Lower body negative pressure identifies altered central vein characteristics without accompanying changes to baroreflexes in astronauts within hours of landing.

Cardiovascular deconditioning and altered baroreflexes predispose returning astronauts to Orthostatic Intolerance. We assessed 7 astronauts (1 female) before and following long-duration spaceflight (146 ± 43 days) with minimal upright posture prior to testing. We applied lower body negative pressure (LBNP) of up to - 30 mmHg to supine astronauts instrumented for continual synchronous measurements of cardiovascular variables, and intermittent imaging the Portal Vein (PV) and Inferior Vena Cava (IVC). During supine rest without LBNP, postflight elevations to total peripheral resistance (TPR; 15.8 ± 4.6 vs. 20.8 ± 7.1 mmHg min/l, p < 0.05) and reductions in stroke volume (SV; 104.4 ± 16.7 vs. 87.4 ± 11.5 ml, p < 0.05) were unaccompanied by changes to heart rate (HR) or estimated central venous pressure (CVP). Small increases to systolic blood pressure (SBP) and diastolic blood pressure (DBP) were not statistically significant. Autoregressive moving average modelling (ARMA) during LBNP did not identify differences to either arterial (DBP → TPR and SBP → HR) or cardiopulmonary (CVP → TPR) baroreflexes consistent with intact cardiovascular control. On the other hand, IVC and PV diameter-CVP relationships during LBNP revealed smaller diameter for a given CVP postflight consistent with altered postflight venous wall dynamics.

Accurate and consistent automatic seismocardiogram annotation without concurrent ECG.

Seismocardiography (SCG) is the measurement of vibrations in the sternum caused by the beating of the heart. Precise cardiac mechanical timings that are easily obtained from SCG are critically dependent on accurate identification of fiducial points. So far, SCG annotation has relied on concurrent ECG measurements. An algorithm capable of annotating SCG without the use any other concurrent measurement was designed. We subjected 18 participants to graded lower body negative pressure. We collected ECG and SCG, obtained R peaks from the former, and annotated the latter by hand, using these identified peaks. We also annotated the SCG automatically. We compared the isovolumic moment timings obtained by hand to those obtained using our algorithm. Mean ± confidence interval of the percentage of accurately annotated cardiac cycles were [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] for levels of negative pressure 0, -20, -30, -40, and -50 mmHg. LF/HF ratios, the relative power of low-frequency variations to high-frequency variations in heart beat intervals, obtained from isovolumic moments were also compared to those obtained from R peaks. The mean differences ± confidence interval were [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] for increasing levels of negative pressure. The accuracy and consistency of the algorithm enables the use of SCG as a stand-alone heart monitoring tool in healthy individuals at rest, and could serve as a basis for an eventual application in pathological cases.

Non-invasive estimation of cardiovascular parameters using ballistocardiography.

Ballistocardiography is a non-invasive technique to estimate heart function and relative changes in cardiac output. The goal of this study was to establish the relationship between ballistocardiogram (BCG) parameters and changes in cardiovascular parameters. A group of 20 subjects performed three different exercises on a force plate. In this study, we have characterized the significant differences induced by static and dynamic squats, and controlled respiration exercises on BCG parameters such as IJ-amplitude and RJ-time. The dynamic squat exercise induced the largest changes in IJ-amplitude (107-123% higher) and the RJ-time (21-23% lower). Furthermore, the IJ-amplitude of the BCG signal was found to be positively related to the cardiac output.

Reduced heart rate variability during sleep in long-duration spaceflight.

Limited data are available to describe the regulation of heart rate (HR) during sleep in spaceflight. Sleep provides a stable supine baseline during preflight Earth recordings for comparison of heart rate variability (HRV) over a wide range of frequencies using both linear, complexity, and fractal indicators. The current study investigated the effect of long-duration spaceflight on HR and HRV during sleep in seven astronauts aboard the International Space Station up to 6 mo. Measurements included electrocardiographic waveforms from Holter monitors and simultaneous movement records from accelerometers before, during, and after the flights. HR was unchanged inflight and elevated postflight [59.6 ± 8.9 beats per minute (bpm) compared with preflight 53.3 ± 7.3 bpm; P < 0.01]. Compared with preflight data, HRV indicators from both time domain and power spectral analysis methods were diminished inflight from ultralow to high frequencies and partially recovered to preflight levels after landing. During inflight and at postflight, complexity and fractal properties of HR were not different from preflight properties. Slow fluctuations (<0.04 Hz) in HR presented moderate correlations with movements during sleep, partially accounting for the reduction in HRV. In summary, substantial reduction in HRV was observed with linear, but not with complexity and fractal, methods of analysis. These results suggest that periodic elements that influence regulation of HR through reflex mechanisms are altered during sleep in spaceflight but that underlying system complexity and fractal dynamics were not altered.

