Search

Cyclooxygenase (COX) is proposed to regulate cerebral blood flow (CBF); however, accurate regional contributions of COX are relatively unknown at baseline and particularly during hypoxia. We hypothesized that COX contributes to both basal and hypoxic cerebral vasodilation, but COX-mediated vasodilation is greater in the posterior versus anterior cerebral circulation. CBF was measured in 9 healthy adults (28 ± 4 yr) during normoxia and isocapnic hypoxia (fraction of inspired oxygen = 0.11), with COX inhibition (oral indomethacin, 100mg) or placebo. Four-dimensional flow magnetic resonance imaging measured cross-sectional area (CSA) and blood velocity to quantify CBF in 11 cerebral arteries. Cerebrovascular conductance (CVC) was calculated (CVC = CBF × 100/mean arterial blood pressure) and hypoxic reactivity was expressed as absolute and relative change in CVC [ΔCVC/Δ pulse oximetry oxygen saturation (SpO2)]. At normoxic baseline, indomethacin reduced CVC by 44 ± 5% (P < 0.001) and artery CSA (P < 0.001), which was similar across arteries. Hypoxia (SpO2 80%-83%) increased CVC (P < 0.01), reflected as a similar relative increase in reactivity (% ΔCVC/-Δ SpO2) across arteries (P < 0.05), in part because of increases in CSA (P < 0.05). Indomethacin did not alter ΔCVC or ΔCVC/Δ SpO2 to hypoxia. These findings indicate that 1) COX contributes, in a largely uniform fashion, to cerebrovascular tone during normoxia and 2) COX is not obligatory for hypoxic vasodilation in any regions supplied by large extracranial or intracranial arteries. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective. We examined the effect of IR as indexed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI) among cognitively asymptomatic middle-aged individuals. We hypothesized that higher HOMA-IR would be associated with reduced flow in macrovessels and lower cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged adults (57 ± 5 yrs) underwent fasting blood draw, phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood flow, particularly within the internal carotid arteries (ICAs), and lower cerebral perfusion in several brain regions including frontal and temporal lobe regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion in individuals with lower HOMA-IR, a relationship not observed among those with higher HOMA-IR. Findings provide novel evidence for an uncoupling of macrovascular blood flow and microvascular perfusion among individuals with higher IR in midlife. [ABSTRACT FROM AUTHOR]

The inability to quantify cerebral blood flow and changes in macrocirculation cross-sectional area in all brain regions impedes robust insight into hypoxic cerebral blood flow control. We applied four-dimensional flow magnetic resonance imaging to quantify cerebral blood flow (ml • min-1) and cross-sectional area (mm²) simultaneously in 11 arteries. In healthy adults, blood pressure, O2 Saturation (SpO2), and end-tidal CO2 were measured at baseline and steady-state hypoxia (FiO2 = 0.11). We investigated left and right: internal carotid, vertebral, middle, anterior, posterior cerebral arteries, and basilar artery. Hypoxia (SpO2 = 80±2%) increased total cerebral blood flow from 621±38 to 742±50 ml • min-1 (p<0.05). Hypoxia increased cerebral blood flow, except in the right posterior cerebral arteries. Hypoxia increased cross-sectional area in the anterior arteries (left and right internal carotid arteries, left and right middle, p<0.05; left and right anterior p = 0.08) but only the right vertebral artery of the posterior circulation. Nonetheless, relative cerebral blood flow distribution and vascular reactivity (Δ%cerebral blood flow • ΔSpO2-1) were not different between arteries. Collectively, moderate hypoxia: (1) increased cerebral blood flow, but relative distribution remains similar to normoxia, (2) evokes similar vascular reactivity between 11 arteries, and (3) increased cross-sectional area primarily in the anterior arteries. This study provides the first wide-ranging, quantitative, functional and structural data regarding intracranial arteries during hypoxia in humans, highlighting cerebral blood flow regulation of microcirculation and macrocirculation differs between anterior and posterior circulation. [ABSTRACT FROM AUTHOR]

