Cerebral autoregulation is preserved in postural tachycardia syndrome.

To test whether cerebral autoregulation is impaired in patients with postural tachycardia syndrome (POTS), we evaluated 17 healthy control subjects and 27 patients with POTS. Blood pressure, heart rate, and cerebral blood velocity (transcranial Doppler) were recorded at rest and during 80 degree head-up tilt (HUT). Static cerebral autoregulation, as assessed from the change in cerebrovascular resistance during HUT, was the same in POTS and in controls. The properties of dynamic cerebral autoregulation were inferred from transfer gain, coherence, and phase of the relationship between blood pressure and cerebral blood velocity estimated from filtered data segments (0.02-0.8 Hz). Dynamic cerebral autoregulation of patients with POTS did not differ from that of controls. The patients' dynamic cerebral autoregulation did not change over the course of HUT, despite increased tachycardia suggestive of worsening orthostatic stress. Inflation of military anti-shock trouser pants substantially reduced the tachycardia of patients with POTS without affecting cerebral autoregulation. Symptoms of orthostatic intolerance were reduced in one-half of the patients following military anti-shock trouser pants inflation. We conclude that cerebral perfusion and autoregulation in many patients with POTS do not differ from that of normal control subjects.     

Dynamic cardiorespiratory interaction during head-up tilt-mediated presyncope

In 28 healthy adults, we compared the dynamic interaction between respiration and cerebral autoregulation in 2 groups of subjects: those who did and did not develop presyncopal symptoms during 70 degrees passive head-up tilt (HUT), i.e., nonpresyncopal (23 subjects) and presyncopal (5 subjects). Airflow, CO2, cerebral blood flow velocity (CBF), ECG, and blood pressure (BP) were recorded. To determine whether influences of mean BP (MBP) and systolic SP (SBP) on CBF were altered in presyncopal subjects, coherencies and transfer functions between these variables and mean and peak CBF (CBFm and CBFp) were estimated. To determine the influence of end-tidal CO2 (ETco2) on CBF, the relative CO2 reactivity (%change in CBFm per mmHg change in ETco2) was calculated. We found that in presyncopal subjects before symptoms during HUT, coherence between SBP and CBFp was higher (P=0.02) and gains of transfer functions between BP (MBP and SBP) and CBFm were larger (MBP, P=0.01; SBP, P=0.01) in the respiratory frequency region. In the last 3 min before presyncope, presyncopals had a reduced relative CO2 reactivity (P=0.005), likely a consequence of the larger decrease in ETco2. We hypothesize that the CO2-mediated increase in resistance attenuates autoregulation such that the relationship between systemic and cerebral hemodynamics is enhanced. Our results suggest that an altered cardiorespiratory interaction involving cerebral hemodynamics may contribute in the cascade of events during tilt that culminate in unexplained syncope.     

Inhibition of nitric oxide synthase does not alter dynamic cerebral autoregulation in humans

The aim of this study was to determine whether inhibition of nitric oxide synthase (NOS) alters dynamic cerebral autoregulation in humans. Beat-to-beat blood pressure (BP) and cerebral blood flow (CBF) velocity (transcranial Doppler) were measured in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). NOS was inhibited by intravenous NG-monomethyl-L-arginine (L-NMMA) infusion. Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. Pressor effects of L-NMMA on cerebral hemodynamics were compared with those of phenylephrine infusion. In the supine position, L-NMMA increased mean BP from 83+/-3 to 94+/-3 mmHg (P < 0.01). However, CBF velocity remained unchanged. Consequently, cerebrovascular resistance index (CVRI) increased by 15% (P < 0.05). BP and CBF velocity variability and transfer function gain at the low frequencies of 0.07-0.20 Hz did not change with L-NMMA infusion. Similar changes in mean BP, CBF velocity, and CVRI were observed after phenylephrine infusion, suggesting that increase in CVRI after L-NMMA was mediated myogenically by increase in arterial pressure rather than a direct effect of cerebrovascular NOS inhibition. During baseline tilt without L-NMMA, steady-state BP increased and CBF velocity decreased. BP and CBF velocity variability at low frequencies increased in parallel by 277% and 217%, respectively (P < 0.05). However, transfer function gain remained unchanged. During tilt with L-NMMA, changes in steady-state hemodynamics and BP and CBF velocity variability as well as transfer gain and phase were similar to those without L-NMMA. These data suggest that inhibition of tonic production of NO does not appear to alter dynamic cerebral autoregulation in humans.     

