Prenatal Nicotine Exposure Blunts the Cardiorespiratory Response to Hypoxia in Lambs

Abstract

Because smoking during pregnancy is a major risk factor for late fetal death and the sudden infant death syndrome, we investigated cardiorespiratory defense mechanisms to hypoxia in 7 prenatally nicotine-exposed (N) lambs (approximate maternal dose: 0.5 mg/kg/day) and 11 control (C) lambs all at an average age of 5 days. The ventilatory response to 10% oxygen (hyperpnea) was significantly attenuated during quiet sleep in N lambs compared with C lambs and in N lambs aroused from sleep later compared with C lambs (161 +/- 90 versus 75 +/- 66 seconds, p < 0.05). The ventilatory response to hypoxia was similar in the two groups during wakefulness (W), whereas the heart rate response (tachycardia) was significantly lower in N lambs compared with C lambs during both activity states. The ventilatory response to hyperoxia was significantly lower in N lambs compared with C lambs during both activity states. Transition from W to quiet sleep was associated with a significant decrease in ventilation in C lambs but not in N lambs. In conclusion, prenatal nicotine exposure, at a dose comparable with moderate smoking, blunts major elements of the cardiorespiratory defense to hypoxia, i.e., the heart rate and ventilatory and arousal responses, and abolishes the normal decrease in ventilation during sleep compared with W.

Environmental tobacco smoke and sudden infant death syndrome: a review

“…Additionally, the cardiovascular response to hypoxia was lower in the exposed group. The maternal plasma level induced by this dose is lower than what is observed in pregnant habitual smokers (Hafstrom et al, 2002).…”

“…The lack of mortality at a 2 mg/kg/day dose, however, does not imply a lack of effect on developing organ systems at lower doses. Hafstrom et al (2002) observed that time from onset of hypoxia to arousal from sleep was significantly longer in exposed lambs than in controls, when nicotine exposure occurred at 0.5 mg/kg/day during the last 49 days of gestation. Additionally, the cardiovascular response to hypoxia was lower in the exposed group.…”

“…Normally, an infant's natural defense to sleep-related hypoxia includes increases in ventilation and heart rate (Hafstrom et al, 2002), followed by an episode of bradycardia, which serves to reduce metabolic demands (Schuen et al, 1997). Survival is facilitated by a series of mechanisms unique to early life, partially dependent on adrenal catecholamine secretion (Slotkin, 1998), ultimately leading to an arousal response or auto resuscitation through gasping.…”

“…They also mention that a relatively small sample size of smokers (n 5 13) may have failed to detect ventilation differences between the groups. Others have suggested the stimulatory effect of CO 2 during hypercapnic exposures may have hidden changes in ventilatory responses to hypoxia (Hafstrom et al, 2002), because subsequent studies in both infants and rat pups have shown a lack of initial tachycardia in response to hypoxia in nicotine exposed subjects (Slotkin et al, 1997;St.-John and Leiter, 1999;Ueda et al, 1999).…”

Central cholinergic regulation of respiration: nicotinic receptors

“…Prenatal nicotine exposure also delays arouse from sleep. These results suggest that prenatal nicotine exposure blunts major elements of the cardiorespiratory defense to hypoxia [112] .…”