Epinephrine reverses the inhibitory influence of aspirin on platelet-vessel wall interactions

The effect of in vitro aspirin treatment and alpha adrenergic receptor stimulation on the interaction of platelets with the subendothelium was studied using citrated human blood obtained from normal control donors. Reconstituted blood following drug treatment was circulated through a chamber which housed everted segments of deendothelialized rabbit aorta. The wall shear rate was 800 sec-1. Surface coverage of platelets were morphometrically evaluated. Aspirin treatment significantly reduced platelet thrombi on exposed subendothelium. However, platelet spreading was increased. There was no significant difference in the total percent coverage of platelets in the vascular surface between the aspirin treated group and normal controls. Epinephrine exposure of aspirin treated platelets completely reversed the effect of alterations induced in platelet behavior by aspirin. Epinephrine exposed aspirin treated platelets had as many platelet thrombi on exposed subendothelium as normal control platelets. In addition, epinephrine treatment decreased the spreading of aspirin treated platelets on the vascular surface. Results of the present study and our earlier findings suggest that the epinephrine induced membrane modulation may be a major mechanism for protecting the hemostatic role of platelets after their function is compromised in vivo and in vitro. The failure of aspirin to offer significant protection in many clinical trials may be due to the presence of a salvage pathway in platelets provided by the mechanism of membrane modulation.