Regulation Of Human Blood Flow Research Articles

Ten days of high dietary sodium does not impair cerebral blood flow regulation in healthy adults.

High dietary sodium impairs cerebral blood flow regulation in rodents and is associated with increased stroke risk in humans. However, the effects of multiple days of high dietary sodium on cerebral blood flow regulation in humans is unknown. Therefore, the purpose of this study was to determine whether ten days of high dietary sodium impairs cerebral blood flow regulation. Ten participants (3F/7M; age: 30±10years; blood pressure (BP): 113±8/62±9mmHg) participated in this randomized, cross-over design study. Participants were placed on 10-day diets that included either low- (1000mg/d), medium- (2300mg/d) or high- (7000mg/d) sodium separated by ≥four weeks. Urinary sodium excretion, beat-to-beat BP (finger photoplethysmography), middle cerebral artery velocity (transcranial Doppler), and end-tidal carbon dioxide (capnography) was measured. Dynamic cerebral autoregulation during a ten-minute baseline was calculated and cerebrovascular reactivity assessed by determining the percent change in middle cerebral artery blood flow velocity to hypercapnia (8% CO2, 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Urinary sodium excretion increased in a stepwise manner (ANOVA P=0.001) from the low, to medium, to high condition. There were no differences in dynamic cerebral autoregulation between conditions. While there was a trend for a difference during cerebrovascular reactivity to hypercapnia (ANOVA P=0.06), this trend was abolished when calculating cerebrovascular conductance (ANOVA: P=0.28). There were no differences in cerebrovascular reactivity (ANOVA P=0.57) or conductance (ANOVA: P=0.73) during hypocapnia. These data suggest that ten days of a high sodium diet does not impair cerebral blood flow regulation in healthy adults.

Mechanisms of bone blood flow regulation in humans.

Bone is a highly vascularized tissue. However, despite the importance of appropriate circulation for bone health, regulation of bone blood flow remains poorly understood. Invasive animal studies suggest that sympathetic activity plays an important role in bone flow control. However, it remains unknown if bone vasculature evidences robust vasoconstriction in response to sympathoexcitatory stimuli. Here, we characterized bone blood flow in young healthy individuals [n = 13, (four females)] in response to isometric handgrip exercise (IHE) and cold pressor test (CPT). These provide a strong stimulus for active vasoconstriction in the inactive muscle, and perhaps also in the bone. During sustained IHE to fatigue and CPT, we measured blood pressure, whole leg blood flow, and tibial perfusion using near-infrared spectroscopy. Tibia perfusion was determined as oxy- and deoxyhemoglobin. For both stimuli, tibial metabolism remained constant (i.e., no change in deoxyhemoglobin) and thus tibial arterial perfusion was represented by oxyhemoglobin. During IHE, oxyhemoglobin declined (beginning -0.20 ± 1.04 μM; end -1.13 ± 3.71 μM, both P < 0.01) slower than whole leg blood flow (beginning -0.85 ± 1.02 cm/s; end -2.72 ± 1.64 cm/s, both P < 0.01). However, during CPT, both oxyhemoglobin (beginning -0.46 ± 1.43 μM; end -0.60 ± 1.59 μM, both P < 0.01) and whole leg blood flow (beginning -1.52 ± 1.63 cm/s; end -0.69 ± 1.51 cm/s, both P < 0.01) declined with a similar timecourse, even though the magnitudes of decline were smaller than during IHE. These responses are likely due to the different timecourses of sympathetically mediated vasoconstriction in bone and muscle. These results indicate that sympathetic innervation of the bone vasculature serves a functional role in the control of flow in young healthy individuals.NEW & NOTEWORTHY The current study is the first one to noninvasively investigate control of bone blood perfusion in vivo in humans, on a moment-by-moment basis. Our results indicate that tibial bone vasculature demonstrates active vasoconstriction in response to sympathoexcitatory stimuli in young healthy individuals. Compared with whole leg vasculature, bone vasoconstrictor response seems to be smaller, delayed, and more variable.

