Hemorrhage at high altitude: impact of sustained hypobaric hypoxia on cerebral blood flow, tissue oxygenation, and tolerance to simulated hemorrhage in humans.

With ascent to high altitude (HA), compensatory increases in cerebral blood flow and oxygen delivery must occur to preserve cerebral metabolism and consciousness. We hypothesized that this compensation in cerebral blood flow and oxygen delivery preserves tolerance to simulated hemorrhage (via lower body negative pressure, LBNP), such that tolerance is similar during sustained exposure to HA vs. low altitude (LA). Healthy humans (4F/4 M) participated in LBNP protocols to presyncope at LA (1130 m) and 5-7 days following ascent to HA (3800 m). Internal carotid artery (ICA) blood flow, cerebral delivery of oxygen (CDO2) through the ICA, and cerebral tissue oxygen saturation (ScO2) were determined. LBNP tolerance was similar between conditions (LA: 1276 ± 304 s vs. HA: 1208 ± 306 s; P = 0.58). Overall, ICA blood flow and CDO2 were elevated at HA vs. LA (P ≤ 0.01) and decreased with LBNP under both conditions (P < 0.0001), but there was no effect of altitude on ScO2 responses (P = 0.59). Thus, sustained exposure to hypobaric hypoxia did not negatively impact tolerance to simulated hemorrhage. These data demonstrate the robustness of compensatory physiological mechanisms that preserve human cerebral blood flow and oxygen delivery during sustained hypoxia, ensuring cerebral tissue metabolism and neuronal function is maintained.

Older females but not males exhibit increases in cerebral blood velocity, despite similar pulsatility increases after high-intensity resistance exercise.

Sex differences in resting cerebral hemodynamics decline with aging. Given that acute resistance exercise (RE) is a hypertensive challenge, it may reveal sex-dependent abnormalities in cerebral hemodynamics. Thus, we hypothesized that cerebral blood velocity and pulsatility responses to RE would be sex-dependent in older adults. Fourteen older females and 11 males (50-68 yr) completed a high-intensity unilateral isokinetic knee flexion/extension exercise. Measurements were collected at baseline, immediately, 5- and 30-min post-RE. Blood pressure was measured via finger photoplethysmography. Mean middle cerebral artery blood velocity (MCAv) and pulsatility were assessed via transcranial Doppler ultrasound. Carotid pulsatility was obtained via duplex ultrasound. MCAv increased immediately after RE in older females [mean difference (d) = 6.02, 95% CI: 1.66 to 10.39 cm/s, P < 0.001] but not in males (d = -0.72, 95% CI: -3.83 to 5.27 cm/s, P = 0.99), followed by similar reductions 5-min post-RE in older females (d = -4.40, 95% CI: -8.81 to -0.10 cm/s, P = 0.045) and males (d = -6.41, 95% CI: -11.19 to -1.62 cm/s, P = 0.003). MCAv pulsatility increased similarly in older females (d = 0.24, 95% CI: 0.11 to 0.40, P < 0.001) and males (d = 0.38, 95% CI: 0.20 to 0.53, P < 0.001), persisting 5-min post-RE. Older females showed smaller increases in carotid pulsatility immediately after RE (d = 0.18, 95% CI: 0.03 to 0.38, P = 0.01) than males (d = 0.48, 95% CI: 0.26 to 0.68, P < 0.001). An exercise-mediated hypertensive stimulus revealed differential sex responses in MCAv and carotid pulsatility but not in cerebral pulsatility. Cerebral pulsatility findings suggest a similar sex susceptibility to cerebrovascular abnormalities following exercise-mediated hypertensive stimulus in older adults.NEW & NOTEWORTHY Sex differences in resting cerebral hemodynamics decline with advancing age as females experience larger reductions in cerebral blood velocity and steeper pulsatility increases than males. However, an exercise-mediated hypertensive stimulus might reveal sex differences in cerebral hemodynamics not apparent at rest. Following high-intensity resistance exercise, older females but not males exhibit increases in cerebral blood velocity, despite similar increases in cerebral pulsatility. The susceptibility to cerebrovascular abnormalities following exercise-mediated hypertensive stimulus appears similar between sexes.