Within individuals, critical power appears sensitive to manipulations in O2 delivery. We asked whether interindividual differences in forearm O2 delivery might account for a majority of the interindividual differences in forearm critical force impulse (critical impulse), the force analog of critical power. Ten healthy men (24.6 ± 7.10 years) completed a maximal effort rhythmic handgrip exercise test (1 sec contraction-2 sec relaxation) for 10 min. The average of contraction impulses over the last 30 sec quantified critical impulse. Forearm brachial artery blood flow (FBF; echo and Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured continuously. O2 delivery (FBF arterial oxygen content (venous blood [hemoglobin] and oxygen saturation from pulse oximetry)) and forearm vascular conductance (FVC; FBF.MAP -1) were calculated. There was a wide range in O2 delivery (59.98-121.15 O2 mL.min-1) and critical impulse (381.5-584.8 N) across subjects. During maximal effort exercise, O2 delivery increased rapidly, plateauing well before the declining forearm impulse and explained most of the interindividual differences in critical impulse (r2 = 0.85, P < 0.01). Both vasodilation (r2 = 0.64, P < 0.001) and the exercise pressor response (r2 = 0.33, P < 0.001) independently contributed to interindividual differences in FBF. In conclusion, interindividual differences in forearm O2 delivery account for most of the interindividual variation in critical impulse. Furthermore, individual differences in pressor response play an important role in determining differences in O2 delivery in addition to vasodilation. The mechanistic origins of this vasodilatory and pressor response heterogeneity across individuals remain to be determined. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/ mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = -0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. [ABSTRACT FROM AUTHOR]

No non-invasive test exists for forearm exercise that allows identification of power-time relationship parameters (W′, critical power) and thereby identification of the heavy-severe exercise intensity boundary and scaling of aerobic metabolic exercise intensity. The aim of this study was to develop a maximal effort handgrip exercise test to estimate forearm critical force (fCF; force analog of power) and establish its repeatability and validity. Ten healthy males (20–43 years) completed two maximal effort rhythmic handgrip exercise tests (repeated maximal voluntary contractions (MVC); 1 s contraction-2 s relaxation for 600 s) on separate days. Exercise intensity was quantified via peak contraction force and contraction impulse. There was no systematic difference between test 1 and 2 for fCFpeak force (p = 0.11) or fCFimpulse (p = 0.76). Typical error was small for both fCFpeak force (15.3 N, 5.5%) and fCFimpulse (15.7 N⋅s, 6.8%), and test re-test correlations were strong (fCFpeak force, r = 0.91, ICC = 0.94, p<0.01; fCFimpulse, r = 0.92, ICC = 0.95, p<0.01). Seven of ten subjects also completed time-to-exhaustion tests (TTE) at target contraction force equal to 10%fCFpeak force. TTE predicted by W′ showed good agreement with actual TTE during the TTE tests (r = 0.97, ICC = 0.97, P<0.01; typical error 0.98 min, 12%; regression fit slope = 0.99 and y intercept not different from 0, p = 0.31). MVC did not predict fCFpeak force (p = 0.37), fCFimpulse (p = 0.49) or W′ (p = 0.15). In conclusion, the poor relationship between MVC and fCF or W′ illustrates the serious limitation of MVC in identifying metabolism-based exercise intensity zones. The maximal effort handgrip exercise test provides repeatable and valid estimates of fCF and should be used to normalize forearm aerobic metabolic exercise intensity instead of MVC. [ABSTRACT FROM AUTHOR]

