Perinatal nicotine exposure. Effects on the defense against hypoxia in lambs

The aim of the present study was to evaluate whether perinatal nicotine exposure could impair cardiorespiratory defense mechanisms to hypoxia. The rationale for this approach is that exposure to tobacco smoke, particularly before birth, is a risk factor for the sudden infant death syndrome as well as for obstructive airway disease in childhood. Chronically instrumented lambs were studied unanesthetized after birth. Ventilatory and cardiovascular variables were recorded in normoxia, acute hypoxia (0.1 FiO2) and brief hyperoxia (1.0 FiO2) in wakefulness (W) and quiet sleep (QS). Time from start of hypoxia to arousal from QS and hemoglobin oxygen saturation (SaO2) at arousal was measured.Arousal from QS was delayed during a low dose postnatal nicotine infusion (N) compared with control (C) and occurred at lower SaO2. The ventilatory response to hypoxia was similar during N and C in W, but was attenuated during N in QS. The blood pressure (BP) and heart rate (HR) responses to hypoxia were similar during N and C.Effects of prenatal nicotine (pN) exposure were studied in lambs exposed to a low dose of nicotine during the last trimester of pregnancy and compared with C. The ventilatory response to hypoxia was similar in the two groups during W, but was attenuated in pN lambs during QS. Arousal occurred later in pN lambs than C. The HR response to hypoxia was attenuated in pN lambs during both W and QS. The ventilatory response to hyperoxia was attenuated in pN lambs during both activity states. C lambs had lower resting minute ventilation ( ) during QS compared with W, whereas N lambs had similar resting during W and QS.Prenatally nicotine-exposed lambs (pN) had similar resting as C but a markedly different breathing pattern. At both 5 and 21 d of age, pN lambs had lower resting tidal volumes (VT) and higher respiratory rates than C. Inspiratory drive (P0.1) and effective impedance were higher in pN lambs compared with C only at 5 d of age. Combined pre- and postnatal nicotine exposure (ppN) had no significant effect compared with prenatal (pN) exposure alone on resting , resting P0.1 or resting effective impedance during both W and QS. Resting VT was significantly higher in ppN lambs than pN lambs during both W and QS. The ventilatory response to hypoxia and hyperoxia was similar in the two groups during both activity states. Time to arousal from QS was similar in the two groups. Resting HR and BP as well as HR and BP responses to hypoxia were similar in both groups during both activity states. Conclusions. Perinatal nicotine exposure blunts cardiorespiratory and arousal responses to acute hypoxia. These effects may be due to attenuation of carotid body oxygen chemoreceptors or the central respiratory integration of their input. Prenatal nicotine exposure affects postnatal breathing pattern indicating altered lung mechanics. Continued postnatal nicotine exposure after prenatal exposure does not further compromise defense mechanisms against hypoxia or the altered breathing pattern after birth. Nicotine substitution may not be safe during pregnancy