Steady-state cerebral blood flow and dynamic cerebral autoregulation during neck flexion and extension in seated healthy young adults.

Neck flexion and extension show differences in various physiological factors, such as sympathetic nerve activity and intracranial pressure (ICP). We hypothesized that differences would exist in steady-state cerebral blood flow and dynamic cerebral autoregulation between neck flexion and extension in seated, healthy young adults. Fifteen healthy adults were studied in the sitting position. Data were collected during neck flexion and extension in random order for 6 min each on the same day. Arterial pressure at the heart level was measured using a cuff sphygmomanometer. Mean arterial pressure at the middle cerebral artery (MCA) level (MAPMCA ) was calculated by subtracting the hydrostatic pressure difference between heart and MCA levels from mean arterial pressure at the heart level. Non-invasive cerebral perfusion pressure (nCPP) was estimated as the MAPMCA minus the non-invasive ICP as determined from transcranial Doppler ultrasonography. Waveforms of arterial pressure in the finger and blood velocity in the MCA (MCAv) were obtained. Dynamic cerebral autoregulation was evaluated by transfer function analysis between these waveforms. The results showed that nCPP was significantly higher during neck flexion than during neck extension (p = 0.004). However, no significant differences were observed in mean MCAv (p = 0.752). Likewise, no significant differences were observed in any of the three indices of dynamic cerebral autoregulation in any frequency range. Although non-invasively estimated cerebral perfusion pressure was significantly higher during neck flexion than during neck extension, no differences in steady-state cerebral blood flow or dynamic cerebral autoregulation were evident between neck flexion and extension in seated healthy adults.

Acquirement of the autonomic nervous system modulation evaluated by heart rate variability in medaka (Oryzias latipes).

Small teleosts have recently been established as models of human diseases. However, measuring heart rate by electrocardiography is highly invasive for small fish and not widely used. The physiological nature and function of vertebrate autonomic nervous system (ANS) modulation of the heart has traditionally been investigated in larvae, transparent but with an immature ANS, or in anesthetized adults, whose ANS activity may possibly be disturbed under anesthesia. Here, we defined the frequency characteristics of heart rate variability (HRV) modulated by the ANS from observations of heart movement in high-speed movie images and changes in ANS regulation under environmental stimulation in unanesthetized adult medaka (Oryzias latipes). The HRV was significantly reduced by atropine (1 mM) in the 0.25-0.65 Hz and by propranolol (100 µM) at 0.65-1.25 Hz range, suggesting that HRV in adult medaka is modulated by both the parasympathetic and sympathetic nervous systems within these frequency ranges. Such modulations of HRV by the ANS in adult medaka were remarkably suppressed under anesthesia and continuous exposure to light suppressed HRV only in the 0.25-0.65 Hz range, indicating parasympathetic withdrawal. Furthermore, pre-hatching embryos did not show HRV and the power of HRV developed as fish grew. These results strongly suggest that ANS modulation of the heart in adult medaka is frequency-dependent phenomenon, and that the impact of long-term environmental stimuli on ANS activities, in addition to development of ANS activities, can be precisely evaluated in medaka using the presented method.

Alteration in facial skin blood flow during acute exposure to -10 and -30° head-down tilt in young human volunteers.

NEW FINDINGS: What is the central question of this study? Facial skin blood flow (SBF) might increase during head-down tilt (HDT). However, the effect of HDT on facial SBF remains controversial. In addition, the changes in facial SBF in the cheek (cheek SBF) during a steeper angle of HDT (>-12° HDT) have not been investigated. What is the main finding and its importance? This study showed that cheek SBF decreased during -30° HDT, alongside increased vascular resistance. Furthermore, vascular impedance was suggested to be elevated, accompanied by an increased hydrostatic pressure gradient caused by HDT. Constriction of the facial skin vascular bed and congestion of venous return owing to the steep angle of HDT can decrease facial SBF. ABSTRACT: Head-down tilt (HDT) has been used to simulate microgravity in ground-based studies and clinical procedures including the Trendelenburg position or in certain surgical operations. Facial skin blood flow (SBF) might be altered by HDT, but the effect of a steeper angle of HDT (>-12° HDT) on facial SBF remains unclear. We examined alterations in facial SBF in the cheek (cheek SBF) using two different angles (-10 and -30°) of HDT and lying horizontal (0°) in a supine position for 10 min, to test the hypothesis that cheek SBF would increase with a steeper angle of HDT. Cheek SBF was measured continuously by laser Doppler flowmetry. Cheek skin vascular resistance and the pulsatility index of cheek SBF were calculated to assess the circulatory effects on the facial skin vascular bed in the cheek. Cheek SBF decreased significantly during -30° HDT. In addition, the resistance in cheek SBF increased significantly during -30° HDT. The pulsatility index of cheek SBF increased during both -10 and -30° HDT. Contrary to our hypothesis, cheek SBF decreased during -30° HDT along with increased skin vascular resistance. Vascular impedance, estimated by the pulsatility index in the cheek SBF, was elevated during both -10 and -30° HDT, and elevated vascular impedance would be related to increased hydrostatic pressure induced by HDT. Skin vascular constriction and venous return congestion would be induced by -30° HDT, leading to deceased cheek SBF. The present study suggested that facial SBF in the cheek decreased during acute exposure to a steep angle of HDT (∼-30° HDT).