The effect of aging on carotid artery wall mechanics during maximal resistance exercise.

INTRODUCTION: Age-related stiffening of the large elastic arteries (e.g., common carotid artery [CCA]) may impair wall dynamics (i.e., strain) and amplify transmission of pulsatile blood flow into the brain with large increases in pressure that occur during maximal resistance exercise (RE). The purpose of this study was to compare CCA arterial wall dynamics, central hemodynamics, and cerebral blood velocity responses during maximal RE between young and older adults. METHODS: Thirty-one young (YA; 26 ± 5 yrs; 23.8 ± 3.3 kg/m2) and 25 older adults (OA; 60 ± 6 yrs; 30.0 ± 5.5 kg/m2) performed a unilateral maximal isokinetic knee flexion/extension exercise protocol (i.e., maximal RE). All measures were recorded at baseline and during the last 10 s of maximal RE. Common carotid artery strain, CCA strain time to peak, and CCA strain rate (i.e., variables of arterial wall dynamics) were analyzed using 2D speckle tracking software from circumferential ultrasound images. Transcranial Doppler was used to measure right middle cerebral artery (MCA) blood velocity. Non-invasive arterial blood pressure measurements were obtained using finger photoplethysmography. RESULTS: Older adults had greater reductions in CCA strain time to peak from baseline to maximal RE (345 ± 39 to 242 ± 52 ms) than YA (308 ± 35 to 247 ± 42 ms; interaction effect, p < 0.01). MCA velocity was similar between YA and OA during maximal RE (p = 0.48), despite a greater arterial pressor response in OA (p < 0.01). CONCLUSION: These data suggest cerebral blood velocity responds similarly during maximal RE among OA compared to YA, despite subtle age-related differences in the pressor and extracranial vascular response during maximal RE.

Firefighter hemodynamic responses to different fire training environments.

Firefighting is associated with an increased risk for a cardiovascular (CV) event, likely due to increased CV strain. The increase in CV strain during firefighting can be attributed to the interaction of several factors such as the strenuous physical demand, sympathetic nervous system activation, increased thermal burden, and the environmental exposure to smoke pollutants. Characterizing the impact of varying thermal burden and pollutant exposure on hemodynamics may help understand the CV burden experienced during firefighting. The purpose of this study was to examine the hemodynamic response of firefighters to training environments created by pallets and straw; oriented strand board (OSB); or simulated fire/smoke (fog). Twenty-three firefighters had brachial blood pressure measured and central blood pressure and hemodynamics estimated from the pressure waveform at baseline, and immediately and 30 minutes after each scenario. The training environment did not influence the hemodynamic response over time (interaction, p > 0.05); however, OSB scenarios resulted in higher pulse wave velocity and blood pressure (environment, p < 0.05). In conclusion, conducting OSB training scenarios appears to create the largest arterial burden in firefighters compared to other scenarios in this study. Environmental thermal burden in combination with the strenuous exercise, and psychological and environmental stress placed on firefighters should be considered when designing fire training scenarios and evaluating CV risk.

Similar Effects of Acute Resistance Exercise on Carotid Stiffness in Males and Females.

Sex differences exist in vascular responses to blood pressure perturbations, such as resistance exercise. Increases in aortic stiffness following acute resistance exercise appear different between sexes, with attenuated increases in females vs. males. Whether sex differences exist in carotid stiffness, following resistance exercise is unknown. This study sought to examine sex differences in carotid stiffness, aortic stiffness, and hemodynamics following acute resistance exercise. Thirty-five participants (18 male) completed 3 sets of 10 repetitions of maximal isokinetic knee extension/flexion. Aortic stiffness and hemodynamics were estimated using an automated oscillometric blood pressure monitor at baseline, 5- and 30-min post-exercise. Carotid stiffness was assessed by ß-stiffness index, pressure-strain elastic modulus and arterial compliance using ultrasonography. Resistance exercise increased aortic stiffness, mean and systolic pressure at 5-min (p<0.01), and pressure-strain elastic modulus at 5-min in both sexes (p<0.05). Arterial compliance decreased at 5- and 30-min post exercise in both sexes (p<0.01). No interaction effects were detected in carotid stiffness, aortic stiffness, and hemodynamics, indicating similar vascular responses between sexes. Our findings indicate that the large arteries appear to stiffen similarly following resistance exercise in males and females when presented with similar blood pressure responses.

