Development of the ventilatory response to hypoxia in Swiss CD-1 mice

We examined developmental changes in breathing pattern and the ventilatory response to hypoxia (7.4% O₂) in unanesthetized Swiss CD-1 mice ranging in age from postnatal day O to 42 (P₀-P₄₂) using head-out plethysmography. The breathing pattern of P₀ mice was unstable. Apneas were frequent at P₀ (occupying 29 ± 6% of total time) but rare by P₃ (5 ± 2% of total time). Tidal volume increased in proportion to body mass (~10-13 ml/kg), but increases in respiratory frequency (f) (55 ± 7, 130 ± 13, and 207 ± 20 cycles/min for P₀, P₃, and P₄₂, respectively) were responsible for developmental increases in minute ventilation (690 ± 90, 1,530 ± 250, and 2,170 ± 430 ml⋅min⁻¹⋅kg⁻¹ for P₀, P₃, and P₄₂, respectively). Between P₀ and P₃, increases in f were mediated by reductions in apnea and inspiratory and expiratory times; beyond P₃ increases were due to reductions in expiratory time. Mice of all ages showed a biphasic hypoxic ventilatory response, which differed in two respects from the response typical of most mammals. First, the initial hyperpnea, which was greatest in mature animals, decreased developmentally from a maximum, relative to control, of 2.58 ± 0.29 in P₀ mice to 1.32 ± 0.09 in P₄₂ mice. Second, whereas ventilation typically falls to or below control in most neonatal mammals, ventilation remained elevated relative to control throughout the hypoxic exposure in P₀ (1.73 ± 0.31), P₃ (1.64 ± 0.29) and P₉ (1.34 ± 0.17) mice but not in P₁₉ or P₄₂ mice.8 page(s

Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of hypoglossal inspiratory output in mice

We examined the effects of in utero nicotine exposure on postnatal development of breathing pattern and ventilatory responses to hypoxia (7.4 % O2) using whole-body plethysmography in mice at postnatal day 0 (P0), P3, P9, P19 and P42. Nicotine delayed early postnatal changes in breathing pattern. During normoxia, control and nicotine-exposed P0 mice exhibited a high frequency of apnoea (fA) which declined by P3 in control animals (from 6.7 ± 0.7 to 2.2 ± 0.7 min−1) but persisted in P3 nicotine-exposed animals (5.4 ± 1.3 min−1). Hypoxia induced a rapid and sustained reduction in fA except in P0 nicotine-exposed animals where it fell initially and then increased throughout the hypoxic period. During recovery, fA increased above control levels in both groups at P0. By P3 this increase was reduced in control but persisted in nicotine-exposed animals. To examine the origin of differences in respiratory behaviour, we compared the activity of hypoglossal (XII) nerves and motoneurons in medullary slice preparations. The frequency and variability of the respiratory rhythm and the envelope of inspiratory activity in XII nerves and motoneurons were indistinguishable between control and nicotine-exposed animals. Activation of postsynaptic nicotine receptors caused an inward current in XII motoneurons that potentiated XII nerve burst amplitude by 25 ± 5 % in control but only 14 ± 3 % in nicotine-exposed animals. Increased apnoea following nicotine exposure does not appear to reflect changes in basal activity of rhythm or pattern-generating networks, but may result, in part, from reduced nicotinic modulation of XII motoneurons