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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.

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Maternal smoking during pregnancy is a risk factor for sudden fetal and infant death as well as obstructive airway disease in childhood. Fetal nicotine exposure affects organ development. The aim of the present study was to investigate effects of fetal nicotine exposure on lung function in young lambs. Nine unanesthetized, awake, prenatally nicotine-exposed lambs (N) (approximate maternal dose: 0.5 mg/kg) and 12 nonexposed control lambs (C) were studied repeatedly for 5 weeks after birth using a pneumotachograph and a computerized method for breath-by-breath determinations. N and C lambs had similar minute ventilation but a markedly different breathing pattern. At both 5 and 21 days, average age, N lambs had significantly lower tidal volumes and higher respiratory rates than C lambs. Inspiratory drive (P(0.1)) and effective impedance were significantly higher in N lambs compared with C lambs only at 5 days. Prenatal nicotine exposure appears to have long-term effects on the postnatal breathing pattern, suggesting altered lung function, e.g., increased airway resistance, decreased lung compliance, or both. The increased inspiratory drive is most likely secondary to increased impedance of the respiratory system. These changes are most marked close to birth but persist during the initial postnatal period.

A decreased ability to arouse from sleep in response to arterial hypoxemia may lead to severe asphyxia and has been proposed as a mechanism of sudden infant death syndrome. Based on previous observations that nicotine exposure, a major environmental risk factor for sudden infant death syndrome, may impair hypoxic defense in neonates, we hypothesized that a short-term infusion of nicotine could impair hypoxic arousal through interference with oxygen-sensing mechanisms. Seven chronically instrumented unanesthetized lambs were studied at the age of 4.6 +/- 1.3 d during normoxia and acute hypoxia (0.1 fraction of inspired oxygen) for 5 min. Ventilation, transcutaneous Hb oxygen saturation, blood pressure, heart rate, and time to arousal were compared during a control saline infusion and during a 0.5 microg x kg(-1) x min(-1) nicotine infusion. Activity states, i.e. wakefulness and quiet sleep as well as arousal, were defined by EEG, nuchal electromyogram, and electrooculogram. Each lamb acted as its own control. Arousal from quiet sleep occurred significantly later during nicotine infusion compared with control (177 +/- 93 versus 57 +/- 41 s, p < 0.01) and at a lower transcutaneous Hb oxygen saturation (60 +/- 12 versus 79 +/- 12%, p < 0.01) (paired t test). The ventilatory response to hypoxia in wakefulness was similar during both conditions but was significantly attenuated in quiet sleep during nicotine infusion (p < 0.001, 2-way ANOVA repeated-measures design). Blood pressure and heart rate responses were similar during both conditions. These results suggest that a brief nicotine exposure blunts oxygen sensitivity in young lambs, a finding of potential relevance for sudden infant death syndrome.