Effect of endotoxin on airway responsiveness to aerosol histamine in sheep.

Effect of endotoxin on airway responsiveness to aerosol histamine in sheep.
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内毒素对绵羊气溶胶组胺气道反应性的影响。

DOI:
10.1152/jappl.1983.54.6.1463
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发表时间:
1983
期刊:
Journal of applied physiology: respiratory, environmental and exercise physiology
影响因子:
--
通讯作者:
Snapper,JR
Snapper,JR
中科院分区:
--
文献类型:
--
作者:
Hutchison,AA;HinsonJr,JM;Brigham,KL;Snapper,JR

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本研究验证了这一假设,即在清醒的绵羊中,内毒素血症会急性增加气道对气雾剂组胺的反应性。对11只绵羊进行了长期器械化,以测量肺淋巴流量、血管压力和肺力学。清醒绵羊在全身体积描记器中进行了研究,该体积描记器设计用于测量动态顺应性(Cdyn)、肺阻力(RL)和功能残气量(FRC)。通过给予5次递增浓度的组胺(0.1-50 mg/ml)呼吸,直至Cdyn降至65%(对照组)或直至给予50 mg/ml组胺,评估肺对气雾剂组胺的反应性。然后输注大肠杆菌内毒素(0.2-0.5微克/千克),并在5小时后内毒素血症肺气雾剂组胺反应性重新测量。11只绵羊中有9只在低浓度组胺作用下,内毒素后Cdyn下降(P <0.05)。将Cdyn降低至对照的65%所需的组胺对数剂量的平均值在内毒素前为1.00 +/- 0.16(SE),内毒素后5小时为0.027 +/- 0.29;即,组胺反应性增加。在最后研究的3只绵羊中,在第二次气雾组胺激发后给予阿托品(0.1 mg/kg iv),并绘制第三条剂量-反应曲线。阿托品不能使内毒素诱导的组胺反应性增加恢复到基线水平。组胺反应性的变化与内毒素诱导的Cdyn、FRC、RL、肺泡-动脉O2差、肺动脉压或肺淋巴流量的变化之间无相关性。
This study tested the hypothesis that in the awake sheep, airway responsiveness to aerosol histamine would be increased acutely by endotoxemia. Eleven sheep were chronically instrumented to allow for measurements of lung lymph flow, vascular pressures, and lung mechanics. Awake sheep were studied in a whole-body plethysmograph designed to measure dynamic compliance (Cdyn), resistance of the lung (RL), and functional residual capacity (FRC). Pulmonary responsiveness to aerosol histamine was assessed by giving five breaths of increasing concentrations of histamine (0.1–50 mg/ml) until Cdyn decreased to 65% (of control) or until 50 mg/ml of histamine had been given. Escherichia coli endotoxin (0.2–0.5 microgram/kg) was then infused, and at 5 h after endotoxemia pulmonary responsiveness to aerosol histamine was remeasured. After endotoxin, 9 of the 11 sheep exhibited decreased Cdyn at a lower concentration of histamine compared with the preendotoxin level (P less than 0.05). The mean of the log dose of histamine necessary to reduce Cdyn to 65% of control was 1.00 +/- 0.16 (SE) before endotoxin and 0.027 +/- 0.29 5 h after endotoxin; i.e., histamine responsiveness was increased. In the last 3 sheep studied, atropine (0.1 mg/kg iv) was given after the second aerosol histamine challenge, and a third dose-response curve was performed. Atropine did not return the endotoxin-induced increase in histamine responsiveness to base line. There was no correlation between the change in histamine responsiveness and the endotoxin-induced changes in Cdyn, FRC, RL, alveolar-arterial O2 difference, pulmonary arterial pressure, or lung lymph flow.