Short-Term Volume Loading Effects on Estimated Intracranial Pressure in Human Volunteers.

BACKGROUND: Short-term fluid loading is used as part of post-spaceflight medical procedures and clinical treatment in hospitals. Hypervolemia with hemodilution induced by rapid fluid infusion reportedly impaired dynamic cerebral autoregulation. However, the effects on intracranial pressure (ICP) remain unknown. Therefore, we estimated ICP noninvasively (nICP) to examine whether rapid fluid infusion would raise ICP.METHODS: Twelve healthy male volunteers underwent two discrete normal saline (NS) infusions (15 and 30 ml · kg-1 stages, NS-15 and NS-30, respectively) at a rate of 100 ml · min-1. The cerebral blood flow (CBF) velocity (CBFv) waveform from the middle cerebral artery obtained by transcranial Doppler ultrasonography was recorded, as was the arterial blood pressure (ABP) waveform at the radial artery obtained by tonometry. We then used these waveforms to calculate nICP, cerebral artery compliance, and the pulsatility index (PI) in an intracranial hydraulic model.RESULTS: nICP increased significantly in both infusion stages from preinfusion (preinfusion: 7.6 ± 3.4 mmHg; NS-15: 10.9 ± 3.3 mmHg; NS-30: 11.7 ± 4.2 mmHg). No significant changes were observed in cerebral artery compliance or PI. Although ABP did not change in any stage, CBFv increased significantly (preinfusion: 67 ± 10 cm · s-1; NS-15: 72 ± 12 cm · s-1; NS-30: 73 ± 12 cm · s-1).DISCUSSION: Hypervolemia with hemodilution induced by rapid fluid infusion caused increases in nICP and CBFv. No changes were observed in cerebral artery compliance or PI related to cerebrovascular impedance. These findings suggest that rapid fluid infusion may raise ICP with increased CBF.Kurazumi T, Ogawa Y, Takko C, Kato T, Konishi T, Iwasaki K. Short-term volume loading effects on estimated intracranial pressure in human volunteers. Aerosp Med Hum Perform. 2022; 93(4):347-353.

Effects of -10° and -30° head-down tilt on cerebral blood velocity, dynamic cerebral autoregulation, and noninvasively estimated intracranial pressure.

Steady-state cerebral blood flow (CBF) and dynamic cerebral autoregulation are reportedly maintained during -10° head-down tilt (HDT) despite slight increases in intracranial pressure (ICP). However, the higher ICP during -30° HDT may alter steady-state CBF and dynamic cerebral autoregulation. The present study hypothesized that steady-state CBF and dynamic cerebral autoregulation would be altered by higher ICP during -30° HDT than during 0° and -10° HDT. Seventeen healthy participants were positioned horizontal (0°) and in -10° HDT and -30° HDT for 10 min in random order on separate days. The arterial blood pressure waveform was obtained using a finger blood pressure device and the cerebral blood velocity waveform in the middle cerebral artery was obtained using transcranial Doppler sonography (TCD) for the last 6 min in each position. ICP was estimated using noninvasive ICP (nICP) based on TCD. Dynamic cerebral autoregulation was evaluated by spectral and transfer function analysis. Although nICP was significantly higher during -30° HDT (12.4 mmHg) than during -10° HDT (8.9 mmHg), no significant differences in steady-state mean cerebral blood velocity or transfer function gain in any frequency ranges were seen among all angles of HDT. Counter to our hypothesis, the present results suggest that steady-state CBF and dynamic cerebral autoregulation may be preserved during short-term -30° HDT despite the higher ICP compared with that during -10° HDT.NEW & NOTEWORTHY This appears to be the first study to evaluate steady-state cerebral blood flow (CBF), dynamic cerebral autoregulation, and intracranial pressure (ICP) during -30° head-down tilt (HDT) compared with those during -10° HDT using noninvasive measurements. The results suggest that steady-state CBF and dynamic cerebral autoregulation are preserved despite the higher ICP during short-term -30° HDT compared with -10° HDT.

