Internal Carotid Blood Flow Research Articles

Increases in Central Arterial Stiffness and Reductions in Diastolic Velocity in the Large Cerebral Arteries are Associated with Age-Related Decline in Cerebral Blood Flow

Background: Advanced aging is characterized by a reduction in cerebral blood flow (CBF) and an increase in central arterial stiffness. Increased central arterial stiffness results in reduced Windkessel effects and augmented pulsatile arterial blood pressure and CBF. These changes are detrimental to small cerebral blood vessels because of increases in biomechanical stresses associated with the augmented pulsatile arterial blood pressure and CBF. Purpose: To examine the associations of central arterial stiffness with cerebral hemodynamics and age-related reductions in CBF. Methods: 171 healthy subjects (20-81 yrs, 63% F) underwent color-coded duplex ultrasonography of the left and right internal carotid (ICA) and vertebral artery (VA) to characterize individual artery blood flow (BF), velocity, pulsatility, and CBF. Structural Magnetic Resonance Imaging (MRI) was used to measure total brain tissue volume (TBV). Carotid β-stiffness and carotid-femoral pulse wave velocity (cfPWV) were measured via applanation tonometry to assess central artery stiffness. Data: Age was negatively associated with global CBF (r = -0.425, p < 0.001), and positively with cfPWV (r = 0.701, p < 0.001), and carotid β-stiffness (r = 0.660, p < 0.001). Arterial stiffness was negative associated with ICA diastolic velocity (r = -0.280, p < 0.001; r = -0.259, p < 0.001) and VA diastolic velocity (r = -0.280, p < 0.001; r = -0.248, p = 0.001) controlling for sex, body mass index (BMI), education, and TBV. Carotid β-stiffness moderated indirect effect between age and CBF through ICA diastolic velocity (index of moderated-mediation -0.47 ± 0.13, [-0.74,-0.23]. cfPWV did not moderate the indirect effect between age and CBF through ICA diastolic velocity (index of moderated-mediation -0.36 ± 0.18, [-0.69, 0.03]. The indirect effect of age on CBF through VA diastolic velocity was not moderated by cfPWV (0.03 ± 0.09, [-0.13, 0.23]) or carotid β-stiffness (-0.17 ± 0.09, [-0.33, 0.01]). Conclusions: Age-related decline in CBF is mediated by the decreases in ICA blood flow diastolic velocity, and this relationship was moderated by carotid β-stiffness. This data suggests that increases in central arterial stiffness and reductions in CBF diastolic velocity in the large cerebral arteries likely plays an important role in age-related decline in CBF. This study was supported by NIH R01HL102457-01 and NIH R01AG033106-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cerebral hemodynamic effects of head-up CPR in a porcine model

AimTo assess the hemodynamic effects of head elevation on cerebral perfusion during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. MethodsVF was induced in eight 65 kg pigs that were treated with CPR after five minutes of no flow. Mean arterial pressure (MAP) was measured at the descending thoracic aorta. Internal carotid artery blood flow (CBF) was measured with an ultrasound probe. Cerebral perfusion pressure (CerPP) was calculated in two ways (CerPPICAP and CerPPreported) using the same intracranial pressure (ICP) measurement. CePPreported was calculated as MAP-ICP. CerPPICAP was calculated by using intracranial arterial pressure (ICAP) – ICP. The animals were switched between head up (HUP) and supine (SUP) CPR every five minutes for a total of twenty minutes of resuscitation. ResultsMAP and coronary perfusion pressure measurements were similar in both CPR positions (p = 0.36 and p = 0.1, respectively). ICP was significantly lower in the HUP CPR group (14.7 ± 1 mm Hg vs 26.9 ± 1 mm Hg, p < 0.001) as was ICAP (30.1 ± 2 mm Hg vs 42.6 ± 1 mmHg, p < 0.001). The proportional decrease in ICP and ICAP resulted in similar CerPPICAP comparing HUP and SUPCPR (p = 0.7). CBF was significantly lower during HUPCPR when compared to SUPCPR (58.5 ± 3 ml/min vs 78 ± 4 ml/min, p < 0.001). A higher CerPPreported was found during the HUP compared to SUP-CPR, when MAP was used (36.6 ± 2 mm Hg vs 23 ± 2 mm Hg, p < 0.001) without correcting for the hydrostatic pressure drop. ConclusionHUP did not affect cerebral perfusion pressure and it significantly decreased internal carotid blood flow.

Differential effects of ibuprofen and indomethacin on cerebral oxygen kinetics in the very preterm baby.

