The physiological mechanism(s) for the regulation of the dynamic pressure-flow relationship of the cerebral circulation are not well understood. We studied the effects of acute cerebral vasoconstriction on the transfer function between spontaneous changes in blood pressure (BP) and cerebral blood flow velocity (CBFV) in 13 healthy subjects (30 ± 7 years). CBFV was measured in the middle cerebral artery using transcranial Doppler. BP was increased stepwise with phenylephrine infusion at 0.5, 1.0 and 2.0 μg kg -1 min -1 . Phenylephrine increased BP by 11, 23 and 37% from baseline, while CBFV increased ( Abbreviations BP, blood pressure; CBFV, cerebral blood flow velocity; CVRI, cerebrovascular resistance index; ETCO 2 , End-tidal CO 2 ; MCA, the middle cerebral artery; SRF, step-response function; TCD, transcranial Doppler; VLF, the very low frequency range from 0.02 to 0.07 Hz; LF, the low frequency range from 0.07 to 0.20 Hz; HF, the high frequency range from 0.20 to 0.35 Hz.Continuous measurement of cerebral blood flow (CBF) velocity with transcranial Doppler (TCD) combined with non-invasive measurement of arterial pressure has made the study of the dynamic pressure-flow relationship of the cerebral circulation practical in humans (Aaslid et al. 1989;Diehl et al. 1995;Panerai et al. 1998;Zhang et al. 1998).Typically, a linear transfer function method has been used to estimate the magnitude and the phase relationship between spontaneous changes in arterial blood pressure (BP) and CBF velocity to assess dynamic cerebral autoregulation, a concept implicating that cerebrovascular resistance responds rapidly to changes in BP to attenuate changes in CBF on a beat-to-beat basis (Aaslid et al. 1989;Zhang et al. 1998). In addition, a second-order linear differential equation has been used to describe the dynamic BP-CBF velocity relationship during induced transient changes in BP using a thigh cuff method (Tiecks et al. 1995). Application of these methods in clinical studies showed that assessment of dynamic autoregulation may provide valuable information for management of patients with cerebrovascular diseases (Haubrich et al. 2003;Reinhard et al. 2004).Despite these developments, the physiological mechanisms underlying the dynamic pressure-flow relationship of the cerebral circulation are not well understood. In particular, the currently used methods assume that beat-to-beat changes in CBF velocity in response to BP are determined mainly, if not solely, by the mechanisms of dynamic autoregulation.

Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 ± 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (< 0.15 Hz) is probably mediated by both sympathetic nerve activity and intrinsic vasomotor rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other, non-neural factors.