Dedhia H V, Banks D E
Department of Medicine, West Virginia University Health Science Center, Morgantown.
Environ Health Perspect. 1994 Dec;102 Suppl 10(Suppl 10):101-5. doi: 10.1289/ehp.94102s10101.
Animals and humans rapidly develop respiratory failure and die within a few days when exposed to 100% oxygen. Postmortem examination of the lungs shows histopathologic features characteristic of diffuse alveolar damage, clinically recognized as adult respiratory distress syndrome (ARDS). At the present time, there is no effective therapy available to alter outcomes in ARDS. Importantly, hypomagnesemia also is frequently observed in critically ill patients at risk of developing ARDS. In a model of hyperoxic lung injury, rats were exposed to 100% oxygen for 48, 64, and 96 hr and several experiments were performed. First, changes in the features of bronchoalveolar lavage and in alveolar macrophage function were compared in rats exposed to room air and those exposed to hyperoxia. Second, we studied the effect of hypomagnesemia on the severity of hyperoxic lung injury. Third, we evaluated the pulmonary responses to high-dose and normal-dose Mg therapy in rats exposed to hyperoxia. In all groups, hyperoxia induced significant changes in the total and differential cell counts with increased lipid peroxidation of lavaged cells, enhanced chemiluminescence from alveolar macrophages, and protein leakage into the alveolar spaces. After 48 hr of hyperoxia, oxygen-free radical formation and hydrogen peroxide production by the alveolar macrophage were diminished compared to baseline, implying a toxic effect of hyperoxia on the alveolar macrophages. Overall, hypomagnesemia tended to magnify the degree of hyperoxic lung injury, while high-dose Mg therapy tended to attenuate the effects of hyperoxia. In conclusion, in this animal model of diffuse alveolar damage, alterations in host serum magnesium levels may modulate the degree of lung damage.
动物和人类在暴露于100%氧气时会迅速发展为呼吸衰竭，并在几天内死亡。肺部的尸检显示出弥漫性肺泡损伤的组织病理学特征，临床上称为成人呼吸窘迫综合征（ARDS）。目前，尚无有效的治疗方法可以改变ARDS的预后。重要的是，低镁血症也经常在有发生ARDS风险的危重病患者中观察到。在高氧肺损伤模型中，将大鼠暴露于100%氧气中48、64和96小时，并进行了多项实验。首先，比较了暴露于室内空气和高氧环境的大鼠支气管肺泡灌洗特征和肺泡巨噬细胞功能的变化。其次，我们研究了低镁血症对高氧肺损伤严重程度的影响。第三，我们评估了高氧暴露大鼠对高剂量和正常剂量镁治疗的肺部反应。在所有组中，高氧均导致总细胞计数和分类细胞计数发生显著变化，灌洗细胞的脂质过氧化增加，肺泡巨噬细胞的化学发光增强，蛋白质渗漏到肺泡腔中。高氧暴露48小时后，与基线相比，肺泡巨噬细胞的氧自由基形成和过氧化氢产生减少，这意味着高氧对肺泡巨噬细胞有毒性作用。总体而言，低镁血症倾向于放大高氧肺损伤的程度，而高剂量镁治疗倾向于减轻高氧的影响。总之，在这个弥漫性肺泡损伤的动物模型中，宿主血清镁水平的改变可能会调节肺损伤的程度。
