Dynamic ventilatory responses in rats: normal development and effects of prenatal nicotine exposure

Infants of smoking mothers are at increased risk of SIDS, one cause of whic h is thought to be due to impaired ventilatory responses. We tested the hyp otheses that prenatal nicotine exposure impairs the development of dynamic carotid chemoreceptor-driven ventilatory responses, and reduces the ability to lower metabolic rate in hypoxia. Osmotic minipumps were implanted into 20 pregnant rats at day 3 of gestation to deliver nicotine (6 mg/kg per day free base) or saline for 4 weeks. Minute ventilation was recorded breath b y breath in rat pups at 3, 8 and 18 days (n = 6, 8 and 6)postnatal in respo nse to 5-sec challenges of 100% O-2 (Dejours test) and 5% O-2 + 5% CO2. Car otid sinus nerve (CSN) responses to hypoxia and CO2 were recorded from 22 c ontrol and 17 nicotine-exposed preparations at ages between 3-20 days. Oxyg en consumption ((V)over dot (O2)) was measured in groups of pups at 3 days (n = 7 each for nicotine and control) and 8 days (n = 5 each for nicotine a nd control) in room air and 10% O-2. There was no detectable effect of nico tine exposure on the development of CSN responses. Ventilatory responses to 5% O-2-5% CO2 increased with age but did not differ between nicotine and c ontrol groups. Ventilatory responses to 100% O-2 were unaffected by nicotin e exposure at 8 and 18 days. However, the 3-day nicotine group showed no si gnificant response to 100% O-2 whereas VE was significantly reduced in the control group by 100% O-2. There was no significant effect of nicotine expo sure on the ability to reduce oxygen consumption in hypoxia at 3 or 8 days, but at 3 days, baseline (room air) variability in oxygen consumption was g reater in the nicotine group. We conclude that nicotine exposure appears to result in abnormal ventilatory responses to withdrawal of baseline periphe ral chemoreceptor drive during a period of early postnatal life. We specula te that a transient abnormality could contribute to a period of instability and increased vulnerability to challenges. (C) 1999 Elsevier Science B.V. All rights reserved.