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The critical closing pressure contribution to dynamic cerebral autoregulation in humans: influence of arterial partial pressure of CO2

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posted on 09.09.2021, 09:53 by Ronney B Panerai, Jatinder S Minhas, Osian Llwyd, Angela SM Salinet, Emmanuel Katsogridakis, Paola Maggio, Thompson G Robinson
KEY POINTS:Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrate that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis (TFA) of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explain the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia. ABSTRACT:Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70 years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV, TCD), end-tidal CO2 (EtCO2 , capnography) and heart rate (ECG) were performed for 5 min at rest (normocapnia) and during hypercapnia induced by breathing 5% CO2 in air. CrCP and the resistance-area product (RAP) were obtained for each cardiac cycle and their dynamic response to a step change in MAP was calculated by means of transfer function analysis (TFA). The recovery of the CBFV response, following a step change in MAP, was mainly due to the contribution of RAP during both breathing conditions. However, CrCP had a highly significant contribution during normocapnia (p<0.0001) and was the sole determinant of changes in the CBFV response, resulting from hypercapnia, which led to a reduction in the autoregulation index (ARI) from 5.70 ± 1.58 (normocapnia) to 4.14 ± 2.05 (hypercapnia; p<0.0001). In conclusion, CrCP makes a very significant contribution to the dynamic CBFV response to changes in MAP and plays a major role in explaining the deterioration of dynamic CA induced by hypercapnia. Further studies are needed to assess the relevance of CrCP contribution in physiological and clinical studies. This article is protected by copyright. All rights reserved.


EPSRC. Grant Number: EP/K041207/1. J.S.M

Dunhill Medical Trust Research Training Fellowship. Grant Number: RTF97/0117



The Journal of physiology, Volume 598, Issue 24, 15 December 2020, Pages 5673-5685

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Department of Cardiovascular Sciences, University of Leicester


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