Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC102

Poster Communications

Determinants of human cerebral pressure-flow velocity relationships: new insights from vascular modeling and Ca2+blockade

Y. Tzeng1, G. S. Chan2, C. K. Willie3, P. N. Ainslie3

1. Surgery & Anaesthesia, University of Otago, Wellington, New Zealand. 2. Graduate School of Biomedical Engineering, University of New South Wales, Sydney, New South Wales, Australia. 3. Department of Human Kinetics, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.

The fundamental determinants of human cerebral pressure-flow relations are not fully understood, particularly the role of vascular mechanical properties in dynamic cerebral autoregulation. Furthermore, whilst the myogenic vascular response is frequently cited as a key determinant of cerebral haemodynamics there are limited experimental descriptions of dynamic pressure-flow relations following cerebral vascular Ca2+ blockade to validate this hypothesis (Zhang et al., 2009). Therefore, we sought to 1) determine whether capacitive blood flow in compliant cerebral vessels driven by the rate of change in blood pressure is an important determinant of middle cerebral artery velocity (MCAv) dynamics, and 2) characterise the impact of vascular myogenic blockade on these cerebral pressure-flow velocity relations in humans. In eight healthy subjects we measured MCAv and mean arterial pressure (MAP) at rest and during oscillatory lower body negative pressure at 0.10 and 0.05 Hz before and after selective cerebral Ca2+ channel blockade (60 mg oral Nimodipine). Cerebral pressure-flow velocity relationships were characterised using transfer function analysis and a regression-based analysis approach based on a two element arterial Windkessel model that incorporates MAP and the rate of change in MAP (dMAP/dt) as predictors of MCAv dynamics. Values are means±SD compared by ANOVA and related using correlation and multiple linear regression analysis. Results show that incorporation of dMAP/dt accounted for a greater proportion of the MCAv variance (R2 range 0.80-0.99) than if only MAP was considered (R2 range 0.05-0.90). Ranking of the standardised beta-coefficients showed that the compliance term was always ranked higher than the conductance term under both control and Ca2+ blockade conditions. Transfer function coherence under the control condition was >0.78 during both OLBNP frequencies and the transfer function phase lead of MCAvmean on MAP was seen in all subjects. The capacitive gain relating dMAP/dt and MCAv was strongly correlated to transfer function gain (0.05 Hz, r=0.93, p<0.01; 0.10 Hz, r=0.91, p<0.01) but not to the phase or coherence. Ca2+ blockade increased the conductive gain relation between MAP and MCAv (-0.00080±0.21 vs. 0.20±0.35, p<0.05) and reduced transfer function phase at 0.05Hz (1.3±0.62 vs. 0.90±0.50 radians, p<0.01). However, capacitive gain and transfer function gain were unaltered. These findings indicate that volume change in compliant cerebral vessels may be an important determinant of dynamic cerebral pressure-flow relations. Data also indicate that Ca2+ channel blockade enhances pressure-driven resistive blood flow that may render the cerebral microcirculation more vulnerable to systemic blood pressure fluctuations.

Where applicable, experiments conform with Society ethical requirements