Cerebral Artery Mean Blood Velocity Research Articles

No Sex Differences in Cerebral Blood Velocity Responses During Resistance Exercise

IntroductionThe brain requires intricate regulation of blood flow to maintain adequate perfusion to the tissue. Resistance exercise (RE) causes large increases in mean arterial pressure that challenges the regulation of cerebral blood flow. It is unknown, however, if the sex differences in blood pressure regulation may alter how cerebral blood flow responds to the large increases in blood pressure induced during RE.PurposeTo determine if the cerebral blood velocity response during an acute bout of RE differs by sex.MethodsTwenty‐nine young, healthy adults (M/F: 17/12; 25 ± 5 yrs; 23.9 ± 3.3 kg/m2) performed 3 sets of 10 repetitions maximal isokinetic knee flexion/extension exercise. Systolic (SBP), diastolic (DBP), and mean (MAP) arterial pressure were measured using finger photoplethysmography and used to calculate pulse pressure (PP). Transcranial Doppler ultrasound (2 MHz) was used to measure right middle cerebral artery mean blood velocity (MCAmv) and calculate pulsatility index ([MCAsystolic ‐ MCAdiastolic velocity]/MCAmv). Conductance was calculated as MCAmv/MAP. The last 30‐sec of a 10‐min baseline and last 10‐sec of the 3rd RE set were averaged for analyses.ResultsOverall, females had higher MCAmv and conductance compared to males (p<0.05). SBP, DBP, MAP, PP, MCAmv increased and conductance decreased similarly for males and females during RE (p<0.05). Pulsatility index did not change during RE in either sex (p>0.05).ConclusionsThe blood pressure and cerebral hemodynamic response during RE was not different between sexes. These data suggest sex may not effect cerebrovascular responses to a large increase in blood pressure incurred during maximal RE in young healthy adults. Blood pressure and cerebral blood velocity responses at baseline and during an acute bout of resistance exercise in young adults. Male (n= 17) Female (n= 12) p for Interaction Baseline Resistance Exercise Baseline Resistance Exercise SBP (mmHg) * 124 ± 10 172 ± 18 123 ± 7 170 ± 27 0.92 DBP (mmHg) * 73 ± 7 99 ± 10 74 ± 7 103 ± 17 0.58 MAP (mmHg) * 93 ± 8 128 ± 13 96 ± 7 132 ± 10 0.80 PP (mmHg) * 52 ± 7 72 ± 11 50 ± 6 67 ± 14 0.42 MCA Mean Velocity (cm/sec) *, ‡ 55 ± 9 65 ± 12 70 ± 15 81 ± 30 0.89 MCA Pulsatility Index 0.90 ± 0.16 0.82 ± 0.14 0.81 ± 0.15 0.82 ± 0.27 0.27 Conductance (cm/sec/mmHg) *, ‡ 0.60 ± 0.09 0.51 ±0.10 0.74 ± 0.17 0.62 ± 0.24 0.39 All data are presented mean ± standard deviation *Main effect for time (p<0.05) ‡Main effect for sex (p<0.05)

Repeatability of Cerebral Vasomotor Reactivity to Hypercapnia in Humans

Impaired cerebrovascular function is a risk factor for the development of various neurocognitive and cerebrovascular diseases including cognitive dysfunction, dementia, Alzheimer’s disease, and stroke. Since hypercapnia elicits a robust cerebral vasodilator response, cerebrovascular function is commonly assessed as an increase in cerebral blood flow to elevations in arterial carbon dioxide (i.e., cerebral vasomotor reactivity ‐ CVMR). Hypercapnia induced by a rebreathing protocol is one such technique used to assess cerebrovascular function. Although this technique is used to evaluate CVMR within and between subjects before and after interventions, to our knowledge, the repeatability of CVMR assessed by rebreathing has not been comprehensively investigated. Moreover, the National Institute of Health’s recent guidelines emphasize the need for rigor and reproducibility of data collection techniques. Accordingly, this study was designed to determine the within‐day repeatability of CVMR response to rebreathing‐induced hypercapnia. Eleven young healthy males (age = 24 ± 3 years, BMI = 24.3 ± 3.8 kgm−2, mean ± SEM) reported to the laboratory following an overnight fast and performed 3 trials of rebreathing‐induced hypercapnia each separated by approximately 2 hours. Heart rate (ECG), respiration (Pneumotrace), beat‐to‐beat blood pressure (Finometer), middle cerebral artery mean blood velocity (MCAv ‐ transcranial Doppler) and breath‐by‐breath end‐tidal carbon dioxide concentration (PETCO2 ‐ capnograph) were continuously measured. Cerebral vascular conductance index (CVCi) was calculated as MCAv divided by mean arterial pressure. CVMR was assessed as the slope of the linear regression between the increase in %MCAv and %CVCi across the range of change in PETCO2 (ΔPETCO2). The increase in %MCAv and %CVCi was also assessed at a ΔPETCO2 of 15 mmHg which was the highest common change in magnitude of hypercapnia achieved across all rebreathing trials among all participants. Repeatability between the 3 trials was assessed using intra class correlation coefficient (ICC). The slopes of %CVCi vs. ΔPETCO2 (3.9 ± 0.4, 3.8 ± 0.3 and 3.6 ± 0.3 %mmHg−1 for 1st, 2nd and 3rd trial respectively, p = 0.82) was not different and showed very good repeatability (ICC = 0.86, p < 0.001) between the 3 rebreathing‐induced hypercapnia trials. Likewise, the % increase in CVCi at ΔPETCO2 of 15 mmHg was not different (40 ± 4, 38 ± 4 and 36 ± 4% for 1st, 2nd and 3rd trial respectively, p = 0.72) and also demonstrated very good repeatability between trials (ICC = 0.86, p < 0.001). Similar results were obtained when MCAv was used as the dependent variable. These results suggest that within‐day CVMR assessed by rebreathing‐induced hypercapnia is highly repeatable and therefore can be used as a reliable index of cerebrovascular function.Support or Funding InformationSupported by UTA College of Nursing and Health Innovation