Bone blood flow regulation in humans

Bone is a highly vascularized organ with an extensive network of arteries, arterioles, and capillaries that is critical for bone development, maintenance, and repair. Despite the importance of bone circulation to bone health, the regulation of blood flow to bone is not well understood in humans. One of the potential factors controlling bone blood flow is the sympathetic nervous system, bone vasculature being innervated by a rich network of sympathetic nerves. While no human studies have been conducted, animal data suggests that sympathetic activation reduces bone blood flow. If this were not the case, bone vasculature would respond simply as a passive pressure system. Therefore, we characterized bone blood flow regulation in health young individuals (N=12 (8M; 4F), 23±0.7 years) in response to isometric handgrip to fatigue (IHE). Sustained IHE is a profound pressor stimulus, resulting in active vasoconstriction in the nonactive leg and progressive increases in blood pressure. During IHE at 30% of maximal voluntary contraction, we measured blood pressure, whole leg blood flow (via Doppler ultrasound), and tibial blood perfusion (via near infrared spectroscopy). Tibial blood perfusion was determined as changes from resting baseline in oxygenated and deoxygenated hemoglobin content. Data is presented as mean change from resting baseline ± standard error. To account for different IHE time courses, all variables were normalized to 100% duration and averaged across individuals. Blood pressure increased progressively to end of IHE (at 10%: 5.46 ± 1.30 mmHg; at 100%: 48.0 ± 4.32 mmHg). Whole leg blood flow decreased progressively throughout IHE, suggesting active sympathetic vasoconstriction in the leg (at 10%: −0.70 ± 0.28 cm/s; at 100%: −2.26 ± 0.50 cm/s). Similarly, tibial oxygenated hemoglobin decreased progressively throughout the test (at 10%: −0.21 ± 0.31 μM; at 100%: −1.19 ± 1.12 μM) whereas tibial deoxygenated hemoglobin did not change significantly throughout IHE (at 10%: 0.06 ± 0.07 μM; at 100%: −0.4 ± 0.32 μM). This indicates that arterial flow (oxygenated hemoglobin) declined while bone metabolism (deoxygenated hemoglobin) remained unchanged in response to IHE. It should be noted that the decline in oxygenated hemoglobin was slower and lesser than that in whole leg blood flow. This data suggests that sympathetic activity is involved in controlling bone circulation, but vasoconstrictor responses is not as fast or as robust in bone as it is in the whole leg.Support or Funding InformationParalyzed Veterans of America (AED)

Arteriovenous oscillations of the redox potential: Is the redox state influencing blood flow?

Objective: Studies on the regulation of human blood flow revealed several modes of oscillations with frequencies ranging from 0.005 to 1 Hz. Several mechanisms were proposed that might influence these oscillations, such as the activity of vascular endothelium, the neurogenic activity of vessel wall, the intrinsic activity of vascular smooth muscle, respiration, and heartbeat. These studies relied typically on non-invasive techniques, for example, laser Doppler flowmetry. Oscillations of biochemical markers were rarely coupled to blood flow.Methods: The redox potential difference between the artery and the vein was measured by platinum electrodes placed in the parallel homonymous femoral artery and the femoral vein of ventilated anesthetized pigs.Results: Continuous measurement at 5 Hz sampling rate using a digital nanovoltmeter revealed fluctuating signals with three basic modes of oscillations: ∼ 1, ∼ 0.1 and ∼ 0.01 Hz. These signals clearly overlap with reported modes of oscillations in blood flow, suggesting coupling of the redox potential and blood flow.Discussion: The amplitude of the oscillations associated with heart action was significantly smaller than for the other two modes, despite the fact that heart action has the greatest influence on blood flow. This finding suggests that redox potential in blood might be not a derivative but either a mediator or an effector of the blood flow control system.

Influence of Hypoxia on Cerebral Blood Flow Regulation in Humans.

The brain is a vital organ that relies on a constant and adequate supply of blood to match oxygen and glucose delivery with the local metabolic demands of active neurones. It is well established that cerebral blood flow is altered in response to both neural activity and humoral stimuli. Thus, augmented neural activation (e.g. visual stimulation) leads to locally increased cerebral blood flow via functional hyperaemia, whereas humoral stimuli (i.e. alterations in arterial PO2 and PCO2) produce global increases in cerebral blood flow. Perhaps not surprisingly, cerebrovascular responses to neural activity and humoral stimuli may not be highly correlated because they reflect different physiological mechanisms for vasodilation. Exquisite regulation of cerebral blood flow is particularly important under hypoxic conditions when cerebral PO2 can be reduced substantially. Indeed, cerebrovascular reactivity to hypoxia determines the capacity of cerebral vessels to respond and compensate for a reduced oxygen supply. This reactivity is dynamic, changing with prolonged exposure to hypoxic environments, and in patients and healthy individuals exposed to chronic intermittent periods of hypoxia. More recently, a number of animal studies have provided evidence that glial cells (i.e. astrocytes) play an important role in regulating cerebral blood flow under normoxic and hypoxic conditions. This review aims to summarize our current understanding of cerebral blood flow control during hypoxia in humans and put into context the underlying neurovascular mechanisms that may contribute to this regulation.

