Increased platelet thromboxane A₂/prostaglandin H₂ receptors in patients with acute myocardial infarction

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 (B_max) per platelet and the dissociation constant (K_d) 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 B_max (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, B_max 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<0.02) with the number of [¹²⁵I]-PTA-OH binding sites (B_max). 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<0.001) and was significantly higher (p<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. The data show that patients with acute myocardial infarction have increased numbers of platelet TXA₂/PGH₂ receptors and that the receptor number is greatest in patients with prolonged ischemic chest pain. The results suggest a possible therapeutic role for specific TXA₂/PGH₂ receptor antagonists in acute coronary ischemic syndromes.