Long-duration spaceflight alters estimated intracranial pressure and cerebral blood velocity.

KEY POINTS: During long-duration spaceflights, some astronauts develop structural ocular changes including optic disc oedema that resemble signs of intracranial hypertension. In the present study, intracranial pressure was estimated non-invasively (nICP) using a model-based analysis of cerebral blood velocity and arterial blood pressure waveforms in 11 astronauts before and after long-duration spaceflights. Our results show that group-averaged estimates of nICP decreased significantly in nine astronauts without optic disc oedema, suggesting that the cephalad fluid shift during long-duration spaceflight rarely increased postflight intracranial pressure. The results of the two astronauts with optic disc oedema suggest that both increases and decreases in nICP are observed post-flight in astronauts with ocular alterations, arguing against a primary causal relationship between elevated ICP and spaceflight associated optical changes. Cerebral blood velocity increased independently of nICP and spaceflight-associated ocular alterations. This increase may be caused by the reduced haemoglobin concentration after long-duration spaceflight. ABSTRACT: Persistently elevated intracranial pressure (ICP) above upright values is a suspected cause of optic disc oedema in astronauts. However, no systematic studies have evaluated changes in ICP from preflight. Therefore, ICP was estimated non-invasively before and after spaceflight to test whether ICP would increase after long-duration spaceflight. Cerebral blood velocity in the middle cerebral artery (MCAv) was obtained by transcranial Doppler sonography and arterial pressure in the radial artery was obtained by tonometry, in the supine and sitting positions before and after 4-12 months of spaceflight in 11 astronauts (10 males and 1 female, 46 ± 7 years old at launch). Non-invasive ICP (nICP) was computed using a validated model-based estimation method. Mean MCAv increased significantly after spaceflight (ANOVA, P = 0.007). Haemoglobin decreased significantly after spaceflight (14.6 ± 0.8 to 13.3 ± 0.7 g/dL, P < 0.001). A repeated measures correlation analysis indicated a negative correlation between haemoglobin and mean MCAv (r = -0.589, regression coefficient = -4.68). The nICP did not change significantly after spaceflight in the 11 astronauts. However, nICP decreased significantly by 15% in nine astronauts without optic disc oedema (P < 0.005). Only one astronaut increased nICP to relatively high levels after spaceflight. Contrary to our hypothesis, nICP did not increase after long-duration spaceflight in the vast majority (>90%) of astronauts, suggesting that the cephalad fluid shift during spaceflight does not systematically or consistently elevate postflight ICP in astronauts. Independently of nICP and ocular alterations, the present results of mean MCAv suggest that long-duration spaceflight may increase cerebral blood flow, possibly due to reduced haemoglobin concentration.

Changes in cerebral oxygen saturation and cerebral blood flow velocity under mild +Gz hypergravity.

We previously reported that cerebral blood flow (CBF) was reduced by even mild +Gz hypergravity. Regional cerebral oxygen saturation as measured by near-infrared spectroscopy (C-rSO2) has been widely used to detect cerebral ischemia in clinical practice. For example, decreases in C-rSO2 reflect reduced CBF or arterial oxygen saturation. Thus it was hypothesized that C-rSO2 would decrease in association with reduced CBF during mild hypergravity. To test this hypothesis, we measured CBF velocity by transcranial Doppler ultrasonography and C-rSO2 during mild +Gz hypergravity while participants were in a sitting position. Among 17 male participants, 15 completed 21 min of exposure to +1.5 Gz generated by short-arm centrifuge. C-rSO2 and mean CBF velocity in the middle cerebral artery (MCBFVMCA) during centrifugation were averaged every 5 min and compared with pre-hypergravity (+1.0 Gz). C-rSO2 did not change significantly throughout centrifugation, although MCBFVMCA gradually decreased from the beginning (-1.2% at 0-5 min), and significantly decreased at 5-10 min (-4.8%), 10-15 min (-6.7%), and 15-20 min (-7.4%). Contrary to our hypothesis, decreases in C-rSO2 were not detected, despite reductions in CBF velocity during hypergravity. Since some assumptions, such as unaltered arteriovenous volume ratio, hemoglobin concentration, extracranial blood flow, and brain activity, need to be satisfied to monitor cerebral ischemia by C-rSO2, the present results suggest that these necessary assumptions for near-infrared spectroscopy are not always applicable, and that cerebral oxygenation may not precisely reflect decreases in CBF under mild +Gz hypergravity. NEW & NOTEWORTHY To our knowledge, this is the first study to evaluate simultaneously cerebral oxygenation monitored by near-infrared spectroscopy and cerebral blood flow (CBF) monitored by transcranial Doppler under +1.5 Gz hypergravity. Contrary to our hypothesis, there was no significant correlation between CBF velocity and regional cerebral oxygen saturation (C-rSO2). However, an incomplete case nearly involving syncope suggests the possibility that C-rSO2 can detect a remarkable decrease in CBF with development of presyncope during +Gz hypergravity.

