Cardiorespiratory effects of nicotine exposure during development.

Exposure to tobacco smoke is a major risk factor for the sudden infant death syndrome. Nicotine is thought to be the ingredient in tobacco smoke that is responsible for a multitude of cardiorespiratory effects during development, and pre- rather than postnatal exposure is considered to be most detrimental. Nicotine interacts with endogenous acetylcholine receptors in the brain and lung, and developmental exposure produces structural changes as well as alterations in neuroregulation. Abnormalities have been described in sympathicovagal balance, arousal threshold and latency, breathing pattern at rest and apnea frequency, ventilatory response to hyperoxia or hypoxia, heart rate regulation and ability to autoresuscitate during severe hypoxia. This review discusses studies performed on infants of smoking mothers and nicotine-exposed animals yielding varying and sometimes inconsistent results that may be due to differences in experimental design, species and the dose of exposure. Taken together however, developmental nicotine exposure appears to induce vulnerability during hypoxia and a potential inability to survive severe asphyxia.

Impaired cardiorespiratory recovery after laryngeal stimulation in nicotine-exposed young lambs.

The hypothesis that postnatal nicotine exposure weakens cardiorespiratory recovery from reflex apnea and bradycardia was tested in eight lambs continuously infused with nicotine from the day of birth at a dose of 1 to 2 mg.kg(-1).d(-1). Eight age-matched lambs infused with saline served as controls. Apnea and bradycardia were elicited by laryngeal stimulation with 1 mL of water (laryngeal chemoreflex) both during air breathing [0.21 fraction of inspired oxygen (FiO(2))] and mild hypoxia (0.10 FiO(2)) at a mean postnatal age of 5 +/- 1, 14 +/- 1, and 28 +/- 1 d. Ventilation, heart rate, and blood pressure were similar in the two groups at rest. In response to laryngeal chemoreflex stimulation, nicotine-treated lambs had a more pronounced decrease in ventilation (p < 0.05), longer reflex apnea (p < 0.001 in 0.21 FiO(2); p < 0.01 in 0.10 FiO(2)), and greater reflex bradycardia (p < 0.01). During reflex apnea, sighs were less efficient in restoring heart rate to prestimulation level, and a greater decrease in heart rate was observed before sighs in nicotine-treated lambs. These effects were most apparent at 5 d of age, when nicotine-treated lambs also had lower ventilation during hypoxia (p < 0.05). The response to hyperoxia was comparable in the two groups at all ages. The ability to terminate laryngeal chemoreflex-induced apnea is attenuated in young lambs continuously exposed to nicotine. This attenuation is present both in normoxia and in hypoxia and is accompanied by reduced effects from sighing on cardiac autoresuscitation.

Prenatal nicotine exposure blunts the cardiorespiratory response to hypoxia in lambs.

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.

Altered breathing pattern after prenatal nicotine exposure in the young lamb.

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.