Cerebrovascular carbon dioxide reactivity is influenced by sex despite comparable hemodynamic and respiratory chemosensitivity in young fit individuals

Cerebral blood flow (CBF) is generally higher in women compared to men at rest. Although accumulating evidence supports sex differences in CBF regulation, findings remain contradictory for dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity to carbon dioxide (CVRCO2). Cardiorespiratory fitness represents an indicator of cardiovascular health. However, we have recently reported that dCA is reduced in young fit men compared to controls, and that dCA is attenuated in young fit women compared to fit men. However, the influence of sex on CVRCO2 in these young fit individuals remains misunderstood. The aim of this study was to examine the influence of sex on CVRCO2 in young fit individuals. Changes in middle cerebral artery mean blood velocity (MCAvmean; transcranial doppler), mean arterial pressure (MAP; photoplethysmography), heart rate (HR; ECG) and pulmonary ventilation (spirometer) were measured in 29 young fit individuals (women n=10, men n=19), in response to changes in end‐tidal partial pressure of carbon dioxide (PETCO2; gas analyzer) during the modified Duffin hyperoxic rebreathing test. Women were tested in the early follicular phase. CVRCO2, as well as hemodynamic and ventilatory chemosensitivity, were characterized using linear regressions on the rebreathing portion of the test after the determined ventilatory recruitment threshold. While age was not different between groups (26 ± 6 vs. 27 ± 5 years, P = 0.92), height: (1.64 ± 0.06 vs. 1.77 ± 0.08 m; P < 0.0001), body weight (60 ± 6 vs. 72 ± 10 kg; P = 0.0009) and maximal oxygen uptake (48.4 ± 3.8 vs. 57.9 ± 6.8 mL−1kg−1min−1; P < 0.0001) were lower in women. At rest, MCAvmean (72 ± 8 cm/s vs. 62 ± 11 cm/s; P = 0.02) and HR (73 ± 8 vs. 64 ± 11 bpm; P = 0.02) were higher in women, whereas MAP was not different between groups (100 ± 19 vs. 97 ± 10 mm Hg; P = 0.73). CVRCO2 was higher in women compared to men, both in absolute (1.59 ± 0.78 vs. 0.35 ± 1.51 cm/s/mm Hg, P = 0.01) and normalized terms (2.19 ± 0.97 vs. 0.54 ± 2.41 %/mm Hg, P = 0.02). Hemodynamic and respiratory chemosensitivity responses during CO2 rebreathing were not different between groups (all P > 0.05). These results indicate that the cerebrovasculature of young fit women is more sensitive to CO2 than men despite comparable hemodynamic and ventilatory chemosensitivity responses.Support or Funding InformationS.I., L.L. and S.M. have been supported by a doctoral training scholarship from the Fonds de recherche du Québec ‐ Santé (FRQS)

Neurovascular Coupling is Not Attenuated During Reflex‐Mediated Sympathetic Activation via Lower Body Negative Pressure in Humans

