to determine the effect of these two drugs on endotoxin-induced pulmonary platelet trapping. Dogs with 51Cr-tagged platelets were injected with 20 mg endotoxin E. coli. The dogs were kept in shock for 2 hours and then sacrificed. The dogs were kept in shock for 2 hours and then sacrified. The amount of platelet sequestration in the lungs was determined by measuring the 51Cr activity in the lungs. The results of the study showed that prostaglandin alone decreases pulmonary platelet trapping induced by endotoxin, but aspirin, either alone or together with prostaglandin E1, has no positive effect. This could be explained by the fact that acetylsalicylic acid depresses endogenous prostaglandin, and thus decreases the blood concentration of available prostaglandin.