Local Control of Blood Flow

ERIC Educational Resources Information Center

Clifford, Philip S.

2011-01-01

Organ blood flow is determined by perfusion pressure and vasomotor tone in the resistance vessels of the organ. Local factors that regulate vasomotor tone include myogenic and metabolic autoregulation, flow-mediated and conducted responses, and vasoactive substances released from red blood cells. The relative importance of each of these factors…

Comparison of choroidal and optic nerve head blood flow regulation during changes in ocular perfusion pressure.

PubMed

Schmidl, Doreen; Boltz, Agnes; Kaya, Semira; Werkmeister, Rene; Dragostinoff, Nikolaus; Lasta, Michael; Polska, Elzbieta; Garhöfer, Gerhard; Schmetterer, Leopold

2012-07-01

We compared the response of choroidal and optic nerve head blood flow (ChBF, ONHBF) in response to an increase in ocular perfusion pressure (OPP) during isometric exercise and during a decrease in OPP during an artificial increase in intraocular pressure (IOP). We included 96 healthy subjects in our study. In 48 subjects OPP was increased by 6 minutes of squatting, and either ONHBF (n = 24) or ChBF (n = 24) was measured continuously. In 48 other healthy subjects either ONHBF (n = 24) or ChBF (n = 24) was measured continuously during a period of artificial increase in IOP using a suction cup. All blood flow measurements were done using laser Doppler flowmetry. During all experiments the response in blood flow was less pronounced than the response in OPP, indicating for flow regulation. During isometric exercise ChBF regulated better than ONHBF (P = 0.023). During artificial IOP increase ONHBF regulated better than ChBF (P = 0.001). Inter-individual variability in blood flow responses was high. During squatting ONHBF decreased considerably below baseline ONHBF when OPP fluctuated in 3 subjects, although OPP still was much higher than at baseline. This phenomenon was not observed in the choroid. Our data indicate that regulation of ChBF and ONHBF during changes in OPP is different and complex. In some subjects performing squatting, considerable ONHBF reductions were observed during OPP fluctuations, although OPP still was high. Whether this predisposes to ocular disease remains unclear.

Genetic and flow anomalies in congenital heart disease.

PubMed

Rugonyi, Sandra

2016-01-01

Congenital heart defects are the most common malformations in humans, affecting approximately 1% of newborn babies. While genetic causes of congenital heart disease have been studied, only less than 20% of human cases are clearly linked to genetic anomalies. The cause for the majority of the cases remains unknown. Heart formation is a finely orchestrated developmental process and slight disruptions of it can lead to severe malformations. Dysregulation of developmental processes leading to heart malformations are caused by genetic anomalies but also environmental factors including blood flow. Intra-cardiac blood flow dynamics plays a significant role regulating heart development and perturbations of blood flow lead to congenital heart defects in animal models. Defects that result from hemodynamic alterations, however, recapitulate those observed in human babies, even those due to genetic anomalies and toxic teratogen exposure. Because important cardiac developmental events, such as valve formation and septation, occur under blood flow conditions while the heart is pumping, blood flow regulation of cardiac formation might be a critical factor determining cardiac phenotype. The contribution of flow to cardiac phenotype, however, is frequently ignored. More research is needed to determine how blood flow influences cardiac development and the extent to which flow may determine cardiac phenotype.

Functional dilatation and medial remodeling of the renal artery in response to chronic increased blood flow.

PubMed

Roan, Jun-Neng; Yeh, Chin-Yi; Chiu, Wen-Cheng; Lee, Chou-Hwei; Chang, Shih-Wei; Jiangshieh, Ya-Fen; Tsai, Yu-Chuan; Lam, Chen-Fuh

2011-01-01

Renal blood flow (RBF) is tightly regulated by several intrinsic pathways in maintaining optimal kidney blood supply. Using a rat model of aortocaval (AC) fistula, we investigated remodeling of the renal artery following prolonged increased blood flow. An AC fistula was created in the infrarenal aorta of anesthetized rats, and changes of blood flow in the renal artery were assessed using an ultrasonic flow probe. Morphological changes and expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 in the remodeled renal artery were analyzed. Blood flow in the renal artery increased immediately after creation of AC fistula, but normal RBF was restored 8 weeks later. The renal artery dilated significantly 8 weeks after operation. Expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 was upregulated shortly after blood flow increase, and returned to baseline levels after 3 weeks. Histological sections showed luminal dilatation with medial thickening and endothelial cell-to-smooth muscle cell attachments in the remodeled renal artery. Increased RBF was accommodated by functional dilatation and remodeling in the medial layer of the renal artery in order to restore normal blood flow. Our results provide important mechanistic insight into the intrinsic regulation of the renal artery in response to increased RBF. Copyright © 2011 S. Karger AG, Basel.

Cardiovascular control during whole body exercise

PubMed Central

Secher, Niels H.

2016-01-01

It has been considered whether during whole body exercise the increase in cardiac output is large enough to support skeletal muscle blood flow. This review addresses four lines of evidence for a flow limitation to skeletal muscles during whole body exercise. First, even though during exercise the blood flow achieved by the arms is lower than that achieved by the legs (∼160 vs. ∼385 ml·min−1·100 g−1), the muscle mass that can be perfused with such flow is limited by the capacity to increase cardiac output (42 l/min, highest recorded value). Secondly, activation of the exercise pressor reflex during fatiguing work with one muscle group limits flow to other muscle groups. Another line of evidence comes from evaluation of regional blood flow during exercise where there is a discrepancy between flow to a muscle group when it is working exclusively and when it works together with other muscles. Finally, regulation of peripheral resistance by sympathetic vasoconstriction in active muscles by the arterial baroreflex is critical for blood pressure regulation during exercise. Together, these findings indicate that during whole body exercise muscle blood flow is subordinate to the control of blood pressure. PMID:27311439

Cardiovascular control during whole body exercise.

PubMed

Volianitis, Stefanos; Secher, Niels H

2016-08-01

It has been considered whether during whole body exercise the increase in cardiac output is large enough to support skeletal muscle blood flow. This review addresses four lines of evidence for a flow limitation to skeletal muscles during whole body exercise. First, even though during exercise the blood flow achieved by the arms is lower than that achieved by the legs (∼160 vs. ∼385 ml·min(-1)·100 g(-1)), the muscle mass that can be perfused with such flow is limited by the capacity to increase cardiac output (42 l/min, highest recorded value). Secondly, activation of the exercise pressor reflex during fatiguing work with one muscle group limits flow to other muscle groups. Another line of evidence comes from evaluation of regional blood flow during exercise where there is a discrepancy between flow to a muscle group when it is working exclusively and when it works together with other muscles. Finally, regulation of peripheral resistance by sympathetic vasoconstriction in active muscles by the arterial baroreflex is critical for blood pressure regulation during exercise. Together, these findings indicate that during whole body exercise muscle blood flow is subordinate to the control of blood pressure. Copyright © 2016 the American Physiological Society.

Intraocular Pressure, Blood Pressure, and Retinal Blood Flow Autoregulation: A Mathematical Model to Clarify Their Relationship and Clinical Relevance

PubMed Central

Guidoboni, Giovanna; Harris, Alon; Cassani, Simone; Arciero, Julia; Siesky, Brent; Amireskandari, Annahita; Tobe, Leslie; Egan, Patrick; Januleviciene, Ingrida; Park, Joshua

2014-01-01

Purpose. This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. Methods. A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. Results. The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. Conclusions. The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics. PMID:24876284

Intraocular pressure, blood pressure, and retinal blood flow autoregulation: a mathematical model to clarify their relationship and clinical relevance.

PubMed

Guidoboni, Giovanna; Harris, Alon; Cassani, Simone; Arciero, Julia; Siesky, Brent; Amireskandari, Annahita; Tobe, Leslie; Egan, Patrick; Januleviciene, Ingrida; Park, Joshua

2014-05-29

This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Sex differences with aging in nutritive skeletal muscle blood flow: impact of exercise training, nitric oxide, and α-adrenergic-mediated mechanisms

PubMed Central

La Favor, Justin D.; Kraus, Raymond M.; Carrithers, Jonathan A.; Roseno, Steven L.; Gavin, Timothy P.

2014-01-01

The incidence of cardiovascular disease increases progressively with age, but aging may affect men and women differently. Age-associated changes in vascular structure and function may manifest in impaired nutritive blood flow, although the regulation of nutritive blood flow in healthy aging is not well understood. The purpose of this study was to determine if nitric oxide (NO)-mediated or α-adrenergic-mediated regulation of nutritive skeletal muscle blood flow is impaired with advanced age, and if exercise training improves age-related deficiencies. Nutritive blood flow was monitored in the vastus lateralis of healthy young and aged men and women via the microdialysis-ethanol technique prior to and following seven consecutive days of exercise training. NO-mediated and α-adrenergic-mediated regulation of nutritive blood flow was assessed by microdialysis perfusion of acetylcholine, sodium nitroprusside, NG-monomethyl-l-arginine, norepinephrine, or phentolamine. Pretraining nutritive blood flow was attenuated in aged compared with young women (7.39 ± 1.5 vs. 15.5 ± 1.9 ml·100 g−1·min−1, P = 0.018), but not aged men (aged 13.5 ± 3.7 vs. young 9.4 ± 1.3 ml·100 g−1·min−1, P = 0.747). There were no age-associated differences in NO-mediated or α-adrenergic-mediated nutritive blood flow. Exercise training increased resting nutritive blood flow only in young men (9.4 ± 1.3 vs. 19.7 ml·100 g−1·min−1, P = 0.005). The vasodilatory effect of phentolamine was significantly reduced following exercise training only in young men (12.3 ± 6.14 vs. −3.68 ± 3.26 ml·100 g−1·min−1, P = 0.048). In conclusion, the age-associated attenuation of resting nutritive skeletal muscle blood flow was specific to women, while the exercise-induced alleviation of α-adrenergic mediated vasoconstriction that was specific to young men suggests an age-associated modulation of the sympathetic response to exercise training. PMID:24951753

Sex differences with aging in nutritive skeletal muscle blood flow: impact of exercise training, nitric oxide, and α-adrenergic-mediated mechanisms.

PubMed

La Favor, Justin D; Kraus, Raymond M; Carrithers, Jonathan A; Roseno, Steven L; Gavin, Timothy P; Hickner, Robert C

2014-08-15

The incidence of cardiovascular disease increases progressively with age, but aging may affect men and women differently. Age-associated changes in vascular structure and function may manifest in impaired nutritive blood flow, although the regulation of nutritive blood flow in healthy aging is not well understood. The purpose of this study was to determine if nitric oxide (NO)-mediated or α-adrenergic-mediated regulation of nutritive skeletal muscle blood flow is impaired with advanced age, and if exercise training improves age-related deficiencies. Nutritive blood flow was monitored in the vastus lateralis of healthy young and aged men and women via the microdialysis-ethanol technique prior to and following seven consecutive days of exercise training. NO-mediated and α-adrenergic-mediated regulation of nutritive blood flow was assessed by microdialysis perfusion of acetylcholine, sodium nitroprusside, N(G)-monomethyl-L-arginine, norepinephrine, or phentolamine. Pretraining nutritive blood flow was attenuated in aged compared with young women (7.39 ± 1.5 vs. 15.5 ± 1.9 ml·100 g(−1)·min(−1), P = 0.018), but not aged men (aged 13.5 ± 3.7 vs. young 9.4 ± 1.3 ml·100 g(−1)·min(−1), P = 0.747). There were no age-associated differences in NO-mediated or α-adrenergic-mediated nutritive blood flow. Exercise training increased resting nutritive blood flow only in young men (9.4 ± 1.3 vs. 19.7 ml·100 g(−1)·min(−1), P = 0.005). The vasodilatory effect of phentolamine was significantly reduced following exercise training only in young men (12.3 ± 6.14 vs. −3.68 ± 3.26 ml·100 g(−1)·min(−1), P = 0.048). In conclusion, the age-associated attenuation of resting nutritive skeletal muscle blood flow was specific to women, while the exercise-induced alleviation of α-adrenergic mediated vasoconstriction that was specific to young men suggests an age-associated modulation of the sympathetic response to exercise training.

Blood flow regulation and oxygen uptake during high-intensity forearm exercise.

PubMed

Nyberg, S K; Berg, O K; Helgerud, J; Wang, E

2017-04-01

The vascular strain is very high during heavy handgrip exercise, but the intensity and kinetics to reach peak blood flow, and peak oxygen uptake, are uncertain. We included 9 young (25 ± 2 yr) healthy males to evaluate blood flow and oxygen uptake responses during continuous dynamic handgrip exercise with increasing intensity. Blood flow was measured using Doppler-ultrasound, and venous blood was drawn from a deep forearm vein to determine arteriovenous oxygen difference (a-vO 2diff ) during 6-min bouts of 60, 80, and 100% of maximal work rate (WR max ), respectively. Blood flow and oxygen uptake increased ( P < 0.05) from 60%WR max [557 ± 177(SD) ml/min; 56.0 ± 21.6 ml/min] to 80%WR max (679 ± 190 ml/min; 70.6 ± 24.8 ml/min), but no change was seen from 80%WR max to 100%WR max Blood velocity (49.5 ± 11.5 to 58.1 ± 11.6 cm/s) and brachial diameter (0.49 ± 0.05 to 0.50 ± 0.06 cm) showed concomitant increases ( P < 0.05) with blood flow from 60% to 80%WR max, whereas no differences were observed in a-vO 2diff Shear rate also increased ( P < 0.05) from 60% (822 ± 196 s -1 ) to 80% (951 ± 234 s -1 ) of WR max The mean response time (MRT) was slower ( P < 0.05) for blood flow (60%WR max 50 ± 22 s; 80%WR max 51 ± 20 s; 100%WR max 51 ± 23 s) than a-vO 2diff (60%WR max 29 ± 9 s; 80%WR max 29 ± 5 s; 100%WR max 20 ± 5 s), but not different from oxygen uptake (60%WR max 44 ± 25 s; 80%WR max 43 ± 14 s; 100%WR max 41 ± 32 s). No differences were observed in MRT for blood flow or oxygen uptake with increased exercise intensity. In conclusion, when approaching maximal intensity, oxygen uptake appeared to reach a critical level at ~80% of WR max and be regulated by blood flow. This implies that high, but not maximal, exercise intensity may be an optimal stimulus for shear stress-induced small muscle mass training adaptations. NEW & NOTEWORTHY This study evaluated blood flow regulation and oxygen uptake during small muscle mass forearm exercise with high to maximal intensity. Despite utilizing only a fraction of cardiac output, blood flow reached a plateau at 80% of maximal work rate and regulated peak oxygen uptake. Furthermore, the results revealed that muscle contractions dictated bulk oxygen delivery and yielded three times higher peak blood flow in the relaxation phase compared with mean values. Copyright © 2017 the American Physiological Society.

Effect of basal forebrain stimulation on extracellular acetylcholine release and blood flow in the olfactory bulb.

PubMed

Uchida, Sae; Kagitani, Fusako

2017-05-12

The olfactory bulb receives cholinergic basal forebrain input, as does the neocortex; however, the in vivo physiological functions regarding the release of extracellular acetylcholine and regulation of regional blood flow in the olfactory bulb are unclear. We used in vivo microdialysis to measure the extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized rats. Focal chemical stimulation by microinjection of L-glutamate into the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which is the main source of cholinergic input to the olfactory bulb, increased extracellular acetylcholine release in the ipsilateral olfactory bulb. When the regional cerebral blood flow was measured using laser speckle contrast imaging, the focal chemical stimulation of the HDB did not significantly alter the blood flow in the olfactory bulb, while increases were observed in the neocortex. Our results suggest a functional difference between the olfactory bulb and neocortex regarding cerebral blood flow regulation through the release of acetylcholine by cholinergic basal forebrain input.

Regulation of Coronary Blood Flow

PubMed Central

Goodwill, Adam G.; Dick, Gregory M.; Kiel, Alexander M.; Tune, Johnathan D.

2018-01-01

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. PMID:28333376

BLOOD PRESSURE REGULATION III: WHAT HAPPENS WHEN ONE SYSTEM MUST SERVE TWO MASTERS: TEMPERATURE AND PRESSURE REGULATION?

PubMed Central

Kenney, W. Larry; Stanhewicz, Anna E.; Bruning, Rebecca S.; Alexander, Lacy M.

2013-01-01

When prolonged intense exercise is performed at high ambient temperatures, cardiac output must meet dual demands for increased blood flow to contracting muscle and to the skin. The literature has commonly painted this scenario as a fierce competition, wherein one circulation preserves perfusion at the expense of the other, with the regulated maintenance of blood pressure as the ultimate goal. This review redefines this scenario as commensalism, an integrated balance of regulatory control where one circulation benefits with little functional effect on the other. In young, healthy subjects, arterial pressure rarely falls to any great extent during either extreme passive heating or prolonged dynamic exercise in the heat. Nor does body temperature rise disproportionately due to a compromised skin blood flow. Rather, it often takes the superimposition of additional stressors – e.g., dehydration or simulated hemorrhage – upon heat stress to substantially impact blood pressure regulation. PMID:23636697

Blood pressure regulation III: what happens when one system must serve two masters: temperature and pressure regulation?

PubMed

Kenney, W Larry; Stanhewicz, Anna E; Bruning, Rebecca S; Alexander, Lacy M

2014-03-01

When prolonged intense exercise is performed at high ambient temperatures, cardiac output must meet dual demands for increased blood flow to contracting muscle and to the skin. The literature has commonly painted this scenario as a fierce competition, wherein one circulation preserves perfusion at the expense of the other, with the regulated maintenance of blood pressure as the ultimate goal. This review redefines this scenario as commensalism, an integrated balance of regulatory control where one circulation benefits with little functional effect on the other. In young, healthy subjects, arterial pressure rarely falls to any great extent during either extreme passive heating or prolonged dynamic exercise in the heat, nor does body temperature rise disproportionately due to a compromised skin blood flow. Rather, it often takes the superimposition of additional stressors--e.g., dehydration or simulated hemorrhage--upon heat stress to substantially impact blood pressure regulation.

Nitric oxide plays a role in the regulation of adrenal blood flow and adrenocorticomedullary functions in the llama fetus

PubMed Central

Riquelme, Raquel A; Sánchez, Gina; Liberona, Leonel; Sanhueza, Emilia M; Giussani, Dino A; Blanco, Carlos E; Hanson, Mark A; Llanos, Aníbal J

2002-01-01

The hypothesis that nitric oxide plays a key role in the regulation of adrenal blood flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6-0.8 of gestation, 11 llama fetuses were surgically prepared for long-term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal i.v. infusion with saline and in five fetuses during fetal i.v. treatment with the nitric oxide synthase inhibitor l-NAME. Adrenal blood flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with l-NAME. Treatment with l-NAME during normoxaemia led to a marked fall in adrenal blood flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline-infused fetuses, acute hypoxaemia elicited an increase in adrenal blood flow and in plasma ACTH, cortisol, adrenaline and noradrenaline concentrations. Treatment with l-NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in adrenal blood flow and in plasma cortisol and adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, l-NAME further enhanced the increase in fetal plasma noradrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of adrenal blood flow and adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus. PMID:12356897

Cyclooxygenase-2 Selectively Controls Renal Blood Flow Through a Novel PPARβ/δ-Dependent Vasodilator Pathway.

PubMed

Kirkby, Nicholas S; Sampaio, Walkyria; Etelvino, Gisele; Alves, Daniele T; Anders, Katie L; Temponi, Rafael; Shala, Fisnik; Nair, Anitha S; Ahmetaj-Shala, Blerina; Jiao, Jing; Herschman, Harvey R; Xiaomeng, Wang; Wahli, Walter; Santos, Robson A; Mitchell, Jane A

2018-02-01

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in inflammation and cancer targeted by nonsteroidal anti-inflammatory drugs. COX-2 is also expressed constitutively in discreet locations where its inhibition drives gastrointestinal and cardiovascular/renal side effects. Constitutive COX-2 expression in the kidney regulates renal function and blood flow; however, the global relevance of the kidney versus other tissues to COX-2-dependent blood flow regulation is not known. Here, we used a microsphere deposition technique and pharmacological COX-2 inhibition to map the contribution of COX-2 to regional blood flow in mice and compared this to COX-2 expression patterns using luciferase reporter mice. Across all tissues studied, COX-2 inhibition altered blood flow predominantly in the kidney, with some effects also seen in the spleen, adipose, and testes. Of these sites, only the kidney displayed appreciable local COX-2 expression. As the main site where COX-2 regulates blood flow, we next analyzed the pathways involved in kidney vascular responses using a novel technique of video imaging small arteries in living tissue slices. We found that the protective effect of COX-2 on renal vascular function was associated with prostacyclin signaling through PPARβ/δ (peroxisome proliferator-activated receptor-β/δ). These data demonstrate the kidney as the principle site in the body where local COX-2 controls blood flow and identifies a previously unreported PPARβ/δ-mediated renal vasodilator pathway as the mechanism. These findings have direct relevance to the renal and cardiovascular side effects of drugs that inhibit COX-2, as well as the potential of the COX-2/prostacyclin/PPARβ/δ axis as a therapeutic target in renal disease. © 2018 The Authors.

Regulation of skeletal muscle blood flow during exercise in ageing humans

PubMed Central

Hearon, Christopher M.

2015-01-01

Abstract The regulation of skeletal muscle blood flow and oxygen delivery to contracting skeletal muscle is complex and involves the mechanical effects of muscle contraction; local metabolic, red blood cell and endothelium‐derived substances; and the sympathetic nervous system (SNS). With advancing age in humans, skeletal muscle blood flow is typically reduced during dynamic exercise and this is due to a lower vascular conductance, which could ultimately contribute to age‐associated reductions in aerobic exercise capacity, a primary predictor of mortality in both healthy and diseased ageing populations. Recent findings have highlighted the contribution of endothelium‐derived substances to blood flow control in contracting muscle of older adults. With advancing age, impaired nitric oxide availability due to scavenging by reactive oxygen species, in conjunction with elevated vasoconstrictor signalling via endothelin‐1, reduces the local vasodilatory response to muscle contraction. Additionally, ageing impairs the ability of contracting skeletal muscle to blunt sympathetic vasoconstriction (i.e. ‘functional sympatholysis’), which is critical for the proper regulation of tissue blood flow distribution and oxygen delivery, and could further reduce skeletal muscle perfusion during high intensity and/or large muscle mass exercise in older adults. We propose that initiation of endothelium‐dependent hyperpolarization is the underlying signalling event necessary to properly modulate sympathetic vasoconstriction in contracting muscle, and that age‐associated impairments in red blood cell adenosine triphosphate release and stimulation of endothelium‐dependent vasodilatation may explain impairments in both local vasodilatation and functional sympatholysis with advancing age in humans. PMID:26332887

Stress and vascular responses: atheroprotective effect of laminar fluid shear stress in endothelial cells: possible role of mitogen-activated protein kinases.

PubMed

Yoshizumi, Masanori; Abe, Jun-Ichi; Tsuchiya, Koichiro; Berk, Bradford C; Tamaki, Toshiaki

2003-03-01

Atherosclerosis preferentially occurs in areas of turbulent blood flow and low fluid shear stress, whereas laminar blood flow and high shear stress are atheroprotective. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), stimulate expression of endothelial cell (EC) genes that may promote atherosclerosis. Recent findings suggest a steady laminar blood flow decreases EC apoptosis and inhibits TNF-mediated EC activation. EC apoptosis or activation is suggested to be involved in plaque erosion, which may lead to platelet aggregation. TNF-alpha regulates gene expression in ECs, in part, by stimulating mitogen-activated protein (MAP) kinases, which phosphorylate transcription factors. We hypothesized that steady laminar flow inhibits cytokine-mediated activation of MAP kinases in ECs. To test this hypothesis, we determined the effects of steady laminar flow (shear stress = 12 dynes/cm(2)) on TNF-alpha-stimulated activity of three MAP kinases in human umbilical vein ECs (HUVEC): extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. TNF-alpha activated ERK1/2, JNK, and p38 maximally at 15 min in HUVEC. Pre-exposing HUVEC for 10 min to flow inhibited TNF-alpha activation of JNK, but showed no significant effect on ERK1/2 or p38 activation. Incubation of HUVEC with PD98059, a specific ERK1/2 inhibitor, blocked the flow-mediated inhibition of TNF activation of JNK. Transfection studies with dominant-negative constructs of the protein kinase MEK5 suggested an important role for big mitogen-activated protein kinase 1 (BMK1) in flow-mediated regulation of EC activation by TNF-alpha. Understanding the mechanisms by which steady laminar flow regulates JNK activation by cytokines may provide insight into the atheroprotective mechanisms induced by laminar blood flow.

Pharmacological activity and protein phosphorylation caused by nitric oxide-releasing microparticles.

PubMed

Yoo, Jin-Wook; Choe, Eun-Sang; Ahn, Sung-Min; Lee, Chi H

2010-01-01

Nitric oxide (NO)-releasing microparticles were developed as a potential treatment option against various blood flow irregulations including sexual dysfunction, atherosclerosis and metal stent-induced restenosis. Polymeric microparticles containing diethylenetriamine diazeniumdiolate (DETA NONOate), a NO donor, were prepared using modified double-emulsion solvent evaporation method to maximize the loading efficacy and stability of DETA NONOate. The pharmacological effects of the NO-releasing microparticles were evaluated by examining the changes in the vaginal blood flow in rats. The effects of NO on the phosphorylation of protein kinase C (PKC) and mitogen activated protein (MAP) kinases in excised vaginal mucosa, such as extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38, were examined using immunoblotting technique to determine whether NO activates PKC, which subsequently plays an integral role in the formation of PKC-MAP kinase modules. The viability of vagina cells (VK2E6E7) upon exposure to NO-releasing microparticles was examined for cytotoxicity assessment. In contrast to rapid and short-term effects of non-formulated DETA NONOate, microparticles containing DETA NONOate exerted beneficial effects on the blood flow (148+/-13%) for an extended period of time, inducing a significant change at 5 min after its application and the maximum blood flow of 172+/-23% at 120 min. The enhanced vaginal blood flow was maintained for up to 210 min and gradually returned to the baseline afterward. The results of Western immunoblotting study displayed differential expression of MAP kinases (ERK1/2 and JNK) upon NO treatment, clearly demonstrating that PKC is involved in the blood flow regulation process. There were no significant changes in cell viability in vaginal cells upon exposure to NO-releasing microparticles as compared with the control. The results of this work supported that NO-releasing microparticles could improve the vaginal blood flow without causing cytotoxic effects and PKC-MAP kinase modules are involved in the NO-induced blood flow regulation process.

Gender differences in myogenic regulation along the vascular tree of the gerbil cochlea.

PubMed

Reimann, Katrin; Krishnamoorthy, Gayathri; Wier, Withrow Gil; Wangemann, Philine

2011-01-01

Regulation of cochlear blood flow is critical for hearing due to its exquisite sensitivity to ischemia and oxidative stress. Many forms of hearing loss such as sensorineural hearing loss and presbyacusis may involve or be aggravated by blood flow disorders. Animal experiments and clinical outcomes further suggest that there is a gender preference in hearing loss, with males being more susceptible. Autoregulation of cochlear blood flow has been demonstrated in some animal models in vivo, suggesting that similar to the brain, blood vessels supplying the cochlea have the ability to control flow within normal limits, despite variations in systemic blood pressure. Here, we investigated myogenic regulation in the cochlear blood supply of the Mongolian gerbil, a widely used animal model in hearing research. The cochlear blood supply originates at the basilar artery, followed by the anterior inferior cerebellar artery, and inside the inner ear, by the spiral modiolar artery and the radiating arterioles that supply the capillary beds of the spiral ligament and stria vascularis. Arteries from male and female gerbils were isolated and pressurized using a concentric pipette system. Diameter changes in response to increasing luminal pressures were recorded by laser scanning microscopy. Our results show that cochlear vessels from male and female gerbils exhibit myogenic regulation but with important differences. Whereas in male gerbils, both spiral modiolar arteries and radiating arterioles exhibited pressure-dependent tone, in females, only radiating arterioles had this property. Male spiral modiolar arteries responded more to L-NNA than female spiral modiolar arteries, suggesting that NO-dependent mechanisms play a bigger role in the myogenic regulation of male than female gerbil cochlear vessels.

Endothelial cells respond to the direction of mechanical stimuli through SMAD signaling to regulate coronary artery size.

PubMed

Poduri, Aruna; Chang, Andrew H; Raftrey, Brian; Rhee, Siyeon; Van, Mike; Red-Horse, Kristy

2017-09-15

How mechanotransduction intersects with chemical and transcriptional factors to shape organogenesis is an important question in developmental biology. This is particularly relevant to the cardiovascular system, which uses mechanical signals from flowing blood to stimulate cytoskeletal and transcriptional responses that form a highly efficient vascular network. Using this system, artery size and structure are tightly regulated, but the underlying mechanisms are poorly understood. Here, we demonstrate that deletion of Smad4 increased the diameter of coronary arteries during mouse embryonic development, a phenotype that followed the initiation of blood flow. At the same time, the BMP signal transducers SMAD1/5/8 were activated in developing coronary arteries. In a culture model of blood flow-induced shear stress, human coronary artery endothelial cells failed to align when either BMPs were inhibited or SMAD4 was depleted. In contrast to control cells, SMAD4- deficient cells did not migrate against the direction of shear stress and increased proliferation rates specifically under flow. Similar alterations were seen in coronary arteries in vivo Thus, endothelial cells perceive the direction of blood flow and respond through SMAD signaling to regulate artery size. © 2017. Published by The Company of Biologists Ltd.

Impaired postprandial tissue regulation of blood flow in insulin resistance: a determinant of cardiovascular risk?

PubMed

Summers, L K; Samra, J S; Frayn, K N

1999-11-01

The insulin resistant state is a major risk factor for coronary artery disease. This increased risk is likely to be due to associated lipid and coagulation abnormalities rather than just abnormalities in glucose metabolism or hyperinsulinaemia alone. Exaggerated postprandial lipaemia is a well-recognised associate of insulin resistance and postprandial hypertriglyceridaemia is particularly important in the development of coronary atheroma. It seems likely that insulin is one of the hormonal regulators of adipose tissue and skeletal muscle blood flow. The reduced blood flow and blunting of the postprandial rise of peripheral blood flow in insulin resistance may decrease chylomicron-triglyceride delivery to muscle in subjects with insulin resistance. This, in turn, will lead to increased production of atherogenic particles. We propose that impaired postprandial vasodilation, already recognised as a key feature of glucose intolerance, is also the cause of impaired lipid metabolism in insulin resistant subjects and predisposes them to cardiovascular disease.

Functional importance of blood flow dynamics and partial oxygen pressure in the anterior pituitary.

PubMed

Schaeffer, Marie; Hodson, David J; Lafont, Chrystel; Mollard, Patrice

2010-12-01

The pulsatile release of hormone is obligatory for the control of a range of important body homeostatic functions. To generate these pulses, endocrine organs have developed finely regulated mechanisms to modulate blood flow both to meet the metabolic demand associated with intense endocrine cell activity and to ensure the temporally precise uptake of secreted hormone into the bloodstream. With a particular focus on the pituitary gland as a model system, we review here the importance of the interplay between blood flow regulation and oxygen tensions in the functioning of endocrine systems, and the known regulatory signals involved in the modification of flow patterns under both normal physiological and pathological conditions. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Intravascular ATP and the regulation of blood flow and oxygen delivery in humans.

PubMed

Crecelius, Anne R; Kirby, Brett S; Dinenno, Frank A

2015-01-01

Regulation of vascular tone is a complex response that integrates multiple signals that allow for blood flow and oxygen supply to match oxygen demand appropriately. Here, we discuss the potential role of intravascular adenosine triphosphate (ATP) as a primary factor in these responses and put forth the hypothesis that deficient ATP release contributes to impairments in vascular control exhibited in aged and diseased populations.

Cerebral blood flow regulation during cognitive tasks

PubMed Central

Sorond, Farzaneh A.; Schnyer, D.M.; Serrador, J.M.; Milberg, W.P.; Lipsitz, L.A.

2008-01-01

Aging is associated with frontal subcortical microangiopathy and executive cognitive dysfunction, suggesting that elderly individuals may have impaired metabolic activation of cerebral blood flow to the frontal lobes. We used transcranial Doppler (TCD) ultrasound to examine the cerebral blood flow response to executive control and visual tasks in the anterior and posterior cerebral circulations and to determine the effects of healthy aging on cerebral blood flow regulation during cognitive tasks. Continuous simultaneous anterior cerebral artery (ACA) and posterior cerebral artery (PCA) blood flow velocities (BFVs) and mean arterial pressure (MAP) were measured in response to word stem completion (WSC) and a visual search (VS) task in 29 healthy subjects (14 young, 30 ± 1.5 years; 15 old, 74 ± 1.4 years). We found that: (1) ACA and PCA blood flow velocities are both significantly increased during WSC and VS cognitive tasks, (2) ACA and PCA activations were task specific in our young volunteers, with ACA > PCA BFV during the WSC task and PCA > ACA BFV during the VS task, (3) while healthy elderly subjects also had PCA > ACA BFV during the VS task, they did not have ACA > PCA activation during the WSC task, and (4) healthy elderly subjects tend to have overall greater increases in BFV during both cognitive tasks. We conclude that TCD can be used to monitor cerebrovascular hemodynamics during the performance of cognitive tasks. Our data suggest that there is differential blood flow increase in the ACA and PCA in young versus elderly subjects during cognitive tasks. PMID:18387547

Flow-Mediated Endothelial Mechanotransduction

PubMed Central

Davies, Peter F.

2011-01-01

Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed. PMID:7624393

Blood clots are rapidly assembled hemodynamic sensors: flow arrest triggers intraluminal thrombus contraction.

PubMed

Muthard, Ryan W; Diamond, Scott L

2012-12-01

Blood clots form under flow during intravascular thrombosis or vessel leakage. Prevailing hemodynamics influence thrombus structure and may regulate contraction processes. A microfluidic device capable of flowing human blood over a side channel plugged with collagen (± tissue factor) was used to measure thrombus permeability (κ) and contraction at controlled transthrombus pressure drops. The collagen (κ(collagen)=1.98 × 10(-11) cm(2)) supported formation of a 20-µm thick platelet layer, which unexpectedly underwent massive platelet retraction on flow arrest. This contraction resulted in a 5.34-fold increase in permeability because of collagen restructuring. Without stopping flow, platelet deposits (no fibrin) had a permeability of κ(platelet)=5.45 × 10(-14) cm(2) and platelet-fibrin thrombi had κ(thrombus)=2.71 × 10(-14) cm(2) for ΔP=20.7 to 23.4 mm Hg, the first ever measurements for clots formed under arterial flow (1130 s(-1) wall shear rate). Platelet sensing of flow cessation triggered a 4.6- to 6.5-fold (n=3, P<0.05) increase in contraction rate, which was also observed in a rigid, impermeable parallel-plate microfluidic device. This triggered contraction was blocked by the myosin IIA inhibitor blebbistatin and by inhibitors of thromboxane A2 (TXA(2)) and ADP signaling. In addition, flow arrest triggered platelet intracellular calcium mobilization, which was blocked by TXA(2)/ADP inhibitors. As clots become occlusive or blood pools following vessel leakage, the flow diminishes, consequently allowing full platelet retraction. Flow dilution of ADP and thromboxane regulates platelet contractility with prevailing hemodynamics, a newly defined flow-sensing mechanism to regulate clot function.

Pancreatic islet blood flow and its measurement

PubMed Central

Jansson, Leif; Barbu, Andreea; Bodin, Birgitta; Drott, Carl Johan; Espes, Daniel; Gao, Xiang; Grapensparr, Liza; Källskog, Örjan; Lau, Joey; Liljebäck, Hanna; Palm, Fredrik; Quach, My; Sandberg, Monica; Strömberg, Victoria; Ullsten, Sara; Carlsson, Per-Ola

2016-01-01

Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting β-cells, endothelium-derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future. PMID:27124642

Flow-mediated dilation and exercise blood pressure in healthy adolescents

USDA-ARS?s Scientific Manuscript database

Objectives: Atherosclerosis is a process that begins in youth. The endothelium plays an essential role in regulating blood flow and protecting against progression of the initial stages of the atherosclerotic process. Few studies have investigated the relationship between aerobic fitness and exerc...

Nitric oxide transport in blood: a third gas in the respiratory cycle.

PubMed

Doctor, Allan; Stamler, Jonathan S

2011-01-01

The trapping, processing, and delivery of nitric oxide (NO) bioactivity by red blood cells (RBCs) have emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We present here an expanded paradigm for the human respiratory cycle based on the coordinated transport of three gases: NO, O₂, and CO₂. By linking O₂ and NO flux, RBCs couple vessel caliber (and thus blood flow) to O₂ availability in the lung and to O₂ need in the periphery. The elements required for regulated O₂-based signal transduction via controlled NO processing within RBCs are presented herein, including S-nitrosothiol (SNO) synthesis by hemoglobin and O₂-regulated delivery of NO bioactivity (capture, activation, and delivery of NO groups at sites remote from NO synthesis by NO synthase). The role of NO transport in the respiratory cycle at molecular, microcirculatory, and system levels is reviewed. We elucidate the mechanism through which regulated NO transport in blood supports O₂ homeostasis, not only through adaptive regulation of regional systemic blood flow but also by optimizing ventilation-perfusion matching in the lung. Furthermore, we discuss the role of NO transport in the central control of breathing and in baroreceptor control of blood pressure, which subserve O₂ supply to tissue. Additionally, malfunctions of this transport and signaling system that are implicated in a wide array of human pathophysiologies are described. Understanding the (dys)function of NO processing in blood is a prerequisite for the development of novel therapies that target the vasoactive capacities of RBCs. © 2011 American Physiological Society.

Centrifuge apparatus

DOEpatents

Sartory, Walter K.; Eveleigh, John W.

1976-01-01

A method and apparatus for operating a continuous flow blood separation centrifuge are provided. The hematocrit of the entrant whole blood is continuously maintained at an optimum constant value by the addition of plasma to the entrant blood. The hematocrit of the separated red cells is monitored to indicate the degree of separation taking place, thereby providing a basis for regulating the flow through the centrifuge.

Nitric oxide, prostaglandins and angiotensin II in the regulation of renal medullary blood flow during volume expansion.

PubMed

Moreno, Carol; Llinás, María T; Rodriguez, Francisca; Moreno, Juan M; Salazar, F Javier

2016-03-01

Regulation of medullary blood flow (MBF) is essential in maintaining renal function and blood pressure. However, it is unknown whether outer MBF (OMBF) and papillary blood flow (PBF) are regulated independently when extracellular volume (ECV) is enhanced. The aim of this study was to determine whether OMBF and PBF are differently regulated and whether there is an interaction between nitric oxide (NO), prostaglandins (PGs) and angiotensin II (Ang II) in regulating OMBF and PBF when ECV is enhanced. To achieve these goals, OMBF and PBF were measured by laser-Doppler in volume-expanded rats treated with a cyclooxygenase inhibitor (meclofenamate, 3 mg/kg) and/or a NO synthesis inhibitor (L-nitro-arginine methyl ester (L-NAME), 3 μg/kg/min) and/or Ang II (10 ng/kg/min). OMBF was unchanged by NO or PGs synthesis inhibition but decreased by 36 % (P < 0.05) when L-NAME and meclofenamate were infused simultaneously. PBF was similarly reduced by L-NAME (12 %), meclofenamate (17 %) or L-NAME + meclofenamate (19 %). Ang II did not modify OMBF, but it led to a similar decrease (P < 0.05) in OMBF when it was administered to rats with reduced NO (32 %), PGs (36 %) or NO and PGs (37 %) synthesis. In contrast, the fall in PBF induced by Ang II (12 %) was enhanced (P < 0.05) by the simultaneous PGs (30 %) or PGs and NO (31 %) synthesis inhibition but not in L-NAME-treated rats (20 %). This study presents novel findings suggesting that blood flows to the outer medulla and renal papilla are differently regulated and showing that there is a complex interaction between NO, PGs and Ang II in regulating OMBF and PBF when ECV is enhanced.

Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo

PubMed Central

Nyman, Lara R.; Ford, Eric

2010-01-01

Pancreatic islets are highly vascularized and arranged so that regions containing β-cells are distinct from those containing other cell types. Although islet blood flow has been studied extensively, little is known about the dynamics of islet blood flow during hypoglycemia or hyperglycemia. To investigate changes in islet blood flow as a function of blood glucose level, we clamped blood glucose sequentially at hyperglycemic (∼300 mg/dl or 16.8 mM) and hypoglycemic (∼50 mg/dl or 2.8 mM) levels while simultaneously imaging intraislet blood flow in mouse models that express green fluorescent protein in the β-cells or yellow fluorescent protein in the α-cells. Using line scanning confocal microscopy, in vivo blood flow was assayed after intravenous injection of fluorescent dextran or sulforhodamine-labeled red blood cells. Regardless of the sequence of hypoglycemia and hyperglycemia, islet blood flow is faster during hyperglycemia, and apparent blood volume is greater during hyperglycemia than during hypoglycemia. However, there is no change in the order of perfusion of different islet endocrine cell types in hypoglycemia compared with hyperglycemia, with the islet core of β-cells usually perfused first. In contrast to the results in islets, there was no significant difference in flow rate in the exocrine pancreas during hyperglycemia compared with hypoglycemia. These results indicate that glucose differentially regulates blood flow in the pancreatic islet vasculature independently of blood flow in the rest of the pancreas. PMID:20071562

A study of renal blood flow regulation using the discrete wavelet transform

NASA Astrophysics Data System (ADS)

Pavlov, Alexey N.; Pavlova, Olga N.; Mosekilde, Erik; Sosnovtseva, Olga V.

2010-02-01

In this paper we provide a way to distinguish features of renal blood flow autoregulation mechanisms in normotensive and hypertensive rats based on the discrete wavelet transform. Using the variability of the wavelet coefficients we show distinctions that occur between the normal and pathological states. A reduction of this variability in hypertension is observed on the microscopic level of the blood flow in efferent arteriole of single nephrons. This reduction is probably associated with higher flexibility of healthy cardiovascular system.

Wavelet-analysis of gastric microcirculation in rats with ulcer bleedings

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Semyachkina-Glushkovskaya, O. V.; Pavlova, O. N.; Bibikova, O. A.; Kurths, J.

2013-10-01

Nitric oxide (NO) plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhagic stress. Because the impaired gastric mucosal blood flow is the major cause of gastroduodenal lesions including ulcer bleeding (UB), we study in this work the NO-ergic mechanism responsible for regulation of this blood flow. Our study is performed in rats with a model of stress-induced UB using laser Doppler flowmetry (LDF) that characterizes the rate of blood flow by measuring a Doppler shift of the laser beam scattered by the moving red blood cells. Numerical analysis of LDF-data is based on the discrete wavelet-transform (DWT) using Daubechies wavelets aiming to quantify influences of NO on the gastric microcirculation. We show that the stress-induced UB is associated with an increased level of NO in the gastric tissue and a stronger vascular sensitivity to pharmacological modulation of NO-production by L-NAME. We demonstrate that wavelet-based analyses of NO-dependent regulation of gastric microcirculation can provide an effective endoscopic diagnostics of a risk of UB.

A protocol for characterizing the impact of collateral flow after distal middle cerebral artery occlusion

PubMed Central

DeFazio, R. Anthony; Levy, Sean; Morales, Carmen L.; Levy, Rebecca V.; Dave, Kunjan R.; Lin, Hung W.; Abaffy, Tatjana; Watson, Brant D.; Perez-Pinzon, Miguel A.; Ohanna, Victoria

2010-01-01

I. SUMMARY In humans and in animal models of stroke, collateral blood flow between territories of the major pial arteries has a profound impact on cortical infarct size. However, there is a gap in our understanding of the genetic determinants of collateral formation and flow, as well as the signaling pathways and neurovascular interactions regulating this flow. Previous studies have demonstrated that collateral flow between branches of the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) can protect mouse cortex from infarction after middle cerebral artery occlusion. Because the number and diameter of collaterals varies among mouse strains and after transgenic manipulations, a combination of methods is required to control for these variations. Here, we report an inexpensive approach to characterizing the cerebrovascular anatomy, and in vivo monitoring of cerebral blood flow as well. Further, we introduce a new, minimally invasive method for the occlusion of distal MCA branches. These methods will permit a new generation of studies on the mechanisms regulating collateral remodeling and cortical blood flow after stroke. PMID:21593993

Evaluation of blood microcirculation parameters by combined use of laser Doppler flowmetry and videocapillaroscopy methods

NASA Astrophysics Data System (ADS)

Volkov, M. V.; Kostrova, D. A.; Margaryants, N. B.; Gurov, I. P.; Erofeev, N. P.; Dremin, V. V.; Zharkikh, E. V.; Zherebtsov, E. A.; Kozlov, I. O.; Dunaev, A. V.

2017-03-01

Laser Doppler flowmetry (LDF) is widely used for diagnosing blood microcirculation diseases. It is well known that the Doppler shift of laser radiation scattered by moving red blood cells (RBC) can be assessed through analyzing photocurrent produced by a photodetector. LDF signal contains information about regulating blood flow rhythms: myogenic, cardiac, nervous and endothelial. The method of videocapillaroscopy (VCS) allows local capillary blood flow velocity evaluation and, using video data processing algorithms, is able to assess RBC velocity changes into capillary. We present the results of simultaneous investigations of changes in tissue perfusion of the distal phalanx of human finger by the LDF as well as changes in capillary blood flow velocity in the nail bed evaluated by the VCS method during arterial occlusion test. The experimental results confirmed the correspondence between blood perfusion and blood flow velocity.

Nonlinear Pressure-Flow Relationship Is Able to Detect Asymmetry of Brain Blood Circulation Associated with Midline Shift

PubMed Central

Lo, Men-Tzung; Peng, C.K.; Novak, Vera; Schmidt, Eric A.; Kumar, Ajay; Czosnyka, Marek

2009-01-01

Abstract Reliable and noninvasive assessment of cerebral blood flow regulation is a major challenge in acute care monitoring. This study assessed dynamics of flow regulation and its relationship to asymmetry of initial computed tomography (CT) scan using multimodal pressure flow (MMPF) analysis. Data of 27 patients (38 ± 15 years old) with traumatic brain injury (TBI) were analyzed. Patients were selected from bigger cohort according to criteria of having midline shift on initial CT scan and intact skull (no craniotomy or bone flap). The MMPF analysis was used to extract the oscillations in cerebral perfusion pressure (CPP) and blood flow velocity (BFV) signals at frequency of artificial ventilation, and to calculate the instantaneous phase difference between CPP and BFV oscillations. Mean CPP-BFV phase difference was used to quantify pressure and flow relationship. The TBI subjects had smaller mean BP-BFV phase shifts (left, 8.7 ± 9.6; right 10.2 ± 8.3 MCAs, mean ± SD) than values previously obtained in healthy subjects (left, 37.3 ± 7.6 degrees; right, 38.0 ± 8.9 degrees; p < 0.0001), suggesting impaired blood flow regulation after TBI. The difference in phase shift between CPP and BFV in the left and right side was strongly correlated to the midline shift (R = 0.78; p < 0.0001). These findings indicate that the MMPF method allows reliable assessment of alterations in pressure and flow relationship after TBI. Moreover, mean pressure-flow phase shift is sensitive to the displacement of midline of the brain, and may potentially serve as a marker of asymmetry of cerebral autoregulation. PMID:19196074

Pre-breeding beef heifer management and season affect mid to late gestation uterine artery hemodynamics

USDA-ARS?s Scientific Manuscript database

Examining uterine blood flow, which regulates nutrient and waste exchange to the developing fetus, is vital to understanding strategies to prevent placental wastage. This study examines uterine blood flow of heifers developed with low-input versus traditional management schemes, which allows us to m...

Investigation of Blood Flow and the Effect of Vasoactive Substances in Cutaneous Blood Vessels of "Xenopus Laevis"

ERIC Educational Resources Information Center

Škorjanc, Aleš; Belušic, Gregor

2015-01-01

In the present study, a preparation of frog skin was presented, which can be used to demonstrate the basic concepts of blood flow regulation in a very clear and attractive way to high school and university students. In a freshly euthanized "Xenopus," a patch of abdominal skin was exposed from the internal side and viewed with a USB…

Regulation of human retinal blood flow by endothelin-1.

PubMed

Polak, Kaija; Luksch, Alexandra; Frank, Barbara; Jandrasits, Kerstin; Polska, Elzbieta; Schmetterer, Leopold

2003-05-01

There is evidence from in vitro and animal studies that endothelin is a major regulator of retinal blood flow. We set out to characterize the role of the endothelin-system in the blood flow control of the human retina. Two studies in healthy subjects were performed. The study design was randomized, placebo-controlled, double-masked, balanced, two-way crossover in protocol A and three way-way crossover in protocol B. In protocol A 18 healthy male subjects received intravenous endothelin-1 (ET-1) in a dose of 2.5 ng kg (-1)min(-1) for 30 min or placebo on two different study days and retinal vessel diameters were measured. In protocol B 12 healthy male subjects received ET-1 in stepwise increasing doses of 0, 1.25, 2.5 and 5 ng kg (-1)min(-1) (each infusion step over 20 min) in co-infusion with the specific ET(A)-receptor antagonist BQ123 (60 microg min (-1)) or placebo or BQ123 alone investigating retinal vessel diameters, retinal blood velocity and retinal blood flow. Measurements of retinal vessel size were done with the Zeiss retinal vessel analyzer. Measurements of blood velocities were done with bi-directional laser Doppler velocimetry. From these measurements retinal blood flow was calculated. In protocol A exogenous ET-1 tended to decrease retinal arterial diameter, but this effect was not significant versus placebo. No effect on retinal venous diameter was seen. In protocol B retinal venous blood velocity and retinal blood flow was significantly reduced after administration of exogenous ET-1. These effects were significantly blunted when BQ-123 was co-administered. By contrast, BQ-123 alone had no effect on retinal hemodynamic parameters. Concluding, BQ123 antagonizes the effects of exogenously administered ET-1 on retinal blood flow in healthy subjects. In addition, the results of the present study are compatible with the hypothesis that ET-1 exerts its vasoconstrictor effects in the retina mainly on the microvessels.

A modeling study on the influence of blood flow regulation on skin temperature pulsations

NASA Astrophysics Data System (ADS)

Tang, Yanliang; Mizeva, Irina; He, Ying

2017-04-01

Nowadays together with known optic techniques of microcirculation blood flow monitoring, skin temperature measurements are developed as well. In this paper, a simple one-dimensional bioheat transfer model was developed to analyse the heat wave transport in biological tissue, where an arteriole vessel with pulsatile blood is located. The simulated results show that the skin temperature oscillation amplitudes attenuate with the increase of blood flow oscillation frequency which gives the same tendency as that in the experiments. The parameter analyses further show that the amplitude of oscillation is also influenced by oscillation amplitude of blood and effective thermal conductivity. When oscillation amplitude of blood flow and effective thermal conductivity increase, the amplitude of skin temperature oscillation increases nonlinearly. Variation of effective thermal convective influence to the time delay of the thermal wave on the skin surface and distort it. Combination of two measurement techniques: one for estimation blood flow oscillations in the microvessels and other to the skin temperature measurement can produce additional information about the skin properties.

Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine.

PubMed

Toda, Noboru; Toda, Hiroshi

2010-12-15

Cigarette smoking is a major risk factor for atherosclerosis, cerebral and coronary vascular diseases, hypertension, and diabetes mellitus. Chronic smoking impairs endothelial function by decreasing the formation of nitric oxide and increasing the degradation of nitric oxide via generation of oxygen free radicals. Nitric oxide liberated from efferent nitrergic nerves is also involved in vasodilatation, increased regional blood flow, and hypotension that are impaired through nitric oxide sequestering by smoking-induced factors. Influence of smoking on nitric oxide-induced blood flow regulation is not necessarily the same in all organs and tissues. However, human studies are limited mainly to the forearm blood flow measurement that assesses endothelial function under basal and stimulated conditions and also determination of penile tumescence and erection in response to endothelial and neuronal nitric oxide. Therefore, information about blood flow regulation in other organs, such as the brain and placenta, has been provided mainly from studies on experimental animals. Nicotine, a major constituent of cigarette smoke, acutely dilates cerebral arteries and arterioles through nitric oxide liberated from nitrergic neurons, but chronically interferes with endothelial function in various vasculatures, both being noted in studies on experimental animals. Cigarette smoke constituents other than nicotine also have some vascular actions. Not only active but also passive smoking is undoubtedly harmful for both the smokers themselves and their neighbors, who should bear in mind that they can face serious diseases in the future, which may result in lengthy hospitalization, and a shortened lifespan. Copyright © 2010 Elsevier B.V. All rights reserved.

[Hemodynamic phenomena in retrobulhar and eyeball vessels].

PubMed

Modrzejewska, Monika

2011-01-01

The purpose of this review was to evaluate factors connected with blood flow and indices regulating vascular diameter and some parameters influencing retrobulbar circulation such as type of vascular resistance, anatomical structure of vascular wall and vessel lumen. Neurogenic and angiogenic factors, rheological blood composition, presence of anatomical and pathological obstructions on blood flow pathway as well as degree of development of collateral circulation pathways--have influence on the volume and blood flow velocity in eyeball. There were discussed bulbar circulation hemodynamics, emphasizing the importance of perfusion pressure. The role of risk factors was underlined for pathological lesions in vessels supplying blood to eyeball and in ophthalmic artery (OA) and its collaterals, in central retinal artery (CRA) as well as posterior ciliary arteries (PCAs), and in venous system carrying away blood from eye. IN CONCLUSION--the results of many studies of retrobulbar blood flow in different types of ophthalmic diseases of the vascular etiopathogenesis indicate that registry of the mean values of blood flow parameters and vascular resistance indices parallel to measurement of blood flow spectrum in OA, CRA, PCAs arteries, might contribute much information to explain or to evaluate nature of pathological changes in retinal and choroidal circulation.

Enteral arginine does not increase superior mesenteric arterial blood flow and but induces mucosal growth in neonatal pigs

USDA-ARS?s Scientific Manuscript database

Arginine is an essential amino acid in neonates synthesized by gut epithelial cells and a precursor for nitric oxide (NO) that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemia-reperfusion models and low plasma levels are ass...

Methods for the determination of skeletal muscle blood flow: development, strengths and limitations.

PubMed

Gliemann, Lasse; Mortensen, Stefan P; Hellsten, Ylva

2018-06-01

Since the first measurements of limb blood flow at rest and during nerve stimulation were conducted in the late 1800s, a number of methods have been developed for the determination of limb and skeletal muscle blood flow in humans. The methods, which have been applied in the study of aspects such as blood flow regulation, oxygen uptake and metabolism, differ in terms of strengths and degree of limitations but most have advantages for specific settings. The purpose of this review is to describe the origin and the basic principles of the methods, important aspects and requirements of the procedures. One of the earliest methods, venous occlusion plethysmography, is a noninvasive method which still is extensively used and which provides similar values as other more direct blood flow methods such as ultrasound Doppler. The constant infusion thermodilution method remains the most appropriate for the determination of blood flow during maximal exercise. For resting blood flow and light-to-moderate exercise, the non-invasive ultrasound Doppler methodology, if handled by a skilled operator, is recommendable. Positron emission tomography with radiolabeled water is an advanced method which requires highly sophisticated equipment and allows for the determination of muscle-specific blood flow, regional blood flows and estimate of blood flow heterogeneity within a muscle. Finally, the contrast-enhanced ultrasound method holds promise for assessment of muscle-specific blood flow, but the interpretation of the data obtained remains uncertain. Currently lacking is high-resolution methods for continuous visualization and monitoring of the skeletal muscle microcirculation in humans.

HIF isoforms in the skin differentially regulate systemic arterial pressure

PubMed Central

Cowburn, Andrew S.; Takeda, Norihiko; Boutin, Adam T.; Kim, Jung-Whan; Sterling, Jane C.; Nakasaki, Manando; Southwood, Mark; Goldrath, Ananda W.; Jamora, Colin; Nizet, Victor; Chilvers, Edwin R.; Johnson, Randall S.

2013-01-01

Vascular flow through tissues is regulated via a number of homeostatic mechanisms. Localized control of tissue blood flow, or autoregulation, is a key factor in regulating tissue perfusion and oxygenation. We show here that the net balance between two hypoxia-inducible factor (HIF) transcription factor isoforms, HIF-1α and HIF-2α, is an essential mechanism regulating both local and systemic blood flow in the skin of mice. We also show that balance of HIF isoforms in keratinocyte-specific mutant mice affects thermal adaptation, exercise capacity, and systemic arterial pressure. The two primary HIF isoforms achieve these effects in opposing ways that are associated with HIF isoform regulation of nitric oxide production. We also show that a correlation exists between altered levels of HIF isoforms in the skin and the degree of idiopathic hypertension in human subjects. Thus, the balance between HIF-1α and HIF-2α expression in keratinocytes is a control element of both tissue perfusion and systemic arterial pressure, with potential implications in human hypertension. PMID:24101470

Dynamics of pulsatile flow in fractal models of vascular branching networks.

PubMed

Bui, Anh; Sutalo, Ilija D; Manasseh, Richard; Liffman, Kurt

2009-07-01

Efficient regulation of blood flow is critically important to the normal function of many organs, especially the brain. To investigate the circulation of blood in complex, multi-branching vascular networks, a computer model consisting of a virtual fractal model of the vasculature and a mathematical model describing the transport of blood has been developed. Although limited by some constraints, in particular, the use of simplistic, uniformly distributed model for cerebral vasculature and the omission of anastomosis, the proposed computer model was found to provide insights into blood circulation in the cerebral vascular branching network plus the physiological and pathological factors which may affect its functionality. The numerical study conducted on a model of the middle cerebral artery region signified the important effects of vessel compliance, blood viscosity variation as a function of the blood hematocrit, and flow velocity profile on the distributions of flow and pressure in the vascular network.

Alterations of choroidal blood flow regulation in young healthy subjects with complement factor H polymorphism.

PubMed

Told, Reinhard; Palkovits, Stefan; Haslacher, Helmuth; Frantal, Sophie; Schmidl, Doreen; Boltz, Agnes; Lasta, Michael; Kaya, Semira; Werkmeister, René M; Garhöfer, Gerhard; Schmetterer, Leopold

2013-01-01

A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis.

Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans.

PubMed

Fuchsjäger-Mayrl, Gabriele; Luksch, Alexandra; Malec, Magdalena; Polska, Elzbieta; Wolzt, Michael; Schmetterer, Leopold

2003-02-01

There is evidence that the choroid has some autoregulatory capacity in response to changes in ocular perfusion pressure (OPP). The mediators of this response are hitherto unidentified. The hypothesis for the current study was that endothelin (ET)-1 and/or angiotensin (ANF)-II may be involved in choroidal vasoconstriction during an increase in OPP. To test this hypothesis a randomized, double-masked, placebo-controlled, three way crossover study was performed in 12 healthy male volunteers. Subjects received on different study days intravenous infusions of the specific ET(A) receptor antagonist BQ-123, the angiotensin converting enzyme inhibitor enalapril or placebo. During these infusion periods subjects were asked to squat for 6 minutes. Choroidal blood flow was measured using a confocal laser Doppler flowmeter and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. BQ-123 and enalapril had no effect on basal blood pressure, pulse rate, intraocular pressure, or choroidal blood flow. During isometric exercise, a pronounced increase in mean arterial pressure paralleled by an increase in OPP was observed. Although choroidal blood flow slightly increased during squatting, the increase was much less pronounced than the increase in OPP, indicating some regulatory potential of the choroid. Enalapril did not alter the choroidal pressure-flow relationship during isometric exercise, but BQ-123 induced a significant leftward shift of the pressure-flow curve (P < 0.001). The present data indicate that ET-1, but not ANG II, plays a role in choroidal blood flow regulation during isometric exercise in healthy humans. Hence, impaired choroidal autoregulation in patients with ocular vascular diseases may arise from an altered endothelin system. Further studies in such patients are warranted to verify this hypothesis.

Bifurcation analysis of nephron pressure and flow regulation

NASA Astrophysics Data System (ADS)

Barfred, Mikael; Mosekilde, Erik; Holstein-Rathlou, Niels-Henrik

1996-09-01

One- and two-dimensional continuation techniques are applied to study the bifurcation structure of a model of renal flow and pressure control. Integrating the main physiological mechanisms by which the individual nephron regulates the incoming blood flow, the model describes the interaction between the tubuloglomerular feedback and the response of the afferent arteriole. It is shown how a Hopf bifurcation leads the system to perform self-sustained oscillations if the feedback gain becomes sufficiently strong, and how a further increase of this parameter produces a folded structure of overlapping period-doubling cascades. Similar phenomena arise in response to increasing blood pressure. The numerical analyses are supported by existing experimental results on anesthetized rats.

Effects of postural changes and removal of vestibular inputs on blood flow to and from the hindlimb of conscious felines

PubMed Central

Yavorcik, K. J.; Reighard, D. A.; Misra, S. P.; Cotter, L. A.; Cass, S. P.; Wilson, T. D.

2009-01-01

Considerable data show that the vestibular system contributes to blood pressure regulation. Prior studies reported that lesions that eliminate inputs from the inner ears attenuate the vasoconstriction that ordinarily occurs in the hindlimbs of conscious cats during head-up rotations. These data led to the hypothesis that labyrinthine-deficient animals would experience considerable lower body blood pooling during head-up postural alterations. The present study tested this hypothesis by comparing blood flow though the femoral artery and vein of conscious cats during 20–60° head-up tilts from the prone position before and after removal of vestibular inputs. In vestibular-intact animals, venous return from the hindlimb dropped considerably at the onset of head-up tilts and, at 5 s after the initiation of 60° rotations, was 66% lower than when the animals were prone. However, after the animals were maintained in the head-up position for another 15 s, venous return was just 33% lower than before the tilt commenced. At the same time point, arterial inflow to the limb had decreased 32% from baseline, such that the decrease in blood flow out of the limb due to the force of gravity was precisely matched by a reduction in blood reaching the limb. After vestibular lesions, the decline in femoral artery blood flow that ordinarily occurs during head-up tilts was attenuated, such that more blood flowed into the leg. Contrary to expectations, in most animals, venous return was facilitated, such that no more blood accumulated in the hindlimb than when labyrinthine signals were present. These data show that peripheral blood pooling is unlikely to account for the fluctuations in blood pressure that can occur during postural changes of animals lacking inputs from the inner ear. Instead, alterations in total peripheral resistance following vestibular dysfunction could affect the regulation of blood pressure. PMID:19793952

Blood clots are rapidly assembled hemodynamic sensors: Flow arrest triggers intraluminal thrombus contraction

PubMed Central

Muthard, Ryan W.; Diamond, Scott L.

2012-01-01

Objective Blood clots form under flow during intravascular thrombosis or vessel leakage. Prevailing hemodynamics influence thrombus structure and may regulate contraction processes. A microfluidic device capable of flowing human blood over a side channel plugged with collagen (± tissue factor) was used to measure thrombus permeability (κ) and contraction at controlled transthrombus pressure drops. Methods and Results The collagen (κcollagen = 1.98 × 10−11 cm2) supported formation of a 20-μm thick platelet layer, which unexpectedly underwent massive platelet retraction upon flow arrest. This contraction resulted in a 5.34-fold increase in permeability due to collagen restructuring. Without stopping flow, platelet deposits (no fibrin) had a permeability of κplatelet = 5.45 × 10−14 cm2 and platelet-fibrin thrombi had κthrombus = 2.71 × 10−14 cm2 for ΔP = 20.7 to 23.4 mm-Hg, the first ever measurements for clots formed under arterial flow (1130 s−1 wall shear rate). Platelet sensing of flow cessation triggered a 4.6 to 6.5-fold (n=3, P<0.05) increase in contraction rate, which was also observed in a rigid, impermeable parallel-plate microfluidic device. This triggered contraction was blocked by the myosin IIA inhibitor blebbistatin and by inhibitors of thromboxane (TXA2) and ADP signaling. In addition, flow arrest triggered platelet intracellular calcium mobilization, which was blocked by TXA2/ADP inhibitors. As clots become occlusive or vessels rupture, flow around developed clots diminishes facilitating full platelet retraction and hemostasis. Conclusion Flow dilution of ADP and thromboxane regulates platelet contractility with prevailing hemodynamics, a newly defined flow sensing mechanism to regulate clot function. PMID:23087356

Neural Vascular Mechanism for the Cerebral Blood Flow Autoregulation after Hemorrhagic Stroke.

PubMed

Xiao, Ming; Li, Qiang; Feng, Hua; Zhang, Le; Chen, Yujie

2017-01-01

During the initial stages of hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, the reflex mechanisms are activated to protect cerebral perfusion, but secondary dysfunction of cerebral flow autoregulation 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. Evoked by the concept of vascular neural network, the unveiled neural vascular mechanism gains more and more attentions. Astrocyte, neuron, pericyte, endothelium, and so forth are formed as a communicate network to regulate with each other as well as the cerebral blood flow. However, the signaling molecules responsible for this communication between these new players and blood vessels are yet to be definitively confirmed. Recent evidence suggested the pivotal role of transcriptional mechanism, including but not limited to miRNA, lncRNA, exosome, and so forth, for the cerebral blood flow autoregulation. In the present review, we sought to summarize the hemodynamic changes and underline neural vascular mechanism for cerebral blood flow autoregulation in stroke-prone state and after hemorrhagic stroke and hopefully provide more systematic and innovative research interests for the pathophysiology and therapeutic strategies of hemorrhagic stroke.

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

PubMed

Poznanski, Jaroslaw; Szczesny, Pawel; Pawlinski, Bartosz; Mazurek, Tomasz; Zielenkiewicz, Piotr; Gajewski, Zdzislaw; Paczek, Leszek

2017-09-01

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. 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. 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. 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.

Activation of somatosensory afferents elicit changes in vaginal blood flow and the urethrogenital reflex via autonomic efferents.

PubMed

Cai, R S; Alexander, M Sipski; Marson, L

2008-09-01

We examined the effects of pudendal sensory nerve stimulation and urethral distention on vaginal blood flow and the urethrogenital reflex, and the relationship between somatic and autonomic pathways regulating sexual responses. Distention of the urethra and stimulation of the pudendal sensory nerve were used to evoke changes in vaginal blood flow (laser Doppler perfusion monitoring) and pudendal motor nerve activity in anesthetized, spinally transected female rats. Bilateral cuts of either the pelvic or hypogastric nerve or both autonomic nerves were made, and blood flow and pudendal nerve responses were reexamined. Stimulation of the pudendal sensory nerve or urethral distention elicited consistent increases in vaginal blood flow and rhythmic firing of the pudendal motor nerve. Bilateral cuts of the pelvic plus hypogastric nerves significantly reduced vaginal blood flow responses without altering pudendal motor nerve responses. Pelvic nerve cuts also significantly reduced vaginal blood flow responses. In contrast, hypogastric nerve cuts did not significantly change vaginal blood flow. Bilateral cuts of the pudendal sensory nerve blocked pudendal motor nerve responses but stimulation of the central end evoked vaginal blood flow and pudendal motor nerve responses. Stimulation of the sensory branch of the pudendal nerve elicits vasodilatation of the vagina. The likely mechanism is via activation of spinal pathways that in turn activate pelvic nerve efferents to produced changes in vaginal blood flow. Climatic-like responses (firing of the pudendal motor nerve) occur in response to stimulation of the pudendal sensory nerve and do not require intact pelvic or hypogastric nerves.

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS)

NASA Technical Reports Server (NTRS)

Low, P. A.; Novak, V.; Spies, J. M.; Novak, P.; Petty, G. W.

1999-01-01

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Erythrocytes Are Oxygen-Sensing Regulators of the Cerebral Microcirculation.

PubMed

Wei, Helen Shinru; Kang, Hongyi; Rasheed, Izad-Yar Daniel; Zhou, Sitong; Lou, Nanhong; Gershteyn, Anna; McConnell, Evan Daniel; Wang, Yixuan; Richardson, Kristopher Emil; Palmer, Andre Francis; Xu, Chris; Wan, Jiandi; Nedergaard, Maiken

2016-08-17

Energy production in the brain depends almost exclusively on oxidative metabolism. Neurons have small energy reserves and require a continuous supply of oxygen (O2). It is therefore not surprising that one of the hallmarks of normal brain function is the tight coupling between cerebral blood flow and neuronal activity. Since capillaries are embedded in the O2-consuming neuropil, we have here examined whether activity-dependent dips in O2 tension drive capillary hyperemia. In vivo analyses showed that transient dips in tissue O2 tension elicit capillary hyperemia. Ex vivo experiments revealed that red blood cells (RBCs) themselves act as O2 sensors that autonomously regulate their own deformability and thereby flow velocity through capillaries in response to physiological decreases in O2 tension. This observation has broad implications for understanding how local changes in blood flow are coupled to synaptic transmission. Copyright © 2016 Elsevier Inc. All rights reserved.

The blood flow in the periodontal ligament regulated by the sympathetic and sensory nerves in the cat.

PubMed

Karita, K; Izumi, H; Tabata, T; Kuriwada, S; Sasano, T; Sanjo, D

1989-01-01

This study was carried out to investigate the nervous control of the blood flow in the periodontal ligament measured by laser Doppler flowmeter. Ten adult cats were anesthetized with pentobarbital sodium (initial dose of 30 mg/kg, i.v. and maintenance dose of 5 mg/kg, i.v.). After enucleating the left eye ball, the superior alveolar nerve was exposed. The bone overlying the labial aspect of the left maxillary canine tooth root was pared away until a transparent layer of bone was left covering the periodontal ligament. A laser light from a probe of the flowmeter fixed at the tooth was beamed through the thinned bone. Three different patterns of responses were observed following the electrical stimulation of the distal end of the cut superior alveolar nerve: an increasing, a decreasing and a biphasic change of blood flow. The application of capsaicin onto the superior alveolar nerve reduced the response of blood flow increase but had no effect on the response of blood flow decrease. On the other hand, the response of blood flow decrease was completely inhibited by the pretreatment with phentolamine while the response of blood flow increase was not affected. The present results suggest that blood flow in the periodontal ligament of cats is controlled by sympathetic alpha-adrenergic fibers for vasoconstriction and by sensory fibers for vasodilation.

The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand.

PubMed

Bekar, Lane K; Wei, Helen S; Nedergaard, Maiken

2012-12-01

Given the brain's uniquely high cell density and tissue oxygen levels bordering on hypoxia, the ability to rapidly and precisely match blood flow to constantly changing patterns in neural activity is an essential feature of cerebrovascular regulation. Locus coeruleus-norepinephrine (LC-NE) projections innervate the cerebral vasculature and can mediate vasoconstriction. However, function of the LC-mediated constriction in blood-flow regulation has never been addressed. Here, using intrinsic optical imaging coupled with an anesthesia regimen that only minimally interferes with LC activity, we show that NE enhances spatial and temporal aspects of functional hyperemia in the mouse somatosensory cortex. Increasing NE levels in the cortex using an α(2)-adrenergic receptor antagonist paradoxically reduces the extent of functional hyperemia while enhancing the surround blood-flow reduction. However, the NE-mediated vasoconstriction optimizes spatial and temporal focusing of the hyperemic response resulting in a sixfold decrease in the disparity between blood volume and oxygen demand. In addition, NE-mediated vasoconstriction accelerated redistribution to subsequently active regions, enhancing temporal synchronization of blood delivery. These observations show an important role for NE in optimizing neurovascular coupling. As LC neuron loss is prominent in Alzheimer and Parkinson diseases, the diminished ability to couple blood volume to oxygen demand may contribute to their pathogenesis.

Nitric oxide in red blood cell adaptation to hypoxia.

PubMed

Zhao, Yajin; Wang, Xiang; Noviana, Milody; Hou, Man

2018-06-01

Nitric oxide (NO) appears to be involved in virtually every aspect of cardiovascular biology. Most attention has been focused on the role of endothelial-derived NO in basal blood flow regulation by relaxing vascular smooth muscle; however, it is now known that NO derived from red blood cells (RBCs) plays a fundamental role in vascular homeostasis by enhancing oxygen (O2) release at the cellular and physiological level. Hypoxia is an often seen problem in diverse conditions; systemic adaptations to hypoxia permit people to adjust to the hypoxic environment at high altitudes and to disease processes. In addition to the cardiopulmonary and hematologic adaptations that support systemic O2 delivery in hypoxia, RBCs assist through newly described NO-based mechanisms, in line with their vital role in O2 transport and delivery. Furthermore, to increase the local blood flow in proportion to metabolic demand, NO regulates membrane mechanical properties thereby modulating RBC deformability and O2 carrying-releasing function. In this review article, we focus on the effect of NO bioactivity on RBC-based mechanisms that regulate blood flow and RBC deformability. RBC adaptations to hypoxia are summarized, with particular attention to NO-dependent S-nitrosylation of membrane proteins and hemoglobin (S-nitrosohemoglobin). The NO/S-nitrosylation/RBC vasoregulatory cascade contributes fundamentally to the molecular understanding of the role of NO in human adaptation to hypoxia and may inform novel therapeutic strategies.

Influence of cerebral blood vessel movements on the position of perivascular synapses.

PubMed

Urrecha, Miguel; Romero, Ignacio; DeFelipe, Javier; Merchán-Pérez, Angel

2017-01-01

Synaptic activity is regulated and limited by blood flow, which is controlled by blood vessel dilation and contraction. Traditionally, the study of neurovascular coupling has mainly focused on energy consumption and oxygen delivery. However, the mechanical changes that blood vessel movements induce in the surrounding tissue have not been considered. We have modeled the mechanical changes that movements of blood vessels cause in neighboring synapses. Our simulations indicate that synaptic densities increase or decrease during vascular dilation and contraction, respectively, near the blood vessel walls. This phenomenon may alter the concentration of neurotransmitters and vasoactive substances in the immediate vicinity of the vessel wall and thus may have an influence on local blood flow.

Neural Control of the Cardiovascular System in Space

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Pawelczyk, James A.; Zuckerman, Julie; Zhang, Rong; Fu, Qi; Iwasaki, Kenichi; Ray, Chet; Blomqvist, C. Gunnar; Lane, Lynda D.; Giller, Cole A.

2003-01-01

During the acute transition from lying supine to standing upright, a large volume of blood suddenly moves from the chest into the legs. To prevent fainting, the blood pressure control system senses this change immediately, and rapidly adjusts flow (by increasing heart rate) and resistance to flow (by constricting the blood vessels) to restore blood pressure and maintain brain blood flow. If this system is inadequate, the brain has a backup plan. Blood vessels in the brain can adjust their diameter to keep blood flow constant. If blood pressure drops, the brain blood vessels dilate; if blood pressure increases, the brain blood vessels constrict. This process, which is called autoregulation, allows the brain to maintain a steady stream of oxygen, even when blood pressure changes. We examined what changes in the blood pressure control system or cerebral autoregulation contribute to the blood pressure control problems seen after spaceflight. We asked: (1) does the adaptation to spaceflight cause an adaptation in the blood pressure control system that impairs the ability of the system to constrict blood vessels on return to Earth?; (2) if such a defect exists, could we pinpoint the neural pathways involved?; and (3) does cerebral autoregulation become abnormal during spaceflight, impairing the body s ability to maintain constant brain blood flow when standing upright on Earth? We stressed the blood pressure control system using lower body negative pressure, upright tilt, handgrip exercise, and cold stimulation of the hand. Standard cardiovascular parameters were measured along with sympathetic nerve activity (the nerve activity causing blood vessels to constrict) and brain blood flow. We confirmed that the primary cardiovascular effect of spaceflight was a postflight reduction in upright stroke volume (the amount of blood the heart pumps per beat). Heart rate increased appropriately for the reduction in stroke volume, thereby showing that changes in heart rate regulation alone cannot be responsible for orthostatic hypotension after spaceflight. All of the astronauts in our study had an increase in sympathetic nerve activity during upright tilting on Earth postflight. This increase was well calibrated for the reduction in stroke volume induced by the upright posture. The results obtained from stimulating the sympathetic nervous system using handgrip exercise or cold stress were also entirely normal during and after spaceflight. No astronaut had reduced cerebral blood flow during upright tilt, and cerebral autoregulation was normal or even enhanced inflight. These experiments show that the cardiovascular adaptation to spaceflight does not lead to a defect in the regulation of blood vessel constriction via sympathetic nerve activity. In addition, cerebral autoregulation is well-maintained. It is possible that despite the increased sympathetic nerve activity, blood vessels did not respond with a greater degree of constriction than occurred preflight, possibly uncovering a limit of vasoconstrictor reserve.

Numerical Models of Human Circulatory System under Altered Gravity: Brain Circulation

NASA Technical Reports Server (NTRS)

Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan; David, Tim

2003-01-01

A computational fluid dynamics (CFD) approach is presented to model the blood flow through the human circulatory system under altered gravity conditions. Models required for CFD simulation relevant to major hemodynamic issues are introduced such as non-Newtonian flow models governed by red blood cells, a model for arterial wall motion due to fluid-wall interactions, a vascular bed model for outflow boundary conditions, and a model for auto-regulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models are solved iteratively using the pseudocompressibility method and dual time stepping. Moving wall boundary conditions from the first-order fluid-wall interaction model are used to study the influence of arterial wall distensibility on flow patterns and wall shear stresses during the heart pulse. A vascular bed modeling utilizing the analogy with electric circuits is coupled with an auto-regulation algorithm for multiple outflow boundaries. For the treatment of complex geometry, a chimera overset grid technique is adopted to obtain connectivity between arterial branches. For code validation, computed results are compared with experimental data for steady and unsteady non-Newtonian flows. Good agreement is obtained for both cases. In sin-type Gravity Benchmark Problems, gravity source terms are added to the Navier-Stokes equations to study the effect of gravitational variation on the human circulatory system. This computational approach is then applied to localized blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other model using an anatomical data set. A three- dimensional anatomical Circle of Willis configuration is reconstructed from human-specific magnetic resonance images using an image segmentation method. The blood flow through these Circle of Willis models is simulated to provide means for studying gravitational effects on the brain circulation under auto-regulation.

Orthostatic blood pressure regulation predicts classroom effort in children.

PubMed

Carapetian, Stephanie; Siedlarz, Monika; Jackson, Sandra; Perlmuter, Lawrence C

2008-04-01

The increase in orthostatic systolic blood pressure associated with the shift in posture from lying to standing requires several compensatory mechanisms to ensure adequate cerebral perfusion. Decreased efficiency in the various mechanisms controlling orthostatic blood pressure regulation can result in dizziness, lightheadedness, and syncope. The degree of effectiveness of orthostatic systolic blood pressure regulation (OBPR) serves as a marker for a variety of problems including fatigue, depression, anxiety, reduced attention, impulsive behavior and reduced volition. In normal children, an insufficient increase in systolic blood pressure in response to upright posture is predictive of mild cognitive and affective problems. The present study examined orthostatic systolic blood pressure regulation in relation to yearlong teachers' evaluations of academic grades and effort in 7-11 year old children. Poorer systolic blood pressure regulation in response to orthostasis was associated with reduced levels of classroom effort, while academic grades were spared. Converging evidence from clinical as well as experimental studies suggests that the linkage between (OBPR) and effort may be partially mediated by sympathetic dysfunction, altered release of neurotransmitters, or reduced cerebral blood flow.

