Clinically relevant concentrations of β2-adrenergic agonists stimulate maximal cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease pulmonary edema in experimental acid-induced lung injury
Clinically relevant concentrations of β2-adrenergic agonists stimulate maximal cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease pulmonary edema in experimental acid-induced lung injury
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DOI：
10.1097/01.ccm.0000129489.34416.0e
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发表时间：
2004-07-01
影响因子：
8.8
通讯作者：
Matthay, MA
中科院分区：
文献类型：
--
作者：
McAuley, DF;Frank, JA;Matthay, MA
目的：确定临床相关的 β(2)-肾上腺素能激动剂空腔浓度是否刺激最大肺泡液清除率，并确定 β(2) 激动剂治疗是否减少实验性急性肺损伤中的肺水肿。设计：前瞻性随机实验室研究。设置。大学附属实验室。科目。 Sprague Dawley 大鼠。干预：正常大鼠肺中的二丁酰环腺苷 (cAMP)、沙美特罗、沙丁胺醇和异丙肾上腺素。沙美特罗在酸诱导肺损伤大鼠模型中的作用。测量和主要结果。基础肺泡液清除率为 7.6 +/- 2.2 %/小时。最大 cAMP 依赖性肺泡液清除率为 32.9 +/- 10.9 %/小时 (p < .05)。外消旋沙丁胺醇10(-5)M、沙美特罗10(-6)M和异丙肾上腺素10(-6)M均刺激肺泡液清除率达到与最大cAMP依赖性肺泡液清除率相当的水平。与基础率相比，外消旋沙丁胺醇 10(-6)M (14.5 +/- 3.0%，p < .05) 和 R-对映异构体 10(-6)M (15.0 +/- 4.6%，p < .05) 均增加肺泡液清除率，但两组之间没有差异。肺泡内注射沙美特罗10(-6)M可减轻酸诱导的肺损伤后肺水肿的程度。沙美特罗治疗后血管外肺水仅增加至 180 +/- 30 μL，而酸损伤后 4 小时，盐水治疗的大鼠为 296 +/- 65 μL（p < .05）。在沙美特罗治疗组中，肺水的减少伴随着 4 小时时肺泡液清除率的 2.4 倍增加。酸损伤后 4 小时，肺内皮通透性（以血管外血浆当量表示）降低至 64 +/- 9 μL，而生理盐水处理的大鼠为 119 +/- 51 μL（p < .05）。 结论：β(2)-肾上腺素能激动剂的临床相关空腔浓度 a) 刺激最大 cAMP 依赖性 b) 通过增加肺泡液清除率和降低内皮通透性，减少酸吸入引起的肺损伤中的肺水肿。需要临床研究来确定β(2)-肾上腺素能激动剂是否可以改善急性肺损伤患者的预后。
Objective: To determine whether clinically relevant airspace concentrations of beta(2)-adrenergic agonists stimulated maximal alveolar fluid clearance rates and to determine whether beta(2) agonist therapy decreased pulmonary edema in experimental acute lung injury.Design: Prospective randomized laboratory investigation.Setting. University-affiliated laboratory.Subjects. Sprague Dawley rats.Interventions: Dibutyryl cyclic adenosine monophosphate (cAMP), salmeterol, albuterol, and isoproterenol in normal rat lung. Salmeterol in a rat model of acid-induced lung injury.Measurements and Main Results. Basal alveolar fluid clearance was 7.6 +/- 2.2 %/hr. Maximal cAMP-dependent alveolar fluid clearance rate was 32.9 +/- 10.9 %/hr (p < .05). Racemic albuterol 10(-5)M, salmeterol 10(-6)M, and isoproterenol 10(-6)M each stimulated alveolar fluid clearance to a level comparable to maximal cAMP-dependent alveolar fluid clearance. Compared with basal rates, alveolar fluid clearance was increased by both racemic albuterol 10(-6)M (14.5 +/- 3.0%, p < .05) and R-enantiomer 10(-6)M (15.0 +/- 4.6%, p < .05), but there was no difference between the two groups. Intra-alveolar salmeterol 10(-6)M attenuated the degree of pulmonary edema following acid-induced lung injury. Extravascular lung water increased to only 180 +/- 30 muL with salmeterol treatment, compared with 296 +/- 65 muL in saline-treated rats 4 hrs after acid injury (p < .05). This decrease in lung water was accompanied by a 2.4-fold increase in the rate of alveolar fluid clearance at 4 hrs in the salmeterol-treated group. Lung endothelial permeability, expressed as extravascular plasma equivalents, was reduced to 64 +/- 9 muL with salmeterol compared with 119 +/- 51 muL in saline-treated rats 4 hrs after acid injury (p < .05).Conclusions: Clinically relevant airspace concentrations of beta(2)-adrenergic agonists a) stimulate maximal cAMP-dependent airspace fluid clearance in normal lungs and b) reduce pulmonary edema in acid aspiration-induced lung injury by increasing alveolar fluid clearance and decreasing endothelial permeability. Clinical studies are required to determine whether beta(2)-adrenergic agonists improve outcome in patients with acute lung injury.