Relationship between arterial stiffness and cognitive function in outpatients with dementia and mild cognitive impairment compared with community residents without dementia.

BACKGROUND: It is unclear whether the dementia patients with Alzheimer's disease (AD) and vascular dementia (VaD) and mixed dementia (MIX, including AD and VaD) would have more developed arterial stiffness as compared with local residents without dementia. The aim of this study was to assess arterial stiffness and cognitive function in different types of dementia patients [AD, VaD, MIX and mild cognitive impairment (MCI)] and community residents without dementia. METHODS: This was a single-center, cross-sectional observational study. We studied a cohort of 600 elderly outpatients with a complaint of memory loss, who were divided into four groups (AD, VaD, MIX and MCI). In addition, they were compared with 55 age-matched local residents without dementia (Controls). We assessed arterial stiffness by brachial-ankle pulse wave velocity (baPWV) and the global cognitive function by the Mini-Mental State Examination (MMSE). RESULTS: The baPWV was higher in AD, VaD and MIX than in MCI and in Controls (P < 0.05). The baPWV was higher in MCI than in Controls (P = 0.021), while MMSE were compatible between them (P = 0.119). The higher baPWV predicted the presence of AD, VaD, MIX and MCI with the odds ratio of 6.46, 8.74, 6.16 and 6.19, respectively. In contrast, there were no difference in baPWV among three different types of dementia (P = 0.191). The linear relationship between baPWV and MMSE was observed in the elderly with MMSE ≥ 23 (R = 0.452, P = 0.033), while it was not in dementia patients (MMSE < 23). CONCLUSIONS: The findings suggest that MCI and dementia patients have stiffer arteries as compared with age-matched local residents, although global cognitive function may be comparable between MCI and the local residents.

Influence of head-up tile and lower body negative pressure on the internal jugular vein.

Head-up tilt (HUT)-induced gravitational stress causes collapse of the internal jugular vein (IJV) by decreasing central blood volume and through mass-effect from the surrounding tissues. Besides HUT, lower body negative pressure (LBNP) is used to stimulate orthostatic stress as an experimental model. Compared to HUT, LBNP has less of a gravitational effect because of the supine position; therefore, we hypothesized that LBNP causes less of a decrease in the cross-sectional area of the IJV compared to HUT. We tested the hypothesis by measuring the cross-sectional area of the IJV using B-mode ultrasonography while inducing orthostatic stress at levels of -40 mmHg LBNP and 60° HUT. The cross-sectional area of IJV decreased from the resting baseline during both LBNP and HUT trials, but the LBNP-induced decrease in the cross-sectional area of IJV was smaller than that of HUT (right, -45% ± 49% vs. -78% ± 27%, p = 0.008; left, -49% ± 27% vs. -78% ± 20%, p = 0.004). Since changes in venous outflow may affect cerebral arterial circulation, the findings of the present study suggest that orthostatic stress induced by different techniques modulates cerebral blood flow regulation through its effect on venous outflow.

Validity of transcranial Doppler ultrasonography-determined dynamic cerebral autoregulation estimated using transfer function analysis.

Transcranial Doppler ultrasonography (TCD) is used widely to evaluate dynamic cerebral autoregulation (dCA). However, the validity of TCD-determined dCA remains unknown because TCD is only capable of measuring blood velocity and thus only provides an index as opposed to true blood flow. To test the validity of TCD-determined dCA, in nine healthy subjects, dCA was evaluated by transfer function analysis (TFA) using cerebral blood flow (CBF) or TCD-measured cerebral blood velocity during a perturbation that induces reductions in TCD-determined dCA, lower body negative pressure (LBNP) at two different stages: LBNP - 15 mmHg and - 50 mmHg. Internal carotid artery blood flow (ICA Q) was assessed as an index of CBF using duplex Doppler ultrasound. The TFA low frequency (LF) normalized gain (ngain) calculated using ICA Q increased during LBNP at - 50 mmHg (LBNP50) from rest (P = 0.005) and LBNP at - 15 mmHg (LBNP15) (P = 0.015), indicating an impaired dCA. These responses were the same as those obtained using TCD-measured cerebral blood velocity (from rest and LBNP15; P = 0.001 and P = 0.015). In addition, the ICA Q-determined TFA LF ngain from rest to LBNP50 was significantly correlated with TCD-determined TFA LF ngain (r = 0.460, P = 0.016) despite a low intraclass correlation coefficient. Moreover, in the Bland-Altman analysis, the difference in the TFA LF ngains determined by blood flow and velocity was within the margin of error, indicating that the two measurement methods can be interpreted as equivalent. These findings suggest that TCD-determined dCA can be representative of actual dCA evaluated with CBF.

