Effects of prenatal cocaine on the ventilatory response to hypoxia in newborn rabbits

Recently, investigators have reported an alteration of postnatal respiratory pattern, deficient hypoxic arousal from sleep, and an increased incidence of sudden infant death syndrome (SIDS) among human infants exposed to cocaine prenatally, thus suggesting that prenatal cocaine exposure may perturb the maturation of respiratory control thereby increasing the risk for SIDS. To investigate the effects of prenatal cocaine on postnatal respiration, we evaluated the ventilatory response to 0.21 F(I)O₂ (baseline) and at 0.15, 0.10, and 0.08 F(I)O₂ by the barometric method on days 4-5 of life in 23 New Zealand White rabbit pups born to cocaine-exposed (30 mg/kg/day of cocaine HCl by continuous subcutaneous infusion), pair-fed and free-fed does. The chamber pressure deflection (proportional to V(T) after appropriate calculation) was computer-sampled at 200 Hz when the unanesthetized pups were resting quietly with no gross body movements. Recording was made after 10 min acclimatization to a specific F(I)O₂. We found that baseline ventilation did not differ significantly among study groups. However, minute ventilation (V̇(I)) inspiratory flow (V(T)/T(I)), tidal volume (V(T)) increased significantly with hypoxia to peak values at 0.08 F(I)O₂ in pair-fed and free-fed pups but these measurements did not increase significantly in cocaine-exposed pups. Our finding of a deficient second phase of the hypoxic ventilatory response among cocaine-exposed pups supports the hypothesis that prenatal cocaine perturbs the maturation of respiratory control. It is likely that manipulation of dose, gestational timing, and route of prenatal cocaine exposure in an animal model will provide a useful tool to probe the maturation of control of breathing and potentially the pathogenic origin of SIDS.