IntroductionCerebral blood flow is tightly coupled with local neuronal activation and metabolism (i.e., neurovascular coupling; NVC). Attenuated NVC has been identified in several chronic diseases, including hypertension, but the underlying mechanism(s) remains unknown. Raised peripheral sympathetic vasoconstrictor activity can play a malevolent role in the pathology of hypertension and might also contribute to the blunted NVC as cerebral arteries are autonomic innervated. However, the role of sympathetic nervous system in the regulation of cerebral blood flow remains controversial. Given this, the purpose of the current study was to test the hypothesis that reflex‐mediated sympathetic activation via lower body negative pressure (LBNP) blunts NVC in humans.MethodsNVC was assessed using a visual stimulation protocol (5 cycles of 30 s eyes closed and 30 s of reading) in 10 young and healthy participants (3 women; aged 25 ± 3 years). In a randomized and counterbalanced order, NVC assessments were made under control conditions and during graded sympathetic activation via LBNP at −20 mmHg and −40 mmHg. Posterior (PCA) and middle cerebral artery (MCA) mean blood velocity (vmean) were determined (transcranial Doppler ultrasound). Vertebral artery blood flow (VAflow) was measured using duplex Doppler ultrasound and vessel wall tracking software. Mean arterial pressure (finger photoplethysmography), stroke volume (Modelflow), heart rate (electrocardiogram) and the partial pressure of end‐tidal carbon dioxide (PetCO2; capnograph) were obtained. Data are presented as mean ± SD.ResultsLBNP to −20 mmHg and −40 mmHg evoked an anticipated reduction in stroke volume and increase in heart rate, while mean arterial pressure was unchanged. Prior to visual stimulation, PCAvmean and MCAvmean were not different between control, −20 LBNP and −40 LBNP conditions (P>0.05), while VAflow was reduced at −40 mmHg (P=0.02 vs. control). Under control conditions, the NVC test evoked a robust increase in PCAvmean (Δ22 ± 4%), a modest increase in MCAvmean (Δ10 ± 3%), and a moderate rise in VAflow (Δ14 ± 5%). The magnitude of these responses was unaffected by LBNP at both −20 mmHg and −40mmHg (PCAvmean Δ23 ± 4% and Δ23 ± 4%; MCAvmean Δ10 ± 1% and Δ11 ± 4%; VAflow Δ15 ± 3% and Δ16 ± 6%; P>0.05). PetCO2 decreased at −20 mmHg (37.0 ± 3.1 mmHg) and −40 mmHg (36.3 ± 3.1 mmHg) LBNP trials compared to control (40.2 ± 3.7mmHg; P=0.004).ConclusionIn summary, these findings indicate that reflex‐mediated sympathetic activation via LBNP does not blunt the NVC response in healthy humans.Support or Funding InformationFunding received from Coordination for the Improvement of Higher Education Personnel (Finance Code 001) (MS), the University of Auckland (JPF, JFRP) and the Health Research Council of New Zealand (JPF, JFRP).

Six weeks of high-intensity interval training to exhaustion attenuates dynamic cerebral autoregulation without influencing resting cerebral blood velocity in young fit men.

Elevated cardiorespiratory fitness (CRF) is associated with reduced dynamic cerebral autoregulation (dCA), but the impact of exercise training per se on dCA remains equivocal. In addition, resting cerebral blood flow (CBF) and dCA after high‐intensity interval training (HIIT) in individuals with already high CRF remains unknown. We examined to what extent 6 weeks of HIIT affect resting CBF and dCA in cardiorespiratory fit men and explored if potential changes are intensity‐dependent. Endurance‐trained men were assigned to group HIIT85 (85% of maximal aerobic power, 1–7 min effort bouts, n = 8) and HIIT115 (115% of maximal aerobic power, 30 sec to 1 min effort bouts, n = 9). Training sessions were completed until exhaustion 3 times/week over 6 weeks. Mean arterial pressure (MAP) and middle cerebral artery mean blood velocity (MCAvmean) were measured continuously at rest and during repeated squat‐stands (0.05 and 0.10 Hz). Transfer function analysis (TFA) was used to characterize dCA on driven blood pressure oscillations during repeated squat‐stands. Neither training nor intensity had an effect on resting MAP and MCAvmean (both P > 0.05). TFA phase during 0.10 Hz squat‐stands decreased after HIIT irrespective of intensity (HIIT85: 0.77 ± 0.22 vs. 0.67 ± 0.18 radians; HIIT115: pre: 0.62 ± 0.19 vs. post: 0.59 ± 0.13 radians, time effect P = 0.048). These results suggest that HIIT over 6 weeks have no apparent benefits on resting CBF, but a subtle attenuation in dCA is seen posttraining irrespective of intensity training in endurance‐trained men.