Dynamic modulation of cerebrovascular resistance as an index of autoregulation under tilt and controlled PET(CO(2))

Transfer function analysis of the arterial blood pressure (BP)-mean flow velocity (MFV) relationship describes an aspect of cerebrovascular autoregulation. We hypothesized that the transfer function relating BP to cerebrovascular resistance (CVRi) would be sensitive to low-frequency changes in autoregulation induced by head-up tilt (HUT) and altered arterial PCO(2). Nine subjects were studied in supine and HUT positions with end-tidal PCO(2) (PET(CO(2))) kept constant at normal levels: +5 and -5 mmHg. The BP-MFV relationship had low coherence at low frequencies, and there were significant effects of HUT on gain only at high frequencies and of PCO(2) on phase only at low frequencies. BP --> CVRi had coherence >0.5 from very low to low frequencies. There was a significant reduction of gain with increased PCO(2) in the very low and low frequencies and with HUT at the low frequency. Phase was affected by PCO(2) in the very low frequencies. Transfer function analysis of BP --> CVRi provides direct evidence of altered cerebrovascular autoregulation under HUT and higher levels of PCO(2).     

Multiresolution wavelet analysis of time-dependent physiological responses in syncopal youths

Our prior studies indicated that postural fainting relates to thoracic hypovolemia. A supranormal increase in initial vascular resistance was sustained by increased peripheral resistance until late during head-up tilt (HUT), whereas splanchnic resistance, cardiac output, and blood pressure (BP) decreased throughout HUT. Our aim in the present study was to investigate the alterations of baroreflex activity that occur in synchrony with the beat-to-beat time-dependent changes in heart rate (HR), BP, and total peripheral resistance (TPR). We proposed that changes of low-frequency Mayer waves reflect sympathetic baroreflex. We used DWT multiresolution analyses to measure their time dependence. We studied 22 patients, 13 to 21 yr old, 14 who fainted within 10 min of upright tilt (fainters) and 8 healthy control subjects. Multiresolution analysis was obtained of continuous BP, HR, and respirations as a function of time during 70 degrees upright tilt at different scales corresponding to frequency bands. Wavelet power was concentrated in scales corresponding to 0.125 and 0.25 Hz. A major difference from control subjects was observed in fainters at the 0.125 Hz AP scale, which progressively decreased from early HUT. The alpha index at 0.125 Hz was increased in fainters. RR interval 0.25 Hz power decreased in fainters and controls but was markedly increased in fainters with syncope and thereafter corresponding to increased vagal tone compared with control subjects at those times only. The data imply a rapid reduction in time-dependent sympathetic baroreflex activity in fainters but not control subjects during HUT.     

Control of cerebral blood velocity with furosemide-induced hypovolemia and upright tilt

The purpose of this study was to test the hypothesis that exacerbated reductions of cerebral blood velocity (CBV) during upright tilt with dehydration are associated with impaired cerebrovascular control. Nine healthy men were tilted head-up (HUT) to 70° for 10 min on two occasions separated by 7 days under euhydration (EUH) and dehydration (DEH; 40 mg of furosemide and water restriction) conditions. Beat-by-beat arterial pressures and CBV were measured during a 5-min supine baseline and during the first (T1) and last (T2) 5 min of HUT. Cerebral autoregulation and arterial baroreflex sensitivity were assessed in the frequency domain with cross-spectral techniques. DEH reduced plasma volume by 10% (P = 0.008) and supine mean CBV (CBV(mean)) by 11% (P = 0.002). Mean arterial pressure (MAP), stroke volume, and baroreflex sensitivity decreased during HUT (P ≤ 0.002), but absolute reductions were similar between hydration conditions, with the exception of stroke volume, which was lower at T1 during DEH than EUH (P = 0.04). CBV(mean) during DEH was lower (7 cm/s) over the course of the entire 10 min of HUT (P ≤ 0.004) than during EUH. Low-frequency oscillations (0.07-0.2 Hz) of MAP and CBV(mean) and MAP-CBV(mean) coherence were higher during DEH than EUH at T1 (P ≤ 0.02), but not at T2. Our results suggest that increased coherence between arterial pressure and CBV with the combination of DEH and HUT are indicative of altered cerebrovascular control. Increased CBV oscillations with DEH may reflect acute protective mechanisms to ensure adequate cerebral perfusion under conditions of reduced central blood volume.     

