Nonlinear modeling of the dynamic effects of arterial pressure and CO2 variations on cerebral blood flow in healthy humans

The effect of spontaneous beat-to-beat mean arterial blood pressure fluctuations and breath-to-breath end-tidal CO₂ fluctuations on beat-to-beat cerebral blood flow velocity variations is studied using the Laguerre-Volterra network methodology for multiple-input nonlinear systems. The observations made from experimental measurements from ten healthy human subjects reveal that, whereas pressure fluctuations explain most of the high-frequency blood flow velocity variations (above 0.04 Hz), end-tidal CO₂ fluctuations as well as nonlinear interactions between pressure and CO₂ have a considerable effect in the lower frequencies (below 0.04 Hz). They also indicate that cerebral autoregulation is strongly nonlinear and dynamic (frequency-dependent). Nonlinearities are mainly active in the low-frequency range (below 0.04 Hz) and are more prominent in the dynamics of the end-tidal CO₂-blood flow velocity relationship. Significant nonstationarities are also revealed by the obtained models, with greater variability evident for the effects of CO₂ on blood flow velocity dynamics.