Uterine artery blood flow, fetal hypoxia and fetal growth

PubMed Central

Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

2015-01-01

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

Minimal role of nitric oxide in basal coronary flow regulation and cardiac energetics of blood-perfused isolated canine heart.

PubMed Central

Saeki, A; Recchia, F A; Senzaki, H; Kass, D A

1996-01-01

1. The role of nitric oxide (NO) in the regulation of basal coronary perfusion and ventricular chamber energetics was studied in isovolumetrically contracting isolated blood-perfused canine hearts. Hearts were cross-perfused by a donor animal prior to isolation, and chamber volume controlled by a servo-pump. Coronary sinus flow and arterial-coronary sinus oxygen difference were measured to determine energetic efficiency. 2. NO synthase (NOS) was competitively inhibited by NG-monomethyl-L-arginine (L-NMMA; 0.5 mg kg-1, intracoronary), resulting in a reduction of acetylcholine (50 micrograms min-1)-induced flow augmentation from 143 to 62% (P < 0.001). 3. NOS inhibition had no significant effect on basal coronary flow. Coronary pressure-flow relationships were determined at a constant cardiac workload by varying mean perfusion pressure between 20 and 150 mmHg. Neither the shape of the relationship, nor the low-pressure value at which flow regulation was substantially diminished were altered by NOS inhibition. 4. Myocardial efficiency was assessed by the relationship between myocardial oxygen consumption and total pressure-volume area (PVA), with cavity volume altered to generate varying PVAs. This relative load-independent measure of energetic efficiency was minimally altered by NOS inhibition. 5. These results contrast with isolated crystalloid-perfused heart experiments and suggest that in hearts with highly controlled ventricular loading and whole-blood perfusion, effects of basal NO production on coronary perfusion and left ventricular energetics are minimal. PMID:8866868

Neurovascular regulation in the ischemic brain.

PubMed

Jackman, Katherine; Iadecola, Costantino

2015-01-10

The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory.

Blood flow of the right and left submandibular gland during unilateral carotid artery occlusion in rat: role of nitric oxide.

PubMed

Vág, J; Hably, C; Fazekas, A; Bartha, J

1999-01-01

The aim of the present study was to investigate the effect of unilateral carotid artery occlusion on the blood flow of submandibular gland in anesthetized rats and identify the role of nitric oxide (NO) in blood flow changes after the artery occlusion. L-NAME (N omega-nitro-L-arginine-methyl-ester; 10 mg/kg/day, per os) dissolved in tap water was used to block nitric oxide synthase. Glandular blood flow was measured using Sapirstein's indicator (86Rb) distribution technique. In the control animals the blood flow of left (ligated side) submandibular gland was lower than in the right (unligated side) one (right: 76.4+/-15.4 ml/min/100 g, 64.1+/-13.4 ml/min/100 g, p<0.01). The blood flow of submandibular glands decreased in NOS blocked group versus control. The vascular resistance after L-NAME treatment was elevated (control: 11+/-2.3 R/kg, L-NAME: 17.5+/-4.1 R/kg, p<0.001). In L-NAME group the difference between blood flow value of the left and right submandibular gland was significantly lower than in the control group (control: -16%, NAME: -8%, p<0.01). The maintenance of the blood flow in the left submandibular gland during ligation of the left common carotid artery could be due to the good vascular anastomotic system at these regions and adaptation of the submandibular vessels to the decreased perfusion pressure. Nitric oxide may have a role in the regulation of blood flow tinder this condition.

Integrative regulation of human brain blood flow

PubMed Central

Willie, Christopher K; Tzeng, Yu-Chieh; Fisher, Joseph A; Ainslie, Philip N

2014-01-01

Herein, we review mechanisms regulating cerebral blood flow (CBF), with specific focus on humans. We revisit important concepts from the older literature and describe the interaction of various mechanisms of cerebrovascular control. We amalgamate this broad scope of information into a brief review, rather than detailing any one mechanism or area of research. The relationship between regulatory mechanisms is emphasized, but the following three broad categories of control are explicated: (1) the effect of blood gases and neuronal metabolism on CBF; (2) buffering of CBF with changes in blood pressure, termed cerebral autoregulation; and (3) the role of the autonomic nervous system in CBF regulation. With respect to these control mechanisms, we provide evidence against several canonized paradigms of CBF control. Specifically, we corroborate the following four key theses: (1) that cerebral autoregulation does not maintain constant perfusion through a mean arterial pressure range of 60–150 mmHg; (2) that there is important stimulatory synergism and regulatory interdependence of arterial blood gases and blood pressure on CBF regulation; (3) that cerebral autoregulation and cerebrovascular sensitivity to changes in arterial blood gases are not modulated solely at the pial arterioles; and (4) that neurogenic control of the cerebral vasculature is an important player in autoregulatory function and, crucially, acts to buffer surges in perfusion pressure. Finally, we summarize the state of our knowledge with respect to these areas, outline important gaps in the literature and suggest avenues for future research. PMID:24396059

The expression dynamics of mechanosensitive genes in extra-embryonic vasculature after heart starts to beat in chick embryo.

PubMed

Rajendran, Saranya; Sundaresan, Lakshmikirupa; Rajendran, Krithika; Selvaraj, Monica; Gupta, Ravi; Chatterjee, Suvro

2016-02-11

Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13. Therefore, we propose a novel in vivo model to study the flow experienced by developing endothelium. Using this model, we aimed to capture the transcriptome dynamics of the pre- and post-flow conditions. RNA was isolated from extra embryonic area vasculosa (EE-AV) pooled from three chick embryos between HH10-HH13 and RNA sequencing was performed. The whole transcriptome sequencing of chick identified up-regulation of some of the previously well-known mechanosensitive genes including NFR2, HAND1, CTGF and KDR. GO analyses of the up-regulated genes revealed enrichment of several biological processes including heart development, extracellular matrix organization, cell-matrix adhesion, cell migration, blood vessel development, patterning of blood vessels, collagen fibril organization. Genes encoding for gap junctions proteins which are involved in vascular remodeling and arterial-venous differentiation, and genes involved in cell-cell adhesion, and ECM interactions were significantly up-regulated. Validation of selected genes through semi quantitative PCR was performed. The study indicates that shear stress plays a major role in development. Through appropriate validation, this platform can serve as an in vivo model to study conditions of disturbed flow in pathology as well as normal flow during development.

Nonoxidative Glucose Consumption during Focal Physiologic Neural Activity

NASA Astrophysics Data System (ADS)

Fox, Peter T.; Raichle, Marcus E.; Mintun, Mark A.; Dence, Carmen

1988-07-01

Brain glucose uptake, oxygen metabolism, and blood flow in humans were measured with positron emission tomography, and a resting-state molar ratio of oxygen to glucose consumption of 4.1:1 was obtained. Physiological neural activity, however, increased glucose uptake and blood flow much more (51 and 50 percent, respectively) than oxygen consumption (5 percent) and produced a molar ratio for the increases of 0.4:1. Transient increases in neural activity cause a tissue uptake of glucose in excess of that consumed by oxidative metabolism, acutely consume much less energy than previously believed, and regulate local blood flow for purposes other than oxidative metabolism.

Effect of Flow on Gene Regulation in Smooth Muscle Cells and Macromolecular Transport Across Endothelial Cell Monolayers

NASA Technical Reports Server (NTRS)

McIntire, Larry V.; Wagner, John E.; Papadaki, Maria; Whitson, Peggy A.; Eskin, Suzanne G.

1996-01-01

Endothelial cells line all of the vessels of the circulatory system, providing a non-thrombogenic conduit for blood flow; they regulate many complex functions in the vasculature, such as coagulation, fibrinolysis, platelet aggregation, vessel tone and growth, and leukocyte traffic; and they form the principal barrier to transport of substances between the blood and the surrounding tissue space. The permeability of endothelial cell changes with environmental stimuli; shear stress, in particular, applied either in vivo, or in vitro, induces changes in protein expression and secretion of vasoactive factors by endothelial cells. The ability to study the effects of shear on the macromolecular permeability of the cerebral vasculature is particularly important, since in no other place is the barrier function of the endothelium more important than in the brain. The endothelial cells of this organ have developed special barrier properties that keep the cerebral system from experiencing any drastic change in composition; together with glial cells, they form the blood brain barrier (BBB). We have studied the effect of flow on bovine BBB using flow chambers and tissue culture systems.

Bang-bang Model for Regulation of Local Blood Flow

PubMed Central

Golub, Aleksander S.; Pittman, Roland N.

2013-01-01

The classical model of metabolic regulation of blood flow in muscle tissue implies the maintenance of basal tone in arterioles of resting muscle and their dilation in response to exercise and/or tissue hypoxia via the evoked production of vasodilator metabolites by myocytes. A century-long effort to identify specific metabolites responsible for explaining active and reactive hyperemia has not been successful. Furthermore, the metabolic theory is not compatible with new knowledge on the role of physiological radicals (e.g., nitric oxide, NO, and superoxide anion, O2−) in the regulation of microvascular tone. We propose a model of regulation in which muscle contraction and active hyperemia are considered the physiologically normal state. We employ the “bang-bang” or “on/off” regulatory model which makes use of a threshold and hysteresis; a float valve to control the water level in a tank is a common example of this type of regulation. Active bang-bang regulation comes into effect when the supply of oxygen and glucose exceeds the demand, leading to activation of membrane NADPH oxidase, release of O2− into the interstitial space and subsequent neutralization of the interstitial NO. Switching arterioles on/off when local blood flow crosses the threshold is realized by a local cell circuit with the properties of a bang-bang controller, determined by its threshold, hysteresis and dead-band. This model provides a clear and unambiguous interpretation of the mechanism to balance tissue demand with a sufficient supply of nutrients and oxygen. PMID:23441827

Influence of cerebral blood vessel movements on the position of perivascular synapses

PubMed Central

DeFelipe, Javier

2017-01-01

Synaptic activity is regulated and limited by blood flow, which is controlled by blood vessel dilation and contraction. Traditionally, the study of neurovascular coupling has mainly focused on energy consumption and oxygen delivery. However, the mechanical changes that blood vessel movements induce in the surrounding tissue have not been considered. We have modeled the mechanical changes that movements of blood vessels cause in neighboring synapses. Our simulations indicate that synaptic densities increase or decrease during vascular dilation and contraction, respectively, near the blood vessel walls. This phenomenon may alter the concentration of neurotransmitters and vasoactive substances in the immediate vicinity of the vessel wall and thus may have an influence on local blood flow. PMID:28199396

Blood temperature and perfusion to exercising and non-exercising human limbs.

PubMed

González-Alonso, José; Calbet, José A L; Boushel, Robert; Helge, Jørn W; Søndergaard, Hans; Munch-Andersen, Thor; van Hall, Gerrit; Mortensen, Stefan P; Secher, Niels H

2015-10-01

What is the central question of this study? Temperature-sensitive mechanisms are thought to contribute to blood-flow regulation, but the relationship between exercising and non-exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non-exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature- and metabolism-sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature-sensitive mechanisms may contribute to blood-flow regulation, but the influence of temperature on perfusion to exercising and non-exercising human limbs is not established. Blood temperature (TB ), blood flow and oxygen uptake (V̇O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher TB and limb V̇O2. Leg and arm vascular conductance during exercise compared with rest was related closely to TB (r(2) = 0.91; P < 0.05), plasma ATP (r(2) = 0.94; P < 0.05) and limb V̇O2 (r(2) = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in TB and limb V̇O2, whereas ABF, arm TB and V̇O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V̇O2. In 12 trained males, increases in femoral TB and LBF during incremental leg exercise were mirrored by similar pulmonary artery TB and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, TB and aerobic metabolism in exercising and non-exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and V̇O2 contribute to the regulation of limb perfusion through control of intravascular ATP. © 2015 The Authors Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Effect of aminophylline on hindlimb blood flow autoregulation during increased metabolism in dogs.

PubMed

Metting, P J; Weldy, D L; Ronau, T F; Britton, S L

1986-06-01

The contribution of adenosine to hindlimb blood flow autoregulation during treadmill exercise or the administration of 2,4-dinitrophenol (DNP) was evaluated in 9 conscious dogs by determining hindlimb vascular bed pressure-flow relationships in the presence and absence of the adenosine receptor site antagonist, aminophylline. Hindlimb pressure-flow relationships were obtained by measuring blood flow during stepwise reductions in perfusion pressure produced with an occlusion cuff located distal to a flow probe on the external iliac artery. The efficiency of autoregulation was quantitated by calculating the closed-loop gain of flow regulation (Gc) at each pressure decrement utilizing the equation Gc = 1 - (% delta flow/% delta pressure). A Gc of one represents perfect autoregulation of flow, and a Gc of zero is indicative of a rigid system. During exercise, Gc averaged 0.44 +/- 0.07. Aminophylline reduced the Gc during exercise to -0.07 +/- 0.06 (P less than 0.05). During DNP administration, Gc averaged 0.54 +/- 0.09 and declined to -0.09 +/- 0.10 in the presence of aminophylline (P less than 0.05). These results support the hypothesis that adenosine is a primary mediator of hindlimb blood flow autoregulation during conditions that increase hindlimb metabolism.

Interaction of the renin-angiotensin system and the renal nerves in the regulation of rat kidney function.

PubMed Central

Handa, R K; Johns, E J

1985-01-01

Stimulation of the renal sympathetic nerves in pentobarbitone anaesthetized rats achieved a 13% reduction in renal blood flow, did not change glomerular filtration rate, but reduced urine flow by 37%, absolute sodium excretion by 37%, and fractional sodium excretion by 34%. Following inhibition of converting enzyme with captopril (0.38 mmol kg-1 h-1), similar nerve stimulation reduced both renal blood flow and glomerular filtration rate by 16%, and although urine flow and absolute sodium excretion fell by 32 and 31%, respectively, the 18% fall in fractional sodium excretion was significantly less than that observed in the absence of captopril. Renal nerve stimulation at low levels, which did not change either renal blood flow or glomerular filtration rate, reduced urine flow, and absolute and fractional sodium excretions by 25, 26 and 23%, respectively. In animals receiving captopril at 0.38 mmol kg-1 h-1, low-level nerve stimulation caused small increases in glomerular filtration rate of 7% and urine flow of 12%, but did not change either absolute or fractional sodium excretions. At one-fifth the dose of captopril (0.076 mmol kg-1 h-1), low-level nerve stimulation did not change renal haemodynamics but decreased urine flow, and absolute and fractional sodium excretions by 10, 10 and 8%, respectively. These results showed that angiotensin II production was necessary for regulation of glomerular filtration rate in the face of modest neurally induced reductions in renal blood flow and was compatible with an intra-renal site of action of angiotensin II preferentially at the efferent arteriole. They also demonstrated that in the rat the action of the renal nerves to decrease sodium excretion was dependent on angiotensin II. PMID:3005558

Influence of the renal endothelin system on the autoregulation of renal blood flow in spontaneously hypertensive rats.

PubMed

Braun, C; Lang, C; Hocher, B; Gretz, N; van der Woude, F J; Rohmeiss, P

1997-01-01

The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.

The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet.

PubMed

Kim, Min Hee; Lee, Jongsung; Jung, Sehyun; Kim, Joo Wan; Shin, Jae-Ho; Lee, Hae-Jeung

2017-04-01

The present study investigated the effect of ginseng berry hot water extract (GBx) on blood flow via the regulation of lipid metabolites and blood coagulation in rats fed a high-fat diet (HFD). Sixty rats were divided into five groups in descending order of body weight. Except for the control group, the other four groups were fed a HFD containing 45% kcal from fat for 11 wk without GBx. GBx groups were then additionally treated by gastric gavage with GBx dissolved in distilled water at 50 (GBx 50) mg/kg, 100 (GBx 100) mg/kg, or 150 (GBx 150) mg/kg body weight for 6 wk along with the HFD. To investigate the effects of GBx on rats fed a HFD, biochemical metabolite, blood coagulation assay, and histological analysis were performed. In the experiments to measure the serum levels of leptin and apolipoprotein B/A, GBx treatment attenuated the HFD-induced increases in these metabolites ( p  < 0.05). Adiponectin and apolipoprotein E levels in GBx-treated groups were significantly higher than the HFD group. Prothrombin time and activated partial thromboplastin time were increased in all GBx-treated groups. In the GBx-treated groups, the serum levels of thromboxane A 2 and serotonin were decreased and concentrations of serum fibrinogen degradation products were increased ( p  < 0.05). Moreover, histomorphometric dyslipidemia-related atherosclerotic changes were significantly improved by treatment with GBx. These results suggest the possibility that GBx can ameliorate blood flow by decreasing intima-media thickness via the regulation of blood coagulation factors related to lipid metabolites in rats fed a HFD.

Functional expression of P2X4 receptor in capillary endothelial cells of the cochlear spiral ligament and its role in regulating the capillary diameter.

PubMed

Wu, T; Dai, M; Shi, X R; Jiang, Z G; Nuttall, A L

2011-07-01

The cochlear lateral wall generates the endocochlear potential (EP), which creates a driving force for the hair cell transduction current and is essential for normal hearing. Blood flow at the cochlear lateral wall is critically important for maintaining the EP. The vulnerability of the EP to hypoxia suggests that the blood flow in the cochlear lateral wall is dynamically and precisely regulated to meet the changing metabolic needs of the cochlear lateral wall. It has been reported that ATP, an important extracellular signaling molecule, plays an essential role in regulating cochlear blood flow. However, the cellular mechanism underlying ATP-induced regional blood flow changes has not been investigated. In the current study, we demonstrate that 1) the P2X4 receptor is expressed in endothelial cells (ECs) of spiral ligament (SL) capillaries. 2) ATP elicits a characteristic current through P2X4 on ECs in a dose-dependent manner (EC(50) = 0.16 mM). The ATP current has a reversal potential at ∼0 mV; is inhibited by 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD), LaCl(3), pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), and extracellular acidosis; and is less sensitive to α,β-methyleneadenosine 5'-triphosphate (α,β-MeATP) and 2'- and 3'-O-(4-benzoyl-benzoyl) adenosine 5'-triphosphate (BzATP). 3) ATP elicits a transient increase of intracellular Ca(2+) in ECs. 4) In accordance with the above in vitro findings, perilymphatic ATP (1 mM) caused dilation in SL capillaries in vivo by 11.5%. N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME), a nonselective inhibitor of nitric oxide synthase, or 5-BDBD, the specific P2X4 inhibitor, significantly blocked the dilation. These findings support our hypothesis that extracellular ATP regulates cochlear lateral blood flow through P2X4 activation in ECs.

Renal sympathetic nerve, blood flow, and epithelial transport responses to thermal stress.

PubMed

Wilson, Thad E

2017-05-01

Thermal stress is a profound sympathetic stress in humans; kidney responses involve altered renal sympathetic nerve activity (RSNA), renal blood flow, and renal epithelial transport. During mild cold stress, RSNA spectral power but not total activity is altered, renal blood flow is maintained or decreased, and epithelial transport is altered consistent with a sympathetic stress coupled with central volume loaded state. Hypothermia decreases RSNA, renal blood flow, and epithelial transport. During mild heat stress, RSNA is increased, renal blood flow is decreased, and epithelial transport is increased consistent with a sympathetic stress coupled with a central volume unloaded state. Hyperthermia extends these directional changes, until heat illness results. Because kidney responses are very difficult to study in humans in vivo, this review describes and qualitatively evaluates an in vivo human skin model of sympathetically regulated epithelial tissue compared to that of the nephron. This model utilizes skin responses to thermal stress, involving 1) increased skin sympathetic nerve activity (SSNA), decreased skin blood flow, and suppressed eccrine epithelial transport during cold stress; and 2) increased SSNA, skin blood flow, and eccrine epithelial transport during heat stress. This model appears to mimic aspects of the renal responses. Investigations of skin responses, which parallel certain renal responses, may aid understanding of epithelial-sympathetic nervous system interactions during cold and heat stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

PubMed Central

Tykocki, Nathan R.; Boerman, Erika M.; Jackson, William F.

2017-01-01

Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes. PMID:28333380

Diagnostic blood-flow monitoring during therapeutic interventions using color Doppler optical coherence tomography

NASA Astrophysics Data System (ADS)

Yazdanfar, Siavash; Kulkarni, Manish D.; Wong, Richard C. K.; Sivak, Michael J., Jr.; Willis, Joseph; Barton, Jennifer K.; Welch, Ashley J.; Izatt, Joseph A.

1998-04-01

A recently developed modality for blood flow measurement holds high promise in the management of bleeding ulcers. Color Doppler optical coherence tomography (CDOCT) uses low- coherence interferometry and digital signal processing to obtain precise localization of tissue microstructure simultaneous with bi-directional quantitation of blood flow. We discuss CDOCT as a diagnostic tool in the management of bleeding gastrointestinal lesions. Common treatments for bleeding ulcers include local injection of a vasoconstrictor, coagulation of blood via thermal contact or laser treatment, and necrosis of surrounding tissue with a sclerosant. We implemented these procedures in a rat dorsal skin flap model, and acquired CDOCT images before and after treatment. In these studies, CDOCT succeeded in identifying cessation of flow before it could be determined visually. Hence, we demonstrate the diagnostic capabilities of CDOCT in the regulation of bleeding in micron-scale vessels.

What determines blood vessel structure? Genetic prespecification vs. hemodynamics.

PubMed

Jones, Elizabeth A V; le Noble, Ferdinand; Eichmann, Anne

2006-12-01

Vascular network remodeling, angiogenesis, and arteriogenesis play an important role in the pathophysiology of ischemic cardiovascular diseases and cancer. Based on recent studies of vascular network development in the embryo, several novel aspects to angiogenesis have been identified as crucial to generate a functional vascular network. These aspects include specification of arterial and venous identity in vessels and network patterning. In early embryogenesis, vessel identity and positioning are genetically hardwired and involve neural guidance genes expressed in the vascular system. We demonstrated that, during later stages of embryogenesis, blood flow plays a crucial role in regulating vessel identity and network remodeling. The flow-evoked remodeling process is dynamic and involves a high degree of vessel plasticity. The open question in the field is how genetically predetermined processes in vessel identity and patterning balance with the contribution of blood flow in shaping a functional vascular architecture. Although blood flow is essential, it remains unclear to what extent flow is able to act on the developing cardiovascular system. There is significant evidence that mechanical forces created by flowing blood are biologically active within the embryo and that the level of mechanical forces and the type of flow patterns present in the embryo are able to affect gene expression. Here, we highlight the pivotal role for blood flow and physical forces in shaping the cardiovascular system.

Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

NASA Technical Reports Server (NTRS)

Glenny, R. W.; Robertson, H. T.; Hlastala, M. P.

2000-01-01

To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

A framework for the modeling of gut blood flow regulation and postprandial hyperaemia

PubMed Central

Jeays, Adam David; Lawford, Patricia Veronica; Gillott, Richard; Spencer, Paul A; Bardhan, Karna Dev; Hose, David Rodney

2007-01-01

After a meal the activity of the gut increases markedly as digestion takes place. Associated with this increase in activity is an increase in blood flow, which has been shown to be dependent on factors such as caloric content and constitution of the meal. Much qualitative work has been carried out regarding mechanisms for the presence of food in a section of gut producing increased blood flow to that section, but there are still many aspects of this process that are not fully understood. In this paper we briefly review current knowledge on several relevant areas relating to gut blood flow, focusing on quantitative data where available and highlighting areas where further research is needed. We then present new data on the effect of feeding on flow in the superior mesenteric artery. Finally, we describe a framework for combining this data to produce a single model describing the mechanisms involved in postprandial hyperaemia. For a section of the model, where appropriate data are available, preliminary results are presented. PMID:17457971

Prostaglandin control of renal circulation in the unanesthetized dog and baboon

NASA Technical Reports Server (NTRS)

Swain, J. A.; Vatner, S. F.; Heyndrickx, G. R.; Boettcher, D. H.

1975-01-01

Effects of indomethacin and meclofenamate, inhibitors of prostaglandin synthesis, were evaluated in the regulation of renal blood flow in conscious and anesthetized dogs and in tranquilized baboons, instrumented with arterial pressure catheters and renal blood flow probes. Indomethacin, 10 mg/kg, did not alter renal blood flow or resistance significantly in the conscious dog. In the anesthetized dog, however, indomethacin caused a reduction in renal blood flow and an elevation of renal vascular resistance. Meclofenamate, 4 mg/kg, reduced renal flow and increased renal vascular resistance in conscious dogs. In conscious dogs and tranquilized primates, indomethacin and meclofenamate reduced the reactive hyperemia in the renal bed. Methoxamine and angiotensin II infused in graded doses induced significantly greater renal vasoconstriction in conscious dogs in the presence of indomethacin. Thus, in the conscious animal, prostaglandins appear to play only a minor part in the control of renal circulation at rest, but they are of greater importance in mediating the renal responses to reactive hyperemia and to vasoconstriction.

Mechanisms of Acupuncture Therapy for Cerebral Ischemia: an Evidence-Based Review of Clinical and Animal Studies on Cerebral Ischemia.

PubMed

Zhu, Wen; Ye, Yang; Liu, Yi; Wang, Xue-Rui; Shi, Guang-Xia; Zhang, Shuai; Liu, Cun-Zhi

2017-12-01

Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.

Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy

PubMed Central

Park, Yang-Gyu; Choi, Jawun; Jung, Hye-Kang; Song, In Kyu; Shin, Yongwhan; Park, Sang-Youel; Seol, Jae-Won

2017-01-01

Early pregnancy is characterized by an increase in the blood volume of the uterus for embryonic development, thereby exerting fluid shear stress (FSS) on the vascular walls. The uterus experiences vascular remodeling to accommodate the increased blood flow. The blood flow-induced FSS elevates the expression of vascular endothelial growth factors (VEGFs) and their receptors, and regulates vascular remodeling through the activation of VEGF receptor-3 (VEGFR-3). However, the mechanisms responsible for FSS-induced VEGFR-3 expression in the uterus during pregnancy are unclear. In this study, we demonstrate that vascular remodeling in the uterus during pregnancy is regulated by FSS-induced VEGFR-3 expression. We examined the association between VEGFR-3 and FSS through in vivo and in vitro experiments. In vivo experiments revealed VEGFR-3 expression in the CD31-positive region of the uterus of pregnant mice; VEGF-C (ligand for VEGFR-3) was undetected in the uterus. These results confirmed that VEGFR-3 expression in the endometrium is independent of its ligand. In vitro studies experiments revealed that FSS induced morphological changes and increased VEGFR-3 expression in human uterine microvascular endothelial cells. Thus, VEGFR-3 activation by FSS is associated with vascular remodeling to allow increased blood flow in the uterus during pregnancy. PMID:28849193

Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

PubMed

Li, Xu; Mao, Xiao-Bo; Hei, Ren-Yi; Zhang, Zhi-Bin; Wen, Li-Ting; Zhang, Peng-Zhi; Qiu, Jian-Hua; Qiao, Li

2011-01-01

A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL). The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2)S) has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2)S in cochlear blood flow regulation and noise protection. The gene and protein expression of the H(2)S synthetase cystathionine-γ-lyase (CSE) in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP), NaHS or DL-propargylglycine (PPG) were locally administered. Local sodium hydrosulfide (NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR), cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage of OHC loss occurred in the PPG group. Our results suggest that H(2)S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension.

PubMed

Novak, Vera; Yang, Albert C C; Lepicovsky, Lukas; Goldberger, Ary L; Lipsitz, Lewis A; Peng, Chung-Kang

2004-10-25

This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals. We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 +/- 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound. A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts. In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.

Amino Acids That Centrally Influence Blood Pressure and Regional Blood Flow in Conscious Rats

PubMed Central

Takemoto, Yumi

2012-01-01

Functional roles of amino acids have increasingly become the focus of research. This paper summarizes amino acids that influence cardiovascular system via the brain of conscious rats. This paper firstly describes why amino acids are selected and outlines how the brain regulates blood pressure and regional blood flow. This section includes a concise history of amino acid neurotransmitters in cardiovascular research and summarizes brain areas where chemical stimulations produce blood pressure changes mainly in anesthetized animals. This is followed by comments about findings regarding several newly examined amino acids with intracisternal stimulation in conscious rats that produce changes in blood pressure. The same pressor or depressor response to central amino acid stimulations can be produced by distinct mechanisms at central and peripheral levels, which will be briefly explained. Thereafter, cardiovascular actions of some of amino acids at the mechanism level will be discussed based upon findings of pharmacological and regional blood flow measurements. Several examined amino acids in addition to the established neurotransmitter amino acids appear to differentially activate brain structures to produce changes in blood pressure and regional blood flows. They may have physiological roles in the healthy brain, but pathological roles in the brain with cerebral vascular diseases such as stroke where the blood-brain barrier is broken. PMID:22690328

Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling.

PubMed

Landskroner-Eiger, Shira; Qiu, Cong; Perrotta, Paola; Siragusa, Mauro; Lee, Monica Y; Ulrich, Victoria; Luciano, Amelia K; Zhuang, Zhen W; Corti, Federico; Simons, Michael; Montgomery, Rusty L; Wu, Dianqing; Yu, Jun; Sessa, William C

2015-10-13

The contribution of endothelial-derived miR-17∼92 to ischemia-induced arteriogenesis has not been investigated in an in vivo model. In the present study, we demonstrate a critical role for the endothelial-derived miR-17∼92 cluster in shaping physiological and ischemia-triggered arteriogenesis. Endothelial-specific deletion of miR-17∼92 results in an increase in collateral density limbs and hearts and in ischemic limbs compared with control mice, and consequently improves blood flow recovery. Individual cluster components positively or negatively regulate endothelial cell (EC) functions in vitro, and, remarkably, ECs lacking the cluster spontaneously form cords in a manner rescued by miR-17a, -18a, and -19a. Using both in vitro and in vivo analyses, we identified FZD4 and LRP6 as targets of miR-19a/b. Both of these targets were up-regulated in 17∼92 KO ECs compared with control ECs, and both were shown to be targeted by miR-19 using luciferase assays. We demonstrate that miR-19a negatively regulates FZD4, its coreceptor LRP6, and WNT signaling, and that antagonism of miR-19a/b in aged mice improves blood flow recovery after ischemia and reduces repression of these targets. Collectively, these data provide insights into miRNA regulation of arterialization and highlight the importance of vascular WNT signaling in maintaining arterial blood flow.

Special functions of valve organs of blood-sucking female mosquitoes

NASA Astrophysics Data System (ADS)

Kim, Boheum; Lee, Sangjoon

2010-11-01

Food-feeding insects usually have valve organs to regulate the sucking flow effectively. Female mosquitoes sucking lots of blood instantaneously have a unique valve system between two pumping organs located in their head. The valve system seems to prevent reverse flow and to grind granule particles such as red blood cells. To understand the functional characteristics of this valve organ in detail, the volumetric flow rate passing through the valves and their interaction with the two-pumps need to be investigated. However, it is very difficult to observe the dynamic behaviors of pumping organs and valve system. In this study, the dynamic motions of valve organs of blood-sucking female mosquitoes were observed under in vivo condition using synchrotron X-ray micro imaging technique. X-ray micro computed tomography was also employed to examine the three-dimensional internal structure of the blood pumping system including valve organs.

A comparison of blood nitric oxide metabolites and hemoglobin functional properties among diving mammals.

PubMed

Fago, Angela; Parraga, Daniel Garcia; Petersen, Elin E; Kristensen, Niels; Giouri, Lea; Jensen, Frank B

2017-03-01

The ability of marine mammals to hunt prey at depth is known to rely on enhanced oxygen stores and on selective distribution of blood flow, but the molecular mechanisms regulating blood flow and oxygen transport remain unresolved. To investigate the molecular mechanisms that may be important in regulating blood flow, we measured concentration of nitrite and S-nitrosothiols (SNO), two metabolites of the vasodilator nitric oxide (NO), in the blood of 5 species of marine mammals differing in their dive duration: bottlenose dolphin, South American sea lion, harbor seal, walrus and beluga whale. We also examined oxygen affinity, sensitivity to 2,3-diphosphoglycerate (DPG) and nitrite reductase activity of the hemoglobin (Hb) to search for possible adaptive variations in these functional properties. We found levels of plasma and red blood cells nitrite similar to those reported for terrestrial mammals, but unusually high concentrations of red blood cell SNO in bottlenose dolphin, walrus and beluga whale, suggesting enhanced SNO-dependent signaling in these species. Purified Hbs showed similar functional properties in terms of oxygen affinity and sensitivity to DPG, indicating that reported large variations in blood oxygen affinity among diving mammals likely derive from phenotypic variations in red blood cell DPG levels. The nitrite reductase activities of the Hbs were overall slightly higher than that of human Hb, with the Hb of beluga whale, capable of longest dives, having the highest activity. Taken together, these results underscore adaptive variations in circulatory NO metabolism in diving mammals but not in the oxygenation properties of the Hb. Copyright © 2016 Elsevier Inc. All rights reserved.

Partial Resuscitative Endovascular Balloon Occlusion of the Aorta (P-REBOA) in a Pig Model (Sus scrofa) with ongoing Resuscitation

DTIC Science & Technology

2016-01-08

occlusion, regulated flow provided perfusion to capillary beds. Following 70 minutes of partial aortic occlusion, damage control surgery and whole blood ... renal function, and were weaned from aortic occlusion more rapidly. CONCLUSIONS: P-REBOA is capable of limiting exsanguination while providing blood ...resuscitation was performed and all animals were survived to 360 minutes. Animals that tolerated distal flow had decreased levels of lactate, preserved

Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic abnormalities

NASA Technical Reports Server (NTRS)

Papadaki, M.; Eskin, S. G.; Ruef, J.; Runge, M. S.; McIntire, L. V.

1999-01-01

Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.

Comparative study between microvascular tone regulation and rheological properties of blood in patients with type 2 diabetes mellitus.

PubMed

Antonova, N; Tsiberkin, K; Podtaev, S; Paskova, V; Velcheva, I; Chaushev, N

2016-01-01

The aim of the study is to investigate the changes of the skin blood flow responses to cold stress in patients with diabetes mellitus type 2 through wavelet analysis of the peripheral skin temperature oscillations and to estimate their relationship with the blood viscosity values. The amplitudes of the skin temperature pulsations (ASTP) were monitored by "Microtest" device ("FM-Diagnostics", Russia); the whole blood viscosity and the shear stresses were measured by Contraves LS30 viscometer (Switzerland) at a steady flow in 9 healthy subjects and in 30 patients with type 2 diabetes mellitus. Power law and Herschel-Bulkley (HB) equations were applied to describe the blood rheology. Both models include consistency (k) and flow index (m), and the HB also gives the yield stress (τ0). The Spearman rank correlations between these parameters and the ASTP in the frequency ranges, corresponding to the myogenic, neurogenic and endothelial mechanisms of the microcirculation tone regulation were calculated. The ASTP values decreased when the blood viscosity increased. The correlation analysis revealed good ASTP-m (r > 0.5) and ASTP-k (r < -0.5) relationships in the endothelial range, while the ASTP-τ0 correlation was weaker (r≈-0.4). These correlations became lower for the ASTP during the cold stress. The results prompt manifestation of endothelial dysfunction in patients with type 2 diabetes.

βENaC acts as a mechanosensor in renal vascular smooth muscle cells that contributes to renal myogenic blood flow regulation, protection from renal injury and hypertension.

PubMed

Drummond, Heather A; Stec, David E

2015-06-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechanodependent response in small renal arteries and arterioles. The response is initiated by vascular smooth muscle cell (VSMC) stretch due to an increase in intraluminal pressure and leads to vasoconstriction. The myogenic response has two important roles as a mechanism of local blood flow autoregulation and protection against systemic blood pressure-induced microvascular damage. However, the molecular mechanisms underlying initiation of myogenic response are unresolved. Although several molecules have been considered initiators of the response, our laboratory has focused on the role of degenerin proteins because of their strong evolutionary link to mechanosensing in the nematode. Our laboratory has addressed the hypothesis that certain degenerin proteins act as mechanosensors in VSMCs. This article discusses the importance of a specific degenerin protein, β Epithelial Na + Channel (βENaC), in pressure-induced vasoconstriction, renal blood flow and susceptibility to renal injury. We propose that loss of the renal myogenic constrictor response delays the correction of renal blood flow that occurs with fluctuations in systemic pressure, which allows pressure swings to be transmitted to the microvasculature, thus increasing the susceptibility to renal injury and hypertension. The role of βENaC in myogenic regulation is independent of tubular βENaC and thus represents a non-tubular role for βENaC in renal-cardiovascular homeostasis.

Cellular and molecular mechanisms regulating vascular tone. Part 1: basic mechanisms controlling cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone.

PubMed

Akata, Takashi

2007-01-01

General anesthetics cause hemodynamic instability and alter blood flow to various organs. There is mounting evidence that most general anesthetics, at clinical concentrations, influence a wide variety of cellular and molecular mechanisms regulating the contractile state of vascular smooth muscle cells (i.e., vascular tone). In addition, in current anesthetic practice, various types of vasoactive agents are often used to control vascular reactivity and to sustain tissue blood flow in high-risk surgical patients with impaired vital organ function and/or hemodynamic instability. Understanding the physiological mechanisms involved in the regulation of vascular tone thus would be beneficial for anesthesiologists. This review, in two parts, provides an overview of current knowledge about the cellular and molecular mechanisms regulating vascular tone-i.e., targets for general anesthetics, as well as for vasoactive drugs that are used in intraoperative circulatory management. This first part of the two-part review focuses on basic mechanisms regulating cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone.

A review of the etiology, associated comorbidities, and treatment of orthostatic hypotension.

PubMed

Perlmuter, Lawrence C; Sarda, Garima; Casavant, Vanessa; Mosnaim, Aron D

2013-01-01

The magnitude of increase in systolic blood pressure in response to the shift from supine to upright posture is considered to reflect the adequacy of orthostatic regulation. Orthostatic integrity is largely maintained by the interaction between the skeletal muscle pump, neurovascular compensation, neurohumoral effects, and cerebral blood flow regulation. Various physiological states and disease conditions may disrupt these mechanisms as seen in vasovagal syncope, dysautonomic orthostatic intolerance, and postural orthostatic tachycardia syndrome. Orthostatic hypotension (OH) and decreased cerebral blood flow are strongly related. Even subclinical OH has been associated to different degrees with impaired cognitive function, decreased effort, reduced motivation, increased hopelessness, and signs of attention-deficit hyperactivity disorder and dementia, diabetes mellitus, and Parkinson disease. Furthermore, subclinical levels of inadequate blood pressure regulation in response to orthostasis have been linked to increased depression and anxiety and intergenerational behavioral sequelae between mother and child. Identifying causes of subclinical and clinical OH is critical in improving quality of life for both children and older adults. A better understanding of the underlying causes responsible for the etiology of OH could lead to a rational design of novel effective therapeutic regimens for the treatment of this condition and associated comorbidities.

Tumor Endothelial Cells

PubMed Central

Dudley, Andrew C.

2012-01-01

The vascular endothelium is a dynamic cellular “organ” that controls passage of nutrients into tissues, maintains the flow of blood, and regulates the trafficking of leukocytes. In tumors, factors such as hypoxia and chronic growth factor stimulation result in endothelial dysfunction. For example, tumor blood vessels have irregular diameters; they are fragile, leaky, and blood flow is abnormal. There is now good evidence that these abnormalities in the tumor endothelium contribute to tumor growth and metastasis. Thus, determining the biological basis underlying these abnormalities is critical for understanding the pathophysiology of tumor progression and facilitating the design and delivery of effective antiangiogenic therapies. PMID:22393533

Rheoencephalography (REG) as a Non-Invasive Monitoring Alternative for the Assessment of Brain Blood Flow

DTIC Science & Technology

2004-09-01

arterial pressure of 40 mmHg, and then held there until experimental intervention, resuscitation, decompensation or death occurred. The experiment was...regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals...Rheoencephalography (REG) as a Non-Invasive Monitoring Alternative for the Assessment of Brain Blood Flow P3 - 12 RTO-MP-HFM-109 experiments we

Blood temperature and perfusion to exercising and non‐exercising human limbs

PubMed Central

Calbet, José A. L.; Boushel, Robert; Helge, Jørn W.; Søndergaard, Hans; Munch‐Andersen, Thor; van Hall, Gerrit; Mortensen, Stefan P.; Secher, Niels H.

