Fewell J E, Smith F G, Ng V K
Department of Physiology and Biophysics, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1.
J Appl Physiol (1985). 2001 May;90(5):1968-76. doi: 10.1152/jappl.2001.90.5.1968.
Experiments were carried out to determine the threshold level of maternal nicotine that impairs protective responses of rat pups to hypoxia. From days 6 or 7 of gestation, pregnant rats received either vehicle or nicotine (1.50, 3.00, or 6.00 mg of nicotine tartrate. kg body wt(-1).day(-1)) or vehicle continuously via a subcutaneous osmotic minipump. On postnatal days 5 or 6, pups were exposed to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N(2) or 3% CO(2)) and their time to last gasp was determined, or they were exposed to intermittent hypoxia and their ability to autoresuscitate from hypoxic-induced primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp or the total number of gasps when the pups were exposed to a single period of hypoxia. The number of successful autoresuscitations on repeated exposure to hypoxia was, however, decreased in pups whose dams had received either 3.00 or 6.00 mg of nicotine tartrate/kg body wt; these dosage regimens produced maternal serum nicotine concentrations of 19 +/- 6 and 35 +/- 8 ng/ml, respectively. Thus our experiments define the threshold level of maternal nicotine that significantly impairs protective responses of 5- to 6-day-old rat pups to intermittent hypoxia such as may occur in human infants during episodes of prolonged sleep apnea or positional asphyxia.
开展了多项实验以确定损害幼鼠对缺氧保护反应的母体尼古丁阈值水平。从妊娠第6天或第7天起，怀孕大鼠通过皮下渗透微型泵持续接受溶剂对照、尼古丁（1.50、3.00或6.00mg酒石酸尼古丁·kg体重⁻¹·天⁻¹）或溶剂对照。在出生后第5天或第6天，幼鼠暴露于通过呼吸缺氧气体混合物（97%N₂或3%CO₂）产生的单次缺氧环境中，并测定其至最后喘息的时间，或者使其暴露于间歇性缺氧环境中，并测定其从缺氧诱导的原发性呼吸暂停中自动复苏的能力。围产期暴露于尼古丁并未改变幼鼠在单次缺氧时的至最后喘息时间或喘息总数。然而，其母鼠接受了3.00或6.00mg酒石酸尼古丁/kg体重的幼鼠，在重复暴露于缺氧时成功自动复苏的次数减少；这些给药方案分别使母体血清尼古丁浓度达到19±6和35±8ng/ml。因此，我们的实验确定了母体尼古丁的阈值水平，该阈值会显著损害5至6日龄幼鼠对间歇性缺氧的保护反应，而这种情况可能发生在人类婴儿长时间睡眠呼吸暂停或体位性窒息发作期间。