Pivotal Role of Heart for Orthostasis: Left Ventricular Untwisting Mechanics and Physical Fitness.

Augmentation of left ventricular (LV) untwisting due to central hypovolemia is likely to be a compensatory mechanism for maintaining stroke volume, which is reduced by a decrease in cardiac filling during orthostatic stress. Orthostatic intolerance observed in both high and low fitness levels may be explained by the impaired response of LV untwisting due to central hypovolemia.

An assessment of hypercapnia-induced elevations in regional cerebral perfusion during combined orthostatic and heat stresses.

We investigated that the effects of hypercapnia-induced elevations in cerebral perfusion during a heat stress on global cerebrovascular responses to an orthostatic challenge. Seven volunteers completed a progressive lower-body negative pressure (LBNP) challenge to presyncope during heat stress, with or without breathing a hypercapnic gas mixture. Administration of the hypercapnic gas mixture increased the partial pressure of end-tidal CO2 greater than pre-heat stress alone, and increased both internal carotid artery (ICA) and vertebral artery (VA) blood flows (P < 0.05). During LBNP, both ICA and VA blood flows with the hypercapnic gas mixture remained elevated relative to the control trial (P < 0.05). However, at the end of LBNP due to pre-syncopal symptoms, both ICA and VA blood flows decreased to similar levels between trials. These findings suggest that hypercapnia-induced cerebral vasodilation is insufficient to maintain cerebral perfusion at the end of LBNP due to pre-syncope in either the anterior or posterior vascular beds.

The effect of muscle metaboreflex on the distribution of blood flow in cerebral arteries during isometric exercise.

The present study examined the effect of muscle metaboreflex on blood flow in different cerebral arteries. Eleven healthy participants performed isometric, one-leg knee extension at 30% maximal voluntary contraction for 2 min. Activated muscle metaboreflex was isolated for 2 min by post-exercise muscle ischemia (PEMI). The contralateral internal carotid (ICA), vertebral (VA), and ipsilateral external carotid arteries (ECA) blood flows were evaluated using Doppler ultrasound. The ICA blood flow increased at the beginning of exercise (P  = 0.004) but returned to the baseline level at the end of exercise (P  = 0.055). In contrast, the VA blood flow increased and it was maintained until the end of the exercise (P = 0.011), while the ECA blood flow gradually increased throughout the exercise (P  = 0.001). These findings indicate that isometric exercise causes a heterogeneous cerebral blood flow response in different cerebral arteries. During PEMI, the conductance of the VA as well as that of the ICA was significantly lower compared with the baseline value (P  = 0.020 and P  = 0.032, at PEMI90), while the conductance of the ECA was not different from the baseline (P  = 0.587), suggesting that the posterior and anterior cerebral vasculature were similarly affected during exercise by activation of muscle metaboreceptors, but not in the non-cerebral artery. Since ECA branches from ICA, the balance in the different influence of muscle metaboreflex on ECA (vasodilation via exercise-induced hypertension) and ICA (vasoconstriction) may contribute to the decrease in ICA blood flow at the end of isometric exercise.

Relationship between cerebral blood flow estimated by transcranial Doppler ultrasound and single-photon emission computed tomography in elderly people with dementia.