2015-01-01

New Findings What is the central question of this study? Temperature‐sensitive mechanisms are thought to contribute to blood‐flow regulation, but the relationship between exercising and non‐exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non‐exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature‐ and metabolism‐sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature‐sensitive mechanisms may contribute to blood‐flow regulation, but the influence of temperature on perfusion to exercising and non‐exercising human limbs is not established. Blood temperature (T B), blood flow and oxygen uptake (V˙O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher T B and limb V˙O2. Leg and arm vascular conductance during exercise compared with rest was related closely to T B (r 2 = 0.91; P < 0.05), plasma ATP (r 2 = 0.94; P < 0.05) and limb V˙O2 (r 2 = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in T B and limb V˙O2, whereas ABF, arm T B and V˙O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V˙O2. In 12 trained males, increases in femoral T B and LBF during incremental leg exercise were mirrored by similar pulmonary artery T B and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, T B and aerobic metabolism in exercising and non‐exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and V˙O2 contribute to the regulation of limb perfusion through control of intravascular ATP. PMID:26268717

Blood Vessel Adaptation with Fluctuations in Capillary Flow Distribution

PubMed Central

Hu, Dan; Cai, David; Rangan, Aaditya V.

2012-01-01

Throughout the life of animals and human beings, blood vessel systems are continuously adapting their structures – the diameter of vessel lumina, the thickness of vessel walls, and the number of micro-vessels – to meet the changing metabolic demand of the tissue. The competition between an ever decreasing tendency of luminal diameters and an increasing stimulus from the wall shear stress plays a key role in the adaptation of luminal diameters. However, it has been shown in previous studies that the adaptation dynamics based only on these two effects is unstable. In this work, we propose a minimal adaptation model of vessel luminal diameters, in which we take into account the effects of metabolic flow regulation in addition to wall shear stresses and the decreasing tendency of luminal diameters. In particular, we study the role, in the adaptation process, of fluctuations in capillary flow distribution which is an important means of metabolic flow regulation. The fluctuation in the flow of a capillary group is idealized as a switch between two states, i.e., an open-state and a close-state. Using this model, we show that the adaptation of blood vessel system driven by wall shear stress can be efficiently stabilized when the open time ratio responds sensitively to capillary flows. As micro-vessel rarefaction is observed in our simulations with a uniformly decreased open time ratio of capillary flows, our results point to a possible origin of micro-vessel rarefaction, which is believed to induce hypertension. PMID:23029014

The Effects of Protein Regulators on the Vascular Remodeling of Japanese Quail Chorioallantoic Membrane

NASA Technical Reports Server (NTRS)

Deshpande, Arati

2004-01-01

Contributing to NASA s mission, the Microgravity Fluid Physics research program conducts experiments to promote space exploration and improvement of processes and products on Earth. One of the projects through this program deals with the affect of regulators on vascular remodeling and angiogenesis. This project is being led by Dr. Patricia Parsons-Wingerter. To perform the experiments, protein regulators are tested on the chorioallantoic membrane (CAM) of the Japanese quail embryos. The different types of regulators used can be broken down into two major groups of stimulators, and inhibitors. Stimulators increase the rate of blood vessel growth and inhibitors decrease of blood vessel growth. The specified regulator proteins include thrombospondin 1 (TSP-1) and a novel vessel tortuosity factor (TF), these are just the ones used in this specific experiment; other various protein regulators can also be used. The novel vessel tortuosity factor (TF) is a special kind of stimulator because it stimulates vessel tortuosity and curvature, rather than actual blood vessel growth. These regulators are being tested on Japanese quail embryos. The Japanese quail embryos naturally form a chorioallantoic membrane (CAM) from which blood flow, vascular remodeling, and angiogenesis can be observed. Chorioallantoic membranes are also easier to use because they are two dimensional when mounted onto a slide for examination. The analysis of the affect of the regulators on the CAM can be studied through PIVPROC; the program is used to analyze the altered blood flow in response to application of TF. Regulators are being thoroughly studied because cardiovascular alterations are the second highest, NASA-defined, risk categories in human space exploration. This research done on the quail is extending to even more projects that will be done on lab animals such as mice and also in human clinical studies like the diabetic retina. Not only will this research be beneficial to further space exploration, but it will also help life here on Earth. The higher understanding of the formation of blood vessels can also help further research in health problems such as diabetes and heart disease.

Modification of activity-dependent increases in cerebellar blood flow by extracellular potassium in anaesthetized rats

PubMed Central

Caesar, Kirsten; Akgören, Nuran; Mathiesen, Claus; Lauritzen, Martin

1999-01-01

The hypothesis that potassium ions mediate activity-dependent increases of cerebral blood flow was examined in rat cerebellar cortex using ion-selective microelectrodes and laser-Doppler flowmetry. Increases of cerebellar blood flow (CeBF) and extracellular potassium concentration ([K+]o) were evoked by stimulation of parallel fibres and climbing fibres, and by microinjection of KCl into the cortex. For parallel fibre stimulation, there was a maximal increase in [K+]o to 6.3 ± 0.5 mm and in CeBF of 122 ± 11%. Climbing fibre stimulation gave a maximal increase in [K+]o to 4.4 ± 0.2 mm and in CeBF of 157 ± 20%. This indicates different maxima for [K+]o and CeBF, dependent on the afferent system activated. [K+]o and CeBF responses evoked by parallel or climbing fibre stimulation increased rapidly at the onset of stimulation, but exhibited different time courses during the remainder of the stimulation period and during return to baseline. Microinjections of KCl into the cortex increased [K+]o to levels comparable to those evoked by parallel fibre stimulation. The corresponding CeBF increases were the same as, or smaller than, for parallel fibre stimulation, and much smaller than for climbing fibre stimulation. This suggests that mediators other than [K+]o are important for activity-dependent cerebral blood flow increases. The present study showed that increased [K+]o is involved in CeBF regulation in the parallel fibre system, but is of limited importance for CeBF regulation in the climbing fibre system. The hypothesis that K+ is a major mediator of activity-dependent blood flow increases is probably not generally applicable to all brain regions and all types of neuronal stimulation. PMID:10517819

Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension

PubMed Central

Novak, Vera; Yang, Albert CC; Lepicovsky, Lukas; Goldberger, Ary L; Lipsitz, Lewis A; Peng, Chung-Kang

2004-01-01

Background This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals. Methods We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 ± 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound. Results A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts. Conclusion In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure. PMID:15504235

The role of blood flow distribution in the regulation of cerebral oxygen availability in fetal growth restriction.

PubMed

Luria, Oded; Bar, Jacob; Kovo, Michal; Malinger, Gustavo; Golan, Abraham; Barnea, Ofer

2012-04-01

Fetal growth restriction (FGR) elicits hemodynamic compensatory mechanisms in the fetal circulation. These mechanisms are complex and their effect on the cerebral oxygen availability is not fully understood. To quantify the contribution of each compensatory mechanism to the fetal cerebral oxygen availability, a mathematical model of the fetal circulation was developed. The model was based on cardiac-output distribution in the fetal circulation. The compensatory mechanisms of FGR were simulated and their effects on cerebral oxygen availability were analyzed. The mathematical analysis included the effects of cerebral vasodilation, placental resistance to blood flow, degree of blood shunting by the ductus venosus and the effect of maternal-originated placental insufficiency. The model indicated a unimodal dependency between placental blood flow and cerebral oxygen availability. Optimal cerebral oxygen availability was achieved when the placental blood flow was mildly reduced compared to the normal flow. This optimal ratio was found to increase as the hypoxic state of FGR worsens. The model indicated that cerebral oxygen availability is increasingly dependent on the cardiac output distribution as the fetus gains weight. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Netrin-1 controls sympathetic arterial innervation.

PubMed

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J C; Kennedy, Timothy E; Zhuang, Zhen; Simons, Michael; Levy, Bernard I; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-07-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

Netrin-1 controls sympathetic arterial innervation

PubMed Central

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J.C.; Kennedy, Timothy E.; Zhuang, Zhen; Simons, Michael; Levy, Bernard I.; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-01-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type–specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs. PMID:24937433

Neurovascular Regulation in the Ischemic Brain

PubMed Central

Jackman, Katherine

2015-01-01

Abstract Significance: The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. Recent Advances and Critical Issues: The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Future Directions: Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory. Antioxid. Redox Signal. 22, 149–160. PMID:24328757

Modulation of radial blood flow during Braille character discrimination task.

PubMed

Murata, Jun; Matsukawa, K; Komine, H; Tsuchimochi, H

2012-03-01

Human hands are excellent in performing sensory and motor function. We have hypothesized that blood flow of the hand is dynamically regulated by sympathetic outflow during concentrated finger perception. To identify this hypothesis, we measured radial blood flow (RBF), radial vascular conductance (RVC), heart rate (HR), and arterial blood pressure (AP) during Braille reading performed under the blind condition in nine healthy subjects. The subjects were instructed to read a flat plate with raised letters (Braille reading) for 30 s by the forefinger, and to touch a blank plate as control for the Braille discrimination procedure. HR and AP slightly increased during Braille reading but remained unchanged during the touching of the blank plate. RBF and RVC were reduced during the Braille character discrimination task (decreased by -46% and -49%, respectively). Furthermore, the changes in RBF and RVC were much greater during the Braille character discrimination task than during the touching of the blank plate (decreased by -20% and -20%, respectively). These results have suggested that the distribution of blood flow to the hand is modulated via sympathetic nerve activity during concentrated finger perception.

Red Cell Physiology and Signaling Relevant to the Critical Care Setting

PubMed Central

Said, Ahmed; Rogers, Stephen; Doctor, Allan

2015-01-01

Purpose of Review Oxygen (O2) delivery, the maintenance of which is fundamental to supporting those with critical illness, is a function of blood O2 content and flow. Here, we review red blood cell (RBC) physiology relevant to disordered O2 delivery in the critically ill. Recent Findings Flow (rather then content) is the focus of O2 delivery regulation: O2 content is relatively fixed, whereas flow fluctuates by several orders of magnitude. Thus, blood flow volume and distribution vary to maintain coupling between O2 delivery and demand. The trapping, processing and delivery of nitric oxide (NO) by RBCs has emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We will review conventional RBC physiology influencing O2 delivery (O2 affinity & rheology) and introduce a new paradigm for O2 delivery homeostasis based on coordinated gas transport and vascular signaling by RBCs. Summary By coordinating vascular signaling in a fashion that links O2 and NO flux, RBCs couple vessel caliber (and thus blood flow) to O2 need in tissue. Malfunction of this signaling system is implicated in a wide array of pathophysiologies and may be explanatory for the dysoxia frequently encountered in the critical care setting. PMID:25888155

Red cell physiology and signaling relevant to the critical care setting.

PubMed

Said, Ahmed; Rogers, Stephen; Doctor, Allan

2015-06-01

Oxygen (O2) delivery, the maintenance of which is fundamental to supporting those with critical illness, is a function of blood O2 content and flow. Here, we review red blood cell (RBC) physiology relevant to disordered O2 delivery in the critically ill. Flow (rather than content) is the focus of O2 delivery regulation. O2 content is relatively fixed, whereas flow fluctuates by several orders of magnitude. Thus, blood flow volume and distribution vary to maintain coupling between O2 delivery and demand. The trapping, processing and delivery of nitric oxide (NO) by RBCs has emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We will review conventional RBC physiology that influences O2 delivery (O2 affinity & rheology) and introduce a new paradigm for O2 delivery homeostasis based on coordinated gas transport and vascular signaling by RBCs. By coordinating vascular signaling in a fashion that links O2 and NO flux, RBCs couple vessel caliber (and thus blood flow) to O2 need in tissue. Malfunction of this signaling system is implicated in a wide array of pathophysiologies and may be explanatory for the dysoxia frequently encountered in the critical care setting.

Regulation of blood flow distribution in skeletal muscle: role of erythrocyte-released ATP.

PubMed

Ellsworth, Mary L; Sprague, Randy S

2012-10-15

The maintenance of adequate tissue O(2) levels in skeletal muscle is vital for normal physiology and requires a well regulated and appropriately distributed convective O(2) supply. Inherent in this fundamental physiological process is the requirement for a mechanism which both senses tissue O(2) need and locally adjusts flow to appropriately meet that need. Over the past several years we and others have suggested that, in skeletal muscle, O(2) carrying erythrocytes participate in the regulation of total blood flow and its distribution by releasing ATP. Importantly, the release of this vasoactive molecule must be both rapid and well controlled if it is to serve an important physiological role. Here we provide insights into three distinct regulated signalling pathways within the erythrocyte that are activated by exposure to reduced O(2) tension or in response to binding of agonists to the prostacyclin or β-adrenergic receptors. Although much has been learned about the role of the erythrocyte in perfusion of skeletal muscle, much remains to be understood. However, what is clear is that the long established passive carrier of O(2) also contributes to the regulation of the distribution of microvascular perfusion in skeletal muscle by virtue of its capacity to release ATP.

The Renal Renin-Angiotensin System

ERIC Educational Resources Information Center

Harrison-Bernard, Lisa M.

2009-01-01

The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and…

The Regulation of Blood Flow and Metabolism in Adipose Tissue: Evidence for a Role of Adenosine

DTIC Science & Technology

1984-10-17

inhibitor of lipolysis. The adminiatra- tion of norepinephrine cauaed an increase in adipoae tlsaue blood flow and lipolyaia. In the presence of nicotinic...hemodynamic parameters recorded. A second intravenous infusion (0.1 to 0.2 ml/ nln ) of saline was then begun and continued for 30 minutes. At 90 minutes...substrate (1.0 mM). Tissue aliquots were incubated for 30 and 60 minutes, in the presence and absence of AOPCP, a 5’-nucleotidase inhibitor (Burger

Factors associated with blood oxygen partial pressure and carbon dioxide partial pressure regulation during respiratory extracorporeal membrane oxygenation support: data from a swine model.

PubMed

Park, Marcelo; Mendes, Pedro Vitale; Costa, Eduardo Leite Vieira; Barbosa, Edzangela Vasconcelos Santos; Hirota, Adriana Sayuri; Azevedo, Luciano Cesar Pontes

2016-01-01

The aim of this study was to explore the factors associated with blood oxygen partial pressure and carbon dioxide partial pressure. The factors associated with oxygen - and carbon dioxide regulation were investigated in an apneic pig model under veno-venous extracorporeal membrane oxygenation support. A predefined sequence of blood and sweep flows was tested. Oxygenation was mainly associated with extracorporeal membrane oxygenation blood flow (beta coefficient = 0.036mmHg/mL/min), cardiac output (beta coefficient = -11.970mmHg/L/min) and pulmonary shunting (beta coefficient = -0.232mmHg/%). Furthermore, the initial oxygen partial pressure and carbon dioxide partial pressure measurements were also associated with oxygenation, with beta coefficients of 0.160 and 0.442mmHg/mmHg, respectively. Carbon dioxide partial pressure was associated with cardiac output (beta coefficient = 3.578mmHg/L/min), sweep gas flow (beta coefficient = -2.635mmHg/L/min), temperature (beta coefficient = 4.514mmHg/ºC), initial pH (beta coefficient = -66.065mmHg/0.01 unit) and hemoglobin (beta coefficient = 6.635mmHg/g/dL). In conclusion, elevations in blood and sweep gas flows in an apneic veno-venous extracorporeal membrane oxygenation model resulted in an increase in oxygen partial pressure and a reduction in carbon dioxide partial pressure 2, respectively. Furthermore, without the possibility of causal inference, oxygen partial pressure was negatively associated with pulmonary shunting and cardiac output, and carbon dioxide partial pressure was positively associated with cardiac output, core temperature and initial hemoglobin.

Differential Interaction of Platelet-Derived Extracellular Vesicles with Leukocyte Subsets in Human Whole Blood.

PubMed

Weiss, René; Gröger, Marion; Rauscher, Sabine; Fendl, Birgit; Eichhorn, Tanja; Fischer, Michael B; Spittler, Andreas; Weber, Viktoria

2018-04-26

Secretion and exchange of biomolecules via extracellular vesicles (EVs) are crucial mechanisms in intercellular communication, and the roles of EVs in infection, inflammation, or thrombosis have been increasingly recognized. EVs have emerged as central players in immune regulation and can enhance or suppress the immune response, depending on the state of donor and recipient cells. We investigated the interaction of blood cell-derived EVs with leukocyte subpopulations (monocytes and their subsets, granulocytes, B cells, T cells, and NK cells) directly in whole blood using a combination of flow cytometry, imaging flow cytometry, cell sorting, and high resolution confocal microscopy. Platelet-derived EVs constituted the majority of circulating EVs and were preferentially associated with granulocytes and monocytes, while they scarcely interacted with lymphocytes. Further flow cytometric differentiation of monocyte subsets provided clear indications for a preferential association of platelet-derived EVs with intermediate (CD14 ++ CD16 + ) monocytes in whole blood.

Properties permitting the renal cortex to be the oxygen sensor for the release of erythropoietin: clinical implications.

PubMed

Halperin, Mitchell L; Cheema-Dhadli, Surinder; Lin, Shih-Hua; Kamel, Kamel S

2006-09-01

The PO2 at this site where erythropoietin release is regulated should vary only when the hemoglobin concentration changes in capillary blood. The kidney cortex is an ideal location for this O2 sensor for four reasons. First, it extracts a small proportion of the oxygen that is delivered in each liter of blood; this makes the PO2 signal easier to recognize. Second, there is a constant ratio of the work performed (consumption of O2) to the renal blood flow rate (delivery of O2). Third, the high renal blood flow rate improves diffusion of O2 from capillaries to this O2 receptor. Fourth, a high renal cortical PCO2 prevents an additional shift of the O2:hemoglobin dissociation curve by other factors from being a confounding variable. This suggests that the GFR and the renal blood flow rate should be examined in patients with unexplained anemia or erythrocytosis.

Nitric Oxide-Mediated Coronary Flow Regulation in Patients with Coronary Artery Disease: Recent Advances

PubMed Central

Toda, Noboru; Tanabe, Shinichi; Nakanishi, Sadanobu

2011-01-01

Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles in the regulation of coronary blood flow through vasodilatation and decreased vascular resistance, and in inhibition of platelet aggregation and adhesion, leading to the prevention of coronary circulatory failure, thrombosis, and atherosclerosis. Endothelial function is impaired by several pathogenic factors including smoking, chronic alcohol intake, hypercholesterolemia, obesity, hyperglycemia, and hypertension. The mechanisms underlying endothelial dysfunction include reduced NO synthase (NOS) expression and activity, decreased NO bioavailability, and increased production of oxygen radicals and endogenous NOS inhibitors. Atrial fibrillation appears to be a risk factor for endothelial dysfunction. Endothelial dysfunction is an important predictor of coronary artery disease (CAD) in humans. Penile erectile dysfunction, associated with impaired bioavailability of NO produced by eNOS and neuronal NOS, is also considered to be highly predictive of ischemic heart disease. There is evidence suggesting an important role of nitrergic innervation in coronary blood flow regulation. Prophylactic and therapeutic measures to eliminate pathogenic factors inducing endothelial and nitrergic nerve dysfunction would be quite important in preventing the genesis and development of CAD. PMID:22942627

The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism

PubMed Central

Jespersen, Sune N; Østergaard, Leif

2012-01-01

Normal brain function depends critically on moment-to-moment regulation of oxygen supply by the bloodstream to meet changing metabolic needs. Neurovascular coupling, a range of mechanisms that converge on arterioles to adjust local cerebral blood flow (CBF), represents our current framework for understanding this regulation. We modeled the combined effects of CBF and capillary transit time heterogeneity (CTTH) on the maximum oxygen extraction fraction (OEFmax) and metabolic rate of oxygen that can biophysically be supported, for a given tissue oxygen tension. Red blood cell velocity recordings in rat brain support close hemodynamic–metabolic coupling by means of CBF and CTTH across a range of physiological conditions. The CTTH reduction improves tissue oxygenation by counteracting inherent reductions in OEFmax as CBF increases, and seemingly secures sufficient oxygenation during episodes of hyperemia resulting from cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF, both lower oxygen tension and CTTH may secure tissue oxygenation. Our model predicts that disturbed capillary flows may cause a condition of malignant CTTH, in which states of higher CBF display lower oxygen availability. We propose that conditions with altered capillary morphology, such as amyloid, diabetic or hypertensive microangiopathy, and ischemia–reperfusion, may disturb CTTH and thereby flow-metabolism coupling and cerebral oxygen metabolism. PMID:22044867

Cancer Cell Glycocalyx Mediates Mechanostransduction and Flow-Regulated Invasion

PubMed Central

Qazi, Henry; Palomino, Rocio; Shi, Zhong-Dong; Munn, Lance L.; Tarbell, John M.

2014-01-01

Mammalian cells are covered by a surface proteoglycan (glycocalyx) layer, and it is known that blood vessel-lining endothelial cells use the glycocalyx to sense and transduce the shearing forces of blood flow into intracellular signals. Tumor cells in vivo are exposed to forces from interstitial fluid flow that may affect metastatic potential but are not reproduced by most in vitro cell motility assays. We hypothesized that glycocalyx-mediated mechanotransduction of interstitial flow shear stress is an un-recognized factor that can significantly enhance metastatic cell motility and play a role in augmentation of invasion. Involvement of MMP levels, cell adhesion molecules (CD44, α3 integrin), and glycocalyx components (heparan sulfate and hyaluronan) were investigated in a cell/collagen gel suspension model designed to mimic the interstitial flow microenvironment. Physiologic levels of flow upregulated MMP levels and enhanced the motility of metastatic cells. Blocking the flow-enhanced expression of MMP actvity or adhesion molecules (CD44 and integrins) resulted in blocking the flow-enhanced migratory activity. The presence of a glycocalyx-like layer was verified around tumor cells, and the degradation of this layer by hyaluronidase and heparinase blocked the flow-regulated invasion. This study shows for the first time that interstitial flow enhancement of metastatic cell motility can be mediated by the cell surface glycocalyx – a potential target for therapeutics. PMID:24077103

Renal and femoral venous blood flows are regulated by different mechanisms dependent on α-adrenergic receptor subtypes and nitric oxide in anesthetized rats.

PubMed

Fioretti, Alexandre C; Ogihara, Cristiana A; Cafarchio, Eduardo M; Venancio, Daniel P; de Almeida, Roberto Lopes; Antonio, Bruno B; Sato, Monica A

2017-12-01

Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injection of different doses of vasoactive drugs which act in arterial vascular beds. Anesthetized adult male Wistar rats underwent to right femoral artery and vein cannulation for hemodynamic recordings and infusion of drugs. Doppler flow probes were placed around the left renal artery and vein, and left femoral artery and vein to evaluate the changes in flood flow. Phenylephrine (PHE) injection (α 1 -adrenergic receptor agonist) elicited vasoconstriction in all arteries and veins. Intravenous prazosin (PZS) (1mg/kg, α 1 -adrenergic receptor blocker) caused renal artery vasodilation, but not in the other beds. Vasoconstrictor effect of PHE was abolished by PZS in all vascular beds, except in femoral vein. Phentolamine (PTL) injection (1mg/kg, α 1 /α 2 -adrenergic receptor blocker) produced renal artery vasodilation with no change in other beds. After PTL, the vasoconstriction evoked by PHE was abolished in all vascular beds. Sodium Nitroprusside (SNP), a nitric oxide donor, elicited vasodilation in all beds, and after PTL but not post PZS injection, SNP enhanced the vasodilatory effect in femoral vein. Our findings suggest that the vasoconstriction in renal and femoral veins is mediated by different subtypes of α-adrenoceptors. The nitric oxide-dependent vasodilation in femoral vein enhances when α 2 -adrenoceptors are not under stimulation, but not in the other vascular beds investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

Blood flow and microgravity

NASA Astrophysics Data System (ADS)

Bureau, Lionel; Coupier, Gwennou; Dubois, Frank; Duperray, Alain; Farutin, Alexander; Minetti, Christophe; Misbah, Chaouqi; Podgorski, Thomas; Tsvirkun, Daria; Vysokikh, Mikhail

2017-01-01

The absence of gravity during space flight can alter cardio-vascular functions partially due to reduced physical activity. This affects the overall hemodynamics, and in particular the level of shear stresses to which blood vessels are submitted. Long-term exposure to space environment is thus susceptible to induce vascular remodeling through a mechanotransduction cascade that couples vessel shape and function with the mechanical cues exerted by the circulating cells on the vessel walls. Central to such processes, the glycocalyx - i.e. the micron-thick layer of biomacromolecules that lines the lumen of blood vessels and is directly exposed to blood flow - is a major actor in the regulation of biochemical and mechanical interactions. We discuss in this article several experiments performed under microgravity, such as the determination of lift force and collective motion in blood flow, and some preliminary results obtained in artificial microfluidic circuits functionalized with endothelium that offer interesting perspectives for the study of the interactions between blood and endothelium in healthy condition as well as by mimicking the degradation of glycocalyx caused by long space missions. A direct comparison between experiments and simulations is discussed. xml:lang="fr"

Vascular reactivity in arterioles from normal and alloxan-diabetic mice: studies on single perfused islets.

PubMed

Lai, En Yin; Jansson, Leif; Patzak, Andreas; Persson, A Erik G

2007-01-01

Pancreatic islets possess an autonomous mechanism of blood flow regulation, independent of that of the exocrine pancreas. To study islet vascular regulation without confounding effects of the exocrine blood vessels, we have developed a technique enabling us to isolate single pancreatic islets and then to perfuse them using their endogenous vasculature for distribution of the medium. This made it possible to directly study the vascular reactivity of islet arterioles to different substances. We confirmed that control of islet blood flow is mainly located at the precapillary level. As expected, administration of angiotensin II and l-nitro-arginine methyl ester contracted islet arterioles, whereas nitric oxide and adenosine dilated them. d-glucose, the main insulin secretagogue, had a selective dilating effect on smooth muscle in islet arterioles but not in glomerular afferent arterioles. The response to glucose was amplified in islet arterioles from diabetic animals, indicating enhanced islet blood perfusion in diabetes. This newly developed technique for perfusing isolated pancreatic islets will provide new insights into islet perfusion control and its possible contributions to the pathogenesis of type 2 diabetes.

Alpha adrenergic regulation of celiac blood flow and plasma catecholamine response during acute heat stress in fed cockerels.

PubMed

Bottje, W G; Harrison, P C

1986-08-01

Hubbard cockerels with chronically implanted electromagnetic blood flow probes on the celiac artery were used to establish a relationship between changes in postprandial celiac mean blood flow (MBF) and plasma catecholamines during a acute heat exposure. Five min after the elevation of ambient temperature from 25 to 37 C, there were concomitant reductions (P less than .05) in celiac MBF, norepinephrine (NE), and heart rate (HR). After 50 min of heat stress, rectal temperature (Tr), respiratory rate (RR), plasma epinephrine (E), and celiac vascular resistance (CVR) were significantly greater (P less than .05) than preheat stress thermoneutral control values. During the thermoneutral recovery period, all parameters returned to values comparable to preheat exposure control with the exception of NE, which tended (P less than .1) to remain lower. To determine the role of the sympathetic nervous system in regulating postprandial celiac MBF during acute heat exposure, chronically instrumented cockerels were infused with phenoxybenzamine, an alpha-adrenergic receptor-blocking agent. Alpha-receptor blockade attenuated both postprandial intestinal hyperemia under thermoneutral conditions as well as the heat-induced reduction of postprandial celiac MBF. The results of these studies implicate the sympathetic nervous system in the regulation of postprandial celiac MBF in heat-stressed cockerels and indicate a possible alpha-adrenergic-mediated mechanism involved in postprandial intestinal hyperemia.

Differential effects of aging and exercise on intra-abdominal adipose arteriolar function and blood flow regulation

PubMed Central

Davis, Robert T.; Stabley, John N.; Dominguez, James M.; Ramsey, Michael W.; McCullough, Danielle J.; Lesniewski, Lisa A.; Delp, Michael D.

2013-01-01

Adipose tissue (AT), which typically comprises an increased percentage of body mass with advancing age, receives a large proportion of resting cardiac output. During exercise, an old age-associated inability to increase vascular resistance within the intra-abdominal AT may compromise the ability of the cardiovascular system to redistribute blood flow to the active musculature, contributing to the decline in exercise capacity observed in this population. We tested the hypotheses that 1) there would be an elevated perfusion of AT during exercise with old age that was associated with diminished vasoconstrictor responses of adipose-resistance arteries, and 2) chronic exercise training would mitigate the age-associated alterations in AT blood flow and vascular function. Young (6 mo; n = 40) and old (24 mo; n = 28) male Fischer 344 rats were divided into young sedentary (YSed), old sedentary (OSed), young exercise trained (YET), or old exercise trained (OET) groups, where training consisted of 10-12 wk of treadmill exercise. In vivo blood flow at rest and during exercise and in vitro α-adrenergic and myogenic vasoconstrictor responses in resistance arteries from AT were measured in all groups. In response to exercise, there was a directionally opposite change in AT blood flow in the OSed group (∼150% increase) and YSed (∼55% decrease) vs. resting values. Both α-adrenergic and myogenic vasoconstriction were diminished in OSed vs. YSed AT-resistance arteries. Exercise training resulted in a similar AT hyperemic response between age groups during exercise (YET, 9.9 ± 0.5 ml·min−1·100−1 g; OET, 8.1 ± 0.9 ml·min−1·100−1 g) and was associated with enhanced myogenic and α-adrenergic vasoconstriction of AT-resistance arteries from the OET group relative to OSed. These results indicate that there is an inability to increase vascular resistance in AT during exercise with old age, due, in part, to a diminished vasoconstriction of AT arteries. Furthermore, the results indicate that exercise training can augment vasoconstriction of AT arteries and mitigate age-related alterations in the regulation of AT blood flow during exercise. PMID:23349454

Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease.

PubMed

Toda, Noboru; Okamura, Tomio

2016-08-01

Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic) nerves and nitric oxide (NO) liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS)/neuronal NOS (nNOS) inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD). Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Virchow-Robin space and aquaporin-4: new insights on an old friend.

PubMed

Nakada, Tsutomu

2014-08-28

Recent studies have strongly indicated that the classic circulation model of cerebrospinal fluid (CSF) is no longer valid. The production of CSF is not only dependent on the choroid plexus but also on water flux in the peri-capillary (Virchow Robin) space. Historically, CSF flow through the Virchow Robin space is known as interstitial flow, the physiological significance of which is now fully understood. This article briefly reviews the modern concept of CSF physiology and the Virchow-Robin space, in particular its functionalities critical for central nervous system neural activities. Water influx into the Virchow Robin space and, hence, interstitial flow is regulated by aquaporin-4 (AQP-4) localized in the endfeet of astrocytes, connecting the intracellular cytosolic fluid space of astrocytes and the Virchow Robin space. Interstitial flow has a functionality equivalent to systemic lymphatics, on which clearance of β-amyloid is strongly dependent. Autoregulation of brain blood flow serves to maintain a constant inner capillary fluid pressure, allowing fluid pressure of the Virchow Robin space to regulate regional cerebral blood flow (rCBF) based on AQP-4 gating. Excess heat produced by neural activities is effectively removed from the area of activation by increased rCBF by closing AQP-4 channels. This neural flow coupling (NFC) is likely mediated by heat generated proton channels.

Intrinsic Cholinergic Mechanisms Regulating Cerebral Blood Flow as a Target for Organophosphate Action

DTIC Science & Technology

1988-10-01

autoregulation, render the cerebral circulation dependent upon systemic circulation exposing brain to ischernic damage or edema in shock or stress...Thus, sharp reductions of arterial pressure, as might occur in hemorrhagic or traumatic shock, will render the cerebral circulation vulnerable to...autoregulated range, rendering local areas of the brain vulnerable to cerebral edema and breakdown of the blood brain barrier. -2- 8. Cerebral blood

Hormonal regulation of fluid and electrolyte metabolism in zero-g and bedrest

NASA Technical Reports Server (NTRS)

Vernikos, Joan

1991-01-01

The study of man in spaceflight has consistently indicated changes in fluid and electrolyte balance. Sodium (Na), Potassium (K), and Calcium (Ca) excretion are increased, accompanied by changes in the levels and responsiveness of adrenal hormones and the sympathetic nervous system (SNS). These hormones and neurohumors are critical to the regulation of blood pressure, blood flow, and blood volume. The primary objectives of the research conducted under this task have been to use -6 deg head down bedrest (BR) as the analog to spaceflight, to determine the long term changes in these systems, their relationship to orthostatic tolerance, and to develop and test suitable countermeasures.

[Individual typological peculiarities of system blood flow, physical capacity for work and cardiac activity regulation in patients with different resistance to periodontal diseases].

PubMed

Bragin, A V

2008-01-01

From position of typological variability of physiological individuality concept-functional constitution types - the principle of organism integrity was substantiated for stomatological pathology. There were isolated typical and specific reactions of cardiac-vessel system in patients with different resistance to periodontal diseases. Each functional type - patients with different levels of usual motion activity - had their own physiological peculiarities of parameters of system blood flow, physical capacity for work and cardiac activity regulation, that determined individual typological organism reaction in cases of maxillo-facial system pathology. The received data gives the objective base for physiological approach to single out the extreme variants of norm for forming risk contingent and groups of resistant people to periodontal diseases.

Mechanical stress regulates transport in a compliant 3D model of the blood-brain barrier.

PubMed

Partyka, Paul P; Godsey, George A; Galie, John R; Kosciuk, Mary C; Acharya, Nimish K; Nagele, Robert G; Galie, Peter A

2017-01-01

Transport of fluid and solutes is tightly controlled within the brain, where vasculature exhibits a blood-brain barrier and there is no organized lymphatic network facilitating waste transport from the interstitial space. Here, using a compliant, three-dimensional co-culture model of the blood-brain barrier, we show that mechanical stimuli exerted by blood flow mediate both the permeability of the endothelial barrier and waste transport along the basement membrane. Application of both shear stress and cyclic strain facilitates tight junction formation in the endothelial monolayer, with and without the presence of astrocyte endfeet in the surrounding matrix. We use both dextran perfusion and TEER measurements to assess the initiation and maintenance of the endothelial barrier, and microparticle image velocimetry to characterize the fluid dynamics within the in vitro vessels. Application of pulsatile flow to the in vitro vessels induces pulsatile strain to the vascular wall, providing an opportunity to investigate stretch-induced transport along the basement membrane. We find that a pulsatile wave speed of approximately 1 mm/s with Womersley number of 0.004 facilitates retrograde transport of high molecular weight dextran along the basement membrane between the basal endothelium and surrounding astrocytes. Together, these findings indicate that the mechanical stress exerted by blood flow is an important regulator of transport both across and along the walls of cerebral microvasculature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factors associated with blood oxygen partial pressure and carbon dioxide partial pressure regulation during respiratory extracorporeal membrane oxygenation support: data from a swine model

PubMed Central

Park, Marcelo; Mendes, Pedro Vitale; Costa, Eduardo Leite Vieira; Barbosa, Edzangela Vasconcelos Santos; Hirota, Adriana Sayuri; Azevedo, Luciano Cesar Pontes

2016-01-01

Objective The aim of this study was to explore the factors associated with blood oxygen partial pressure and carbon dioxide partial pressure. Methods The factors associated with oxygen - and carbon dioxide regulation were investigated in an apneic pig model under veno-venous extracorporeal membrane oxygenation support. A predefined sequence of blood and sweep flows was tested. Results Oxygenation was mainly associated with extracorporeal membrane oxygenation blood flow (beta coefficient = 0.036mmHg/mL/min), cardiac output (beta coefficient = -11.970mmHg/L/min) and pulmonary shunting (beta coefficient = -0.232mmHg/%). Furthermore, the initial oxygen partial pressure and carbon dioxide partial pressure measurements were also associated with oxygenation, with beta coefficients of 0.160 and 0.442mmHg/mmHg, respectively. Carbon dioxide partial pressure was associated with cardiac output (beta coefficient = 3.578mmHg/L/min), sweep gas flow (beta coefficient = -2.635mmHg/L/min), temperature (beta coefficient = 4.514mmHg/ºC), initial pH (beta coefficient = -66.065mmHg/0.01 unit) and hemoglobin (beta coefficient = 6.635mmHg/g/dL). Conclusion In conclusion, elevations in blood and sweep gas flows in an apneic veno-venous extracorporeal membrane oxygenation model resulted in an increase in oxygen partial pressure and a reduction in carbon dioxide partial pressure 2, respectively. Furthermore, without the possibility of causal inference, oxygen partial pressure was negatively associated with pulmonary shunting and cardiac output, and carbon dioxide partial pressure was positively associated with cardiac output, core temperature and initial hemoglobin. PMID:27096671

[Acid-base equilibrium and the brain].

PubMed

Rabary, O; Boussofara, M; Grimaud, D

1994-01-01

In physiological conditions, the regulation of acid-base balance in brain maintains a noteworthy stability of cerebral pH. During systemic metabolic acid-base imbalances cerebral pH is well controlled as the blood/brain barrier is slowly and poorly permeable to electrolytes (HCO3- and H+). Cerebral pH is regulated by a modulation of the respiratory drive, triggered by the early alterations of interstitial fluid pH, close to medullary chemoreceptors. As blood/brain barrier is highly permeable to Co2, CSF pH is corrected in a few hours, even in case of severe metabolic acidosis and alkalosis. Conversely, during ventilatory acidosis and alkalosis the cerebral pH varies in the same direction and in the same range than blood pH. Therefore, the brain is better protected against metabolic than ventilatory acid-base imbalances. Ventilatory acidosis and alkalosis are able to impair cerebral blood flow and brain activity through interstitial pH alterations. During respiratory acidosis, [HCO3-] increases in extracellular fluids to control cerebral pH by two main ways: a carbonic anhydrase activation at the blood/brain and blood/CSF barriers level and an increase in chloride shift in glial cells (HCO3- exchanged for Cl-). During respiratory alkalosis, [HCO3-] decreases in extracellular fluids by the opposite changes in HCO3- transport and by an increase in lactic acid synthesis by cerebral cells. The treatment of metabolic acidosis with bicarbonates may induce a cerebral acidosis and worsen a cerebral oedema during ketoacidosis. Moderate hypocapnia carried out to treat intracranial hypertension is mainly effective when cerebral blood flow is high and vascular CO2 reactivity maintained. Hypocapnia may restore an altered cerebral blood flow autoregulation. Instrumental hypocapnia requires a control of cerebral perfusion pressure and cerebral arteriovenous difference for oxygen, to select patients for whom this kind of treatment may be of benefit, to choose the optimal level of hypocapnia and to avoid any deleterious effect. If hypocapnia is maintained over several days, an adaptation of CSF pH may limit the therapeutic effect on the cerebral blood flow and the intracranial pressure.

DIRECTIONAL FLUID TRANSPORT ACROSS ORGAN-BLOOD BARRIERS: PHYSIOLOGY AND CELL BIOLOGY

PubMed Central

Caceres, Paulo S.; Benedicto, Ignacio; Lehmann, Guillermo L.; Rodriguez-Boulan, Enrique J.

