Trans-cerebral HCO₃⁻ and PCO₂ exchange during acute respiratory acidosis and exercise-induced metabolic acidosis in humans

Abstract

This study investigated trans-cerebral internal jugular venous-arterial bicarbonate ([HCO3−]) and carbon dioxide tension (PCO2) exchange utilizing two separate interventions to induce acidosis: 1) acute respiratory acidosis via elevations in arterial PCO2 (PaCO2) (n = 39); and 2) metabolic acidosis via incremental cycling exercise to exhaustion (n = 24). During respiratory acidosis, arterial [HCO3−] increased by 0.15 ± 0.05 mmol ⋅ l−1 per mmHg elevation in PaCO2 across a wide physiological range (35 to 60 mmHg PaCO2; P < 0.001). The narrowing of the venous-arterial [HCO3−] and PCO2 differences with respiratory acidosis were both related to the hypercapnia-induced elevations in cerebral blood flow (CBF) (both P < 0.001; subset n = 27); thus, trans-cerebral [HCO3−] exchange (CBF × venous-arterial [HCO3−] difference) was reduced indicating a shift from net release toward net uptake of [HCO3−] (P = 0.004). Arterial [HCO3−] was reduced by −0.48 ± 0.15 mmol ⋅ l−1 per nmol ⋅ l−1 increase in arterial [H+] with exercise-induced acidosis (P < 0.001). There was no relationship between the venous-arterial [HCO3−] difference and arterial [H+] with exercise-induced acidosis or CBF; therefore, trans-cerebral [HCO3−] exchange was unaltered throughout exercise when indexed against arterial [H+] or pH (P = 0.933 and P = 0.896, respectively). These results indicate that increases and decreases in systemic [HCO3−] – during acute respiratory/exercise-induced metabolic acidosis, respectively – differentially affect cerebrovascular acid-base balance (via trans-cerebral [HCO3−] exchange).

Assessing central and peripheral respiratory chemoreceptor interaction in humans

“…For example, during hyperoxic rebreathing techniques, the central chemoreflex threshold is ∼40–42 Torr (e.g., Boulet et al., 2016; Duffin & McAvoy, 1988), at which the end‐tidal values are likely to approximate brainstem tissue levels (e.g., Boulet et al., 2016; Casey et al., 1987). However, this feature is not the case when breathing ambient air or fixed fractional increases in CO 2 , because the usual arrangement is that of the steady state, where any measured end‐tidal CO 2 value is likely to be 6–8 Torr lower than tissue values (e.g., Caldwell et al., 2022). Thus, when interpreting a VRT of ∼40 Torr CO 2 from experiments using rebreathing techniques, it is difficult to make comparisons to experiments using steady‐state techniques (i.e., the present study).…”

“…However, this feature is not the case when breathing ambient air or fixed fractional increases in CO 2 , because the usual arrangement is that of the steady state, where any measured end-tidal CO 2 value is likely to be 6-8 Torr lower than tissue values (e.g., Caldwell et al, 2022).…”

The jugular venous‐to‐arterial PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ difference during rebreathing and end‐tidal forcing: Relationship with cerebral perfusion

“…By contrast, during ETF, the within‐individuals P jv‐a CO 2 appears less variable than with rebreathing, but the mean P jv‐a CO 2 decreases at each stage, probably as a result of the influence of CVR. This produces a relatively predictable stage‐wise decrease in P jv‐a CO 2 because of the steady‐state nature of each $${P_{{\mathrm{aC}}{{\mathrm{O}}_{\mathrm{2}}}}}$$stage (Caldwell et al., 2021). This difference between methods could be the result of normal between‐individual physiological variability in the rate of rise of the relevant parameters ($${P_{{\mathrm{aC}}{{\mathrm{O}}_{\mathrm{2}}}}}$$, P jv CO 2 and/or CBF), or the result of the dynamic nature of the $${P_{{\mathrm{aC}}{{\mathrm{O}}_{\mathrm{2}}}}}$$ ramp during rebreathing increasing the technical variability involved in simultaneous arterial and jugular venous blood draws.…”

Acid–base balance and cerebrovascular regulation

“…This narrowing is likely attributable to increases in [HCO 3 -] and CO 2 'wash-out' due to higher CBF with hypercapnia; for example, the venous-arterial HCO 3 and CO 2 differences were each related to increases in CBF (both P < 0.001). Data are from Caldwell et al (2021a).…”

“…6) – a change likely attributable to increased intracellular HCO 3 – ‘wash‐out’ as the reduction in trans‐cerebral [HCO 3 – ] difference is related to the hypercapnic CBF response (Caldwell et al . 2021 a ). Arvidsson and colleagues (1981) showed that intravenous infusion of NaHCO 3 in hypercapnic dogs causes a 50−70% reduction in CBF (from hypercapnic elevation) paralleled by a reduction in arterial–venous O 2 difference such that was unaltered.…”