Responses of cerebral blood velocity and tissue oxygenation to low-frequency oscillations during simulated haemorrhagic stress in humans.

NEW FINDINGS: What is the central question of this study? Do low-frequency oscillations in arterial pressure and cerebral blood velocity protect cerebral blood velocity and oxygenation during central hypovolaemia? What is the main finding and its importance? Low-frequency oscillations in arterial pressure and cerebral blood velocity attenuate reductions in cerebral oxygen saturation but do not protect absolute cerebral blood velocity during central hypovolaemia. This finding indicates the potential importance of haemodynamic oscillations in maintaining cerebral oxygenation and therefore viability of tissues during challenges to cerebral blood flow and oxygen delivery. ABSTRACT: Tolerance to both real and simulated haemorrhage varies between individuals. Exaggerated low-frequency (∼0.1 Hz) oscillations in mean arterial pressure and brain blood flow [indexed via middle cerebral artery velocity (MCAv)] have been associated with improved tolerance to reduced central blood volume. The mechanism for this association has not been explored. We hypothesized that inducing low-frequency oscillations in arterial pressure and cerebral blood velocity would attenuate reductions in cerebral blood velocity and oxygenation during simulated haemorrhage. Fourteen subjects (11 men and three women) were exposed to oscillatory (0.1 and 0.05 Hz) and non-oscillatory (0 Hz) lower-body negative pressure profiles with an average chamber pressure of -60 mmHg (randomized and counterbalanced order). Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe via near-infrared spectroscopy. Tolerance was higher during the two oscillatory profiles compared with the 0 Hz profile (0.05 Hz, P = 0.04; 0.1 Hz, P = 0.09), accompanied by attenuated reductions in stroke volume (P < 0.001) and cerebral oxygenation of the frontal lobe (P ≤ 0.02). No differences were observed between profiles for reductions in mean arterial pressure (P = 0.17) and MCAv (P = 0.30). In partial support of our hypothesis, cerebral oxygenation, but not cerebral blood velocity, was protected during the oscillatory profiles. Interestingly, more subjects tolerated the oscillatory profiles compared with the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of haemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissues during haemorrhagic stress.

Sex Differences in Aortic Hemodynamics Following Acute Exercise: Wave Separation Analysis.

The importance of sex differences in the control of blood pressure responses to exercise is controversial. It is unknown whether the potential sex differences are a result of magnitude differences in forward or reflected pressure waves. The purpose of this study was to investigate sex differences in BP following acute exercise using wave separation analysis. Sixty-eight adults (36 females) participated in the study. Aerobic capacity was measured during a graded cycle ergometry test. Central pulse wave analysis was derived from the radial pulse using applanation tonometry and separated into forward and reflected pressure waves before, and 15 min and 30 min after maximum aerobic exercise. Both males and females exhibited significantly decreased brachial SBP (p<0.05) following acute exercise. However, only males exhibited a significant decrease in forward wave pressure (p<0.05). Reflected wave pressure was decreased following exercise in both sex (p<0.05) with no sex difference. Males and females differ in blood pressure control following maximal exercise. Results show that males rely on both central and peripheral hemodynamic modifications, whereas females mostly rely on peripheral modifications. The preferential peripheral adaptations in females may provide insight regarding mechanisms of blood pressure control and the disproportionate development of hypertension in young men compared to women.

No Evidence of Racial Differences in Endothelial Function and Exercise Blood Flow in Young, Healthy Males Following Acute Antioxidant Supplementation.