Precordial acceleration signals improve the performance of diastolic timed vibrations.

BACKGROUND AND OBJECTIVE: This paper introduces a seismocardiography based methodology of predicting the start and the end of diastole to be used in diastolic timed vibrations (DTV), which provides non-invasive emergency treatment of acute coronary thrombosis by applying direct mechanical vibrations to the patient chest during diastole of heart cycles. It is proposed that seismocardiogram (SCG), in combination with electrocardiogram (ECG), provides a new means of diastole prediction. METHODS: An accelerometer was placed on the sternum of 120 healthy participants and 22 ischemic heart patients to record precordial accelerations created by the heart. The accelerometer signal was used to extract SCG and phonocardiogram (PCG). Two independent trained experts annotated the extracted signals based on the timings of the start and end of diastole. RESULTS: In the ischemic heart disease population by using 15 consecutive SCG cycles, the start and end of diastole was predicted in the upcoming cycles with 95 percentile error margin of 10.7 ms and 5.8 ms, respectively. These error margins were 7.4 ms and 3.5 ms, respectively, for normal participants. CONCLUSION: The results provide that prediction of the aortic valve closure point in the SCG signal helps start the vibrator in time to cover most of the isovolumic relaxation period. Also, through prediction of the mitral valve closure point in the SCG signal, safety of the technique can be assessed through prediction of the amount of unwanted vibrations applied during the isovolumic contraction period.

Muscle sympathetic nerve activity during intermittent handgrip exercise.

AIM: This study evaluated whether central command plays an important role in activating muscle sympathetic nerve activity (MSNA) during short-term maximal handgrip contractions. METHODS: The increase in MSNA was examined while influence of minimizing for other factors such as mechanoreflex, metaboreflex and fatigue during repetitive exercise in seven 19- to 26-year-old participants. Maximal voluntary handgrips (15-s contraction with a 45-s relaxation) were performed 10 times with a 15-s pause between alternate hands. MSNA was recorded from the tibial nerve analyzed using the burst frequency (BF) and total sympathetic nerve activity. RESULTS: The BF increased with the first unit, from 14.9±1.8 bursts·min-1 at baseline to 27.7±3.4 bursts·min-1 during contraction. The increase in the MSNA during contractions remained unchanged throughout the repetitions. The BF declined to baseline during the relaxation periods. The peak grip force decreased from 333±25 N for the first grip to 216±20 N for the last contraction. The MSAN increase remained constant despite a possible reduction in mechanoreflex during exercise as indicated from decreased maximal handgrip force. CONCLUSION: We suggested that the MSNA response was induced mainly by central command during short-term maximal handgrip contraction without metaboreflex influence and attenuated mechanoreflex input.

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.

Cardiovascular regulation during long-duration spaceflights to the International Space Station.

Early evidence from long-duration flights indicates general cardiovascular deconditioning, including reduced arterial baroreflex gain. The current study investigated the spontaneous baroreflex and markers of cardiovascular control in six male astronauts living for 2-6 mo on the International Space Station. Measurements were made from the finger arterial pressure waves during spontaneous breathing (SB) in the supine posture pre- and postflight and during SB and paced breathing (PB, 0.1 Hz) in a seated posture pre- and postflight, as well as early and late in the missions. There were no changes in preflight measurements of heart rate (HR), blood pressure (BP), or spontaneous baroreflex compared with in-flight measurements. There were, however, increases in the estimate of left ventricular ejection time index and a late in-flight increase in cardiac output (CO). The high-frequency component of RR interval spectral power, arterial pulse pressure, and stroke volume were reduced in-flight. Postflight there was a small increase compared with preflight in HR (60.0 ± 9.4 vs. 54.9 ± 9.6 beats/min in the seated posture, P < 0.05) and CO (5.6 ± 0.8 vs. 5.0 ± 1.0 l/min, P < 0.01). Arterial baroreflex response slope was not changed during spaceflight, while a 34% reduction from preflight in baroreflex slope during postflight PB was significant (7.1 ± 2.4 vs. 13.4 ± 6.8 ms/mmHg), but a smaller average reduction (25%) during SB (8.0 ± 2.1 vs. 13.6 ± 7.4 ms/mmHg) was not significant. Overall, these data show no change in markers of cardiovascular stability during long-duration spaceflight and only relatively small changes postflight at rest in the seated position. The current program routine of countermeasures on the International Space Station provided sufficient stimulus to maintain cardiovascular stability under resting conditions during long-duration spaceflight.

