Snapper J R, Lu W, Lefferts P L, Thabes J S
Center for Lung Research, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
J Appl Physiol (1985). 1998 May;84(5):1610-4. doi: 10.1152/jappl.1998.84.5.1610.
To further define the role of platelet-activating factor (PAF) in endotoxin-induced lung dysfunction, we examined the effect of ABT-299, a specific and potent PAF-receptor antagonist, on the response to endotoxemia in six chronically instrumented awake sheep. We administered Escherichia coli endotoxin (0.5 microg/kg) intravenously with or without pretreatment with ABT-299 while monitoring mean pulmonary arterial pressure (Ppa), mean systemic arterial pressure (Psa), dynamic compliance of the lungs (Cdyn), and functional residual capacity (FRC). Endotoxin administration caused pulmonary hypertension, reduced Cdyn, leukopenia, and hypoxemia while having no significant effect on Psa or FRC. Administration of ABT-299 did not affect any of the measured variables at baseline. Pretreatment with ABT-299 attenuated the peak Ppa seen after endotoxin administration but had minimal effects on endotoxin-induced changes in Cdyn, white blood cell count, or alveolar-to-arterial oxygen difference. ABT-299 was shown to completely block the pulmonary hypertension and reduction in Cdyn seen after intravenous administration of exogenous PAF. We conclude that PAF does not play an essential role in the sheep's response to endotoxin.
为了进一步明确血小板活化因子（PAF）在内毒素诱导的肺功能障碍中的作用，我们在六只长期植入仪器的清醒绵羊中，研究了特异性强效PAF受体拮抗剂ABT-299对内毒素血症反应的影响。我们在监测平均肺动脉压（Ppa）、平均体动脉压（Psa）、肺动态顺应性（Cdyn）和功能残气量（FRC）的同时，静脉注射大肠杆菌内毒素（0.5微克/千克），注射时或预先不预先使用ABT-299。内毒素给药导致肺动脉高压、Cdyn降低、白细胞减少和低氧血症，而对Psa或FRC无显著影响。给予ABT-299在基线时不影响任何测量变量。预先使用ABT-299可减弱内毒素给药后出现的Ppa峰值，但对内毒素诱导的Cdyn、白细胞计数或肺泡-动脉氧分压差变化影响最小。结果表明，ABT-299可完全阻断静脉注射外源性PAF后出现的肺动脉高压和Cdyn降低。我们得出结论，PAF在绵羊对内毒素的反应中不发挥重要作用。
