NOREPINEPHRINE-INDUCED HUMAN PLATELET ACTIVATION IN-VIVO IS ONLY PARTLY COUNTERACTED BY ASPIRIN

Background Epinephrine and mental stress may, via platelet stimulation , enhance the risk of thrombus formation. Norepinephrine is more likel y than epinephrine to activate platelets in vivo because of higher lev els in plasma but is less well studied in this respect. The antiplatel et drug of choice for patients with coronary artery disease, aspirin, maybe less effective during sympathoadrenal activation. We therefore i nvestigated platelet responses in vivo to exogenous norepinephrine wit h and without aspirin pretreatment. Methods and Results Platelet aggre gability in vivo was assessed in 11 healthy male subjects, by filtrago metry ex vivo (which reflects platelet aggregability in vivo) and by m easurements of plasma beta-thromboglobulin (beta-TG, which reflects pl atelet secretion). Norepinephrine infusions elevated venous plasma nor epinephrine from 1.5 to 4 and 15 nmol/L, respectively, and enhanced pl atelet aggregability (filtragometry) concentration dependently (P<.001 ). Platelet secretion (beta-TG levels) increased during high-dose infu sion (P<.01). Aspirin pretreatment (500 mg orally 12 hours earlier) re duced the excretion of 11-dehydrothromboxane B-2 by 62+/-5% (P<.001) a nd attenuated platelet aggregability at rest (P<.05) but not the effec t of norepinephrine infusion on platelet aggregability. Conversely, re sting plasma beta-TG levels and the urinary excretion of high-molecula r-weight beta-TG were not altered by aspirin pretreatment, whereas the norepinephrine-induced increase in plasma beta-TG was abolished. Conc lusions Norepinephrine, at plasma levels easily attained during exerci se, enhances platelet aggregability and platelet secretion in vivo in healthy humans. Aspirin may be less effective as an antithrombotic dru g during sympathoadrenal activation in humans.