Breath-to-breath hypercapnic response in neonatal rats: temperature dependency of the chemoreflexes and potential implications for breathing stability

Abstract

The breathing of newborns is destabilized by warm temperatures. We hypothesized that in unanesthetized, intact newborn rats, body temperature (T(B)) influences the peripheral chemoreflex response (PCR response) to hypercapnia. To test this, we delivered square-wave challenges of 8% CO(2) in air to postnatal day 4-5 (P4-P5) rats held at a T(B) of 30 degrees C (Cold group, n = 11), 33 degrees C (Cool group, n = 10), and 35 degrees C thermoneutral zone group [thermoneutral zone (TNZ) group, n = 11], while measuring ventilation (Ve) directly with a pneumotach and mask. Cool animals were challenged with 8% CO(2) balanced in either air or hyperoxia (n = 10) to identify the PCR response. Breath-to-breath analysis was performed on 30 room air breaths and every breath of the 1-min CO(2) challenge. As expected, warmer T(B) was associated with an unstable breathing pattern in room air: TNZ animals had a coefficient of variation in Ve (Ve CV%) that was double that of animals held at cooler T(B) (P < 0.001). Hyperoxia markedly suppressed the hypercapnic ventilatory response over the first 10 breaths (or approximately 4 s), suggesting that this domain is dominated by the PCR response. The PCR response (P = 0.03) and total response (P = 0.04) were significantly greater in TNZ animals compared with hypothermic animals. The total response had a significant, negative relationship with Vco(2) (R(2) = 0.53; P < 0.001). Breathing stability was positively related to the total response (R(2) = 0.36; P < 0.001) and to a lesser extent, the PCR response (R(2) = 0.19; P = 0.01) and was negatively related to Vco(2) (R(2) = 0.34; P < 0.001). ANCOVA confirmed a significant effect of T(B) alone on breathing stability (P < 0.01), with no independent effects of Vco(2) (P = 0.41), the PCR response (P = 0.82), or the total Ve response (P = 0.08). Our data suggest that in early postnatal life, the chemoreflex responses to CO(2) are highly influenced by T(B), and while related to breathing stability, are not predictors of stability after accounting for the independent effect of T(B).

Bradycardia in serotonin-deficientPet-1−/−mice: influence of respiratory dysfunction and hyperthermia over the first 2 postnatal weeks

“…Experiments were performed using a setup that allows for precise control of T b and the accurate determination of tidal volume (VT) in neonatal animals, where the Tb-Ta difference is very small (8). Briefly, the animal chamber (volume ϳ40 ml) was constructed from a water-jacketed glass cylinder.…”

“…Pet-1 Ϫ/Ϫ and lmx-1b Ϫ/Ϫ mice that have reduced or absent 5-HT neurons, respectively, experience more apneas and reduced V E in the first few postnatal days (11,16). Increasing T a destabilizes neonatal breathing, in part from a concomitant rise in body temperature (T b ) and changes in metabolic drive (4,6,8). Given the interaction between respiratory and HR control, it is possible that, with warming, reduced and destabilized V E leads to more frequent, augmented bradycardias, especially in the absence of medullary 5-HT.…”

The ventilatory response to hypoxia and hypercapnia is absent in the neonatal fat-tailed dunnart

“…As our analysis of the hypercapnic response was limited to the period following 5min exposure to CO 2 (representing the integrated response of both the peripheral and central chemoreceptors), it is possible that the ventilatory response in the dunnart peaks before 5min of exposure. In neonatal rats, V E has been shown to decrease slightly between 3 and 5min though it was still significantly elevated at 5min with respect to baseline (Cummings and Frappell, 2009). Alternatively, it may be that the reduced response we observed was due to the small size of the dunnarts.…”

“…Despite the reduced breathing in newborns subjected to acute hypoxia, they still hyperventilate because of a larger drop in the rate of oxygen consumption (V O2 ) compared with V E . While the hypercapnic ventilatory response of most newborn species is reduced compared with that of adults Davis et al, 2006), unlike hypoxia, it is sustained over time by a persistent increase in tidal volume (V T ), despite a gradual decline in the initial respiratory frequency (f) increase (Bonora et al, 1994;Cummings and Frappell, 2009). Exceptions to these patterns exist, however, with the neonatal North American opossum (another marsupial) demonstrating an unusually large ventilatory response to hypoxia and a hypometabolic response to hypercapnia (Farber, 1972), which attenuates with age .…”

Effects of Hydrogen Sulfide Synthesis Inhibitors on Posthypoxic Ventilatory Behavior in the C57BL/6J Mouse

“…The primary endpoint of our study was the presence or absence of one or more apneas during the first minute of reoxygenation, with apneas being defined as an absence of breathing activity, as measured by plethysmography, lasting longer than two breaths. The CV for respiratory frequency has been used previously as a marker of respiratory stability in rodents [13][14][15] and was calculated for each animal at rest and during the posthypoxic/reoxygenation period. CV and the presence or absence of apneic episodes were compared between saline and each HSSI group.…”