This study investigated the effects of acute antioxidant supplementation on endothelial function, exercise blood flow and oxidative stress biomarkers in 9 young African American compared to 10 Caucasian males (25.7±1.2 years). We hypothesized that African American males would have lower exercise blood flow and endothelial responsiveness compared to Caucasian males, and these responses would be improved following antioxidant supplementation. Ultrasonography was used to measure blood flow during handgrip exercise. Endothelial function was assessed using flow-mediated dilation, and lipid peroxidation was assessed by measuring levels of malondialdehyde-thiobarbituric acid reactive substances. African American males exhibited lower endothelial function than Caucasians at baseline (8.3±1.7 vs. 12.2±1.7%) and the difference was ameliorated with antioxidant supplementation (10.7±1.9% vs. 10.8±1.8%), but the interaction was not significant (p=0.10). There were no significant changes in malondialdehyde-thiobarbituric acid reactive substances following antioxidant supplementation. There was a significant increase in brachial blood flow and forearm vascular conductance with exercise but no differences with antioxidant supplementation. There were no group differences in exercise responses and no differences with antioxidant supplementation, suggesting a lack of influence of oxidative stress during exercise in this cohort.

The effect of oscillatory hemodynamics on the cardiovascular responses to simulated hemorrhage during isocapnia.

During cerebral hypoperfusion induced by lower body negative pressure (LBNP), cerebral tissue oxygenation is protected with oscillatory arterial pressure and cerebral blood flow at low frequencies (0.1 Hz and 0.05 Hz), despite no protection of cerebral blood flow or oxygen delivery. However, hypocapnia induced by LBNP contributes to cerebral blood flow reductions, and may mask potential protective effects of hemodynamic oscillations on cerebral blood flow. We hypothesized that under isocapnic conditions, forced oscillations of arterial pressure and blood flow at 0.1 Hz and 0.05 Hz would attenuate reductions in extra- and intracranial blood flow during simulated hemorrhage using LBNP. Eleven human participants underwent three LBNP profiles: a nonoscillatory condition (0 Hz) and two oscillatory conditions (0.1 Hz and 0.05 Hz). End-tidal (et) CO2 and etO2 were clamped at baseline values using dynamic end-tidal forcing. Cerebral tissue oxygenation (ScO2), internal carotid artery (ICA) blood flow, and middle cerebral artery velocity (MCAv) were measured. With clamped etCO2, neither ICA blood flow (ANOVA P = 0.93) nor MCAv (ANOVA P = 0.36) decreased with LBNP, and these responses did not differ between the three profiles (ICA blood flow: 0 Hz: 2.2 ± 5.4%, 0.1 Hz: -0.4 ± 6.6%, 0.05 Hz: 0.2 ± 4.8%; P = 0.56; MCAv: 0 Hz: -2.3 ± 7.8%, 0.1 Hz: -1.3 ± 6.1%, 0.05 Hz: -3.1 ± 5.0%; P = 0.87). Similarly, ScO2 did not decrease with LBNP (ANOVA P = 0.21) nor differ between the three profiles (0 Hz: -2.6 ± 3.3%, 0.1 Hz: -1.6 ± 1.5%, 0.05 Hz: -0.2 ± 2.8%; P = 0.13). Contrary to our hypothesis, cerebral blood flow and tissue oxygenation were protected during LBNP with isocapnia, regardless of whether hemodynamic oscillations were induced.NEW & NOTEWORTHY We examined the role of forcing oscillations in arterial pressure and blood flow at 0.1 Hz and 0.05 Hz on extra- and intracranial blood flow and cerebral tissue oxygenation during simulated hemorrhage (using lower body negative pressure, LBNP) under isocapnic conditions. Contrary to our hypothesis, both cerebral blood flow and cerebral tissue oxygenation were completely protected during simulated hemorrhage with isocapnia, regardless of whether oscillations in arterial pressure and cerebral blood flow were induced. These findings highlight the protective effect of preventing hypocapnia on cerebral blood flow under simulated hemorrhage conditions.

The reciprocal relationship between cardiac baroreceptor sensitivity and cerebral autoregulation during simulated hemorrhage in humans.

