N-ACETYLCYSTEINE IN EXPERIMENTAL AND CLINICAL ACUTE LUNG INJURY
N-ACETYLCYSTEINE IN EXPERIMENTAL AND CLINICAL ACUTE LUNG INJURY
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DOI：
10.1016/0002-9343(91)90284-5
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发表时间：
1991-09-30
影响因子：
5.9
通讯作者：
BERNARD, GR
中科院分区：
文献类型：
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作者：
BERNARD, GR
在临床上，肺损伤表现为以下一种或多种特征：气体交换改变、呼吸困难、静态顺应性降低和非流体静力性肺水肿。尽管许多抗氧化剂已经在体外系统和动物模型中进行了研究，但只有一些抗氧化剂处于发育阶段，或者可以安全用于临床试验。最近积累的大量证据支持白细胞激活涉及大量高活性氧自由基释放的假设，过氧化氢是脓毒症患者弥漫性微血管和组织损伤的部分原因。动物模型中的粒细胞耗竭降低了动态肺顺应性下降的程度，以及内毒素给药引起的气流阻力、淋巴流量和低氧血症的增加。我们假设，从粒细胞消耗中获得的部分益处是由于有效去除氧自由基的主要来源。在自由基清除剂的列表中，n -乙酰半胱氨酸脱颖而出，因为它在至少一种被认为是由自由基器官损伤继发的人类疾病（对乙酰氨基酚或扑热息痛过量）中已被证实有用。它是一种非常安全的药物，具有广泛的毒性治疗窗口。越来越多的动物研究表明，该药物在预防和治疗涉及有毒氧的肺损伤方面具有疗效。我们制定了一项随机双盲方案，用于研究已确定的成人呼吸窘迫综合征（ADRS）患者静脉注射n -乙酰半胱氨酸。这项试验的结果是初步的。然而，他们表明，血浆和红细胞谷胱甘肽水平在ADRS患者中降低，n -乙酰半胱氨酸增加血浆半胱氨酸以及血浆和红细胞谷胱甘肽。也有迹象表明，这种治疗对心肺生理学有良好的影响，包括胸片水肿评分、肺血管阻力、静态顺应性、氧气输送和氧气消耗的改善。
Clinically, lung injury is characterized by one or more of the following: altered gas exchange, dyspnea, decreased static compliance, and nonhydrostatic pulmonary edema. Although many antioxidants have been investigated in in vitro systems and in animal models, only some are at the developmental stage, or safe for clinical trials. Considerable evidence has recently accumulated supporting the hypothesis that leukocyte activation involves release of large quantities of highly reactive oxygen radicals, and hydrogen peroxide is partially responsible for diffuse microvascular and tissue injury in septic patients. Granulocyte depletion in animal models reduces the degree of fall in dynamic lung compliance and the increase in airflow resistance, lymph flow, and hypoxemia secondary to endotoxin administration. We hypothesized that the partial benefit derived from granulocyte depletion was due to the effective removal of a major source of oxygen radicals. Among the list of free radical scavengers, N-acetylcysteine stands out, because of its established usefulness in at least one human disease thought to be secondary to free radical organ damage (acetaminophen or paracetamol overdose). It is an extremely safe agent with a wide toxic-therapeutic window. An increasing number of animal studies indicate efficacy for this agent in the prevention and therapy of lung injury involving toxic oxygen species. We developed a randomized, double-blind protocol for the study of intravenous N-acetylcysteine in patients with established adult respiratory distress syndrome (ADRS). Results of this trial are preliminary. Nevertheless, they indicate that plasma and red cell glutathione levels are decreased in ADRS patients, and that N-acetyl-cysteine increases plasma cysteine as well as plasma and red cell glutathione. There are also indications that cardiopulmonary physiology is favorably affected by such therapy including improvements in chest radiograph edema scores, pulmonary vascular resistance, static compliance, oxygen delivery, and oxygen consumption.