Transcranial Doppler (TCD) ultrasonography is a noninvasive technique allowing continuous recording of cerebral blood flow (CBF) velocity. However, it is unclear whether the CBF estimated by TCD would be reliable for the comparison between individuals. The present study aimed to clarify the relationship between middle cerebral artery blood flow (MCA BF) measured by TCD and regional and total CBF measured by single-photon emission computed tomography (SPECT-CBF) with a quantification software program, a three-dimensional stereotaxic region of interest template. We recruited 91 elderly subjects with and without dementia. MCA blood flow velocity (MCA V) and middle cerebral artery cross-sectional area (AM) were measured by TCD and magnetic resonance angiography, respectively. MCA BF was calculated by the product of MCA V and AM. Diastolic or mean MCA V and MCA BF were significantly correlated with SPECT-CBF in several segments. Interestingly, the correlation coefficient in the temporal segment of SPECT-CBF was higher than those of the other segments. Moreover, correlations between MCA BF and SPECT-CBF were stronger as compared with those between MCA V and SPECT-CBF. These findings suggest that both mean MCA V and MCA BF with TCD ultrasonography would be useful for CBF comparison between individuals especially in the temporal region, although estimated blood flow with arterial area seems to be better than using simple flow velocity. NEW & NOTEWORTHY Correlations between middle cerebral artery blood flow (MCA BF) calculated by the product of MCA blood flow velocity (MCA V) and middle cerebral artery cross-sectional area and regional and total cerebral blood flow (CBF) measured by single-photon emission computed tomography (SPECT-CBF) were stronger as compared with those between MCA V and SPECT-CBF. These findings suggest that both mean MCA V and MCA BF would be useful for CBF comparison between individuals although estimated blood flow with arterial area seems to be better than using simple flow velocity.

Impact of Short-Term Training Camp on Aortic Blood Pressure in Collegiate Endurance Runners.

To investigate the influence of short-term vigorous endurance training on aortic blood pressure (BP), pulse wave analysis was performed in 36 highly trained elite collegiate endurance runners before and after a 7-day intense training camp. Subjects participated three training sessions per day, which mainly consisted of long distance running and sprint training to reach the daily target distance of 26 km. After the camp, they were divided into two groups based on whether the target training was achieved. Aortic systolic BP, pulse pressure, and tension-time index (TTI, a surrogate index of the myocardial oxygen demand) were significantly elevated after the camp in the accomplished group but not in the unaccomplished group, whereas the brachial BP remained unchanged in both groups. The average daily training distance was significantly correlated with the changes in aortic systolic BP (r = 0.608, p = 0.0002), pulse pressure (r = 0.415, p = 0.016), and TTI (r = 0.438, p = 0.011). These results suggest that aortic BP is affected by a short-term vigorous training camp even in highly trained elite endurance athletes presumably due to a greater training volume compared to usual.

Relationship between the severity of cerebral white matter hyperintensities and sympathetic nervous activity in older adults.

AIM: White matter hyperintensities (WMH), visualized on brain magnetic resonance imaging, represent an abnormality related to the development of geriatric syndromes. Recently, it has been found that low sympathetic nervous activity might be associated with physical and cognitive dysfunction in older adults. Therefore, we investigated the relationship between the severity of cerebral WMH and sympathetic nervous activity, measured by the heart rate variability. METHODS: We carried out a cross-sectional study of 39 older patients. Holter recording was carried out for 30 min. From the RR intervals on the electrocardiogram, the standard deviation of the normal-to-normal intervals, the standard deviation of all normal-to-normal intervals in all the five segments of the entire recording, low frequency (LF), high frequency (HF) and LF/HF were calculated. In regard to the WMH, periventricular hyperintensities and deep white matter hyperintensities (DWMH) were rated according to the Fazekas classification. The WMH were also rated semiquantitatively according to the methods developed by Junque (periventricular hyperintensities) and de Groot (DWMH). RESULTS: The LF/HF showed significant negative correlations with the total and regional periventricular hyperintensities, as well as DWMH. Multiple regression analysis showed that the negative associations remained significant between the LF/HF and DWMH (total, temporal, occipital). Furthermore, fall risk index significantly correlated with the LF/HF, total and the occipital DWMH. CONCLUSIONS: The severity of the DWMH was associated with the LF/HF and the fall risk, one of the important geriatric syndromes, suggesting that WMH, sympathetic nervous dysfunction and geriatric syndrome are interrelated to each other. Geriatr Gerontol Int 2018; 18: 569-575.

Internal carotid, external carotid and vertebral artery blood flow responses to 3 days of head-out dry immersion.

