Dorn G W, Liel N, Trask J L, Mais D E, Assey M E, Halushka P V
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29425.
Circulation. 1990 Jan;81(1):212-8. doi: 10.1161/01.cir.81.1.212.
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)
血小板与导致不稳定型心绞痛和急性心肌梗死的冠状动脉闭塞性血栓形成有关。血小板参与这些综合征的证据包括缺血事件期间血栓素A2合成增加以及体外对激动剂的敏感性增强。为了确定急性心肌梗死和不稳定型心绞痛患者血小板血栓素A2/前列腺素H2（TXA2/PGH2）受体的密度和亲和力，在洗涤后的血小板中于平衡状态下测定了每个血小板的最大结合位点数（Bmax）以及TXA2/PGH2受体拮抗剂[125I]-PTA-OH的解离常数（Kd）。与对照组（2206±203个位点/血小板，n = 8）相比，急性心肌梗死患者的Bmax显著更高（p = 0.006）（4468±672个位点/血小板，n = 9）。在患者冠状动脉疾病临床稳定时进行再次研究，心肌梗死组的Bmax值已恢复到正常范围内。与对照组相比，急性心肌梗死患者中[125I]-PTA-OH的解离常数无显著差异。在急性心肌梗死患者中，胸痛持续时间与[125I]-PTA-OH结合位点数（Bmax）呈正相关（r = 0.71，p＜0.02）。在聚集研究中评估了体外血小板对TXA2/PGH2模拟物U46619的敏感性。最大聚集速度（斜率）与血小板TXA2/PGH2受体数量相关（r = 0.67，p＜0.001），并且与其他研究组相比，急性心肌梗死患者的最大聚集速度显著更高（p＜0.02）。不稳定型心绞痛、急性心肌梗死和对照组之间，血栓素模拟物U46619的聚集EC50值无显著差异。（摘要截短于250字）