BackgroundIbuprofen is preferred to indomethacin for treatment of a significant patent ductus arteriosus (PDA) in preterm babies despite indomethacin being associated with a lower risk of intraventricular haemorrhage. This difference is thought to relate to the discrepant effects of each medication on cerebral oxygen kinetics yet the effect of ibuprofen on cerebral perfusion is uncertain.MethodsForty-eight babies < 30 weeks with a significant PDA, defined by echocardiography, were randomly assigned to either indomethacin or ibuprofen (n = 24 per group) and stratified by gestation and chronologic age. Cerebral blood flow [total internal carotid blood flow (TICF)] and oxygen physiology [oxygen delivery (modCerbDO2) and consumption (modCerbVO2)] were measured using cranial Doppler ultrasound and near-infrared spectroscopy, and cerebral oxygen extraction (cFTOE) calculated, immediately before and following administration. Temporal and treatment related changes were analysed.ResultsA fixed effect of time was seen for TICF (p = 0.03) and therefore modCerbDO2 (p = 0.046) and cFTOE (p = 0.04) for indomethacin alone. In the indomethacin group, TICF and modCerbDO2 fell from baseline to 5 and 30 min respectively (TICF p < 0.01, cDO2 p = 0.01) before increasing from 5 min to 24 h (p < 0.01) and 30 min and 24 h (p < 0.01) timepoints. cFTOE peaked at 30 min (p = 0.02) returning to baseline at 24 h. There was a parallel increase in arterial lactate.ConclusionIndomethacin significantly reduces cerebral blood flow soon after administration, resulting in a parallel increase in oxygen extraction and arterial lactate. This implies that the balance of oxygen kinetics at the time of treatment may be critical in very preterm babies with significant PDA.

The Effects of Exercise on the Sport Concussion Assessment Tool 3 (SCAT3)

There are 3.8 million sports‐related concussions reported annually. Although there is a growing number of sports‐related concussions, there is a lack of evidence‐based methods to evaluate, treat, predict, and monitor recovery in athletes. Today, concussions are clinically diagnosed using self‐reported symptoms and by examining posture, neurocognition, ocular/vestibular control, and various imaging techniques. The Sport Concussion Assessment Tool (SCAT) is widely used on the sideline along with other methods to diagnose a concussion. However, current studies use control groups that are rested (i.e baseline) without considering the effect of intense exercise and contact (not related to head) that a player may have experienced during a game. To obtain this data we developed a mobile tent‐based laboratory that permits us to collect data on the field during a rugby match. SCAT3 questionnaires were performed within 3 hours following a rugby match in players who experienced a head injury or completed the match without a head injury. Additional measures included beat‐by‐beat blood pressure (Finometer), heartrate, common and internal carotid blood flow, and end‐tidal CO2 (nasal cannula) during rest, in the seated and supine position. A principal component analysis was performed on the 26 listed symptoms on the SCAT3 and Mann‐Whitney U‐test on the resulting 4 components. There were a total 209 players (67 female, 142 males; 33 ± 13 years) who just played a match, with 80 who experienced a head injury and 129 controls. Self‐reported symptoms were significantly greater in players who experienced a head injury 26.16 ± 17.6 vs control 8.93 ± 11.5, P&lt;.001. A principal component analysis on our entire dataset produced 4 symptom components: (1) Cognitive‐Sensory (2) Emotional‐Affective (3) Hypersensitive (4) Headache. A Mann‐Whitney U‐tests showed significant differences between the concussed and control groups for the following symptom components: Cognitive‐Sensory (p&lt;0.001), Headache (p&lt;0.001), Emotional‐Affective (p&lt;0.004), and Hypersensitive (p&lt;0.001). This data suggests that the SCAT3 symptoms were greater in the players with a head injury, but that some of the control players who just played an intense match also show an increased number of symptoms and severity. Further analysis and violin plots on each of the 4 components showed that the symptom component named “Headache” composed of; Pressure in the Head, Headache, Feeling Slowed down, Dizziness, Don’t Feel Right may provide a better indicator of concussion in players that just played an intense match. Future work is needed to examine how these components can be used along with current physiological measures to better assess a concussion in players that just came off the field.