Cerebral Blood-Flow Regulation During Hemorrhage.

Massive uncontrolled blood loss can occur under a variety of conditions including trauma, as a complication of childbirth or surgery, ruptured ulcers, clotting disorders, and hemorrhagic fevers. Across the continuum of hemorrhage, loss of blood volume is a significant challenge to the maintenance of cerebral perfusion. During the initial stages of hemorrhage, reflex mechanisms are activated to protect cerebral perfusion, but persistent blood loss will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Hemorrhage represents a unique physiological stress to the brain, as it influences each of these regulatory mechanisms, resulting in complex interplay that ultimately challenges the ability of the brain to maintain adequate perfusion. Early studies of actual hemorrhage in humans employed blood loss protocols up to 1000 mL, but did not include any measurements of cerebral blood flow. As ethical considerations necessarily constrain the use of human volunteers for massive blood loss studies that induce irreversible shock, most of what is known about cerebral blood-flow responses to hemorrhage has been determined from animal models. Limitations of species differences regarding regulatory mechanisms, anatomy, and the effect of anesthesia, however, must be considered. Advances in monitoring technologies, and a recent renewed interest in understanding cerebral blood-flow regulation in humans, however, is rapidly accelerating knowledge in this field.

Near-infrared photons: a non-invasive probe for studying bone blood flow regulation in humans.

The study of bone blood flow regulation in humans has always represented a difficult task for the clinician and the researcher. Classical measurement techniques imply the presence of ionizing radiation or contrast agents, or they are slow or cannot be repeated too often in time. In the present review, we would like to give a perspective on how the optical approach might overcome some of these problems and give unique solutions to the study of bone blood flow regulation. We hope that the present contribution will encourage the scientific community to put a greater attention on this approach.

Blood flow restriction without sympathetic vasoconstriction in ageing skeletal muscle during exercise.

Blood flow restriction without sympathetic vasoconstriction in ageing skeletal muscle during exercise.

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

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

The Vascular Aspect of Glaucoma ‐ What should we look at?

AbstractPurpose Glaucoma is an optic neuropathy of unknown origin. Increased intraocular pressure is the most important risk factor for the disease. In addition, reduced ocular perfusion pressure has been identified as a risk factor for glaucomatous optic neuropathy.Methods In a variety of studies we have focused on the complex interaction between intraocular pressure, mean arterial blood pressure, ocular perfusion pressure and ocular blood flow. In these studies various strategies were used to manipulate intraocular pressure, mean arterial blood pressure and ocular perfusion pressure and choroidal and optic nerve head blood flow were measured.Results In vivo the capacity of choroidal and optic nerve head blood flow to regulate its vascular tone during changes in ocular perfusion pressure strongly depends on the way how perfusion pressure is manipulated. Generally ocular vascular beds regulate better during changes in blood pressure than during changes in intraocular pressure.Conclusion With the improved understanding of ocular blood flow regulation in humans our understanding of perfusion abnormalities in glaucoma has also increased. Most importantly these studies show that any reduction in intraocular pressure has a strong impact on ocular blood flow regulation.

Comfortable at just below your critical speed: how is blood flow distribution coupled to muscle fibre recruitment during exercise?

Comfortable at just below your critical speed: how is blood flow distribution coupled to muscle fibre recruitment during exercise?

