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)