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中的肺泡液体清除有影响，以确定肺泡空间中的儿茶酚胺清除是否与大鼠和人肺的液体转运能力相关，以及内源性儿茶酚胺水平是否通过囊性纤维化跨膜传导调节因子（CFTR）刺激肺泡液清除在人的肺里。我们发现，营养不良损害了阿米洛利不敏感和双丁酰cGMP敏感的肺泡液体清除率，但这种影响是部分可逆的再喂养，谷氨酸钠治疗，或β-肾上腺素能受体激动剂治疗。前列腺素类似物不改变基础肺泡液体清除率和正常剂量的特布他林对肺泡液体清除率的影响，但在给予大剂量β_2-肾上腺素能拮抗剂后，可恢复其作为β_1-肾上腺素能拮抗剂的刺激作用。UTP和异丙肾上腺素的联合治疗使肺泡液体清除率增加了280%的基础值。UTP在存在和不存在异丙肾上腺素的情况下的影响被废除的P2嘌呤受体和氯离子通道的阻断剂。大鼠和人肺中肺泡腔中的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。在离体人肺中，外源性肾上腺素而非去甲肾上腺素通过CFTR刺激肺泡液体清除。这些研究表明，肺泡液体清除率在肺切除术后肺水肿的消退中起重要作用。对于肺切除术后暴露于肺水肿的患者，可考虑使用β-肾上腺素能受体激动剂治疗。

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.