Wang Jianpu, Oldner Anders, Winskog Calle, Edston Erik, Walther Sten M
Centre for Teaching and Research in Disaster Medicine and Traumatology, University of Linköping, Linköping, Sweden.
Crit Care Med. 2006 Jun;34(6):1731-7. doi: 10.1097/01.CCM.0000218815.46611.63.
To test the hypothesis that the endothelin system is involved in chlorine gas-induced lung injury.
Experimental study.
Academic research laboratory.
Twenty-four domestic juvenile pigs.
Anesthetized, ventilated pigs were exposed to chlorine gas (400 parts per million in air) for 20 mins and then randomly allocated to four groups (n=6 in each group). The tezosentan pretreatment group received the dual endothelin receptor antagonist tezosentan 20 mins before and hyperoxic gas (Fio2 0.6) after chlorine gas exposure. The tezosentan postinjury treatment group received hyperoxic gas after chlorine gas exposure and tezosentan 60 mins later. Animals in the oxygen group received hyperoxic gas after chlorine gas exposure. Pigs in the fourth group (air) were ventilated with room air (Fio2 0.21) throughout the experiment.
Hemodynamics, gas exchange, lung mechanics, and plasma endothelin-1 were evaluated for 6 hrs. Chlorine gas exposure induced an increase in circulating endothelin-1 by 90% (p<.05). The acute chlorine gas-induced rise in pulmonary vascular resistance was partly blocked by tezosentan pretreatment (p<.001). Tezosentan postinjury treatment also decreased pulmonary vascular resistance to levels significantly lower than in the air and oxygen groups (p<.001). Recovery of peak airway pressure was better in the tezosentan-treated groups than in the air group. There were significant linear relationships between circulating endothelin-1 and pulmonary vascular resistance (r=.47, p<.001) and endothelin-1 and peak airway pressure (r=.41, p<.001). These relationships were modified by tezosentan.
Tezosentan modified chlorine gas-induced pulmonary dysfunction, indicating that the endothelin system is involved in this mode of acute lung injury.
验证内皮素系统参与氯气所致肺损伤这一假说。
实验研究。
学术研究实验室。
24头家猪幼崽。
对麻醉并通气的猪暴露于氯气（空气中百万分之400）20分钟，然后随机分为四组（每组n = 6）。替唑生坦预处理组在氯气暴露前20分钟接受双重内皮素受体拮抗剂替唑生坦，并在氯气暴露后接受高氧气体（Fio2 0.6）。替唑生坦损伤后治疗组在氯气暴露后接受高氧气体，并在60分钟后接受替唑生坦。氧气组动物在氯气暴露后接受高氧气体。第四组（空气组）猪在整个实验过程中用室内空气（Fio2 0.21）通气。
评估血流动力学、气体交换、肺力学和血浆内皮素-1达6小时。氯气暴露使循环内皮素-1增加90%（p <.05）。替唑生坦预处理部分阻断了急性氯气诱导的肺血管阻力升高（p <.001）。替唑生坦损伤后治疗也使肺血管阻力降至显著低于空气组和氧气组的水平（p <.001）。替唑生坦治疗组的气道峰值压力恢复情况优于空气组。循环内皮素-1与肺血管阻力之间存在显著线性关系（r =.47，p <.001），内皮素-1与气道峰值压力之间也存在显著线性关系（r =.41，p <.001）。这些关系因替唑生坦而改变。
替唑生坦改善了氯气诱导的肺功能障碍，表明内皮素系统参与了这种急性肺损伤模式。
