Abu-Zidan F M, Walther S, Lennquist S
Department of Surgery, University Hospotal, Linköping, Sweden.
Pharmacol Toxicol. 1996 Jan;78(1):23-7. doi: 10.1111/j.1600-0773.1996.tb00175.x.
The effects of bolus doses (0.2-2 micrograms) of platelet-activating factor (PAF) on systemic and pulmonary arterial pressures were tested in five juvenile pigs, and were demonstrated to have a biphasic effect. There was an initial drop in the mean systemic arterial pressure within seconds, followed by an increase within 1-2 min., whereas mean pulmonary arterial pressure only rose. The response was dose-related and did not include tachyphylaxis. The pressures returned to baseline within 10 min. After confirming these results a novel specific PAF receptor antagonist (BB-882) was given as a 1 mg/kg bolus followed by a continuous infusion of 2 mg/kg/hr, and a third dose response curve was repeated with ten-fold higher PAF doses (2-20 micrograms). BB-882 effectively counteracted these effects. Six pigs were given a continuous infusion of BB-882 33 mg/kg/hr for 5 hr and were compared with another group of five pigs given vehicle only. In this high dose BB-882 did not affect the intravascular pressures. These results indicate that BB-882 is a potent PAF receptor antagonist in juvenile pigs.
在5只幼年猪身上测试了大剂量（0.2 - 2微克）血小板活化因子（PAF）对体循环和肺动脉压的影响，结果显示其具有双相作用。给药后数秒内平均体循环动脉压会出现初始下降，随后在1 - 2分钟内升高，而平均肺动脉压仅升高。该反应与剂量相关且不存在快速耐受性。血压在10分钟内恢复至基线水平。在确认这些结果后，给予一种新型特异性PAF受体拮抗剂（BB - 882），静脉推注剂量为1毫克/千克，随后以2毫克/千克/小时的速度持续输注，然后用剂量高出10倍（2 - 20微克）的PAF重复进行第三次剂量反应曲线测试。BB - 882有效抵消了这些影响。6只猪以33毫克/千克/小时的速度持续输注BB - 882 5小时，并与另一组仅给予赋形剂的5只猪进行比较。在这个高剂量下，BB - 882并未影响血管内压力。这些结果表明，BB - 882在幼年猪中是一种有效的PAF受体拮抗剂。
