Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.
Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.
复制标题
内毒素后，血栓素 A2 介导肺血管收缩，但不介导通透性。
DOI：
10.1172/jci111062
复制
发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Hildebrandt,J
中科院分区：
文献类型：
--
作者：
Winn,R;Harlan,J;Nadir,B;Harker,L;Hildebrandt,J
本文观察了选择性血栓素合成酶抑制剂达唑西本(Dazoxiben，Dazoxiben)对静脉注射大肠杆菌内毒素(1微克/kg)引起肺淋巴瘘的清醒山羊体循环和肺血流动力学、二十烷基类化合物和肺通透性的影响。动物接受内毒素治疗，要么不治疗，要么预先注射内毒素(25 mg/kg)，然后维持滴注达唑西苯(每小时10 mg/kg)。在未经治疗的动物中，肺动脉(PPA)26.8 cm H2O和楔压(PW)13.5 cm H2O的峰值与血浆血栓素B2(T×B2)的峰值升高同时发生。心输出量(QT)的最大下降也发生在同一时间。肺淋巴流量(QL)在此期间增加，内毒素后持续升高至少6h。TxB2水平在2小时内从13.1 ng/ml的峰值回升至0.7 ng/ml。在达唑西苯治疗的动物中，TXB2的血浆浓度从未显著升高。PPA和PW增加明显减少，QT减少是一过性的。治疗组动物的生活质量在内毒素后30min开始升高，2小时达高峰，但改善程度不如未治疗组。此外，在接受治疗的动物中，淋巴-血浆蛋白比率显著增加。两组动物血浆前列腺素(PG)F2α和6-keto-PGF1α浓度均在内毒素作用后升高，且治疗组升高更明显。我们的结论是，选择性抑制血栓素可以改善内毒素血症的许多不利血流动力学后果，但不能阻止肺通透性的改变。
The effect of dazoxiben, a selective thromboxane (Tx) synthetase inhibitor, on systemic and pulmonary hemodynamics, eicosanoids, and lung permeability was assessed in awake goats with lung lymph fistulae following infusion of Escherichia coli endotoxin (1 microgram/kg). Animals received endotoxin either with no treatment or pretreatment with a bolus (25 mg/kg) followed by a maintenance infusion (10 mg/kg per h) of dazoxiben. In untreated animals, the peak rise of 26.8 cm H2O in pulmonary artery (Ppa) and of 13.5 cm H2O in wedge (Pw) pressures occurred at the same time as the peak elevations in plasma thromboxane B2 (T X B2). Maximum reduction in cardiac output (Qt) also occurred at the same time. Lung lymph flow (QL) increased during this period and remained elevated for at least 6 h after endotoxin. T X B2 levels had returned from a peak of 13.1 to 0.7 ng/ml by 2 h. In dazoxiben-treated animals, plasma concentrations of T X B2 were never significantly elevated. Increases in Ppa and Pw were markedly reduced and decreased Qt was transient. QL in treated animals began to increase by 30 min after endotoxin and reached a peak by 2 h. Increased QL in treated animals was not as great as in the untreated animals. Moreover, lymph-plasma protein ratios increased significantly in treated animals. Plasma prostaglandin (PG)F2 alpha and 6-keto-PGF1 alpha concentrations were elevated in both groups after endotoxin with values significantly greater in treated animals. We conclude that selective inhibition of Tx ameliorates many adverse hemodynamic consequences of endotoxemia but does not prevent lung permeability changes.