2018-01-01

Directional fluid flow is an essential process for embryo development as well as for organ and organism homeostasis. Here, we review the diverse structure of various organ-blood barriers, the driving forces, transporters and polarity mechanisms that regulate fluid transport across them, focusing on kidney-, eye- and brain-blood barriers. We end by discussing how cross-talk between barrier epithelial and endothelial cells, perivascular cells and basement membrane signaling contribute to generate and maintain organ-blood barriers. PMID:28003183

Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

PubMed

Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

2015-06-01

Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

The endocrine system in space flight

NASA Astrophysics Data System (ADS)

Leach, C. S.; Johnson, P. C.; Cintron, N. M.

Hormones are important effectors of the body's response to microgravity in the areas of fluid and electrolyte metabolism, erythropoiesis, and calcium metabolism. For many years antidiuretic hormone, cortisol and aldosterone have been considered the hormones most important for regulation of body fluid volume and blood levels of electrolytes, but they cannot account totally for losses of fluid and electrolytes during space flight. We have now measured atrial natriuretic factor (ANF), a hormone recently shown to regulate sodium and water excretion, in blood specimens obtained during flight. After 30 or 42 h of weightlessness, mean ANF was elevated. After 175 or 180 h, ANF had decreased by 59%, and it changed little between that time and soon after landing. There is probably an increase in ANF early inflight associated with the fluid shift, followed by a compensatory decrease in blood volume. Increased renal blood flow may cause the later ANF decrease. Erythropoietin (Ep), a hormone involved in the control of red blood cell production, was measured in blood samples taken during the first Spacelab mission and was significantly decreased on the second day of flight, suggesting also an increase in renal blood flow. Spacelab-2 investigators report that the active vitamin D metabolite 1α, 25-dihydroxyvitamin D 3 increased early in the flight, indicating that a stimulus for increased bone resorption occurs by 30 h after launch.

Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels

PubMed Central

Yu, Jun; Bergaya, Sonia; Murata, Takahisa; Alp, Ilkay F.; Bauer, Michael P.; Lin, Michelle I.; Drab, Marek; Kurzchalia, Teymuras V.; Stan, Radu V.; Sessa, William C.

2006-01-01

Caveolae in endothelial cells have been implicated as plasma membrane microdomains that sense or transduce hemodynamic changes into biochemical signals that regulate vascular function. Therefore we compared long- and short-term flow-mediated mechanotransduction in vessels from WT mice, caveolin-1 knockout (Cav-1 KO) mice, and Cav-1 KO mice reconstituted with a transgene expressing Cav-1 specifically in endothelial cells (Cav-1 RC mice). Arterial remodeling during chronic changes in flow and shear stress were initially examined in these mice. Ligation of the left external carotid for 14 days to lower blood flow in the common carotid artery reduced the lumen diameter of carotid arteries from WT and Cav-1 RC mice. In Cav-1 KO mice, the decrease in blood flow did not reduce the lumen diameter but paradoxically increased wall thickness and cellular proliferation. In addition, in isolated pressurized carotid arteries, flow-mediated dilation was markedly reduced in Cav-1 KO arteries compared with those of WT mice. This impairment in response to flow was rescued by reconstituting Cav-1 into the endothelium. In conclusion, these results showed that endothelial Cav-1 and caveolae are necessary for both rapid and long-term mechanotransduction in intact blood vessels. PMID:16670769

Importance of the splanchnic vascular bed in human blood pressure regulation.

NASA Technical Reports Server (NTRS)

Rowell, L. B.; Detry, J.-M. R.; Blackmon, J. R.; Wyss, C.

1972-01-01

Three-part experiment in which five subjects were exposed to lower body negative pressure (LBNP) at -50 mm Hg below the iliac crests. Duration of LBNP to earliest vagal symptoms was 7 to 21 min; all data are expressed as changes from control period to the last measurements before these symptoms. In part I, forearm blood flow (by Whitney gauge) fell 45% during LBNP. In part II, splanchnic blood flow (from arterial clearance hepatic extraction of indocyanine green) fell 32% and splanchnic vascular resistance rose 30%. In part III, cardiac output fell 28%, stroke volume 51%, and central blood volume 21%. Total peripheral resistance and heart rate rose 19% and 52%. Of the reduction in total vascular conductance, decreased splanchnic conductance accounted for approximately 33%; skin plus muscle conductance decreased similarly.

Functional morphology and patterns of blood flow in the heart of Python regius.

PubMed

Starck, J Matthias

2009-06-01

Brightness-modulated ultrasonography, continuous-wave Doppler, and pulsed-wave Doppler-echocardiography were used to analyze the functional morphology of the undisturbed heart of ball pythons. In particular, the action of the muscular ridge and the atrio-ventricular valves are key features to understand how patterns of blood flow emerge from structures directing blood into the various chambers of the heart. A step-by-step image analysis of echocardiographs shows that during ventricular diastole, the atrio-ventricular valves block the interventricular canals so that blood from the right atrium first fills the cavum venosum, and blood from the left atrium fills the cavum arteriosum. During diastole, blood from the cavum venosum crosses the muscular ridge into the cavum pulmonale. During middle to late systole the muscular ridge closes, thus prohibiting further blood flow into the cavum pulmonale. At the same time, the atrio-ventricular valves open the interventricular canal and allow blood from the cavum arteriosum to flow into the cavum venosum. In the late phase of ventricular systole, all blood from the cavum pulmonale is pressed into the pulmonary trunk; all blood from the cavum venosum is pressed into both aortas. Quantitative measures of blood flow volume showed that resting snakes bypass the pulmonary circulation and shunt about twice the blood volume into the systemic circulation as into the pulmonary circulation. When digesting, the oxygen demand of snakes increased tremendously. This is associated with shunting more blood into the pulmonary circulation. The results of this study allow the presentation of a detailed functional model of the python heart. They are also the basis for a functional hypothesis of how shunting is achieved. Further, it was shown that shunting is an active regulation process in response to changing demands of the organism (here, oxygen demand). Finally, the results of this study support earlier reports about a dual pressure circulation in Python regius.

Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice.

PubMed

Hotta, Harumi; Uchida, Sae; Kagitani, Fusako; Maruyama, Naoki

2011-05-01

We examined whether activity of the nucleus basalis of Meynert (NBM) regulates regional cerebral cortical blood flow (rCBF) in mice, using laser speckle and laser Doppler flowmetry. In anesthetized mice, unilateral focal stimulation, either electrical or chemical, of the NBM increased rCBF of the ipsilateral cerebral cortex in the frontal, parietal and occipital lobes, independent of changes in systemic blood pressure. Most of vasodilative responses to low intensity stimuli (2 times threshold intensity: 2T) were abolished by atropine (a muscarinic cholinergic blocker), whereas responses to higher intensity stimuli (3T) were abolished by atropine and mecamylamine (a nicotinic cholinergic blocker). Blood flow changes were largest when the tip of the electrode was located within the area containing cholinergic neurons shown by choline acetyltransferase-immunocytochemistry. These results suggest that cholinergic projections from basal forebrain neurons in mice cause vasodilation in the ipsilateral cerebral cortex by a combination of muscarinic and nicotinic mechanisms, as previously found in rats and cats.

The interrelationship of research in the laboratory and the field to assess hydration status and determine mechanisms involved in water regulation during physical activity.

PubMed

Stachenfeld, Nina S

2014-05-01

Changes in skin blood and sweating are the primary mechanisms for heat loss in humans. A hot, humid environment concomitant with dehydration limits the ability to increase skin blood flow for the purpose of transferring heat from the body core to skin surface and evaporate sweat to maintain core temperature within safe limits during exercise. Adequate hydration improves thermoregulation by maintaining blood volume to support skin blood flow and sweating. Humans rely on fluid intake to maintain total body water and blood volume, and have developed complex mechanisms to sense changes in the amount and composition of fluid in the body. This paper addresses the interrelationship of research in the laboratory and the field to assess hydration status involved in body water and temperature regulation during exercise. In the controlled setting of a research laboratory, investigators are able to investigate the contributions of volume and tonicity of fluid in the plasma to body water and temperature regulation during exercise and recovery. For example, laboratory studies have shown that tonicity in a rehydration beverage maintains the thirst mechanism (and stimulates drinking), and contributes to the ongoing stimulation of renal fluid retention hormones, ultimately leading to a more complete rehydration. Research in the field cannot control the environment precisely, but these studies provide a natural, 'real-life' setting to study fluid and temperature regulation during exercise. The conditions encountered in the field are closest to the environment during competition, and data collected in the field can have an immediate impact on performance and safety during exercise. There is an important synergy between these two methods of collecting data that support performance and protect athletes from harm during training and improve performance during competition.

Independent effects of heart-head distance and caudal blood pooling on blood pressure regulation in aquatic and terrestrial snakes.

PubMed

Seymour, Roger S; Arndt, Joachim O

2004-03-01

Changes in orientation in a gravitational field markedly alter the patterns of blood pressure and flow in animals, especially tall or long ones such as giraffes or snakes. Vertical orientation tends to reduce blood flow and pressure in the head for two major reasons. First, the increased vertical blood column above the heart creates a gravitational hydrostatic pressure against which the heart must work. Second, expansion of dependent vessels in the lower extremities causes blood pooling and reduces return of venous blood to the heart, thereby lowering flow and pressure. For most animals, it is difficult to separate these two effects, but snakes offer the possibility of bending the animal in the region of the heart and manipulating the two ends of the body independently. We studied baroregulatory responses in terrestrial pythons (Liasis fuscus) and aquatic file snakes (Acrochordus arafurae) by tilting only the front or rear parts and then the whole animal. Changes in head blood pressure during partial tilts added up to the change during full tilt. The vertical distance to the head had twice as much influence on head blood pressure than did blood pooling in the pythons and four times as much in file snakes. This accounts for the cephalad location of the heart in terrestrial species compared with aquatic ones.

Magnetic resonance imaging-based computational modelling of blood flow and nanomedicine deposition in patients with peripheral arterial disease

PubMed Central

Hossain, Shaolie S.; Zhang, Yongjie; Fu, Xiaoyi; Brunner, Gerd; Singh, Jaykrishna; Hughes, Thomas J. R.; Shah, Dipan; Decuzzi, Paolo

2015-01-01

Peripheral arterial disease (PAD) is generally attributed to the progressive vascular accumulation of lipoproteins and circulating monocytes in the vessel walls leading to the formation of atherosclerotic plaques. This is known to be regulated by the local vascular geometry, haemodynamics and biophysical conditions. Here, an isogeometric analysis framework is proposed to analyse the blood flow and vascular deposition of circulating nanoparticles (NPs) into the superficial femoral artery (SFA) of a PAD patient. The local geometry of the blood vessel and the haemodynamic conditions are derived from magnetic resonance imaging (MRI), performed at baseline and at 24 months post intervention. A dramatic improvement in blood flow dynamics is observed post intervention. A 500% increase in peak flow rate is measured in vivo as a consequence of luminal enlargement. Furthermore, blood flow simulations reveal a 32% drop in the mean oscillatory shear index, indicating reduced disturbed flow post intervention. The same patient information (vascular geometry and blood flow) is used to predict in silico in a simulation of the vascular deposition of systemically injected nanomedicines. NPs, targeted to inflammatory vascular molecules including VCAM-1, E-selectin and ICAM-1, are predicted to preferentially accumulate near the stenosis in the baseline configuration, with VCAM-1 providing the highest accumulation (approx. 1.33 and 1.50 times higher concentration than that of ICAM-1 and E-selectin, respectively). Such selective deposition of NPs within the stenosis could be effectively used for the detection and treatment of plaques forming in the SFA. The presented MRI-based computational protocol can be used to analyse data from clinical trials to explore possible correlations between haemodynamics and disease progression in PAD patients, and potentially predict disease occurrence as well as the outcome of an intervention. PMID:25878124

Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy.

PubMed

Park, Yang-Gyu; Choi, Jawun; Jung, Hye-Kang; Song, In Kyu; Shin, Yongwhan; Park, Sang-Youel; Seol, Jae-Won

2017-10-01

Early pregnancy is characterized by an increase in the blood volume of the uterus for embryonic development, thereby exerting fluid shear stress (FSS) on the vascular walls. The uterus experiences vascular remodeling to accommodate the increased blood flow. The blood flow‑induced FSS elevates the expression of vascular endothelial growth factors (VEGFs) and their receptors, and regulates vascular remodeling through the activation of VEGF receptor-3 (VEGFR-3). However, the mechanisms responsible for FSS-induced VEGFR-3 expression in the uterus during pregnancy are unclear. In this study, we demonstrate that vascular remodeling in the uterus during pregnancy is regulated by FSS-induced VEGFR-3 expression. We examined the association between VEGFR-3 and FSS through in vivo and in vitro experiments. In vivo experiments revealed VEGFR-3 expression in the CD31-positive region of the uterus of pregnant mice; VEGF-C (ligand for VEGFR‑3) was undetected in the uterus. These results confirmed that VEGFR-3 expression in the endometrium is independent of its ligand. In vitro studies experiments revealed that FSS induced morphological changes and increased VEGFR-3 expression in human uterine microvascular endothelial cells. Thus, VEGFR-3 activation by FSS is associated with vascular remodeling to allow increased blood flow in the uterus during pregnancy.

Cardiovascular adaptations supporting human exercise-heat acclimation.

PubMed

Périard, Julien D; Travers, Gavin J S; Racinais, Sébastien; Sawka, Michael N

2016-04-01

This review examines the cardiovascular adaptations along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses during exercise-heat acclimation. The cardiovascular system is well recognized as an important contributor to exercise-heat acclimation that acts to minimize physiological strain, reduce the risk of serious heat illness and better sustain exercise capacity. The upright posture adopted by humans during most physical activities and the large skin surface area contribute to the circulatory and blood pressure regulation challenge of simultaneously supporting skeletal muscle blood flow and dissipating heat via increased skin blood flow and sweat secretion during exercise-heat stress. Although it was traditionally held that cardiac output increased during exercise-heat stress to primarily support elevated skin blood flow requirements, recent evidence suggests that temperature-sensitive mechanisms may also mediate an elevation in skeletal muscle blood flow. The cardiovascular adaptations supporting this challenge include an increase in total body water, plasma volume expansion, better sustainment and/or elevation of stroke volume, reduction in heart rate, improvement in ventricular filling and myocardial efficiency, and enhanced skin blood flow and sweating responses. The magnitude of these adaptations is variable and dependent on several factors such as exercise intensity, duration of exposure, frequency and total number of exposures, as well as the environmental conditions (i.e. dry or humid heat) in which acclimation occurs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

pCO2 and pH regulation of cerebral blood flow

PubMed Central

Yoon, SeongHun; Zuccarello, Mario; Rapoport, Robert M.

2012-01-01

CO2 serves as one of the fundamental regulators of cerebral blood flow (CBF). It is widely considered that this regulation occurs through pCO2-driven changes in pH of the cerebral spinal fluid (CSF), with elevated and lowered pH causing direct relaxation and contraction of the smooth muscle, respectively. However, some findings also suggest that pCO2 acts independently of and/or in conjunction with altered pH. This action may be due to a direct effect of CSF pCO2 on the smooth muscle as well as on the endothelium, nerves, and astrocytes. Findings may also point to an action of arterial pCO2 on the endothelium to regulate smooth muscle contractility. Thus, the effects of pH and pCO2 may be influenced by the absence/presence of different cell types in the various experimental preparations. Results may also be influenced by experimental parameters including myogenic tone as well as solutions containing significantly altered HCO3− concentrations, i.e., solutions routinely employed to differentiate the effects of pH from pCO2. In sum, it appears that pCO2, independently and in conjunction with pH, may regulate CBF. PMID:23049512

Cerebral blood flow velocity declines before arterial pressure in patients with orthostatic vasovagal presyncope

NASA Technical Reports Server (NTRS)

Dan, Dan; Hoag, Jeffrey B.; Ellenbogen, Kenneth A.; Wood, Mark A.; Eckberg, Dwain L.; Gilligan, David M.

2002-01-01

OBJECTIVES: We studied hemodynamic changes leading to orthostatic vasovagal presyncope to determine whether changes of cerebral artery blood flow velocity precede or follow reductions of arterial pressure. BACKGROUND: Some evidence suggests that disordered cerebral autoregulation contributes to the occurrence of orthostatic vasovagal syncope. We studied cerebral hemodynamics with transcranial Doppler recordings, and we closely examined the temporal sequence of changes of cerebral artery blood flow velocity and systemic arterial pressure in 15 patients who did or did not faint during passive 70 degrees head-up tilt. METHODS: We recorded photoplethysmographic arterial pressure, RR intervals (electrocardiogram) and middle cerebral artery blood flow velocities (mean, total, mean/RR interval; Gosling's pulsatility index; and cerebrovascular resistance [mean cerebral velocity/mean arterial pressure, MAP]). RESULTS: Eight men developed presyncope, and six men and one woman did not. Presyncopal patients reported light-headedness, diaphoresis, or a sensation of fatigue 155 s (range: 25 to 414 s) before any cerebral or systemic hemodynamic change. Average cerebral blood flow velocity (CBFV) changes (defined by an iterative linear regression algorithm) began 67 s (range: 9 to 198 s) before reductions of MAP. Cerebral and systemic hemodynamic measurements remained constant in nonsyncopal patients. CONCLUSIONS: Presyncopal symptoms and CBFV changes precede arterial pressure reductions in patients with orthostatic vasovagal syncope. Therefore, changes of cerebrovascular regulation may contribute to the occurrence of vasovagal reactions.

Dilator and constrictor response of renal vasculature during acute renal hypotension in anesthetized goats. Role of nitric oxide.

PubMed

Diéguez, Godofredo; García-Villalón, Angel Luis

2011-01-01

The relative role of NO derived from endothelium NO synthase (eNOS) and neuronal NO synthase (nNOS) in renovascular reactivity during renal hypotension is unknown. To examine this issue, we recorded the effects of unspecific inhibitor of NO synthase N(w)-nitro-L-arginine methyl esther (L-NAME) and inhibitor of nNOS 7-nitroindazole monosodium salt (7-NINA) on renal vasodilator and vasoconstrictor responses in anesthetized goats during renal hypotension by constricting the abdominal aorta. Intrarenal administration of L-NAME and hypotension, either untreated or treated with L-NAME, decreased resting renal blood flow, and the increases in renal blood flow by acetylcholine but not those by sodium nitroprusside were tempered, and the decreases by norepinephrine and angiotensin II were augmented. Intraperitoneal administration of 7-NINA did not affect, and 7-NINA+hypotension decreased renal blood flow, and under these conditions the increases in renal blood flow by acetylcholine and sodium nitroprusside were not modified, and the decreases by norepinephrine and angiotensin II were slightly (during 7-NINA) or consistently augmented (7-NINA+hypotension). Therefore, NO derived from eNOS plays a significant role, while that derived from nNOS plays a little role, if any, to regulate renal blood flow and to mediate acetylcholine-induced vasodilation, as well to modulate renal vasoconstriction by norepinephrine and angiotensin II. Copyright © 2011 Elsevier Inc. All rights reserved.

4D Subject-Specific Inverse Modeling of the Chick Embryonic Heart Outflow Tract Hemodynamics

PubMed Central

Goenezen, Sevan; Chivukula, Venkat Keshav; Midgett, Madeline; Phan, Ly; Rugonyi, Sandra

2015-01-01

Blood flow plays a critical role in regulating embryonic cardiac growth and development, with altered flow leading to congenital heart disease. Progress in the field, however, is hindered by a lack of quantification of hemodynamic conditions in the developing heart. In this study, we present a methodology to quantify blood flow dynamics in the embryonic heart using subject-specific computational fluid dynamics (CFD) models. While the methodology is general, we focused on a model of the chick embryonic heart outflow tract (OFT), which distally connects the heart to the arterial system, and is the region of origin of many congenital cardiac defects. Using structural and Doppler velocity data collected from optical coherence tomography (OCT), we generated 4D (3D + time) embryo-specific CFD models of the heart OFT. To replicate the blood flow dynamics over time during the cardiac cycle, we developed an iterative inverse-method optimization algorithm, which determines the CFD model boundary conditions such that differences between computed velocities and measured velocities at one point within the OFT lumen are minimized. Results from our developed CFD model agree with previously measured hemodynamics in the OFT. Further, computed velocities and measured velocities differ by less than 15% at locations that were not used in the optimization, validating the model. The presented methodology can be used in quantifications of embryonic cardiac hemodynamics under normal and altered blood flow conditions, enabling an in depth quantitative study of how blood flow influences cardiac development. PMID:26361767

Evaluation of spontaneous low-frequency oscillations in cerebral hemodynamics with time-series red-green-blue images

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Mustari, Afrina; Nakamura, Naoki; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Kokubo, Yasuaki

2017-02-01

The brain relies on a continuous and adequate supply of blood flow, bringing the nutrients that it needs and removing the waste products of metabolism. It is thus one of the most tightly regulated systems in the body, whereby a whole range of mechanisms act to maintain this supply, despite changes in blood pressure etc. Failure of these mechanisms is found in a number of devastating cerebral diseases, including stroke, vascular dementia and brain injury and trauma. Spontaneous contraction and relaxation of arterioles (and in some instances venules) termed vasomotion has been observed in an extensive variety of tissues and species. Vasomotion has a beneficial effect on tissue oxygenation and enhance blood flow. Although vasomotion is strictly a local phenomenon, the regulation of contractile activity of vascular smooth muscle cells is dependent on the complex interplay between vasodilator and vasoconstrictor stimuli from circulating hormones, neurotransmitters, endothelial derived factors, and blood pressure. Therefore, evaluation of the spontaneous oscillations in cerebral vasculatures might be a useful tool for assessing risk and investigating different treatment strategies in neurological disorders, such as traumatic brain injury, seizure, ischemia, and stroke. In the present study, we newly propose a method to visualize the spontaneous low-frequency oscillation of cerebral blood volume based on the sequential RGB images of exposed brain.

Multiplexed immunophenotyping of human antigen-presenting cells in whole blood by polychromatic flow cytometry

PubMed Central

Fung, Erik; Esposito, Laura; Todd, John A.; Wicker, Linda S.

2010-01-01

We describe two modular protocols for immunostaining and multiparameter flow cytometric analysis of major human antigen-presenting cells (dendritic cells, monocytes, B lymphocytes) in minimally manipulated whole blood. Simultaneous detection of up to eight colors is enabled by careful selection and testing of cell-subset-defining monoclonal antibodies (anchor markers) in the appropriate fluorochrome combinations, to demonstrate the quantification of surface expression levels of molecules involved in chemotaxis (e.g. CX3CR1, CCR2), adhesion (e.g. CD11b, CD62L), antigen presentation (e.g. CD83, CD86, CD209) and immune regulation (e.g. CD101) on circulating antigen-presenting cells. Each immunostaining reaction requires as little as 50–100 μl of peripheral whole blood, no density-gradient separation, and the entire procedure from preparation of reagents to flow cytometry can be completed in <5 h. PMID:20134434

Ocular hemodynamics and glaucoma: the role of mathematical modeling.

PubMed

Harris, Alon; Guidoboni, Giovanna; Arciero, Julia C; Amireskandari, Annahita; Tobe, Leslie A; Siesky, Brent A

2013-01-01

To discuss the role of mathematical modeling in studying ocular hemodynamics, with a focus on glaucoma. We reviewed recent literature on glaucoma, ocular blood flow, autoregulation, the optic nerve head, and the use of mathematical modeling in ocular circulation. Many studies suggest that alterations in ocular hemodynamics play a significant role in the development, progression, and incidence of glaucoma. Although there is currently a limited number of studies involving mathematical modeling of ocular blood flow, regulation, and diseases (such as glaucoma), preliminary modeling work shows the potential of mathematical models to elucidate the mechanisms that contribute most significantly to glaucoma progression. Mathematical modeling is a useful tool when used synergistically with clinical and laboratory data in the study of ocular blood flow and glaucoma. The development of models to investigate the relationship between ocular hemodynamic alterations and glaucoma progression will provide a unique and useful method for studying the pathophysiology of glaucoma.

50 years of computer simulation of the human thermoregulatory system.

PubMed

Hensley, Daniel W; Mark, Andrew E; Abella, Jayvee R; Netscher, George M; Wissler, Eugene H; Diller, Kenneth R

2013-02-01

This paper presents an updated and augmented version of the Wissler human thermoregulation model that has been developed continuously over the past 50 years. The existing Fortran code is translated into C with extensive embedded commentary. A graphical user interface (GUI) has been developed in Python to facilitate convenient user designation of input and output variables and formatting of data presentation. Use of the code with the GUI is described and demonstrated. New physiological elements were added to the model to represent the hands and feet, including the unique vascular structures adapted for heat transfer associated with glabrous skin. The heat transfer function and efficacy of glabrous skin is unique within the entire body based on the capacity for a very high rate of blood perfusion and the novel capability for dynamic regulation of blood flow. The model was applied to quantify the absolute and relative contributions of glabrous skin flow to thermoregulation for varying levels of blood perfusion. The model also was used to demonstrate how the unique features of glabrous skin blood flow may be recruited to implement thermal therapeutic procedures. We have developed proprietary methods to manipulate the control of glabrous skin blood flow in conjunction with therapeutic devices and simulated the effect of these methods with the model.

Cerebral Autoregulation Is Minimally Influenced by the Superior Cervical Ganglion in Two- Week-Old Lambs, and Absent in Preterm Lambs Immediately Following Delivery

PubMed Central

Czynski, Adam J.; Terry, Michael H.; Deming, Douglas D.; Power, Gordon G.; Buchholz, John N.; Blood, Arlin B.

2013-01-01

Cerebral vessels in the premature newborn brain are well supplied with adrenergic nerves, stemming from the superior cervical ganglia (SCG), but their role in regulation of blood flow remains uncertain. To test this function twelve premature or two-week-old lambs were instrumented with laser Doppler flow probes in the parietal cortices to measure changes in blood flow during changes in systemic blood pressure and electrical stimulation of the SCG. In lambs delivered prematurely at ∼129 days gestation cerebral perfusion and driving pressure demonstrated a direct linear relationship throughout the physiologic range, indicating lack of autoregulation. In contrast, in lambs two-weeks of age, surgical removal of one SCG resulted in ipsilateral loss of autoregulation during pronounced hypertension. Electrical stimulation of one SCG elicited unilateral increases in cerebral resistance to blood flow in both pre-term and two-week-old lambs, indicating functioning neural pathways in the instrumented, anesthetized lambs. We conclude cerebral autoregulation is non-functional in preterm lambs following cesarean delivery. Adrenergic control of cerebral vascular resistance becomes effective in newborn lambs within two-weeks after birth but SCG-dependent autoregulation is essential only during pronounced hypertension, well above the normal range of blood pressure. PMID:24349256

Effect of body position and ventilation on umbilical artery and venous blood flows during delayed umbilical cord clamping in preterm lambs.

PubMed

Hooper, Stuart B; Crossley, Kelly J; Zahra, Valerie A; van Vonderen, Jeroen; Moxham, Alison; Gill, Andrew W; Kluckow, Martin; Te Pas, Arjan B; Wallace, Euan M; Polglase, Graeme R

2017-07-01

While delayed umbilical cord clamping (UCC) is thought to facilitate placental to infant blood transfusion, the physiological factors regulating flow in the umbilical arteries and veins during delayed UCC is unknown. We investigated the effects of gravity, by changing fetal height relative to the placenta, and ventilation on umbilical blood flows and the cardiovascular transition during delayed UCC at birth. Catheters and flow probes were implanted into preterm lambs (128 days) prior to delivery to measure pulmonary, carotid, umbilical artery (UaBF) and umbilical venous (UvBF) blood flows. Lambs were placed either 10 cm below or 10 cm above the ewe. Ventilation commenced 2-3 min before UCC and continued for 30 min after UCC. Gravity reduced umbilical and cerebral flows when lambs were placed below the midline, but the reduction in UaBF and UvBF was similar. Ventilation during delayed UCC reduced UvBF and UaBF by similar amounts, irrespective of the lamb's position, such that flows into and out of the placenta remained balanced. The effects of ventilation on umbilical flows were much greater than the effects of gravity, but no net placental to lamb blood transfusion could be detected under any condition. Cardiovascular parameters, cerebral oxygen kinetics and final blood volumes were similar in both groups 5 min after UCC. Gravity caused small transient effects on umbilical and cerebral flow, but given changes were similar in umbilical arteries and veins, no net placental transfusion was detected. Ventilation during delayed UCC has a markedly greater influence on cardiovascular function in the newborn. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Dynamic Infrared Thermography Study of Blood Flow Relative to Lower Limp Position

NASA Astrophysics Data System (ADS)

Stathopoulos, I.; Skouroliakou, K.; Michail, C.; Valais, I.

2015-09-01

Thermography is an established method for studying skin temperature distribution. Temperature distribution on body surface is influenced by a variety of physiological mechanisms and has been proven a reliable indicator of various physiological disorders. Blood flow is an important factor that influences body heat diffusion and skin temperature. In an attempt to validate and further elucidate thermal models characterizing the human skin, dynamic thermography of the lower limp in horizontal and vertical position was performed, using a FLIR T460 thermographic camera. Temporal variation of temperature was recorded on five distinct points of the limp. Specific points were initially cooled by the means of an ice cube and measurements of the skin temperature were obtained every 30 seconds as the skin temperature was locally reduced and afterwards restored at its initial value. The return to thermal balance followed roughly the same pattern for all points of measurement, although the heating rate was faster when the foot was in horizontal position. Thermal balance was achieved faster at the spots that were positioned on a vein passage. Our results confirm the influence of blood flow on the thermal regulation of the skin. Spots located over veins exhibit different thermal behaviour due to thermal convection through blood flow. Changing the position of the foot from vertical to horizontal, effectively affects blood perfusion as in the vertical position blood circulation is opposed by gravity.

Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair.

PubMed

Yu, Jun; Fernández-Hernando, Carlos; Suarez, Yajaira; Schleicher, Michael; Hao, Zhengrong; Wright, Paulette L; DiLorenzo, Annarita; Kyriakides, Themis R; Sessa, William C

2009-10-13

Blood vessel formation during ischemia and wound healing requires coordination of the inflammatory response with genes that regulate blood vessel assembly. Here we show that the reticulon family member 4B, aka Nogo-B, is upregulated in response to ischemia and is necessary for blood flow recovery secondary to ischemia and wound healing. Mice lacking Nogo-B exhibit reduced arteriogenesis and angiogenesis that are linked to a decrease in macrophage infiltration and inflammatory gene expression in vivo. Bone marrow-derived macrophages isolated from Nogo knock-out mice have reduced spreading and chemotaxis due to impaired Rac activation. Bone marrow reconstitution experiments show that Nogo in myeloid cells is necessary to promote macrophage homing and functional recovery after limb ischemia. Thus, endogenous Nogo coordinates macrophage-mediated inflammation with arteriogenesis, wound healing, and blood flow control.

Multimodal Pressure-Flow Analysis: Application of Hilbert Huang Transform in Cerebral Blood Flow Regulation

NASA Astrophysics Data System (ADS)

Lo, Men-Tzung; Hu, Kun; Liu, Yanhui; Peng, C.-K.; Novak, Vera

2008-12-01

Quantification of nonlinear interactions between two nonstationary signals presents a computational challenge in different research fields, especially for assessments of physiological systems. Traditional approaches that are based on theories of stationary signals cannot resolve nonstationarity-related issues and, thus, cannot reliably assess nonlinear interactions in physiological systems. In this review we discuss a new technique called multimodal pressure flow (MMPF) method that utilizes Hilbert-Huang transformation to quantify interaction between nonstationary cerebral blood flow velocity (BFV) and blood pressure (BP) for the assessment of dynamic cerebral autoregulation (CA). CA is an important mechanism responsible for controlling cerebral blood flow in responses to fluctuations in systemic BP within a few heart-beats. The MMPF analysis decomposes BP and BFV signals into multiple empirical modes adaptively so that the fluctuations caused by a specific physiologic process can be represented in a corresponding empirical mode. Using this technique, we showed that dynamic CA can be characterized by specific phase delays between the decomposed BP and BFV oscillations, and that the phase shifts are significantly reduced in hypertensive, diabetics and stroke subjects with impaired CA. Additionally, the new technique can reliably assess CA using both induced BP/BFV oscillations during clinical tests and spontaneous BP/BFV fluctuations during resting conditions.

The endocrine system in space flight

NASA Technical Reports Server (NTRS)

Leach, C. S.; Johnson, P. C.; Cintron, N. M.

1988-01-01

A trial natriuretic factor (ANF), a hormone recently shown to regulate sodium and water excretion, has been measured in blood specimens obtained during flight. After 30 or 42 h of weightlessness, mean ANF was elevated. After 175 or 180 h, ANF has increased by 59 percent, and it changed little between that time and soon after landing. There is probably an increase in ANF early inflight associated with the fluid shift, followed by a compensatory decrease in blood volume. Increased renal blood flow may cause the later ANF decrease. Erythropoietin (Ep), a hormone involved in the control of red blood cell proudction, was measured in blood samples taken during the first Spacelab mission and was significantly decreased on the second day of flight, suggesting also an increase in renal blood flow. Spacelab-2 investigators report that the active vitamin D metabolite 1 alpha, 25-dihydroxyvitamin D-3 increased early in the flight, indicating that a stimulus for increased bone resorption occurs by 30 h after launch.

Control of skeletal muscle perfusion at the onset of dynamic exercise

NASA Technical Reports Server (NTRS)

Delp, M. D.

1999-01-01

At the onset of exercise there is a rapid increase in skeletal muscle vascular conductance and blood flow. Several mechanisms involved in the regulation of muscle perfusion have been proposed to initiate this hyperemic response, including neural, metabolic, endothelial, myogenic, and muscle pump mechanisms. Investigators utilizing pharmacological blockade of cholinergic muscarinic receptors and sympathectomy have concluded that neither sympathetic cholinergic nor adrenergic neural mechanisms are involved in the initial hyperemia. Studies have also shown that the time course for vasoactive metabolite release, diffusion, accumulation, and action is too long to account for the rapid increase in vascular conductance at the initiation of exercise. Furthermore, there is little or no evidence to support an endothelium or myogenic mechanism as the initiating factor in the muscle hyperemia. Thus, the rise in muscle blood flow does not appear to be explained by known neural, metabolic, endothelial, or myogenic influences. However, the initial hyperemia is consistent with the mechanical effects of the muscle pump to increase the arteriovenous pressure gradient across muscle. Because skeletal muscle blood flow is regulated by multiple and redundant mechanisms, it is likely that neural, metabolic, and possibly endothelial factors become important modulators of mechanically induced exercise hyperemia following the first 5-10 s of exercise.

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites.

PubMed

Steffensen, Lasse Bach; Mortensen, Martin Bødtker; Kjolby, Mads; Hagensen, Mette Kallestrup; Oxvig, Claus; Bentzon, Jacob Fog

2015-09-01

Atherosclerosis develops initially at branch points and in areas of high vessel curvature. Moreover, experiments in hypercholesterolemic mice have shown that the introduction of disturbed flow in straight, atherosclerosis-resistant arterial segments turns them highly atherosclerosis susceptible. Several biomechanical mechanisms have been proposed, but none has been demonstrated. In the present study, we examined whether a causal link exists between disturbed laminar flow and the ability of the arterial wall to retain lipoproteins. Lipoprotein retention was detected at natural predilection sites of the murine thoracic aorta 18 hours after infusion of fluorescently labeled low-density lipoprotein. To test for causality between blood flow and the ability of these areas to retain lipoproteins, we manipulated blood flow in the straight segment of the common carotid artery using a constrictive collar. Disturbed laminar flow did not affect low-density lipoprotein influx, but increased the ability of the artery wall to bind low-density lipoprotein. Concordantly, disturbed laminar flow led to differential expression of genes associated with phenotypic modulation of vascular smooth muscle cells, increased expression of proteoglycan core proteins associated with lipoprotein retention, and of enzymes responsible for chondroitin sulfate glycosaminoglycan synthesis and sulfation. Blood flow regulates genes associated with vascular smooth muscle cell phenotypic modulation, as well as the expression and post-translational modification of lipoprotein-binding proteoglycan core proteins, and the introduction of disturbed laminar flow vastly augments the ability of a previously resistant, straight arterial segment to retain lipoproteins. © 2015 American Heart Association, Inc.

Cutaneous Microvascular Blood Flow and Reactivity in Hypoxia

PubMed Central

Treml, Benedikt; Kleinsasser, Axel; Stadlbauer, Karl-Heinz; Steiner, Iris; Pajk, Werner; Pilch, Michael; Burtscher, Martin; Knotzer, Hans

2018-01-01

As is known, hypoxia leads to an increase in microcirculatory blood flow of the skin in healthy volunteers. In this pilot study, we investigated microcirculatory blood flow and reactive hyperemia of the skin in healthy subjects in normobaric hypoxia. Furthermore, we examined differences in microcirculation between hypoxic subjects with and without short-term acclimatization, whether or not skin microvasculature can acclimatize. Fourty-six healthy persons were randomly allocated to either short-term acclimatization using intermittent hypoxia for 1 h over 7 days at an FiO2 0.126 (treatment, n = 23) or sham short-term acclimatization for 1 h over 7 days at an FiO2 0.209 (control, n = 23). Measurements were taken in normoxia and at 360 and 720 min during hypoxia (FiO2 0.126). Microcirculatory cutaneous blood flow was assessed with a laser Doppler flowmeter on the forearm. Reactive hyperemia was induced by an ischemic stimulus. Measurements included furthermore hemodynamics, blood gas analyses and blood lactate. Microcirculatory blood flow increased progressively during hypoxia (12.3 ± 7.1–19.0 ± 8.1 perfusion units; p = 0.0002) in all subjects. The magnitude of the reactive hyperemia was diminished during hypoxia (58.2 ± 14.5–40.3 ± 27.4 perfusion units; p = 0.0003). Short-term acclimatization had no effect on microcirculatory blood flow. When testing for a hyperemic response of the skin's microcirculation we found a diminished signal in hypoxia, indicative for a compromised auto-regulative circulatory capacity. Furthermore, hypoxic short-term acclimatization did not affect cutaneous microcirculatory blood flow. Seemingly, circulation of the skin was unable to acclimatize using a week-long short-term acclimatization protocol. A potential limitation of our study may be the 7 days between acclimatization and the experimental test run. However, there is evidence that the hypoxic ventilatory response, an indicator of acclimatization, is increased for 1 week after short-term acclimatization. Then again, 1 week is what one needs to get from home to a location at significant altitude. PMID:29559919

Short-term effect of beta-adrenoreceptor blocking agents on ocular blood flow.

PubMed

Sato, T; Muto, T; Ishibashi, Y; Roy, S

2001-10-01

In this study the acute effect of the topically-delivered non-selective beta-blockers timolol and carteolol, and the selective beta-blocker betaxolol, were evaluated with respect to ocular blood flow, intraocular pressure (IOP) and vessel resistance in rabbits' eyes. In a double masked randomized design, one eye of each subject (n = 9) received two drops of 0.5 % timolol or 2 % cartelol or 0.5 % betaxolol ophthalmic solution and a separate group of nine rabbits received two drops of placebo consisting of physiological saline in both eyes to serve as control. Using hydrogen clearance method, ciliary body blood flow (CiBF), choroidal blood flow (CBF), and retinal blood flow (RBF) were measured. IOP and systemic mean arterial pressure (MAP) of each subject were measured under same condition before and after the administration of respective drugs to calculate the ocular perfusion pressure (OPP) and vessel resistance. In timolol- and carteolol-treated eyes significant reduction was observed in IOP (p < 0.01), CiBF (p < 0.01), CBF (p < 0.01) and RBF (p < 0.01) compared to control eyes. However, in betaxolol-treated eyes a marginal reduction in IOP was observed accompanied by significant increase in CiBF (p < 0.01) and RBF (p < 0.05). The non-selective beta-blocker-treated eyes tended to have increased vessel resistance, whereas, selective beta-blocker-treated eyes tended to have decreased vessel resistance. Our current results comparing non-selective and selective beta-blockers suggest that the selective beta-blocker betaxolol may be more appropriate for maintenance of retinal blood flow in situations with low perfusion. Currently the mechanism for regulation of IOP is unclear; however, the findings from this study indicate that decreased CiBF may contribute to reduction in IOP.

