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* To whom correspondence should be addressed. E-mail: gmitsis{at}bmsr.usc.edu.
The effects of orthostatic stress, induced by lower body negative pressure (LBNP), on cerebral hemodynamics were examined in a nonlinear context. Spontaneous fluctuations of beat-to-beat mean arterial blood pressure (MABP) in the finger, mean cerebral blood flow velocity (MCBFV) in the middle cerebral artery, as well as breath-by-breath end-tidal CO2 concentration (PETCO2) were measured continuously in ten healthy subjects under resting conditions and during graded LBNP to presyncope. A two-input nonlinear Laguerre-Volterra network model was employed to study the dynamic effects of MABP and PETCO2 changes, as well as their nonlinear interactions, on MCBFV variations in the very low (VLF; below 0.04 Hz), low (LF; 0.04-0.15 Hz) and high frequency (HF; 0.15-0.30 Hz) ranges. Dynamic cerebral autoregulation was described by the model terms corresponding to MABP, while cerebral vasomotor reactivity was described by the model PETCO2 terms. Results: 1) The nonlinear model terms reduced the output prediction normalized mean square error substantially (by 15-20%) and had a prominent effect in the VLF range, both under resting conditions and during LBNP. 2) Whereas MABP fluctuations dominated in the HF range and played a significant role in the VLF and LF ranges, changes in PETCO2 accounted for a considerable fraction of the VLF and LF MCBFV variations, especially at high LBNP levels. 3) The magnitude of the linear and nonlinear MABP-MCBFV Volterra kernels increased substantially above -30 mm Hg LBNP in the VLF range, implying impaired dynamic autoregulation. In contrast, the magnitude of the PETCO2-MCBFV kernels reduced during LBNP at all frequencies, suggesting attenuated cerebral vasomotor reactivity under dynamic conditions. We speculate that these changes may reflect a progressively reduced cerebrovascular reserve to compensate for the increasingly unstable systemic circulation during orthostatic stress that could ultimately lead to cerebral hypoperfusion and syncope.
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