EPINEPHRINE SENSITIZES HUMAN PLATELETS IN-VIVO AND IN-VITRO AS STUDIED BY FIBRINOGEN BINDING AND P-SELECTIN EXPRESSION

Epinephrine (Epi) infusion influences platelet activation markers in v ivo, but in vitro studies have mainly examined supraphysiological Epi concentrations and have yielded conflicting results. In this study who le-blood flowcytometric measurements of platelet fibrinogen binding an d P-selectin expression were used to compare enhancement of ADP (0.1 t o 10 mu mol/L)-induced platelet activation by Epi infusion in vivo (0. 1 and 0.4 nmol.kg(-1).min(-1)) and by Epi in vitro (10 and 50 nmol/L) in nine healthy volunteers. ADP caused concentration-dependent increas es in the percentage of platelets that bound fibrinogen (from 4.4+/-0. 9% to 69.9+/-4.2%) and that expressed P-selectin (from 4.5+/-0.5% to 4 4.2+/-3.8%). Fibrinogen and P-selectin binding indices (FgBI and PSBI; calculated from mean fluorescence intensity and percentage of positiv e cells) also increased from 0.18+/-0.03 to 11.70+/-1.99 for FgBI and from 0.22+/-0.03 to 2.34+/-0.29 for PSBI. Epi concentration-dependentl y enhanced fibrinogen binding and P-selectin expression in vitro (by a pproximate to 30% at the midportion of the ADP curve at 10 nmol/L Epi; P<.001 for both by ANOVAs). High-dose Epi infusion enhanced FgBI simi larly and increased maximal P-selectin expression by 38%. Epi (50 nmol /L in vitro) enhanced platelet activation further, whether samples wer e taken with or without prior Epi infusion. Total expression of glycop rotein IIb/IIIa was unaffected by Epi infusion, but glycoprotein Ib ex pression per platelet was reduced (P<.05). These in vivo and in vitro effects of Epi on platelet responses to agonist stimulation indicate a prothrombotic potential for sympathoadrenal activation in humans.