The pulsating brain: A review of experimental and clinical studies of intracranial pulsatility

PubMed Central

2011-01-01

The maintenance of adequate blood flow to the brain is critical for normal brain function; cerebral blood flow, its regulation and the effect of alteration in this flow with disease have been studied extensively and are very well understood. This flow is not steady, however; the systolic increase in blood pressure over the cardiac cycle causes regular variations in blood flow into and throughout the brain that are synchronous with the heart beat. Because the brain is contained within the fixed skull, these pulsations in flow and pressure are in turn transferred into brain tissue and all of the fluids contained therein including cerebrospinal fluid. While intracranial pulsatility has not been a primary focus of the clinical community, considerable data have accrued over the last sixty years and new applications are emerging to this day. Investigators have found it a useful marker in certain diseases, particularly in hydrocephalus and traumatic brain injury where large changes in intracranial pressure and in the biomechanical properties of the brain can lead to significant changes in pressure and flow pulsatility. In this work, we review the history of intracranial pulsatility beginning with its discovery and early characterization, consider the specific technologies such as transcranial Doppler and phase contrast MRI used to assess various aspects of brain pulsations, and examine the experimental and clinical studies which have used pulsatility to better understand brain function in health and with disease. PMID:21349153

Niceritrol prevents the decrease in red blood cell 2,3-diphosphoglycerate and neuropathy in streptozotocin-induced diabetic rats.

PubMed

Hotta, N; Nakamura, J; Kakuta, H; Fukasawa, H; Koh, N; Sakakibara, F; Mori, K; Sakamoto, N

1995-01-01

Nerve ischemia/hypoxia has been linked to the pathogenesis of diabetic complications. Red blood cell 2,3-diphosphoglycerate is an important regulator of peripheral tissue oxygenation; however, the relationship between 2,3-diphosphoglycerate concentration and diabetic complications has not been studied in detail. This investigation focused on the relationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic nerve blood flow in streptozotocin-induced diabetic rats. The effect of treatment with niceritrol, a nicotinic acid derivative that acts as a vasodilator and reduces serum lipid concentrations, on 2,3-diphosphoglycerate concentration and diabetic neuropathy was also examined. Untreated diabetic rats had significantly lower concentrations of red blood cell 2,3-diphosphoglycerate, higher concentrations of serum total cholesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal rats. Niceritrol prevented these abnormalities without correcting hyperglycemia in diabetic rats, but had no effect on these parameters in normal rats. Red blood cell 2,3-diphosphoglycerate concentration and motor nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These observations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeutic effect on this condition by improving endoneurial ischemia/hypoxia.

Mathematical Modeling of Renal Hemodynamics in Physiology and Pathophysiology

PubMed Central

Sgouralis, Ioannis; Layton, Anita T.

2015-01-01

In addition to the excretion of metabolic waste and toxin, the kidney plays an indispensable role in regulating the balance of water, electrolyte, acid-base, and blood pressure. For the kidney to maintain proper functions, hemodynamic control is crucial. In this review, we describe representative mathematical models that have been developed to better understand the kidney's autoregulatory processes. We consider mathematical models that simulate glomerular filtration, and renal blood flow regulation by means of the myogenic response and tubuloglomerular feedback. We discuss the extent to which these modeling efforts have expanded the understanding of renal functions in health and disease. PMID:25765886

Effects of age and hypertension on α1-adrenoceptors in the major source arteries of the rat bladder and penis.

PubMed

Yono, Makoto; Tanaka, Takanori; Tsuji, Shigeki; Irie, Shin; Sakata, Yukikuni; Otani, Masayuki; Yoshida, Masaki; Latifpour, Jamshid

2011-11-16

α(1)-Adrenoceptors regulate blood pressure, regional vascular resistance and tissue blood flow. As aging and hypertension may impact pelvic arterial blood flow resulting in bladder and penile dysfunction, we investigated effects of age and hypertension on α(1)-adrenoceptors in the major source arteries of the rat bladder and penis. Using radioligand receptor binding, real-time reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent microsphere infusion techniques, we compared 3 and 22-month-old male Fischer rats, and male normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Twenty-two-month-old rats and SHRs had significantly higher total α(1)-adrenoceptor density in the internal iliac artery and lower blood flow to the bladder and penis than 3-month-old and WKY rats, respectively. RT-PCR data showed an age and hypertension related increase in the expression of α(1B)-adrenoceptor mRNA in the internal iliac, vesical and internal pudendal arteries and a switch from α(1A) predominance in 3-month-old and WKY rats to α(1B)>α(1A) in 22-month-old rats and SHRs. Our data indicate the presence of age and hypertension related alterations in vascular α(1)-adrenoceptor subtype distribution and in blood flow to the rat bladder and penis. These findings suggest that pharmacological blockade of the vascular α(1B)-adrenoceptor, which could increase pelvic blood flow, may contribute to the improvement of bladder and penile dysfunctions in animal models for aging and hypertension. Copyright © 2011 Elsevier B.V. All rights reserved.

Light therapy modulates serotonin levels and blood flow in women with headache. A preliminary study.

PubMed

Tomaz de Magalhães, Miriam; Núñez, Silvia Cristina; Kato, Ilka Tiemy; Ribeiro, Martha Simões

2016-01-01

In this study, we looked at the possible effects of low-level laser therapy (LLLT) on blood flow velocity, and serotonin (5-HT) and cholinesterase levels in patients with chronic headache associated with temporomandibular disorders (TMD). LLLT has been clinically applied over the past years with positive results in analgesia and without the report of any side effects. The understanding of biological mechanisms of action may improve clinical results and facilitate its indication. Ten patients presenting headache associated with TMD completed the study. An 830-nm infrared diode laser with power of 100 mW, exposure time of 34 s, and energy of 3.4 J was applied on the tender points of masseter and temporal muscle. Blood flow velocity was determined via ultrasound Doppler velocimetry before and after laser irradiation. The whole blood 5-HT and cholinesterase levels were evaluated three days before, immediately, and three days after laser irradiation. Pain score after treatment decreased to a score of 5.8 corresponding to 64% of pain reduction (P < 0.05). LLLT promoted a decrease in the blood flow velocity (P < 0.05). In addition, the 5-HT levels were significantly increased three days after LLLT (P < 0.05). The cholinesterase levels remained unchanged at the analyzed time points (P > 0.05). Our findings indicated that LLLT regulates blood flow in the temporal artery after irradiation and might control 5-HT levels in patients suffering with tension-type headache associated to TMD contributing to pain relief. © 2016 by the Society for Experimental Biology and Medicine.

Thromboxane plays a role in postprandial jejunal oxygen uptake and capillary exchange.

PubMed

Alemayehu, A; Chou, C C

1990-09-01

The effects of a thromboxane A2 (TxA2)-endoperoxide receptor antagonist, SQ 29548, on jejunal blood flow, oxygen uptake, and capillary filtration coefficient (Kfc) were determined in anesthetized dogs under resting conditions and during the presence of predigested food in the jejunal lumen in three series of experiments. In series 1, 2.0 micrograms intra-arterial administration of SQ 29548 was found to abolish completely the vasoconstrictor action of graded doses (0.05-2.0 micrograms) of intra-arterial injection of a TxA2-endoperoxide analogue, U44069. SQ 29548 (2.0 micrograms ia) per se did not significantly alter resting jejunal blood flow, oxygen uptake, capillary pressure, or Kfc. Before SQ 29548, placement of food plus bile into the jejunal lumen increased blood flow +42 +/- 9%, oxygen uptake +28 +/- 7%, and Kfc +24 +/- 6%. After SQ 29548, the food placement increased blood flow +37 +/- 8%, oxygen uptake +52 +/- 11%, and Kfc +63 +/- 20%. The food-induced increases in oxygen uptake and Kfc after SQ 29548 were significantly greater than those induced before the blocking of TxA2-endoperoxide receptors by SQ 29548. Our study indicates that endogenous thromboxane does not play a role in regulating jejunal blood flow, capillary filtration, and oxygen uptake under resting conditions. However, it plays a role in limiting the food-induced increases in jejunal oxygen uptake and capillary exchange capacity without influencing the food-induced hyperemia.

Separating genetic and hemodynamic defects in neuropilin 1 knockout embryos.

PubMed

Jones, Elizabeth A V; Yuan, Li; Breant, Christine; Watts, Ryan J; Eichmann, Anne

2008-08-01

Targeted inactivation of genes involved in murine cardiovascular development frequently leads to abnormalities in blood flow. As blood fluid dynamics play a crucial role in shaping vessel morphology, the presence of flow defects generally prohibits the precise assignment of the role of the mutated gene product in the vasculature. In this study, we show how to distinguish between genetic defects caused by targeted inactivation of the neuropilin 1 (Nrp1) receptor and hemodynamic defects occurring in homozygous knockout embryos. Our analysis of a Nrp1 null allele bred onto a C57BL/6 background shows that vessel remodeling defects occur concomitantly with the onset of blood flow and cause death of homozygous mutants at E10.5. Using mouse embryo culture, we establish that hemodynamic defects are already present at E8.5 and continuous circulation is never established in homozygous mutants. The geometry of yolk sac blood vessels is altered and remodeling into yolk sac arteries and veins does not occur. To separate flow-induced deficiencies from those caused by the Nrp1 mutation, we arrested blood flow in cultured wild-type and mutant embryos and followed their vascular development. We find that loss of Nrp1 function rather than flow induces the altered geometry of the capillary plexus. Endothelial cell migration, but not replication, is altered in Nrp1 mutants. Gene expression analysis of endothelial cells isolated from freshly dissected wild-type and mutants and after culture in no-flow conditions showed down-regulation of the arterial marker genes connexin 40 and ephrin B2 related to the loss of Nrp1 function. This method allows genetic defects caused by loss-of-function of a gene important for cardiovascular development to be isolated even in the presence of hemodynamic defects.

Mathematical modeling of the human body during water replacement and dehydration: body water changes.

PubMed

Downey, D; Seagrave, R C

2000-03-01

A model of the human body that integrates the variables involved in temperature regulation and blood gas transport within the cardiovascular and respiratory systems is presented here. It expands upon previous work to describe the competition between skin and muscles when both require increased blood flows during exercise and/or heat stress. First, a detailed study of the control relations used to predict skin blood flow was undertaken. Four other control relations employed in the model were also examined and modified as indicated by empirical results found in literature. Internal responses to exercise and/or heat stress can affect both thermoregulation and the cardiorespiratory system. Dehydration was studied in addition to complete water replacement during similar environmental and exercise situations. Control relations for skin blood flow and evaporative heat loss were modified and a water balance was added to study how the loss of water through sweat can be limiting. Runoff from sweating as a function of relative humidity was introduced along with evaporation, and these results were compared to data to validate the model.

Autonomic control of the eye

PubMed Central

McDougal, David H.; Gamlin, Paul D.

2016-01-01

The autonomic nervous system influences numerous ocular functions. It does this by way of parasympathetic innervation from postganglionic fibers that originate from neurons in the ciliary and pterygopalatine ganglia, and by way of sympathetic innervation from postganglionic fibers that originate from neurons in the superior cervical ganglion. Ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction, respectively. Superior cervical ganglion neurons project to the dilator pupillae muscle of the iris to control pupil dilation. Ocular blood flow is controlled both via direct autonomic influences on the vasculature of the optic nerve, choroid, ciliary body, and iris, as well as via indirect influences on retinal blood flow. In mammals, this vasculature is innervated by vasodilatory fibers from the pterygopalatine ganglion, and by vasoconstrictive fibers from the superior cervical ganglion. Intraocular pressure is regulated primarily through the balance of aqueous humor formation and outflow. Autonomic regulation of ciliary body blood vessels and the ciliary epithelium is an important determinant of aqueous humor formation; autonomic regulation of the trabecular meshwork and episcleral blood vessels is an important determinant of aqueous humor outflow. These tissues are all innervated by fibers from the pterygopalatine and superior cervical ganglia. In addition to these classical autonomic pathways, trigeminal sensory fibers exert local, intrinsic influences on many of these regions of the eye, as well as on some neurons within the ciliary and pterygopalatine ganglia. PMID:25589275

TRPV4 channels: physiological and pathological role in cardiovascular system.

PubMed

Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2015-11-01

TRPV4 channels are non-selective cation channels permeable to Ca(2+), Na(+), and Mg(2+) ions. Recently, TRPV4 channels have received considerable attention as these channels are widely expressed in the cardiovascular system including endothelial cells, cardiac fibroblasts, vascular smooth muscles, and peri-vascular nerves. Therefore, these channels possibly play a pivotal role in the maintenance of cardiovascular homeostasis. TRPV4 channels critically regulate flow-induced arteriogenesis, TGF-β1-induced differentiation of cardiac fibroblasts into myofibroblasts, and heart failure-induced pulmonary edema. These channels also mediate hypoxia-induced increase in proliferation and migration of pulmonary artery smooth muscle cells and progression of pulmonary hypertension. These channels also maintain flow-induced vasodilation and preserve vascular function by directly activating Ca(2+)-dependent KCa channels. Furthermore, these may also induce vasodilation and maintain blood pressure indirectly by evoking the release of NO, CGRP, and substance P. The present review discusses the evidences and the potential mechanisms implicated in diverse responses including arteriogenesis, cardiac remodeling, congestive heart failure-induced pulmonary edema, pulmonary hypertension, flow-induced dilation, regulation of blood pressure, and hypoxic preconditioning.

A Nonlinear Dynamic Approach Reveals a Long-Term Stroke Effect on Cerebral Blood Flow Regulation at Multiple Time Scales

PubMed Central

Hu, Kun; Lo, Men-Tzung; Peng, Chung-Kang; Liu, Yanhui; Novak, Vera

2012-01-01

Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary physiological signals. PMID:22807666

PPAR-γ Regulates Carnitine Homeostasis and Mitochondrial Function in a Lamb Model of Increased Pulmonary Blood Flow

PubMed Central

Rafikov, Ruslan; Kumar, Sanjiv; Hou, Yali; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Fineman, Jeffrey R.; Black, Stephen M.

2012-01-01

Objective Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-γ expression in Shunt lambs. Thus, this study was carried out to determine if there is a causal link between loss of PPAR-γ signaling and carnitine dysfunction, and whether the PPAR-γ agonist, rosiglitazone preserves carnitine homeostasis in Shunt lambs. Methods and Results siRNA-mediated PPAR-γ knockdown significantly reduced carnitine palmitoyltransferases 1 and 2 (CPT1 and 2) and carnitine acetyltransferase (CrAT) protein levels. This decrease in carnitine regulatory proteins resulted in a disruption in carnitine homeostasis and induced mitochondrial dysfunction, as determined by a reduction in cellular ATP levels. In turn, the decrease in cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90 interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment preserved carnitine homeostasis and attenuated the development of mitochondrial dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved eNOS/Hsp90 interactions and NO signaling. Conclusion Our study indicates that PPAR-γ signaling plays an important role in maintaining mitochondrial function through the regulation of carnitine homeostasis both in vitro and in vivo. Further, it identifies a new mechanism by which PPAR-γ regulates NO signaling through Hsp90. Thus, PPAR-γ agonists may have therapeutic potential in preventing the endothelial dysfunction in children with increased pulmonary blood flow. PMID:22962578

Propranolol and atropine do not alter choroidal blood flow regulation during isometric exercise in healthy humans.

PubMed

Polska, Elzbieta; Luksch, Alexandra; Schering, Joanne; Frank, Barbara; Imhof, Andrea; Fuchsjäger-Mayrl, Gabriele; Wolzt, Michael; Schmetterer, Leopold

2003-01-01

Recent studies indicate that the human choroid has a considerable capacity to keep blood flow constant despite exercise-induced increases in perfusion pressure. The mechanisms underlying this vasoconstrictor response remain unclear. We hypothesized that pharmacological modulation of the autonomic nervous system may alter the choroidal pressure/flow relationship during squatting. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, three-way crossover study in 15 healthy male volunteers. Subjects received, on different study days, intravenous infusions of the beta-adrenoceptor antagonist propranolol, the muscarinic receptor antagonist atropine, or placebo. During these infusions, subjects performed squatting for 6 min. Choroidal blood flow was assessed with laser Doppler flowmetry and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. As expected, propranolol reduced basal pulse rate, whereas atropine increased pulse rate, indicating that the drugs were administered at systemically effective doses. None of the drugs altered the choroidal pressure/flow relationship during isometric exercise. These data indicate that the regulatory vasoconstrictor capacity of the choroid during exercise is not affected by systemic blockade of beta-adrenoceptors or muscarinic receptors.

Clarification of the circulatory patho-physiology of anaesthesia - implications for high-risk surgical patients.

PubMed

Wolff, Christopher B; Green, David W

2014-12-01

The paper examines the effects of anaesthesia on circulatory physiology and their implications regarding improvement in perioperative anaesthetic management. Changes to current anaesthetic practice, recommended recently, such as the use of flow monitoring in high risk patients, are already beginning to have an impact in reducing complications but not mortality [1]. Better understanding of the patho-physiology should help improve management even further. Analysis of selected individual clinical trials has been used to illustrate particular areas of patho-physiology and how changes in practice have improved outcome. There is physiological support for the importance of achieving an appropriate rate of oxygen delivery (DO2), particularly following induction of anaesthesia. It is suggested that ensuring adequate DO2 during anaesthesia will avoid development of oxygen debt and hence obviate the need to induce a high, compensatory, DO2 in the post-operative period. In contrast to the usual assumptions underlying strategies requiring a global increase in blood flow [1] by a stroke volume near maximization strategy, blood flow control actually resides entirely at the tissues not at the heart. This is important as the starting point for understanding failed circulatory control as indicated by 'volume dependency'. Local adjustments in blood flow at each individual organ - auto-regulation - normally ensure the appropriate local rate of oxygen supply, i.e. local DO2. Inadequate blood volume leads to impairment of the regulation of blood flow, particularly in the individual tissues with least capable auto-regulatory capability. As demonstrated by many studies, inadequate blood flow first occurs in the gut, brain and kidney. The inadequate blood volume which occurs with induction of anaesthesia is not due to blood volume loss, but probably results from redistribution due to veno-dilation. The increase in venous capacity renders the existing blood volume inadequate to maintain venous return and pre-load. Blood volume shifted to the veins will, necessarily, also reduce the arterial volume. As a result stroke volume and cardiac output fall below normal with little or no change in peripheral resistance. The resulting pre-load dependency is often successfully treated with colloid infusion and, in some studies, 'inotropic' agents, particularly in the immediate post-operative phase. Treatment during the earliest stage of anaesthesia can avoid the build up of oxygen debt and may be supplemented by drugs which maintain or restore venous tone, such as phenylephrine; an alternative to volume expansion. Interpretation of circulatory patho-physiology during anaesthesia confirms the need to sustain appropriate oxygen delivery. It also supports reduction or even elimination of supplementary crystalloid maintenance infusion, supposedly to replace the "mythical" third space loss. As a rational evidence base for future research it should allow for further improvements in anaesthetic management. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Alternative RNA splicing in the endothelium mediated in part by Rbfox2 regulates the arterial response to low flow

PubMed Central

Butty, Vincent L; Boutz, Paul L; Begum, Shahinoor; Kimble, Amy L; Sharp, Phillip A; Burge, Christopher B

2018-01-01

Low and disturbed blood flow drives the progression of arterial diseases including atherosclerosis and aneurysms. The endothelial response to flow and its interactions with recruited platelets and leukocytes determine disease progression. Here, we report widespread changes in alternative splicing of pre-mRNA in the flow-activated murine arterial endothelium in vivo. Alternative splicing was suppressed by depletion of platelets and macrophages recruited to the arterial endothelium under low and disturbed flow. Binding motifs for the Rbfox-family are enriched adjacent to many of the regulated exons. Endothelial deletion of Rbfox2, the only family member expressed in arterial endothelium, suppresses a subset of the changes in transcription and RNA splicing induced by low flow. Our data reveal an alternative splicing program activated by Rbfox2 in the endothelium on recruitment of platelets and macrophages and demonstrate its relevance in transcriptional responses during flow-driven vascular inflammation. PMID:29293084

Impact of rosiglitazone and glyburide on nitrosative stress and myocardial blood flow regulation in type 2 diabetes mellitus.

PubMed

Pop-Busui, Rodica; Oral, Elif; Raffel, David; Byun, Jaeman; Bajirovic, Valida; Vivekanandan-Giri, Anuradha; Kellogg, Aaron; Pennathur, Subramaniam; Stevens, Martin J

2009-07-01

Cardiovascular disease, the leading cause of death in patients with type 2 diabetes mellitus (T2DM), is usually preceded by endothelial dysfunction and altered myocardial blood flow (MBF) regulation. Hyperglycemia, oxidative-nitrosative stress, systemic inflammation, and insulin resistance are implicated in the pathogenesis of abnormal MBF regulation, myocardial ischemia, and apoptosis. However, the impact of oral antihyperglycemic therapy on myocardial perfusion is controversial. Our objective was to explore the effect of rosiglitazone and glyburide on nitrosative stress and MBF regulation in subjects with T2DM. [(13)N]ammonia positron emission tomography and cold pressor testing were used in 27 diabetic subjects (mean age, 49 +/- 11 years; glycohemoglobin, 7% +/- 1.5%) randomized to either rosiglitazone 8 mg/d or glyburide 10 mg/d for 6 months. Isotope dilution gas chromatography-mass spectrometry was used to quantify plasma 3-nitrotyrosine, a stable marker of reactive nitrogen species. At 6 months, there were no significant differences between groups in the mean glycohemoglobin, blood pressure, or plasma lipids. Rosiglitazone significantly reduced plasma nitrotyrosine, high-sensitivity C-reactive protein, and von Willebrand antigen (P < .03 for all) and significantly increased plasma adiponectin (P < .05). No significant changes in these parameters were observed with glyburide. Treatment with glyburide, but not rosiglitazone, resulted in a significant deterioration in both resting and stress MBF. Rosiglitazone, but not glyburide, ameliorated markers of nitrosative stress and inflammation in subjects with T2DM without impairing myocardial perfusion.

Arterial blood gas management in retrograde cerebral perfusion: the importance of carbon dioxide.

PubMed

Ueno, K; Takamoto, S; Miyairi, T; Morota, T; Shibata, K; Murakami, A; Kotsuka, Y

2001-11-01

Many interventional physiological assessments for retrograde cerebral perfusion (RCP) have been explored. However, the appropriate arterial gas management of carbon dioxide (CO2) remains controversial. The aim of this study is to determine whether alpha-stat or pH-stat could be used for effective brain protection under RCP in terms of cortical cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and distribution of regional cerebral blood flow. Fifteen anesthetized dogs (25.1+/-1.1 kg) on cardiopulmonary bypass (CPB) were cooled to 18 degrees C under alpha-stat management and had RCP for 90 min under: (1), alpha-stat; (2), pH-stat; or (3), deep hypothermic (18 degrees C) antegrade CPB (antegrade). RCP flow was regulated for a sagittal sinus pressure of around 25 mmHg. CBF was monitored by a laser tissue flowmeter. Serial analyses of blood gas were made. The regional cerebral blood flow was measured with colored microspheres before discontinuation of RCP. CBF and CMRO2 were evaluated as the percentage of the baseline level (%CBF, %CMRO2). The oxygen content of arterial inflow and oxygen extraction was not significantly different between the RCP groups. The %CBF and %CMRO2 were significantly higher for pH-stat RCP than for alpha-stat RCP. The regional cerebral blood flow, measured with colored microspheres, tended to be higher for pH-stat RCP than for alpha-stat RCP, at every site in the brain. Irrespective of CO2 management, regional differences were not significant among any site in the brain. CO2 management is crucial for brain protection under deep hypothermic RCP. This study revealed that pH-stat was considered to be better than alpha-stat in terms of CBF and oxygen metabolism in the brain. The regional blood flow distribution was considered to be unchanged irrespective of CO2 management.

Effect of GnRH and hCG on progesterone concentration and ovarian and luteal blood flow in diestrous mares.

PubMed

Brito, L F C; Baldrighi, J M; Wolf, C A; Ginther, O J

2017-01-01

The objective of the present study was to investigate the effect of reproductive hormones (GnRH, hCG, LH and progesterone) on the regulation of corpus luteum (CL) and ovarian blood flow. Diestrous mares received a single treatment of saline, 100μg gonadorelin (GnRH), or 1500IU hCG 10days after ovulation. Plasma LH and progesterone concentrations, resistance index (RI) for ovarian artery blood-flow, and percentage of corpus luteum (CL) with color-Doppler signals of blood flow were determined immediately before treatment (hour 0) and at hours 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 6. In the GnRH group, LH increased (P<0.0001) between hours 0 and 0.25 and then progressively decreased; concentration of LH was not affected in the saline and hCG groups. Progesterone concentration was not different among groups. In the GnRH group, RI tended (P<0.07) to decrease between hours 0 and 1.5 and increased (P<0.01) between hours 1.5 and 4. In the hCG group, two transient RI decreases (P<0.05) occurred before hour 2. The percentage change from hour 0 in the percentage of CL with blood-flow signals was greater at hour 0.5 in the GnRH group than in the saline group and was intermediate in the hCG group. The similarity among groups in progesterone concentration indicated that changes in progesterone were not involved in the GnRH and hCG stimulation of ovarian vascular perfusion. Effects of treatment might have been mediated through LH; however, since hCG biological activity is primarily LH-like, the differences in timing and degree of ovarian and luteal blood flow changes after GnRH or hCG administration in the present study suggest that GnRH might have a direct effect on ovarian blood vessels and vascular control. Copyright © 2016. Published by Elsevier B.V.

Relationship between cerebral blood flow and blood pressure in long-term heart transplant recipients.

PubMed

Smirl, Jonathan D; Haykowsky, Mark J; Nelson, Michael D; Tzeng, Yu-Chieh; Marsden, Katelyn R; Jones, Helen; Ainslie, Philip N

2014-12-01

Heart transplant recipients are at an increased risk for cerebral hemorrhage and ischemic stroke; yet, the exact mechanism for this derangement remains unclear. We hypothesized that alterations in cerebrovascular regulation is principally involved. To test this hypothesis, we studied cerebral pressure-flow dynamics in 8 clinically stable male heart transplant recipients (62±8 years of age and 9±7 years post transplant, mean±SD), 9 male age-matched controls (63±8 years), and 10 male donor controls (27±5 years). To increase blood pressure variability and improve assessment of the pressure-flow dynamics, subjects performed squat-stand maneuvers at 0.05 and 0.10 Hz. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal carbon dioxide were continuously measured during 5 minutes of seated rest and throughout the squat-stand maneuvers. Cardiac baroreceptor sensitivity gain and cerebral pressure-flow responses were assessed with linear transfer function analysis. Heart transplant recipients had reductions in R-R interval power and baroreceptor sensitivity low frequency gain (P<0.01) compared with both control groups; however, these changes were unrelated to transfer function metrics. Thus, in contrast to our hypothesis, the increased risk of cerebrovascular complication after heart transplantation does not seem to be related to alterations in cerebral pressure-flow dynamics. Future research is, therefore, warranted. © 2014 American Heart Association, Inc.

Acute tamponade alters subendo- and subepicardial pressure-flow relations differently during vasodilation.

PubMed

Kingma, J G; Martin, J; Rouleau, J R

1994-07-01

Instantaneous diastolic left coronary artery pressure-flow relations (PFR) shift during acute tamponade as pressure surrounding the heart increases. Coronary pressure at zero flow (Pf = 0) on the linear portion of the PFR is the weighted mean of the different myocardial waterfall pressures, the distribution of which varies across the left ventricular wall during diastole. However, instantaneous PFR measured in large epicardial coronary arteries cannot be used to estimate Pf = 0 in the different myocardial tissue layers. During coronary vasodilatation in a capacitance-free model, myocardial PFR differs from subendocardium to subepicardium. Therefore, we studied the effects of acute tamponade during maximal pharmacology induced coronary vasodilatation on myocardial PFR in in situ anesthetized dogs. Tamponade reduced cardiac output, aortic pressure, and coronary blood flow. Results demonstrate that different mechanisms influence distribution of myocardial blood flow during tamponade. Subepicardial vascular resistance is unchanged and the extrapolated Pf = 0 is increased, thereby shifting PFR to a higher intercept on the pressure axis. Subendocardial vascular resistance is increased while the extrapolated Pf = 0 remains unchanged. Results indicate that in the setting of acute tamponade with coronary vasodilatation different mechanisms regulate the distribution of myocardial blood flow: in the subepicardium only outflow pressure increases, whereas in the subendocardium only vascular resistance increases.

Blood pressure long term regulation: A neural network model of the set point development

PubMed Central

2011-01-01

Background The notion of the nucleus tractus solitarius (NTS) as a comparator evaluating the error signal between its rostral neural structures (RNS) and the cardiovascular receptor afferents into it has been recently presented. From this perspective, stress can cause hypertension via set point changes, so offering an answer to an old question. Even though the local blood flow to tissues is influenced by circulating vasoactive hormones and also by local factors, there is yet significant sympathetic control. It is well established that the state of maturation of sympathetic innervation of blood vessels at birth varies across animal species and it takes place mostly during the postnatal period. During ontogeny, chemoreceptors are functional; they discharge when the partial pressures of oxygen and carbon dioxide in the arterial blood are not normal. Methods The model is a simple biological plausible adaptative neural network to simulate the development of the sympathetic nervous control. It is hypothesized that during ontogeny, from the RNS afferents to the NTS, the optimal level of each sympathetic efferent discharge is learned through the chemoreceptors' feedback. Its mean discharge leads to normal oxygen and carbon dioxide levels in each tissue. Thus, the sympathetic efferent discharge sets at the optimal level if, despite maximal drift, the local blood flow is compensated for by autoregulation. Such optimal level produces minimum chemoreceptor output, which must be maintained by the nervous system. Since blood flow is controlled by arterial blood pressure, the long-term mean level is stabilized to regulate oxygen and carbon dioxide levels. After development, the cardiopulmonary reflexes play an important role in controlling efferent sympathetic nerve activity to the kidneys and modulating sodium and water excretion. Results Starting from fixed RNS afferents to the NTS and random synaptic weight values, the sympathetic efferents converged to the optimal values. When learning was completed, the output from the chemoreceptors became zero because the sympathetic efferents led to normal partial pressures of oxygen and carbon dioxide. Conclusions We introduce here a simple simulating computational theory to study, from a neurophysiologic point of view, the sympathetic development of cardiovascular regulation due to feedback signals sent off by cardiovascular receptors. The model simulates, too, how the NTS, as emergent property, acts as a comparator and how its rostral afferents behave as set point. PMID:21693057

Neural control of renal tubular sodium reabsorption of the dog.

PubMed

DiBona, G F

1978-04-01

The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies demonstrate adrenergic nerve terminals in direct contact with basement membranes of mammalian renal tubular epithelial cells. Low level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. The antinatriuresis is prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney upon renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. Reflex diminutions in renal nerve activity (left atrial distention, stellate ganglion stimulation) produce a decrease in renal tubular sodium reabsorption independent of glomerular filtration rate or renal blood flow. The anatomically described adrenergic innervation of the renal tubules participates in the direct regulation of renal tubular sodium reabsorption.

Regional blood flow in sea turtles: implications for heat exchange in an aquatic ectotherm.

PubMed

Hochscheid, Sandra; Bentivegna, Flegra; Speakman, John R

2002-01-01

Despite substantial knowledge on thermoregulation in reptiles, the mechanisms involved in heat exchange of sea turtles have not been investigated in detail. We studied blood flow in the front flippers of two green turtles, Chelonia mydas, and four loggerhead turtles, Caretta caretta, using Doppler ultrasound to assess the importance of regional blood flow in temperature regulation. Mean blood flow velocity and heart rate were determined for the water temperature at which the turtles were acclimated (19.3 degrees-22.5 degrees C) and for several experimental water temperatures (17 degrees-32 degrees C) to which the turtles were exposed for a short time. Flipper circulation increased with increasing water temperature, whereas during cooling, flipper circulation was greatly reduced. Heart rate was also positively correlated with water temperature; however, there were large variations between individual heart rate responses. Body temperatures, which were additionally determined for the two green turtles and six loggerhead turtles, increased faster during heating than during cooling. Heating rates were positively correlated with the difference between acclimation and experimental temperature and negatively correlated with body mass. Our data suggest that by varying circulation of the front flippers, turtles are capable of either transporting heat quickly into the body or retaining heat inside the body, depending on the prevailing thermal demands.

Enhancing cell-free layer thickness by bypass channels in a wall.

PubMed

Saadatmand, M; Shimogonya, Y; Yamaguchi, T; Ishikawa, T

2016-07-26

When blood flows near a wall, red blood cells (RBCs) drift away from the wall and a cell-free layer (CFL) is formed adjacent to the wall. Controlling the CFL thickness is important for preventing adhesion of cells in the design of biomedical devices. In this study, a novel wall configuration with stenoses and bypass channels is proposed to increase the CFL thickness. We found that the presence of bypass channels modified the spatial distribution of cells and substantially increased the CFL downstream of the stenosis. A single-bypass geometry with 5% hematocrit (Hct) blood flow showed a 1.7μm increase in CFL thickness compared to without the bypass. In the case of three bypass channels, a 3μm increase in CFL thickness was observed. The CFL enhancement was observed up to 10% Hct, but no significant enhancement of CFL was indicated for 20% Hct blood flow. The mechanism of the CFL enhancement was investigated using a numerical simulation of the flow field. The results showed that the distance between each streamline and the corner of the stenosis compared with size of RBC was important parameter in regulating CFL thickness. These results show the potential of the proposed mechanism to prevent adhesion of cells to biomedical devices. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effects of capillary transit time heterogeneity (CTH) on brain oxygenation

PubMed Central

Angleys, Hugo; Østergaard, Leif; Jespersen, Sune N

2015-01-01

We recently extended the classic flow–diffusion equation, which relates blood flow to tissue oxygenation, to take capillary transit time heterogeneity (CTH) into account. Realizing that cerebral oxygen availability depends on both cerebral blood flow (CBF) and capillary flow patterns, we have speculated that CTH may be actively regulated and that changes in the capillary morphology and function, as well as in blood rheology, may be involved in the pathogenesis of conditions such as dementia and ischemia-reperfusion injury. The first extended flow–diffusion equation involved simplifying assumptions which may not hold in tissue. Here, we explicitly incorporate the effects of oxygen metabolism on tissue oxygen tension and extraction efficacy, and assess the extent to which the type of capillary transit time distribution affects the overall effects of CTH on flow–metabolism coupling reported earlier. After incorporating tissue oxygen metabolism, our model predicts changes in oxygen consumption and tissue oxygen tension during functional activation in accordance with literature reports. We find that, for large CTH values, a blood flow increase fails to cause significant improvements in oxygen delivery, and can even decrease it; a condition of malignant CTH. These results are found to be largely insensitive to the choice of the transit time distribution. PMID:25669911

Oxygen-limited thermal tolerance in Antarctic fish investigated by MRI and (31)P-MRS.

PubMed

Mark, F C; Bock, C; Pörtner, H O

2002-11-01

The hypothesis of an oxygen-limited thermal tolerance was tested in the Antarctic teleost Pachycara brachycephalum. With the use of flow-through respirometry, in vivo (31)P-NMR spectroscopy, and MRI, we studied energy metabolism, intracellular pH (pH(i)), blood flow, and oxygenation between 0 and 13 degrees C under normoxia (PO(2): 20.3 to 21.3 kPa) and hyperoxia (PO(2): 45 kPa). Hyperoxia reduced the metabolic increment and the rise in arterial blood flow observed under normoxia. The normoxic increase of blood flow leveled off beyond 7 degrees C, indicating a cardiovascular capacity limitation. Ventilatory effort displayed an exponential rise in both groups. In the liver, blood oxygenation increased, whereas in white muscle it remained unaltered (normoxia) or declined (hyperoxia). In both groups, the slope of pH(i) changes followed the alpha-stat pattern below 6 degrees C, whereas it decreased above. In conclusion, aerobic scope declines around 6 degrees C under normoxia, marking the pejus temperature. By reducing circulatory costs, hyperoxia improves aerobic scope but is unable to shift the breakpoint in pH regulation or lethal limits. Hyperoxia appears beneficial at sublethal temperatures, but no longer beyond when cellular or molecular functions become disturbed.

PHYSIOLOGICAL ACTIVITY OF THE BROWN ADIPOSE TISSUE.

DTIC Science & Technology

Studies were performed to clarify the influence of various factors which might be involved in vascular regulation. Topical application of lidocain ...and treatment with reserpine effectively blocked, while denervation of brown fat, syrosingopine and atropine were ineffective to prevent the blood flow

Choroidal hemodynamic changes during isometric exercise in patients with inactive central serous chorioretinopathy.

PubMed

Tittl, Michael; Maar, Noemi; Polska, Elzbieta; Weigert, Günther; Stur, Michael; Schmetterer, Leopold

2005-12-01

Imaging studies suggest that the choroidal vasculature may be altered in central serous chorioretinopathy. Little is known, however, about the regulation of ocular blood flow in patients with central serous chorioretinopathy (CSC). The hypothesis for the present study was that choroidal blood flow changes during an increase in ocular perfusion pressure induced by isometric exercise may be altered in CSC. An observer-masked, two-cohort study was performed in 14 nonsmoking patients with chronic-relapsing but inactive CSC and in 14 healthy nonsmoking volunteers. Both groups were matched for age and sex. Subfoveal choroidal blood flow (CBF) was assessed with laser Doppler flowmetry, and ocular perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and intraocular pressure (IOP). Changes of CBF during isometric exercise over a period of 6 minutes were measured. Whereas the increase of MAP, the pulse rate, and the OPP were comparable between the two study groups, subfoveal CBF increased significantly more in the group of patients with CSC (P < 0.001). IOP remained unchanged in both groups during isometric exercise. At an 85% increase in OPP, subfoveal CBF was approximately twice as high in the patients with CSC compared with the healthy control group. The data indicate an abnormal subfoveal CBF regulation in patients with relapsing CSC compared with age-matched, nonsmoking, healthy volunteers during isometric exercise.

Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans.

PubMed

Trangmar, Steven J; Chiesa, Scott T; Stock, Christopher G; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

2014-07-15

Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra-cranial blood flow), middle cerebral artery velocity (MCA Vmean), arterial-venous differences and blood temperature in 10 trained males during incremental cycling to exhaustion in the heat (35°C) in control, dehydrated and rehydrated states. Dehydration reduced body mass (75.8 ± 3 vs. 78.2 ± 3 kg), increased internal temperature (38.3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12-23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast decline in cerebral perfusion with dehydration was accompanied by increased O2 extraction (P < 0.05), resulting in a maintained cerebral metabolic rate for oxygen (CMRO2). In all conditions, reductions in ICA and MCA Vmean were associated with declining cerebral vascular conductance, increasing jugular venous noradrenaline, and falling arterial carbon dioxide tension (P aCO 2) (R(2) ≥ 0.41, P ≤ 0.01) whereas CCA flow and conductance were related to elevated blood temperature. In conclusion, dehydration accelerated the decline in CBF by decreasing P aCO 2 and enhancing vasoconstrictor activity. However, the circulatory strain on the human brain during maximal exercise does not compromise CMRO2 because of compensatory increases in O2 extraction. © 2014 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans

PubMed Central

Trangmar, Steven J; Chiesa, Scott T; Stock, Christopher G; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

2014-01-01

Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra-cranial blood flow), middle cerebral artery velocity (MCA Vmean), arterial–venous differences and blood temperature in 10 trained males during incremental cycling to exhaustion in the heat (35°C) in control, dehydrated and rehydrated states. Dehydration reduced body mass (75.8 ± 3 vs. 78.2 ± 3 kg), increased internal temperature (38.3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12–23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast decline in cerebral perfusion with dehydration was accompanied by increased O2 extraction (P < 0.05), resulting in a maintained cerebral metabolic rate for oxygen (CMRO2). In all conditions, reductions in ICA and MCA Vmean were associated with declining cerebral vascular conductance, increasing jugular venous noradrenaline, and falling arterial carbon dioxide tension () (R2 ≥ 0.41, P ≤ 0.01) whereas CCA flow and conductance were related to elevated blood temperature. In conclusion, dehydration accelerated the decline in CBF by decreasing and enhancing vasoconstrictor activity. However, the circulatory strain on the human brain during maximal exercise does not compromise CMRO2 because of compensatory increases in O2 extraction. PMID:24835170

OXYGEN TRANSPORT IN THE MICROCIRCULATION AND ITS REGULATION

PubMed Central

Pittman, Roland N.