Effects of electrical muscle stimulation on cerebral blood flow

BackgroundElectrical muscle stimulation (EMS) induces involuntary muscle contraction. Several studies have suggested that EMS has the potential to be an alternative method of voluntary exercise; however, its effects on cerebral blood flow (CBF) when applied to large lower limb muscles are poorly understood. Thus, the purpose of this study was to examine the effects of EMS on CBF, focusing on whether the effects differ between the internal carotid (ICA) and vertebral (VA) arteries.MethodsThe participants performed the experiments under EMS and control (rest) conditions in a randomized crossover design. The ICA and VA blood flow were measured before and during EMS or control. Heart rate, blood pressure, minute ventilation, oxygen uptake, and end-tidal partial pressure of carbon dioxide (PETCO2) were monitored and measured as well.ResultsThe ICA blood flow increased during EMS [Pre: 330 ± 69 mL min−1; EMS: 371 ± 81 mL min−1, P = 0.001, effect size (Cohen’s d) = 0.55]. In contrast, the VA blood flow did not change during EMS (Pre: 125 ± 47 mL min−1; EMS: 130 ± 45 mL min−1, P = 0.26, effect size = 0.12). In the EMS condition, there was a significant positive linear correlation between ΔPETCO2 and ΔICA blood flow (R = 0.74, P = 0.02). No relationships were observed between ΔPETCO2 and ΔVA blood flow (linear: R = − 0.17, P = 0.66; quadratic: R = 0.43, P = 0.55).ConclusionsThe present results indicate that EMS increased ICA blood flow but not VA blood flow, suggesting that the effects of EMS on cerebral perfusion differ between anterior and posterior cerebral circulation, primarily due to the differences in cerebrovascular response to CO2.

A method to evaluate dynamic cerebral pressure-flow relationships in the conscious rat.

The classic dogma of cerebral autoregulation is that cerebral blood flow is steadily maintained across a wide range of perfusion pressures. This has been challenged by recent studies suggesting little to no "autoregulatory plateau" in the relationship between cerebral blood flow and blood pressure (BP). Therefore, the mechanisms underlying the cerebral pressure-flow relationship still require further understanding. Here, we present a novel approach to examine dynamic cerebral autoregulation in conscious Wistar rats (n = 16) instrumented to measure BP and internal carotid blood flow (iCBF), as an indicator of cerebral blood flow. Transient reductions in BP were induced by occluding the vena cava via inflation of a chronically implanted intravascular silicone balloon. Falls in BP were paralleled by progressive decreases in iCBF, with no evidence of a steady-state plateau. No significant changes in internal carotid vascular resistance (iCVR) were observed. In contrast, intravenous infusions of the vasoactive drug sodium nitroprusside (SNP) produced a similar fall in BP but increases in iCBF and decreases in iCVR were observed. These data suggest a considerable confounding influence of vasodilatory drugs such as SNP on cerebrovascular tone in the rat, making them unsuitable to investigate cerebral autoregulation. We demonstrate that our technique of transient vena cava occlusion produced reliable and repeatable depressor responses, highlighting the potential for our approach to permit assessment of the dynamic cerebral pressure-flow relationship over time in conscious rats.NEW & NOTEWORTHY We present a novel technique to overcome the use of vasoactive agents when studying cerebrovascular dynamics in the conscious rat. Our method of vena cava occlusion to reduce BP was associated with decreased iCBF and no change in iCVR. In contrast, comparable BP falls with intravenous SNP increased iCBF and reduced iCVR. Thus, the dynamic cerebral pressure-flow relationship shows a narrower, less level autoregulatory plateau than conventionally thought. We confirm our method allows repeatable assessment of cerebrovascular dynamics in conscious rats.

Renal Oxygen Sensing Mechanisms May Contribute to Maintaining Cerebral Perfusion During Acute Anemia

Introduction The integrative physiological response to anemia is complex and incompletely understood. We utilized data from studies of acute anemia in rodents to determine the relationship between changes in blood oxygen content (CaO2) and the heterogenous response of the kidney, heart and brain. We hypothesize that renal hypoxia sensing mechanisms contribute to adaptive physiological responses to maintain cerebral oxygen delivery (DO2) during acute anemia. Methods With animal care committee approval, we synthesized novel and published data from 5 previously published studies. Outcomes included: assessment of the relationship between CaO2 and microvascular renal and brain PO2 (phosphorescence quenching of oxyphor G4); cardiac output (CO) and renal and cerebral blood flow (ultrasound Doppler); hypoxia induced cellular responses (brain and kidney erythropoietin (EPO) mRNA and serum protein levels (ELISA)). Statistical analysis (SigmaPlot 14) was performed by ANOVA, Holm-Sidak and Mann-Whitney rank sum test when appropriate. Significance was assigned at p<0.05. Results In two models of anemia (hemodilution and RBC antibody mediated), acute reductions in blood CaO2 were associated with larger decreases in renal microvascular PO2, relative to brain microvascular PO2 (p<0.05). After acute hemodilution, there was a strong relationship between CaO2 and renal microvascular PO2 (r2=0.75). The magnitude of reduction in renal microvascular PO2 correlated with the degree of renal EPO mRNA expression and serum EPO protein levels. The magnitude of the increase in EPO mRNA was much larger in the kidney than in the brain (p<0.03). While no change in renal blood flow was observed in either model, a significant increase in common carotid and internal carotid blood flow was observed in both models (p<0.012). When DO2 was assessed, the kidney DO2 was reduced at all levels of anemia (p<0.01) whereas brain tissue DO2 was maintained in mild and moderate (Hb 90 and 70 g/L) (p=0.44) anemia but reduced in severe anemia (Hb 50 g/L) (p<0.02). The role of active cardiovascular increases in brain blood flow and maintained DO2 during anemia was impaired by systemic beta blockade, suggesting that active cardiovascular mechanisms are required to maintain optimal brain DO2 during anemia. Discussion Our analysis demonstrated: evidence of quantitative renal PO2 sensing of changes in CaO2; the clamping of renal blood flow (reduced DO2) during anemia may be a central mechanism allowing for sensing of changes in CaO2; reduced arterial CaO2 resulted in a local renal hypoxia response (increased serum EPO) and may have initiated the cardiovascular response to increase cerebral blood flow and maintain cerebral DO2. Inhibition of the adrenergic system impaired these responses and resulted in reduced brain DO2. Understanding the heterogeneous adaptive responses to acute anemia may inform clinical practice and optimize management of acutely anemia patients.

