Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation.

We examined the effects of 30 min of exposure to either +3GX (front-to-back) or +GZ (head-to-foot) centrifugation on cerebrovascular responses to 80 degrees head-up tilt (HUT) in 14 healthy individuals. Both before and after +3 GX or +3 GZ centrifugation, eye-level blood pressure (BP(eye)), end tidal PCO2 (PET(CO2)), mean cerebral flow velocity (CFV) in the middle cerebral artery (transcranial Doppler ultrasound), cerebral vascular resistance (CVR), and dynamic cerebral autoregulatory gain (GAIN) were measured with subjects in the supine position and during subsequent 80 degrees HUT for 30 min. Mean BP(eye) decreased with HUT in both the GX (n = 7) and GZ (n = 7) groups (P < 0.001), with the decrease being greater after centrifugation only in the GZ group (P < 0.05). PET(CO2) also decreased with HUT in both groups (P < 0.01), but the absolute level of decrease was unaffected by centrifugation. CFV decreased during HUT more significantly after centrifugation than before centrifugation in both groups (P < 0.02). However, these greater decreases were not associated with greater increases in CVR. In the supine position after centrifugation compared with before centrifugation, GAIN increased in both groups (P < 0.05, suggesting an autoregulatory deficit), with the change being correlated to a measure of otolith function (the linear vestibulo-ocular reflex) in the GX group (r = 0.76, P < 0.05) but not in the GZ group (r = 0.24, P = 0.60). However, GAIN was subsequently restored to precentrifugation levels during postcentrifugation HUT (i.e., as BP(eye) decreased), suggesting that both types of centrifugation resulted in a leftward shift of the cerebral autoregulation curve. We speculate that this leftward shift may have been due to vestibular activation (especially during +GX) or potentially to an adaptation to reduced cerebral perfusion pressure during +GZ.

Cerebral vasoconstriction precedes orthostatic intolerance after parabolic flight.

The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to before) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO(2) (P(ET)CO(2)) were measured while supine and during 80 degrees HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n = 7) or intolerant (OI) (n = 6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P(ET)CO(2) with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P(ET)CO(2). The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group postflight, particularly during the final 30 s of HUT (p < 0.05). However, this accentuated decrease in MCA MFV was not correlated to the greater decrease in P(ET)CO(2) during the same period (R = 0.20, p = 0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypoperfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P(ET)CO(2).

Vertical shift in cerebral autoregulation curve: a graded head-up tilt study.

According to the classical theory of cerebral autoregulation, cerebral blood flow (CBF) will be maintained at a near-constant level for cerebral perfusion pressure (CPP) within the range of 60-150 mmHg. In recent years, however, studies with contradicting results have demonstrated a change in CBF when the level of CPP had not changed significantly. It is suggested that a shift in the autoregulation curve may have taken place along the horizontal axis or along the vertical axis. This paper describes previously unreported findings of a graded head-up tilt (HUT) study which was designed as a preliminary experiment to test the protocol for possible use on astronauts upon returning from space-flight. Data from this study tend to support the findings of previous studies regarding possible shifts in the cerebral autoregulation curve. Five female and four male healthy volunteers were exposed to HUT for 5 minutes at each angle of 30 degrees, 60 degrees, and 90 degrees. Throughout the test, cerebrovascular and cardiovascular responses were evaluated by use of continuous acquisition of mean flow velocity (MFV) from the right middle cerebral artery with transcranial Doppler sonograhy, mean arterial blood pressure (MABP, Finapres) and heart rate (HR, ECG). Based on the last 60 seconds of data at each tilt angle and baseline, the percentage changes in MFV from baseline were found to be similar to those in MABP at the level of the brain (MABPbrain), and both were significant (p<0.05) at the 60 degrees (-9.1 +/- 7% for MABP brain, -9.8 +/- 5% for MFV) and 90 degrees (-13 degrees +/- 8%, -12.0 +/- 6%) positions. Heart rate (HR) increased significantly (p<0.05) from the baseline at 30 degrees (6.3 +/- 5%) through 90 degrees (23.3 +/- 8%). The trend toward decreasing MFV in normal subjects, even while MABP brain remained within the normal limits of cerebral autoregulation, may suggest a downward shift of the cerebral blood flow plateau in the classic cerebral autoregulation curve.

Complexity of middle cerebral artery blood flow velocity: effects of tilt and autonomic failure.