Tilt-table testing of patients with pacemaker and recurrent syncope

The diagnosis of recurrent syncope in patients with pacemakers (PM) is quite challenging and the etiology of syncope is often multifactorial. To portray the mechanism of syncope in PM patients, we report the results of head-up tilt table testing (HUT) in a series of patients with PM, originally implanted for reasons other than neurally mediated syncope, referred due to syncope or pre-syncope (aborted syncope, vertigo, suspected orthostatic hypotension).Forty-one patients with PM undergoing a HUT in our syncope unit between January 1st, 2007 and December 31st 2011 were included. A standard HUT protocol with nitroglycerine provocation was used and the test results were classified according to current guidelines. Baseline data were retrieved from the medical records.Overall, 54% of patients had a positive response to HUT. Vasodepressor or orthostatic hypotensive response were the most prevalent responses accounting for 72% of patients with a positive test. There were no differences between groups with positive or negative test result regarding age, gender, resting blood pressure and heart rate, daily fluid intake, pacing mode, pacing indication or pacing rhythm at rest.HUT in patients with pacemakers has a high diagnostic yield. Although, the majority of patients had a vasodepressor or orthostatic hypotensive response, cardioinhibitory response leading to syncope was also seen.     

Baroreflex control of muscle sympathetic nerve activity in postural orthostatic tachycardia syndrome

Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive tachycardia during orthostasis. To test the hypothesis that patients with POTS have decreased sympathetic neural responses to baroreflex stimuli, we measured heart rate (HR) and muscle sympathetic nerve activity (MSNA) responses to three baroreflex stimuli including vasoactive drug boluses (modified Oxford technique), Valsalva maneuver, and head-up tilt (HUT) in POTS patients and healthy control subjects. The MSNA response to the Valsalva maneuver was significantly greater in the POTS group (controls, 26 +/- 7 vs. POTS, 48 +/- 6% of baseline MSNA/mmHg; P = 0.03). POTS patients also had an exaggerated MSNA response to 30 degrees HUT (controls, 123 +/- 24 vs. POTS, 208 +/- 30% of baseline MSNA; P = 0.03) and tended to have an exaggerated response to 45 degrees HUT (controls, 137 +/- 27 vs. POTS, 248 +/- 58% of baseline MSNA; P = 0.10). Sympathetic baroreflex sensitivity calculated during administration of the vasoactive drug boluses also tended to be greater in the POTS patients; however, this did not reach statistical significance (P = 0.15). Baseline MSNA values during supine rest were not different between the groups (controls, 23 +/- 4 vs. POTS, 16 +/- 5 bursts/100 heartbeats; P = 0.30); however, resting HR was significantly higher in the POTS group (controls, 58 +/- 3 vs. POTS, 82 +/- 4 beats/min; P = 0.0001). Our results suggest that POTS patients have exaggerated MSNA responses to baroreflex challenges compared with healthy control subjects, although resting supine MSNA values did not differ between the groups.     

Syncope, cerebral perfusion, and oxygenation.