Dynamic cerebral autoregulation after confinement in an isolated environment for 14 days.

BACKGROUND: To develop human space exploration, it is necessary to study the effects of an isolated and confined environment, as well as a microgravity environment, on cerebral circulation. However, no studies on cerebral circulation in an isolated and confined environment have been reported. Therefore, we investigated the effects of a 14-day period of confinement in an isolated environment on dynamic cerebral autoregulation. METHODS: We participated in an isolation and confinement experiment conducted by the Japan Aerospace Exploration Agency in 2016. Eight healthy males were isolated and confined in a facility for 14 days. Data were collected on the days immediately before and after confinement. Arterial blood pressure waveforms were obtained using a finger blood pressure monitor, and cerebral blood flow velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography for 6 min during quiet rest in a supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between spontaneous variability of beat-to-beat mean arterial blood pressure and mean cerebral blood flow velocity. RESULTS: Transfer function gain in the low- and high-frequency ranges increased significantly (0.54 ± 0.07 to 0.69 ± 0.09 cm/s/mmHg and 0.80 ± 0.05 to 0.92 ± 0.09 cm/s/mmHg, respectively) after the confinement. CONCLUSION: The increases observed in transfer function gain may be interpreted as indicating less suppressive capability against transmission from arterial blood pressure oscillation to cerebral blood flow velocity fluctuation. These results suggest that confinement in an isolated environment for 14 days may impair dynamic cerebral autoregulation. TRIAL REGISTRATION: UMIN000020703 , Registered 2016/01/22.

The effect of mild decrement in plasma volume simulating short-duration spaceflight on intracranial pressure.

Short-duration spaceflight induces an approximately 10% reduction in plasma volume, which leads to mild volume depletion. In a previous study, we found that mild volume depletion improved dynamic cerebral autoregulation. However, the effect of mild volume depletion on intracranial pressure (ICP) remains unknown. Therefore, we estimated ICP noninvasively (nICP), and calculated two indices relating to ICP, the cerebral artery compliance and the cerebral blood flow pulsatility index (PI), to examine whether ICP would decrease due to a mild decrement in plasma volume. In our previous experiment, fourteen subjects were administered 0.2 mg/kg of furosemide in a supine position to simulate an approximately 10% reduction in plasma volume induced by short-duration spaceflight. We re-analyzed the cerebral blood flow velocity waveform from the middle cerebral artery obtained by transcranial Doppler and the arterial blood pressure waveform at the radial artery obtained by tonometry to estimate nICP and to calculate cerebral artery compliance and PI using mathematical analysis based on an intracranial hydraulic model. All indices were compared between before and after furosemide administration. There were no significant changes in nICP and cerebral artery compliance. However, PI decreased significantly from before to after furosemide administration (0.78 ± 0.10 to 0.74 ± 0.09, p = 0.009). Decreases in ICP were not observed during the 10% reduction in plasma volume. Although cerebral artery compliance did not change, PI decreased significantly. These findings suggest that the impedance of distal cerebral arteries would be reduced in response to mild decreases in plasma volume induced by short-duration spaceflight.

Time-Dependent Changes in Cerebral Blood Flow and Arterial Pressure During Mild +Gz Hypergravity.