We examined spectral fractal characteristics of middle cerebral artery (MCA) mean blood flow velocity (MFV) and mean arterial blood pressure adjusted to the level of the brain (MAPbrain) during graded tilt (5 min supine, -10 degrees, 10 degrees, 30 degrees, 60 degrees, -10 degrees, supine) in eight autonomic failure patients and age- and sex-matched controls. From supine to 60 degrees, patients had a larger drop in MAPbrain (62 +/- 4.7 vs. 23 +/- 4.5 mmHg, P < 0.001; means +/- SE) and MFV (16.4 +/- 3.8 vs. 7.0 +/- 2.5 cm/s, P < 0.001) than in controls. From supine to 60 degrees, there was a trend toward a decrease in the slope of the fractal component (beta) of MFV (MFV-beta) in both the patients and the controls, but only the patients had a significant decrease in MFV-beta (supine: patient = 2.21 +/- 0.18, control = 1.99 +/- 0.60; 60 degrees: patient = 1.46 +/- 0.24, control = 1.62 +/- 0.19). The beta value of MAPbrain (MAPbrain-beta; 2.19 +/- 0.05) was not significantly different between patients and controls and did not change with tilt. High and low degrees of regulatory complexity are indicated by values of beta close to 1.0 and 2.0, respectively. The increase in fractal complexity of cerebral MFV in the patients with tilt suggests an increase in the degree of autoregulation in the patients. This may be related to the drop in MAPbrain. The different response of MFV-beta compared with that of MAPbrain-beta also indicates that MFV-beta is related to the regulation of cerebral vascular resistance and not systemic blood pressure.

Cerebrovascular and cardiovascular responses to graded tilt in patients with autonomic failure.

BACKGROUND AND PURPOSE: Patients with autonomic nervous system failure often experience symptoms of orthostatic intolerance while standing. It is not known whether these episodes are caused primarily by a reduced ability to regulate arterial blood pressure or whether changes in cerebral autoregulation may also be implicated. METHODS: Eleven patients and eight healthy age- and sex-matched control subjects were studied during a graded-tilt protocol. Changes in their steady state middle cerebral artery mean flow velocities (MFV), measured by transcranial Doppler, brain-level mean arterial blood pressures (MABPbrain), and the relationship between the two were assessed. RESULTS: Significant differences between patients and control subjects (P < .05) were found in both their MFV and MABPbrain responses to tilt. Patients' MFV dropped from 60 +/- 10.2 cm/s in the supine position to 44 +/- 14.0 cm/s at 60 degrees head-up tilt, whereas MABPbrain fell from 109 +/- 11.7 to 42 +/- 16.9 mm Hg. By comparison, controls' MFV dropped from 54 +/- 7.8 cm/s supine to 51 +/- 8.8 cm/s at 60 degrees, whereas MABPbrain went from 90 +/- 11.2 to 67 +/- 8.2 mm Hg. Linear regression showed no significant difference in the MFV-MABPbrain relationship between patients and control subjects, with slopes of 0.228 +/- 0.09 cm.s-1.mm Hg-1 for patients and 0.136 +/- 0.16 cm.s-1.mm Hg-1 for control subjects. CONCLUSIONS: The present study found significant differences between patients and control subjects in their MFV and MABPbrain responses to tilt but no difference in the autoregulatory MFV-MABPbrain relationship. These results suggest that patients' decreased orthostatic tolerance may primarily be the result of impaired blood pressure regulation rather than a deficiency in cerebral autoregulation.

Transfer function analysis of cerebral autoregulation dynamics in autonomic failure patients.

BACKGROUND AND PURPOSE: Autonomic nervous system diseases affect systemic blood pressure regulation. Patients with autonomic nervous system diseases have consistently larger drops in blood pressure associated with standing than the normal population. Autonomic dysfunction and/or these changes in blood pressure may affect dynamic cerebral autoregulation. METHODS: Heart rate, mean blood flow velocity (MBFV) of the middle cerebral artery via transcranial Doppler ultrasound, mean arterial blood pressure adjusted to brain level (MABPbrain) via Finapres, and end tidal CO2 were measured continuously during graded tilt (after 5 minutes in supine position as baseline, -10 degrees, +10 degrees, +30 degrees, +60 degrees, -10 degrees, and supine recovery) in autonomic failure patients and their age- and sex-matched control subjects. The dynamic response of MBFV to spontaneous variations in MABPbrain was investigated by cross-spectral analysis. The transfer gain and phase relationships between MBFV and MABPbrain were determined from the final 256 beats of each 5-minute-tilt segment. The transfer gain was normalized to mean MABPbrain and MBFV and then converted to decibels (dB). RESULTS: MBFV variation (0.03 to 0.14 Hz) preceded MABPbrain by similar phase angles in patients and control subjects and in all tilt conditions (patients: 31 +/- 5 degrees; control subjects: 30 +/- 5 degrees; mean +/- SEM). Patients had a higher supine gain than control subjects (P < .05). Both patients and control subjects showed a significant decrease in gain with tilt and by 60 degrees the patients were not different from the control subjects (supine to 60 degrees: patients = 5.23 +/- 0.77 to -1.65 +/- 0.89 dB; control subjects = 1.74 +/- 0.82 to -1.80 +/- 0.62 dB). CONCLUSIONS: These data indicate an altered, yet present, autoregulatory response with autonomic failure.

