Studies using transfer function analyses have shown that the relation between arterial pressure (AP) and transcranial Doppler-derived cerebral blood flow velocity (CBFV) oscillations during resting conditions can be used to predict the CBFV response to a sudden blood pressure reduction during leg-cuff deflation. This analytic approach may be particularly useful in elderly patients if it can identify those at risk of cerebral hypoperfusion during orthostatic hypotension. If elderly people have impairments in cerebral autoregulation that allow changes in AP to be passively transferred to CBFV, then the resting transfer function relating these signals may be a particularly good predictor of the CBFV response to orthostasis in these individuals.
Normal cerebral autoregulation acts like a high-pass filter and blunts the transfer of low- frequency AP oscillations (<0.2 Hz) onto CBFV. Therefore, we hypothesized that the transfer function describing the dynamic relation between AP and CBFV would yield poor predictions of the low-frequency CBFV response to posture change in healthy young subjects. Moreover, in the higher frequency range of the cardiac cycle (0.7-1.4 Hz), where cerebral autoregulatory mechanisms are presumably not operative, we postulated that the transfer function would provide a good prediction of the CBFV response to orthostasis. Accordingly, in this study we computed the transfer function between resting AP and CBFV, used the corresponding impulse response function to predict the CBFV response to sudden pressure changes during standing, and compared the predicted and observed responses between groups of healthy young and healthy elderly subjects.
We carried out the transfer function analysis for healthy young and elderly subjects and predicted the CBFV for a sudden change in AP (induced by posture change, i.e., sitting to standing) by considering impulse responses (obtained by inverse Fourier transform of transfer function) containing different frequency ranges. The physiologically important frequency ranges 0.05-0.2 Hz (low-frequency) and 0.7-1.4 Hz (heart-beat frequency) are selected for prediction. The prediction for both the groups was poor when only low-frequency changes are considered. The prediction dramatically improved when the high-frequency oscillations were considered but it happened only in the case of healthy elderly subjects but not healthy young subjects. The above results suggests the following:
The results of this study elucidate several important aspects of pressure-flow relationships in the middle cerebral artery circulation, and their alterations in healthy elderly subjects. First, using transfer function analyses, it is evident in young subjects that the linear relationship between arterial pressure and middle cerebral artery blood flow velocity during sitting steady-state conditions is altered during orthostatic stress across a wide range of physiologic frequencies. This finding suggests that various regulatory responses to transient hypotension during standing blunt the transmission of arterial pressure changes onto cerebral blood flow. Moreover, it suggests that the mechanisms governing pressure-flow relations during basal conditions are different from those engaged during a perturbation such as standing. The mechanisms called into play during active standing include low-frequency (< 0.2 Hz) vascular responses in the peripheral cerebral circulation (e.g., autoregulatory myogenic vasodilitation) and systemic circulation (vasoconstriction), as well as heartbeat-frequency (0.7-1.4 Hz) systemic hemodynamic responses [e.g., cardiovagal baroreflexes that increase heart rate].
Second, our analysis suggests that in healthy elderly subjects, low-frequency cerebral autoregulation remains intact, but higher frequency regulatory mechanisms affecting cerebral blood flow velocity are altered. Thus, heartbeat-frequency arterial pressure oscillations are passively transmitted to cerebral blood flow in supine and upright positions, without intervening adaptive responses. This finding may reflect vascular stiffening in the older subjects, leading to more passive transmission of pressure onto CBFV. Furthermore, the increase in cerebral blood flow pulsatility seen in young subjects during posture change may reflect rapid circulatory adjustments in the cerebral vasculature, which loses compliance with advancing age. The increased systolic pulse wave amplification observed in the young group may be due to greater cardioacceleration. Elderly subjects have impaired cardioacceleration during orthostatic stress that may be responsible for diminished pulse amplification.
Third, our study suggests that a linear model may not be appropriate to predict changes in cerebral blood flow during orthostatic stress. The simple linear relationship between pressure and flow that describes the resting state, may not be adequate to describe the multiple interacting control mechanisms that maintain blood pressure and cerebral blood flow during posture change.