Effect of platelet-activating factor-receptor antagonism on endotoxin-induced lung dysfunction in sheep.
Effect of platelet-activating factor-receptor antagonism on endotoxin-induced lung dysfunction in sheep.
复制标题
血小板活化因子受体拮抗作用对内毒素引起的绵羊肺功能障碍的影响。
DOI：
10.1152/jappl.1998.84.5.1610
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Thabes,JS
中科院分区：
文献类型：
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作者：
Snapper,JR;Lu,W;Lefferts,PL;Thabes,JS
为了进一步明确血小板激活因子(PAF)在内毒素诱导的肺功能障碍中的作用，我们研究了一种特异而有效的PAF受体拮抗剂ABT-299对6只慢性仪器化清醒绵羊内毒素血症反应的影响。静脉注射大肠埃希菌内毒素(0.5μg/kg)，监测平均肺动脉压、平均体动脉压、肺动态顺应性和功能残气量。内毒素治疗可引起肺动脉高压、Cdyn降低、白细胞减少和低氧血症，而对PSA和FRC无明显影响。应用ABT-299不影响基线时的任何测量变量。ABT-299可减轻内毒素注射后出现的峰值PPA，但对内毒素诱导的Cdyn、白细胞计数或肺泡至动脉血氧差的变化影响甚微。ABT-299可完全阻断静脉注射外源性PAF后的肺动脉高压和Cdyn降低。我们的结论是，PAF在绵羊对内毒素的反应中并不起重要作用。
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 administeredEscherichia coliendotoxin (0.5 μg/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.