During standing, both the position of the cerebral circulation and the reductions in mean arterial pressure (MAP) and cardiac output challenge cerebral autoregulatory (CA) mechanisms. Syncope is most often associated with the upright position and can be provoked by any condition that jeopardizes cerebral blood flow (CBF) and regional cerebral tissue oxygenation (cO(2)Hb). Reflex (vasovagal) responses, cardiac arrhythmias, and autonomic failure are common causes. An important defense against a critical reduction in the central blood volume is that of muscle activity ("the muscle pump"), and if it is not applied even normal humans faint. Continuous tracking of CBF by transcranial Doppler-determined cerebral blood velocity (V(mean)) and near-infrared spectroscopy-determined cO(2)Hb contribute to understanding the cerebrovascular adjustments to postural stress; e.g., MAP does not necessarily reflect the cerebrovascular phenomena associated with (pre)syncope. CA may be interpreted as a frequency-dependent phenomenon with attenuated transfer of oscillations in MAP to V(mean) at low frequencies. The clinical implication is that CA does not respond to rapid changes in MAP; e.g., there is a transient fall in V(mean) on standing up and therefore a feeling of lightheadedness that even healthy humans sometimes experience. In subjects with recurrent vasovagal syncope, dynamic CA seems not different from that of healthy controls even during the last minutes before the syncope. Redistribution of cardiac output may affect cerebral perfusion by increased cerebral vascular resistance, supporting the view that cerebral perfusion depends on arterial inflow pressure provided that there is a sufficient cardiac output.     

Low-frequency oscillation of sympathetic nerve activity decreases during development of tilt-induced syncope preceding sympathetic withdrawal and bradycardia

Sympathetic activation during orthostatic stress is accompanied by a marked increase in low-frequency (LF, approximately 0.1-Hz) oscillation of sympathetic nerve activity (SNA) when arterial pressure (AP) is well maintained. However, LF oscillation of SNA during development of orthostatic neurally mediated syncope remains unknown. Ten healthy subjects who developed head-up tilt (HUT)-induced syncope and 10 age-matched nonsyncopal controls were studied. Nonstationary time-dependent changes in calf muscle SNA (MSNA, microneurography), R-R interval, and AP (finger photoplethysmography) variability during a 15-min 60 degrees HUT test were assessed using complex demodulation. In both groups, HUT during the first 5 min increased heart rate, magnitude of MSNA, LF and respiratory high-frequency (HF) amplitudes of MSNA variability, and LF and HF amplitudes of AP variability but decreased HF amplitude of R-R interval variability (index of cardiac vagal nerve activity). In the nonsyncopal group, these changes were sustained throughout HUT. In the syncopal group, systolic AP decreased from 100 to 60 s before onset of syncope; LF amplitude of MSNA variability decreased, whereas magnitude of MSNA and LF amplitude of AP variability remained elevated. From 60 s before onset of syncope, MSNA and heart rate decreased, index of cardiac vagal nerve activity increased, and AP further decreased to the level at syncope. LF oscillation of MSNA variability decreased during development of orthostatic neurally mediated syncope, preceding sympathetic withdrawal, bradycardia, and severe hypotension, to the level at syncope.     

Is there diurnal variation in initial and delayed orthostatic hypotension during standing and head-up tilt?

Moving rapidly from a supine to a standing posture is a common daily activity, yet a significant physiological challenge. Syncope can result from the development of initial orthostatic hypotension (IOH) involving a transient fall in systolic/diastolic blood pressure (BP) of >40/20 mm Hg within the first 15 s, and/or a delayed orthostatic hypotension (DOH) involving a fall in systolic/diastolic BP of >20/10 mm Hg within 15 min of posture change. Although epidemiological data indicate a heightened syncope risk in the morning, little is known about the diurnal variation in the IOH and DOH mechanisms associated with postural change. The authors hypothesized that the onset of IOH and DOH occurs sooner, and the associated cardiorespiratory and cerebrovascular changes are more pronounced, in the early morning. At 06:00 and 16:00 h, 17 normotensive volunteers, aged 26 ± 1 yrs (mean ± SE), completed a protocol involving supine rest, an upright stand, and a 60° head-up tilt (HUT) during which continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv), mean arterial BP (MAP), heart rate, and end-tidal Pco(2) (P(ET)co(2)) were obtained. Mean MCAv was ～12% lower at baseline in the morning (p ≤ .01) and during the HUT (p ?.30). In conclusion, although there is a marked reduction in MCAv in the morning, there is an absence of diurnal variation in the onset of and associated physiological responses associated with IOH and DOH. These responses, at least in this population, are unlikely contributors to the diurnal variation in orthostatic tolerance.     