BACKGROUND: Artificial hypergravity has been proposed to prevent or treat various forms of physiological deconditioning experienced during spaceflight. We have previously reported that cerebral blood flow decreased at 15-21 min of +1.5-Gz centrifugation without decreases in arterial pressure at heart level. We reanalyzed our previous data to clarify time-dependent changes in cerebral blood flow and arterial pressure during mild +Gz hypergravity. METHOD: We reanalyzed data for 0-20 min during +1.5-Gz centrifugation on 13 male subjects for whom physiological data were steadily recorded. Mean cerebral blood flow velocity in the middle cerebral artery (MCBFVMCA), mean arterial pressure at heart level (MAPheart), and middle cerebral artery level (MAPMCA) during centrifugation were averaged every 5 min and compared with prehypergravity data (+1.0 Gz, 5 min). RESULTS: MAPheart did not change significantly, but MAPMCA decreased significantly throughout centrifugation compared to prehypergravity data (-16.7% to -24.7%). MCBFVMCA tended to be decreased at 0-5 min of +1.5-Gz centrifugation (-3.3%), but this was not statistically significant. MCBFVMCA was significantly decreased at 5-10 min (-5.5%). MCBFVMCA at 10-15 min and 15-20 min were also significantly decreased to almost the same level (-6.9% and -6.8%, respectively). DISCUSSION: No significant change in MAPheart was detected, whereas MAPMCA decreased significantly from the beginning of +1.5-Gz centrifugation. On the other hand, MCBFVMCA gradually decreased and became roughly flat in the latter half of 20-min centrifugation. Understanding the different time-dependent changes in cerebral blood flow and arterial pressure under mild +Gz hypergravity might be important for implementation of centrifuging as a countermeasure for spaceflight-induced deconditioning.Konishi T, Kurazumi T, Kato T, Takko C, Ogawa Y, Iwasaki K. Time-dependent changes in cerebral blood flow and arterial pressure during mild +Gz hypergravity. Aerosp Med Hum Perform. 2018; 89(9):787-791.

Non-Invasive Intracranial Pressure Estimation During Combined Exposure to CO2 and Head-Down Tilt.

BACKGROUND: Exposure to carbon dioxide (CO2) and cephalad fluid shift are considered factors that affect intracranial pressure (ICP) during spaceflight. Increases in ICP were reported during cephalad fluid shift induced by head-down tilt (HDT), while little is known regarding the effect of additional CO2 during HDT on ICP. Therefore, we tested the hypothesis that this combination increases ICP more than HDT alone. METHODS: There were 15 healthy male volunteers who underwent 4 types of 10-min interventions consisting of Placebo/Supine (air and supine), CO2/Supine (3% CO2 and supine, CO2 alone), Placebo/HDT (air and -10° HDT, HDT alone), and CO2/HDT (3% CO2 and -10° HDT, combination). Using arterial blood pressure (ABP) and cerebral blood flow velocity waveforms, ICP was estimated noninvasively before and during the four interventions. Two calculation methods were employed. One is based on the signal transformation from ABP to ICP with the intracranial component as a "black box" system (nICP_BB), and the other is based on the equation ICP = ABP - cerebral perfusion pressure, reflecting critical closing pressure (nICP_CrCP). RESULTS: Both nICP_BB and nICP_CrCP significantly increased during Placebo/HDT and CO2/HDT, although there was no statistically significant difference between the nICP indexes of these two interventions. DISCUSSION: Increases in ICP were observed during both Placebo/HDT and CO2/HDT. Contrary to our hypothesis, the combination of 3% CO2 and -10° HDT did not increase ICP remarkably compared to -10° HDT alone. Therefore, the addition of 3% CO2 is considered to have little effect on increasing ICP during cephalad fluid shift.Kurazumi T, Ogawa Y, Yanagida R, Morisaki H, Iwasaki K. Non-invasive intracranial pressure estimation during combined exposure to CO2 and head-down tilt. Aerosp Med Hum Perform. 2018; 89(4):365-370.

Dynamic Cerebral Autoregulation During the Combination of Mild Hypercapnia and Cephalad Fluid Shift.

