CO 2 Reactivity in Brain Relies on Blood Pressure Regulation as Well as Arteriolar Vaso-Reactivity

Abstract

Introduction:

Carbon dioxide (CO₂)-reactivity of middle cerebral artery blood velocity (MCAv) is a well-established method to study cerebrovascular physiology. Changing blood CO₂ by hyperventilation or CO₂ retention is an artificial stimulus to the neurovascular coupling of arterioles spread throughout the brain, normally linking blood flow to local neuronal activity.

Methods:

By recording MCAv simultaneously with arterial blood pressure (ABP) in 14 young and healthy volunteers, this study aims to answer the theoretical question of whether changes in MCAv should be ascribed exclusively to cerebral vaso-reactivity, to changes in ABP or to a combination of both. Both signals were analyzed by determining the first (Sys1) and second systolic peak (Sys2) and the diastolic flow velocity 560 ms after upstroke onset (D560).

Results:

Hyperventilation resulted in an average decrease of 1.9% in end tidal CO₂ (ETCO₂) and was accompanied by a significant decrease in MCAv (Sys1 -26, Sys2 -28, and D560 -28 cm/s) whereas ABP parameters remained unaltered (Sys1 +7, Sys2 +5, and D560 -1 mmHg). Carbon dioxide (CO₂) retention resulted in an average increase of 1.7% in ETCO₂ and was accompanied by an increase in MCAv (Sys1 +16, Sys2 +27, and D560 +29 cm/s) as well as in ABP (Sys1 +16, Sys2 +24, and D560 +13 mmHg). The apparent resistance (aR), defined as the ratio of ABP divided by MCAv, increased during hyperventilation (Sys1 +0.5, Sys2 +0.6, and D560 +0.8 mm Hg/cm/s) but remained the same during CO₂ retention (Sys1 +0.02, Sys2 +0.04, and D560 -0.01 mm Hg/cm/s).

Conclusion:

We conclude that in young healthy volunteers, hyperventilation reduces MCAv by arteriolar vasoconstriction whereas CO₂ retention increases MCAv by increasing ABP.

Keywords

arterial stiffness arterial acceleration arterial blood pressure blood flow velocity transcranial Doppler non-invasive blood pressure

Get full access to this article

View all access options for this article.

References

Ainslie

Duffin

. Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation. Am J Physiol Regul Integr Comp Physiol. 2009;296(5):R1473-R1495. doi:10.1152/ajpregu.91008.2008.

Skow

Brothers

Claassen

JAHR

, et al. On the use and misuse of cerebral hemodynamics terminology using transcranial Doppler ultrasound: a call for standardization. Am J Physiol Heart Circ Physiol. 2022;323(2):H350-H357.

Bydén

Segernäs

Thulesius

, et al. Cerebrovascular reserve capacity as a predictor of postoperative delirium: a pilot study. Front Surg. 2021;8:658849. doi:10.3389/fsurg.2021.658849.

Reinhard

Schwarzer

Briel

, et al. Cerebrovascular reactivity predicts stroke in high-grade carotid artery disease. Neurology. 2014;83(16):1424-1431.

Douvas

Moris

Karaolanis

Bakoyiannis

Georgopoulos

. Evaluation of cerebrovascular reserve capacity in symptomatic and asymptomatic internal carotid stenosis with transcranial Doppler. Physiol Res. 2016;65(6):917-925. doi:10.33549/physiolres.933303.

Kim

Hughes

Lipford

, et al. Relationship between cerebrovascular reactivity and cognition among people with risk of cognitive decline. Front Physiol. 2021;12:645342. doi:10.3389/fphys.2021.645342.

Hosford

Gourine

. What is the key mediator of the neurovascular coupling response? Neurosci Biobehav Rev. 2019;96:174-181.

Tavel

. Hyperventilation syndrome: why is it regularly overlooked? Am J Med. 2021;134(1):13-15. doi:10.1016/j.amjmed.2020.07.006.

Hoiland

Fisher

Ainslie

. Regulation of the cerebral circulation by arterial carbon dioxide. Compr Physiol. 2019;9(3):1101-1154. doi:10.1002/cphy.c180021.

10.