Simultaneous cerebrovascular and cardiovascular responses during presyncope.

BACKGROUND AND PURPOSE: Presyncope, characterized by symptoms and signs indicative of imminent syncope, can be aborted in many situations before loss of consciousness occurs. The plasticity of cerebral autoregulation in healthy humans and its behavior during this syncopal prodrome are unclear, although systemic hemodynamic instability has been suggested as a key factor in the precipitation of syncope. Using lower body negative pressure (LBNP) to simulate central hypovolemia, we previously observed falling mean flow velocities (MFVs) with maintained mean arterial blood pressure (MABP). These findings, and recent reports suggesting increased vascular tone within the cerebral vasculature at presyncope, cannot be explained by the classic static cerebral autoregulation curve; neither can they be totally explained by a recent suggestion of a rightward shift in this curve. METHODS: Four male and five female healthy volunteers were exposed to presyncopal LBNP to evaluate their cerebrovascular and cardiovascular responses by use of continuous acquisition of MFV from the right middle cerebral artery with transcranial Doppler sonography, MABP (Finapres), and heart rate (ECG). RESULTS: At presyncope, MFV dropped on average by 27.3 +/- 14% of its baseline value (P < .05), while MABP remained at 2.0 +/- 27% above its baseline level. Estimated cerebrovascular resistance increased during LBNP. The percentage change from baseline to presyncope in MFV and MABP revealed consistent decreases in MFV before MABP. CONCLUSIONS: Increased estimated cerebrovascular resistance, falling MFV, and constant MABP are evidence of an increase in cerebral vascular tone with falling flow, suggesting a downward shift in the cerebral autoregulation curve. Cerebral vessels may have a differential sensitivity to sympathetic drive or more than one type of sympathetic innervation. Future work to induce dynamic changes in MABP during LBNP may help in assessing the plasticity of the cerebral autoregulation mechanism.

Simultaneous transcranial Doppler and arterial blood pressure response to lower body negative pressure.

Microgravity induces fluid shifts which can alter the cardiovascular responses of astronauts both during space flight and on return to Earth. The decrease in orthostatic tolerance in astronauts returning from a weightless environment can be modelled in ground-based studies using lower body negative pressure (LBNP). This study examined the physiological changes induced by LBNP and determined a reliable method of predicting the onset of presyncope to enable evaluation of countermeasures for loss of orthostatic tolerance, such as glycerol-induced hyperhydration. Six healthy male subjects, aged 18 to 45 years, were each subjected to two LBNP tests, with or without glycerol ingestion. Continuous, non-invasive measurements of middle cerebral artery blood flow velocities (CBF) by transcranial Doppler, arterial blood pressure (Finapres ABP), ECG and LBNP box pressures were recorded during each test. Negative pressure was increased in three minute intervals until symptoms of presyncope were observed. An increase in heart rate (HR), a relatively constant mean ABP and a steady decline in mean CBF were consistently observed as the box pressure was decreased. The continuous on-line measurements clearly showed consistent dynamic changes in both CBF and ABP waveforms in response to changes in LBNP. At the onset of presyncope, sudden drops in mean ABP, HR and mean CBF were typically noted, the latter providing the earliest indication of presyncope. The time required to re-establish original baseline values of CBF and ABP after release of box pressure varied widely from six to over ten minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral blood flow velocities by transcranial Doppler during parabolic flight.

Microgravity is produced for 20 to 30 seconds in NASA's KC-135 aircraft at the end of a 2 G pullup for each of 40 parabolas per flight. Continuous transcranial Doppler ultrasound, arterial blood pressure, and acceleration levels were recorded for 12 male and 8 female healthy subjects without known cardiovascular or cerebrovascular disease. Recordings were made throughout 10 parabolas per subject in each of the supine, sitting, and standing postures. The data were digitized for off-line analysis using Fast Fourier Transform and other signal processing methods. A phase lag in changes to transcranial Doppler waveforms from the onset of acceleration was more pronounced in the standing position than in the sitting position. There was less of a phase lag in the supine position. These ultrasound changes preceded the more delayed variations in arterial blood pressure. The KC-135 provides a unique short-term environment that allows measurement of the human response to variations in acceleration but limits physiological monitoring of responses to a steady state of microgravity.