Cerebrovascular function response to prolonged sitting combined with a high-glycemic index meal: A double-blind, randomized cross-over trial.

Acute prolonged sitting leads to cerebrovascular disruptions. However, it is unclear how prolonged sitting interacts with other common behaviors, including high- (HGI) and low-glycemic index (LGI) meals. Using a double-blind randomized cross-over design, this study evaluated the effects of prolonged (3hr) sitting, with a high- (HGI; GI: 100) or low-glycemic index (LGI; GI: 19) meal on total brain blood flow (QBrain ) and executive function. Eighteen young, healthy, active participants (22.6 [3.1] y, 33% F, 24.3 [3.7] kg/m2 ) sat for 3hr after consuming an HGI or LGI meal. Using Doppler ultrasound to measure internal carotid (ICA) and vertebral (VA) artery blood flow, QBrain was calculated: (ICA blood flow + VA blood flow) × 2. Executive function was assessed using the Stroop Test and Trail Making Test-Part B. Brain fog was measured using a modified Borg Category Scale with Ratio properties (CR10). Following 3hr of sitting, there was a significant decrease in QBrain with time (p=.001, ES = -0.26), though there were nonsignificant interaction (p=.216) and condition effects (p=.174). Brain fog increased (p=.024, ES = 0.27) and Stroop reaction time worsened with time (p=.001, ES: -0.40), though there were nonsignificant condition effects for brain fog (p=.612) and the Stroop test (p=.445). There was a nonsignificant condition effect (p=.729) for the Trail Making Test-Part B, but completion time improved with time (p=.001, ES = -0.40). In conclusion, 3hr of prolonged sitting decreases QBrain and executive function independent of glycemic index in young, healthy adults.

Cerebral Blood Flow in the Internal Carotid Artery Throughout the Menstrual Cycle in Young, Healthy Women

BackgroundPrevious reports suggest female sex hormones may affect cerebral blood flow and cerebral flow velocity in women. The purpose of this study was to examine whether changes in cerebral blood flow occur throughout the menstrual cycle phases that are associated with fluctuations in sex hormones in young, healthy women.MethodsA subset of eight female participants (mean age 25 yrs) from our previously published study (Favre &amp; Serrador, 2019) underwent one minute of supine steady‐state cerebral blood flow measurements in the internal carotid artery. Women were studied at three different time points across the menstrual cycle: the early‐follicular (EF) phase associated with low levels of estrogen and progesterone, the late‐follicular (LF) phase associated with high levels of estrogen and low levels of progesterone, and the mid‐luteal (ML) phase associated with high levels of both estrogen and progesterone. Cerebral blood flow in the internal carotid artery was measured using duplex ultrasonography. Beat‐by‐beat blood pressure, end‐tidal CO2, ECG, and middle cerebral flow velocity (MCAv) using transcranial Doppler ultrasonography were also obtained.ResultsThere were no statistically significant changes (P=0.269) in internal carotid blood flow across the menstrual cycle phases (EF=203.9±42.2, LF=227.0±53.7, ML=203.2±47.8 ml/min). When examined as a percent of flow from the early follicular phase, there were also no significant changes (P=0.207) across the menstrual cycle (EF=100.0±0.0, LF=111.6±14.5, ML=100.8±17.0 %). Additionally, there were no significant changes (P=0.488) in MCAv (EF=84.7±19.9, LF=89.5±21.2, ML=87.9±24.1 cm/s). End‐tidal CO2 significantly decreased (P=0.025) during the mid‐luteal phase compared to the late follicular phase (EF=38.0±3.0, LF=39.3±2.8, ML=37.0±3.1 mmHg). There were no significant changes (P=0.174) in internal carotid velocity (EF=41.5±7.0, LF=44.8±7.7, ML=40.1±9.2 cm/s) or internal carotid diameter (P=0.327) across the menstrual cycle phases (EF=0.45±0.02, LF=0.46±0.03, ML=0.46±0.01 cm).ConclusionAlthough we did not observe statistically significant changes in internal carotid blood flow across the menstrual cycle phases, we recognize that women demonstrated a 11% increase in flow during the late follicular phase, corresponding to a large effect size (Partial Eta Squared= 0.201). Because of our small sample size, we cannot rule out the possibility that the fluctuations in female sex hormones affect cerebral blood flow. Additionally, it is possible that the decreased end‐tidal CO2 in the mid‐luteal phase hid an underlying increase in cerebral blood flow. However, a larger sample of women is needed to conclude whether cerebral blood flow is affected throughout the menstrual cycle phases.Support or Funding InformationThis work was supported by the Pharmacology, Physiology and Neuroscience Department at Rutgers Biomedical and Health Sciences.

