Hasan S U, Pinsky C, Cates D B, Nowaczyk B J, Gibson D A, Rigatto H
Department of Paediatrics, University of Manitoba, Winnipeg, Canada.
J Dev Physiol. 1990 Sep;14(3):171-9.
In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal.
在胎羊中，注射吗啡会引发呼吸暂停，随后出现呼吸急促；在呼吸急促期间，胎儿会觉醒。我们检验了这样一个假设：阿片类拮抗剂纳洛酮会阻断这些反应。在14只妊娠123至140天的胎羊中，我们测量了脑电活动（ECoG）、眼动（EOG）、膈肌活动（EMGdi）、血压和羊膜压力。在低电压脑电活动期间，将吗啡（1毫克/千克）注入胎儿颈静脉。在注射吗啡前、呼吸暂停期间吗啡注射后不久以及呼吸急促达到最大值期间，按随机顺序给予生理盐水或纳洛酮（0.1、0.5和2.0毫克）。单独使用生理盐水对呼吸或行为没有影响。当在注射吗啡前给予生理盐水和纳洛酮时，呼吸暂停的时长分别为26.6±7.7分钟和19.5±7.0分钟（标准误，P = 0.25），而持续性呼吸急促的时长分别为104.8±11.4分钟和29.6±8.4分钟（P = 0.001）。当在最大呼吸反应期间给予纳洛酮时，呼吸时长从92.2±8.4分钟（生理盐水）降至8.8±2.9分钟（P = 0.001）。呼吸输出（fEMGdi×f）也从生理盐水给药后的6545±912任意单位降至纳洛酮给药后的3841±629任意单位（P = 0.05）。随着呼吸反应的减弱，觉醒消失。纳洛酮对呼吸暂停的影响可忽略不计，而对呼吸急促有强烈抑制作用，这表明吗啡可能作用于两个不同的中枢区域或两种阿片受体亚型，从而产生呼吸暂停、呼吸急促和觉醒。
