Rosenthal R E, Chanderbhan R, Marshall G, Fiskum G
Department of Emergency Medicine, George Washington University Medical Center, Washington, D.C. 20037.
Free Radic Biol Med. 1992;12(1):29-33. doi: 10.1016/0891-5849(92)90055-l.
Hydroxyethyl starch conjugated deferoxamine (DFO) was administered to rats following resuscitation from 6.5 min cardiac arrest (CA) in an attempt to prevent the iron-catalyzed production of oxygen free radicals which may lead to neurologic injury and ultimately death following restoration of spontaneous circulation (ROSC). Brain conjugated dienes were analyzed spectrophotometrically 4 and 24 hr following ROSC, and were found to be significantly elevated when compared to non-ischemic controls. Hydroxyethyl starch-DFO treated rats demonstrated no increased conjugated diene production at either period. Neurologic injury was significantly less in drug treated rats surviving 24 or 72 hours when compared to controls. While mortality was similar in drug treated or control rats for the first 24 hours following ROSC, delayed mortality (days 1-10) was significantly less in drug treated animals, presumably as a result of neurologic protection afforded by post-ischemic drug administration. Administration of DFO conjugated to hydroxyethyl starch appears to modulate the neurologic injury which occurs during brain ischemia and reperfusion.
在大鼠经历6.5分钟心脏骤停(CA)复苏后,给予其羟乙基淀粉偶联去铁胺(DFO),以试图防止铁催化产生氧自由基,这种自由基可能导致神经损伤,并最终在自主循环恢复(ROSC)后导致死亡。在ROSC后4小时和24小时,用分光光度法分析脑共轭二烯,发现与非缺血对照组相比,其显著升高。羟乙基淀粉 - DFO处理的大鼠在这两个时间段均未表现出共轭二烯生成增加。与对照组相比,存活24小时或72小时的药物治疗大鼠的神经损伤明显减轻。虽然在ROSC后的最初24小时内,药物治疗组和对照组大鼠的死亡率相似,但药物治疗动物的延迟死亡率(第1 - 10天)明显较低,这可能是由于缺血后给药提供了神经保护作用。给予与羟乙基淀粉偶联的DFO似乎可以调节脑缺血和再灌注期间发生的神经损伤。