Konduri G G, Fewell J E
Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan 48201.
Pediatr Res. 1992 Aug;32(2):222-5. doi: 10.1203/00006450-199208000-00019.
Experiments were done to determine if endogenous opiates cause the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs. Five lambs were anesthetized and instrumented for sleep staging and measurement of arterial Hb oxygen saturation. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing 5% oxygen. The experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen, once the lamb aroused from sleep. After each lamb had been exposed to 5% oxygen during 100 consecutive epochs of sleep, naloxone--an opiate antagonist--was given i.v. in a dose of 3 mg/kg as a bolus. The animals continued to be exposed to 5% oxygen during six more epochs of sleep after the administration of naloxone. Arousal occurred from both sleep states during rapidly developing hypoxemia but was delayed in active sleep compared to quiet sleep. The arterial Hb oxygen saturation at arousal was significantly lower, and the time to arousal was significantly longer with repeated exposure to hypoxemia during both quiet sleep and active sleep. Naloxone did not alter this arousal response decrement to hypoxemia. Thus, our data provide evidence that endogenous opiates do not play a major role in causing the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs.
开展实验以确定内源性阿片类物质是否会导致羔羊在睡眠期间反复暴露于低氧血症后出现觉醒反应减弱。对5只羔羊进行麻醉,并安装用于睡眠分期和测量动脉血红蛋白氧饱和度的仪器。术后不早于3天,在对照期(此时羔羊呼吸21%氧气)和实验期(此时羔羊呼吸5%氧气)的安静睡眠和主动睡眠期间进行测量。一旦羔羊从睡眠中醒来,在每个时间段通过将吸入气体混合物改回21%氧气来终止实验期。在每只羔羊连续100个睡眠时间段暴露于5%氧气后,静脉注射一剂3 mg/kg的阿片类拮抗剂纳洛酮。给药后,动物在另外6个睡眠时间段继续暴露于5%氧气。在快速发展的低氧血症期间,两种睡眠状态均会出现觉醒,但与安静睡眠相比,主动睡眠中的觉醒延迟。在安静睡眠和主动睡眠期间,反复暴露于低氧血症后,觉醒时的动脉血红蛋白氧饱和度显著降低,觉醒时间显著延长。纳洛酮并未改变这种对低氧血症的觉醒反应减弱。因此,我们的数据表明,内源性阿片类物质在导致羔羊睡眠期间反复暴露于低氧血症后出现的觉醒反应减弱中并不起主要作用。