NEW FINDINGS: What is the central question of this study? The extent to which weightlessness associated with a fluid shift from the peripheral to the central circulation influences the blood flow in each cerebral artery remains unknown. The present study was designed to explore the effect of short-term weightlessness conditions on both anterior and posterior cerebral blood flow. What is the main finding and its importance? Short-term weightlessness affects both anterior and posterior cerebral vasculature. However, a heterogeneous cerebral blood flow response in each cerebral artery did not occur during 3 days of dry immersion. We have recently demonstrated that a heterogeneous cerebral blood flow (CBF) response in each cerebral artery might contribute to the maintenance of circulatory homeostasis in the brain. However, the extent to which weightlessness associated with a fluid shift from the peripheral to the central circulation influences the distribution of CBF in each cerebral artery remains unknown. We hypothesized that a dry immersion-induced fluid shift (weightlessness conditions) would cause a heterogeneous CBF response in each cerebral artery. During and after 3 days of dry immersion, the blood flows in the internal carotid (ICA), external carotid (ECA) and vertebral arteries (VA) were measured by Doppler ultrasonography using an 8 MHz linear transducer. Although the 3 days of dry immersion and the 2 days recovery period did not change the blood flow in each cerebral artery, the conductance in both ICA and VA decreased during dry immersion on days 2 and 3 (ICA, 2.95 and 3.23 ml min-1  mmHg-1 ; VA, 1.10 and 1.05 ml min-1  mmHg-1 , respectively) from the baseline (ICA, 3.47 ml min-1  mmHg-1 , P = 0.027; VA, 1.23 ml min-1  mmHg-1 , P = 0.004). In addition, Pearson correlation analysis demonstrated that the 3 days of dry immersion induced a decrease in cardiac output (P = 0.004) that was associated with changes in ICA (P = 0.046) and VA blood flow (P = 0.021), but not ECA blood flow (P = 0.466). These findings suggest that short exposures to weightlessness, acting via a cephalad redistribution of fluid volume and blood flow in the human body, influenced the cerebral vasculature in each cerebral artery but did not cause a heterogeneous CBF response in each cerebral artery.

Dynamic cerebral autoregulation is unrelated to decrease in external carotid artery blood flow during acute hypotension in healthy young men.

NEW FINDINGS: What is the central question of this study? Dynamic cerebral autoregulation (CA) is impaired by sympathetic blockade, and the external carotid artery (ECA) vascular bed may prevent adequate internal carotid artery blood flow. We examined whether α1 -receptor blockade-induced attenuation of dynamic CA is related to reduced ECA vasoconstriction. What is the main finding and its importance? α1 -Receptor blockade attenuated dynamic CA, but in contrast to our hypothesis did not affect the ECA blood flow response to acute hypotension. These findings suggest that the recovery of cerebral blood flow during acute hypotension is unrelated to vasoconstriction within the ECA territory. External carotid artery (ECA) vasoconstriction may defend internal carotid artery (ICA) blood flow during acute hypotension. We hypothesized that the α1 -receptor blockade-induced delay in ICA recovery to the baseline level from acute hypoperfusion is related to attenuated ECA vasoconstriction. The ICA and ECA blood flow were determined by duplex ultrasound during thigh-cuff release-induced acute hypotension while the α1 -receptor blocker prazosin [1 mg (20 kg)(-1) ] was administered to nine seated young healthy men. Both ICA (mean ± SD; by 17 ± 8%, P = 0.005) and ECA (by 37 ± 15%, P < 0.001) blood flow decreased immediately after occluded thigh-cuff release, with a more rapid ICA blood flow recovery to the baseline level (9 ± 5 s) than for the ECA blood flow (17 ± 5 s; P = 0.019). The ICA blood flow recovery from hypoperfusion was delayed with prazosin (17 ± 4 s versus control 9 ± 5 s, P = 0.006), whereas ECA recovery remained unchanged (P = 0.313) despite a similar reduction in mean arterial pressure (-20 ± 4 mmHg versus control -23 ± 7 mmHg, P = 0.148). These findings suggest that α1 -receptor blockade-induced attenuation of the ICA blood flow response to acute hypotension is unrelated to the reduction in ECA blood flow. The sympathetic nervous system via the ECA vascular bed does not contribute to dynamic CA during acute hypotension.

Acute effect of coffee drinking on dynamic cerebral autoregulation.

