Quantifying cerebrovascular reactivity in anterior and posterior cerebral circulations during voluntary breath holding

Abstract

New Findings: What is the central question of this study? We developed and validated a ‘stimulus index’ (SI; ratio of end-tidal partial pressures of CO2 and O2) method to quantify cerebrovascular reactivity (CVR) in anterior and posterior cerebral circulations during breath holding. We aimed to determine whether the magnitude of CVR is correlated with breath-hold duration. What is the main finding and its importance? Using the SI method and transcranial Doppler ultrasound, we found that the magnitude of CVR of the anterior and posterior cerebral circulations is not positively correlated with physiological or psychological break-point during end-inspiratory breath holding. Our study expands the ability to quantify CVR during breath holding and elucidates factors that affect break-point. The central respiratory chemoreflex contributes to blood gas homeostasis, particularly in response to accumulation of brainstem CO2. Cerebrovascular reactivity (CVR) affects chemoreceptor stimulation inversely through CO2 washout from brainstem tissue. Voluntary breath holding imposes alterations in blood gases, eliciting respiratory chemoreflexes, potentially contributing to breath-hold duration (i.e. break-point). However, the effects of cerebrovascular reactivity on break-point have yet to be determined. We tested the hypothesis that the magnitude of CVR contributes directly to breath-hold duration in 23 healthy human participants. We developed and validated a cerebrovascular stimulus index methodology [SI; ratio of end-tidal partial pressures of CO2 and O2 (PET,CO2/PET,O2)] to quantify CVR by correlating measured and interpolated values of PET,CO2 (r = 0.95, P < 0.0001), PET,CO2 (r = 0.98, P < 0.0001) and SI (r = 0.94, P < 0.0001) during rebreathing. Using transcranial Doppler ultrasound, we then quantified the CVR of the middle (MCAv) and posterior (PCAv) cerebral arteries by plotting cerebral blood velocity against interpolated SI during a maximal end-inspiratory breath hold. The MCAv CVR magnitude was larger than PCAv (P = 0.001; +70%) during breath holding. We then correlated MCAv and PCAv CVR with the physiological (involuntary diaphragmatic contractions) and psychological (end-point) break-point, within individuals. There were significant inverse but modest relationships between both MCAv and PCAv CVR and both physiological and psychological break-points (r < −0.53, P < 0.03). However, these relationships were absent when MCAv and PCAv cerebrovascular conductance reactivity was correlated with both physiological and psychological break-points (r > −0.42; P > 0.06). Although central chemoreceptor activation is likely to be contributing to break-point, our data suggest that CVR-mediated CO2 washout from central chemoreceptors plays no role in determining break-point, probably because of a reduced arterial-to-tissue CO2 gradient during breath holding.