The age‐related reduction in cerebral blood flow affects vertebral artery more than internal carotid artery blood flow

Ageing reduces cerebral blood flow (CBF), while mean arterial pressure (MAP) becomes elevated. According to 'the selfish brain' hypothesis of hypertension, a reduction in vertebral artery blood flow (VA) leads to increased sympathetic activity and thus increases MAP. In twenty-two young (24±3years; mean±SD) and eleven elderly (70±5years) normotensive men, duplex ultrasound evaluated whether the age-related reduction in CBF affects VA more than internal carotid artery (ICA) blood flow. Pulse-contour analysis evaluated MAP while near-infrared spectroscopy determined frontal lobe oxygenation and transcranial Doppler middle cerebral artery mean blood velocity (MCA Vmean ). During supine rest, MAP (90±13 versus 78±9mmHg; P<0·001) was elevated in the older subjects while their frontal lobe oxygenation (68±7% versus 77±7%; P<0·001), MCA Vmean (49±9 versus 60±12cm s-1 ; P=0·016) and CBF (754±112 versus 900±144mlmin-1 ; P=0·004) were low reflected in VA (138±48 versus 219±50mlmin-1 ; P<0·001) rather than in ICA flow (616±96 versus 680±120mlmin-1 ; P=0·099). In conclusion, blood supply to the brain and its oxygenation are affected by ageing and the age-related decline in VA flow appears to be four times as large as that in ICA and could be important for the age-related increase in MAP.

Dynamic cerebral carbon dioxide reactivity at rest and during exercise

The cerebral vasculature is highly sensitive to direct arterial carbon dioxide tension (PaCO2) changes. Hypocapnia causes cerebral vasoconstriction, while hypercapnia causes cerebral vasodilation to maintain the brain tissue PCO2 within narrow limits. The cerebral blood flow (CBF) responses to PaCO2 changes should be quick, but the cerebral vasculature sensitivity as cerebral CO2 is measured during steady‐state vascular responses. Therefore, the CBF time response to PaCO2 changes remains unknown. The purpose of this study was to examine dynamic cerebral CO2 reactivity at rest and during exercise using the frequency domain analysis.Seven healthy young subjects participated in the study. At rest and during exercise (30% VO2max and cycling exercise), the dynamic CO2 reactivity was calculated based on the transfer function analysis between the end‐tidal CO2 (PETCO2) and the middle cerebral artery mean blood velocity (MCAvm), using a binary white‐noise sequence (0%–7% inspired CO2 fraction). Dynamic characteristics of the respiratory controller showed a low‐pass filter characteristic for regulating ventilation, and the dynamic gain was decreased gradually to 0.7 at 0.02 Hz. However, the gain from PETCO2 to MCAvm (dynamic CO2 reactivity) remained reasonably constant up to 0.02 Hz. Moreover, it did not change during exercise.These findings suggest that the dynamic cerebral CO2 reactivity is reflected in slow to fast PaCO2 changes, and does not change during exercise. In terms of CO2 homeostasis, the cerebral CO2 reactivity may be a more important physiological mechanism to adapt to fast CO2 changes than the ventilatory response to PaCO2 changes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Dynamic Cerebral Autoregulation Is Maintained during High-Intensity Interval Exercise.

High-intensity interval exercise (HIIE) is more effective at increasing metabolic and cardiovascular health compared with moderate-intensity continuous exercise for patients with cardiovascular disease, but exhaustive high-intensity continuous exercise attenuates dynamic cerebral autoregulation (CA). This study assessed the effect of HIIE on dynamic CA. Nine healthy men (age, 24 ± 3 yr; mean ± SD) warmed up at 50%-60% maximal workload (Wmax) for 5 min before HIIE including four 4-min bouts of exercise at 80%-90% Wmax interspaced by four 3-min bouts at 50% to 60% Wmax. Transcranial Doppler determined middle cerebral artery mean blood velocity (MCA Vmean), and brachial artery catheterization determined mean arterial pressure (MAP). Dynamic CA was evaluated by transfer function analysis of changes in MAP and MCA Vmean. The HIIE increased MAP (from 92 ± 9 to 104 ± 10 mm Hg; P < 0.0125), whereas MCA Vmean did not change. Transfer function phase increased and coherence decreased during HIIE (P < 0.0125 vs rest, respectively), whereas gain was unchanged. The results suggest that dynamic CA is unaffected during HIIE, indicating that the brain is protected from fluctuations in MAP. Thus, we propose that HIIE may be beneficial for brain-related health as maintenance of cerebral perfusion in contrast to high-intensity continuous exercise.

