Arachidonic acid induced mortality in animals - an appropriate model for the evaluation of antithrombotic drugs?

Sodium arachidonate (1.1 mg/kg b.w.) was injected into a marginal ear vein of rabbits according to SILVER M.J. et al. (1). 94% of the animals died within a few minutes. We investigated to what extent these lethal effects of arachidonic acid (possibly caused by embolizing platelet thrombi) can be prevented by potential antithrombotic drugs. As indicated in the tables the animals are protected by some compounds, especially the nonsteroidal anti-inflammatory agents, in a dose-dependent manner. However, the results of this in vivo model showed no correlation with the potency of the drugs for inhibiting platelet aggregation and inhibition of experimental thrombosis. It is therefore reasonable to assume that the drug effects in this model reflect an overall inhibition of prostaglandins including thromboxanes.