Impaired cerebrovascular autoregulation and reduced CO₂ reactivity after long duration spaceflight

Long duration habitation on the International Space Station (ISS) is associated with chronic elevations in arterial blood pressure in the brain compared with normal upright posture on Earth and elevated inspired CO(2). Although results from short-duration spaceflights suggested possibly improved cerebrovascular autoregulation, animal models provided evidence of structural and functional changes in cerebral vessels that might negatively impact autoregulation with longer periods in microgravity. Seven astronauts (1 woman) spent 147 ± 49 days on ISS. Preflight testing (30-60 days before launch) was compared with postflight testing on landing day (n = 4) or the morning 1 (n = 2) or 2 days (n = 1) after return to Earth. Arterial blood pressure at the level of the middle cerebral artery (BP(MCA)) and expired CO(2) were monitored along with transcranial Doppler ultrasound assessment of middle cerebral artery (MCA) blood flow velocity (CBFV). Cerebrovascular resistance index was calculated as (CVRi = BP(MCA)/CBFV). Cerebrovascular autoregulation and CO(2) reactivity were assessed in a supine position from an autoregressive moving average (ARMA) model of data obtained during a test where two breaths of 10% CO(2) were given four times during a 5-min period. CBFV and Doppler pulsatility index were reduced during -20 mmHg lower body negative pressure, with no differences pre- to postflight. The postflight indicator of dynamic autoregulation from the ARMA model revealed reduced gain for the CVRi response to BP(MCA) (P = 0.017). The postflight responses to CO(2) were reduced for CBFV (P = 0.056) and CVRi (P = 0.047). These results indicate that long duration missions on the ISS impaired dynamic cerebrovascular autoregulation and reduced cerebrovascular CO(2) reactivity.     

Naloxone-like influence of TRH and ACTH-(4-7) on hypothalamic blood flow autoregulation in the rat

The influence of intracerebroventricularly (ICV) administered thyrotropin-releasing hormone pGlu-His-Pro-NH2 (TRH), pGlu-His-Phe-NH2 (TRH analog, (TRHa)), Met-Glu-His-Phe(ACTH-(4-7)) and His-Phe-Arg-Trp-Gly (ACTH-(6-10)) on autoregulation of cerebral blood flow was studied in anesthetized, ventilated rats. Autoregulatory capacity of the cerebrovascular bed was tested by hypothalamic blood flow (HBF) and total cerebral blood volume (CBV) determinations during consecutive stepwise lowering of the systemic mean arterial pressure to 80, 60 and 40 mmHg, by hemorrhage. None of the peptides caused a change in resting HBF or CBV upon ICV administration (5 micrograms/kg). However, the same dose of TRH, TRHa and ACTH-(4-7) resulted in impairment of autoregulation. ACTH-(6-10) was not effective. Thus, the disturbed autoregulation may be due to the presence of the dipeptide Glu-His which is common to TRH, TRHa and ACTH-(4-7).     

A nonlinear dynamic approach reveals a long-term stroke effect on cerebral blood flow regulation at multiple time scales

Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary physiological signals.     

Does nitric oxide buffer arterial blood pressure variability in humans?

Animal studies suggest that nitric oxide (NO) plays an important role in buffering short-term arterial pressure variability, but data from humans addressing this hypothesis are scarce. We evaluated the effects of NO synthase (NOS) inhibition on arterial blood pressure (BP) variability in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). Systemic NOS was blocked by intravenous infusion of N(G)-monomethyl-L-arginine (L-NMMA). Electrocardiogram and beat-by-beat BP in the finger (Finapres) were recorded continuously for 6 min, and brachial cuff BP was recorded before and after L-NMMA in each body position. BP and R-R variability and their transfer functions were quantified by power spectral analysis in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.35 Hz) ranges. L-NMMA infusion increased supine BP (systolic, 109 +/- 4 vs. 122 +/- 3 mmHg, P = 0.03; diastolic, 68 +/- 2 vs. 78 +/- 3 mmHg, P = 0.002), but it did not affect supine R-R interval or BP variability. Before L-NMMA, HUT decreased HF R-R variability (P = 0.03), decreased transfer function gain (LF, 12 +/- 2 vs. 5 +/- 1 ms/mmHg, P = 0.007; HF, 18 +/- 3 vs. 3 +/- 1 ms/mmHg, P = 0.002), and increased LF BP variability (P < 0.0001). After L-NMMA, HUT resulted in similar changes in BP and R-R variability compared with tilt without L-NMMA. Increased supine BP after L-NMMA with no effect on BP variability during HUT suggests that tonic release of NO is important for systemic vascular tone and thus steady-state arterial pressure, but NO does not buffer dynamic BP oscillations in humans.     

