Development of Carotid Chemoreceptor Dynamic and Steady‐State Sensitivity to CO₂ in the Newborn Lamb

Abstract

The maturation of carotid chemoreceptor steady‐state and dynamic responses to CO2 in newborn lambs was measured. In total, sixteen fibres (13 lambs) were studied at 3–4 days, nineteen fibres (13 lambs) at 5–9 days and twenty‐one fibres (17 lambs) at 10–24 days after birth. Steady‐state CO2 sensitivity was measured over a range of arterial CO2 pressures (Pa,CO2) at four levels of arterial O2 pressure (Pa,O2): hyperoxia (Hyp), 115–150 mmHg; normoxia (Nx), 90–105 mmHg; moderate hypoxia (ModHx), 40–60 mmHg; and severe hypoxia (SvHx), 20–35 mmHg. Steady‐state CO2 sensitivity was present at all ages, and a significant effect of age (P < 0.001) and Pa,O2 (P < 0.025) (ANOVA) was observed. Older lambs were unable to sustain an increase in chemoreceptor discharge during SvHx as CO2 was increased. Dynamic CO2 sensitivity was measured by producing alternations in end‐tidal CO2 levels (etCO2) (alternation amplitude, 1.23 ± 0.07% (mean ±s.e.m.); etCO2, 7.56 ± 0.15%) over 2–8 s at two Pa,O2 levels only: 80–100 (Nx) and 40–60 mmHg (ModHx). Peak and trough values of the oscillation in chemoreceptor discharge were plotted against maximum and minimum etCO2 for the control and CO2‐loaded breaths. Dynamic CO2 sensitivity was calculated as the slope between these points. Dynamic CO2 sensitivity was greater than steady‐state sensitivity in Nx (P < 0.05) and ModHx (P < 0.01, Student's paired t test). Unlike steady‐state CO2 sensitivity, there was no significant effect of age or Pa,O2 on dynamic sensitivity (P > 0.39 and P > 0.68, respectively, ANOVA). Our results show that the neonatal lamb possesses a carotid body steady‐state CO2 sensitivity within a few days of birth, an age when hypoxia sensitivity is low. This CO2 sensitivity increases with age, perhaps due to the increasing interaction between CO2 and O2. Dynamic sensitivity of the carotid body to CO2 is mature at birth and does not increase with age, as predicted if the response of the carotid body to rapid changes in CO2 is independent of the sensitivity to the partial pressure of O2 (PO2).

Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

“…This positive interaction has been confirmed in recent studies carried out on goats, lambs, piglets, cats, rats, and mice (Daristotle et al 1987;Wolsink et al 1992;Carroll et al 1993;Tankersley et al 1994Tankersley et al , 2004Pepper et al 1995;Calder et al 1997), although some early studies showed a negative interaction in cats (Ou et al 1976). We compared the ventilatory response to hypoxic hypercapnia between CS-and FA-exposed mice.…”

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

“…The CO 2 response of the isolated carotid body is present in young animals and generally equal to the adult response. The multiplicative interaction between hypercapnia and hypoxia increases over the course of development, but the intrinsic CO 2 sensitivity of the carotid body under normoxic conditions does not vary much as a function of age (Pepper et al, 1995;Calder et al, 1997;Bamford et al, 1999). The contribution of peripheral chemoreceptors to the normoxic hypercapnic ventilatory response in intact animals is stable in the neonatal period of development in humans as well, but the interactive effects of CO 2 -O 2 at the carotid body seem to increase as babies mature (Søvik and Lossius, 2004).…”

Development of Ventilatory Response to Transient Hypercapnia and Hypercapnic Hypoxia in Term Infants

“…Preterm infants displayed an age-related increase in steady-state CO 2 sensitivity (10, 11), whereas term infants showed no such postnatal development (12, 13). Dynamic CO 2 sensitivity was unchanged during the first month in neonatal lambs (8,14), whereas in piglets the relative contribution of peripheral chemoreceptors to CO 2 stimulation increased postnatally (15).Ultimately, the combined effects of PCO 2 , arterial PO 2 , and pH determine the level of ventilation. Nonlinear interaction between PCO 2 and PO 2 , i.e.…”

“…Nonlinear interaction between PCO 2 and PO 2 , i.e. increased CO 2 chemosensitivity at increasing levels of hypoxia, has been described in carotid and aortic nerve recordings (7,8,16) and in ventilatory responses in animals (17, 18) and adult humans (19). Whether interaction between PCO 2 and PO 2 is present at birth and whether it increases postnatally differs from one species to another (7,16,20 …”