PURPOSE: Drinking coffee causes caffeine-induced physiological alterations such as increases in arterial blood pressure, sympathetic nerve activity, cerebral vasoconstriction, etc., and these physiological alterations may be associated with a reduced risk of cerebral vascular disease. However, the effect of coffee drinking on dynamic cerebral blood flow (CBF) regulation remains unclear. The aim of this study was to test our hypothesis that coffee drinking enhances dynamic cerebral autoregulation. METHOD: Twelve healthy young subjects participated in the present study. After a 5 min baseline measurement in a semi-recumbent position on the hospital bed, each subject drank water (CON) as a placebo condition or coffee beverage (Coffee INT). Arterial blood pressure and middle cerebral artery blood velocity (MCAv) were measured continuously throughout the experiment. At 30 min after the intake of either water or coffee, dynamic cerebral autoregulation was examined using a thigh cuffs occlusion and release technique. Each condition was randomly performed on a different day. RESULT: Under Coffee INT condition, mean arterial blood pressure was increased (P = 0.01) and mean MCAv was decreased (P = 0.01) from the baseline. The rate of regulation (RoR), as an index of dynamic cerebral autoregulation, during coffee condition was significantly higher than that during CON (P = 0.0009). CONCLUSION: The findings of the present study suggest that coffee drinking augments dynamic CBF regulation with cerebral vasoconstriction. This phenomenon may be associated with a reduction in the risk of cerebral vascular disease.

Near-infrared spectroscopy determined cerebral oxygenation with eliminated skin blood flow in young males.

We estimated cerebral oxygenation during handgrip exercise and a cognitive task using an algorithm that eliminates the influence of skin blood flow (SkBF) on the near-infrared spectroscopy (NIRS) signal. The algorithm involves a subtraction method to develop a correction factor for each subject. For twelve male volunteers (age 21 ± 1 yrs) +80 mmHg pressure was applied over the left temporal artery for 30 s by a custom-made headband cuff to calculate an individual correction factor. From the NIRS-determined ipsilateral cerebral oxyhemoglobin concentration (O2Hb) at two source-detector distances (15 and 30 mm) with the algorithm using the individual correction factor, we expressed cerebral oxygenation without influence from scalp and scull blood flow. Validity of the estimated cerebral oxygenation was verified during cerebral neural activation (handgrip exercise and cognitive task). With the use of both source-detector distances, handgrip exercise and a cognitive task increased O2Hb (P < 0.01) but O2Hb was reduced when SkBF became eliminated by pressure on the temporal artery for 5 s. However, when the estimation of cerebral oxygenation was based on the algorithm developed when pressure was applied to the temporal artery, estimated O2Hb was not affected by elimination of SkBF during handgrip exercise (P = 0.666) or the cognitive task (P = 0.105). These findings suggest that the algorithm with the individual correction factor allows for evaluation of changes in an accurate cerebral oxygenation without influence of extracranial blood flow by NIRS applied to the forehead.

Ultrasound tagged near infrared spectroscopy does not detect hyperventilation-induced reduction in cerebral blood flow.

INTRODUCTION: Continuous non-invasive monitoring of cerebral blood flow (CBF) may be important during anaesthesia and several options are available. We evaluated the CerOx monitor that employs ultrasound tagged near infrared spectroscopy to estimate changes in a CBF index (CFI). METHODS: Seven healthy males (age 21-26 years) hyperventilated and were administered phenylephrine to increase mean arterial pressure by 20-30 mmHg. Frontal lobe tissue oxygenation (ScO2) and CFI were obtained using the CerOx and mean blood flow velocity in the middle cerebral artery (MCAv mean) was determined by transcranial Doppler. Blood flow in the internal and external carotid artery (ICAf and ECAf) was determined using duplex ultrasonography and forehead skin blood flow (SkBF) and oxygenation (S skin O2) by laser Doppler and white light spectroscopy. RESULTS: During hyperventilation MCAv mean and ICAf decreased by 44% (median; interquartile range 40-49; p = 0.016) and 46% (40-53; p = 0.03), respectively. Conversely, CFI increased by 9% (2-31; p = 0.016), while no significant change was observed in ScO2. SkBF increased by 19% (9-53; p = 0.016) and S skin O2 by 6% (1-7; p = 0.047), although ECAf was unchanged. Administration of phenylephrine was not associated with any changes in MCAv mean, ICAf, ECAf, ScO2, SkBF, S skin O2, or CFI. CONCLUSION: The CerOx was able to detect a stable CBF during administration of phenylephrine. However, during hyperventilation MCAv mean and ICAf decreased while CFI increased, likely due to an increase in superficial tissue oxygenation. Thus, CFI does not provide an unbiased evaluation of changes in CBF.