Measures of Heart‐Rate Variability Immediately Post Concussion

There 1.6 to 3.8 million sports‐related concussions reported annually. Despite the growing number of sports‐related concussions, there is a lack of evidence‐based methods to evaluate, treat, predict, and monitor recovery in affected athletes. The pathophysiology undermining the changes in the brain post injury remains unknown. Increasing studies have shown there is autonomic nervous system (ANS) dysfunction following brain injury. Heart rate variability can be used as a method to measure autonomic nervous system anomalies to aid in the detection of concussions. To obtain this data we have developed a mobile tent‐based laboratory that allows us to gather data on the field during a rugby match. Data were collected acutely post‐injury to provide a rapid assessment of concussion effects on the cerebrovascular physiology. The conditions are that athletes all played in a rugby match before enrolling in the study. If the athlete experienced an injury, they had to be assessed by a medical team who classified them as having a concussion. If they did not require any further medical treatment, they were given the option to participate in our study. To assess the autonomic effects of concussion we measured beat‐by‐beat blood pressure (Finometer), heart rate, common and internal carotid blood flow, and end‐tidal CO2 using a nasal cannula during rest, both in the seated and supine position. In a subgroup of 15 players collected last August (6 controls, 9 concussed, Mean age= 30, range= 19–66 yrs) out of our large study (195 players (88 with concussions) we had players perform a SCAT total number of symptoms as well as Symptom Severity Score. Concussed players had significantly higher SCAT total number of symptoms (8 ± 3 vs 4 ± 3, P=0.04) and trending towards a higher Symptom Severity Score (23± 14 vs 10 ± 9, P=0.08). Mean RR Interval in concussed players (seated: 685 ± 41 vs supine: 720 ± 61 ms) compared to controls (seated: 734 ± 90 vs supine: 786 ± 90 ms). Examining postural changes in heart rate variability we found that concussed players demonstrated significant changes in the Low Frequency (LF) ratio seated/supine (Concussed: 1.09 ± 0.47 v Controls: 0.46 ± 0.16) and no change in the High Frequency (HF) ratio seated/supine (Concussed: 0.61 ± 0.21 vs Controls: 0.77 ± 0.29, P=0.3). The SCAT total number of symptoms was significantly correlated to ratio of seated/supine in the LF range in concussed players (r=0.71, P=0.03) but not the HF ratio (r=.48, P=.18). This subset of data suggests that there are changes in heart rate variability immediately post‐concussion, which may be correlated with the number of symptoms following a hit to the head. This data also supports that measures are dependent on posture. The LF frequency increases in the seated position in concussed players suggesting an increase in sympathetic activity, compared to decreasing in controls. Future work is needed to examine how immediate measures of heart rate and brain blood flow in seated and supine are predictive of concussion outcomes.Support or Funding InformationThis work was supported by Dept. of Pharmacology, Physiology, and Neuroscience, Rutgers.