Delayed vasoconstrictor response to venous pooling in the calf is associated with high orthostatic tolerance to LBNP.

Central blood volume loss to venous pooling in the lower extremities and vasoconstrictor response are commonly viewed as key factors to distinguish between individuals with high and low tolerance to orthostatic stress. In this study, we analyzed calf vasoconstriction as a function of venous pooling during simulated orthostatic stress. We hypothesized that high orthostatic tolerance (OT) would be associated with greater vasoconstrictor responses to venous pooling compared with low OT. Nineteen participants underwent continuous stepped lower body negative pressure at -10, -20, -30, -40, -50, and -60 mmHg each for 5 min or until exhibiting signs of presyncope. Ten participants completed the lower body negative pressure procedure without presyncope and were categorized with high OT; the remaining nine were categorized as having low OT. Near-infrared spectroscopy measurements of vasoconstriction (Hachiya T, Blaber A, Saito M. Acta Physiologica 193: 117-127, 2008) in calf muscles, along with heart rate (HR) responses for each participant, were evaluated in relation to calf blood volume, estimated by plethysmography. The slopes of this relationship between vasoconstriction and blood volume were not different between the high- and low-tolerance groups. However, the onset of vasoconstriction in the high-tolerance group was delayed. Greater HR increments in the low-tolerance group were also observed as a function of lower limb blood pooling. The delayed vasoconstriction and slower HR increments in the high-tolerance group to similar venous pooling in the low group may suggest a greater vascular reserve and possible delayed reduction in venous return.

Reducing incapacitating symptoms during space flight: is postural deficiency syndrome an applicable model?

Severe and prolonged unmitigated SAS and SMS related symptoms have been thoroughly described in Astronauts during adaptation periods for orbital flight and post orbital flight. It has recently been shown that there is a strong correlation between these symptoms most often suffered by astronauts to that of the symptoms of patients suffering from Postural Deficiency Syndrome (PDS) on Earth that have been successfully assessed, diagnosed and treated. International peer-reviewed literature identifies PDS as a trauma induced medical condition which originates from central neural dysregulation of sensory-motor and cognitive controls; these dysfunctions can be accurately identified, measured, and monitored via a specific ocular-vestibular-postural monitoring system along with relevant clinical data. This higher level of understanding is necessary in order to reach the next stage of success for humans living and working in Space. Central sensory-motor and cognitive controls dysfunction underlie symptoms that can adversely impact and reflect alteration of eye-hand coordination, fine tuned dexterity, body positioning in space, space projection and trajectory control, perception of environment/obstacles, orientation in space and time, sensory motor and cognitive aspects of decision making, sensory-motor/cognitive error proneness. All of these factors are necessary for Astronaut's mission capabilities, while both carrying out operations in Space and performing the tasks required during and after re-entry. The objective of this paper is to elucidate how PDS related medical conditions are currently assessed, identified and monitored, and how these methodologies and technologies translate into a potential for better understanding of astronauts' potential incapacitation during space flight operations.

New paradigm for understanding in-flight decision making errors: a neurophysiological model leveraging human factors.

Human factors centered aviation accident analyses report that skill based errors are known to be cause of 80% of all accidents, decision making related errors 30% and perceptual errors 6%1. In-flight decision making error is a long time recognized major avenue leading to incidents and accidents. Through the past three decades, tremendous and costly efforts have been developed to attempt to clarify causation, roles and responsibility as well as to elaborate various preventative and curative countermeasures blending state of the art biomedical, technological advances and psychophysiological training strategies. In-flight related statistics have not been shown significantly changed and a significant number of issues remain not yet resolved. Fine Postural System and its corollary, Postural Deficiency Syndrome (PDS), both defined in the 1980's, are respectively neurophysiological and medical diagnostic models that reflect central neural sensory-motor and cognitive controls regulatory status. They are successfully used in complex neurotraumatology and related rehabilitation for over two decades. Analysis of clinical data taken over a ten-year period from acute and chronic post-traumatic PDS patients shows a strong correlation between symptoms commonly exhibited before, along side, or even after error, and sensory-motor or PDS related symptoms. Examples are given on how PDS related central sensory-motor control dysfunction can be correctly identified and monitored via a neurophysiological ocular-vestibular-postural monitoring system. The data presented provides strong evidence that a specific biomedical assessment methodology can lead to a better understanding of in-flight adaptive neurophysiological, cognitive and perceptual dysfunctional status that could induce in flight-errors. How relevant human factors can be identified and leveraged to maintain optimal performance will be addressed.

Heart rate responses at onset of contraction.

