The interactive effects of posture and biological sex on the control of muscle sympathetic nerve activity during rhythmic handgrip exercise.

Body posture and biological sex exhibit independent effects on the sympathetic neural responses to dynamic exercise. However, the neural mechanisms (e.g., baroreflex) by which posture impacts sympathetic outflow during rhythmic muscular contractions, and whether biological sex affects posture-mediated changes in efferent sympathetic nerve traffic during exercise, remain unknown. Thus, we tested the hypotheses that increases in muscle sympathetic nerve activity (MSNA) would be greater during upright compared with supine rhythmic handgrip (RHG) exercise, and that females would demonstrate smaller increases in MSNA during upright RHG exercise than males. Twenty young (30 [6] yr; means [SD]) individuals (9 males, 11 females) underwent 6 min of supine and upright (head-up tilt 45°) RHG exercise at 40% maximal voluntary contraction with continuous measurements of MSNA (microneurography), blood pressure (photoplethysmography), and heart rate (electrocardiogram). In the pooled group, absolute MSNA burst frequency (P < 0.001), amplitude (P = 0.009), and total MSNA (P < 0.001) were higher during upright compared with supine RHG exercise. However, body posture did not impact the peak change in MSNA during RHG exercise (range: P = 0.063-0.495). Spontaneous sympathetic baroreflex gain decreased from rest to RHG exercise (P = 0.006) and was not impacted by posture (P = 0.347). During upright RHG exercise, males demonstrated larger increases in MSNA burst amplitude (P = 0.002) and total MSNA (P = 0.001) compared with females, which coincided with greater reductions in sympathetic baroreflex gain among males (P = 0.004). Collectively, these data indicate that acute attenuation of baroreflex-mediated sympathoinhibition permits increases in MSNA during RHG exercise and that males exhibit a greater reserve for efferent sympathetic neural recruitment during orthostasis than females.NEW & NOTEWORTHY The impact of posture and sex on cardiovascular control during rhythmic handgrip (RHG) exercise is unknown. We show that increases in muscle sympathetic nerve activity (MSNA) during RHG are partly mediated by a reduction in sympathetic baroreflex gain. In addition, males demonstrate larger increases in total MSNA during upright RHG than females. These data indicate that the baroreflex partly mediates increases in MSNA during RHG and that males have a greater sympathetic vasoconstrictor reserve than females.

The interactive effects of age and sex on the neuro-cardiovascular responses during fatiguing rhythmic handgrip exercise.

The impact of age on exercise pressor responses is equivocal, likely because of sex-specific neuro-cardiovascular changes with age. However, assessments of the interactive effects of age and sex on muscle sympathetic nerve activity (MSNA) responses to exercise are lacking. We tested the hypothesis that older females would exhibit exaggerated increases in blood pressure (BP) and MSNA discharge patterns during handgrip exercise compared with similarly aged males and young adults. Twenty-five young (25 (2) years; mean (SD)) males (YM; n = 12) and females (YF; n = 13) and 23 older (71 (5) years) males (OM; n = 11) and females (OF; n = 12) underwent assessments of BP, total peripheral resistance (TPR; Modelflow) and MSNA action potential (AP) discharge patterns (microneurography) during incremental rhythmic handgrip exercise and post-exercise circulatory occlusion (PECO). OM demonstrated larger ∆BP and ∆TPR from baseline than YM (both P < 0.001) despite smaller increases in ∆APs/burst (OM: 0.4 (3) vs. YM: 5 (3) spikes/burst, P < 0.001) and ∆AP clusters/burst (OM: 0.1 (1) vs. YM: 1.8 (1) clusters/burst, P < 0.001) during exercise. Testosterone was lower in OM than YM (P < 0.001) and was inversely related to ∆BP but positively related to ∆AP clusters/burst in males (both P = 0.03). Conversely, YF and OF demonstrated similar ∆BP and ∆AP discharge during exercise (range: P = 0.75-0.96). Age and sex did not impact haemodynamics or AP discharge during PECO (range: P = 0.08-0.94). Altogether, age-related changes in neuro-cardiovascular reactivity exist in males but not females during fatiguing exercise and seem to be related to testosterone. This sex-specific impact of age underscores the importance of considering biological sex when assessing age-related changes in neuro-cardiovascular control during exercise. KEY POINTS: Older males have the largest increase in blood pressure despite having the smallest increases in sympathetic vasomotor outflow during rhythmic handgrip exercise. Young males demonstrate greater increases in sympathetic action potential (AP) discharge compared with young females during rhythmic handgrip exercise. Older adults (regardless of sex) demonstrate smaller increases in muscle sympathetic nerve activity (MSNA) burst amplitude and total AP clusters compared with young adults during exercise, as well as smaller increases in integrated MSNA burst frequency, incidence and total MSNA activity during post-exercise circulatory occlusion (i.e. independent effect of age). Males, but not females (regardless of age), reflexively modify AP conduction velocity during exercise. Our results indicate that age and sex independently and interactively impact the neural and cardiovascular homeostatic adjustments to fatiguing small muscle mass exercise.