Neural activity and network during cognitive tasks in heat‐stressed individuals

Reductions in cerebral blood flow accompanying heat stress‐induced hypocapnia via hyperventilation are likely to decrease the cognitive function, but the mechanism remains unknown. Using electroencephalographic event‐related potentials (EEG‐ERP) and functional magnetic resonance imaging (fMRI), we evaluated temporal (EEG) and spatial (fMRI) characteristics during cognitive tasks in heat‐stressed humans. Healthy young volunteers performed a visual cognitive task (Go/No‐go task) before (i.e., normothermia) and during heat stress on separate days. The external canal temperature during heat stress was increased by ~ 1.1°C from the normothermic condition. Decreased cerebral blood flow during heat stress was confirmed by reductions in middle cerebral artery blood velocity (MCAV) and internal carotid blood flow in the EEG‐ERP trial. The amplitudes of the Go‐P300 (i.e., execution) and No‐go‐P300 (i.e., inhibition) components were decreased during heat stress. In the fMRI trial, we observed broadly activated brain regions, including the dorsolateral and ventrolateral prefrontal cortices, and motor‐related areas such as the supplementary motor area and premotor area during heat stress rather than during normothermia. These results suggest that heat stress increases the load of neural activity while performing cognitive tasks, relative to normothermia, while heat stress reduced cerebral blood flow and neural activity.Support or Funding InformationJSPS KAKENHI 18H03166This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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 2min. Activated muscle metaboreflex was isolated for 2min 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.

Hemodilution Improves Shear‐Mediated Transduction of Vasodilatory Signals in Human Cerebral and Systemic Circulations

Shear stress (SS) regulates blood flow within the systemic and cerebral circulation. For example, in clinical populations (e.g. hemochromatosis), endothelium‐dependent flow‐mediated dilation (FMD) is improved and impaired by increases and decreases in whole blood viscosity (WBV), respectively. We tested the hypothesis that reductions in WBV would attenuate both cerebrovascular CO2 reactivity and brachial FMD in healthy males (n=9). Internal carotid (ICA) and brachial artery (BA) blood flow, as well as cerebrovascular CO2 reactivity and FMD, were measured prior to and following isovolumic hemodilution with 5% human serum albumin (20% removal/replacement of blood volume). Hemodilution reduced hematocrit (42.7±2.5 vs. 34.7±2.0 %; P&lt;0.01) and WBV (3.6±0.2 vs. 2.7±0.2 cP; P&lt;0.01). Resting ICA blood flow increased by 19% (328.7±66.3 vs. 389.9±91.0 mL · dL−1; P&lt;0.01) while SS was unaltered (13.4±3.2 vs. 12.5±2.6 dyn · cm−2; P=0.17). BA blood flow (41.0±18.9 vs. 54.6±34.1 mL · min−1; P=0.31) and SS (2.54±1.15 vs. 3.00±2.83 dyn · cm−2; P=0.66) were unaltered following hemodilution. Despite a similarly unaltered SS area under the curve stimulus (733.4±296.6 vs. 996.1±571.1 au3; P=0.20), BA FMD increased by 130% (3.9±2.3 vs. 9.0±4.3%; P=0.02). In contrast, however, neither absolute [24.3±7.4 vs. 30.1±13.5 ΔCBF (mL/dL) · ΔmmHg PaCO2; P=0.10] or relative [7.6±3.1 vs. 8.5±4.1 %ΔCBF · mmHg PaCO2; P=0.28) CO2 reactivity were altered following hemodilution despite a reduced SS stimulus throughout the reactivity test (main effect, P&lt;0.01). Therefore, despite the differing influence of hemodilution on cerebral and systemic circulations, both were more responsive for a given SS stimulus following hemodilution.Support or Funding InformationRyan L. Hoiland was supported by a Natural Sciences and Engineering Research Council of Canada Post Graduate Scholarship. Dr. David MacLeod is supported through the Duke University Human Physiology &amp; Pharmacology Laboratory. Prof. Philip Ainslie is supported by the Natural Sciences and Engineering Research Council of Canada and Canada Research Chairs.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of Nitric Oxide Bioavailability on the Progressive Cerebral and Peripheral Circulatory Impairments During Aging and Alzheimer's Disease.

