In utero cocaine exposure: effect on neonatal breathing in guinea pigs.
Cocaine (COC) abuse during pregnancy may be a factor in the development of neonatal breathing abnormalities. To examine this possibility, pregnant Dunkin-Hartley guinea pigs were treated daily with s.c. injections of saline or 2, 6 or 12 mg/kg of COC during the second half of gestation. Treatments were assigned randomly to pregnant dams. Neonatal weight, breathing, ECG and EEG were recorded in unsedated animals using noninvasive techniques at intervals for 3 weeks after birth. Neonatal weight on Day 1 was decreased by exposure to the two highest doses of COC (P less than .05). The effects of drug treatment, day of study and response to inhalation of 5% CO2 were analyzed by repeated measures analysis of variance. A significant drug-, day- and CO2-effect on tidal volume (VT) and inspiratory minute volume (VI) was observed (P less than .01). COC exposure in utero increased the weight-normalized neonatal VT and VI on room air and 5% CO2 during the first 2 weeks of life in the absence of a measurable effect of drug exposure upon breathing frequency, heart rate or EEG power. The increase in VT and VI may be caused by an increase in metabolic rate (hyperpnea) or an alteration of ventilatory control (hyperventilation). Either mechanism could represent functional teratogenesis and either results in a greater ventilatory effort which increases the work of breathing and the consumption of oxygen. An increase in oxygen demand due to an increase in metabolism or an increase in ventilatory effort might compromise some neonates and contribute to an increased incidence of sudden-infant-death.
Olsen
G D
GD
Department of Pharmacology, School of Medicine, Oregon Health Sciences University, Portland.
Weil
J A
JA
D000818:Animals; D000831:Animals, Newborn; D003042:Cocaine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004569:Electroencephalography; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007279:Injections, Subcutaneous; D008098:Litter Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012119:Respiration / Q000187:drug effects*; D013990:Tidal Volume / Q000187:drug effects
D003042:Cocaine