Directional sensitivity of dynamic cerebral autoregulation during spontaneous fluctuations in arterial blood pressure at rest

Abstract

Directional sensitivity, the more efficient response of cerebral autoregulation to increases, compared to decreases, in mean arterial pressure (MAP), has been demonstrated with repeated squat-stand maneuvers (SSM). In 43 healthy subjects (26 male, 23.1 ± 4.2 years old), five min. recordings of cerebral blood velocity (bilateral Doppler ultrasound), MAP (Finometer), end-tidal CO₂ (capnograph), and heart rate (ECG) were obtained during sitting (SIT), standing (STA) and SSM. A new analytical procedure, based on autoregressive-moving average models, allowed distinct estimates of the autoregulation index (ARI) by separating the MAP signal into its positive (MAP_+D) and negative (MAP_-D) derivatives. ARI_+D was higher than ARI_-D (p < 0.0001), SIT: 5.61 ± 1.58 vs 4.31 ± 2.16; STA: 5.70 ± 1.24 vs 4.63 ± 1.92; SSM: 4.70 ± 1.11 vs 3.31 ± 1.53, but the difference ARI_+D-ARI_-D was not influenced by the condition. A bootstrap procedure determined the critical number of subjects needed to identify a significant difference between ARI_+D and ARI_-D, corresponding to 24, 37 and 38 subjects, respectively, for SSM, STA and SIT. Further investigations are needed on the influences of sex, aging and other phenotypical characteristics on the phenomenon of directional sensitivity of dynamic autoregulation.

Keywords: Cerebral autoregulation; cerebral blood flow; multivariate modelling; posture; squat-stand maneuver.

Figure 1.

Separation of the original mean arterial blood pressure (MAP) signal (a) into its positive (b) and negative (c) derivatives for a 22 year-old male subject during the repeated squat-stand maneuver at 0.05 Hz. (d) time-integral of the positive derivative signal; (e) time-integral of the negative derivative signal. After linear detrending of the signals in (d) and (e), (f) shows the integrated positive (P_+D) and negative (P_−D) derivative signals used as inputs to a multivariate autoregressive-moving average (ARMA) model with middle cerebral artery velocity (MCAv) as output. The mathematical derivation of P_+D and P_-D is described in Methods (Mathematical background).

Figure 2.

Representative results from the same subject as in Figure 1 for the right middle cerebral artery during sitting (a,d,g,j), standing (b,e,h,k) and repeated squat-stand maneuver at 0.05 Hz (c,f,i,l). (a–c) middle cerebral artery velocity (MCAv), (d–f) original mean arterial blood pressure, (g–i) integrated positive (continuous line) and negative (dashed line) derivatives of mean arterial blood pressure (BP), and (j–l) normalized MCAv responses to a step change in the original MAP (dotted line) and to the integrated positive (continuous line) and negative (dashed line) derivatives of MAP. Signals in (a–i) have been windowed (Hanning) after removing their mean values. The corresponding values of the autoregulation index (ARI) for the MCAv step responses were, 7.7, 3.7, and 2.7 (j); 5.2, 4.6, and 4.0 (k); and 4.0, 3.1, and 1.5 (l) for the original, integrated positive and negative derivatives of MAP, respectively.

Figure 3.

Population averages of normalized middle cerebral artery velocity step responses (SRMCAv) estimated from the integrated positive (continuous line) and negative (dashed line) derivatives of mean arterial blood pressure (MAP), compared with the responses obtained with the original MAP signal (dotted line), for the right (a,c,e) and left (b,d,f) hemispheres. (a,b) sitting position, (c standing position and (e,f) repeated squat-stand maneuver at 0.05 Hz. The error bars correspond to the largest ±1 SE of the three responses, at the point of occurrence.

Figure 4.

Population (n = 43) mean values of the autoregulation index (ARI) averaged for both hemispheres, estimated from the original mean arterial blood pressure (BP) signal (dotted line) and the integrated positive (continuous line) and negative (dashed line) derivatives of BP. The error bars correspond to ±1 SE. Both effects of condition (SSM, SIT, STAND) and estimation source were highly significant (p < 0.0001) in a 2-way ANOVA, without the interaction of effects.

Figure 5.

Number of significant differences between ARI values derived from the integrated positive and negative derivatives of mean arterial blood pressure, expressed in percent of the 10,000 runs performed with the bootstrap method. The critical sample size (N_crit) for each condition, is given by the intercept of the horizontal 95% line (long dashed line) with each curve, corresponding to repeated squat-stand maneuver (continuous line, N_crit= 24), standing (dotted line N_crit= 37) and sitting (dashed line, N_crit= 38).