Determinants of the dynamic cerebral critical closing pressure response to changes in mean arterial pressure

Objective. Cerebral critical closing pressure (CrCP) represents the value of arterial blood pressure (BP) where cerebral blood flow (CBF) becomes zero. Its dynamic response to a step change in mean BP (MAP) has been shown to reflect CBF autoregulation, but robust methods for its estimation are lacking. We aim to improve the quality of estimates of the CrCP dynamic response. Approach. Retrospective analysis of 437 healthy subjects (aged 18-87 years, 218 males) baseline recordings with measurements of cerebral blood velocity in the middle cerebral artery (MCAv, transcranial Doppler), non-invasive arterial BP (Finometer) and end-tidal CO2 (EtCO2, capnography). For each cardiac cycle CrCP was estimated from the instantaneous MCAv-BP relationship. Transfer function analysis of the MAP and MCAv (MAP-MCAv) and CrCP (MAP-CrCP) allowed estimation of the corresponding step responses (SR) to changes in MAP, with the output in MCAv (SRVMCAv) representing the autoregulation index (ARI), ranging from 0 to 9. Four main parameters were considered as potential determinants of the SRVCrCP temporal pattern, including the coherence function, MAP spectral power and the reconstruction error for SRVMAP, from the other three separate SRs. Main results. The reconstruction error for SRVMAP was the main determinant of SRVCrCP signal quality, by removing the largest number of outliers (Grubbs test) compared to the other three parameters. SRVCrCP showed highly significant (p<0.001) changes with time, but its amplitude or temporal pattern was not influenced by sex or age. The main physiological determinants of SRVCrCP were the ARI and the mean CrCP for the entire five-minute baseline period. The early phase (2-3 s) of SRVCrCP response was influenced by heart rate whereas the late phase (10-14 s) was influenced by diastolic BP. Significance. These results should allow better planning and quality of future research and clinical trials of novel metrics of cerebral blood flow regulation.