Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine
Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine
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DOI：
10.1097/01.ccm.0000201403.70636.0f
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发表时间：
2006-03-01
影响因子：
8.8
通讯作者：
Matthay, MA
中科院分区：
文献类型：
--
作者：
Sakuma, T;Gu, X;Matthay, MA
目标。由于几项实验研究表明，β -肾上腺素能受体激活后产生的环腺苷一磷酸可以显著刺激肺泡液的清除，我们确定急性肺损伤患者肺水肿液和血浆中内源性儿茶酚胺的水平是否高到足以刺激肺泡液的清除。设计：观察性临床研究。学术大学医院和实验室。患者：急性肺水肿加离体人肺21例。患者样本中儿茶酚胺水平的测量和这些儿茶酚胺水平对离体人肺肺泡液清除率影响的对照实验室研究。测量和主要结果。静压性肺水肿（n = 6）和急性肺损伤（n = 15）患者肺水肿液和血浆中肾上腺素和去甲肾上腺素的浓度与10(-9)M（范围1-8 × 10(-9) M）相似。因此，我们测试了10(-9)M肾上腺素或去甲肾上腺素是否刺激离体人肺的肺泡液清除，发现这些肾上腺素或去甲肾上腺素浓度不刺激肺泡液清除。然而，较高浓度的肾上腺素（10(-7)M），而不是去甲肾上腺素（10(-7)M），显著刺激肺泡液清除率比对照组高84%。囊性纤维化跨膜传导调节抑制剂格列本脲（10(-5)M）和CFTR(inh)-172 （10(-5) M）完全抑制肾上腺素诱导的肺泡液清除刺激。这些结果表明肺水肿液中内源性儿茶酚胺浓度可能不足以刺激肺泡液清除。相比之下，外源性儿茶酚胺进入远端空气空间可以刺激人肺的肺泡液清除，这种作用部分是由囊性纤维化跨膜传导调节剂介导的。因此，可能需要外源性单磷酸环腺苷依赖性刺激来加速肺水肿患者肺部肺泡水肿的消退。
Objectives. Because several experimental studies have demonstrated that cyclic adenosine monophosphate generation following beta-adrenoceptor activation can markedly stimulate alveolar fluid clearance, we determined whether the endogenous levels of catecholamines that occur in the pulmonary edema fluid and plasma of patients with acute lung injury are high enough to stimulate alveolar fluid clearance in the human lung.Design: Observational clinical Study.Setting. Academic university hospital and laboratory.Patients: Twenty-one patients with acute pulmonary edema plus ex vivo human lungs.Interventions. Measurements of catecholamine levels in patient samples and controlled laboratory studies of the effects of these catecholamine levels on the rates of alveolar fluid clearance in ex vivo human lungs.Measurements and Main Results. The concentrations of both epinephrine and norepinephrine in the pulmonary edema fluid and plasma were similar to 10(-9) M (range of 1-8 x 10(-9) M) in hydrostatic pulmonary edema (n = 6) and acute lung injury patients (n = 15). We therefore tested whether 10(-9) M epinephrine or norepinephrine stimulated alveolar fluid clearance in isolated human lungs and found that these epinephrine or norepinephrine concentrations did not stimulate alveolar fluid clearance. However, higher concentrations of epinephrine (10(-7) M), but not norepinephrine (10(-7) M), significantly stimulated alveolar fluid clearance by 84% above control. Glibenclamide (10(-5) M) and CFTR(inh)-172 (10(-5) M), cystic fibrosis transmembrane conductance regulator inhibitors, completely inhibited the epinephrine-induced stimulation of alveolar fluid clearance.Conclusions. These results indicate that endogenous catecholamine concentrations in pulmonary edema fluid are probably not sufficient to stimulate alveolar fluid clearance. In contrast, administration of exogenous catecholamines into the distal airspaces can stimulate alveolar fluid clearance in the human lung, an effect that is mediated in part by cystic fibrosis transmembrane conductance regulator. Therefore, exogenous cyclic adenosine monophosphate-dependent stimulation will probably be required to accelerate the resolution of alveolar edema in the lungs of patients with pulmonary edema.