BACKGROUND: Mild hypercapnia combined with a cephalad fluid shift [e.g., that occurring during spaceflight or laparoscopic surgery with head-down tilt (HDT)] might affect cerebral autoregulation. However, no reports have described the effects of the combination on dynamic cerebral autoregulation. Therefore, we tested the hypothesis that the combination of mild hypercapnia and a cephalad fluid shift would attenuate dynamic cerebral autoregulation. METHODS: There were 15 healthy male volunteers who were exposed to 4 10-min protocols in which they received air in the supine position (Placebo/Supine), 3% carbon dioxide (CO2) in the supine position (CO2/Supine), air with -10° HDT (Placebo/HDT) and 3% CO2 with -10° HDT (CO2/HDT). Dynamic cerebral autoregulation was evaluated using a transfer function analysis of the beat-to-beat variability in mean arterial blood pressure (ABP) and mean cerebral blood flow (CBF) velocity. RESULTS: The phase in the low-frequency range was significantly lower during CO2/HDT than all other protocols, where CO2/HDT was -25% lower than Placebo/Supine (CO2/HDT, 0.49 ± 0.21; Placebo/Supine, 0.65 ± 0.16 radians). The transfer function gain in the low-frequency range was significantly higher during CO2/HDT than all other protocols, where CO2/HDT was 26% higher than Placebo/Supine (CO2/HDT, 1.08 ± 0.34; Placebo/Supine, 0.86 ± 0.28 cm · s-1 · mmHg-1). However, neither the CO2/Supine nor Placebo/HDT showed significant differences compared with the Placebo/Supine. DISCUSSION: Even short-term exposure to 3% CO2 plus HDT increased synchrony and the magnitude of transmission between ABP and CBF in the low-frequency range. Thus, the combination of mild hypercapnia and a cephalad fluid shift attenuated dynamic cerebral autoregulation.Kurazumi T, Ogawa Y, Yanagida R, Morisaki H, Iwasaki K. Dynamic cerebral autoregulation during the combination of mild hypercapnia and cephalad fluid shift. Aerosp Med Hum Perform. 2017; 88(9):819-826.

Speed ratio but cabin temperature positively correlated with increased heart rates among professional drivers during car races.

OBJECTIVES: The present study measures heart rate (HR) on a number of professional race-car drivers during actual car races through annual seasons to test hypotheses that faster relative speed and higher cabin temperature would induce higher HR. METHODS: Heart rates in fifteen male drivers (31.2 ± 5.5 years old) were obtained by chest-strap sensors during official-professional 13 races. Average HR was calculated while the driver was racing from the start to the end of each race. RESULTS: The average HR during races was 164.5 ± 15.1 beats min-1 and the average amount of time each driver spent driving per race was 54.2 ± 13.7 min. Average HR significantly and positively correlated with mean speed ratio (P < 0.001), but not with the average cabin temperatures (P = 0.533, range 25.6-41.8 °C) by the multiple linear regression analysis. Both average HR and mean speed ratio were significantly lower under wet, than dry conditions (151.9 ± 16.5 vs. 168.3 ± 12.5 beats min-1, 86.9 ± 4.4 vs. 93.4 ± 1.5 %). CONCLUSIONS: The cardiovascular system of drivers is considerably stressed at extremely high HR. This high average HR positively correlated with mean speed ratio, suggesting that faster driving speed would induce greater cardiovascular stress to professional drivers during actual races. However, contrary to our hypothesis, cabin temperature was not significantly correlated with average HR. It is speculated that direct body cooling systems used in this professional race category work well against increases in HR by thermal stress under the temperature range found herein.

The relationship between widespread changes in gravity and cerebral blood flow.

OBJECTIVES: We investigated the dose-effect relationship between wide changes in gravity from 0 to 2.0 Gz (Δ0.5 Gz) and cerebral blood flow (CBF), to test our hypothesis that CBF has a linear relationship with levels of gravity. SUBJECTS AND METHODS: Ten healthy seated men were exposed to 0, 0.5, 1.0, 1.5, and 2.0 Gz for 21 min, by using a tilt chair and a short-arm human centrifuge. Steady-state CBF velocity (CBFV) in the middle cerebral artery by transcranial Doppler ultrasonography, mean arterial pressure (MAP) at the heart level (MAPHeart), heart rate, stroke volume, cardiac output and respiratory conditions were obtained for the last 6 min at each gravity level. Then, MAP in the middle cerebral artery (MAPMCA), reflecting cerebral perfusion pressure, was estimated. RESULTS: Steady-state CBFV decreased stepwise from 0.5 to 2.0 Gz. Steady-state heart rate, stroke volume, estimated MAPMCA and end-tidal carbon dioxide pressure (ETCO2) also changed stepwise from hypogravity to hypergravity. On the other hand, steady-state MAPHeart and cardiac output did not change significantly. Steady-state CBFV positively and linearly correlated with estimated MAPMCA and ETCO2 in most subjects. CONCLUSION: The present study demonstrated stepwise gravity-induced changes in steady-state CBFV from 0.5 to 2.0 Gz despite unchanged steady-state MAPHeart. The combined effects of reduced MAPMCA and ETCO2 likely led to stepwise decreases in CBFV. We caution that a mild increase in gravity from 0 to 2.0 Gz reduces CBF, even if arterial blood pressure at the heart level is maintained.

