• Critical care medicine · Jul 2016

    Alda-1 Attenuates Lung Ischemia-Reperfusion Injury by Reducing 4-Hydroxy-2-Nonenal in Alveolar Epithelial Cells.

    • Jie Ding, Quanyi Zhang, Qipeng Luo, Yongquan Ying, Yiwei Liu, Yinan Li, Wei Wei, Fuxia Yan, and Hao Zhang.
    • 1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 2Departmen... more t of Anesthesiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3Department of Surgery and Center for Pediatric Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. less
    • Crit. Care Med. 2016 Jul 1; 44 (7): e544-52.

    ObjectivesExcessive oxidative stress is a main cause of lung ischemia-reperfusion injury, which often results in respiratory insufficiency after open-heart surgery for a cardiopulmonary bypass. Previous studies demonstrate that the activation of aldehyde dehydrogenase-2 could significantly reduce the oxidative stress mediated by toxic aldehydes and attenuate cardiac and cerebral ischemia-reperfusion injury. However, both the involvement of aldehydes and the protective effect of the aldehyde dehydrogenase-2 agonist, Alda-1, in lung ischemia-reperfusion injury remain unknown.DesignProspective laboratory and animal investigation were conducted.SettingState Key Laboratory of Cardiovascular Disease.SubjectsPrimary human pulmonary alveolar epithelial cells, human pulmonary microvascular endothelial cells, and Sprague-Dawley rats.InterventionsA hypoxia/reoxygenation cell-culture model of human pulmonary alveolar epithelial cell, human pulmonary microvascular endothelial cell, and an isolated-perfused lung model were applied to mimic lung ischemia-reperfusion injury. We evaluated the effects of Alda-1 on aldehyde dehydrogenase-2 quantity and activity, on aldehyde levels and pulmonary protection.Measurements And Main ResultsWe have demonstrated that ischemia-reperfusion-induced pulmonary injury concomitantly induced aldehydes accumulation in human pulmonary alveolar epithelial cells and lung tissues, but not in human pulmonary microvascular endothelial cells. Moreover, Alda-1 pretreatment significantly elevated aldehyde dehydrogenase-2 activity, increased surfactant-associated protein C, and attenuated elevation of 4-hydroxy-2-nonenal, apoptosis, intercellular adhesion molecule-1, inflammatory response, and the permeability of pulmonary alveolar capillary barrier, thus alleviated injury.ConclusionsOur study indicates that the accumulation of 4-hydroxy-2-nonenal plays an important role in lung ischemia-reperfusion injury. Alda-1 pretreatment can attenuate lung ischemia-reperfusion injury, possibly through the activation of aldehyde dehydrogenase-2, which in turn removes 4-hydroxy-2-nonenal in human pulmonary alveolar epithelial cells. Alda-1 pretreatment has clinical implications to protect lungs during cardiopulmonary bypass.

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