Mechanism of protection against arachidonate induced sudden death by glucocorticoid

Dexamethasone at a dose of 6 mg.kg-1 given to rabbits for three days prior to challenge with sodium arachidonate (2 mg.kg-1) intravenously, improved survival from 0% to 90% (p less than 0.01). Dexamethasone, given for shorter periods prior to arachidonate injection resulted in survival rates from 17% to 40%. In dexamethasone (3 days) treated rabbits, plasma thromboxane B2 concentrations were only increased by 30% compared with increases of 950% in untreated rabbits (p less than 0.001). Dexamethasone treated rabbits did not exhibit pulmonary thrombosis as did untreated rabbits given arachidonate. However, platelet rich plasma from both control and treated rabbits was aggregated by 0.2 mM arachidonate in vitro. The mechanism of the protective effect of dexamethasone appears to be related to induction of enzymes or stimulation of clearance of injected arachidonic acid, since steroid treated rabbits cleared labeled arachidonic acid more rapidly than untreated rabbits.