Cerebral hemodynamics during orthostatic stress assessed by nonlinear modeling

Georgios D. Mitsis, Rong Zhang, Benjamin D. Levine, Vasilis Z. Marmarelis

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63 Scopus citations


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 10 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, whereas cerebral vasomotor reactivity was described by the model PETCO2 terms. 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. 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. The magnitude of the linear and nonlinear MABP-MCBFV Volterra kernels increased substantially above -30 mmHg 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.

Original languageEnglish (US)
Pages (from-to)354-366
Number of pages13
JournalJournal of applied physiology
Issue number1
StatePublished - 2006


  • Laguerre-Volterra network
  • Lower body negative pressure
  • Mean cerebral blood flow velocity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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