Fletcher J R, Ramwell P W
Circ Shock. 1980;7(3):299-308.
Prostacyclin (PGI2) is a major metabolite of arachidonic acid and is synthesized in vascular endothelial cells. It is a potent inhibitor of platelet aggregation and a known vasodilator. Because of the effects of PGI2 on platelet function, this study was designed to determine the efficacy of prostacyclin in endotoxin shock and on endotoxin-induced platelet aggregation in dogs. Thrombocytopenia is characteristic of septic shock and is believed to be related to platelet clumping, and thereby, to participate in the pathophysiology of endotoxin shock. Twenty-four males dogs were given an LD50 dose of Escherichia coli endotoxin (1 mg/kg). Twelve of these animals were treated with PGI2 (20 ng/kg/min) by continuous infusion from 15 minutes before, and for 4 hours after the injection of endotoxin. Parameters determined were mean arterial pressure, cardiac output, pulmonary arterial pressure, heart rate, platelet and white blood cell counts, and arterial blood gases. In animals given endotoxin alone, only 42% (5/12) survived, whereas, with PGI2 treatment, 83% (10/12) survived (P < 0.05). Prostacyclin therapy did not alter the rise in pulmonary arterial pressure, but did further decrease the mean systemic arterial pressure. There was a transient attenuation of the thrombocytopenia, and minimal effects on the granulocytopenia. Despite the fact that the PGI2-treated animals had greater decreases in blood pressures, 83% of the animals did survive. These findings suggest that PGI2 may have some protective effects in endotoxin shock. Serratia marcescens endotoxin caused dose-dependent platelet aggregation in canine platelet-rich plasma in vitro. Antiaggregating agents such as indomethacin (0.2-1 microgram/ml), and aspirin (0.2-1 microgram/ml), PGE1 (0.1-1 microgram/ml) and PGI2 (0.1-1 microgram/ml), added 1 minute before endotoxin (1 microgram/ml), had no apparent effect on the endotoxin-induced platelet aggregation. These findings suggest that endotoxin-induced platelet aggregation may be caused by a mechanism that is unrelated to cAMP and/or the arachidonic acid prostaglandin system.
前列环素（PGI2）是花生四烯酸的主要代谢产物，在血管内皮细胞中合成。它是血小板聚集的强效抑制剂，也是已知的血管扩张剂。鉴于PGI2对血小板功能的影响，本研究旨在确定前列环素对内毒素休克的疗效以及对犬内毒素诱导的血小板聚集的作用。血小板减少是脓毒性休克的特征，被认为与血小板聚集有关，进而参与内毒素休克的病理生理学过程。给24只雄性犬静脉注射半数致死量的大肠杆菌内毒素（1毫克/千克）。其中12只动物在注射内毒素前15分钟开始，持续输注PGI2（20纳克/千克/分钟），共4小时。测定的参数包括平均动脉压、心输出量、肺动脉压、心率、血小板和白细胞计数以及动脉血气。仅给予内毒素的动物中，只有42%（5/12）存活，而接受PGI2治疗的动物中，83%（10/12）存活（P<0.05）。前列环素治疗并未改变肺动脉压的升高，但确实进一步降低了平均体动脉压。血小板减少有短暂缓解，对粒细胞减少影响极小。尽管接受PGI2治疗的动物血压下降幅度更大，但83%的动物确实存活了下来。这些发现表明，PGI2可能在内毒素休克中具有一定的保护作用。粘质沙雷氏菌内毒素在体外可使犬富含血小板血浆发生剂量依赖性血小板聚集。在内毒素（1微克/毫升）注射前1分钟加入抗聚集剂，如吲哚美辛（0.2 - 1微克/毫升）、阿司匹林（0.2 - 1微克/毫升）、PGE1（0.1 - 1微克/毫升）和PGI2（0.1 - 1微克/毫升），对内皮素诱导的血小板聚集无明显影响。这些发现表明，内毒素诱导的血小板聚集可能是由一种与环磷酸腺苷（cAMP）和/或花生四烯酸前列腺素系统无关的机制引起的。
