Evidence for bi‐directional feedback regulation of blood pressure and cerebral blood flow in humans

Abstract

Blood pressure regulation is widely recognised 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 blood pressure. This study examined the feedback relationships between short-term fluctuations in blood pressure (BP) and cerebral blood flow in humans under baseline and combined beta1-adrenergic (Metoprolol tartrate 0.2 mg/kg) and muscarinic cholinergic blockade (Glycopyrrolate 0.2 mg boluses) conditions. To determine the causal relations among haemodynamic variables, BP, middle cerebral artery blood velocity (MCAv), heart period, and end-tidal CO2 time-series were decimated, low pass filtered (<0.07 Hz), fitted to vector autoregressive moving average models and tested for Granger's causality in the time domain. Result showed that i) at baseline changes in BP and MCAv often interact in a closed-loop with a dominant causal direction from MCAv to BP; ii) beta-adrenergic blockade shifted the dominant causal direction from BP to MCAv with an increase in the proportion of individuals with unidirectional interactions, and iii) combined beta-adrenergic and cholinergic blockade frequently uncoupled BP-MCAv interactions. These results suggest that, between-subjects, cerebral pressure-flow interactions at time scales <0.07 Hz are frequently bi-directional, and that in the presence of an intact autonomic nervous system BP may be regulated by reflex pathways sensitive to changes in cerebral blood flow.