A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized that the reciprocal relationship between cardiac baroreflex sensitivity (BRS) and CA would be maintained during sustained central hypovolemia induced by lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n = 51; 23F/28M) completed a LBNP protocol to presyncope. Subjects were classified as high tolerant (HT; completion of -60 mmHg LBNP stage, ≥20-min) or low tolerant (LT; did not complete -60 mmHg LBNP stage, <20-min). R-R intervals (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), and middle cerebral artery velocity (MCAv) were measured continuously. Cardiac BRS was calculated in the time domain (ΔHR/ΔSAP) and frequency domain (RRI-SAP low frequency (LF) transfer function gain), and CA was calculated in the time domain (ΔMCAv/ΔMAP) and frequency domain (MAP-mean MCAv LF transfer function gain). There was a moderate relationship between cardiac BRS and CA for the group of 51 subjects in both the time (R = -0.54, P < 0.0001) and frequency (R = 0.61, P < 0.001) domains; there was a stronger relationship in the HT group (R = 0.73) compared to the LT group (R = 0.31) in the frequency domain (P = 0.08), but no difference between groups in the time domain (HT: R = -0.73 vs. LT: R = -0.63; P = 0.27). These findings suggest that an interaction between BRS and CA may be an important compensatory mechanism that contributes to tolerance to simulated hemorrhage in young healthy adults.

A comparison of protocols for simulating hemorrhage in humans: step versus ramp lower body negative pressure.

Lower body negative pressure (LBNP) elicits central hypovolemia, and it has been used to simulate the cardiovascular and cerebrovascular responses to hemorrhage in humans. LBNP protocols commonly use progressive stepwise reductions in chamber pressure for specific time periods. However, continuous ramp LBNP protocols have also been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between these two LBNP profiles. Healthy human subjects (N = 19; age, 27 ± 4 y; 7 female/12 male) completed a 1) step LBNP protocol (5-min steps) and 2) continuous ramp LBNP protocol (3 mmHg/min), both to presyncope. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), cerebral oxygen saturation (ScO2), and end-tidal CO2 (etCO2) were measured. LBNP tolerance, via the cumulative stress index (CSI, summation of chamber pressure × time at each pressure), and hemodynamic responses were compared between the two protocols. The CSI (step: 911 ± 97 mmHg/min vs. ramp: 823 ± 83 mmHg/min; P = 0.12) and the magnitude of central hypovolemia (%Δ SV, step: -54.6% ± 2.6% vs. ramp: -52.1% ± 2.8%; P = 0.32) were similar between protocols. Although there were no differences between protocols for the maximal %Δ HR (P = 0.88), the %Δ MAP during the step protocol was attenuated (P = 0.05), and the reductions in MCAv, PCAv, ScO2, and etCO2 were greater (P ≤ 0.08) when compared with the ramp protocol at presyncope. These results indicate that when comparing cardiovascular responses to LBNP across different laboratories, the specific pressure profile must be considered as a potential confounding factor.NEW & NOTEWORTHY Ramp lower body negative pressure (LBNP) protocols have been utilized to simulate the continuous nature of bleeding injuries. However, it unknown if tolerance or the physiological responses to ramp LBNP are similar to the more common stepwise LBNP protocol. We report similar tolerance between the two protocols, but the step protocol elicited a greater increase in cerebral oxygen extraction in the presence of reduced blood flow, presumably facilitating the matching of metabolic supply and demand.

Assessment of Cerebrovascular Dynamics and Cognitive Function with Acute Aerobic Exercise in Persons with Multiple Sclerosis.

