Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Resuscitation Science Center CHOP Research Institute, Philadelphia, Pennsylvania.
Am J Physiol Cell Physiol. 2021 Aug 1;321(2):C269-C275. doi: 10.1152/ajpcell.00022.2021. Epub 2021 Jun 16.
Carbon monoxide (CO) is an odorless and colorless gas with multiple sources that include engine exhaust, faulty furnaces, and other sources of incomplete combustion of carbon compounds such as house fires. The most serious complications for survivors of consequential CO exposure are persistent neurological sequelae occurring in up to 50% of patients. CO inhibits mitochondrial respiration by specifically binding to the heme a in the active site of CIV-like hydrogen sulfide, cyanide, and phosphides. Although hyperbaric oxygen remains the cornerstone for treatment, it has variable efficacy requiring new approaches to treatment. There is a paucity of cellular-based therapies in the area of CO poisoning, and there have been recent advancements that include antioxidants and a mitochondrial substrate prodrug. The succinate prodrugs derived from chemical modification of succinate are endeavored to enhance delivery of succinate to cells, increasing uptake of succinate into the mitochondria, and providing metabolic support for cells. The therapeutic intervention of succinate prodrugs is thus potentially applicable to patients with CO poisoning via metabolic support for fuel oxidation and possibly improving efficacy of HBO therapy.
一氧化碳（CO）是一种无味无色的气体，其来源包括发动机尾气、故障熔炉以及其他含碳化合物不完全燃烧的来源，如房屋火灾。CO 暴露后果最严重的并发症是多达 50%的患者出现持续的神经后遗症。CO 通过特异性结合 CIV 样硫化氢、氰化物和膦化物活性部位的血红素 a 来抑制线粒体呼吸。尽管高压氧仍然是治疗的基石，但它的疗效存在变异性，需要新的治疗方法。在 CO 中毒领域，细胞治疗的方法很少，最近的进展包括抗氧化剂和线粒体底物前药。通过琥珀酸的化学修饰衍生的琥珀酸前药旨在增强琥珀酸向细胞的递送，增加琥珀酸进入线粒体的摄取，并为细胞提供代谢支持。琥珀酸前药的治疗干预因此可能适用于 CO 中毒患者，通过为燃料氧化提供代谢支持，可能提高 HBO 治疗的疗效。
