Chierchia S, Patrono C
Fed Proc. 1987 Jan;46(1):81-8.
The role of platelet and vascular arachidonate metabolism in ischemic heart disease can be derived from direct measurements and/or inhibitor trials. Direct measurements have yielded somewhat conflicting results, largely related to analytical problems and ex vivo platelet activation during blood sampling. On the other hand, inhibitor trials have clearly established the following: 1) thromboxane (TX) A2-dependent platelet activation plays an important role in the dynamic process of coronary thrombosis in unstable angina, 2) TXA2 does not appear to mediate coronary vasospasm, as seen in variant angina, 3) endogenous prostacyclin (PGI2) is not released in response to myocardial ischemia and is unlikely to regulate coronary blood flow, and 4) exogenous PGI2 is of limited therapeutic benefit. The demonstration that low-dose aspirin (0.5-1.0 mg/(kg X day] is a selective inhibitor of TXA2-dependent platelet function provides a conceptual and practical framework for the rational design of future trials. Moreover, the identification of major enzymatic metabolites of TXB2 in plasma (11-dehydro-TXB2) and urine (2,3-dinor-TXB2) and development of appropriate analytical techniques offer the opportunity for better defining the pathophysiological role of TXA2 in humans.
血小板和血管花生四烯酸代谢在缺血性心脏病中的作用可通过直接测量和/或抑制剂试验得出。直接测量得出的结果有些相互矛盾，这在很大程度上与分析问题以及采血过程中的体外血小板激活有关。另一方面，抑制剂试验明确证实了以下几点：1）血栓素（TX）A2依赖性血小板激活在不稳定型心绞痛冠状动脉血栓形成的动态过程中起重要作用；2）如在变异型心绞痛中所见，TXA2似乎并不介导冠状动脉痉挛；3）内源性前列环素（PGI2）不会因心肌缺血而释放，也不太可能调节冠状动脉血流；4）外源性PGI2的治疗益处有限。低剂量阿司匹林（0.5 - 1.0 mg/(kg×天)）是TXA2依赖性血小板功能的选择性抑制剂这一发现，为未来试验的合理设计提供了概念和实践框架。此外，血浆中TXB2主要酶代谢产物（11 - 脱氢 - TXB2）和尿液中（2,3 - 二去甲 - TXB2）的鉴定以及适当分析技术的发展，为更好地确定TXA2在人体内的病理生理作用提供了机会。
