Cerebrovascular reactivity to carbon dioxide is not influenced by variability in the ventilatory sensitivity to carbon dioxide

Abstract

Recent work demonstrated an influence of ventilation on cerebrovascular reactivity to CO 2 ; however, the concomitant influence of changes in mean arterial blood pressure (MAP) on ventilation-induced differences in cerebral blood flow (CBF) has yet to be examined in this context.Healthy participants (n = 15; 25 ± 3 years of age; 179 ± 6 cm height; 74 ± 10 kg weight; 3 female) underwent end-tidal forcing to increase their partial pressure of end-tidal CO 2 by +3, +6 and +9 mmHg above baseline in 5-min sequential steps while maintaining iso-oxia. This protocol was then repeated twice, with participants hyperventilating and hypoventilating by ∼30% compared to the first trial. Intra-cranial and extra-cranial CBF were measured using ultrasound. The MAP (finger photo-plethysmography) was higher during the hyperventilation and hypoventilation trials compared to normal ventilation (main effects, P < 0.05 for both). While internal carotid artery blood flow was higher during the hyperventilation trial compared to normal ventilation (P = 0.01), this was due to a higher MAP, as indicated by analysis of conductance values (P = 0.68) or inclusion of MAP in covariate analysis (P = 0.11). Global CBF (P = 0.11) and vertebral artery blood flow (P = 0.93) were unaffected by the magnitude of ventilation. Further, CO 2 reactivity was not affected by the different breathing trials (P > 0.05 for all). Retrospective analysis of a larger data set (n = 53) confirmed these observations and demonstrated no relationships between the ventilatory and global CBF response to hypercapnia (r 2 = 0.04; P = 0.14). Therefore, when differences in MAP are accounted for, cerebrovascular CO 2 reactivity (assessed via end-tidal forcing) is independent of the magnitude of ventilation.

Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis

“…Our results are consistent with several other studies that have reported that CVR is larger in the hypercapnic range compared to the hypocapnic range (Kety & Schmidt, 1948b;Ramsay et al 1993;Ito et al 2000;2003;Willie et al 2012;Coverdale et al 2014;Hoiland et al 2019). The relatively higher hypercapnic reactivity is probably partly a result of hypercapnia-induced elevations in blood flow to elicit an additive shear stress mediated vasodilatory response (Carter et al 2016;Hoiland et al 2017), such as increases in nitric oxide bioavailability (Mashour & Boock, 1999), as well as the CO 2 induced vasopressor response (Willie et al 2012;Regan et al 2014;Howe et al 2020;Webb et al 2020). A key new finding of this investigation is the paradoxical increase in hypocapnic CVR and reduction in hypercapnic CVR following NaHCO 3 infusion when expressed as CBF vs. [H + ] (rather than P aCO 2 ) ( Figs.…”

“…Notably, this method of arterial blood gas alteration provides a lesser end‐tidal‐to‐arterial gradient, precludes any independent influence of on cerebrovascular CO 2 reactivity (Howe et al . 2020) and therefore provides an accurate stimulus–response relationship (Fisher, 2016; Fisher et al . 2018).…”

“…Both P ETCO 2 and P ETO 2 were controlled using a custom-designed dynamic end-tidal forcing system to effectively regulate end-tidal gases across wide ranges of P ETCO 2 and P ETO 2 independent of ventilation (V E ); this device has been described in detail elsewhere (Tymko et al 2015;2016). Notably, this method of arterial blood gas alteration provides a lesser end-tidal-to-arterial P CO 2 gradient, precludes any independent influence ofV E on cerebrovascular CO 2 reactivity (Howe et al 2020) and therefore provides an accurate stimulus-response relationship (Fisher, 2016;Fisher et al 2018). Respiratory flow, tidal volume (V T ) and respiratory rate (RR) were measured by a pneumotachograph (MLT1000L; ADInstruments) paired with a spirometer (FE141; ADInstruments).…”

Internal carotid and brachial artery shear‐dependent vasodilator function in young healthy humans

“…CO 2 inhalation from a reservoir/Douglas bag), precludes any influence of V̇ E on CVR (Howe et al . 2020), and therefore provides an accurate quantification of stimulus response relationships (Fisher, 2016; Fisher et al . 2018).…”

“…Notably, this method of arterial blood gas manipulation provides lesser arterial-to-end-tidal gradients of P ET CO 2 than other methods of blood gas manipulation (e.g. CO 2 inhalation from a reservoir/Douglas bag), precludes any influence of VĖ on CVR (Howe et al 2020), and therefore provides an accurate quantification of stimulus response relationships (Fisher, 2016;Fisher et al 2018). This gas delivery system was used for both the cFMD and CVR tests described below.…”