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

Cummings KJ, Frappell PB. Breath-to-breath hypercapnic response in neonatal rats: temperature dependency of the chemoreflexes and potential implications for breathing stability. Am J Physiol Regul Integr Comp Physiol 297: R124-R134, 2009. First published May 6, 2009; doi:10.1152/ajpregu.91011.2008.-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% CO2 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 ((V) over dot E) 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 T-B was associated with an unstable breathing pattern in room air: TNZ animals had a coefficient of variation in (V) over dot E ((V) over dot E 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 similar to 4s), 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 (V) over dot CO2 (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 (V) over dot CO2 (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 (V) over dot CO2 (P = 0.41), the PCR response (P = 0.82), or the total (V) over dot E response (P = 0.08). Our data suggest that in early postnatal life, the chemoreflex responses to CO2 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.