Cerebrovascular Reactivity and Cognitive Function in Hypertensive and Non‐Hypertensive Adults

Hypertension and its vascular consequences contribute to cognitive dysfunction. Accelerated cerebrovascular aging in hypertension may impair cognitive function by impairing cerebrovascular reactivity. Cerebrovascular reactivity in hypertension is often assessed by manipulating CO2, which may not directly reflect reactivity occurring from changes in metabolic supply and neuronal demand during a cognitive task (i.e. neurovascular coupling). The purpose of this study was to compare macro‐ and microvascular hemodynamics at rest and during cognitive activity (Stroop task) in 30 middle‐aged, medicated hypertensive (HTN) and 30 age‐, sex‐, and body mass index (BMI)‐matched non‐HTN adults (56±6 yrs, BMI 28.2±2.9 kg/m2; 32 men). Brachial mean pressure (MP) was measured from an oscillometric cuff. Macrovascular measures included common carotid artery (CCA) mean blood flow from ultrasound and middle cerebral artery (MCA) mean blood velocity from transcranial Doppler. Conductance was calculated as blood flow and mean velocity relative to MP for CCA and MCA, respectively. Microvascular measures included prefrontal cortex (PFC) oxy‐(O2Hb) and deoxyhemoglobin (HHb), and tissue saturation index (TSI) via near‐infrared spectroscopy. Data were analyzed using a 2×2 repeated measures ANOVA but are expressed as change from baseline. Accuracy and hit reaction times were computed to assess cognitive performance. Stroop accuracy (Non‐HTN 95±4%, HTN 95±3%) and reaction time (Non‐HTN 960±142 ms, HTN 998±148 ms) were similar between groups (p&gt;0.05). CCA and MCA conductance were not altered during Stroop (p&gt;0.05). PFC HHb decreased similarly in both groups (p&lt;0.05), while TSI response during Stroop tended to differ (p=0.09) between groups. A significant interaction revealed HTN increased O2Hb during Stroop, while O2Hb was unaltered in Non‐HTN. Differences in O2Hb responses remained when expressed relative to MP. Changes in PFC TSI were positively associated with Stroop accuracy in HTN (r=0.41, p&lt;0.05) but not Non‐HTN (r=0.16, p&gt;0.05). Our data indicate that HTN and Non‐HTN have similar pressure‐mediated macrovascular hyperemia to cognitive activity resulting in a maintenance of macrovascular conductance. HTN exhibit greater increases in O2Hb to achieve similar cognitive performance compared to Non‐HTN, perhaps suggestive of early cerebral aging in HTN. The augmented O2Hb response may contribute to overall tissue oxygenation (TSI) which is associated with preserved cognitive performance in HTN.Support or Funding InformationSupported by an AHA Pre‐Doctoral Fellowship and Foundation Research Grant from ACSMThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of hypoxia on cerebrovascular and cognitive function during moderate intensity exercise

Exercise in hypoxia places added demands on the brain and cerebrovasculature that can impact cognitive function. The purpose of this study was to investigate the effect of acute hypoxia on cerebrovascular hemodynamics, markers of neuro-steroidal modulation and brain-blood barrier (BBB) integrity, and cognition during exercise. Thirty healthy participants (21±4yrs., BMI 24.0±2.6kg∙m−2; 15 men) were randomized to both a≈2.5h normoxic (FiO2 20.0%) and hypoxic (FiO2 12.5%) condition on two separate days. After 1.25h, participants underwent 10min of exercise-alone (cycling at 55% HRmax) and 15min of exercise+cognitive testing. Prefrontal cortex (PFC) tissue oxygenation and middle cerebral artery (MCA) mean blood velocity (MnV) were measured using near-infrared spectroscopy and transcranial Doppler respectively at rest, during exercise-alone, and during exercise+cognitive testing. Salivary levels of dehydroepiandosterone [DHEA], DHEA-sulfate [DHEAS]) and neuron specific enolase (NSE) were measured pre and post exercise. Cognition was assessed using standard metrics of accuracy and reaction time (RT), and advanced metrics from drift-diffusion modeling across memory recognition, N-Back and Flanker tasks. MCA MnV increased from rest to exercise (p<0.01) and was unchanged with addition of cognitive testing during exercise in both normoxia and hypoxia. PFC oxygenation increased during exercise (p<0.05) and was further increased with addition of cognitive challenge in normoxia but decreased during exercise in hypoxia (p<0.05) with further reductions occurring with addition of cognitive tasks (p<0.05). DHEA and NSE increased and decreased post-exercise, respectively, in both normoxia and hypoxia (p<0.01). Accuracy on cognitive tasks was similar in normoxia compared to hypoxia, while RT was slower in hypoxia vs normoxia across memory recognition (p<0.01) and Flanker tasks (p=0.04). Drift-diffusion modeling suggested changes in memory RT were due to increases in caution (p<0.01). Overall cognitive performance is maintained during exercise in hypoxia concomitant with slower RT in select cognitive tasks and reduced oxygenation in the PFC. These changes were accompanied by slight increases in neuro-steroidal modulation but appear independent of changes in NSE, a biomarker of BBB integrity. Maintained accuracy and select increases in RT during hypoxic exercise may be related behavioral changes in caution.