We tested the hypothesis that the initial heart rate (HR) response at the onset of maximal handgrip contraction is altered after training. 17 volunteers (nine trained and eight controls) performed ten intermittent static handgrip contractions with maximal effort, alternating between 15-s contractions and 15-s pauses. High-intensity static handgrip training was performed using the nondominant arm alone for 4 weeks. Handgrip force (HGF) and HR were analyzed for the initial 7 s of every static handgrip exercise. Peak HR (pre-training: 94.5 +/- 12.8 beats/min; post-training: 89.7 +/- 10.2 beats/min, p < 0.05) decreased. However, the magnitude of HR change at the onset of contraction remained constant (pre-training: 23.0 +/- 7.7 beats/min; post-training: 25.7 +/- 6.5 beats/min, p = 0.0767), while the HR responses in the subsequent bouts increased after training (p < 0.001). The resting HR decreased (pre-training: 71.5 +/- 9.3 beats/min; post-training 64.1 +/- 5.7 beats/min, p < 0.05). Maximal HGF increased by 11.1 % in trained arms and by 8.7 % in untrained arms, although an increase in maximal forearm girth was only observed in the trained arm (2.0 %, p < 0.0001). Although high-intensity training modulated the abrupt HR responses, the magnitude of the response remained unchanged at the onset of maximal forearm contraction and the resting HR significantly decreased.

Near-infrared spectroscopy provides an index of blood flow and vasoconstriction in calf skeletal muscle during lower body negative pressure.

AIM: Near-infrared spectroscopy (NIRS) has been used previously for forearm blood flow estimation at rest and during exercise. In this study we applied NIRS to selectively monitor deep calf oxygenated haemoglobin (Hb) responses in order to estimate blood flow changes in the calf muscle during lower body negative pressure (LBNP). The purpose of this study was to test the hypothesis that changes in calf skeletal muscle oxygenated-Hb, after the removal of superficial tissue responses, were related to blood flow changes during orthostatic stress, and to determine the efficacy of using NIRS measurements as an index of vasoconstriction. METHODS: Twenty-nine subjects participated in this study. All attempted a graded LBNP trial from baseline (0 mmHg) to -60 mmHg LBNP in 10 mmHg steps at 5-min intervals. Calf blood flow changes were estimated by oxygenated-Hb responses in relation to changes in mercury strain gauge plethysmography and muscle sympathetic nerve activity (MSNA). RESULTS: Calf selective deep oxygenated-Hb decreased continuously from -10 mmHg LBNP. Regression analysis showed that oxygenated-Hb was significantly related to declines in plethysmography evaluations of blood flow [oxygenated-Hb = (-1.57 +/- 0.26) + (1.86 +/- 0.49) plethysmography, r(2) = 0.87 +/- 0.09]. Changes in MSNA (total activity) were also inversely related to oxygenated-Hb (slope < 0, P = 0.037; r(2) = 0.52 +/- 0.15). CONCLUSION: These results suggest that changes in selective deep calf oxygenated-Hb can be utilized to estimate calf muscle blood flow changes that are most likely caused by vasoconstriction during graded LBNP.

Effect of acute exposure to 3660 m altitude on orthostatic responses and tolerance.

Orthostatic reflexes were examined at 375 m and after 60 min of exposure in a hypobaric chamber at 3660 m using a 20-min 70 degrees head-up tilt (HUT) test. Mean arterial blood pressure, R wave-R wave interval (RRI), and mean cerebral blood flow velocity (MFV) were examined with coarse-graining spectral analysis. Of 14 subjects, 7 at 375 m and 12 at 3660 m were presyncopal. Immediately on arrival to high altitude, breathing frequency and MFV increased, and endtidal PCO2, RRI, RRI complexity, and the parasympathetic nervous system indicator decreased. MFV was similar in HUT at both altitudes. The sympathetic nervous system indicator increased with tilt at 3660 m, whereas parasympathetic nervous system indicator decreased with tilt at both altitudes. Multiple regression analysis of supine variables from either 375 or 3660 m and the time to presyncope at 3660 m indicated that, after 1 h of exposure, increased presyncope at altitude was the result of 1). ineffective peripheral vasoconstriction, despite increased cardiac sympathetic nervous system activity with HUT, and 2). insufficient cerebral perfusion owing to cerebral vasoconstriction as the result of hypoxic hyperventilation-induced hypocapnia.

Inspiratory CO2 increases orthostatic tolerance during repeated tilt.