Advanced aging, vascular dysfunction, and nitric oxide (NO) bioavailability are recognized risk factors for Alzheimer's disease (AD). However, the contribution of AD, per se, to this putative pathophysiological mechanism is still unclear. To better answer this point, we quantified cortical perfusion with arterial spin labeling (PVC-CBF), measured ultrasound internal carotid (ICA), and femoral (FA) artery blood flow in a group of patients with similar age (~78 years) but different cognitive impairment (i.e., mild cognitive impairment MCI, mild AD-AD1, moderate AD-AD2, and severe AD-AD3) and compared them to young and healthy old (aged-matched) controls. NO-metabolites and passive leg-movement (PLM) induced hyperemia were used to assess systemic vascular function. Ninety-eight individuals were recruited for this study. PVC-CBF, ICA, and FA blood flow were markedly (range of 9–17%) and significantly (all p < 0.05) reduced across the spectrum from YG to OLD, MCI, AD1, AD2, AD3 subjects. Similarly, plasma level of nitrates and the values of PLM were significantly reduced (range of 8–26%; p < 0.05) among the six groups. Significant correlations were retrieved between plasma nitrates, PLM and PVC-CBF, CA, and FA blood flow. This integrative and comprehensive approach to vascular changes in aging and AD showed progressive changes in NO bioavailability and cortical, extracranial, and peripheral circulation in patients with AD and suggested that they are directly associated with AD and not to aging. Moreover, these results suggest that AD-related impairments of circulation are progressive and not confined to the brain. The link between cardiovascular and the central nervous systems degenerative processes in patients at different severity of AD is likely related to the depletion of NO.

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

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 3days 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 3days 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 8MHz linear transducer. Although the 3days of dry immersion and the 2days 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 3.23mlmin-1 mmHg-1 ; VA, 1.10 and 1.05mlmin-1 mmHg-1 , respectively) from the baseline (ICA, 3.47mlmin-1 mmHg-1 , P=0.027; VA, 1.23mlmin-1 mmHg-1 , P=0.004). In addition, Pearson correlation analysis demonstrated that the 3days 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.

Regional Cerebral Blood Flow Responses to Graded Sympathetic Activation in Young Healthy Subjects

Numerous studies have investigated cerebral blood flow (CBF) responses during orthostatic stress, primarily using middle cerebral artery (MCA) blood velocity. Due to methodological limitations associated with this measurement, there has been a recent transition towards measuring blood flow in vertebral (VA), internal carotid (ICA) and external carotid arteries (ECA) using duplex Doppler ultrasound. Limited studies have simultaneously characterized the response of all these cerebral vessels to simulated orthostatic stress. Likewise, previous studies examining the influence of the sympathetic nervous system on the cerebral vasculature have also relied mainly on MCA velocity measures, primarily performed during infusion of α-adrenergic receptor agonists or antagonists. PURPOSE: To investigate regional CBF responses to a moderate and high level of reflex-mediated sympathetic activation via lower body negative pressure (LBNP) at -10 and -40 Torr, respectively. METHODS: In 8 young men, beat-to-beat arterial pressure (finger photoplethysmography), heart rate (ECG), VA, ICA, ECA and brachial artery blood flow (duplex Doppler ultrasound) and MCA blood velocity (transcranial Doppler) were measured at rest and during 5 min of -10 and -40 Torr LBNP performed in random order. Conductance was calculated as blood flow of the respective artery/mean arterial pressure. RESULTS: In both LBNP trials, there was a significant decrease in brachial artery blood flow and conductance (-10 Torr: -26.0±10.6 % baseline; -40 Torr: -42.3±4.4 % baseline, p=0.006). In contrast, VA, ICA and ECA blood flow and conductance were unaffected (e.g., VA conductance, -10 Torr: -5.8±4.6 % baseline; -40 Torr: -0.03±2.5 % baseline, p=0.654). MCA blood velocity was also unchanged by LBNP (p=0.648). CONCLUSION: Despite the large sympathetically-mediated reductions in brachial artery conductance, cerebral vascular conductance, assessed in multiple arteries, was unaffected by graded sympathetic activation with LBNP. These preliminary data suggest minimal direct effect of reflex-mediated elevations in sympathetic nerve activity on CBF. Supported by NIH grant 1 RO1 HL 127071.

Acute Effects of Walking on Human Internal Carotid Blood Flow

Due to technical limitations of measuring systems, human cerebral blood flow was considered to be highly regulated and relatively constant. New data now strongly suggest that brain blood flow is very dynamic and depends directly on cyclic aortic pressures that interact with retrograde pressure pulses from foot impacts. Recently, we and others have published that ergometer exercise (bicycle, no foot impacts) increases human cerebral blood flow. We also have reported that running, with relatively high foot impacts (4–5 G forces), dramatically modulates brain blood flow with the complex interaction of central aortic pressures and stride rates. Surprisingly, the effects of walking (minimal foot impacts and G forces) on cerebral blood flow have not been reported. Accordingly, we tested the hypothesis that walking modulates cerebral blood flow. In 12 healthy young adults (20 ± 3 years, 6 males/6 females) we used noninvasive duplex ultrasound (3 ms, 0.07 mm; 40db: time, space, and dynamic resolutions; respectively) to measure internal carotid artery blood velocities (BV) and lumen diameters (LD). Internal carotid (hemispheric cerebral) blood flow (CBF, ml/min) was calculated as the product of lumen area and BV [(π × (LD2)/4 × BV)]. Control (upright, resting, and fasting) CBF was calculated and compared to values obtained during steady state walking at 1.0 m/s and 2.0 m/s. Noninvasive heart rate (HR), mean blood pressure (MBP), and cerebral vascular resistance (CVR=MBP/CBF), were also determined (mean/SD; with * = p&lt;0.05 versus control). HR (bpm) Mean BP (mmHg) CBF (ml/min) CVR (units) Control 75/16 97/10 449/155 0.24/0.09 1.0 m/s 87/16* 93/10 558/204* 0.20/0.11* 2.0 m/s 94/19* 94/10 602/205* 0.18/0.07* Preliminary results suggest that relatively low foot impacts during walking significantly affect CBF. Waveform morphology is dependent on the timing convolution of the heart rate and stride rates. Thus, there is a continuum of hemodynamic effects on human brain blood flow within pedaling, walking, and running. These activities may optimize brain perfusion, function, and overall sense of wellbeing during exercise.