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.

Heat stress exacerbates the reduction in middle cerebral artery blood velocity during prolonged self-paced exercise.

This study examined the influence of hyperthermia on middle cerebral artery mean blood velocity (MCA Vmean). Eleven cyclists undertook a 750 kJ self-paced time trial in HOT (35 °C) and COOL (20 °C) conditions. Exercise time was longer in HOT (56 min) compared with COOL (49 min; P < 0.001). Power output in HOT was significantly lower from 40% of work completed onward (P < 0.01). Rectal temperature increased to 39.6 ± 0.6 °C (HOT) and 38.8 ± 0.5 °C (COOL; P < 0.01). Skin temperature, skin blood flow, and heart rate were higher throughout HOT compared with COOL (P < 0.05). A similar increase in ventilation (P < 0.05) and decrease in end-tidal partial pressure of CO2 (PETCO2 ; P < 0.05) occurred in both conditions. Arterial blood pressure and oxygen uptake were lower from 50% of work completed onward in HOT compared with COOL (P < 0.01). MCA Vmean increased at 10% in both conditions (P < 0.01), decreasing thereafter (P < 0.01) and to a greater extent in HOT from 40% of work completed onward (P < 0.05). Therefore, despite a comparable ventilatory response and PETCO2 in the HOT and COOL conditions, the greater level of thermal strain developing in the heat appears to have exacerbated the reduction in MCA Vmean, in part via increases in peripheral blood flow and a decrease in arterial blood pressure.

Possible influences of exercise-intensity-dependent increases in non-cortical hemodynamic variables on NIRS-based neuroimaging analysis during cognitive tasks: Technical note.

[Purpose]Functional near-infrared spectroscopy (fNIRS) provides functional imaging of cortical activations by measuring regional oxy- and deoxy-hemoglobin (Hb) changes in the forehead during a cognitive task. There are, however, potential problems regarding NIRS signal contamination by non-cortical hemodynamic (NCH) variables such as skin blood flow, middle cerebral artery blood flow, and heart rate (HR), which are further complicated during acute exercise. It is thus necessary to determine the appropriate post-exercise timing that allows for valid NIRS assessment during a task without any increase in NCH variables. Here, we monitored post-exercise changes in NCH parameters with different intensities of exercise.[Methods]Fourteen healthy young participants cycled 30, 50 and 70% of their peak oxygen uptake (Vo2peak) for 10 min per intensity, each on different days. Changes in skin blood flow velocity (SBFv), middle cerebral artery mean blood velocity (MCA Vmean) and HR were monitored before, during, and after the exercise.[Results]Post-exercise levels of both SBFv and HR in contrast to MCA Vmean remained high compared to basal levels and the times taken to return to baseline levels for both parameters were delayed (2-8 min after exercise), depending upon exercise intensity.[Conclusion]These results indicate that the delayed clearance of NCH variables of up to 8 min into the post-exercise phase may contaminate NIRS measurements, and could be a limitation of NIRS-based neuroimaging studies.

Influence of muscle metaboreceptor stimulation on middle cerebral artery blood velocity in humans.

Regional anaesthesia to attenuate skeletal muscle afferent feedback abolishes the exercise-induced increase in middle cerebral artery mean blood velocity (MCA Vmean). However, such exercise-related increases in cerebral perfusion are not preserved during post exercise muscle ischaemia (PEMI) where the activation of metabolically sensitive muscle afferents is isolated. We tested the hypothesis that a hyperventilation-mediated decrease in the arterial partial pressure of CO2, hence cerebral vasoconstriction, masks the influence of muscle metaboreceptor stimulation on MCA Vmean during PEMI. Ten healthy men (20±1years old) performed two trials of fatiguing isometric hand-grip exercise followed by PEMI, in control conditions and with end-tidal CO2 (P ET ,CO2) clamped at ∼1mmHg above the resting partial pressure. In the control trial, P ET ,CO2 decreased from rest during hand-grip exercise and PEMI, while MCA Vmean was unchanged from rest. By design, P ET ,CO2 remained unchanged from rest throughout the clamp trial, while MCA Vmean increased during hand-grip (+10.6±1.8cms(-1)) and PEMI (+9.2±1.6cms(-1); P<0.05 versus rest and control trial). Increases in minute ventilation and mean arterial pressure during hand-grip and PEMI were not different in the control and P ET ,CO2 clamp trials (P>0.05). These findings indicate that metabolically sensitive skeletal muscle afferents play an important role in the regional increase in cerebral perfusion observed in exercise, but that influence can be masked by a decrease in P ET ,CO2 when they are activated in isolation during PEMI.