The importance of nitric oxide (NO) in regulating cerebral blood flow (CBF) remains unresolved, due in part to methodological approaches, which lack a comprehensive assessment of both global and regional effects. Importantly, NO synthase (NOS) expression and activity appear greater in some anterior brain regions, suggesting region‐specific NOS influence on CBF. We hypothesized that NO contributes to basal CBF in healthy adults, in a regionally distinct pattern that predominates in the anterior circulation. Fourteen healthy adults (7 females; 24 ± 5 years) underwent two magnetic resonance imaging (MRI) study visits with saline (placebo) or the NOS inhibitor, L‐NMMA, administered in a randomized, single‐blind approach. 4D flow MRI quantified total and regional macrovascular CBF, whereas arterial spin labelling (ASL) MRI quantified total and regional microvascular perfusion. L‐NMMA (or volume‐matched saline) was infused intravenously for 5 min prior to imaging. L‐NMMA reduced CBF (L‐NMMA: 722 ± 100 vs. placebo: 771 ± 121 ml/min, P = 0.01) with similar relative reductions (5–7%) in anterior and posterior cerebral circulations, due in part to the reduced cross‐sectional area of 9 of 11 large cerebral arteries. Global microvascular perfusion (ASL) was reduced by L‐NMMA (L‐NMMA: 42 ± 7 vs. placebo: 47 ± 8 ml/100g/min, P = 0.02), with 7–11% reductions in both hemispheres of the frontal, parietal and temporal lobes, and in the left occipital lobe. We conclude that NO contributes to macrovascular and microvascular regulation including larger artery resting diameter. Contrary to our hypothesis, the influence of NO on cerebral perfusion appears regionally uniform in healthy young adults. Key points: Cerebral blood flow (CBF) is vital for brain health, but the signals that are key to regulating CBF remain unclear.Nitric oxide (NO) is produced in the brain, but its importance in regulating CBF remains controversial since prior studies have not studied all regions of the brain simultaneously.Using modern MRI approaches, a drug that inhibits the enzymes that make NO (L‐NMMA) reduced CBF by up to 11% in different brain regions.NO helps maintain proper CBF in healthy adults. These data will help us understand whether the reductions in CBF that occur during ageing or cardiovascular disease are related to shifts in NO signalling. [ABSTRACT FROM AUTHOR]

The authors discuss research published within the issue concerning stiffness and blood flow problems in downstream and upstream arteries. Topics covered include the effects of the stiffness of large artery on cerebral and skeletal muscle vasculature, greater pulsability of the middle cerebral artery (MCA) compared to the gastrocnemius feed artery and the dependence of MCA on nitrous oxide to elicit dilatation.

A monoexponential model characterizing cerebral blood velocity dynamics at the onset of exercise may mask dynamic responses by the cerebrovasculature countering large fluctuations of middle cerebral artery blood velocity (MCAv) and cerebral perfusion pressure (CPP) oscillations. Therefore, the purpose of this study was to determine whether the use of a monoexponential model attributes initial fluctuations of MCAv at the start of exercise as a time delay (TD). Twenty‐three adults (10 women, 23.9 ± 3.3 yrs; 23.7 ± 2.4 kg/m2) completed 2 min of rest followed by 3 mins of recumbent cycling at 50 W. MCAv, CPP, and Cerebrovascular Conductance index (CVCi), calculated as CVCi = MCAv/MAP × 100 mmHg, were collected, a lowpass filter (0.2 Hz) was applied, and averaged into 3‐second bins. MCAv data were then fit to a monoexponential model [ΔMCAv(t) = Amp(1 – e−(t−TD)/τ)]. TD, tau (τ), and mean response time (MRT = TD + τ) were obtained from the model. Subjects exhibited a TD of 20.2 ± 18.1 s. TD was directly correlated with MCAv nadir (MCAvN), r = −0.560, p = 0.007, which occurred at similar times (16.5 ± 15.3 vs. 20.2 ± 18.1 s, p = 0.967). Regressions indicated CPP as the strongest predictor of MCAvN (Ra2$$ {R}_a^2 $$ = 0.36). Fluctuations in MCAv were masked using a monoexponential model. To adequately understand cerebrovascular mechanisms during the transition from rest to exercise, CPP and CVCi must also be analyzed. A concurrent drop in cerebral perfusion pressure and middle cerebral artery blood velocity at the start of exercise forces the cerebrovasculature to respond to maintain cerebral blood flow. The use of a monoexponential model characterizes this initial phase as a time delay and masks this large important response. [ABSTRACT FROM AUTHOR]