Effect of an acute increase in central blood volume on cerebral hemodynamics.

Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV.

The effect of an acute increase in central blood volume on the response of cerebral blood flow to acute hypotension.

The purpose of the present study was to examine whether the response of cerebral blood flow to an acute change in perfusion pressure is modified by an acute increase in central blood volume. Nine young, healthy subjects voluntarily participated in this study. To measure dynamic cerebral autoregulation during normocapnic and hypercapnic (5%) conditions, the change in middle cerebral artery mean blood flow velocity was analyzed during acute hypotension caused by two methods: 1) thigh-cuff occlusion release (without change in central blood volume); and 2) during the recovery phase immediately following release of lower body negative pressure (LBNP; -50 mmHg) that initiated an acute increase in central blood volume. In the thigh-cuff occlusion release protocol, as expected, hypercapnia decreased the rate of regulation, as an index of dynamic cerebral autoregulation (0.236 ± 0.018 and 0.167 ± 0.025 s(-1), P = 0.024). Compared with the cuff-occlusion release, the acute increase in central blood volume (relative to the LBNP condition) with LBNP release attenuated dynamic cerebral autoregulation (P = 0.009). Therefore, the hypercapnia-induced attenuation of dynamic cerebral autoregulation was not observed in the LBNP release protocol (P = 0.574). These findings suggest that an acute change in systemic blood distribution modifies dynamic cerebral autoregulation during acute hypotension.

Impact of short-term training camp on arterial stiffness in endurance runners.

Lack of elasticity in the central artery causes an increase in left ventricular (LV) afterload. Although regular moderate-intensity endurance exercise improves cardiovascular function, including arterial destiffening, little is known about the effect of short-term vigorous exercise on cardiovascular function (i.e., the interaction between cardiac and arterial functions). We measured arterial stiffness [via pulse wave velocity from the heart to ankle (haPWV)] and LV contractility (via systolic interval time) before and after a 1-week training camp in a total of 33 regularly highly-trained collegiate endurance runners. They participated in three training sessions per day which mainly consisted of long-distance running and sprint training. The averaged running distance was ≈ 44% longer during the camp than the regular training program. After the camp, heart rate at rest and haPWV were significantly increased, whereas blood pressure remained unchanged. Although a ratio of pre-ejection period and LV ejection time (PEP/LVET, an index of blunted LV contractility) was unaltered, presumably due to the large variability of individual response, there was a significant correlation between changes in haPWV and PEP/LVET (r = 0.54, P < 0.01). These results suggest that, in regularly highly-trained endurance athletes, arterial stiffness increases after a training camp characterized by greater training volume (vs. regular training), and that the individual response in arterial stiffness correlates with the corresponding changes in myocardial contractility.

Blood flow in internal carotid and vertebral arteries during graded lower body negative pressure in humans.

NEW FINDINGS: What is the central question of this study? Recently, the heterogeneity of the cerebral arterial circulation has been argued. Orthostatic tolerance may be associated with an orthostatic stress-induced change in blood flow in vertebral arteries rather than in internal carotid arteries, because vertebral arteries supply blood to the medulla oblongata, which is the location of important cardiac, vasomotor and respiratory control centres. What is the main finding and its importance? The effect of graded orthostatic stress on vertebral artery blood flow is different from that on internal carotid artery blood flow. This response allows for the possibility that orthostatic tolerance may be associated with haemodynamic changes in posterior rather than anterior cerebral blood flow. Recently, the heterogeneity of the cerebral arterial circulation has been argued, but the characteristics of vertebral artery (VA) and internal carotid artery (ICA) blood flow during graded orthostatic stress remain unknown. We hypothesized that the change in blood flow in VA is not similar to that in ICA blood flow during graded orthostatic stress. We measured blood flows in both ICA and VA during graded lower body negative pressure (LBNP; -20, -35 and -50 mmHg) by using two colour-coded ultrasound systems. The effect of graded orthostatic stress on the VA blood flow was different from that on the ICA blood flow (LBNP × artery, P = 0.006). The change in ICA blood flow was associated with the level of LBNP (r = 0.287, P = 0.029), and a reduction in ICA blood flow from pre-LBNP was observed during -50 mmHg LBNP (from 411 ± 35 to 311 ± 40 ml min(-1) , P = 0.044) without symptoms of presyncope. In contrast, VA blood flow was unchanged during graded LBNP compared with the baseline (P = 0.597) relative to the reduction in ICA blood flow and thus there was no relationship between VA blood flow and the level of LBNP (r = 0.167, P = 0.219). These findings suggest that the change in ICA blood flow is due to the level of LBNP during graded orthostatic stress, but the change in VA blood flow is different from that in ICA blood flow across the different levels of LBNP. These findings provide the possibility that posterior cerebral blood flow decreases only during severe orthostatic stress and is therefore more likely to be linked with orthostatic tolerance.

