FitzGerald G A, Brash A R, Falardeau P, Oates J A
J Clin Invest. 1981 Nov;68(5):1272-6. doi: 10.1172/jci110373.
The rate of secretion of prostacyclin (PGI2) into the circulation of normal man was estimated by measurement of the 2,3-dinor-6-keto-PGF1 alpha (D) and 15-keto-13,14-dihydro-2,3-dinor-6-keto-PGF1 alpha (KDD) urinary metabolites of PGI2. Subjects received 6-h intravenous infusions of vehicle alone and PGI2 at 0.1, 0.4, and 2.0 ng/kg per min in random order. The fractional elimination of the metabolites was independent of the rate of PGI2 infusion. 6.8 +/- 0.3% of the infused PGI2 appeared as D and 4.1 +/- 0.4% as KDD. The regression of infused PGI2 upon the quantities of the two metabolites excreted in excess of control values permitted estimation of the rate of entry of endogenous PGI2 into the circulation corresponding to a given quantity of metabolite excreted. Using the quantities excreted in the 24 h from commencement of the infusions the estimated rates were 0.08 +/- 0.02 ng/kg per min from D and 0.10 +/- 0.03 from KDD. Studies with exogenous PGI2 suggest that infusion rates 2--4 ng/kg per min are required to achieve the threshold for inhibition of platelet function (ex vivo) in man. Although not precluding a role for PGI2 in local platelet-vessel wall interactions, the much lower estimates obtained in this study suggest that endogenous PGI2 is unlikely to act as a circulating antiplatelet agent in healthy man.
通过测量前列环素（PGI2）的2,3-二去甲-6-酮-PGF1α（D）和15-酮-13,14-二氢-2,3-二去甲-6-酮-PGF1α（KDD）尿代谢产物，估算了正常男性体内前列环素（PGI2）分泌入循环的速率。受试者以随机顺序接受单独静脉输注载体以及分别以0.1、0.4和2.0 ng/kg每分钟的速率静脉输注PGI2，持续6小时。代谢产物的消除分数与PGI2输注速率无关。输注的PGI2中6.8±0.3%以D形式出现，4.1±0.4%以KDD形式出现。根据输注的PGI2与超过对照值排泄的两种代谢产物量之间的回归关系，可以估算出与给定排泄量代谢产物相对应的内源性PGI2进入循环的速率。利用输注开始后24小时内排泄的量，从D估算的速率为0.08±0.02 ng/kg每分钟，从KDD估算的速率为0.10±0.03 ng/kg每分钟。对外源性PGI2的研究表明，在人体中需要2 - 4 ng/kg每分钟的输注速率才能达到抑制血小板功能（体外）的阈值。虽然不排除PGI2在局部血小板 - 血管壁相互作用中的作用，但本研究中获得的低得多的估算值表明，内源性PGI2不太可能在健康男性中作为循环抗血小板剂发挥作用。