Peripheral artery disease (PAD) is a vascular pathology with high prevalence among the aging population. PAD is associated with decreased cognitive performance, but the underlying mechanisms remain obscure. Normal brain function critically depends on an adequate adjustment of cerebral blood supply to match the needs of active brain regions via neurovascular coupling (NVC). NVC responses depend on healthy microvascular endothelial function. PAD is associated with significant endothelial dysfunction in peripheral arteries, but its effect on NVC responses has not been investigated. This study was designed to test the hypothesis that NVC and peripheral microvascular endothelial function are impaired in PAD. We enrolled 11 symptomatic patients with PAD and 11 age- and sex-matched controls. Participants were evaluated for cognitive performance using the Cambridge Neuropsychological Test Automated Battery and functional near-infrared spectroscopy to assess NVC responses during the cognitive n-back task. Peripheral microvascular endothelial function was evaluated using laser speckle contrast imaging. We found that cognitive performance was compromised in patients with PAD, evidenced by reduced visual memory, short-term memory, and sustained attention. We found that NVC responses and peripheral microvascular endothelial function were significantly impaired in patients with PAD. A positive correlation was observed between microvascular endothelial function, NVC responses, and cognitive performance in the study participants. Our findings support the concept that microvascular endothelial dysfunction and neurovascular uncoupling contribute to the genesis of cognitive impairment in older PAD patients with claudication. Longitudinal studies are warranted to test whether the targeted improvement of NVC responses can prevent or delay the onset of PAD-associated cognitive decline. [ABSTRACT FROM AUTHOR]

Central adiposity is associated with greater sympathetic support of blood pressure. b-adrenergic receptors (b-AR) buffer sympathetically mediated vasoconstriction and b-AR-mediated vasodilation is attenuated in preclinical models of obesity. With this information, we hypothesized b-AR vasodilation would be lower in obese compared with normal weight adults. Because b-AR vasodilation in normal weight adults is limited by cyclooxygenase (COX) restraint of nitric oxide synthase (NOS), we further explored the contributions of COX and NOS to b-AR vasodilation in this cohort. Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured and forearm vascular conductance (FVC) was calculated (FVC = FBF/MAP). The rise in FVC from baseline (DFVC) was quantified during graded brachial artery infusion of isoproterenol (Iso, 1-12 ng/100 g/min) in normal weight (n = 36) and adults with obesity (n = 22) (18-40 yr old). In a subset of participants, Iso-mediated vasodilation was examined before and during inhibition of NOS [NG-monomethyl-L-arginine (L-NMMA)], COX (ketorolac), and NOS þ COX (L-NMMA þ ketorolac). Iso-mediated increases in FVC did not differ between groups (P = 0.57). L-NMMA attenuated Iso-mediated DFVC in normal weight (P = 0.03) but not adults with obesity (P = 0.27). In normal weight adults, ketorolac increased Iso-mediated DFVC (P < 0.01) and this response was lost with concurrent L-NMMA (P = 0.67). In contrast, neither ketorolac (P = 0.81) nor ketorolac þ L-NMMA (P = 0.40) altered Iso-mediated DFVC in adults with obesity. Despite shifts in COX and NOS, b-AR vasodilation is preserved in young adults with obesity. These data highlight the presence of a compensatory shift in microvascular control mechanisms in younger humans with obesity. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) is a common condition and an important health concern. In addition to metabolic and cardiovascular risks, SD associates with decreases in cognitive performance. Neurovascular coupling (NVC, "functional hyperemia") is a critical homeostatic mechanism, which maintains adequate blood supply to the brain during periods of intensive neuronal activity. To determine whether SD alters NVC responses and cognitive performance, cognitive and hemodynamic NVC assessments were conducted prior to and 24 h post-SD in healthy young male individuals (n = 10, 27 ± 3 years old). Cognition was evaluated with a battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Hemodynamic components of NVC were measured by transcranial Doppler sonography (TCD) during cognitive stimulation, dynamic retinal vessel analysis (DVA) during flicker light stimulation, and functional near infrared spectroscopy (fNIRS) during finger tapping motor task. Cognitive assessments revealed impairments in reaction time and sustained attention after 24 h of SD. Functional NIRS analysis revealed that SD significantly altered hemodynamic responses in the prefrontal cortex and somatosensory cortex during a motor task. NVC-related vascular responses measured by DVA and TCD did not change significantly. Interestingly, TCD detected decreased task-associated cerebral blood flow (CBF) in the right middle cerebral artery in sleep deprived participants. Our results demonstrate that 24 h of SD lead to impairments in cognitive performance together with altered CBF and hemodynamic components of cortical NVC responses. [ABSTRACT FROM AUTHOR]

