Effect of Intermittent Hypercapnia on Respiratory Control in Rat Pups

Abstract

Preterm infants are subject to fluctuations in blood gas status associated with immature respiratory control. Intermittent hypoxia during early postnatal life has been shown to increase chemoreceptor sensitivity and destabilize the breathing pattern; however, intermittent hypercapnia remains poorly studied. Therefore, to test the hypothesis that intermittent hypercapnia results in altered respiratory control, we examined the effects of daily exposure to intermittent hypercapnia on the ventilatory response to subsequent hypercapnic and hypoxic exposure in neonatal rat pups. Exposure cycles consisted of 5 min of intermittent hypercapnia (5% CO₂, 21% O₂, balance N₂) followed by 10 min of normoxia. Rat pups were exposed to 18 exposure cycles each day for 1 week, from postnatal day 7 to 14. We analyzed diaphragm electromyograms (EMGs) from pups exposed to subsequent acute hypercapnic (5% CO₂) and hypoxic (12% O₂) challenges. In response to a subsequent hypercapnia challenge, there was no significant difference in the ventilatory response between control and intermittent hypercapnia-exposed groups. In contrast, intermittent hypercapnia-exposed rat pups showed an enhanced ventilatory response to hypoxic challenge with an increase in minute EMG to 118 ± 14% of baseline versus 107 ± 13% for control pups (p < 0.05). We speculate that prior hypercapnic exposure may increase peripheral chemoreceptor response to subsequent hypoxic exposures and result in perturbed neonatal respiratory control.

Comparative Control of Respiration

“…However, Rezzonico and Mortola (1988) did find persistent reductions in the ventilatory response to CO 2 of rats exposed as newborns to 7% CO 2 for 7 days. Findings support the former (Steggerda et al, 2010), but these authors also show a significant effect of hypercapnia on the subsequent ventilatory response to hypoxia. The different results in these studies may be due to the higher levels of CO 2 in both the initial exposure period (7% vs 5%) and the subsequent testing (10% vs 5%) in the Rezzonico and Mortola study versus the other two.…”

Combined effects of intermittent hyperoxia and intermittent hypercapnic hypoxia on respiratory control in neonatal rats

“…Intermittent hypercapnia likely affects the HCVR through the same mechanism, but blood pH and bicarbonate concentrations were not measured here. Although relatively short daily exposures to intermittent hypercapnia did not alter the HCVR of neonatal rats in a previous study (only 18 cycles d −1 ; Steggerda et al, 2010), more continuous exposures to intermittent hypercapnia (as employed in the present study) should be a stronger stimulus for metabolic compensation.…”

“…Pawar et al (2008) noted that (1) carotid body sensitization is easier to elicit in neonates (i.e., observed after fewer hypoxic episodes), (2) chronic intermittent hypoxia promotes carotid body hyperplasia in neonates but not in adult rats, and (3) carotid body O 2 sensitivity remains enhanced at least 50 days after neonates are returned to normoxia but recovers in less than 10 days in adults. Similarly, there is at least some evidence that chronic intermittent hypercapnia alone can increase the HVR of neonatal rats (Steggerda et al, 2010); the mechanisms underlying this effect have not been studied.…”

Periodicity During Hypercapnic and Hypoxic Stimulus Is Crucial in Distinct Aspects of Phrenic Nerve Plasticity

“…It has been suggested that intermittent hypoxia might have a beneficial role in sleep related breathing disorders and could be a viable means of restoring respiratory functions in ventilatory control disorders Narwani 2009, Gaultier 2008). However, although intermittent hypercapnia results in altered respiratory control, its short and long-term effects on respiratory control remain poorly studied (Steggerda et al 2010).…”