William M Wooding

Intravenous arachidonate in the mouse: A model for the evaluation of antithrombotic drugs

Abstract The intravenous administration of arachidonate to mice offers a rapid, convenient, and effective in vivo model for the study of platelet aggregation and thrombosis, as well as the evaluation of potential antithrombotic drugs. Following intravenous administration in the mouse, there is dose-dependent cyanosis and respiratory distress with death at doses about 100 mg/kg. The rabbit is much more sensitive to the effects of intravenous arachidonate with death occurring at doses of 1 mg/kg; the rat shows an intermediate sensitivity. There is a relative specificity for the arachidonate effect: administration of certain other unsaturated fatty acids produces only minimal respiratory distress at equivalent doses. Respiratory distress in the mouse can be correlated with histologic evidence of platelet aggregation in the microvasculature of the lungs, but not in the heart or brain. Several nonsteroidal anti-inflammatory drugs (NSAID) which are known to be inhibitors of collagen-induced platelet aggregation and release, as well as inhibitors of prostaglandin synthetase, are able to block the effect of arachidonate in vivo . ADP inhibitors (dipyridamole, adenosine, and VK 744) are also effective in blocking the effects of arachidonate in vivo . Both the NSAID and the ADP inhibitors also block arachidonate-induced platelet aggregation in vitro .