BACKGROUND: Cognitive dysfunction in multiple sclerosis (MS) may partially stem from inadequate cerebral blood flow. Cerebral blood flow and cognitive function improve with aerobic exercise in healthy adults. The effect of aerobic exercise on cerebrovascular hemodynamics and cognitive performance in persons with MS is unclear. The acute effect of aerobic exercise versus quiet rest on cerebrovascular hemodynamics and cognitive performance in relapsing-remitting MS was examined. METHODS: Sixteen adults with relapsing-remitting MS underwent cerebrovascular hemodynamics and cognitive performance testing before, 2 minutes after, and 30 minutes after aerobic exercise (20-minute treadmill walking, 60% peak oxygen consumption) and a time-matched seated control. Brachial blood pressure was obtained via an oscillometric cuff. Right middle cerebral artery (MCA) blood velocity was measured via transcranial Doppler and used to calculate mean velocity, pulsatility index (PI), and conductance. Carotid artery stiffness was measured via ultrasonography and tonometry. Cognitive performance (accuracy, reaction time) was assessed using a modified flanker task. RESULTS: Exercise elicited significant increases in mean pressure and carotid artery stiffness and decreases in MCA conductance at 2 minutes after exercise, which subsided by 30 minutes (P < .05). Exercise did not significantly alter MCA PI. Flanker reaction time decreased during posttesting in both conditions (P < .05). There were no condition × time interactions for cognitive performance. CONCLUSIONS: Persons with MS seem resilient to exercise-induced acute changes in MCA PI despite transient carotid stiffening, potentially via reductions in MCA conductance. These data suggest that changes in cognitive performance after acute aerobic exercise are not directly related to transient cerebrovascular responses in persons with MS.

The impact of acute central hypovolemia on cerebral hemodynamics: does sex matter?

Trauma-induced hemorrhage is a leading cause of disability and death due, in part, to impaired perfusion and oxygenation of the brain. It is unknown if cerebrovascular responses to blood loss are differentiated based on sex. We hypothesized that compared to males, females would have reduced tolerance to simulated hemorrhage induced by maximal lower body negative pressure (LBNP), and this would be associated with an earlier reduction in cerebral blood flow and cerebral oxygenation. Healthy young males (n = 29, 26 ± 4 yr) and females (n = 23, 27 ± 5 yr) completed a step-wise LBNP protocol to presyncope. Mean arterial pressure (MAP), stroke volume (SV), middle cerebral artery velocity (MCAv), end-tidal CO2 (etCO2), and cerebral oxygen saturation (ScO2) were measured continuously. Unexpectedly, tolerance to LBNP was similar between the sexes (males, 1,604 ± 68 s vs. females, 1,453 ± 78 s; P = 0.15). Accordingly, decreases (%Δ) in MAP, SV, MCAv, and ScO2 were similar between males and females throughout LBNP and at presyncope (P ≥ 0.20). Interestingly, although decreases in etCO2 were similar between the sexes throughout LBNP (P = 0.16), at presyncope, the %Δ etCO2 from baseline was greater in males compared to females (-30.8 ± 2.6% vs. -21.3 ± 3.0%; P = 0.02). Contrary to our hypothesis, sex does not influence tolerance, or the central or cerebral hemodynamic responses to simulated hemorrhage. However, the etCO2 responses at presyncope do suggest potential sex differences in cerebral vascular sensitivity to CO2 during central hypovolemia.NEW & NOTEWORTHY Tolerance and cerebral blood velocity responses to simulated hemorrhage (elicited by lower body negative pressure) were similar between male and female subjects. Interestingly, the change in etCO2 from baseline was greater in males compared to females at presyncope, suggesting potential sex differences in cerebral vascular sensitivity to CO2 during simulated hemorrhage. These findings may facilitate development of individualized therapeutic interventions to improve survival from hemorrhagic injuries in both men and women.

Peaks and valleys: oscillatory cerebral blood flow at high altitude protects cerebral tissue oxygenation.

