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 (TB) influences the peripheral chemoreflex response (PCR response) to hypercapnia. To test this, we delivered square-wave challenges of 8% CO2 in air to postnatal day 4–5 (P4–P5) rats held at a TB of 30°C (Cold group, n = 11), 33°C (Cool group, n = 10), and 35°C thermoneutral zone group [thermoneutral zone (TNZ) group, n = 11], while measuring ventilation (V̇e) directly with a pneumotach and mask. Cool animals were challenged with 8% CO2 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 CO2 challenge. As expected, warmer TB was associated with an unstable breathing pattern in room air: TNZ animals had a coefficient of variation in V̇e (V̇e CV%) that was double that of animals held at cooler TB ( P < 0.001). Hyperoxia markedly suppressed the hypercapnic ventilatory response over the first 10 breaths (or ∼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 V̇co2 ( R2 = 0.53; P < 0.001). Breathing stability was positively related to the total response ( R2 = 0.36; P < 0.001) and to a lesser extent, the PCR response ( R2 = 0.19; P = 0.01) and was negatively related to V̇co2 ( R2 = 0.34; P < 0.001). ANCOVA confirmed a significant effect of TB alone on breathing stability ( P < 0.01), with no independent effects of V̇co2 ( P = 0.41), the PCR response ( P = 0.82), or the total V̇e response ( P = 0.08). Our data suggest that in early postnatal life, the chemoreflex responses to CO2 are highly influenced by TB, and while related to breathing stability, are not predictors of stability after accounting for the independent effect of TB.