Case report: (Pre)syncopal symptoms associated with a negative internal jugular venous pressure.

A siphon is suggested to support cerebral blood flow but appears not to be established because internal jugular venous (IJV) pressure is close to zero in upright humans. Thus, in eleven young healthy males, IJV pressure was 9 ± 1 mmHg (mean ± SE) when supine and fell to 3 ± 1 mmHg when seated, and middle cerebral artery mean blood velocity (MCA Vmean; P < 0.007) and the near-infrared spectroscopy-determined frontal lobe oxygenation (ScO2; P = 0.028) also decreased. Another subject, however, developed (pre)syncopal symptoms while seated and his IJV pressure decreased to −17 mmHg. Furthermore, his MCA Vmean decreased and yet within the time of observation ScO2 was not necessarily affected. These findings support the hypothesis that a negative IJV pressure that is a prerequisite for creation of a siphon provokes venous collapse inside the dura, and thereby limits rather than supports CBF.

Hyperthermia modulates regional differences in cerebral blood flow to changes in CO2.

The purpose of this study was to assess blood flow responses to changes in carbon dioxide (CO2) in the internal carotid artery (ICA), external carotid artery (ECA), and vertebral artery (VA) during normothermic and hyperthermic conditions. Eleven healthy subjects aged 22 ± 2 (SD) yr were exposed to passive whole body heating followed by spontaneous hypocapnic and hypercapnic challenges in normothermic and hyperthermic conditions. Right ICA, ECA, and VA blood flows, as well as left middle cerebral artery (MCA) mean blood velocity (Vmean), were measured. Esophageal temperature was elevated by 1.53 ± 0.09°C before hypocapnic and hypercapnic challenges during heat stress. Whole body heating increased ECA blood flow and cardiac output by 130 ± 78 and 47 ± 26%, respectively (P < 0.001), while blood flow (or velocity) in the ICA, MCA, and VA was reduced by 17 ± 14, 24 ± 18, and 12 ± 7%, respectively (P < 0.001). Regardless of the thermal conditions, ICA and VA blood flows and MCA Vmean were decreased by hypocapnic challenges and increased by hypercapnic challenges. Similar responses in ECA blood flow were observed in hyperthermia but not in normothermia. Heat stress did not alter CO2 reactivity in the MCA and VA. However, CO2 reactivity in the ICA was decreased (3.04 ± 1.17 vs. 2.23 ± 1.03%/mmHg; P = 0.039) but that in the ECA was enhanced (0.45 ± 0.47 vs. 0.95 ± 0.61%/mmHg; P = 0.032). These results indicate that hyperthermia is capable of altering dynamic cerebral blood flow regulation.

Effects of acute hypoxia on cerebrovascular responses to carbon dioxide

In normoxic conditions, a reduction in arterial carbon dioxide tension causes cerebral vasoconstriction, thereby reducing cerebral blood flow and modifying dynamic cerebral autoregulation (dCA). It is unclear to what extent these effects are altered by acute hypoxia and the associated hypoxic ventilatory response (respiratory chemoreflex). This study tested the hypothesis that acute hypoxia attenuates arterial CO2 tension-mediated regulation of cerebral blood flow to help maintain cerebral O2 homeostasis. Eight subjects performed three randomly assigned respiratory interventions following a resting baseline period, as follows: (1) normoxia (21% O2); (2) hypoxia (12% O2); and (3) hypoxia with wilful restraint of the respiratory chemoreflex. During each intervention, 0, 2.0, 3.5 or 5.0% CO2 was sequentially added (8 min stages) to inspired gas mixtures to assess changes in steady-state cerebrovascular CO2 reactivity and dCA. During normoxia, the addition of CO2 increased internal carotid artery blood flow and middle cerebral artery mean blood velocity (MCA Vmean), while reducing dCA (change in phase = -0.73 ± 0.22 rad, P = 0.005). During acute hypoxia, internal carotid artery blood flow and MCA Vmean remained unchanged, but cerebrovascular CO2 reactivity (internal carotid artery, P = 0.003; MCA Vmean, P = 0.031) and CO2-mediated effects on dCA (P = 0.008) were attenuated. The effects of hypoxia were not further altered when the respiratory chemoreflex was restrained. These findings support the hypothesis that arterial CO2 tension-mediated effects on the cerebral vasculature are reduced during acute hypoxia. These effects could limit the degree of hypocapnic vasoconstriction and may help to regulate cerebral blood flow and cerebral O2 homeostasis during acute periods of hypoxia.