Understanding how the brain allocates resources to match the demands of active neurons under physiological conditions is critically important. Increased metabolic demands of active brain regions are matched with hemodynamic responses known as neurovascular coupling (NVC). Several methods that allow noninvasive assessment of brain activity in humans detect NVC and early detection of NVC impairment may serve as an early marker of cognitive impairment. Therefore, non-invasive NVC assessments may serve as a valuable tool to detect early signs of cognitive impairment and dementia. Working memory tasks are routinely employed in the evaluation of cognitive task-evoked NVC responses. However, recent attempts that utilized functional near-infrared spectroscopy (fNIRS) or transcranial Doppler sonography (TCD) while using a similar working memory paradigm did not provide convincing evidence for the correlation of the hemodynamic variables measured by these two methods. In the current study, we aimed to compare fNIRS and TCD in their performance of differentiating NVC responses evoked by different levels of working memory workload during the same working memory task used as cognitive stimulation. Fourteen healthy young individuals were recruited for this study and performed an n-back cognitive test during TCD and fNIRS monitoring. During TCD monitoring, the middle cerebral artery (MCA) flow was bilaterally increased during the task associated with greater cognitive effort. fNIRS also detected significantly increased activation during a more challenging task in the left dorsolateral prefrontal cortex (DLPFC), and in addition, widespread activation of the medial prefrontal cortex (mPFC) was also revealed. Robust changes in prefrontal cortex hemodynamics may explain the profound change in MCA blood flow during the same cognitive task. Overall, our data support our hypothesis that both TCD and fNIRS methods can discriminate NVC evoked by higher demand tasks compared to baseline or lower demand tasks. [ABSTRACT FROM AUTHOR]

Although systemic sex‐specific differences in cardiovascular responses to exercise are well established, the comparison of sex‐specific cerebrovascular responses to exercise has gone under‐investigated especially, during high intensity exercise. Therefore, our purpose was to compare cerebrovascular responses in males and females throughout a graded exercise test (GXT). Twenty‐six participants (13 Females and 13 Males, 24 ± 4 yrs.) completed a GXT on a recumbent cycle ergometer consisting of 3‐min stages. Each sex completed 50W, 75W, 100W stages. Thereafter, power output increased 30W/stage for females and 40W/stage for males until participants were unable to maintain 60‐80 RPM. The final stage completed by the participant was considered maximum workload(Wmax). Respiratory gases (End‐tidal CO2, EtCO2), middle cerebral artery blood velocity (MCAv), heart rate (HR), non‐invasive mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) were continuously recorded on a breath‐by‐breath or beat‐by‐beat basis. Cerebral perfusion pressure, CPP = MAP (0. 7,355 distance from heart‐level to doppler probe) and cerebral vascular conductance index, CVCi = MCAv/CPP 100mmHg were calculated. The change from baseline (Δ) in MCAv was similar between the sexes during the GXT (p =.091, ωp2 = 0.05). However, ΔCPP (p <.001, ωp2 = 0.25) was greater in males at intensities ≥ 80% Wmax and ΔCVCi (p =.005, ωp2 = 0.15) was greater in females at 100% Wmax. Δ End‐tidal CO2 (ΔEtCO2) was not different between the sexes during exercise (p =.606, ωp2 = −0.03). These data suggest there are sex‐specific differences in cerebrovascular control, and these differences may only be identifiable at high and severe intensity exercise. [ABSTRACT FROM AUTHOR]