INTRODUCTION: The partial pressure of end tidal CO2 (PetCO2) is known to decrease with head-up tilt. Decreases in arterial CO2 reduce cerebral blood flow (CBF) and may increase the incidence of presyncope. We measured cerebral and central cardiovascular responses to repeated tilt where: 1) PetCO2 was allowed to change with tilt (eucapnic): and 2) PetCO2 was clamped at supine levels (isocapnic). METHODS: In eight healthy subjects breath-by-breath measurements were made of ventilation (VE) and PetCO2 along with beat-by-beat measurements of blood pressure (BP), heart rate (HR) and middle cerebral artery mean flow velocities (MFV). Following 30-min in the supine position, a series of six 10-min 90 degrees head-up tilts were performed, with 30-s of supine between each. Presyncopal subjects were returned immediately to the supine position. RESULTS: Statistical comparisons were made between the supine, and the first and last minute of the first tilt. BP, HR responses were not different between the eu- and isocapnic conditions; however, by the end of the first tilt VE was significantly higher than supine. MFV and BP at brain level decreased and HR increased from supine to tilt. MFV was higher in the isocapnic compared with the eucapnic condition but decreased from the beginning to the end of the first tilt in both conditions (i.e., tilt #1: eucap. 49.4 to 46.7; isocap. 65.0 to 59.6 cm s(-1); p < 0.05) while the BP remained constant. Five subjects were presyncopal in the study. With isocapnic tilt, presyncopal time was not reduced but was extended in four of the five subjects (2.2, 5.5, 6.3 and 31 min) yet at presyncope the values for MFV, BP and HR were the same in both conditions. CONCLUSIONS: Inspiratory CO2 contributed to increased MFV at the beginning of tilt and increased orthostatic tolerance.

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.

Coarse graining spectral analysis of HR and BP variability in patients with autonomic failure.

We examined heart rate and blood pressure variability (HRV and BPV) during graded tilt (5 min in each position: supine, -10 degrees, 10 degrees, 30 degrees, 60 degrees, -10 degrees, supine) in autonomic failure patients and age-matched controls. Heart rate was not different between patients and controls and increased with tilt (P < 0.001). Total HRV was reduced in patients (P < 0.03). Patients had reduced low-frequency (0-0.15 Hz) HRV and BPV (P < 0.005). With tilt, low-frequency BPV increased in controls, whereas high-frequency (> 0.15 Hz) BPV increased in patients. The slope of the fractal component (beta) for HRV and BPV was not different between patients and controls. HRV-beta increased (1.5-1.9, P < 0.01) with tilt, but BPV-beta (approximately 1.8) was unaffected. Values of beta close to 1 indicate high signal regulatory complexity, and values of beta close to 2 indicate low complexity. HRV and BPV provide clear evidence of impaired sympathetic and parasympathetic autonomic nervous system response to tilt with autonomic failure. The similarity in signal complexity with reduced fractal and harmonic spectral power, in patients compared with controls, suggests unchanged cardiovascular neural input and integration with reduced output in autonomic failure.

Cardiorespiratory interactions during fixed-pace resistive breathing.

We tested the hypothesis that the arterial baroreflex was important in the origin of respiratory sinus arrhythmia (RSA) under conditions of normal and resistive breathing. That is, mechanical effects of breathing [indicated by instantaneous lung volume (ILV)] would directly influence left ventricular stroke volume (LVSV), which in turn would influence systolic arterial blood pressure (SABP), causing variation in R-R interval through the baroreflex. Eight healthy young subjects (four men and four women) were monitored in the supine position while breathing with a fixed frequency (0.2 Hz) and tidal volume for 15 min through each of three resistances (R0, R1, and R2) producing inspiratory (-) and expiratory (+) pressures of +/- 1.6, +/- 5.4, and +/- 16.6 cmH2O, respectively. LVSV was estimated by stroke distance [(SDist); by Doppler ultrasound]. There were no differences across R0, R1, and R2 for the mean values of R-R interval, SDist, or SABP. Cross-spectral analysis showed that, at R0, each value of R-R interval, SDist, and SABP lagged ILV by approximately 80 degrees. At R1 and R2, phase was reduced from ILV to SDist and R-R interval, and the transfer magnitude for SDist (R2 only), SABP, and R-R interval increased. The transfer magnitude from SDist to SABP significantly increased as a function of resistance breathing, whereas that from SABP to R-R interval significantly decreased. There were no changes in phase relationships from SDist to SABP to R-R interval. Thus the magnitude of RSA (ILV to R-R interval) was increased, but the transfer through the arterial baroreflex (SABP to R-R interval) was reduced. Although factors other than the arterial baroreflex are probably involved in the genesis of RSA, the constant phase relationship across the levels of breathing resistance among SDist, SABP, and R-R interval suggests an important functional link caused by mechanical effects of breathing.