Toyofuku T, Koyama S, Kobayashi T, Kusama S, Ueda G
First Department of Internal Medicine, Sinshu University School of Medicine, Nagano, Japan.
J Clin Invest. 1989 Jun;83(6):2063-9. doi: 10.1172/JCI114117.
The role of charged sites on the permeability characteristics of the pulmonary microvascular barrier were investigated using chronically instrumented unanesthetized sheep. In one series of experiments we studied the effects of the cationic amphiphile, dodecyl trimethylamine (DTA; 297 mol wt), and the anionic amphiphile, SDS (288 mol wt), on lung lymph flow rates (Ql), lung lymph to plasma protein ratios (L/P), pulmonary hemodynamics, and systemic hemodynamics. DTA significantly increased both Ql and L/P, whereas SDS had a more modest and transient effect on these variables. In a second series of experiments the polycations polybrene and poly-l-lysine were found to have very similar effects as those of DTA. In another series of experiments we tested the pretreatment inhibition potential of chlorpheniramine (an H1 receptor antagonist), dibutyryl-cyclic AMP (db-cAMP), and the calcium channel antagonists verapamil and nifedipine on polybrene-induced lung injury. We found that only verapamil and db-cAMP significantly attenuated the permeability effects of polybrene. We conclude that both cationic amphiphiles and polycations cause hemodynamic and permeability alterations in the pulmonary circulation of unanesthetized sheep. In addition, the permeability alterations induced by polybrene can be modulated by intracellular calcium and/or cAMP levels.
使用长期植入仪器的未麻醉绵羊，研究了带电位点对肺微血管屏障通透性特征的作用。在一系列实验中，我们研究了阳离子两亲物十二烷基三甲基胺（DTA；分子量297）和阴离子两亲物十二烷基硫酸钠（SDS；分子量288）对肺淋巴流速（Ql）、肺淋巴与血浆蛋白比率（L/P）、肺血流动力学和全身血流动力学的影响。DTA显著增加了Ql和L/P，而SDS对这些变量的影响较为适度且短暂。在第二系列实验中，发现聚阳离子多聚溴化乙锭和聚-L-赖氨酸与DTA具有非常相似的作用。在另一系列实验中，我们测试了氯苯那敏（一种H1受体拮抗剂）、二丁酰环磷腺苷（db-cAMP）以及钙通道拮抗剂维拉帕米和硝苯地平对多聚溴化乙锭诱导的肺损伤的预处理抑制潜力。我们发现只有维拉帕米和db-cAMP能显著减轻多聚溴化乙锭的通透性作用。我们得出结论，阳离子两亲物和聚阳离子都会导致未麻醉绵羊肺循环中的血流动力学和通透性改变。此外，多聚溴化乙锭诱导的通透性改变可通过细胞内钙和/或cAMP水平进行调节。
