Reports of research work funded by grants prior to 2014
University of Otago Wellington
Defining the role of Arterial Elasticity in the regulation of Cerebral Blood Flow
Department of Surgery and Anaesthesia
For decades physiologists have believed that cerebral arteries are rigid vessels incapable of passively buffering brain blood flow. As a result, most research into brain blood flow regulation have focused on cerebral autoregulation (CA) of vascular smooth muscle tone, ignoring passive elastic properties of the arterial wall. However, despite their widespread use, we have previously found that few metrics of CA demonstrate statistical associations with each other to support a common functional basis. Considering that the cerebral microcirculation is susceptible to sheer-stress injury, which can result in cerebrovascular degeneration and cognitive impairment, we sought to redefine the role of arterial Windkessel properties (i.e. resistance and compliance) in the regulation of cerebral blood flow using experimental and computational modeling approaches.
We hypothesised that 1) middle cerebral blood velocity (MCAv) dynamics during or following a transient blood pressure stimulus can be explained by linear cerebrovascular Windkessel properties, and 2) the intracranial vasculature constitutes a compliant Windkessel capable of passively smoothing blood flow variations. Eighteen volunteers underwent controlled blood pressure manipulations including bilateral thigh cuff deflation (TC), sit to stand (STS) manoeuvres, and oscillatory lower body negative pressure (OLBNP) at 4 frequencies between 0.03 to 0.10 Hz under normocapnic and hypercapnic (5% CO2) conditions. Pressure-flow recordings were analysed using a Windkessel modelling approach that partitions the resistance and compliance contributions to MCAv dynamics. Blood velocity signals were also recorded (n=6) at the level of the internal carotid artery (ICA), middle cerebral artery (MCA), and straight sinus (SS), and analysed using flow-flow transfer function analysis.
Results showed that the Windkessel model explained over half of the MCAv recovery dynamics following TC (89 ± 1.9%), STS (89 ± 3.6 %) and during 0.07 Hz (73 ± 4 %) and 0.10 Hz (89 ± 1.5 %) OLBNP. Hypercapnia did not alter Windkessel model fits (mean square error, p=0.75), but enhanced linear resistive blood flow consistent with cerebral vasodilation (p<0.05). Flow-flow transfer functions between the IC and SS, and MCA and SS revealed a pattern of decrease gain values at higher frequencies consistent with a low-pass filter. These findings suggest that: 1) MCAv dynamics during acute blood pressure challenges can be explained by Windkessel properties independent of CA: 2) haemodynamic effects of hypercapnoea during transient blood pressure challenges primarily reflect changes in Windkessel properties rather than CA impairment; and 3) cerebral flow waves undergo characteristic Windkessel smoothing as they travel along the cerebrovascular path.
It has been suggested that exposure to decades of repetitive pulse wave propagation through the cerebrovascular bed can result in neurovascular degeneration and the eventual development of morbid conditions such as Alzheimer’s disease and vascular dementia. This hypothesis, acknowledged in a recent American Heart Association/Stroke Association statement, challenges the traditional view of beta amyloid deposition and neurofibrillary tangles being the primary cause of brain damage. Contrary to established assumptions, our study showed that cerebral arteries are distensible/compliant organs and therefore capable of militating against intimal sheer stress, which can otherwise cause endothelial stripping, thrombosis, and microinfarction. Our result challenges a central tenet in cerebrovascular physiology and has the potential to yield new insights into how the brain is protected from changes in blood pressure. Future studies should apply the techniques we have developed to confirm the possible involvement of cerebral Windkessel in the causation of pulse-wave related neurovascular injury in patient cohorts.