Dose-Effect Relationship Between Mild Levels of Hypergravity and Autonomic Circulatory Regulation.

INTRODUCTION: The dose-effect relationships between different levels of hypergravity (>+1.0 Gz) and steady-state hemodynamic parameters have been reported in several studies. However, little has been reported on the dose-effect relationship between hypergravity levels and estimates of autonomic circulatory regulation, such as heart rate variability, arterial pressure variability, and spontaneous cardiac baroreflex sensitivity. We investigated dose-effect relationships between hypergravity levels from +1.0 Gz to +2.0 Gz (Δ0.5 Gz) and autonomic circulatory regulation to test our hypothesis that autonomic circulatory regulation has a linear relationship with hypergravity levels. METHODS: Using a short-arm human centrifuge, 10 healthy seated men were subjected to +1.0 Gz, +1.5 Gz, and +2.0 Gz hypergravity. We evaluated steady-state hemodynamic parameters and autonomic circulatory regulation indices. Heart rate variability, arterial pressure variability, and spontaneous cardiac baroreflex sensitivity between arterial pressure and R-R interval variabilities were assessed by spectral analysis, sequence analysis, and transfer function analysis. RESULTS: Steady-state heart rate, stroke volume, and sequence slope (indicating spontaneous cardiac baroreflex sensitivity in response to rapid changes in arterial pressure) showed linear correlations with increases in gravity (from +1.0 Gz to +2.0 Gz). On the other hand, steady-state cardiac output, steady-state systolic arterial pressure, and low-frequency power of diastolic arterial pressure (indicating peripheral vasomotor sympathetic activity) remained unchanged with gravity increases. CONCLUSION: Contrary to our hypothesis, the present study suggested that autonomic circulatory regulations show complex changes with hypergravity levels. Spontaneous cardiac baroreflex sensitivity reduces in a dose-dependent manner from +1.0 Gz to +2.0 Gz, whereas peripheral vasomotor sympathetic activity seems to be maintained.

The Effects of Flumazenil After Midazolam Sedation on Cerebral Blood Flow and Dynamic Cerebral Autoregulation in Healthy Young Males.

BACKGROUND: It is unknown whether flumazenil antagonizes the decrease in cerebral blood flow or the alteration in dynamic cerebral autoregulation induced by midazolam. We, therefore, investigated the effects on cerebral circulation of flumazenil administered after midazolam, to test our hypothesis that, along with complete reversal of sedation, flumazenil antagonizes the alterations in cerebral circulation induced by midazolam. METHODS: Sixteen healthy young male subjects received midazolam followed by flumazenil. The modified Observer's Assessment of Alertness/Sedation (OAA/S) scale and bispectral index (BIS) were used to assess levels of sedation/awareness. For evaluation of cerebral circulation, steady-state mean cerebral blood flow velocity (MCBFV) was measured by transcranial Doppler ultrasonography. In addition, dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between mean arterial pressure (MAP) variability and MCBFV variability. RESULTS: During midazolam sedation, defined by an OAA/S score of 3 (responds only after name is called loudly and/or repeatedly), BIS, steady-state MAP, steady-state CBFV, and transfer function gain decreased significantly compared with baseline. After flumazenil administration, an OAA/S score of 5 (responds readily to name spoken in a normal tone) was confirmed. Then, BIS and MAP returned to the same level as baseline. However, steady-state MCBFV showed a further significant decrease compared with that under midazolam sedation, and the decreased transfer function gain persisted. CONCLUSIONS: Contrary to our hypothesis, the present results suggest that despite complete antagonism of the sedative effects of midazolam, flumazenil would not reverse the alterations in cerebral circulation induced by midazolam.

Sustained mild hypergravity reduces spontaneous cardiac baroreflex sensitivity.