Age- and sex-related differences in sympathetic vascular transduction and neurohemodynamic balance in humans.

Bursts of muscle sympathetic nerve activity (MSNA) and the ensuing vasoconstriction are pivotal determinants of beat-by-beat blood pressure regulation. Although age and sex impact blood pressure regulation, how these factors affect the central and peripheral arcs of the baroreflex remains unclear. In 27 young [25 (SD 3) yr] males (YM; n = 14) and females (YF; n = 13) and 23 older [71 (SD 5) yr] males (OM; n = 11) and females (OF; n = 12), femoral artery blood flow, blood pressure, and MSNA were recorded for 10 min of supine rest. Sympathetic baroreflex sensitivity (i.e., central arc) was quantified as the relationship between diastolic blood pressure and MSNA burst incidence. Signal averaging was used to determine sympathetic vascular transduction into leg vascular conductance (LVC) for 12 cardiac cycles following MSNA bursts (i.e., peripheral arc). Older adults demonstrated attenuated sympathetic transduction into LVC (both P < 0.001) following MSNA bursts, and smaller increases in sympathetic transduction as a function of MSNA burst size and firing pattern compared with young adults (range, P = 0.004-0.032). YM (r2 = 0.36; P = 0.032) and OM (r2 = 0.51; P = 0.014) exhibited an inverse relationship between the central and peripheral arcs of the baroreflex, whereas females did not (YF, r2 = 0.03, P = 0.621; OF, r2 = 0.06, P = 0.445). MSNA burst incidence was inversely related to sympathetic transduction in YM and OF (range, P = 0.03-0.046) but not in YF or OM (range, P = 0.360-0.603). These data indicate that age is associated with attenuated sympathetic vascular transduction, whereas age- and sex-specific changes are present in the relationship between the central and peripheral arcs of the baroreflex regulation of blood pressure.NEW & NOTEWORTHY Sympathetic vascular transduction is attenuated in older compared with young adults, regardless of biological sex. Males, but not females (regardless of age), demonstrate an inverse relationship between central (sympathetic baroreflex sensitivity) and peripheral (sympathetic vascular transduction) components of the baroreflex arc. Young males and older females exhibit an inverse relationship between resting sympathetic outflow and sympathetic vascular transduction. Our results indicate that age and sex exert independent and interactive effects on sympathetic vascular transduction and sympathetic neurohemodynamic balance in humans.

Effects of biological sex and oral contraception on the sympathetic neurocirculatory adjustments to static handgrip exercise in humans.

