Research Center, University Hospital La Fe, Valencia, Spain.
Thromb Haemost. 2011 Apr;105(4):663-9. doi: 10.1160/TH10-08-0550. Epub 2011 Feb 8.
Aspirin treatment is essential in patients with acute myocardial infarction (AMI) to block platelet thromboxane (TXA)₂ synthesis. Epinephrine is known to enhance platelet reactivity induced by other agonists and to be elevated in patients with AMI due to stress. Our objective was to study the influence of epinephrine on platelet TXA₂ synthesis in patients treated with aspirin for AMI at early onset (within 48 hours) and the potential biochemical mechanisms involved in the functional response. Washed platelets from 45 patients with AMI and 10 aspirin-free controls were stimulated with arachidonic acid (AA) or AA + epinephrine, and aggregation and TXA₂ synthesis were evaluated. Full platelet aggregation was recorded in 8/45 patients (18%) with a partial TXA₂ inhibition (86%) vs. the aspirin-free controls. Platelets from the remaining 37 patients did not aggregate to AA and had TXA₂ inhibition >95%. However, when platelets were simultaneously stimulated with AA + epinephrine, in 25/37 patients a large intensity of aggregation (73%) was observed and a 5.5-fold increase in TXA₂ synthesis, although this remained residual (<5% of aspirin-free controls). This residual-TXA₂ was critical in the functional response, as demonstrated by the complete inhibition by TXA₂ receptor blockade or additional aspirin in vitro. The phosphatidylinositol-3-kinase activity and the cytosolic calcium levels participated in this platelet response elicited by a receptor cooperation mechanism, while the Rho/p160(ROCK) pathway or the blockade of the ADP receptors (P2Y1, P2Y12) were without effect. Residual-cyclooxygenase -1 activity and epinephrine enhance TXA₂-dependent platelet function, which may reduce the clinical benefit of aspirin in patients with AMI.
阿司匹林治疗急性心肌梗死（AMI）患者至关重要，可阻断血小板血栓素（TXA）₂合成。肾上腺素已知可增强其他激动剂诱导的血小板反应性，并因应激而在 AMI 患者中升高。我们的目的是研究肾上腺素对阿司匹林早期（48 小时内）治疗的 AMI 患者血小板 TXA₂合成的影响，以及涉及功能反应的潜在生化机制。用花生四烯酸（AA）或 AA +肾上腺素刺激来自 45 名 AMI 患者和 10 名无阿司匹林对照组的洗涤血小板，并评估聚集和 TXA₂合成。在 45 名 AMI 患者中有 8/45 名（18%）患者记录到完全血小板聚集，TXA₂抑制率为 86%，与无阿司匹林对照组相比。其余 37 名患者的血小板对 AA 没有聚集，且 TXA₂抑制率>95%。然而，当血小板同时用 AA +肾上腺素刺激时，在 25/37 名患者中观察到强烈的聚集强度（73%），TXA₂合成增加了 5.5 倍，尽管这仍然是残留的（<无阿司匹林对照组的 5%）。这种残留的 TXA₂在功能反应中是至关重要的，如通过 TXA₂受体阻断或体外额外的阿司匹林完全抑制所证明的那样。磷酸肌醇-3-激酶活性和细胞溶质钙水平参与了这种由受体合作机制引起的血小板反应，而 Rho/p160（ROCK）途径或 ADP 受体（P2Y1、P2Y12）的阻断则没有效果。残留的环氧化酶-1 活性和肾上腺素增强了 TXA₂依赖性血小板功能，这可能会降低 AMI 患者阿司匹林的临床获益。
