Mechanisms responsible for alveolar fluid reabsorption during peri-operative period

本研究的目的是确定营养不良、选择性β-肾上腺素能激动剂和嘌呤受体是否对大鼠肺的肺泡液清除有影响，确定肺泡间隙的儿茶酚胺清除是否与大鼠和人肺的液体运输能力相关，以及内源性儿茶酚胺水平是否通过人肺囊性纤维化跨膜传导调节剂（CFTR）刺激肺泡液清除。我们发现营养不良损害了阿米洛利不敏感和二丁基cgmp敏感的肺泡液清除，但这种影响可以通过重新喂食、谷氨酸钠治疗或β-肾上腺素能激动剂治疗部分逆转。前列腺素类似物不改变基底肺泡液清除率和正常剂量特布他林对肺泡液清除率的影响，但在高剂量β_2-肾上腺素拮抗剂的作用下，恢复了β_1-肾上腺素拮抗剂在离体大鼠肺中的刺激作用。联合治疗UTP和异丙肾上腺素增加肺泡液清除率280%的基础值。在异丙肾上腺素存在和不存在的情况下，UTP的作用被P2嘌呤受体阻滞剂和氯通道所消除。大鼠和人肺泡间隙儿茶酚胺清除率与肺泡液清除率相关。水肿液中内源性儿茶酚胺浓度不足以刺激急性肺水肿的消退。外源性肾上腺素，而非去甲肾上腺素，通过体外人肺CFTR刺激肺泡液清除。这些研究表明肺泡液清除在肺切除术患者肺水肿的消退中起重要作用。在肺切除术后暴露于肺水肿的患者中，可以考虑β -肾上腺素能激动剂治疗。

The objectives of this study were to determine whether malnutrition, selective β-adrenergic agonists, and purinoceptors had effects on alveolar fluid clearance in rat lungs, to determine whether catecholamine clearance from the alveolar spaces was correlated with the fluid transport capacity of the rat and human lungs, and to whether endogenous levels of catecholamine stimulated alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator (CFTR) in human lungs. We found that malnutrition impaired amiloride-insensitive and dibutyryl cGMP-sensitive alveolar fluid clearance, but this effect was partially reversible by re-feeding, treatment with sodium glutamate, or β-adrenergic agonist therapy. Prostaglandin analogues do not change basal alveolar fluid clearance and the effect of terbutaline at normal dose on alveolar fluid clearance, but restored the stimulatory effect as a β_1-adrenergic antagonist in ex vivo rat lungs with an administration of high-dose β_2-adrenergic antagonist. A combined treatment of UTP and isoproterenol increased alveolar fluid clearance by 280% basal value. The effects of UTP in the presence and absence of isoproterenol were abolished by blockers of a P2 purinoceptor and chloride channels. Catecholamine clearance rate from the alveolar spaces is correlated with alveolar fluid clearance in the rat and human lungs. Endogenous catecholamine concentrations in edema fluid were not sufficient to stimulate the resolution of acute pulmonary edema. Exogenous epinephrine, but not norepinephrine, stimulated alveolar fluid clearance via CFTR in ex vivo human lung. These studies indicate that alveolar fluid clearance play an important role in resolution of pulmonary edema of patients who underwent pulmonary resection. Beta-adrenergic agonist therapy may be considered in a patient exposed to pulmonary edema after pulmonary resection.