Grunstein M M, Grunstein J S
J Appl Physiol Respir Environ Exerc Physiol. 1982 Nov;53(5):1063-70. doi: 10.1152/jappl.1982.53.5.1063.
The respiratory responses to systemic infusion of the opioid peptide, [D-Ala2, D-Leu5]enkephalin (ENK) were determined in 39 unanesthetized tracheotomized rabbits (age range 1-20 days). At all ages, ventilation (VE), measured in a body plethysmograph, was depressed after ENK infusion in association with a decrease in CO2 elimination (VCO2) and body temperature. The degree of VE depression varied inversely with increasing age and was directly related to changes in mean inspiratory flow (i.e., VT/TI) while the ratio of inspiratory to total breath duration (TI/TT) was unaltered, except in rabbits under about 1 wk of age. Maturational differences in the VE response to ENK were related to age-dependent variation in the stability of the central inspiratory activity, which was manifested as periodic breathing with apnea in rabbits under about 5 days of age. Since the initial inspiratory volume-time profile was little affected by ENK and vagal afferent influence on respiration was not diminished, the depression in VE could be explained by an inhibition of the central inspiratory "off-switch" threshold and delay in central inspiratory "on-switching." All effects of ENK were reversed by the opiate antagonist, naloxone.
在39只未麻醉、已做气管切开术的家兔(年龄范围1 - 20天)中测定了对全身性输注阿片肽[D - Ala2,D - Leu5]脑啡肽(ENK)的呼吸反应。在所有年龄段,通过体容积描记法测量的通气量(VE)在输注ENK后均降低,同时伴有二氧化碳排出量(VCO2)和体温下降。VE降低的程度与年龄增长呈反比,且与平均吸气流量的变化直接相关(即潮气量/吸气时间),而吸气时间与总呼吸时间的比值(TI/TT)未改变,约1周龄以下的家兔除外。对ENK的VE反应的成熟差异与中枢吸气活动稳定性的年龄依赖性变化有关,这在约5日龄以下的家兔中表现为周期性呼吸伴呼吸暂停。由于初始吸气容积 - 时间曲线受ENK影响很小,且迷走神经传入对呼吸的影响未减弱,VE降低可通过中枢吸气“关闭开关”阈值的抑制和中枢吸气“开启开关”延迟来解释。ENK的所有作用均被阿片拮抗剂纳洛酮逆转。