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 triggering role in the onset of acute coronary syndromes. However, its mechanism 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 severely damaged vessel wall at shear rate conditions modelling stenotic vessels in the porcine model. The selected epinephrine concentrations (0.5 micromol/l-1 mmol/l) alone or in combination with collagen or ADP did not affect platelet aggregation in vitro either in whole blood or in PRP, although porcine platelets express alpha2-adrenergic receptors as assessed by PCR. In vitro and ex vivo perfusion experiments were performed using the Badimon chamber at high shear rate conditions (1690 s(-1)). In vitro, epinephrine (130 nmol/l) increased platelet deposition on severely damaged vessel wall (exposing tunica media; approximately 1.6-fold, p <0.05) or immobilized collagen (2.2-fold, p <0.01). Ex vivo perfusion experiments were performed from animals that received intravenous epinephrine infusion for one hour at a low (0.3 microg/kg/min; approximately 17 nmol/l in plasma, at 20 min of the infusion) and a high dose (1.0 microg/kg/min; approximately 106 nmol/l in plasma, at 20 min of the infusion). Only the low dose temporarily increased platelet deposition on severely damaged vessel wall during the first 30 min of infusion [2.4-fold (p <0.05) and 4.2-fold (p <0.01) at 10 and 30 min of the infusion respectively] declining afterwards. Thus, in flow conditions typical of atherosclerotic arteries, a sudden physiological release of epinephrine can temporarily enhance platelet deposition on severely damaged vessel wall while an extensive exposure leads to refractoriness.
Badimon
L
L
Cardiovascular Research Center, IIBB/CSIC-Institut de Recerca del Hospital Santa Creu i Sant Pau, Barcelona, Spain.
Martínez-González
J
J
Royo
T
T
Lassila
R
R
Badimon
J J
JJ
D000818:Animals; D001792:Blood Platelets / Q000473:pathology; D003327:Coronary Disease / Q000097:blood* / Q000503:physiopathology*; D003331:Coronary Vessels / Q000294:innervation / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood*; D010974:Platelet Aggregation; D013552:Swine; D013564:Sympathetic Nervous System / Q000503:physiopathology
D004837:Epinephrine