Key points: Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion.Near‐infrared spectroscopy (NIRS) is an established technique for characterizing the transport and utilization of oxygen through the microcirculation.Here we compared a combined NIRS–DCS system with conventional measures of oxygen delivery and utilization during handgrip exercise. The data show good concurrent validity between convective oxygen delivery and DCS‐derived blood flow index, as well as between oxygen extraction at the conduit and microvascular level.We then manipulated forearm arterial perfusion pressure by adjusting the position of the exercising arm relative to the position of the heart. The data show that microvascular perfusion can be uncoupled from convective oxygen delivery, and that tissue saturation seemingly compensates to maintain skeletal muscle oxygen consumption.Taken together, these data support a novel role for NIRS–DCS in understanding the determinants of muscle oxygen consumption at the microvascular level. Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion. Combining DCS with near‐infrared spectroscopy (NIRS) introduces exciting possibilities for understanding the determinants of muscle oxygen consumption; however, no investigation has directly compared NIRS–DCS to conventional measures of oxygen delivery and utilization in an exercising limb. To address this knowledge gap, nine healthy males performed rhythmic handgrip exercise with simultaneous measurements by NIRS–DCS, Doppler blood flow and venous oxygen content. The two approaches showed good concurrent validity, with directionally similar responses between: (a) Doppler‐derived forearm blood flow and DCS‐derived blood flow index (BFI), and (b) venous oxygen saturation and NIRS‐derived tissue saturation. To explore the utility of combined NIRS–DCS across the physiological spectrum, we manipulated forearm arterial perfusion pressure by altering the arm position above or below the level of the heart. As expected, Doppler‐derived skeletal muscle blood flow increased with exercise in both arm positions, but with markedly different magnitudes (below: +424.3 ± 41.4 ml/min, above: +306 ± 12.0 ml/min, P = 0.002). In contrast, DCS‐derived microvascular BFI increased to a similar extent with exercise, regardless of arm position (P = 0.65). Importantly, however, the time to reach BFI steady state was markedly slower with the arm above the heart, supporting the experimental design. Notably, we observed faster tissue desaturation at the onset of exercise with the arm above the heart, resulting in similar muscle oxygen consumption profiles throughout exercise. Taken together, these data support a novel role for NIRS–DCS in understanding the determinants of skeletal muscle oxygen utilization non‐invasively and throughout exercise. Key points: Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion.Near‐infrared spectroscopy (NIRS) is an established technique for characterizing the transport and utilization of oxygen through the microcirculation.Here we compared a combined NIRS–DCS system with conventional measures of oxygen delivery and utilization during handgrip exercise. The data show good concurrent validity between convective oxygen delivery and DCS‐derived blood flow index, as well as between oxygen extraction at the conduit and microvascular level.We then manipulated forearm arterial perfusion pressure by adjusting the position of the exercising arm relative to the position of the heart. The data show that microvascular perfusion can be uncoupled from convective oxygen delivery, and that tissue saturation seemingly compensates to maintain skeletal muscle oxygen consumption.Taken together, these data support a novel role for NIRS–DCS in understanding the determinants of muscle oxygen consumption at the microvascular level. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that women exhibit greater vasodilator responses to β-adrenoceptor stimulation compared with men. We further hypothesized women exhibit a greater contribution of nitric oxide synthase and cyclooxygenase to β-adrenergic-mediated vasodilation compared with men. Forearm blood flow (Doppler ultrasound) was measured in young men (n = 29, 26 ± 1 yr) and women (n = 33, 25 ± 1 yr) during intra-arterial infusion of isoproterenol (β-adrenergic agonist). In subset of subjects, isoproterenol responses were examined before and after local inhibition of nitric oxide synthase [NGmonomethyl- L-arginine (L-NMMA); 6 male/10 female] and/or cyclooxygenase (ketorolac; 5 male/5 female). Vascular conductance (blood flow ÷ mean arterial pressure) was calculated to assess vasodilation. Vascular conductance increased with isoproterenol infusion (P < 0.01), and this effect was not different between men and women (P = 0.41). L-NMMA infusion had no effect on isoproterenol-mediated dilation in men (P > 0.99) or women (P = 0.21). In contrast, ketorolac infusion markedly increased isoproterenol- mediated responses in both men (P < 0.01) and women (P = 0.04) and this rise was lost with subsequent L-NMMA infusion (men, P < 0.01; women, P < 0.05). β-Adrenergic vasodilation is not different between men and women and sex differences in the independent contribution of nitric oxide synthase and cyclooxygenase to β-mediated vasodilation are not present. However, these data are the first to demonstrate β-adrenoceptor activation of cyclooxygenase suppresses nitric oxide synthase signaling in human forearm microcirculation and may have important implications for neurovascular control in both health and disease. [ABSTRACT FROM AUTHOR]