Schaafsma

. A new method for correcting middle cerebral artery flow velocity for age by calculating Z-scores. J Neurosci Methods. 2018;307:1-7.

11.

Truijen

Van Lieshout

Wesselink

Westerhof

. Noninvasive continuous hemodynamic monitoring. J Clin Monit Comput. 2012;26(4):267-278.

12.

Uzunay

Selvi

Bedel

Karakoyun

. Comparison of ETCO2 value and blood gas PCO2 value of patients receiving non-invasive mechanical ventilation treatment in emergency department. SN Compr Clin Med. 2021;3(8):1717-1721. doi:10.1007/s42399-021-00935-y.

13.

Schaafsma

. Improved parameterization of the transcranial Doppler signal. Ultrasound Med Biol. 2012;38(8):1451-1459.

14.

Brasil

Romeijn

Haspels

Paiva

Schaafsma

. Improved transcranial Doppler waveform analysis for intracranial hypertension assessment in patients with traumatic brain injury. Neurocrit Care. 2024;40(3):931-940.

15.

Schaafsma

. Harvey with a modern twist: how and why conducting arteries amplify the pressure wave originating from the heart. Med Hypotheses. 2014;82(5):589-594.

16.

Crippa

Zama Cavicchi

Taccone

. Cerebral autoregulation is influenced by carbon dioxide levels in anoxic brain injury. Neurocrit Care. 2023;39(3):697-700. doi:10.1007/s12028-023-01676-7.

17.

Ackerman

Zilkha

Bull

JWD

, et al. The relationship of the CO2 reactivity of cerebral vessels to blood pressure and mean resting blood flow. Neurology. 1973;23:21-26.

18.

Ringelstein

Sievers

Ecker

Schneider

Otis

. Noninvasive assessment of CO2-induced cerebral vasomotor response in normal individuals and patients with internal carotid artery occlusions. Stroke. 1988;19(8):963-969. doi:10.1161/01.str.19.8.963.

19.

Klingelhöfer

Sander

. Doppler CO2 test as an indicator of cerebral vasoreactivity and prognosis in severe intracranial hemorrhages. Stroke. 1992;23(7):962-966. doi:10.1161/01.str.23.7.962.

20.

Schaafsma

Molanus

van Rooijen

. Vascular aging entails arterial dilatation in addition to increased arterial stiffness. J Vasc Ultrasound. 2024;48(3):141-149. doi:10.1177/15443167241257626.

21.

Tsacopoulos

Magistretti

. Metabolic coupling between glia and neurons. J Neurosci. 1996;16(3):877-885. doi:10.1523/JNEUROSCI.16-03-00877.1996.

22.

Price

Hoyda

Ferguson

. The area postrema: a brain monitor and integrator of systemic autonomic state. Neuroscientist. 2008;14(2):182-194. doi:10.1177/1073858407311100.

23.

Sobczyk

Fierstra

Venkatraghavan

, et al. Measuring cerebrovascular reactivity: sixteen avoidable pitfalls. Front Physiol. 2021;12:665049.

24.

Liu

De Vis

. Cerebrovascular reactivity (CVR) MRI with CO2 challenge: a technical review. Neuroimage. 2019;187:104-115. doi:10.1016/j.neuroimage.2018.03.047.

25.

Miyakawa

. Mechanisms of blood pressure oscillation caused by central nervous system ischemic response. Jpn J Physiol. 1988;38(4):399-425. doi:10.2170/jjphysiol.38.399.

26.

Vriens

Kraaier

Musbach

Wieneke

van Huffelen

. Transcranial pulsed Doppler measurements of blood velocity in the middle cerebral artery: reference values at rest and during hyperventilation in healthy volunteers in relation to age and sex. Ultrasound Med Biol. 1989;15(1):1-8.

27.

Ackerstaff

Keunen

van Pelt

Montauban van Swijndregt

Stijnen

. Influence of biological factors on changes in mean cerebral blood flow velocity in normal ageing: a transcranial Doppler study. Neurol Res. 1990;12(3):187-191.

28.

Jarrett

Shields

Broxterman

, et al. Imaging transcranial Doppler ultrasound to measure middle cerebral artery blood flow: the importance of measuring vessel diameter. Am J Physiol Regul Integr Comp Physiol. 2020;319(1):R33-R42.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB