Role of 5-hydroxytryptamine in endotoxin-induced respiratory failure of pigs.
Role of 5-hydroxytryptamine in endotoxin-induced respiratory failure of pigs.
复制标题
5-羟色胺在内毒素诱导的猪呼吸衰竭中的作用。
DOI：
10.1164/arrd.1987.135.1.93
复制
发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Olson,NC
中科院分区：
文献类型：
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作者：
Olson,NC
用5-羟色胺（5-HT）、去甲肾上腺素、前列腺素F2α（PGF 2 α）和血管紧张素Ⅱ（Ang Ⅱ）分别阻断酮色林（Ketanserin）和酮色林（Ketanserin）后，观察了猪肺血管和气道对外源性5-HT、去甲肾上腺素、PGF 2 α和Ang Ⅱ的反应。酮色林可阻断5-HT诱导的气道和肺动脉压力升高，而去甲肾上腺素、PGF 2 α或血管紧张素II引起的气道和肺动脉压力升高未被酮色林显著改变，表明酮色林对5-HT 2受体的特异性相对较高。将大肠杆菌内毒素（055-B5）以5μg/kg/h静脉输注麻醉的10 ~ 14周龄猪，随后以2 μg/kg/h持续3.5 h，观察内源性5-HT在内毒素诱导的呼吸衰竭中的作用。内毒素前以300 µg/kg输注酮色林，内毒素血症期间以67 µg/kg/h输注酮色林。在阶段1期间（即，酮色林对内毒素引起的肺血管阻力和肺泡-动脉氧分压差的增加以及心脏指数和肺动态顺应性的降低无明显影响。然而，在第二阶段（即，2 ~ 4.5h）内毒素血症时，酮色林可减轻内毒素所致的肺动脉高压，降低肺血管阻力、肺泡死腔通气量和肺泡-动脉氧分压差。酮色林还减弱了2期支气管收缩和心脏指数降低，但未改变内毒素诱导的肺泡毛细血管通透性增加。这些结果表明，5-HT在介导早期（即，< 2 h）对内毒素的反应。然而，2小时后，5-HT显着有助于低氧血症的内毒素血症猪的发展，这是由于部分通气/灌注不平等。
The porcine pulmonary vascular and airway responses to exogenous 5-hydroxytryptamine (5-HT), norepinephrine, prostaglandin F2α(PGF2α), and angiotensin II were evaluated before and after ketanserin, a 5-HT2receptor antagonist. Ketanserin blocked the 5-HT-induced increases in airway and pulmonary artery pressures, whereas the increases in airway and pulmonary artery pressures caused by norepinephrine, PGF2α, or angiotensin II were not significantly modified by ketanserin, indicating a relatively high degree of specificity for 5-HT2receptors. The role of endogenous 5-HT in mediating endotoxin-induced respiratory failure was evaluated by treating pigs with ketanserin.Escherichia coliendotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5µg/kg the first h, followed by 2 µg/kg/h for 3.5 h. Ketanserin was infused at 300 µg/kg before endotoxin plus 67 µg/kg/h during endotoxemia. During Phase 1 (i.e., 0 to 2 h), the endotoxin-induced increases in pulmonary vascular resistance and room air alveolar-arterial oxygen difference and the decreased cardiac index and lung dynamic compliance were not significantly modified by ketanserin. However, during Phase 2 (i.e., 2 to 4.5 h) endotoxemia, ketanserin attenuated the endotoxin-induced pulmonary hypertension and the increases in pulmonary vascular resistance, alveolar dead space ventilation, and alveolar-arterial oxygen difference. Ketanserin also attenuated the Phase 2 bronchoconstriction and the decreased cardiac index, but did not modify the endotoxin-induced increase in alveolar-capillary permeability. These results indicate that 5-HT plays little or no role in mediating the early (i.e., < 2 h) response to endotoxin. However, after 2 h, 5-HT significantly contributes to the development of hypoxemia in endotoxemic pigs and this is due in part to ventilation/perfusion inequalities.