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
Herz. 1986 Apr;11(2):116-26.
There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore, an understanding of factors which impact on platelet performance is important. The present study was undertaken 1. to characterize during evolving myocardial infarction (MI) 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 MI were studied. 22 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 minutes. In 15 of these patients, who had an anterior MI, transcardiac platelet function and response to PGI2 were studied. The results are as follows: Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, are elevated three and ten fold. 6-keto-prostaglandin F1 alpha, the stable end product of PGI2, is less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets, circulating during evolving MI ("ischemic platelets") are hyperaggregable in response to adenosine diphosphate and relatively resistent to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic adenosine monophosphate and the cAMP response to PGI2 are diminished. The platelet hyper-reactivity is most intense early during infarct evolution and decreases with time. Transcardiac measurements indicate that thromboxane is produced across the ischemic/infarcting compartment in ten of 15 patients with anterior MI. The antiplatelet effect of PGI2 is greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving MI characterized by a pro-aggregatory environment, heightened platelet re-activity, both in the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequence of the data are that the infarct patient in the acute phase may benefit from platelet function suppression and requires significantly greater doses of prostacyclin than normal subjects. The data also suggest future directions for therapeutic manipulation of platelet hyper-reactivity in the setting of acute myocardial ischemia.
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. 描述在急性心肌梗死（MI）进展过程中，外周循环及缺血/梗死心肌区域内血小板的活性，确定推测血小板活性过高的部位；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例患者置入动脉和冠状窦导管，并静脉输注PGI2，剂量为13±4.5 ng/kg/min（均值±标准差），持续90分钟。其中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。结果如下：作为血小板活性体内指标的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比值向左偏移。在急性心肌梗死进展过程中循环的血小板（“缺血性血小板”），对二磷酸腺苷的反应性过高，且在体内和体外对PGI2相对抵抗。血小板环磷酸腺苷浓度及对PGI2的环磷酸腺苷反应降低。血小板高反应性在梗死进展早期最为强烈，并随时间降低。经心脏测量表明，15例前壁心肌梗死患者中有10例在缺血/梗死区域产生血栓素。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、外周和冠状动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，急性期梗死患者可能从血小板功能抑制中获益，且所需的前列环素剂量比正常受试者大得多。这些数据还为急性心肌缺血情况下血小板高反应性的治疗性干预指明了未来方向。