Introduction.Oscillatory patterns in arterial pressure and blood flow (at ∼0.1 Hz) may protect tissue oxygenation during conditions of reduced cerebral perfusion and/or hypoxia. We hypothesized that inducing oscillations in arterial pressure and cerebral blood flow at 0.1 Hz would protect cerebral blood flow and cerebral tissue oxygen saturation during exposure to a combination of simulated hemorrhage and sustained hypobaric hypoxia.Methods.Eight healthy human subjects (4 male, 4 female; 30.1 ± 7.6 year) participated in two experiments at high altitude (White Mountain, California, USA; altitude, 3800 m) following rapid ascent and 5-7 d of acclimatization: (1) static lower body negative pressure (LBNP, control condition) was used to induce central hypovolemia by reducing chamber pressure to -60 mmHg for 10 min(0 Hz), and; (2) oscillatory LBNP where chamber pressure was reduced to -60 mmHg, then oscillated every 5 s between -30 mmHg and -90 mmHg for 10 min(0.1 Hz). Measurements included arterial pressure, internal carotid artery (ICA) blood flow, middle cerebral artery velocity (MCAv), and cerebral tissue oxygen saturation (ScO2).Results.Forced 0.1 Hz oscillations in mean arterial pressure and mean MCAv were accompanied by a protection of ScO2(0.1 Hz: -0.67% ± 1.0%; 0 Hz: -4.07% ± 2.0%;P = 0.01). However, the 0.1 Hz profile did not protect against reductions in ICA blood flow (0.1 Hz: -32.5% ± 4.5%; 0 Hz: -19.9% ± 8.9%;P = 0.24) or mean MCAv (0.1 Hz: -18.5% ± 3.4%; 0 Hz: -15.3% ± 5.4%;P = 0.16).Conclusions.Induced oscillatory arterial pressure and cerebral blood flow led to protection of ScO2during combined simulated hemorrhage and sustained hypoxia. This protection was not associated with the preservation of cerebral blood flow suggesting preservation of ScO2may be due to mechanisms occurring within the microvasculature.

Aging reduces cerebral blood flow regulation following an acute hypertensive stimulus.

Aging increases arterial stiffness, which has a negative impact on cerebral blood flow (CBF) regulation (decreases CBF and increases CBF pulsatility). The association between arterial stiffness and CBF pulsatility may, in part, explain the relationship between elevated blood pressure (BP) fluctuations and end-organ disease with aging. To understand the mechanisms by which large BP alterations influence cerebral blood flow regulation in both young and old, we examined the effects of age on central and cerebral blood flow regulation following an acute hypertensive stimulus [resistance-exercise (RE)]. Measurements were obtained pre and immediately, 5, and 30 min post-RE in young (n = 35) and older (n = 26) adults. Measurements included cerebral blood velocity (CBv), CBv pulsatility, central pulse-wave velocity (PWV), beta-stiffness index (ß), and carotid blood flow pulsatility. Central hemodynamics and BP were continuously recorded. Mean CBv increased immediately post-RE only in the young and decreased below baseline at 5 min post-RE in both groups (interaction, P < 0.05). Older adults had a greater increase in CBv pulsatility immediately post-RE compared with the young (interaction, P < 0.05). Mean BP was higher and carotid pulsatility was lower in the older group and increased immediately post-RE in both groups (P < 0.05). PWV increased immediately post-RE (P < 0.05). There were no changes in ß. In conclusion, with aging, greater central arterial stiffness leads to a greater transmission of pulsatile blood velocity from the systemic circulation to the cerebral circulation following an acute hypertensive stress.NEW & NOTEWORTHY Reductions in cerebral blood flow and increases in flow pulsatility with aging are associated to cerebrovascular disease; however, little is known about how an acute hypertensive stimulus effects cerebral blood flow regulation in an aged population. Following the hypertensive stimulus, older adults elicit an attenuated increase in cerebral blood velocity and greater transmission of pulsatile velocity to the brain compared with young adults, demonstrating reduced cerebral blood flow regulation to elevated blood pressure responses with aging.

Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults.

IMPACT STATEMENT: We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.

Preserved ability to blunt sympathetically-mediated vasoconstriction in exercising skeletal muscle of young obese humans.