Resistance exercise is an efficacious stimulus for improving cognitive function in older adults, which may be mediated by the upregulation of blood-borne neurotrophic growth factors (NTFs) like brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). However, the NTF response to resistance exercise and training in older adults is poorly understood. Therefore, the purpose of this study was to characterize the timing and magnitude of the NTF response following an acute bout of resistance exercise before and after 8 weeks of resistance training. Ten cognitively normal, older adults (ages 60-77 years, five men) were examined. The acute NTF response to resistance exercise was assessed via serum samples drawn at designated time points following exercise. This procedure was then repeated following 8 weeks of resistance training. BDNF increased immediately post-exercise (Δ9% pre-training, Δ11% post-training) then returned to resting levels while IGF-1 remained stable following resistance exercise before and after 8 weeks of resistance training. Basal levels of both NTFs were unaffected by the 8 week training period. We report a transient increase in serum BDNF following a bout of resistance exercise in older adults, which could have implications for the design of interventions seeking to maximize cognitive function in older adults. [ABSTRACT FROM AUTHOR]

R5532 --> 888.18 --> Cerebral blood flow (CBF) dynamic response to moderate‐intensity exercise has a time delay (TD) of ~ 40s. This is dramatically longer compared to other physiological responses to exercise (e.g. skeletal muscle blood flow <10 s) and CBF response to other stimuli (e.g. hypercapnia, thigh cuff occlusion, ~ 10‐20 s). A possible explanation is that a rest‐to‐exercise transition induces a brief hypotensive response due to intensity dependent rapid vasodilation of the periphery (exercise‐onset hypotension, EoH). Purpose: To determine if the magnitude and timing of EoH, effectively reduces CBF at exercise onset causing the longer observed TD. To test this, we modelled CBF kinetic response to light‐intensity exercise to mitigate the magnitude of EoH and determine if components of the CBF response were quickened in young healthy adults. Methods: 26 young healthy adults (13 Women, 23.8 ± 4 yrs; 23.9 ± 2.9 kg/m2) completed a rest (2min seated quietly, BL) to exercise (3 minutes at 50W, EX) transition on a recumbent cycle ergometer. Middle cerebral artery velocity (MCAv; transcranial doppler) and mean arterial pressure (MAP; finger photoplethysmography) were measured on a heartbeat‐by‐heartbeat basis. End‐tidal CO2 (EtCO2) was measured using breath‐by‐breath capnography. Cerebral vascular conductance index (CVCi) was calculated as (CVCi = MCAv/MAP *100 mmHg). Change in MCAv data (ΔMCAv = MCAvEX‐MCAvBL) were averaged into 2 s bins and fit to a monoexponential model (ΔMCAv(t)= Amp(1‐e‐(t‐TD)/ τ)). Time delay (TD), tau (τ), and mean response time (MRT = TD + τ) were obtained from the model. Several subjects (N=11) exhibited little to no TD (TD < 1 s), these subjects (FAST) were separated out and compared to individuals with longer TDs (TD ≥ 3 s; SLOW). Comparisons were made using an independent t‐test. Results: All data is mean±SD. In total, subjects exhibited a TD of 15.4 ± 18.2 s, τ of 79.8 ± 139.7, and MRT of 95.3 ± 134.9 s. This coincided with a ΔMAPNADIR (‐14.5 ± 8.2 mmHg), ΔMCAvNADIR (‐5.7 ± 5.8 cm/s) which occurred at similar times (14.0 ± 17.2 vs. 18.6 ± 14.4 s; p=0.30 MAPNADIR vs. MCAvNADIR), and ΔCVCiMAX (25.3 ± 34.0 cm/s/100mmHg). When data were split, the FAST group experienced a faster TD compared to SLOW (0.01 ± 0.01 vs. 26.8 ± 16.4 s; p<0.001). ΔMCAvNADIR although different (‐1.0 ± 4.0 vs. ‐9.1 ± 4.2 cm/s; p<0.001, FAST vs. SLOW), occurred at similar times (20.5 ± 17.3 vs. 17.3 ± 12.5 s; p=0.59, FAST vs. SLOW). ΔMAPNADIR (‐14.4 ± 10.4 vs. ‐14.6 ± 6.5 mmHg; p=0.97) and CVCiMAX (22.1 ± 25.4 vs. 27.6 ± 39.9 cm/s/100mmHg; p=0.56 FAST vs. SLOW) were not different between groups. There were no other differences between groups regrading demographic, EtCO2, or other kinetic variables. Discussion: Our data indicates EoH is related to the initial drop in CBF and TD during light‐exercise is faster (15.9 s) when compared to previous research during moderate‐intensity exercise (~40 s). However, our data identifies fast responders who have minimal TD and MCAvNADIR responses without differing EoH at the same absolute exercise intensity. Therefore, these data reveal monoexponential CBF models ignore initial perturbances to CBF and disregard potentially important cerebrovascular mechanisms occurring prior to model predicted blood flow increases. [ABSTRACT FROM AUTHOR]