Head-to-foot gravitational force >1G (+Gz hypergravity) augments venous pooling in the lower body and reduces central blood volume during exposure, compared with 1Gz. Central hypovolemia has been reported to reduce spontaneous cardiac baroreflex sensitivity. However, no investigations have examined spontaneous cardiac baroreflex sensitivity during exposure to sustained mild +Gz hypergravity. We therefore hypothesized that mild +Gz hypergravity would reduce spontaneous cardiac baroreflex sensitivity, compared with 1Gz. To test this hypothesis, we examined spontaneous cardiac baroreflex sensitivity in 16 healthy men during exposure to mild +Gz hypergravity using a short-arm centrifuge. Beat-to-beat arterial blood pressure (tonometry) and R-R interval (electrocardiography) were obtained during 1Gz and 1.5Gz exposures. Spontaneous cardiac baroreflex sensitivity was assessed by sequence slope and transfer function gain. Stroke volume was calculated from the arterial pressure waveform using a three-element model. All indices of spontaneous cardiac baroreflex sensitivity decreased significantly (up slope: 18.6±2.3→12.7±1.6ms/mmHg, P<0.001; down slope: 19.0±2.5→13.2±1.3ms/mmHg, P=0.002; transfer function gain in low frequency: 14.4±2.2→10.1±1.1ms/mmHg, P=0.004; transfer function gain in high frequency: 22.2±7.5→12.4±3.5ms/mmHg, P<0.001). Stroke volume decreased significantly (88±5→80±6ml, P=0.025). Moreover, although systolic arterial pressure variability increased, R-R interval variability did not increase. These results suggest that even mild +Gz hypergravity reduces spontaneous cardiac baroreflex sensitivity, increasing the risk of cardiovascular disturbance during the exposure.

Blunted cutaneous vasoconstriction and increased frequency of presyncope during an orthostatic challenge under moderate heat stress in the morning.

PURPOSE: In normothermia, the tolerance time to presyncope during an orthostatic challenge is shortened during the early morning. Heat stress reduces tolerance to presyncope and the degree of cutaneous vasoconstriction prior to presyncope. However, whether these changes show diurnal variations remains unknown. Therefore, we examined diurnal changes in orthostatic tolerance and cutaneous vascular conductance (CVC) during an orthostatic challenge under moderate heat stress. METHODS: Each lower body negative pressure (LBNP) under normothermia and whole body heat stress was applied for 7 min or until the appearance of presyncopal symptoms in 16 males at both 08:00 (a.m.) and 17:00 hours (p.m.). Measurements included internal and skin temperatures, forearm skin blood flow, arterial pressure, and heart rate. CVC was calculated as skin blood flow/mean arterial pressure, normalized to CVC prior to LBNP and expressed as %CVC. RESULTS: The average tolerance time in eight subjects exhibiting presyncopal symptoms due to LBNP and moderate heat stress was significantly shorter in the a.m. than in the p.m. (3.7 ± 0.8 versus 6.7 ± 0.3 min, respectively; P = 0.005). Neither %CVC during LBNP in these subjects under moderate heat stress nor normothermia were significantly decreased in the a.m. (P > 0.05, respectively). CONCLUSIONS: These findings indicate an orthostatic challenge even during moderate heat stress that led to an increase in the frequency of presyncope, especially in the morning. The reduction in tolerance was accompanied by blunted cutaneous vasoconstriction prior to presyncope. Hence, diurnal changes in cutaneous vascular responses during combined orthostatic and heat stresses should contribute, at least partly, to heat-induced orthostatic intolerance in the morning.

Differential effects of mild central hypovolemia with furosemide administration vs. lower body suction on dynamic cerebral autoregulation.

Diuretic-induced mild hypovolemia with hemoconcentration reportedly improves dynamic cerebral autoregulation, whereas central hypovolemia without hemoconcentration induced by lower body negative pressure (LBNP) has no effect or impairs dynamic cerebral autoregulation. This discrepancy may be explained by different blood properties, by degrees of central hypovolemia, or both. We investigated the effects of equivalent central hypovolemia induced by furosemide administration or LBNP application on dynamic cerebral autoregulation to test our hypothesis that mild central hypovolemia due to furosemide administration enhances dynamic cerebral autoregulation in contrast to LBNP. Seven healthy male subjects received 0.4 mg/kg furosemide and LBNP, with equivalent decreases in central venous pressure (CVP). Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between beat-to-beat mean arterial blood pressure (MAP) and mean cerebral blood flow velocity (MCBFV). CVP decreased by ∼3-4 mmHg with both furosemide administration (∼26 mg) and LBNP (approximately -20 mmHg). Steady state MCBFV remained unchanged with both techniques, whereas MAP increased significantly with furosemide administration. Coherence and transfer function gain in the low and high frequency ranges with hypovolemia due to furosemide administration were significantly lower than those due to LBNP (ANOVA interaction effects, P < 0.05), although transfer function gain in the very low frequency range did not change. Our results suggest that although the decreases in CVP were equivalent between furosemide administration and LBNP, the resultant central hypovolemia differentially affected dynamic cerebral autoregulation. Mild central hypovolemia with hemoconcentration resulting from furosemide administration may enhance dynamic cerebral autoregulation compared with LBNP.