Despite the rich innervation of the cerebral vasculature by both sympathetic and parasympathetic nerves [1], the role of autonomic control in cerebral circulation and, particularly, cerebral hemodynamics is not entirely clear [2]. Previous animal studies have reported inconsistent results regarding the effects of electrical stimulation or denervation on cerebral blood flow (CBF), cerebral pressure-flow relationship, and cerebral vessel response to metabolic stimuli [3]- [5]. Moreover, with the advance of transcranial Doppler ultrasound (TCD), which yields accurate-measurements of CBF velocity (CBFV) with high time resolution [6], it has been found that in humans CBFV in the middle cerebral artery decreased substantially during lower body negative pressure (LBNP) and head-up tilt in the absence of systemic hypotension, which suggests the presence of cerebral vasoconstriction associated with augmented sympathetic nerve activity during orthostatic stress [7]. These observations were based on assessing static measures of cerebral circulation, i.e., mean values of artevial blood pressure (ABP) and CBF with a low time resolution.However, the dynamic nature of cerebral autoregulation has been revealed using TCD measurements, to examine both the CBFV response to experimentally induced ABP changes [8]-[10] and the dynamic relation between spontaneous beat-to-beat ABP and CBFV variations [11]-[14]. These latter studies have revealed that dynamic autoregulation during resting conditions is frequency dependent, with slow ABP changes being attenuated more effectively by the cerebrovascular bed [14]. In this context, autonomic control of dynamic cerebral autoregulation was studied more recently by examining the dynamic relation between beat-to-beat ABP and CBFV variations during autonomic ganglion blockade. Transfer function analysis revealed a significant increase in the gain between ABP and CBFV from 0.02 to 0.07 Hz, suggesting altered autoregulation and active autonomic control [15].The cerebrovascular bed is exquisitely sensitive to changes in arterial CO 2 [1]. Recent studies have shown that small, spontaneous fluctuations of arterial CO 2 tension around the mean, assessed by end-tidal CO 2 (P ETCO 2 ) measurements, have a significant effect on slow fluctuations of both CBFV [12], [16] as well as regional blood flow, assessed by blood oxygen level-dependent functional magnetic resonance imaging [17], [18]. Furthermore, it has been suggested that cerebral hemodynamics are characterized by nonlinearities, both on the basis of low coherence values between ABP and mean CBFV (MCBFV) below 0.07 Hz [14] and by exploring the use of linear autoregressive models and the presence of nonlinear dynamics [19]. Consequently, we and others have shown that nonlinear Volterra models and/or multivariate models that incorporate P ETCO 2 variability are able to explain a considerably larger fraction of CBFV variability [12]
Methods
Experimental MethodsTwelve healthy subjects (nine men) with a mean age of 29 ± 6 years, height of 174 ± 10 cm...