While biological sex affects the neurocirculatory adjustments to exercise, the effects of sex hormones on sympathetic action potential (AP) patterns and ensuing vascular transduction remain unknown. We tested the hypothesis that males, and females using oral contraceptive pills (OCPs), would demonstrate larger increases in sympathetic activation and sympathetic vascular transduction compared with naturally menstruating females during static handgrip exercise (SHG) and postexercise circulatory occlusion (PECO). Young males [n = 14, 25 (5) yr], females using OCPs [n = 16, 24 (6) yr], and naturally menstruating females [n = 18, 26 (4) yr] underwent assessments of multiunit muscle sympathetic nerve activity (MSNA)/AP discharge patterns (microneurography) and femoral artery blood flow (ultrasound) during fatiguing SHG at 40% maximum voluntary contraction and 2-min PECO. Sympathetic vascular transduction was determined as the quotient of the change in leg vascular conductance (LVC) and MSNA/AP discharge. Males demonstrated greater increases in APs/burst [males: Δ7 (6) vs. midluteal: Δ2 (3), P = 0.028] and total AP clusters [males: Δ5 (3) vs. midluteal: Δ2 (3), P = 0.008] compared with naturally menstruating females only but not those using OCPs during exercise (APs/burst: P = 0.171, total clusters: P = 0.455). Sympathetic vascular transduction of MSNA burst amplitude, APs/burst, and total AP clusters was greater in males and females using OCPs compared with naturally menstruating females (range: P = 0.004-0.044). In contrast, during PECO no group differences were observed in AP discharge (range: P = 0.510-0.872), and AP discharge was not related to LVC during PECO (range: P = 0.08-0.949). These data indicate that biological sex and OCP use impact the central generation of AP discharge, as well as the transduction of these neuronal messages into peripheral vasoconstriction during static exercise.

Differential regulation of sympathetic neural burst frequency and amplitude throughout normal pregnancy: a longitudinal study.

Sympathetic activation is a hallmark of pregnancy. However, longitudinal assessments of muscle sympathetic nerve activity (MSNA) in pregnancy are scarce and have primarily focused on burst occurrence (frequency) at rest, despite burst strength (amplitude) representing distinct characteristics of sympathetic outflow. Thus, we assessed MSNA burst amplitude distributions in healthy women to determine the impact of normal pregnancy on neural discharge patterns in response to orthostatic stress. Twenty-six women were studied longitudinally during pre-, early- (4-8 wk of gestation), and late (32-36 wk) pregnancy, as well as postpartum (6-10 wk after delivery). MSNA, blood pressure (BP), and heart rate (HR) were measured in the supine posture and during graded head-up tilt (30° and 60° HUT). Mean and median MSNA burst amplitudes were used to characterize burst amplitude distribution. In late pregnancy, women demonstrated smaller increases in HR (P < 0.001) during 60° HUT and larger increases in systolic BP (P = 0.043) throughout orthostasis, compared with prepregnancy. The increase in MSNA burst frequency during late- relative to prepregnancy (Late: Δ14[10] vs. Pre: Δ21[9] bursts/min; P = 0.001) was smaller during 60° HUT, whereas increases in burst incidence were smaller in late- relative to prepregnancy throughout orthostasis (P = 0.009). Nonetheless, median burst amplitude was smaller throughout orthostasis in late compared with prepregnancy (P = 0.038). Thus, while supine MSNA burst frequency was greater in late pregnancy, increases in burst frequency and strength during orthostasis were attenuated. These smaller, orthostatically induced MSNA increases may reflect natural adaptions of pregnancy serving to prevent sympathetic hyper-reactivity that is common in pathological states.

Acute hypoxia impairs posterior cerebral bioenergetics and memory in man.

Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (∼7 h) on central executive (Go/No-Go) and non-executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2 ). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6 h of passive exposure to both normoxia and hypoxia (12% O2 ), in a randomized block cross-over single-blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No-Go task (P = 0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P = 0.005 vs. normoxia) and recall components (P = 0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P = 0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P = 0.19 vs. normoxia) or accuracy (P = 0.20 vs. normoxia) during the Go/No-Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P > 0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia. NEW FINDINGS: What is the central question of this study? We sought to examine the effects of acute hypoxia on central executive (selective attention and response inhibition) and non-executive (memory) performance and the extent to which impairments are potentially related to reductions in regional cerebral blood flow and oxygen delivery. What is the main finding and its importance? Memory was impaired in acute hypoxia, and this was accompanied by a selective reduction in posterior cerebral artery oxygen delivery. In contrast, selective attention and response inhibition remained well preserved. These findings suggest that memory is selectively vulnerable to hypoxia.

