Control of Cerebral Blood Flow by Blood Gases

Abstract

Cerebrovascular reactivity can be measured as the cerebrovascular flow response to a hypercapnic challenge. The many faceted responses of cerebral blood flow to combinations of blood gas challenges are mediated by its vasculature’s smooth muscle and can be comprehensively described by a simple mathematical model. The model accounts for the blood flow during hypoxia, anemia, hypocapnia, and hypercapnia. The main hypothetical basis of the model is that these various challenges, singly or in combination, act via a common regulatory pathway: the regulation of intracellular hydrogen ion concentration. This regulation is achieved by membrane transport of strongly dissociated ions to control their intracellular concentrations. The model assumes that smooth muscle vasoconstriction and vasodilation and hence cerebral blood flow, are proportional to the intracellular hydrogen ion concentration. Model predictions of the cerebral blood flow responses to hypoxia, anemia, hypocapnia, and hypercapnia match the form of observed responses, providing some confidence that the theories on which the model is based have some merit.

Cerebral blood flow, cerebrovascular reactivity and their influence on ventilatory sensitivity

“…Because the magnitude of diffusion of CO 2 across the BBB is dependent on the P btCO 2 -P aCO 2 gradient, the prevailing P & Wray, 1993;Duffin et al, 2021;Severinghaus & Lassen, 1967) and ventilatory (Cleary et al, 2020;Jensen et al, 1988) responses to CO 2 .…”

“…Duffin (2009),Duffin et al (2021) andYamashiro & Kato (2021). (a) Stylized P btCO 2 -P aCO 2 gradient at rest and with sudden CBF changes incorporating compartmental equilibration detailed in Figure3.…”

Does breathing pattern affect cerebrovascular reactivity?

“…Located in the medulla oblongata near the ventral surface, these CO 2 sensors are placed to monitor medullary tissue [H + ] and regulate lung ventilation accordingly. Pertinent to respiratory chemoreflex testing, the cerebrovascular smooth muscle controlling cerebral and medullary blood flow also responds to changes in arterial blood gases (Duffin et al, 2021b; Willie et al., 2012), such as hypoxia (Cohen et al., 1967; Mardimae et al., 2012) and hypercapnia (Battisti‐Charbonney et al., 2011; Hoiland et al., 2019).…”

“…Both studies (Ogoh et al., 2019; Howe et al., 2020) examined the effects of voluntary control of breathing on the CBF response to CO 2 , CVR. With voluntary control of breathing proceeding from the cortex via corticospinal pathways (Lipski et al., 1986) and CBF control via local cerebrovascular smooth muscle (Duffin et al., 2021b), one might assume that interaction between voluntary control of breathing and CVR is unlikely. However, CBF responds to MAP in addition to CO 2 (Battisti‐Charbonney et al., 2011), and voluntary control of breathing affects MAP via changes in sympathetic control and, consequently, CBF (Howe et al., 2020).…”

Acid–base balance and cerebrovascular regulation

“…While Stewart's physiochemical approach is as clinically useful as the conventional approach (Rastegar, 2009) – as well as providing an alternative explanation for regulation of [H + ] (Duffin et al . 2021) – this review has adopted the traditional bicarbonate‐centred approach to acid–base balance as this is likely to be familiar to physiology readers. Details on this important debate are provided elsewhere (Sirker et al .…”