Roth D M, Burke S E, Lefer A M
Pharmacology. 1983;27(3):169-75. doi: 10.1159/000137866.
Sodium arachidonate given intravenously at a dose of 2 mg/kg is uniformly lethal in rabbits. Rabbits die within 2-5 min following a dramatic decrease in mean arterial blood pressure (MABP), and in circulating platelets, and a large increase in plasma thromboxane B2 (TxB2) concentration. The nonsteroidal anti-inflammatory agent, ibuprofen, given 15 min prior to challenge with sodium arachidonate, significantly protects against the abrupt decrease in MABP and in circulating platelets and prevents the increase in circulating TxB2 concentrations. These rabbits all survive the lethal effects of arachidonic acid when given ibuprofen at doses of 0.75, 6.25 or 12.5 mg/kg intravenously 15 min prior to arachidonate challenge. At 0.375 mg/kg, only 20% of the animals survive. Concomitant with survival is a significant attenuation of the decrease in MABP (84 +/- 8 mm Hg without ibuprofen vs. 1 +/- 1 to 33 +/- 12 mm Hg with 12.5-0.75 mg/kg ibuprofen). Similarly, these rabbits show a greatly reduced loss of circulating platelets, and virtually no increases in the formation of TxB2. Ibuprofen protects against arachidonate-induced sudden death in a dose-related manner. The mechanism of the protection appears to involve prevention of adherence or aggregation of platelets and the subsequent formation of thromboxane A2. The net result is prevention of pulmonary thrombosis, the major pathological event in triggering sudden death.
以2毫克/千克的剂量静脉注射花生四烯酸钠对兔子具有一致的致死性。兔子在平均动脉血压（MABP）、循环血小板急剧下降以及血浆血栓素B2（TxB2）浓度大幅升高后的2 - 5分钟内死亡。在注射花生四烯酸钠前15分钟给予非甾体抗炎药布洛芬，可显著防止MABP和循环血小板的突然下降，并阻止循环TxB2浓度的升高。当在注射花生四烯酸钠前15分钟静脉注射0.75、6.25或12.5毫克/千克剂量的布洛芬时，这些兔子均能从花生四烯酸的致死作用中存活下来。在0.375毫克/千克的剂量下，只有20%的动物存活。与存活相伴的是MABP下降的显著减轻（未使用布洛芬时为84±8毫米汞柱，使用12.5 - 0.75毫克/千克布洛芬时为1±1至33±12毫米汞柱）。同样，这些兔子循环血小板的损失大大减少，并且TxB2的形成几乎没有增加。布洛芬以剂量相关的方式预防花生四烯酸诱导的猝死。其保护机制似乎涉及防止血小板的黏附或聚集以及随后血栓素A2的形成。最终结果是预防肺血栓形成，这是引发猝死的主要病理事件。
