Circulation, Vol 81, 212-218, Copyright © 1990 by American Heart Association
GW Dorn 2d, N Liel, JL Trask, DE Mais, ME Assey and PV Halushka
Platelets have been implicated in the formation of occlusive intracoronary
thrombi leading to unstable angina pectoris and acute myocardial
infarction. Evidence of platelet involvement in these syndromes includes
increased thromboxane A2 synthesis during ischemic events and enhanced in
vitro sensitivity to agonists. To determine the density and affinity of
platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors in patients
with acute myocardial infarction and unstable angina pectoris, the maximum
number of binding sites (Bmax) per platelet and the dissociation constant
(Kd) of the TXA2/PGH2 receptor antagonist, [125I]-PTA-OH, was determined at
equilibrium in washed platelets. Patients with acute myocardial infarction
had a significantly (p = 0.006) higher Bmax (4,468 +/- 672 sites/platelet,
n = 9) compared with controls (2,206 +/- 203 sites/platelet, n = 8).
Restudied at a time when the patients' coronary artery disease was
clinically stable, Bmax values for the myocardial infarction group had
returned to within normal limits. The dissociation constant for [125I]-
PTA-OH was not significantly different in the acute myocardial infarction
patients compared with controls. In patients with acute myocardial
infarction, the duration of chest pain was positively correlated (r = 0.71,
p less than 0.02) with the number of [125I]-PTA- OH binding sites (Bmax).
In vitro platelet sensitivity to the TXA2/PGH2 mimetic, U46619, was
assessed in aggregation studies. The maximal velocity of aggregation
(slope) correlated with platelet TXA2/PGH2 receptor number (r = 0.67, p
less than 0.001) and was significantly higher (p less than 0.02) in the
acute myocardial infarction patients compared with the other study groups.
There was no significant difference in the aggregation EC50 values for the
thromboxane mimetic U46619 between unstable angina, acute myocardial
infarction, and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Increased platelet thromboxane A2/prostaglandin H2 receptors in patients with acute myocardial infarction
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29425.
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