Progressive handgrip exercise: evidence of nitric oxide-dependent vasodilation and blood flow regulation in humans

In the peripheral circulation, nitric oxide (NO) is released in response to shear stress across vascular endothelial cells. We sought to assess the degree to which NO contributes to exercise-induced vasodilation in the brachial artery (BA) and to determine the potential of this approach to noninvasively evaluate NO bioavailability. In eight young (25 ± 1 yr) healthy volunteers, we used ultrasound Doppler to examine BA vasodilation in response to handgrip exercise (4, 8, 12, 16, 20, and 24 kg) with and without endothelial NO synthase blockade [intra-arterial N(G)-monomethyl-L-arginine (L-NMMA), 0.48 mg · dl(-1) · min(-1)]. Higher exercise intensities evoked significant BA vasodilation (4-12%) that was positively correlated with the hyperemic stimulus (r = 0.98 ± 0.003, slope = 0.005 ± 0.001). During NO blockade, BA vasodilation at the highest exercise intensity was reduced by ∼70% despite similar exercise-induced increases in shear rate (control, +224 ± 30 s(-1); L-NMMA, +259 ± 46 s(-1)). The relationship and slope of BA vasodilation with increasing shear rate was likewise reduced (r = 0.48 ± 0.1, slope = 0.0007 ± 0.0005). We conclude that endothelial NO synthase inhibition with L-NMMA abolishes the relationship between shear stress and BA vasodilation during handgrip exercise, providing clear evidence of NO-dependent vasodilation in this experimental model. These results support this paradigm as a novel and valid approach for a noninvasive assessment of NO-dependent vasodilation in humans.

Control system analysis of visually evoked blood flow regulation in humans under normocapnia and hypercapnia

Objective: Among other factors, the cerebral blood flow (CBF) is regulated in accordance to the arterial CO 2 tension and the cortical activity. The CO 2 test is commonly used to measure the vascular reserve capacity. Most functional imaging studies rely on the activity-flow coupling (AFC). We aimed to combine both challenges in order to increase the insight into mechanisms of CBF regulation. Methods: Fifteen healthy students underwent a functional transcranial Doppler test using a visual stimulation paradigm: firstly under normocapnia and secondly under conditions of hypercapnia. Hypercapnia was induced by breathing a carbogene gas mixture of 5% CO 2 and 95% O 2. The entire time course of flow velocity adaptation in the posterior cerebral artery (PCA) was analyzed mathematically using a control system approach. Results: Resting CBF velocities increased by nearly 26% under conditions of hypercapnia, whereas the slight increase in arterial blood pressure (ABP) and the decrease in the Pourcelot–Pulsatility index (PI) were statistically not significant. From the control system parameters which were time delay, rate time, gain, attenuation and natural frequency, only the parameter rate time, indicative for the initial steepness of flow velocity increase, showed a statistically significant decrease, consistently for the peak systolic and enddiastolic flow velocity data. As concluded from the unchanged gain parameter the absolute amount of blood flow evoked by the same visual stimulus increased also by 26%. Conclusion: Evaluated by Doppler measurements hypercapnia seems to influence the AFC in two ways: It decreases the steepness of the initial increase in blood flow velocity and enhances the absolute amount of blood flow evoked by the same stimulus.

A positive family history of premature coronary artery disease is associated with impaired endothelium-dependent coronary blood flow regulation.

The aim of the study was to determine whether a positive family history of coronary artery disease is related to impaired coronary blood flow regulation. In 150 patients with angiographically normal or minimally diseased coronary vessels, risk factors for coronary artery disease, the extent of atherosclerosis and endothelium-dependent vasomotor responses to acetylcholine, and endothelium-independent blood flow regulation by papaverine or adenosine were assessed. Coronary blood flow responses to acetylcholine were reduced in a dose-dependent manner in patients with a positive family history (P=0.030). By multivariate analysis, hypercholesterolemia (P=0.001), age (P=0.002), and a positive family history (P=0.008) remained predictors of coronary blood flow increase to acetylcholine. The extent of atherosclerotic coronary artery disease was, by multivariate analysis, an additional independent predictor of acetylcholine-induced blood flow (P=0.014), but also of endothelium-independent blood flow regulation (P=0.001). A positive family history had additive effects in addition to the other risk factors, such as hypercholesterolemia or increased age. Angiotensin-converting-enzyme genotype polymorphism had no influence either on endothelium-dependent or endothelium-independent coronary blood flow responses. However, in a subset of 28 patients, homocysteine (which is, in part, genetically determined) was inversely related to maximal acetylcholine-induced blood flow regulation (r=-0.47, P=0.012). The results of this study demonstrate, for the first time, that a positive family history of coronary artery disease is an important predictor of impaired endothelium-dependent coronary blood flow regulation in humans. The influence of a positive family history is independent of other well known risk factors but instead aggravates endothelial vasodilator dysfunction associated with hypercholesterolemia and increased age, suggesting important interacting effects between genetic and environmental risk factors.