Determinants of human cerebral pressure–flow velocity relationships: new insights from vascular modelling and Ca²⁺channel blockade

The fundamental determinants of human dynamic cerebral autoregulation are poorly understood, particularly the role of vascular compliance and the myogenic response. We sought to 1) determine whether capacitive blood flow associated with vascular compliance and driven by the rate of change in mean arterial blood pressure (dMAP/dt) is an important determinant of middle cerebral artery velocity (MCAv) dynamics and 2) characterise the impact of myogenic blockade on these cerebral pressure-flow velocity relations in humans. We measured MCAv and mean arterial pressure (MAP) during oscillatory lower body negative pressure (n =8) at 0.10 and 0.05 Hz before and after cerebral Ca²⁺ channel blockade (nimodipine). Pressure-flow velocity relationships were characterised using transfer function analysis and a regression-based Windkessel analysis that incorporates MAP and dMAP/dt as predictors of MCAv dynamics. Results show that incorporation of dMAP/dt accounted for more MCAv variance (R² 0.80-0.99) than if only MAP was considered (R2 0.05-0.90). 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 phase or coherence. Ca²⁺ channel blockade increased the conductive gain relation between MAP and MCAv (P<0.05), and reduced phase at 0.05 Hz (P<0.01). Capacitive and transfer function gain were unaltered. The findings suggest capacitive blood flow is an important determinant of cerebral haemodynamics that bears strong relations to some metrics of dynamic cerebral autoregulation derived from transfer function analysis, and that Ca²⁺ channel blockade enhances pressure-driven resistive blood flow but does not alter capacitive blood flow. the causes and effects of cerebrovascular diseases such as stroke and dementia.