ABSTRACT
While perinatal nicotine effects on ventilation have been widely investigated, the prenatal impact of nicotine treatment during gestation on both breathing and neural circuits involved in respiratory control remains unknown. We examined the effects of nicotine, from embryonic day 5 (E5) to E20, on baseline ventilation, the two hypoxic ventilatory response components and in vivo tyrosine hydroxylase (TH) activity in carotid bodies and brainstem areas, assessed at postnatal day 7 (P7), P11 and P21. In pups prenatally exposed to nicotine, baseline ventilation and hypoxic ventilatory response were increased at P7 (+48%) and P11 (+46%), with increased tidal volume (p<0.05). Hypoxia blunted frequency response at P7 and revealed unstable ventilation at P11. In carotid bodies, TH activity increased by 20% at P7 and decreased by 48% at P11 (p<0.05). In most brainstem areas it was reduced by 20-33% until P11. Changes were resolved by P21. Prenatal nicotine led to postnatal ventilatory sequelae, partly resulting from impaired maturation of peripheral chemoreceptors and brainstem integrative sites.
Subject(s)
Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Prenatal Exposure Delayed Effects , Respiration/drug effects , Respiratory System , Age Factors , Animals , Animals, Newborn , Brain Chemistry/drug effects , Chromatography, High Pressure Liquid , Electrochemistry , Embryo, Mammalian , Female , Hypoxia/physiopathology , Levodopa/metabolism , Male , Pregnancy , Rats , Rats, Sprague-Dawley , Respiratory System/drug effects , Respiratory System/embryology , Respiratory System/growth & development , Tidal Volume/drug effects , Tidal Volume/physiology , Tyrosine 3-Monooxygenase/metabolismABSTRACT
PURPOSE: To investigate the effects of subchronic ozone exposure on rat lung ventilation using hyperpolarized (HP) (3)He MRI. MATERIALS AND METHODS: A total of 24 Sprague-Dawley rats, distributed in one control group and four groups exposed to 0.5 ppm ozone concentration for two days or six days, either continuously (22 hours/day) or alternatingly (12 hours/day). A three-step MRI protocol was designed and applied to each animal, including: 1) (3)He gas distribution images acquired at inspiratory capacity, 2) measurements of intrapulmonary (3)He diffusion coefficients, and 3) dynamic ventilation acquisitions performed during lung filling with (3)He. RESULTS: No differentiation between animals exposed to ozone and control animals was observed from the ventilation images obtained at inspiratory capacity. The (3)He diffusion coefficients were not statistically different from one group to another. Ventilation defects, appearing as delayed lung filling regions and heterogeneous lung filling, were observed in the dynamic lung ventilation image series. The percentage of animals with ventilation defects in the control, two-day, and six-day exposed groups were equal to 20%, 43% and 75%, respectively. In the subgroup of the animals exposed six days for 12 hours per day, the percentage of animals exhibiting ventilation defects was equal to 85%. CONCLUSION: Heterogeneous obstructive patterns in an experimental animal model of subchronic ozone exposure were observed using HP (3)He MRI.