2012-01-01

Cells require energy to carry out their functions and they typically use oxidative phosphorylation to generate the needed ATP. Thus, cells have a continuous need for oxygen which they receive by diffusion from the blood through the interstitial fluid. The circulatory system pumps oxygen-rich blood through a network of increasingly minute vessels, the microcirculation. The structure of the microcirculation is such that all cells have at least one nearby capillary for diffusive exchange of oxygen and red blood cells release the oxygen bound to hemoglobin as they traverse capillaries. This review focuses first on the historical development of techniques to measure oxygen at various sites in the microcirculation, including the blood, interstitium and cells. Next, approaches are described as to how these techniques have been employed to make discoveries about different aspects of oxygen transport. Finally, ways in which oxygen might participate in the regulation of blood flow toward matching oxygen supply to oxygen demand is discussed. Overall, the transport of oxygen to the cells of the body is one of the most critical functions of the cardiovascular system and it is in the microcirculation where the final local determinants of oxygen supply, oxygen demand and their regulation are decided. PMID:23025284

Anatomy and Physiology of the Blood-Brain Barrier

PubMed Central

Serlin, Yonatan; Shelef, Ilan; Knyazer, Boris; Friedman, Alon

2015-01-01

Essential requisite for the preservation of normal brain activity is to maintain a narrow and stable homeostatic control in the neuronal environment of the CNS. Blood flow alterations and altered vessel permeability are considered key determinants in the pathophysiology of brain injuries. We will review the present-day literature on the anatomy, development and physiological mechanisms of the blood-brain barrier, a distinctive and tightly regulated interface between the CNS and the peripheral circulation, playing a crucial role in the maintenance of the strict environment required for normal brain function. PMID:25681530

Regulation of choroidal blood flow during combined changes in intraocular pressure and arterial blood pressure.

PubMed

Polska, Elzbieta; Simader, Christian; Weigert, Günter; Doelemeyer, Arno; Kolodjaschna, Julia; Scharmann, Ole; Schmetterer, Leopold

2007-08-01

To test the hypothesis that human choroidal blood flow (ChBF) may depend, not only on ocular perfusion pressure (OPP), but also on absolute mean arterial pressure (MAP) and intraocular pressure (IOP). There were two study days in an open design. On the first day, OPP was varied by elevating IOP during a squatting-induced increase in MAP (28 subjects). On the second day, only the IOP was increased (17 subjects). IOP was raised in stepwise increments by using the suction cup Subfoveal ChBF (laser Doppler flowmetry), MAP, and IOP were assessed, and OPP was calculated as (2/3)(MAP - IOP). For correlation analysis, data from all subjects were pooled according to IOP and MAP, and correlation analyses were performed. When data from study day 1 were grouped according to IOP, no correlation was observed between ChBF and MAP; but ChBFs were lower, the higher the IOP (P < 0.001). When data were grouped according to MAP, a significant correlation was found between ChBF and IOP (P < 0.001), but correlations were independent of MAP. When data of study day 2 were pooled according to IOP, a correlation between ChBF and OPP was seen only at IOP > 40 mm Hg (P < 0.05). The data confirm previously published observations that the choroid shows some autoregulatory capacity during changes in OPP. In addition, the data indicate that the choroid regulates its blood flow better during exercise-induced changes in MAP than during an experimental increase in IOP.

Mathematical modeling of renal hemodynamics in physiology and pathophysiology.

PubMed

Sgouralis, Ioannis; Layton, Anita T

2015-06-01

In addition to the excretion of metabolic waste and toxin, the kidney plays an indispensable role in regulating the balance of water, electrolyte, acid-base, and blood pressure. For the kidney to maintain proper functions, hemodynamic control is crucial. In this review, we describe representative mathematical models that have been developed to better understand the kidney's autoregulatory processes. We consider mathematical models that simulate glomerular filtration, and renal blood flow regulation by means of the myogenic response and tubuloglomerular feedback. We discuss the extent to which these modeling efforts have expanded the understanding of renal functions in health and disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Rotary Blood Pump

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr. (Inventor); Akkerman, James W. (Inventor); Aber, Gregory S. (Inventor); VanDamm, George A. (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

1996-01-01

A rotary blood pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial and radial clearances of blades associated with the flow straightener, inducer portion, impeller portion and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with cross-linked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

Rotary blood pump

NASA Astrophysics Data System (ADS)

Bozeman, Richard J.; Akkerman, James W.; Aber, Greg S.; Vandamm, George A.; Bacak, James W.; Svejkovsky, Paul A.; Benkowski, Robert J.

1993-11-01

A rotary blood pump is presented. The pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial, and radial clearances of the blades associated with the flow straightener, inducer portion, impeller portion, and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with crosslinked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

Development of a new control device for stabilizing blood level in reservoir during extracorporeal circulation.

PubMed

Momose, Naoki; Yamakoshi, Rie; Kokubo, Ryo; Yasuda, Toru; Iwamoto, Norio; Umeda, Chinori; Nakajima, Itsuro; Yanagisawa, Mitsunobu; Tomizawa, Yasuko

2010-03-01

We developed a simple device that stabilizes the blood level in the reservoir of the extracorporeal circulation open circuit system by measuring the hydrostatic pressure of the reservoir to control the flow rate of the arterial pump. When the flow rate of the venous return decreases, the rotation speed of the arterial pump is automatically slowed down. Consequently, the blood level in the reservoir is stabilized quickly between two arbitrarily set levels and never falls below the pre-set low level. We conducted a basic experiment to verify the operation of the device, using a mock circuit with water. Commercially available pumps and reservoir were used without modification. The results confirmed that the control method effectively regulates the reservoir liquid level and is highly reliable. The device possibly also functions as a safety device.

Rotary blood pump

NASA Technical Reports Server (NTRS)

Bozeman, Richard J. (Inventor); Akkerman, James W. (Inventor); Aber, Greg S. (Inventor); Vandamm, George A. (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

1993-01-01

A rotary blood pump is presented. The pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial, and radial clearances of the blades associated with the flow straightener, inducer portion, impeller portion, and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with crosslinked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

Autonomic control of body temperature and blood pressure: influences of female sex hormones.

PubMed

Charkoudian, Nisha; Hart, Emma C J; Barnes, Jill N; Joyner, Michael J

2017-06-01

Female reproductive hormones exert important non-reproductive influences on autonomic regulation of body temperature and blood pressure. Estradiol and progesterone influence thermoregulation both centrally and peripherally, where estradiol tends to promote heat dissipation, and progesterone tends to promote heat conservation and higher body temperatures. Changes in thermoregulation over the course of the menstrual cycle and with hot flashes at menopause are mediated by hormonal influences on neural control of skin blood flow and sweating. The influence of estradiol is to promote vasodilation, which, in the skin, results in greater heat dissipation. In the context of blood pressure regulation, both central and peripheral hormonal influences are important as well. Peripherally, the vasodilator influence of estradiol contributes to the lower blood pressures and smaller risk of hypertension seen in young women compared to young men. This is in part due to a mechanism by which estradiol augments beta-adrenergic receptor mediated vasodilation, offsetting alpha-adrenergic vasoconstriction, and resulting in a weak relationship between muscle sympathetic nerve activity and total peripheral resistance, and between muscle sympathetic nerve activity and blood pressure. After menopause, with the loss of reproductive hormones, sympathetic nerve activity, peripheral resistance and blood pressure become more strongly related, and sympathetic nerve activity (which increases with age) becomes a more important contributor to the prevailing level of blood pressure. Continuing to increase our understanding of sex hormone influences on body temperature and blood pressure regulation will provide important insight for optimization of individualized health care for future generations of women.

Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice.

PubMed

Mergia, Evanthia; Thieme, Manuel; Hoch, Henning; Daniil, Georgios; Hering, Lydia; Yakoub, Mina; Scherbaum, Christina Rebecca; Rump, Lars Christian; Koesling, Doris; Stegbauer, Johannes

2018-03-23

Nitric oxide (NO) modulates renal blood flow (RBF) and kidney function and is involved in blood pressure (BP) regulation predominantly via stimulation of the NO-sensitive guanylyl cyclase (NO-GC), existing in two isoforms, NO-GC1 and NO-GC2. Here, we used isoform-specific knockout (KO) mice and investigated their contribution to renal hemodynamics under normotensive and angiotensin II-induced hypertensive conditions. Stimulation of the NO-GCs by S -nitrosoglutathione (GSNO) reduced BP in normotensive and hypertensive wildtype (WT) and NO-GC2-KO mice more efficiently than in NO-GC1-KO. NO-induced increase of RBF in normotensive mice did not differ between the genotypes, but the respective increase under hypertensive conditions was impaired in NO-GC1-KO. Similarly, inhibition of endogenous NO increased BP and reduced RBF to a lesser extent in NO-GC1-KO than in NO-GC2-KO. These findings indicate NO-GC1 as a target of NO to normalize RBF in hypertension. As these effects were not completely abolished in NO-GC1-KO and renal cyclic guanosine monophosphate (cGMP) levels were decreased in both NO-GC1-KO and NO-GC2-KO, the results suggest an additional contribution of NO-GC2. Hence, NO-GC1 plays a predominant role in the regulation of BP and RBF, especially in hypertension. However, renal NO-GC2 appears to compensate the loss of NO-GC1, and is able to regulate renal hemodynamics under physiological conditions.

Endocannabinoids in cerebrovascular regulation

PubMed Central

Ruisanchez, Éva; Leszl-Ishiguro, Miriam; Sándor, Péter; Pacher, Pál

2016-01-01

The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation. PMID:26825517

Endocannabinoids in cerebrovascular regulation.

PubMed

Benyó, Zoltán; Ruisanchez, Éva; Leszl-Ishiguro, Miriam; Sándor, Péter; Pacher, Pál

2016-04-01

The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation.

Modeling of Kidney Hemodynamics: Probability-Based Topology of an Arterial Network.

PubMed

Postnov, Dmitry D; Marsh, Donald J; Postnov, Dmitry E; Braunstein, Thomas H; Holstein-Rathlou, Niels-Henrik; Martens, Erik A; Sosnovtseva, Olga

2016-07-01

Through regulation of the extracellular fluid volume, the kidneys provide important long-term regulation of blood pressure. At the level of the individual functional unit (the nephron), pressure and flow control involves two different mechanisms that both produce oscillations. The nephrons are arranged in a complex branching structure that delivers blood to each nephron and, at the same time, provides a basis for an interaction between adjacent nephrons. The functional consequences of this interaction are not understood, and at present it is not possible to address this question experimentally. We provide experimental data and a new modeling approach to clarify this problem. To resolve details of microvascular structure, we collected 3D data from more than 150 afferent arterioles in an optically cleared rat kidney. Using these results together with published micro-computed tomography (μCT) data we develop an algorithm for generating the renal arterial network. We then introduce a mathematical model describing blood flow dynamics and nephron to nephron interaction in the network. The model includes an implementation of electrical signal propagation along a vascular wall. Simulation results show that the renal arterial architecture plays an important role in maintaining adequate pressure levels and the self-sustained dynamics of nephrons.

KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine

PubMed Central

Goodwill, Adam G.; Fu, Lijuan; Noblet, Jillian N.; Casalini, Eli D.; Berwick, Zachary C.; Kassab, Ghassan S.; Tune, Johnathan D.

2016-01-01

Hydrogen peroxide (H2O2) and voltage-dependent K+ (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli. PMID:26825518

KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine.

PubMed

Goodwill, Adam G; Fu, Lijuan; Noblet, Jillian N; Casalini, Eli D; Sassoon, Daniel; Berwick, Zachary C; Kassab, Ghassan S; Tune, Johnathan D; Dick, Gregory M

2016-03-15

Hydrogen peroxide (H2O2) and voltage-dependent K(+) (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli. Copyright © 2016 the American Physiological Society.

Enteral Arginine Does Not Increase Superior Mesenteric Arterial Blood Flow but Induces Mucosal Growth in Neonatal Pigs123

PubMed Central

Puiman, Patrycja J.; Stoll, Barbara; van Goudoever, Johannes B.; Burrin, Douglas G.

2011-01-01

Arginine is an essential amino acid in neonates synthesized by gut epithelial cells and a precursor for NO that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemia-reperfusion models and low plasma levels are associated with necrotizing enterocolitis. We hypothesized that enteral arginine is a specific stimulus for neonatal intestinal blood flow and mucosal growth under conditions of total parenteral nutrition (TPN) or partial enteral nutrition (PEN). We first tested the dose dependence and specificity of acute (3 h) enteral arginine infusion on superior mesenteric artery (SMA) blood flow in pigs fed TPN or PEN. We then determined whether chronic (4 d) arginine supplementation of PEN increases mucosal growth and if this was affected by treatment with the NO synthase inhibitor, NG-nitro-l-arginine methyl ester (L-NAME). Acute enteral arginine infusion increased plasma arginine dose dependently in both TPN and PEN groups, but the plasma response was markedly higher (100–250%) in the PEN group than in the TPN group at the 2 highest arginine doses. Baseline SMA blood flow was 90% higher in the PEN (2.37 ± 0.32 L⋅kg−1⋅h−1) pigs than in the TPN pigs (1.23 ± 0.17 L⋅kg−1⋅h−1), but was not affected by acute infusion individually of arginine, citrulline, or other major gut fuels. Chronic dietary arginine supplementation in PEN pigs induced mucosal growth in the intestine, but this effect was not prevented by treatment with L-NAME. Intestinal crypt cell proliferation, protein synthesis, and phosphorylation of mammalian target of rapamycin and p70S6 kinase were not affected by dietary arginine. We conclude that partial enteral feeding, but not acute enteral arginine, increases SMA blood flow in the neonatal pig. Furthermore, supplementing arginine in partial enteral feeding modestly increases intestinal mucosal growth and was NO independent. PMID:21106927

Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo.

PubMed

Thuesen, Anne D; Andersen, Henrik; Cardel, Majken; Toft, Anja; Walter, Steen; Marcussen, Niels; Jensen, Boye L; Bie, Peter; Hansen, Pernille B L

2014-08-15

Voltage-gated Ca(2+) (Cav) channels play an essential role in the regulation of renal blood flow and glomerular filtration rate (GFR). Because T-type Cav channels are differentially expressed in pre- and postglomerular vessels, it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed with the use of two T-type Cav knockout (Cav3.1(-/-) and Cav3.2(-/-)) mouse strains. Continuous recordings of blood pressure and heart rate, para-aminohippurate clearance (renal plasma flow), and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild-type (WT) and Cav3.1(-/-) and Cav3.2(-/-) mice. The contractility of afferent and efferent arterioles was determined in isolated perfused blood vessels. Efferent arterioles from Cav3.2(-/-) mice constricted significantly more in response to a depolarization compared with WT mice. GFR was increased in Cav3.2(-/-) mice with no significant changes in renal plasma flow, heart rate, and blood pressure. Cav3.1(-/-) mice had a higher renal plasma flow compared with WT mice, whereas GFR was indistinguishable from WT mice. No difference in the concentration response to K(+) was observed in isolated afferent and efferent arterioles from Cav3.1(-/-) mice compared with WT mice. Heart rate was significantly lower in Cav3.1(-/-) mice compared with WT mice with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intrarenal arteries in response to a small depolarization. In conclusion, Cav3.2 channels support dilatation of efferent arterioles and affect GFR, whereas Cav3.1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Cav3.2 and Cav3.1, respectively, may account for the observed effects. Copyright © 2014 the American Physiological Society.

Range of control of cardiovascular variables by the hypothalamus

NASA Technical Reports Server (NTRS)

Smith, O. A.; Stephenson, R. B.; Randall, D. C.

1974-01-01

New methodologies were utilized to study the influence of the hypothalamus on the cardiovascular system. The regulation of myocardial activity was investigated in monkeys with hypothalamic lesions that eliminate cardiovascular responses. Observations showed that a specific part of the hypothalamus regulates changes in myocardial contractility that accompanies emotion. Studies of the hypothalamus control of renal blood flow showed the powerful potential control of this organ over renal circulation.

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling

PubMed Central

Schiffner, René; Bischoff, Sabine Juliane; Lehmann, Thomas; Rakers, Florian; Rupprecht, Sven; Reiche, Juliane; Matziolis, Georg; Schubert, Harald; Schwab, Matthias; Huber, Otmar; Schmidt, Martin

2017-01-01

Background: Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. Methods: Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored. Urapidil was used for α1A-adrenergic receptor blockade in dosages, which did not modify the MABP-response to blood loss. Western blot and quantitative reverse transcription polymerase chain reactions were used to determine adrenergic receptor expression in brain arterioles. Results: During hypovolemia subcortical CBF was maintained at 81 ± 6% of baseline, whereas cortical CBF decreased to 40 ± 4% (p < 0.001). Reperfusion led to peak CBFs of about 70% above baseline in both brain regions. α1A-Adrenergic blockade massively reduced subcortical CBF during hemorrhage and reperfusion, and prevented hyperperfusion during reperfusion in the cortex. α1A-mRNA expression was significantly higher in the cortex, whereas α1D-mRNA expression was higher in the subcortex (p < 0.001). Conclusions: α1-Adrenergic receptors are critical for perfusion redistribution: activity of the α1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the α1D-receptor subtype may determine the magnitude of redistribution responses. PMID:28492488

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling.

PubMed

Schiffner, René; Bischoff, Sabine Juliane; Lehmann, Thomas; Rakers, Florian; Rupprecht, Sven; Reiche, Juliane; Matziolis, Georg; Schubert, Harald; Schwab, Matthias; Huber, Otmar; Schmidt, Martin

2017-05-11

Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored. Urapidil was used for α1A-adrenergic receptor blockade in dosages, which did not modify the MABP-response to blood loss. Western blot and quantitative reverse transcription polymerase chain reactions were used to determine adrenergic receptor expression in brain arterioles. During hypovolemia subcortical CBF was maintained at 81 ± 6% of baseline, whereas cortical CBF decreased to 40 ± 4% ( p < 0.001). Reperfusion led to peak CBFs of about 70% above baseline in both brain regions. α1A-Adrenergic blockade massively reduced subcortical CBF during hemorrhage and reperfusion, and prevented hyperperfusion during reperfusion in the cortex. α1A-mRNA expression was significantly higher in the cortex, whereas α1D-mRNA expression was higher in the subcortex ( p < 0.001). α1-Adrenergic receptors are critical for perfusion redistribution: activity of the α1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the α1D-receptor subtype may determine the magnitude of redistribution responses.

Neurophysiological, metabolic and cellular compartments that drive neurovascular coupling and neuroimaging signals

PubMed Central

Moreno, Andrea; Jego, Pierrick; de la Cruz, Feliberto; Canals, Santiago

2013-01-01

Complete understanding of the mechanisms that coordinate work and energy supply of the brain, the so called neurovascular coupling, is fundamental to interpreting brain energetics and their influence on neuronal coding strategies, but also to interpreting signals obtained from brain imaging techniques such as functional magnetic resonance imaging. Interactions between neuronal activity and cerebral blood flow regulation are largely compartmentalized. First, there exists a functional compartmentalization in which glutamatergic peri-synaptic activity and its electrophysiological events occur in close proximity to vascular responses. Second, the metabolic processes that fuel peri-synaptic activity are partially segregated between glycolytic and oxidative compartments. Finally, there is cellular segregation between astrocytic and neuronal compartments, which has potentially important implications on neurovascular coupling. Experimental data is progressively showing a tight interaction between the products of energy consumption and neurotransmission-driven signaling molecules that regulate blood flow. Here, we review some of these issues in light of recent findings with special attention to the neuron-glia interplay on the generation of neuroimaging signals. PMID:23543907

Cerebral blood flow and oxygenation in infants after birth asphyxia. Clinically useful information?

PubMed

Greisen, Gorm

2014-10-01

The term 'luxury perfusion' was coined nearly 50 years ago after observation of bright-red blood in the cerebral veins of adults with various brain pathologies. The bright-red blood represents decreased oxygen extraction and hence the perfusion is 'luxurious' compared to oxygen needs. Gradual loss of cellular energy charge during the hours following severe birth asphyxia was observed twenty years later by sequential cranial magnetic resonance spectroscopy. This led to the concept of delayed energy failure that is linked to mitochondrial dysfunction and apoptotic cell death. Abnormally increased perfusion and lack of normal cerebral blood flow regulation are also typically present, but whether the perfusion abnormalities at this secondary stage are detrimental, beneficial, or a mere epiphenomenon remains elusive. In contrast, incomplete reoxygenation of the brain during and following resuscitation is likely to compromise outcome. The clinical value of cerebral oximetry in this context can only be examined in a randomised clinical trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simultaneous real-time quantification of blood flow and vascular growth in the chick embryo using optical coherence tomography

NASA Astrophysics Data System (ADS)

Kowalski, William J.; Teslovich, Nikola C.; Chen, Chia-Yuan; Keller, Bradley B.; Pekkan, Kerem

2014-03-01

Experimental and clinical data indicate that hemodynamic forces within the embryo provide critical biomechanical cues for cardiovascular morphogenesis, growth, and remodeling and that perturbed flow is a major etiology of congenital heart disease. However, embryonic flow-growth relationships are largely qualitative and poorly defined. In this work, we provide a quantitative analysis of in vivo flow and growth trends in the chick embryo using optical coherence tomography (OCT) to acquire simultaneous velocity and structural data of the right vitelline artery continuously over a ten hour period beginning at stage 16 (hour 54). We obtained 3D vessel volumes (15 μm lateral, 4.3 μm axial resolutions, 6 μm slice spacing) at 60 minute intervals, taking a B-scan time series totaling one cardiac cycle at each slice. Embryos were maintained at a constant 37°C and 60% humidity during the entire acquisition period through an inhouse built chamber. The 3D vessel lumen geometries were reconstructed manually to assess growth. Blood flow velocity was computed from the central B-scan using red blood cell particle image velocimetry. The use of extended OCT imaging as a non-invasive method for continuous and simultaneous flow and structural data can enhance our understanding of the biomechanical regulation of critical events in morphogenesis. Data acquired will be useful to validate predictive finite-element 3D growth models.

Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig.

PubMed

Dyson, Rebecca M; Palliser, Hannah K; Lakkundi, Anil; de Waal, Koert; Latter, Joanna L; Clifton, Vicki L; Wright, Ian M R

2014-09-17

Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion-reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29-36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68-71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion-reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Visible light optical coherence tomography measure retinal oxygen metabolic response to systemic oxygenation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yi, Ji; Liu, Wenzhong; Chen, Siyu; Backman, Vadim; Sheibani, Nader; Sorenson, Christine M.; Fawzi, Amani A.; Linsenmeier, Robert A.; Zhang, Hao F.

2016-03-01

The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Using visible light optical coherence tomography (vis-OCT), we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO2) noninvasively in rat eyes. The rMRO2 was calculated by concurrent measurement of blood flow and blood oxygen saturation (sO2). Blood flow was calculated by the principle of Doppler optical coherence tomography, where the phase shift between two closely spaced A-lines measures the axial velocity. The distinct optical absorption spectra of oxy- and deoxy-hemoglobin provided the contrast for sO2 measurement, combined with the spectroscopic analysis of vis-OCT signal within the blood vessels. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery, and rMRO2 increased from the highly regulated retinal circulation (RC) under hypoxia, by 0.28+/-0.08 μL/min (p<0.001), and 0.20+/-0.04 μL/min (p<0.001) per 100 mmHg systemic pO2 reduction, respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation (CC).

Factors Released from Endothelial Cells Exposed to Flow Impact Adhesion, Proliferation, and Fate Choice in the Adult Neural Stem Cell Lineage.

PubMed

Dumont, Courtney M; Piselli, Jennifer M; Kazi, Nadeem; Bowman, Evan; Li, Guoyun; Linhardt, Robert J; Temple, Sally; Dai, Guohao; Thompson, Deanna M

2017-08-15

The microvasculature within the neural stem cell (NSC) niche promotes self-renewal and regulates lineage progression. Previous work identified endothelial-produced soluble factors as key regulators of neural progenitor cell (NPC) fate and proliferation; however, endothelial cells (ECs) are sensitive to local hemodynamics, and the effect of this key physiological process has not been defined. In this study, we evaluated adult mouse NPC response to soluble factors isolated from static or dynamic (flow) EC cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. Flow increases EC release of neurogenic factors and of heparin sulfate glycosaminoglycans that increase their bioactivity, likely underlying the enhanced neuronal differentiation. Additionally, endothelial factors, especially from static conditions, promoted adherent growth. Together, our data suggest that blood flow may impact proliferation, adhesion, and the neuron-glial fate choice of adult NPCs, with implications for diseases and aging that reduce flow.

Fibrin, γ’-fibrinogen, and trans-clot pressure gradient control hemostatic clot growth during human blood flow over a collagen/tissue factor wound

PubMed Central

Muthard, Ryan W.; Welsh, John D.; Brass, Lawrence F.; Diamond, Scott L.

2015-01-01

SUMMARY Objective Biological and physical factors interact to modulate blood response in a wounded vessel, resulting in a hemostatic clot or an occlusive thrombus. Flow and pressure differential (ΔP) across the wound from the lumen to the extravascular compartment may impact hemostasis and the observed core/shell architecture. We examined physical and biological factors responsible for regulating thrombin mediated clot growth. Approach and Results Using factor XIIa-inhibited human whole blood perfused in a microfluidic device over collagen/tissue factor at controlled wall shear rate and ΔP, we found thrombin to be highly localized in the P-selectin+ core of hemostatic clots. Increasing ΔP from 9 to 29 mm-Hg (wall shear rate = 400 s−1) reduced P-selectin+ core size and total clot size due to enhanced extravasation of thrombin. Blockade of fibrin polymerization with 5 mM GPRP dysregulated hemostasis by enhancing both P-selectin+ core size and clot size at 400 s−1 (20 mm-Hg). For whole blood flow (no GPRP), the thickness of the P-selectin-negative shell was reduced under arterial conditions (2000 s−1, 20 mm-Hg). Consistent with the antithrombin-1 activity of fibrin implicated with GPRP, anti-γ’-fibrinogen antibody enhanced core-localized thrombin, core size, and overall clot size, especially at venous (100 s−1) but not arterial wall shear rates (2000 s−1). Pathological shear (15,000 s−1) and GPRP synergized to exacerbate clot growth. Conclusions Hemostatic clotting was dependent on core-localized thrombin that (1) triggered platelet P-selectin display and (2) was highly regulated by fibrin and the trans-clot ΔP. Also, γ’-fibrinogen had a role in venous but not arterial conditions. PMID:25614284

Partial antagonism of endothelin 1-induced vasoconstriction in the human choroid by topical unoprostone isopropyl.

PubMed

Polska, Elzbieta; Doelemeyer, Arno; Luksch, Alexandra; Ehrlich, Paulina; Kaehler, Nils; Percicot, Christine L; Lambrou, George N; Schmetterer, Leopold

2002-03-01

There is increasing evidence that reduced ocular blood flow plays a role in the pathogenesis of glaucoma. In patients with normal-tension glaucoma, ocular blood flow abnormalities may be associated with dysfunction of the endothelin 1 (ET-1) regulation system. To test the hypothesis that unoprostone, a topical docosanoid, may affect ET-1--induced vasoconstriction in the human choroid. In a placebo-controlled, randomized, double-masked, 2-way crossover design, ET-1 (2.5 ng/kg per minute for 150 minutes) was administered intravenously to 24 healthy individuals. Thirty minutes after the start of ET-1 infusion, 1 drop of unoprostone or placebo was instilled into the right eye. After another 30 minutes, 2 drops of unoprostone or placebo was topically administered. This procedure was continued and the dose was increased further until 4 drops of unoprostone or placebo was reached. Subfoveal and pulsatile choroidal blood flow were assessed using laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude, respectively. Administration of exogenous ET-1 decreased choroidal blood flow (mean +/- SEM, 17% +/- 2%; P<.001) and fundus pulsation amplitude (mean +/- SEM, 19% +/- 2%; P<.001). This effect was significantly blunted when topical unoprostone was coadministered (mean +/- SEM decrease in choroidal blood flow, 7% +/- 2%; P =.04 vs. placebo; mean +/- SEM decrease in fundus pulsation amplitude, 12% +/- 2%; P<.001 vs. placebo). There is a functional antagonism between ET-1 and topical unoprostone in the choroidal vasculature. Our findings of a functional antagonism between ET-1 and topical unoprostone in the choroidal vasculature may be important in vascular eye diseases associated with increased ET-1.

Human cerebral autoregulation before, during and after spaceflight.

PubMed

Iwasaki, Ken-ichi; Levine, Benjamin D; Zhang, Rong; Zuckerman, Julie H; Pawelczyk, James A; Diedrich, André; Ertl, Andrew C; Cox, James F; Cooke, William H; Giller, Cole A; Ray, Chester A; Lane, Lynda D; Buckey, Jay C; Baisch, Friedhelm J; Eckberg, Dwain L; Robertson, David; Biaggioni, Italo; Blomqvist, C Gunnar

2007-03-15

Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head-down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by-beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (+/- s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(-1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low-frequency gain decreased significantly (P < 0.05) by 26, 23 and 27% after 1 and 2 weeks in space and on landing day, respectively, compared with preflight values, which is also consistent with improved autoregulation. We conclude that human cerebral autoregulation is preserved, and possibly even improved, by short-duration spaceflight.

Differential blood flow responses to CO2 in human internal and external carotid and vertebral arteries

PubMed Central

Sato, Kohei; Sadamoto, Tomoko; Hirasawa, Ai; Oue, Anna; Subudhi, Andrew W; Miyazawa, Taiki; Ogoh, Shigehiko

2012-01-01

Arterial CO2 serves as a mediator of cerebral blood flow (CBF), and its relative influence on the regulation of CBF is defined as cerebral CO2 reactivity. Our previous studies have demonstrated that there are differences in CBF responses to physiological stimuli (i.e. dynamic exercise and orthostatic stress) between arteries in humans. These findings suggest that dynamic CBF regulation and cerebral CO2 reactivity may be different in the anterior and posterior cerebral circulation. The aim of this study was to identify cerebral CO2 reactivity by measuring blood flow and examine potential differences in CO2 reactivity between the internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA). In 10 healthy young subjects, we evaluated the ICA, ECA, and VA blood flow responses by duplex ultrasonography (Vivid-e, GE Healthcare), and mean blood flow velocity in middle cerebral artery (MCA) and basilar artery (BA) by transcranial Doppler (Vivid-7, GE healthcare) during two levels of hypercapnia (3% and 6% CO2), normocapnia and hypocapnia to estimate CO2 reactivity. To characterize cerebrovascular reactivity to CO2, we used both exponential and linear regression analysis between CBF and estimated partial pressure of arterial CO2, calculated by end-tidal partial pressure of CO2. CO2 reactivity in VA was significantly lower than in ICA (coefficient of exponential regression 0.021 ± 0.008 vs. 0.030 ± 0.008; slope of linear regression 2.11 ± 0.84 vs. 3.18 ± 1.09% mmHg−1: VA vs. ICA, P < 0.01). Lower CO2 reactivity in the posterior cerebral circulation was persistent in distal intracranial arteries (exponent 0.023 ± 0.006 vs. 0.037 ± 0.009; linear 2.29 ± 0.56 vs. 3.31 ± 0.87% mmHg−1: BA vs. MCA). In contrast, CO2 reactivity in ECA was markedly lower than in the intra-cerebral circulation (exponent 0.006 ± 0.007; linear 0.63 ± 0.64% mmHg−1, P < 0.01). These findings indicate that vertebro-basilar circulation has lower CO2 reactivity than internal carotid circulation, and that CO2 reactivity of the external carotid circulation is markedly diminished compared to that of the cerebral circulation, which may explain different CBF responses to physiological stress. PMID:22526884

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

PubMed

Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral capsaicin effect at one remote site. There was an accompanying decrease and an increase in the proportion of body fat in visceral and subcutaenous compartments, respectively. Taken together, if oral capsaicin could regulate adipose tissue distribution, the process might involve the effect of intestinal mucosal afferent nerves in modulating intestinal and visceral adipose tissue blood flow. The hypothesis that the intestinal mucosal afferent mechanism is a plausible therapeutic target for abating visceral obesity deserves to be further evaluated.

The Oscillating Component of the Internal Jugular Vein Flow: The Overlooked Element of Cerebral Circulation

PubMed Central

Sisini, Francesco; Toro, Eleuterio; Gambaccini, Mauro; Zamboni, Paolo

2015-01-01

The jugular venous pulse (JVP) provides valuable information about cardiac haemodynamics and filling pressures and is an indirect estimate of the central venous pressure (CVP). Recently it has been proven that JVP can be obtained by measuring the cross-sectional area (CSA) of the IJV on each sonogram of an ultrasound B-mode sonogram sequence. It has also been proven that during its pulsation the IJV is distended and hence that the pressure gradient drives the IJV haemodynamics. If this is true, then it will imply the following: (i) the blood velocity in the IJV is a periodic function of the time with period equal to the cardiac period and (ii) the instantaneous blood velocity is given by a time function that can be derived from a flow-dynamics theory that uses the instantaneous pressure gradient as a parameter. The aim of the present study is to confirm the hypothesis that JVP regulates the IJV blood flow and that pressure waves are transmitted from the heart toward the brain through the IJV wall. PMID:26783380

Gene regulation by mechanical forces

NASA Technical Reports Server (NTRS)

Oluwole, B. O.; Du, W.; Mills, I.; Sumpio, B. E.

1997-01-01

Endothelial cells are subjected to various mechanical forces in vivo from the flow of blood across the luminal surface of the blood vessel. The purpose of this review was to examine the data available on how these mechanical forces, in particular cyclic strain, affect the expression and regulation of endothelial cell function. Studies from various investigators using models of cyclic strain in vitro have shown that various vasoactive mediators such as nitric oxide and prostacyclin are induced by the effect of mechanical deformation, and that the expression of these mediators may be regulated at the transcription level by mechanical forces. There also seems to be emerging evidence that endothelial cells may also act as mechanotransducers, whereby the transmission of external forces induces various cytoskeletal changes and second messenger cascades. Furthermore, it seems these forces may act on specific response elements of promoter genes.

Regulation of Coronary Blood Flow in Health and Ischemic Heart Disease

PubMed Central

Duncker, Dirk J.; Koller, Akos; Merkus, Daphne; Canty, John M.

2018-01-01

The major factors determining myocardial perfusion and oxygen delivery have been elucidated over the past several decades, and this knowledge has been incorporated into the management of patients with ischemic heart disease (IHD). The basic understanding of the fluid mechanical behavior of coronary stenoses has also been translated to the cardiac catheterization laboratory where measurements of coronary pressure distal to a stenosis and coronary flow are routinely obtained. However, the role of perturbations in coronary microvascular structure and function, due to myocardial hypertrophy or coronary microvascular dysfunction, in IHD is becoming increasingly recognized. Future studies should therefore be aimed at further improving our understanding of the integrated coronary microvascular mechanisms that control coronary blood flow, and of the underlying causes and mechanisms of coronary microvascular dysfunction. This knowledge will be essential to further improve the treatment of patients with IHD. PMID:25475073

Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells

PubMed Central

Watkins, Stacey; Robel, Stefanie; Kimbrough, Ian F.; Robert, Stephanie M.; Ellis-Davies, Graham; Sontheimer, Harald

2014-01-01

Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites, and energy substrates from the blood to the brain. They maintain endothelial tight junctions that form the blood-brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumors that use the perivascular space for invasion and co-opt existing vessels as satellite tumors form. Here we use a clinically relevant mouse model of glioma and find that glioma cells, as they populate the perivascular space of pre-existing vessels, displace astrocytic endfeet from endothelial or vascular smooth muscle cells. This causes a focal breach in the BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma cells seize control over regulation of vascular tone through Ca2+-dependent release of K+. These findings have important clinical implications regarding blood flow in the tumor-associated brain and the ability to locally deliver chemotherapeutic drugs in disease. PMID:24943270

Evaluation of renal oxygen homeostasis in a preclinical animal model to elucidate difference in blood quality after transfusion.

PubMed

Baek, Jin Hyen; Yalamanoglu, Ayla; Moon, So-Eun; Gao, Yamei; Buehler, Paul W

2018-03-01

Red blood cell (RBC) oxygen (O 2 ) delivery may be impacted at the tissue, cellular, and molecular levels after storage duration, preservation strategies, and pathogen reduction. Collectively, the preclinical measurement of arterial and venous PO 2 , systemic blood flow, tissue hypoxia-inducible factors (HIFs), pimonidazole adduction, and erythropoietin (EPO) regulation can serve to elucidate differential RBC quality after storage and processing. Donor guinea pig blood was collected, leukoreduced, and stored at 4°C in AS-3 for 1 (fresh) or 14 (stored) days. RBC variables-2,3-diphosphoglycerate, adenosine triphosphate, hemoglobin, morphology, deformability, and in vivo recovery at 24 hours-were measured at each storage duration. Recipient guinea pigs were exchange transfused until 80% volume replacement was achieved. Arterial and venous blood gases, systemic blood flow, renal HIF-1α and HIF-2α, renal EPO mRNA, plasma EPO, and renal tissue pimonidazole adduction were measured after transfusion. RBC variables declined significantly with storage; however, hemolysis and in vivo recovery remained within the allowable limits for human blood storage. Posttransfusion arterial and venous PO 2 and systemic blood flow decreased, and renal HIFs, EPO mRNA, and pimonidazole adducts increased. Subsequently, EPO accumulated in plasma indicating decreased O 2 availability in the kidneys. Conversely, all variables remained at basal levels in the fresh blood group. The evaluation of renal O 2 homeostasis after transfusion represents an effective approach to defining RBC quality between predicate and novel processing. Methods are adapted from standardized techniques and ideal for preclinical evaluation. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Angiogenesis-regulating microRNAs and ischemic stroke

PubMed Central

Yin, Ke-Jie; Hamblin, Milton; Chen, Y. Eugene

2014-01-01

Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and post-stroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke-associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis. PMID:26156265

Flow and pressure regulation in the cardiovascular system. [engineering systems model

NASA Technical Reports Server (NTRS)

Iberall, A.

1974-01-01

Principles and descriptive fragments which may contribute to a model of the regulating chains in the cardiovascular system are presented. Attention is given to the strain sensitivity of blood vessels, the law of the autonomy of the heart beat oscillator, the law of the encapsulation of body fluids, the law of the conservation of protein, the law of minimum 'arterial' pressure, the design of the 'mammalian' kidney, questions of homeokinetic organization, and the development of self-regulatory chains. Details concerning the development program for the heart muscle are considered along with the speed of response of the breathing rate and the significance of the pulmonary vascular pressure-flow characteristics.