Effects of posture changes on dynamic cerebral autoregulation during early pregnancy in women with obesity and/or sleep apnea.

The incidence of syncope during orthostasis increases in early human pregnancy, which may be associated with cerebral blood flow (CBF) dysregulation in the upright posture. In addition, obesity and/or sleep apnea per se may influence CBF regulation due to their detrimental impacts on cerebrovascular function. However, it is unknown whether early pregnant women with obesity and/or sleep apnea could have impaired CBF regulation in the supine position and whether this impairment would be further exacerbated in the upright posture. Dynamic cerebral autoregulation (CA) was evaluated using transfer function analysis in 33 women during early pregnancy (13 with obesity, 8 with sleep apnea, 12 with normal weight) and 15 age-matched nonpregnant women during supine rest. Pregnant women also underwent a graded head-up tilt (30° and 60° for 6 min each). We found that pregnant women with obesity or sleep apnea had a higher transfer function low-frequency gain compared with nonpregnant women in the supine position (P = 0.026 and 0.009, respectively) but not normal-weight pregnant women (P = 0.945). Conversely, the transfer function low-frequency phase in all pregnancy groups decreased during head-up tilt (P = 0.001), but the phase was not different among pregnant groups (P = 0.180). These results suggest that both obesity and sleep apnea may have a detrimental effect on dynamic CA in the supine position during early pregnancy. CBF may be more vulnerable to spontaneous blood pressure fluctuations in early pregnant women during orthostatic stress compared with supine rest due to less efficient dynamic CA, regardless of obesity and/or sleep apnea.

Effect of breath-hold on the responses of arterial blood pressure and cerebral blood velocity to isometric exercise.

PURPOSE: The present study examined the effect of breath-hold without a Valsalva maneuver during isometric exercise on arterial blood pressure (ABP) and cerebral blood flow (CBF). METHODS: Twenty healthy adults (15 men and five women) randomly performed only breath-hold without a Valsalva maneuver (BH), and an isometric handgrip exercise for 30 s at 40% of individual maximal voluntary contraction with continuous breathing (IHG) and with breath-hold without the Valsalva maneuver (IHG-BH). Mean ABP (MAP) and blood velocity in the middle (MCA Vmean) and posterior cerebral arteries (PCA Vmean) were continuously measured throughout each protocol. RESULTS: MAP was elevated during the IHG-BH compared with IHG (P < 0.001) and BH (P = 0.001). Similarly, both MCA Vmean and PCA Vmean were higher during IHG-BH compared with IHG and BH (all P < 0.001). Moreover, the relative change in MAP from the baseline was correlated with that in both cerebral blood velocities during the BH (MCA Vmean: r = 0.739, P < 0.001 and PCA Vmean: r = 0.570, P = 0.009) and IHG-BH (MCA Vmean: r = 0.755, P < 0.001 and PCA Vmean: r = 0.617, P = 0.003) condition, but not the IHG condition (P = 0.154 and P = 0.306). CONCLUSION: These results indicate that during isometric exercise, a breath-hold enhances an exercise-induced increase in MAP and, consequently, MCA Vmean and PCA Vmean.

Influence of cardiac output response to the onset of exercise on cerebral blood flow.

PURPOSE: Change in cardiac output (Q) contributes to cerebral blood flow (CBF) regulation at rest and even during steady-state exercise. At the onset of cycling exercise, Q increases acutely and largely via muscle pump. The purpose of the present study was to examine whether onset exercise-induced a large increase in Q contributes to CBF regulation at the onset of exercise. METHODS: In 20 young healthy participants (10 males and 10 females), Q, mean arterial pressure (MAP), and mean blood velocities of middle and posterior cerebral arteries (MCA Vm and PCA Vm) were continuously measured during light cycling exercise for 3 min. RESULTS: At the onset of exercise, Q increased acutely to the peak (P < 0.001), while the CBF peak responses were not significantly higher than the values during the steady-state exercise (MCA Vm and PCA Vm; P = 0.183 and P = 0.101, respectively). The change in Q was correlated with that of MCA Vm or PCA Vm from resting baseline to the steady-state exercise (r = 0.404, P < 0.001 and r = 0.393, P < 0.001, respectively). However, the change in Q was not correlated with that of MCA Vm or PCA Vm at the onset of exercise (P = 0.853 and P = 0.893, respectively). Any sex differences in the onset response of peripheral and cerebral hemodynamics to exercise were not observed. CONCLUSION: These findings suggest that the acute change in Q does not contribute to CBF regulation at the onset of exercise for protecting cerebral vasculature against a large and acute elevation in Q at the onset of exercise.