Few data exist identifying the influence of age on midthigh muscle composition. Further understanding how muscle composition of the midthigh changes with aging may improve current exercise prescriptions. PURPOSE: To examine the influence of chronological age on midthigh composition in 142 women (49.1±17.7 years, 164.5±7.1 cm, 66.6±10.7 kg). METHODS: Midthigh peripheral quantitative computed tomography scans were completed at the 40% site of the right femur and were analyzed using BoneJ software. Muscle density (MuD), cross-sectional area (mCSA), and intramuscular fat area (IMAT) were derived from the scans. One-way ANOVA compared group means by decade 20-29 (n=28), 30-39 (n=21), 40-49 (n=22), 50-59 (n=25), 60-69 (n=29), ≥70 years (n=17), while Dunnett's test performed post-hoc pairwise comparisons with the youngest group. Spearman's correlations examined each parameters association with age. A significance level of p<0.05 was selected a priori. RESULTS: MuD and mCSA displayed significant negative associations with age (r=-0.58 and r=-0.67, respectively, both p<0.01), while IMAT displayed a significant positive association with age (r=0.17, p=0.04). Group differences were observed for MuD (p<0.01), mCSA (p<0.01), IMAT (p=0.029). Dunnett's test revealed that MuD was significantly greater in the 20-29 years group compared to both age groups ≥60 years (81.5±1.2mg/cm³ vs 79.1±2.2mg/cm³ and 78.2±2.9mg/cm³, respectively; both p<0.01), and mCSA was significantly greater in the 20-29 years group compared to each age group ≥50 years (104.4±15.4cm² vs 85.9±14.3cm², 78.8±12.4cm², and 72.3±14.5cm², respectively, all p<0.01). IMAT was significantly greater in ≥70 years group compared to the 20-29 years group (6.23±2.3cm² vs 4.3±1.8cm², p=0.04). Interestingly, MuD, a surrogate for muscle quality, displayed smaller age-related decreases than mCSA (MuD: -3.9% vs mCSA: -29.7%) between the 20-29 and ≥70 years group. CONCLUSIONS: The current observations reveal that increased age displayed significant associations with midthigh muscle composition (MuD, mCSA, IMAT). However, future research is needed to identify which muscle composition parameter(s) contribute most effectively to maintaining muscle strength and physical performance with advanced age. [ABSTRACT FROM AUTHOR]