STUDY ON THE IN-VITRO INFLUENCE OF ALPHA( 2)-AGONISTS ON THE THROMBOCYTE FUNCTION AND DENSITY OF THROMBOCYTE

alpha(2)-Agonists are being used increasingly in anaesthesia and inten sive care medicine because of their antihypertensive, analgesic and se dative properties. Platelets bear alpha(2)-receptors on the cell surfa ce. Stimulation of these receptors by agonists induces platelet aggreg ation. The present study examined whether in vitro incubation of blood with the alpha(2)-agonists clonidine and dexmedetomidine decreases al pha(2)-receptor density and hereby influences platelet aggregation, Me thods. Whole blood of 20 healthy volunteers was incubated over 24 h at 37 degrees C with 1 ng/ml clonidine or 1 or 10 ng/ml dexmedetomidine. Induced platelet aggregation was determined by means of turbidometry. Epinephrine (22 mu mol/l) or collagen (20 mg/l) served as inductors. The density of alpha(2)-receptors was measured in radioligand assays w ith H-3-Yohimbine. Phentolamine was used to assess unspecific binding. The data were analyzed with an analysis of variance. Results. Neither 1 ng/ml clonidine nor 1 ng/ml dexmedetomidine altered platelet aggreg ation or alpha(2)-receptor density in comparison with the control samp le, As a major result we found that 10 ng/ml dexmedetomidine caused a significant (P<0.05) reduction in epinephrine-induced platelet aggrega tion (16.0 +/- 5.4%, n=20, mean +/- SEM) compared with the control (46 .0 +/- 1.3%, n=20). alpha(2)-Receptor density was nor any different fr om the control. Conclusions. This in vitro study showed that clinicall y relevant concentrations of 1 ng/ml clonidine or dexmedetomidine did not alter platelet aggregation or alpha(2)-receptor density, even afte r 24 h exposure, However, 10 ng/ml dexmedetomidine was found to dimini sh significantly epinephrine-induced platelet aggregation, but did not change alpha(2)-receptor density. This result showed that desensitiza tion of platelet aggregation can occur without quantitative changes in alpha(2)-receptors.