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.

Integrated respiratory chemoreflex-mediated regulation of cerebral blood flow in hypoxia: Implications for oxygen delivery and acute mountain sickness.

NEW FINDINGS: What is the central question of this study? To what extent do hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness? What is the main finding and its importance? We provide evidence for site-specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness. ABSTRACT: The aim of the present study was to determine the extent to which hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF) and oxygen delivery (CDO2 ), with corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy men were randomly assigned single blind to 7 h of passive exposure to both normoxia (21% O2 ) and hypoxia (12% O2 ). The peripheral and central respiratory chemoreflex, internal carotid artery, external carotid artery (ECA) and vertebral artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in internal carotid artery CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, vertebral artery and ECA CDO2 were preserved, and the former was attributable to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P < 0.001), whereas the central respiratory chemoreflex remained unchanged (P > 0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (Lake Louise score, r = 0.546-0.709, P = 0.004-0.043; Environmental Symptoms Questionnaires-Cerebral symptoms score, r = 0.587-0.771, P = 0.001-0.027, n = 4). Collectively, these findings highlight the site-specific regulation of CBF in hypoxia that maintains CDO2 selectively in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilatation might represent a hitherto unexplored haemodynamic risk factor implicated in the pathophysiology of AMS.

Does respiratory drive modify the cerebral vascular response to changes in end-tidal carbon dioxide?

NEW FINDINGS: What is the central question of this study? There is an interaction between the regulatory systems of respiration and cerebral blood flow, because the mediator (CO2 ) is the same for both physiological systems. We examined whether the traditional method for determining cerebrovascular reactivity to CO2 is modified by changes in respiration. What is the main finding and its importance? Cerebrovascular reactivity was modified by voluntary changes in respiration during hypercapnia. This finding suggests that an alteration in the respiratory system may result in under- or overestimation of cerebrovascular reactivity determined by traditional methods in healthy adults. ABSTRACT: The cerebral vasculature is sensitive to changes in the arterial partial pressure of CO2 . This physiological mechanism has been well established as a cerebrovascular reactivity to CO2 (CVR). However, arterial CO2 may not be an independent variable in the traditional method for assessment of CVR, because the cerebral blood flow response is also affected by the activation of respiratory drive or higher centres in the brain. We hypothesized that CVR is modified by changes in respiration. To test our hypothesis, in the present study, 10 young, healthy subjects performed hyper- or hypoventilation to change end-tidal CO2 ( PET,CO2 ) with different concentrations of CO2 in the inhaled gas (0, 2.0 and 3.5%). We measured middle cerebral artery mean blood flow velocity by transcranial Doppler ultrasonography to identify the cerebral blood flow response to change in PET,CO2 during each set of conditions. In each set of conditions, PET,CO2 was significantly altered by changes in ventilation, and middle cerebral artery mean blood flow velocity changed accordingly. However, the relationship between changes in middle cerebral artery mean blood flow velocity and PET,CO2 as a response curve of CVR was reset upwards and downwards by hypo- and hyperventilation, respectively, compared with CVR during normal ventilation. The findings of the present study suggest the possibility that an alteration in respiration might lead to under- or overestimation of CVR determined by the traditional methods.

Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise.

