Selecting representative ages for developmental changes of respiratory irregularities and hypoxic ventilatory response in rats

Apnea frequency and the weak ventilatory response to hypoxia are a major clinical correlates of the immaturity of respiratory control system in preterm neonates. Rats are frequently used as model to study the respiratory control during development. However, little is known about the postnatal ages that best represent these respiratory irregularities and the hypoxic ventilatory response. Using plethysmography, we assessed baseline minute ventilation, ventilatory response to moderate hypoxia (FiO2 = 12%, 20 min) and apnea frequency in awake and non-anesthetized rats at the postnatal ages of 1, 4, 7, 12, 21 and 90 days old (P1, P4, P7, P12, P21, and P90, respectively). Baseline minute ventilation slightly increased in P4 (~25% vs P1) then gradually decreased with age (age effect: p < 0.05). The lowest level of ventilation was observed in P90 (p < 0.01 vs all ages). Minute ventilation (% from baseline) in response to hypoxia showed the well-known biphasic pattern in all rats at 12 days old or less. Minute ventilation at the initial phase of the hypoxic response was not significantly different between P1, P4, between P7, P12 and between P21, P90. The late phase of the hypoxic response was similar between P1, P4, and between P21, P90, but was significantly different between P7 and P12 (p < 0.05). Under baseline or hypoxic condition, the higher number of apnea frequency (spontaneous and post- sigh) was observed in P1, it then decreased progressively with age (age effect: p < 0.01 for baseline;p < 0.001 for hypoxia). These results suggest that when P4, P7 and P12 are selected to represent the age-dependent changes of the hypoxic ventilatory response in rats, the P1 rats should be included to better describe the age-dependence of apnea frequency.

Ovariectomy at 3 or 10 weeks of age does not affect the ventilatory response to hypoxia in adult rats

Although an ovariectomy is the routine approach used to study the role of ovarian hormones on respiratory control, the results have often been contradictory. We tested the hypothesis that the ventilatory response to hypoxia is modified by the age at which the ovariectomy is performed. Female rats were ovariectomized either atan early (3 weeks old, i.e., prepubertal) or late (10 weeks old, i.e., adult) stage, and ventilation was then assessed at 12 weeks of age using whole-body plethysmography. The control group included sham-operated rats that had undergone the same surgical procedure but were not ovariectomized. Independent of the age at which surgery was performed, ovariectomy significantly decreased circulating progesterone and 17-b-estradiol levels without re-ducing them below their detection threshold. Despite that decrease, there was no difference in baseline minute ventilation or in the ventilatory response to hypoxia (FiO2 = 12%, 20 min;expressed as the percentage of increase from baseline) between ovariectomized and shamoperated rats. These results suggest that ovariectomy at either a young or at an adult age is insufficient to completely suppress circulating hormones and disrupt the regulation of ventilation.