Is the Cushing mechanism a dynamic blood pressure-stabilizing system? Insights from Granger causality analysis of spontaneous blood pressure and cerebral blood flow

Blood pressure (BP) regulation is widely recognized as being integral to the control of end-organ perfusion, but it remains unclear whether end-organ perfusion also plays a role in driving changes in BP. A randomized and placebo-controlled study design was followed to examine feedback relationships between very-low-frequency fluctuations in BP and cerebral blood flow (CBF) in humans under placebo treatment and α1-adrenergic blockade. To determine the causal relations among hemodynamic variables, BP, middle cerebral artery blood velocity (MCAv), and end-tidal CO 2 time-series were decimated, low-pass filtered (<0.07 Hz), fitted to vector autoregressive models, and tested for Granger causality in the time domain. Results showed that 1) at baseline, changes in BP and MCAv often interact in a closed-loop; and 2) α1-adrenergic blockade results in the dominant causal direction from BP to MCAv. These results suggest that, between subjects, cerebral pressure-flow interactions at time scales < 0.07 Hz are frequently bidirectional, and that in the presence of an intact autonomic nervous system BP may be regulated by reflex pathways sensitive to changes in CBF.