We examined whether a change in posterior cerebral artery flow velocity (PCAv) reflected the posterior cerebral blood flow in healthy subjects during both static and dynamic exercise. PCAv and vertebral artery (VA) blood flow, as an index of posterior cerebral blood flow, were continuously measured during an exercise trial using transcranial Doppler (TCD) ultrasonography and Doppler ultrasound, respectively. Static handgrip exercise significantly increased both PCAv and VA blood flow. Increasing intensity of dynamic exercise further increased VA blood flow from moderate exercise, while PCAv decreased to almost resting level. During both static and dynamic exercise, the PCA cerebrovascular conductance (CVC) index significantly decreased from rest (static and high-intensity dynamic exercise, -11.5 ± 12.2% and -18.0 ± 16.8%, means ± SD, respectively) despite no change in the CVC of VA. These results indicate that vasoconstriction occurred at PCA but not VA during exercise-induced hypertension. This discrepancy in vascular response to exercise between PCA and VA may be due to different cerebral arterial characteristics. Therefore, to determine the effect of exercise on posterior cerebral circulation, at least, we need to carefully consider which cerebral artery to measure, regardless of exercise mode.NEW & NOTEWORTHY We examined whether transcranial Doppler-determined flow velocity in the posterior cerebral artery can be used as an index of cerebral blood flow during exercise. However, the changes in posterior cerebral artery flow velocity during exercise do not reflect vertebral artery blood flow.

Effect of increases in cardiac contractility on cerebral blood flow in humans.

The effect of acute increases in cardiac contractility on cerebral blood flow (CBF) remains unknown. We hypothesized that the external carotid artery (ECA) downstream vasculature modifies the direct influence of acute increases in heart rate and cardiac function on CBF regulation. Twelve healthy subjects received two infusions of dobutamine [first a low dose (5 µg·kg-1·min-1) and then a high dose (15 µg·kg-1·min-1)] for 12 min each. Cardiac output, blood flow through the internal carotid artery (ICA) and ECA, and echocardiographic measurements were performed during dobutamine infusions. Despite increases in cardiac contractility, cardiac output, and arterial pressure with dobutamine, ICA blood flow and conductance slightly decreased from resting baseline during both low- and high-dose infusions. In contrast, ECA blood flow and conductance increased appreciably during both low- and high-dose infusions. Greater ECA vascular conductance and corresponding increases in blood flow may protect overperfusion of intracranial cerebral arteries during enhanced cardiac contractility and associated increases in cardiac output and perfusion pressure. Importantly, these findings suggest that the acute increase of blood perfusion attributable to dobutamine administration does not cause cerebral overperfusion or an associated risk of cerebral vascular damage.NEW & NOTEWORTHY A dobutamine-induced increase in cardiac contractility did not increase internal carotid artery blood flow despite an increase in cardiac output and arterial blood pressure. In contrast, external carotid artery blood flow and conductance increased. This external cerebral blood flow response may assist with protecting from overperfusion of intracranial blood flow.

Coupling between arterial and venous cerebral blood flow during postural change.

In supine humans the main drainage from the brain is through the internal jugular vein (IJV), but the vertebral veins (VV) become important during orthostatic stress because the IJV is partially collapsed. To identify the effect of this shift in venous drainage from the brain on the cerebral circulation, this study addressed both arterial and venous flow responses in the "anterior" and "posterior" parts of the brain when nine healthy subjects (5 men) were seated and flow was manipulated by hyperventilation and inhalation of 6% carbon dioxide (CO2). From a supine to a seated position, both internal carotid artery (ICA) and IJV blood flow decreased (P = 0.004 and P = 0.002), while vertebral artery (VA) flow did not change (P = 0.348) and VV flow increased (P = 0.024). In both supine and seated positions the ICA response to manipulation of end-tidal CO2 tension was reflected in IJV (r = 0.645 and r = 0.790, P < 0.001) and VV blood flow (r = 0.771 and r = 0.828, P < 0.001). When seated, the decrease in ICA blood flow did not affect venous outflow, but the decrease in IJV blood flow was associated with the increase in VV blood flow (r = 0.479, P = 0.044). In addition, the increase in VV blood flow when seated was reflected in VA blood flow (r = 0.649, P = 0.004), and the two flows were coupled during manipulation of the end-tidal CO2 tension (supine, r = 0.551, P = 0.004; seated, r = 0.612, P < 0001). These results support that VV compensates for the reduction in IJV blood flow when seated and that VV may influence VA blood flow.

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.