Pittet J F, Wiener-Kronish J P, McElroy M C, Folkesson H G, Matthay M A
Cardiovascular Research Institute, University of California, San Francisco 94143.
J Clin Invest. 1994 Aug;94(2):663-71. doi: 10.1172/JCI117383.
Exogenous administration of beta-adrenergic agonists has previously been reported to increase lung liquid clearance by stimulation of active sodium transport across the alveolar epithelium. We hypothesized for this study that endogenous release of epinephrine in septic shock would stimulate liquid clearance from the airspaces in rats. Liquid clearance from the air spaces was measured by the concentration of protein over 4 h in a test solution of 5% albumin instilled into one lung. Bacteremic rats developed severe systemic hypotension and metabolic acidosis that was associated with a 100-fold rise in plasma epinephrine levels. There was a 100% increase in liquid clearance from the airspaces of the lung in the bacteremic compared with control rats. To determine the mechanisms responsible for this accelerated lung liquid clearance, amiloride (10(-3) M), a sodium transport inhibitor, was added to the air spaces. Amiloride prevented the increase in liquid clearance from the airspaces, indicating that this effect depended on increased uptake of sodium across the lung epithelium. The addition of propranolol (10(-4) or 10(-5) M) to the instillate also prevented the acceleration in alveolar liquid clearance in the bacteremic rats. We conclude that the release of endogenous catecholamines associated with septic shock markedly stimulates fluid clearance from the distal airspaces of the lung by a beta-adrenergic mediated stimulation of active sodium transport across the epithelial barrier. This data provides evidence for a previously unrecognized mechanism that can protect against or hasten the resolution of alveolar edema in pathological conditions, such as septic shock, that are associated with the endogenous release of catecholamines.
先前有报道称，外源性给予β-肾上腺素能激动剂可通过刺激钠主动转运穿过肺泡上皮来增加肺液清除率。我们在本研究中推测，脓毒性休克时内源性肾上腺素的释放会刺激大鼠气腔内的液体清除。通过向一侧肺内注入5%白蛋白测试溶液，在4小时内测定蛋白质浓度来测量气腔内的液体清除情况。菌血症大鼠出现严重的全身性低血压和代谢性酸中毒，同时血浆肾上腺素水平升高100倍。与对照大鼠相比，菌血症大鼠肺气腔内的液体清除率增加了100%。为了确定导致这种肺液清除加速的机制，将钠转运抑制剂氨氯地平（10⁻³ M）加入气腔。氨氯地平可阻止气腔内液体清除率的增加，表明这种效应依赖于钠跨肺上皮摄取的增加。向注入液中加入普萘洛尔（10⁻⁴或10⁻⁵ M）也可阻止菌血症大鼠肺泡液体清除的加速。我们得出结论，脓毒性休克相关内源性儿茶酚胺的释放通过β-肾上腺素能介导刺激钠主动转运穿过上皮屏障，显著刺激了肺远端气腔内的液体清除。该数据为一种先前未被认识的机制提供了证据，该机制可在与内源性儿茶酚胺释放相关的病理状况（如脓毒性休克）中预防或加速肺泡水肿的消退。