Cardiovascular adaptations to moderate anemia maintain cerebral perfusion but are inadequate to prevent renal and splanchnic tissue hypoxia

Mild to moderate anemia is associated with increased organ injury and mortality in surgical patients by undefined mechanisms. We hypothesize that anemia‐induced tissue hypoxia is a potential unifying mechanism. A transgenic mouse model, with luciferase fused to hypoxia inducible factor (HIF ODD‐Luciferase) was utilized to assess the impact of acute antibody‐mediated anemia on adaptive cardiovascular responses, tissue PO2 (PtO2), and HIF expression. A red blood cell (RBC)‐specific antibody (TER119) induced anemia, reducing hemoglobin concentrations from 144±9 to 94±11 g/L (p&lt;0.006) via intravascular hemolysis and RBC sequestration in the spleen and liver. Anemia‐induced cardiovascular adaptations included: 1) increased peripheral arterial oxygen saturation (p=0.018); 2) increased cardiac output (26%, p=0.011); 3) increased internal carotid blood flow (80%, p&lt;0.001); and 4) augmented cerebrovascular reactivity relative to control mice (p&lt;0.001). All of these mechanisms contributed to the maintenance of brain PtO2 (Control vs. Anemia: 23±10 vs.23±5 mmHg O2, p=0.935). By contrast, no increase in renal blood flow occurred (p=0.239), and kidney PtO2 decreased in anemic mice (21±4 vs. 13±4 mmHg O2, p&lt;0.001). Molecular adaptations to tissue hypoxia included increased HIF‐1α expression within the dorsal renal and hepatic region (30%, p=0.006), and ventral gut region (72%, p=0.017). These findings demonstrate anemia‐induced tissue hypoxia is heterogeneous and organ‐specific and support the hypothesis that renal and splanchnic hypoxia may contribute to increased organ injury and mortality in anemic perioperative patients.Support or Funding InformationThe project described was supported by the St. Michael's Hospital AHSC AFP Innovation Fund Grant Support

Impact of aerobic fitness on cerebral blood flow and cerebral vascular responsiveness to CO2 in young and older men.

We sought to test the hypothesis that brain blood flow and cerebral vascular responsiveness to carbon dioxide (CVRCO2 ) are greater in aerobically trained young and old individuals compared to their untrained counterparts. In 11 young trained {[23 (20-26) years] [mean (95% confidence interval)]}, 10 young untrained [25 (22-28) years], 8 older trained [65 (61-69) years], and 9 older untrained [67 (64-71) years] healthy individuals, Doppler ultrasound of the internal carotid (ICA) and vertebral (VA) artery blood flow were determined, along with middle cerebral artery mean flow velocity (MCA Vmean ). Bilateral ICA blood flow was higher in trained individuals when compared to untrained (≈31%, P<0.05), but was not influenced by age. VA blood flow was not affected by age or cardiorespiratory fitness. MCA Vmean was reduced with age [59.5 (55.0-64.1) cm/s young vs 43.6 (38.4-48.9) cm/s old, P<0.05] with no significant effect of training observed. MCA CVRCO2 were not significantly affected by either age or training status, while ICA CVRCO2 tended to be elevated in the old trained group. These findings indicate that endurance training enhances bilateral ICA but not VA blood flow in both young and older individuals.

Intrauterine inflammation, cerebral oxygen consumption and susceptibility to early brain injury in very preterm newborns

BackgroundIn utero exposure to inflammation results in elevated cerebral oxygen consumption. This increased metabolic demand may contribute to the association between chorioamnionitis and intraventricular haemorrhage (P/IVH). We hypothesised that intrauterine...