Mueller H S, Rao P S, Greenberg M A, Buttrick P M, Sussman I I, Levite H A, Grose R M, Perez-Davila V, Strain J E, Spaet T H
Circulation. 1985 Dec;72(6):1336-45. doi: 10.1161/01.cir.72.6.1336.
There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore an understanding of factors that influence platelet performance is important. This study was undertaken (1) to characterize during evolving myocardial infarction platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and (2) to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving myocardial infarction were studied. Twenty-two patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 min. In 15 patients with anterior myocardial infarction, transcardiac platelet function and response to PGI2 were studied. Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold. 6-Keto-prostaglandin F 1 alpha, the stable end product of PGI2, was less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets circulating during evolving myocardial infarction ("ischemic platelets") were hyperaggregable in response to ADP and relatively resistant to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic AMP and the cyclic AMP response to PGI2 were diminished. The platelet hyperreactivity, expressed by plasma beta-TG, platelet aggregation, and PGI2-induced inhibition of aggregation, was most intense early during infarct evolution and decreased with time. The increased platelet performance resulted in "platelet fatigue," indicated by decreased contents of beta-TG of the ischemic platelet and decreased TxA2 production in response to collagen. However, the ischemic platelet produced twice normal TxA2 in response to arachidonic acid (stimulus and substrate), demonstrating a heightened metabolic capacity. TxA2 was produced across the ischemic/infarcting compartment in 10 of 15 patients with anterior myocardial infarction. The antiplatelet effect of PGI2 was greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving myocardial infarction, characterized by a proaggregatory environment, heightened platelet reactivity in both the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequences of the data are that the patient in the acute phase of myocardial infarction may benefit from suppression of platelet function and requires significantly greater doses of PGI2 than normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
越来越多的证据表明血小板在急性缺血性心脏病的发病机制中起重要作用。因此，了解影响血小板功能的因素很重要。本研究旨在：（1）在急性心肌梗死进展过程中，描绘外周循环以及缺血/梗死心肌区域内血小板的活性，确定推测的血小板活性增强部位；（2）评估前列环素（PGI2）的作用，PGI2是一种最有效的抗血小板药物和血管扩张剂。共研究了59例急性心肌梗死患者。22例患者通过动脉和冠状窦导管进行监测，并接受PGI2静脉输注，剂量为13±4.5 ng/kg/min（均值±标准差），持续90分钟。对15例前壁心肌梗死患者研究了经心脏的血小板功能及对PGI2的反应。体内血小板活性指标β-血小板球蛋白（β-TG）和血栓素B2（TxB2）的血浆水平分别升高了3倍和10倍。PGI2的稳定终产物6-酮-前列腺素F1α低于10 pg/ml，反映了TxB2/PGI2比值左移。急性心肌梗死进展过程中循环的血小板（“缺血性血小板”）对ADP反应性高聚集，且在体内和体外对PGI2相对抵抗。血小板环磷酸腺苷（cAMP）浓度及对PGI2的cAMP反应降低。由血浆β-TG、血小板聚集及PGI2诱导的聚集抑制所表现出的血小板高反应性在梗死进展早期最为强烈，并随时间降低。血小板功能增强导致“血小板疲劳”，表现为缺血性血小板β-TG含量降低及对胶原反应时TxA2生成减少。然而，缺血性血小板对花生四烯酸（刺激物和底物）反应生成的TxA2是正常水平的两倍，表明其代谢能力增强。15例前壁心肌梗死患者中有10例在缺血/梗死区域生成TxA2。PGI2的抗血小板作用大大减弱。总之，这些数据确定了急性心肌梗死进展过程中血小板行为的异常模式，其特征为促聚集环境、外周和冠脉循环中血小板反应性增强以及对PGI2相对抵抗。这些数据的临床意义在于，心肌梗死急性期患者可能从血小板功能抑制中获益，且所需PGI2剂量比正常受试者大得多。（摘要截选至400词）
