A sudden increase in plasma epinephrine levels transiently enhances platelet deposition on severely damaged arterial wall - Studies in a porcine model

Epidemiologic evidence has shown that sympathoadrenal activation plays a tr iggering role in the onset of acute coronary syndromes. However, its mechan ism is not yet clearly understood. The aim of this study was to assess the effect of a sudden increase in epinephrine on platelet deposition on severe ly damaged vessel wall at shear rate conditions modelling stenotic vessels in the porcine model. The selected epinephrine concentrations (0.5 mu mol/l -1 mol/l) alone or in combination with collagen or ADP did not affect plate let aggregation in vitro either in whole blood or in PRP, although porcine platelets express alpha(2)-adrenergic receptors as assessed by PCR. In vitr o and ex vivo perfusion esperiments were performed using the Badimon chambe r at high shear rate conditions (1690 s(-1)). In vitro, epinephrine (130 nm ol/l) increased platelet deposition on severely damaged vessel wall (exposi ng tunica media; approximate to 16-fold, p <0.05) or immobilized collagen ( 2.2-fold, p <0.01). Ex ville perfusion experiments were performed from anim als that received intravenous epinephrine infusion for one hour at a low (0 .3 mu g/kg/min; approximate to 17 nmol/l in plasma, at 20 min of the: infus ion) and a high dose (1.0 mu g/kg/min; approximate to 106 nmol/l in plasma, at 20 min of the infusion). Only the low dose temporarily increased platel et deposition on severely damaged vessel wall during the first 30 min of in fusion [2.4-fold (p <0.05) and 4.2-fold (p <0.01) at 10 and 30 min of the i nfusion respectively] declining afterwards. Thus, in Row conditions typical of atherosclerotic arteries, a sudden physiological release of epinephrine can temporarily enhance platelet deposition on severely damaged vessel wal l while an extensive exposure leads to refractoriness.