Influence of skin blood flow and source-detector distance on near-infrared spectroscopy-determined cerebral oxygenation in humans.

Most near-infrared spectroscopy (NIRS) apparatus fails to isolate cerebral oxygenation from an extracranial contribution although they use different source-detector distances. Nevertheless, the effect of different source-detector distances and change in extracranial blood flow on the NIRS signal has not been identified in humans. This study evaluated the extracranial contribution, as indicated by forehead skin blood flow (SkBF) to changes in the NIRS-determined cerebral oxyhaemoglobin concentration (O2 Hb) by use of a custom-made multidistance probe. Seven males (age 21 ± 1 year) were in a semi-recumbent position, while extracranial blood flow was restricted by application of four different pressures (+20 to +80 mmHg) to the left temporal artery. The O2 Hb was measured at the forehead via a multidistance probe (source-detector distance; 15, 22·5 and 30 mm), and SkBF was determined by laser Doppler. Heart rate and blood pressure were unaffected by application of pressure to the temporal artery, while SkBF gradually decreased (P<0·001), indicating that extracranial blood flow was manipulated without haemodynamic changes. Also, O2 Hb gradually decreased with increasing applied pressure (P<0·05), and the decrease was related to that in SkBF (r = 0·737, P<0·01) independent of the NIRS source to detector distance. These findings suggest that the NIRS-determined cerebral oxyhaemoglobin is affected by change in extracranial blood flow independent of the source-detector distance from 15 to 30 mm. Therefore, new algorithms need to be developed for unbiased NIRS detection of cerebral oxygenation.

Enhanced muscle pump during mild dynamic leg exercise inhibits sympathetic vasomotor outflow.

Muscle sympathetic nerve activity (MSNA) is not increased during leg cycling at light and mild intensities, despite activation of central command and the exercise pressor reflex. We determined whether increasing central blood volume and loading the cardiopulmonary baroreceptors modulate sympathetic vasomotor outflow during leg cycling. To this end, we changed the pedaling frequency to enhance skeletal muscle pump. Subjects performed two leg cycle exercises at differential pedal rates of 60 and 80 rpm (60EX and 80EX trials) for two conditions (with and without MSNA measurement). In each trial, subjects completed leg cycling with a differential workload to maintain constant oxygen consumption (VO2). MSNA was recorded via microneurography at the right median nerve of the elbow. Without MSNA measurement, thoracic impedance, stroke volume (SV), and cardiac output (CO) were measured non-invasively using impedance cardiography. Heart rate and VO2 during exercise did not differ between the 60EX and 80EX trials. Changes in thoracic impedance, SV, and CO during the 80EX trial were greater than during the 60EX trial. MSNA during the 60EX trial was unchanged compared with that at rest (25.8 ± 3.1 [rest] to 28.3 ± 3.4 [exercise] bursts/min), whereas a significant decrease in MSNA was observed during the 80EX trial (25.8 ± 2.8 [rest] to 19.7 ± 2.0 [exercise] bursts/min). These results suggest that a muscle pump-induced increase in central blood volume, and thereby loading of cardiopulmonary baroreceptors, could inhibit sympathetic vasomotor outflow during mild dynamic leg exercise, despite activation of central command and the exercise pressor reflex.