Sympathetic vasoconstriction is attenuated in exercising muscles to assist in matching of blood flow with metabolic demand. This "functional sympatholysis" may be impaired in young obese individuals due to greater sympathetic activation and/or reduced local vasodilatory capacity of both small and large arteries, but this remains poorly understood. We tested the hypothesis that functional sympatholysis is impaired in obese individuals compared with normal-weight counterparts. In 36 obese and normal-weight young healthy adults (n = 18/group), we measured forearm blood flow and calculated forearm vascular conductance (FVC) responses to reflex increases in sympathetic nerve activity induced by lower body negative pressure (LBNP) at rest and during rhythmic handgrip exercise at 15% and 30% of the maximal voluntary contraction (MVC). FVC was normalized to lean forearm mass. In normal-weight individuals, LBNP evoked a decrease in FVC (-16.1 ± 5.7%) in the resting forearm, and the reduction in FVC (15%MVC: -8.1 ± 3.3%; 30%MVC: -1.0 ± 4.0%) was blunted during exercise in an intensity-dependent manner (P < 0.05). Similarly, in obese individuals, LBNP evoked a comparable decrease in FVC (-10.9 ± 5.7%) in the resting forearm, with the reduction in FVC (15%MVC: -9.7 ± 3.3%; 30%MVC: -0.3 ± 4.0%) also blunted during exercise in an intensity-dependent manner (P < 0.05). The magnitude of sympatholysis was similar between groups (P > 0.05) and was intensity-dependent (P < 0.05). Our findings suggest that functional sympatholysis is not impaired in young obese individuals without overt cardiovascular diseases.

Healthy aging and carotid performance: strain measures and ß-stiffness index.

Arterial stiffness is related to the risk of cardiovascular disease (CVD) and increases with aging. Functional impairment of the arterial wall can occur before structural changes and can be detectable before CVD symptoms. The elastic properties of the carotid arterial wall during the cardiac cycle can be evaluated by standard 2-dimensional (2D) ultrasound longitudinal or circumferential imaging of vascular deformation (strain) using speckle tracking. The purpose of this study was to compare standard 2D ultrasound circumferential and longitudinal images of vascular tissue motion and strain using speckle tracking in young and older individuals. Participants underwent recording of 2D ultrasound circumferential and longitudinal images of the common carotid artery. Circumferential carotid strain (CS) and CS rate were obtained and analyzed via speckle tracking software. Following the strain analysis, the circumferential strain ß-stiffness (C-ß) was calculated. Conventional longitudinal ß-stiffness (L-ß) was calculated and non-invasive blood pressure measurements were obtained from carotid artery pressure measurements in a resting supine position using applanation tonometry. C-ß was significantly higher than L-ß, and the association with age was greater (r = .824 vs. r = .547). CS and CS rate were significantly higher in the young compared to the older group. L-ß does not explain as much of the age-dependent differences in the carotid artery compared with C-ß. This is possibly due to the inclusion of whole arterial wall motion and deformation observed in the CS image. The ability of C-ß to accurately predict the future risk of CVD independent of age still needs further investigation.

Effect of upper body position on arterial stiffness: influence of hydrostatic pressure and autonomic function.

OBJECTIVE: To evaluate changes in arterial stiffness with positional change and whether the stiffness changes are due to hydrostatic pressure alone or if physiological changes in vasoconstriction of the conduit arteries play a role in the modulation of arterial stiffness. METHODS: Thirty participants' (male = 15, 24 ±â€Š4 years) upper bodies were positioned at 0, 45, and 72° angles. Pulse wave velocity (PWV), cardio-ankle vascular index, carotid beta-stiffness index, carotid blood pressure (cBP), and carotid diameters were measured at each position. A gravitational height correction was determined using the vertical fluid column distance (mmHg) between the heart and carotid artery. Carotid beta-stiffness was calibrated using three methods: nonheight corrected cBP of each position, height corrected cBP of each position, and height corrected cBP of the supine position (theoretical model). Low frequency systolic blood pressure variability (LFSAP) was analyzed as a marker of sympathetic activity. RESULTS: PWV and cardio-ankle vascular index increased with position (P < 0.05). Carotid beta-stiffness did not increase if not corrected for hydrostatic pressure. Arterial stiffness indices based on Method 2 were not different from Method 3 (P = 0.65). LFSAP increased in more upright positions (P < 0.05) but diastolic diameter relative to diastolic pressure did not (P > 0.05). CONCLUSION: Arterial stiffness increases with a more upright body position. Carotid beta-stiffness needs to be calibrated accounting for hydrostatic effects of gravity if measured in a seated position. It is unclear why PWV increased as this increase was independent of blood pressure. No difference between Methods 2 and 3 presumably indicates that the beta-stiffness increases are only pressure dependent, despite the increase in vascular sympathetic modulation.