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

Am J Physiol Regul Integr Comp Physiol. 2018 Sep 1;315(3):R484-R495. doi: 10.1152/ajpregu.00032.2018. Epub 2018 Apr 18.

Abstract

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.

Keywords: Cushing mechanism; Granger causality; blood pressure; cerebral blood flow; sympathetic control.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adrenergic alpha-1 Receptor Antagonists / administration & dosage*
  • Adult
  • Blood Flow Velocity
  • Blood Pressure / drug effects*
  • Cardiovascular System / innervation*
  • Cerebrovascular Circulation / drug effects*
  • Double-Blind Method
  • Electrocardiography
  • Heart Rate / drug effects
  • Homeostasis
  • Humans
  • Male
  • Middle Cerebral Artery / diagnostic imaging
  • Middle Cerebral Artery / drug effects*
  • Middle Cerebral Artery / physiology
  • Models, Cardiovascular*
  • Photoplethysmography
  • Prazosin / administration & dosage*
  • Reflex
  • Stochastic Processes
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / physiology
  • Time Factors
  • Ultrasonography, Doppler, Pulsed
  • Ultrasonography, Doppler, Transcranial / methods
  • Young Adult

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Prazosin