Influence of cholinergic blockade on the cerebral blood flow response to exercise in humans (1183.3)

Administration of the muscarinic cholinergic receptor blocker glycopyrrolate reportedly attenuates the exercise‐induced increase in middle cerebral artery mean blood velocity. We sought to determine the cholinergic contribution to blood flow in the internal carotid artery (ICA; duplex Doppler ultrasound) during low (42±9 Watts; mean±SE) and moderate (110±11 Watts) intensity leg cycling in seven young male subjects (21±1 yr). Mean arterial pressure (MAP) and heart rate (HR; ECG) were continuously monitored. Stroke volume (SV) was determined offline using Modelflow and cardiac output calculated (CO=HR×SV). Exercise trials were conducted under control (no drug) conditions and after cholinergic blockade by administration of glycopyrrolate. Cholinergic blockade increased resting CO (6.8±0.4 to 8.7±0.5 L/min; P&lt;0.05) and MAP (79±2 to 89±3 mmHg), while the responses to exercise were similar. ICA blood flow increased similarly from rest during low and moderate intensity exercise under control (271±34, 333±27 and 361±28 mL/min, respectively, P&lt;0.05) and cholinergic blockade conditions (315±43, 384±33 and 390±38 mL/min, respectively), with ICA blood flow always being higher with cholinergic blockade (P&lt;0.05). These findings indicate that the cholinergic contribution to the internal carotid artery blood flow responses to dynamic exercise in humans is minimal.

A Decrease in Spatially Resolved Near-Infrared Spectroscopy-Determined Frontal Lobe Tissue Oxygenation by Phenylephrine Reflects Reduced Skin Blood Flow

Spatially resolved near-infrared spectroscopy-determined frontal lobe tissue oxygenation (ScO2) is reduced with administration of phenylephrine, while cerebral blood flow may remain unaffected. We hypothesized that extracranial vasoconstriction explains the effect of phenylephrine on ScO2. We measured ScO2 and internal and external carotid as well as vertebral artery blood flow in 7 volunteers (25 [SD 4] years) by duplex ultrasonography during IV infusion of phenylephrine, together with middle cerebral artery mean blood velocity, forehead skin blood flow, and mean arterial blood pressure. During phenylephrine infusion, mean arterial blood pressure increased, while ScO2 decreased by -19% ± 3% (mean ± SE; P = 0.0005). External carotid artery (-27.5% ± 3.0%) and skin blood flow (-25.4% ± 7.8%) decreased in response to phenylephrine administration, and there was a relationship between ScO2 and forehead skin blood flow (Pearson r = 0.55, P = 0.042, 95% confidence interval [CI], = 0.025-0.84; Spearman r = 0.81, P < 0.001, 95% CI, 0.49-0.94) and external carotid artery conductance (Pearson r = 0.62, P = 0.019, 95% CI, 0.13 to 0.86; Spearman r = 0.64, P = 0.012, 95% CI, 0.17-0.88). These findings suggest that a phenylephrine-induced decrease in ScO2, as determined by INVOS-4100 near-infrared spectroscopy, reflects vasoconstriction in the extracranial vasculature rather than a decrease in cerebral oxygenation.

Relationship between aerobic endurance training and dynamic cerebral blood flow regulation in humans

The incidence of orthostatic intolerance is elevated in endurance-trained individuals. We sought to test the hypothesis that aerobic endurance training is associated with an attenuated control of the cerebral vasculature. Endurance trained (ET, n = 13) and age-matched untrained (UT, n = 11) individuals (peak O2 consumption, mean ± SEM; 63 ± 1 vs 42 ± 1 mL/min/kg, P < 0.05) were examined while supine and seated upright. Dynamic cerebral autoregulation (CA) was assessed by calculation of the rate of regulation (RoR) from the arterial blood pressure (ABP) and middle cerebral artery (MCA) mean blood velocity (V mean ) responses to a bilateral thigh cuff release, which evoked a transient hypotension. Cerebral oxygenation (oxyhemoglobin; HbO2 ) was determined with near-infrared spectroscopy. When seated upright, cuff release evoked a greater decrease in ABP (P < 0.001), MCA V mean (P = 0.096) and HbO2 (P < 0.001) in ET compared with UT. However, RoR was similar in ET and UT individuals while seated upright (to 0.193 ± 0.039 vs 0.129 ± 0.029/s, P > 0.05), and there was no significant difference in the relative change in RoR from the supine to upright positions (ΔRoR: -65 ± 7 and -69 ± 7%, for ET and UT, respectively). These findings suggest that aerobic endurance training is not associated with an attenuation in dynamic CA.