Failure of cerebral autoregulation as a cause of brain dysfunction in the elderly.

Cerebral blood flow in relation to change in arterial pressure was measured in 11 elderly patients with postural hypotension. Seven patients with symptoms showed bilateral or unilateral failure of cerebral autoregulation, while the four asymptomatic patients did not. Variations in cerebral autoregulation would explain why some elderly people with minor falls of systemic arterial pressure develop clinical signs of cerebral ischaemia whereas others with greater falls in blood pressure remain asymptomatic. Elderly patients with impaired autoregulation may be at risk of brain damage from minor falls in blood pressure.     

Differential effects of lower body negative pressure and upright tilt on splanchnic blood volume

Upright posture and lower body negative pressure (LBNP) both induce reductions in central blood volume. However, regional circulatory responses to postural changes and LBNP may differ. Therefore, we studied regional blood flow and blood volume changes in 10 healthy subjects undergoing graded lower-body negative pressure (-10 to -50 mmHg) and 8 subjects undergoing incremental head-up tilt (HUT; 20 degrees , 40 degrees , and 70 degrees ) on separate days. We continuously measured blood pressure (BP), heart rate, and regional blood volumes and blood flows in the thoracic, splanchnic, pelvic, and leg segments by impedance plethysmography and calculated regional arterial resistances. Neither LBNP nor HUT altered systolic BP, whereas pulse pressure decreased significantly. Blood flow decreased in all segments, whereas peripheral resistances uniformly and significantly increased with both HUT and LBNP. Thoracic volume decreased while pelvic and leg volumes increased with HUT and LBNP. However, splanchnic volume changes were directionally opposite with stepwise decreases in splanchnic volume with LBNP and stepwise increases in splanchnic volume during HUT. Splanchnic emptying in LBNP models regional vascular changes during hemorrhage. Splanchnic filling may limit the ability of the splanchnic bed to respond to thoracic hypovolemia during upright posture.     

Dynamic cerebral autoregulation is preserved during acute head-down tilt.

Complete ganglion blockade alters dynamic cerebral autoregulation, suggesting links between systemic autonomic traffic and regulation of cerebral blood flow velocity. We tested the hypothesis that acute head-down tilt, a physiological maneuver that decreases systemic sympathetic activity, would similarly disrupt normal dynamic cerebral autoregulation. We studied 10 healthy young subjects (5 men and 5 women; age 21 +/- 0.88 yr, height 169 +/- 3.1 cm, and weight 76 +/- 6.1 kg). ECG, beat-by-beat arterial pressure, respiratory rate, end-tidal CO2 concentration, and middle cerebral blood flow velocity were recorded continuously while subjects breathed to a metronome. We recorded data during 5-min periods and averaged responses from three Valsalva maneuvers with subjects in both the supine and -10 degrees head-down tilt positions (randomized). Controlled-breathing data were analyzed in the frequency domain with power spectral analysis. The magnitude of input-output relations were determined with cross-spectral techniques. Head-down tilt significantly reduced Valsalva phase IV systolic pressure overshoot from 36 +/- 4.0 (supine position) to 25 +/- 4.0 mmHg (head down) (P = 0.03). Systolic arterial pressure spectral power at the low frequency decreased from 5.7 +/- 1.6 (supine) to 4.4 +/- 1.6 mmHg2 (head down) (P = 0.02), and mean arterial pressure spectral power at the low frequency decreased from 3.3 +/- 0.79 (supine) to 2.0 +/- 0.38 mmHg2 (head down) (P = 0.05). Head-down tilt did not affect cerebral blood flow velocity or the transfer function magnitude and phase angle between arterial pressure and cerebral blood flow velocity. Our results show that in healthy humans, mild physiological manipulation of autonomic activity with acute head-down tilt has no effect on the ability of the cerebral vasculature to regulate flow velocity.     

Vasomotor instability preceding tilt-induced syncope: does respiration play a role?

Lipsitz, Lewis A., Raymond Morin, Margaret Gagnon, DanKiely, and Aharon Medina. Vasomotor instability precedingtilt-induced syncope: does respiration play a role? J. Appl. Physiol. 83(2): 383-390, 1997.This studyaimed to determine whether alterations in cardiovascular dynamicsbefore syncope are related to changes in spontaneous respiration.Fifty-two healthy subjects underwent continuous heart rate (HR),arterial blood pressure (BP), and respiratory measurements during10-min periods of spontaneous and paced breathing (0.25 Hz) in thesupine and 60° head-up tilt positions. Data were evaluated by powerspectrum and transfer function analyses. During tilt, 27 subjectsdeveloped syncope or presyncope and 25 remained asymptomatic. Subjectswith tilt-induced syncope had significantly greater increases inlow-frequency (0.04-0.15 Hz) systolic BP, diastolic BP, and HRpower during tilt than the asymptomatic subjects(P  0.01). This difference waspresent during spontaneous but not paced breathing. However, averagetidal volume, respiratory rate, minute ventilation, proportion ofbreaths below 0.15 Hz, and low-frequency respiratory power during tilt did not differ between syncopal and nonsyncopal subjects. Transfer magnitudes between low-frequency respiration and BP, and between BP andinterbeat interval, were also similar between groups. Thus vasomotorinstability before syncope is not related to alterations in respirationor the cardiovagal baroreflex but may reflect oscillating centralsympathetic outflow to the vasculature.

     

WISE 2005: altered cerebrovascular autoregulation after 60 day head-down bed rest

We tested the hypothesis that 60 days of head-down bed rest (HDBR) would affect cerebrovascular autoregulation and that this change would be correlated with changes in tolerance to the upright posture. Twenty-four healthy women (32 +/- 4 yrs) participated in a 60-d bed rest study at the MEDES Clinic in Toulouse, France. End tidal CO2 (ETCO2), continuous blood pressure (BP), middle cerebral artery (MCA) velocity and time to presyncope (endpoint) were measured during an orthostatic tolerance test conducted before/after bed rest. Given the large range of change in tolerance even within assigned countermeasure groups, we separated subjects for this analysis on the basis of the change in endpoint (Delta endpoint) pre- to post-bed rest. Autoregulation and CO2 responsiveness were evaluated on a different day from a two-breath test with intermittent hypercapnic exposure. Autoregressive moving average (ARMA) modeled the two confounding inputs, BP and CO2, on cerebrovascular blood flow. The cerebrovascular resistance index (CVRi) was expected to decrease following a decrease in BP at the MCA to assist in maintenance of cerebral blood flow. Subjects with the smallest Delta endpoint after bed rest had a 78% increase in the gain of the BP --> CVRi response. Meanwhile, the groups with greater decline in orthostatic tolerance post-HDBR had no change in the gain of this response. ETCO2 was lower overall following HDBR, decreasing from 41.8 +/- 3.4 to 40.2 +/- 3.0 in supine rest, 37.9 +/- 3.4 to 33.3 +/- 4.0 in early tilt, and 29.5 +/- 4.4 to 27.1 +/- 5.1 at pre-syncope. There was however, higher MCA velocity at any ETCO2 for post- compared to pre-HDBR. In summary, changes in autoregulation were found only in those subjects who had the smallest change from pre- to post-HDBR orthostatic tolerance. The changes may assist in buffering changes in cerebral blood flow during orthostatic hypotension post-HDBR. The reduction in ETCO2 after bed rest might be due to a change in chemoreceptor response to blood CO2, but the cerebrovascular system seems to have completely compensated.