Macro- and microscale variables regulate stent haemodynamics, fibrin deposition and thrombomodulin expression

PubMed Central

Jiménez, Juan M.; Prasad, Varesh; Yu, Michael D.; Kampmeyer, Christopher P.; Kaakour, Abdul-Hadi; Wang, Pei-Jiang; Maloney, Sean F.; Wright, Nathan; Johnston, Ian; Jiang, Yi-Zhou; Davies, Peter F.

2014-01-01

Drug eluting stents are associated with late stent thrombosis (LST), delayed healing and prolonged exposure of stent struts to blood flow. Using macroscale disturbed and undisturbed fluid flow waveforms, we numerically and experimentally determined the effects of microscale model strut geometries upon the generation of prothrombotic conditions that are mediated by flow perturbations. Rectangular cross-sectional stent strut geometries of varying heights and corresponding streamlined versions were studied in the presence of disturbed and undisturbed bulk fluid flow. Numerical simulations and particle flow visualization experiments demonstrated that the interaction of bulk fluid flow and stent struts regulated the generation, size and dynamics of the peristrut flow recirculation zones. In the absence of endothelial cells, deposition of thrombin-generated fibrin occurred primarily in the recirculation zones. When endothelium was present, peristrut expression of anticoagulant thrombomodulin (TM) was dependent on strut height and geometry. Thinner and streamlined strut geometries reduced peristrut flow recirculation zones decreasing prothrombotic fibrin deposition and increasing endothelial anticoagulant TM expression. The studies define physical and functional consequences of macro- and microscale variables that relate to thrombogenicity associated with the most current stent designs, and particularly to LST. PMID:24554575

[Anesthesia for surgery of degenerative and abnormal cervical spine].

PubMed

Béal, J L; Lopin, M C; Binnert, M

1993-01-01

A feature common to all congenital or inflammatory abnormalities of the cervical spine is an actual or potential reduction in the lumen of the spinal canal. The spinal cord and nerve roots are at risk. During intubation, and positioning the patient on the table, all untoward movements of the cervical spine may lead to spinal cord compression. Abnormalities of the cervical spine carry the risk of a difficult intubation. If there is much debate as to what constitutes optimum management of the airway, there is no evidence that any one method is the best. Recognizing the possible instability and intubating with care, are probably much more important in preserving neurological function than any particular mode of intubation. During maintenance of anaesthesia, the main goal is to preserve adequate spinal cord perfusion in order to prevent further damage. Spinal cord blood flow seems to be regulated by the same factors as cerebral blood flow. Hypercapnia increases cord blood flow while hypocapnia decreases it. Therefore, normocapnia or mild hypocapnia is recommended. Induced hypotension is frequently used to decrease blood loss. However, in patients with a marginally perfused spinal cord, the reduction in blood flow may cause ischaemia of the spinal cord and may therefore be relatively contraindicated. In addition to standard intraoperative monitoring, spinal cord monitoring is almost mandatory. Monitoring somatosensory evoked potentials is used routinely. However, the major limitation is that this technique only monitors dorsal column function; theoretically, motor paralysis can occur despite a lack of change in recorded signals. Neurogenic motor evoked potentials may now be used to monitor anterior spinal cord integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigation of the blood behaviour and vascular diseases by using mathematical physic principles

NASA Astrophysics Data System (ADS)

Yardimci, Ahmet; Simsek, Buket

2017-07-01

In this paper we prepare a short survey for using of mathematical physic principles in blood flow and vascular diseases researches. The study of the behavior of blood flow in the blood vessels provides understanding on connection between flow and the development of dieseases such as atherosclerosis, thrombosis, aneurysms etc. and how the flow dynamics is changed under these conditions. Blood flow phenomena are often too complex that it would be possible to describe them entirely analytically, although simple models, such as Poiseuille model, can still provide some insight into blood flow. Blood is not an "ideal fluid" and energy is lost as flowing blood overcomes resistance. Resistance to blood flow is a function of viscosity, vessel radius, and vessel length. So, mathematical Physic principles are useful tools for blood flow research studies. Blood flow is a function of pressure gradient and resistance and resistance to flow can be estimates using Poiseuille's law. Reynold's number can be used to determine whether flow is laminar or turbulent.

Absence of regulation of human polymorphonuclear oxidative burst by interleukin-10, interleukin-4, interleukin-13 and transforming growth factor-beta in whole blood.

PubMed

Réglier-Poupet, H; Hakim, J; Gougerot-Pocidalo, M A; Elbim, C

1998-12-01

Cytokines such as IL-10, IL-4, IL-13 and TGF-beta play a major role in the regulation of immune responses and are considered as anti-inflammatory agents mainly due to their actions on monocytes. These cytokines are also known to participate in the regulation of PMN activities. However, few and contradictory results have been reported on their direct and priming effects on the PMN oxidative burst, which is essential for killing bacteria. We used a flow cytometry method to study the effects of these cytokines on the PMN oxidative burst; we also used whole blood to avoid PMN activation related to isolation procedures and in order to simulate the in vivo situation more closely. None of the cytokines tested had direct or priming effects on PMN H2O2 production. We also show for the first time that these cytokines do not modulate TNF priming of the PMN oxidative burst in response to N-formyl peptides (fMLP). These results show that the anti-bacterial activity of PMN, in terms of the PMN respiratory burst, is not down regulated by these anti-inflammatory cytokines in whole blood.

Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow.

PubMed

Xu, Shouyu; Liu, Xueyun; Chen, Zhenhuang; Li, Gaoquan; Chen, Qin; Zhou, Guoqing; Ma, Ruijie; Yao, Xinmiao; Huang, Xiao

2016-12-15

Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can produce similar effects upon muscles to that of high-intensity resistance training (HIRT) while overcoming many of the restrictions to HIRT that occurs in a clinical setting. However, the potential molecular mechanisms of BFR induced muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR and reveal possible clinical therapeutic targets for atrophy cases. We performed genome wide screening with microarray analysis to identify unique differentially expressed genes during rat muscle hypertrophy. We then successfully separated the differentially expressed genes from BRF treated soleus samples by comparing the Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and immunohistochemistry (IHC) we also analyzed other related differentially expressed genes. Results suggested that muscle hypertrophy induced by BFR is essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and MAPK pathways act as positive regulators in controlling protein synthesis where ubiquitin-proteasome acts as a negative regulator. This represents the first general genome wide level investigation of the gene expression profile in the rat soleus after BFR treatment. This may aid our understanding of the molecular mechanisms regulating and controlling muscle hypertrophy and provide support to the BFR strategies aiming to prevent muscle atrophy in a clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

Transcranial Doppler monitoring in Parkinson's disease: cerebrovascular compensation of orthostatic hypotension.

PubMed

Haubrich, Christina; Pies, Katrin; Dafotakis, Manuel; Block, Frank; Kloetzsch, Christof; Diehl, Rolf R

2010-10-01

Despite of precipitous blood pressure falls in Parkinson's Disease (PD) patients, they may not experience syncope or postural complaints. Can cerebral blood flow regulation explain why orthostatic hypotension (OH) has often no accompanying symptoms? In patients with PD and OH (18 asymptomatic; 8 symptomatic), arterial blood pressure (ABP) as well as Doppler-detected cerebral blood flow velocity (CBFV) in middle and posterior cerebral arteries (MCA and PCA) were monitored during head-up tilt and compared with 25 controls and eight non-PD-OH patients. Analysis included the transfer function between slow spontaneous pressure and flow-oscillations. ABP and CBFV were maintained at significantly higher levels in asymptomatic than symptomatic PD-OH (ABP: 85.7 ± 10.5 vs. 66.9 ± 12.5%; MCA-FV: 83.3 ± 9.3 vs. 66.1 ± 6.8%; PCA-FV: 84.4 ± 12.2 vs. 65.9 ± 9.3% of supine). When orthostatic complaints occurred, CBFV depended directly on ABP changes (MCA r(2) = 0.64; PCA r(2) = 0.62; both p < 0.05). Despite of a tilt-induced blood pressure instability in PD-OH, the transfer function parameters did not differ from normal [phase: MCA: 46.6 ± 20.5°; PCA 39.2 ± 28.8°, gain: MCA 2.0 ± 0.7; PCA 2.9 ± 1.6)]. Results showed a normal autoregulatory response to downward blood pressure shifts in PD. Moreover, orthostatic blood pressure instability is compensated equally sufficient in anterior and posterior parts of cerebral circulation. Whether in PD patients, OH becomes symptomatic rather seems to depend on blood pressure falling below the autoregulated range. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Analysis of skin blood microflow oscillations in patients with rheumatic diseases

NASA Astrophysics Data System (ADS)

Mizeva, Irina; Makovik, Irina; Dunaev, Andrey; Krupatkin, Alexander; Meglinski, Igor

2017-07-01

Laser Doppler flowmetry (LDF) has been applied for the assessment of variation in blood microflows in patients with rheumatic diseases and healthy volunteers. Oscillations of peripheral blood microcirculation observed by LDF have been analyzed utilizing a wavelet transform. A higher amplitude of blood microflow oscillations has been observed in a high frequency band (over 0.1 Hz) in patients with rheumatic diseases. Oscillations in the high frequency band decreased in healthy volunteers in response to the cold pressor test, whereas lower frequency pulsations prevailed in patients with rheumatic diseases. A higher perfusion rate at normal conditions was observed in patients, and a weaker response to cold stimulation was observed in healthy volunteers. Analysis of blood microflow oscillations has a high potential for evaluation of mechanisms of blood flow regulation and diagnosis of vascular abnormalities associated with rheumatic diseases.

Fibro-vascular coupling in the control of cochlear blood flow.

PubMed

Dai, Min; Shi, Xiaorui

2011-01-01

Transduction of sound in the cochlea is metabolically demanding. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF) is a physiological necessity. Yet despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained. We report on a local control mechanism for regulating inner ear blood flow involving fibrocyte signaling. Fibrocytes in the super-strial region are spatially distributed near pre-capillaries of the spiral ligament of the albino guinea pig cochlear lateral wall, as demonstrably shown in transmission electron microscope and confocal images. Immunohistochemical techniques reveal the inter-connected fibrocytes to be positive for Na+/K+ ATPase β1 and S100. The connected fibrocytes display more Ca(2+) signaling than other cells in the cochlear lateral wall as indicated by fluorescence of a Ca(2+) sensor, fluo-4. Elevation of Ca(2+) in fibrocytes, induced by photolytic uncaging of the divalent ion chelator o-nitrophenyl EGTA, results in propagation of a Ca(2+) signal to neighboring vascular cells and vasodilation in capillaries. Of more physiological significance, fibrocyte to vascular cell coupled signaling was found to mediate the sound stimulated increase in cochlear blood flow (CBF). Cyclooxygenase-1 (COX-1) was required for capillary dilation. The findings provide the first evidence that signaling between fibrocytes and vascular cells modulates CBF and is a key mechanism for meeting the cellular metabolic demand of increased sound activity.

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

NASA Technical Reports Server (NTRS)

Crandall, C. G.; Zhang, R.; Levine, B. D.

2000-01-01

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.

21 CFR 870.2120 - Extravascular blood flow probe.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Extravascular blood flow probe. 870.2120 Section... blood flow probe. (a) Identification. An extravascular blood flow probe is an extravascular ultrasonic or electromagnetic probe used in conjunction with a blood flowmeter to measure blood flow in a...

21 CFR 870.2120 - Extravascular blood flow probe.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Extravascular blood flow probe. 870.2120 Section... blood flow probe. (a) Identification. An extravascular blood flow probe is an extravascular ultrasonic or electromagnetic probe used in conjunction with a blood flowmeter to measure blood flow in a...

21 CFR 870.2120 - Extravascular blood flow probe.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Extravascular blood flow probe. 870.2120 Section... blood flow probe. (a) Identification. An extravascular blood flow probe is an extravascular ultrasonic or electromagnetic probe used in conjunction with a blood flowmeter to measure blood flow in a...

21 CFR 870.2120 - Extravascular blood flow probe.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Extravascular blood flow probe. 870.2120 Section... blood flow probe. (a) Identification. An extravascular blood flow probe is an extravascular ultrasonic or electromagnetic probe used in conjunction with a blood flowmeter to measure blood flow in a...

Regulation of calcium channels in smooth muscle: New insights into the role of myosin light chain kinase

PubMed Central

Martinsen, A; Dessy, C; Morel, N

2014-01-01

Smooth muscle myosin light chain kinase (MLCK) plays a crucial role in artery contraction, which regulates blood pressure and blood flow distribution. In addition to this role, MLCK contributes to Ca2+ flux regulation in vascular smooth muscle (VSM) and in non-muscle cells, where cytoskeleton has been suggested to help Ca2+ channels trafficking. This conclusion is based on the use of pharmacological inhibitors of MLCK and molecular and cellular techniques developed to down-regulate the enzyme. Dissimilarities have been observed between cells and whole tissues, as well as between large conductance and small resistance arteries. A differential expression in MLCK and ion channels (either voltage-dependent Ca2+ channels or non-selective cationic channels) could account for these observations, and is in line with the functional properties of the arteries. A potential involvement of MLCK in the pathways modulating Ca2+ entry in VSM is described in the present review. PMID:25483583

Microfluidic strategy to investigate dynamics of small blood vessel function

NASA Astrophysics Data System (ADS)

Yasotharan, Sanjesh; Bolz, Steffen-Sebastian; Guenther, Axel

2010-11-01

Resistance arteries (RAs, 30-300 microns in diameter) that are located within the terminal part of the vascular tree regulate the laminar perfusion of tissue with blood, via the peripheral vascular resistance, and hence controls the systemic blood pressure. The structure of RAs is adapted to actively controlling flow resistance by dynamically changing their diameter, which is non-linearly dependent on the temporal variation of the transmural pressure, perfusion flow rate and spatiotemporal changes in the chemical environment. Increases in systemic blood pressure (hypertension) resulting from pathologic changes in the RA response represent the primary risk factor for cardiovascular diseases. We use a microfluidic strategy to investigate small blood vessels by quantifying structural variations within the arterial wall, RA outer contour and diameter over time. First, we document the artery response to vasomotor drugs that were homogeneously applied at step-wise increasing concentration. Second, we investigate the response in the presence of well-defined axial and circumferential heterogeneities. Artery per- and superfusion is discussed based on microscale PIV measurements of the fluid velocity on both sides of the arterial wall. Structural changes in the arterial wall are quantified using cross-correlation and proper orthogonal decomposition analyses of bright-field micrographs.

Engaging Neuroscience to Advance Translational Research in Brain Barrier Biology

PubMed Central

Neuwelt, Edward A.; Bauer, Björn; Fahlke, Christoph; Fricker, Gert; Iadecola, Constantino; Janigro, Damir; Leybaert, Luc; Molnar, Zoltan; O’Donnell, Martha; Povlishock, John; Saunders, Norman; Sharp, Frank; Stanimirovic, Danica; Watts, Ryan; Drewes, Lester

2012-01-01

Preface The delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by brain barriers, the most well known of which are the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier. Recent studies have shown numerous additional roles of these barriers, including an involvement in neurodevelopment, control of cerebral blood flow, and, when barrier integrity is impaired, a contribution to the pathology of many common CNS disorders such as Alzheimer’s disease, Parkinson’s disease and stroke. Thus, many key areas of neuroscientific investigation are shared with the ‘brain barriers sciences’. However, despite this overlap there has been little crosstalk. This lack of crosstalk is of more than academic interest as our emerging understanding of the neurovascular unit (NVU), composed of local neuronal circuits, glia, pericytes and the endothelium, illustrates how the brain dynamically modulates its blood flow, metabolism, and electrophysiological regulation. A key insight is that the barriers are an essential part of the NVU and as such are influenced by all cellular elements of this unit. PMID:21331083

Mathematical modeling of kidney transport.

PubMed

Layton, Anita T

2013-01-01

In addition to metabolic waste and toxin excretion, the kidney also plays an indispensable role in regulating the balance of water, electrolytes, nitrogen, and acid-base. In this review, we describe representative mathematical models that have been developed to better understand kidney physiology and pathophysiology, including the regulation of glomerular filtration, the regulation of renal blood flow by means of the tubuloglomerular feedback mechanisms and of the myogenic mechanism, the urine concentrating mechanism, epithelial transport, and regulation of renal oxygen transport. We discuss the extent to which these modeling efforts have expanded our understanding of renal function in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

Dissociation of Blood Volume and Flow in Regulation of Salt and Water Balance in Burn Patients,

DTIC Science & Technology

1991-09-01

with the diagnosis of the Syndrome of Inappropriate An- lowing resuscitation. Whether there is an additional role of al- tidiuretic Hormone Secretion...osmolarity. demonstrates a remarkable, if not astounding, paradox. It really flies Leaf and Bartter then, in a brilliant series of experiments in humans

Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis

PubMed Central

Otten, Cécile; Renz, Marc

2018-01-01

Endothelial cells respond to different levels of fluid shear stress through adaptations of their mechanosensitivity. Currently, we lack a good understanding of how this contributes to sculpting of the cardiovascular system. Cerebral cavernous malformation (CCM) is an inherited vascular disease that occurs when a second somatic mutation causes a loss of CCM1/KRIT1, CCM2, or CCM3 proteins. Here, we demonstrate that zebrafish Krit1 regulates the formation of cardiac valves. Expression of heg1, which encodes a binding partner of Krit1, is positively regulated by blood-flow. In turn, Heg1 stabilizes levels of Krit1 protein, and both Heg1 and Krit1 dampen expression levels of klf2a, a major mechanosensitive gene. Conversely, loss of Krit1 results in increased expression of klf2a and notch1b throughout the endocardium and prevents cardiac valve leaflet formation. Hence, the correct balance of blood-flow-dependent induction and Krit1 protein-mediated repression of klf2a and notch1b ultimately shapes cardiac valve leaflet morphology. PMID:29364115

Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution.

PubMed

Nozaki, Yuichi; Fujita, Koji; Wada, Koichiro; Yoneda, Masato; Shinohara, Yoshiyasu; Imajo, Kento; Ogawa, Yuji; Kessoku, Takaomi; Nakamuta, Makoto; Saito, Satoru; Masaki, Naohiko; Nagashima, Yoji; Terauchi, Yasuo; Nakajima, Atsushi

2015-12-17

Although many factors and molecules that are closely associated with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported, the role of endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) in the pathogenesis of NAFLD/NASH remains unclear. We therefore investigated the role of eNOS-derived NO in NAFLD pathogenesis using systemic eNOS-knockout mice fed a high-fat diet. eNOS-knockout and wild-type mice were fed a basal diet or a high-fat diet for 12 weeks. Lipid accumulation and inflammation were evaluated in the liver, and various factors that are closely associated with NAFLD/NASH and hepatic tissue blood flow were analyzed. Lipid accumulation and inflammation were more extensive in the liver and lipid accumulation was less extensive in the visceral fat tissue in eNOS-knockout mice, compared with wild-type mice, after 12 weeks of being fed a high-fat diet. While systemic insulin resistance was comparable between the eNOS-knockout and wild-type mice fed a high-fat diet, hepatic tissue blood flow was significantly suppressed in the eNOS-knockout mice, compared with the wild-type mice, in mice fed a high-fat diet. The microsomal triglyceride transfer protein activity was down-regulated in eNOS-knockout mice, compared with wild-type mice, in mice fed a high-fat diet. A deficiency of eNOS-derived NO may exacerbate the early-stage of NASH pathogenesis by changing the fat distribution in a mouse model via the regulation of hepatic tissue blood flow.

Noxious heat and scratching decrease histamine-induced itch and skin blood flow.

PubMed

Yosipovitch, Gil; Fast, Katharine; Bernhard, Jeffrey D

2005-12-01

The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.

Effect of flow rate and temperature on transmembrane blood pressure drop in an extracorporeal artificial lung.

PubMed

Park, M; Costa, E L V; Maciel, A T; Barbosa, E V S; Hirota, A S; Schettino, G de P; Azevedo, L C P

2014-11-01

Transmembrane pressure drop reflects the resistance of an artificial lung system to blood transit. Decreased resistance (low transmembrane pressure drop) enhances blood flow through the oxygenator, thereby, enhancing gas exchange efficiency. This study is part of a previous one where we observed the behaviour and the modulation of blood pressure drop during the passage of blood through artificial lung membranes. Before and after the induction of multi-organ dysfunction, the animals were instrumented and analysed for venous-venous extracorporeal membrane oxygenation, using a pre-defined sequence of blood flows. Blood flow and revolutions per minute (RPM) of the centrifugal pump varied in a linear fashion. At a blood flow of 5.5 L/min, pre- and post-pump blood pressures reached -120 and 450 mmHg, respectively. Transmembrane pressures showed a significant spread, particularly at blood flows above 2 L/min; over the entire range of blood flow rates, there was a positive association of pressure drop with blood flow (0.005 mmHg/mL/minute of blood flow) and a negative association of pressure drop with temperature (-4.828 mmHg/(°Celsius). These associations were similar when blood flows of below and above 2000 mL/minute were examined. During its passage through the extracorporeal system, blood is exposed to pressure variations from -120 to 450 mmHg. At high blood flows (above 2 L/min), the drop in transmembrane pressure becomes unpredictable and highly variable. Over the entire range of blood flows investigated (0-5500 mL/min), the drop in transmembrane pressure was positively associated with blood flow and negatively associated with body temperature. © The Author(s) 2014.

Axial Pump

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr. (Inventor); Akkerman, James W. (Inventor); Aber, Gregory S. (Inventor); VanDamm, George Arthur (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

1997-01-01

A rotary blood pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial and radial clearances of blades associated with the flow straightener, inducer portion, impeller portion and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with cross-linked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

Reduction of myocardial blood flow reserve in idiopathic dilated cardiomyopathy without overt heart failure and its relation with functional indices: an echo-Doppler and positron emission tomography study.

PubMed

Morales, Maria-Aurora; Neglia, Danilo; L'Abbate, Antonio

2008-08-01

Myocardial blood flow during pharmacological vasodilatation is depressed in patients with idiopathic dilated cardiomyopathy even the in absence of overt heart failure; the extent of myocardial blood flow abnormalities is not predictable by left ventricular ejection fraction (LVEF) and diastolic dimensions. To assess whether myocardial blood flow impairment in idiopathic dilated cardiomyopathy without overt heart failure can be related to Doppler-derived dP/dt and to echocardiographically determined left ventricular end systolic stress - which is linked to myocardial blood flow reserve in advanced disease. Twenty-six patients, New York Heart Association Class I-II, (LVEF 37.4 +/- 1.4%, left ventricular diastolic dimensions 62.6 +/- 0.9 mm) underwent resting/dipyridamole [13N]NH3 flow positron emission tomography and an ultrasonic study. Regional myocardial blood flow values (ml/min per g) were computed from positron emission tomography data in 13 left ventricular (LV) myocardial regions and averaged to provide mean myocardial blood flow and myocardial blood flow reserve, defined as dipyridamole/resting mean myocardial blood flow ratio. Resting myocardial blood flow was 0.686 +/- 0.045, dipyridamole myocardial blood flow 1.39 +/- 0.15 and myocardial blood flow reserve 2.12 +/- 0.2, lower than in controls (P < 0.01). The ratio dP/dt was directly related to dipyridamole myocardial blood flow and myocardial blood flow reserve (r = 0.552 and 0.703, P < 0.005 and P < 0.0001); no relation was found between myocardial blood flow and LVEF left ventricular diastolic dimensions, and left ventricular end systolic stress. In idiopathic dilated cardiomyopathy patients without overt heart failure, the extent of myocardial blood flow reserve impairment is related to dP/dt but not to more classical indices of left ventricular function.

The diving paradox: new insights into the role of the dive response in air-breathing vertebrates.

PubMed

Davis, Randall W; Polasek, Lori; Watson, Rebecca; Fuson, Amanda; Williams, Terrie M; Kanatous, Shane B

2004-07-01

When aquatic reptiles, birds and mammals submerge, they typically exhibit a dive response in which breathing ceases, heart rate slows, and blood flow to peripheral tissues is reduced. The profound dive response that occurs during forced submergence sequesters blood oxygen for the brain and heart while allowing peripheral tissues to become anaerobic, thus protecting the animal from immediate asphyxiation. However, the decrease in peripheral blood flow is in direct conflict with the exercise response necessary for supporting muscle metabolism during submerged swimming. In free diving animals, a dive response still occurs, but it is less intense than during forced submergence, and whole-body metabolism remains aerobic. If blood oxygen is not sequestered for brain and heart metabolism during normal diving, then what is the purpose of the dive response? Here, we show that its primary role may be to regulate the degree of hypoxia in skeletal muscle so that blood and muscle oxygen stores can be efficiently used. Paradoxically, the muscles of diving vertebrates must become hypoxic to maximize aerobic dive duration. At the same time, morphological and enzymatic adaptations enhance intracellular oxygen diffusion at low partial pressures of oxygen. Optimizing the use of blood and muscle oxygen stores allows aquatic, air-breathing vertebrates to exercise for prolonged periods while holding their breath.

Gap Junction Regulation of Vascular Tone: Implications of Modulatory Intercellular Communication During Gestation

PubMed Central

Ampey, Bryan C.; Morschauser, Timothy J.; Lampe, Paul D.

2017-01-01

In the vasculature, gap junctions (GJ) play a multifaceted role by serving as direct conduits for cell–cell intercellular communication via the facilitated diffusion of signaling molecules. GJs are essential for the control of gene expression and coordinated vascular development in addition to vascular function. The coupling of endothelial cells to each other, as well as with vascular smooth muscle cells via GJs, plays a relevant role in the control of vasomotor tone, tissue perfusion and arterial blood pressure. The regulation of cell-signaling is paramount to cardiovascular adaptations of pregnancy. Pregnancy requires highly developed cell-to-cell coupling, which is affected partly through the formation of intercellular GJs by Cx43, a gap junction protein, within adjacent cell membranes to help facilitate the increase of uterine blood flow (UBF) in order to ensure adequate perfusion for nutrient and oxygen delivery to the placenta and thus the fetus. One mode of communication that plays a critical role in regulating Cx43 is the release of endothelial-derived vasodilators such as prostacyclin (PGI2) and nitric oxide (NO) and their respective signaling mechanisms involving second messengers (cAMP and cGMP, respectively) that are likely to be important in maintaining UBF. Therefore, the assertion we present in this review is that GJs play an integral if not a central role in maintaining UBF by controlling rises in vasodilators (PGI2 and NO) via cyclic nucleotides. In this review, we discuss: (1) GJ structure and regulation; (2) second messenger regulation of GJ phosphorylation and formation; (3) pregnancy-induced changes in cell-signaling; and (4) the role of uterine arterial endothelial GJs during gestation. These topics integrate the current knowledge of this scientific field with interpretations and hypotheses regarding the vascular effects that are mediated by GJs and their relationship with vasodilatory vascular adaptations required for modulating the dramatic physiological rises in uteroplacental perfusion and blood flow observed during normal pregnancy. PMID:25015806

Regulation of local subcutaneous blood flow in patients with psoriasis and effects of antipsoriatic treatment on subcutaneous blood flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klemp, P.

1985-08-01

Local regulation of the doubled subcutaneous blood flow (SBF) rates in psoriatic lesional skin was studied in 8 patients using a traumatic epicutaneous /sup 133/Xe labeling washout technique. Venous stasis of 40 mm Hg induced a significant reduction in the SBF (-34%, p less than 0.01), i.e., a normal vasoconstrictor response. Limb elevation of 40 cm above heart level induced no statistical changes in the SBF (p = 0.50), i.e., a normal local autoregulation response. This indicates normal, local regulation mechanisms of SBF in psoriasis. In another 8 patients, the effect on SBF of a 4-week antipsoriatic treatment with tarmore » was studied in lesional and symmetrically nonlesional skin areas. One patient was clear of psoriasis on day 22, and was followed only to that time. The mean pretreatment SBF in lesional skin areas was 3.87 +/- SD 0.78 ml X (100 g X min)-1, which was not statistically different from measurements on days 3, 7, 14, and 21 after treatment had started. Between day 21 and day 28, the SBF decreased significantly to 3.38 +/- SD 0.78 ml X (100 g X min)-1, p less than 0.05. The difference between the pretreatment SBF and SBF at the end of treatment was statistically significant, p less than 0.05. The changes in SBF in symmetrically nonlesional skin areas were statistically nonsignificant during the period of treatment. Pretreatment SBF was 2.60 +/- SD 1.08 (N = 8), and on day 28 was 1.91 +/- SD 0.74 ml X (100 g X min)-1 (N = 7). However, the tendency of a decreasing SBF at the end of treatment was a clear trend, since SBF in 6 of 7 patients decreased during the third week and in the patient who was discharged on day 22, a decrease in the SBF was observed on days 14 and 21.« less

The effects of hypertension on the cerebral circulation

PubMed Central

Pires, Paulo W.; Dams Ramos, Carla M.; Matin, Nusrat

2013-01-01

Maintenance of brain function depends on a constant blood supply. Deficits in cerebral blood flow are linked to cognitive decline, and they have detrimental effects on the outcome of ischemia. Hypertension causes alterations in cerebral artery structure and function that can impair blood flow, particularly during an ischemic insult or during periods of low arterial pressure. This review will focus on the historical discoveries, novel developments, and knowledge gaps in 1) hypertensive cerebral artery remodeling, 2) vascular function with emphasis on myogenic reactivity and endothelium-dependent dilation, and 3) blood-brain barrier function. Hypertensive artery remodeling results in reduction in the lumen diameter and an increase in the wall-to-lumen ratio in most cerebral arteries; this is linked to reduced blood flow postischemia and increased ischemic damage. Many factors that are increased in hypertension stimulate remodeling; these include the renin-angiotensin-aldosterone system and reactive oxygen species levels. Endothelial function, vital for endothelium-mediated dilation and regulation of myogenic reactivity, is impaired in hypertension. This is a consequence of alterations in vasodilator mechanisms involving nitric oxide, epoxyeicosatrienoic acids, and ion channels, including calcium-activated potassium channels and transient receptor potential vanilloid channel 4. Hypertension causes blood-brain barrier breakdown by mechanisms involving inflammation, oxidative stress, and vasoactive circulating molecules. This exposes neurons to cytotoxic molecules, leading to neuronal loss, cognitive decline, and impaired recovery from ischemia. As the population ages and the incidence of hypertension, stroke, and dementia increases, it is imperative that we gain a better understanding of the control of cerebral artery function in health and disease. PMID:23585139

Neural correlates of the classic color and emotional stroop in women with abuse-related posttraumatic stress disorder.

PubMed

Bremner, J Douglas; Vermetten, Eric; Vythilingam, Meena; Afzal, Nadeem; Schmahl, Christian; Elzinga, Bernet; Charney, Dennis S

2004-03-15

The anterior cingulate and medial prefrontal cortex play an important role in the inhibition of responses, as measured by the Stroop task, as well as in emotional regulation. Dysfunction of the anterior cingulate/medial prefrontal cortex has been implicated in posttraumatic stress disorder (PTSD). The purpose of this study was to use the Stroop task as a probe of anterior cingulate function in PTSD. Women with early childhood sexual abuse-related PTSD (n = 12) and women with abuse but without PTSD (n = 9) underwent positron emission tomographic measurement of cerebral blood flow during exposure to control, color Stroop, and emotional Stroop conditions. Women with abuse with PTSD (but not abused non-PTSD women) had a relative decrease in anterior cingulate blood flow during exposure to the emotional (but not color) classic Stroop task. During the color Stroop there were also relatively greater increases in blood flow in non-PTSD compared with PTSD women in right visual association cortex, cuneus, and right inferior parietal lobule. These findings add further evidence for dysfunction of a network of brain regions, including anterior cingulate and visual and parietal cortex, in abuse-related PTSD.

History of International Society for Cerebral Blood Flow and Metabolism

PubMed Central

Paulson, Olaf B; Kanno, Iwao; Reivich, Martin; Sokoloff, Louis

2012-01-01

Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the fast growing research led to a demand for a specialized journal. In this scientific environment, the International Society for Cerebral Blood Flow and Metabolism (ISCBFM) and its official Journal of Cerebral Metabolism were established in 1981 and has since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success of the society and strengthened the research. PMID:22186671

Exercise hyperaemia: magnitude and aspects on regulation in humans

PubMed Central

Saltin, Bengt

2007-01-01

The primary function of the cardiovascular system is to supply oxygen to tissues and organs in the body. When muscles contract the aerobic demands are met by an increase in oxygen delivery both at the systemic and the regional levels, a match that is very close and holds at submaximal exercise and when small muscle group contract also at vigorous intensities. The level of muscle perfusion reached is 250 ml min−1 (100 g)−1 in muscle of sedentary subjects and in endurance-trained athletes 400 ml min−1 (100 g)−1 has been reported. These levels of peak exercise hyperaemia equal what has been observed in other species. One consequence of these high muscle blood flows is that the human heart cannot support an optimal blood flow in whole body exercise (arms and legs combined) and sympathetically mediated vasoconstriction, also in arterioles feeding active limb muscles, contributes to matching peripheral resistance in order to maintain blood pressure. Respiratory muscles appear to have a higher priority for a blood flow than limb and torso muscles. There is no consensus in regard to which locally produced substances elicit the vasodilatation when muscle contracts. In addition to NO, data are presented for various metabolites of arachidonic acid and also on ATP, possibly released from the red cells. Using blockers of nitric oxide synthase (l-NMMA or l-NAME) and the enzymes producing epoxyeicosatrienoic acid (EET) (sulpaphenozole or tetraetylammonium chloride) or prostaglandins (indomethacin), muscle blood flow may be reduced by up to 25–40%. Evaluating the exact role of ATP has to await further studies in humans and especially the use of specific ATP receptor blockers. PMID:17640931

Concomitant administration of nitrous oxide and remifentanil reduces oral tissue blood flow without decreasing blood pressure during sevoflurane anesthesia in rabbits.

PubMed

Kasahara, Masataka; Ichinohe, Tatsuya; Okamoto, Sota; Okada, Reina; Kanbe, Hiroaki; Matsuura, Nobuyuki

2015-06-01

To determine whether continuous administration of nitrous oxide and remifentanil—either alone or together—alters blood flow in oral tissues during sevoflurane anesthesia. Eight male tracheotomized Japanese white rabbits were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF) were recorded in the absence of all test agents and after administration of the test agents (50 % nitrous oxide, 0.4 μg/kg/min remifentanil, and their combination) for 20 min. Nitrous oxide increased SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except DBP. Combined administration of nitrous oxide and remifentanil recovered SBP, DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained lower than control values. Our findings suggest that concomitant administration of nitrous oxide and remifentanil reduces blood flow in oral tissues without decreasing blood pressure during sevoflurane anesthesia in rabbits.

Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases

NASA Technical Reports Server (NTRS)

Boo, Yong Chool; Jo, Hanjoong

2003-01-01

Vascular endothelial cells are directly and continuously exposed to fluid shear stress generated by blood flow. Shear stress regulates endothelial structure and function by controlling expression of mechanosensitive genes and production of vasoactive factors such as nitric oxide (NO). Though it is well known that shear stress stimulates NO production from endothelial nitric oxide synthase (eNOS), the underlying molecular mechanisms remain unclear and controversial. Shear-induced production of NO involves Ca2+/calmodulin-independent mechanisms, including phosphorylation of eNOS at several sites and its interaction with other proteins, including caveolin and heat shock protein-90. There have been conflicting results as to which protein kinases-protein kinase A, protein kinase B (Akt), other Ser/Thr protein kinases, or tyrosine kinases-are responsible for shear-dependent eNOS regulation. The functional significance of each phosphorylation site is still unclear. We have attempted to summarize the current status of understanding in shear-dependent eNOS regulation.

Assessment of cerebral blood flow autoregulation (CBF AR) with rheoencephalography (REG): studies in animals

NASA Astrophysics Data System (ADS)

Popovic, Djordje; Bodo, Michael; Pearce, Frederick; van Albert, Stephen; Garcia, Alison; Settle, Tim; Armonda, Rocco

2013-04-01

The ability of cerebral vasculature to regulate cerebral blood flow (CBF) in the face of changes in arterial blood pressure (SAP) or intracranial pressure (ICP) is an important guard against secondary ischemia in acute brain injuries, and official guidelines recommend that therapeutic decisions be guided by continuous monitoring of CBF autoregulation (AR). The common method for CBF AR monitoring, which rests on real-time derivation of the correlation coefficient (PRx) between slow oscillations in SAP and ICP is, however, rarely used in clinical practice because it requires invasive ICP measurements. This study investigated whether the correlation coefficient between SAP and the pulsatile component of the non-invasive transcranial bioimpedance signal (rheoencephalography, REG) could be used to assess the state and lower limit of CBF AR. The results from pigs and rhesus macaques affirm the utility of REG; however, additional animal and clinical studies are warranted to assess selectivity of automatic REG-based evaluation of CBF AR.

Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

PubMed

Schmidl, D; Polska, E; Kiss, B; Sacu, S; Garhofer, G; Schmetterer, L

2010-01-01

Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.

Optical measurement of blood flow in exercising skeletal muscle: a pilot study

NASA Astrophysics Data System (ADS)

Wang, Detian; Baker, Wesley B.; Parthasarathy, Ashwin B.; Zhu, Liguo; Li, Zeren; Yodh, Arjun G.

2017-07-01

Blood flow monitoring during rhythm exercising is very important for sports medicine and muscle dieases. Diffuse correlation spectroscopy(DCS) is a relative new invasive way to monitor blood flow but suffering from muscle fiber motion. In this study we focus on how to remove exercise driven artifacts and obtain accurate estimates of the increase in blood flow from exercise. Using a novel fast software correlator, we measured blood flow in forearm flexor muscles of N=2 healthy adults during handgrip exercise, at a sampling rate of 20 Hz. Combining the blood flow and acceleration data, we resolved the motion artifact in the DCS signal induced by muscle fiber motion, and isolated the blood flow component of the signal from the motion artifact. The results show that muscle fiber motion strongly affects the DCS signal, and if not accounted for, will result in an overestimate of blood flow more than 1000%. Our measurements indicate rapid dilation of arterioles following exercise onset, which enabled blood flow to increase to a plateau of 200% in 10s. The blood flow also rapidly recovered to baseline following exercise in 10s. Finally, preliminary results on the dependence of blood flow from exercise intensity changes will be discussed.

Residual right portal branch flow after first-step ALPPS: artifact or homeostatic response?

PubMed

De Carlis, Luciano; Sguinzi, Raffaella; De Carlis, Riccardo; Di Sandro, Stefano; Mangoni, Jacopo; Aseni, Paolo; Giacomoni, Alessandro; Vanzulli, Angelo

2014-09-01

Mutual interactions between portal vein and hepatic artery can be documented during hepatobiliary surgery. Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a recently introduced surgical technique which can also represent a unique living human model to investigate intrahepatic blood circulation. We report three consecutive cases in which a residual right portal branch flow was clearly detectable after first-step ALPPS, and try to further investigate this unexpected finding with intraoperative clamping tests. Every patient was evaluated with CT scan 7 days after first-step ALPPS and Intraoperative Doppler Ultrasonography (IOUS) at both steps of the procedure. In every patient, CT scan and second-step IOUS demonstrated a clear hepatopetal flow distally to the divided right portal branch. The flow was present after right biliary duct clamping and stopped after right total hilar clamping as well as after right hepatic artery occlusion. Neither cross-portal circulation between the two hemilivers nor trans-sinusoidal backflow from the hepatic veins can explain these findings, which are rather consistent with a refilling of the occluded portal branch through the opening of intrahepatic arterioportal shunts (APS). APS could represent the simplest homeostatic mechanism that regulate intrahepatic blood flow.

Importance of Nitric Oxide for Local Increases of Blood Flow in Rat Cerebellar Cortex During Electrical Stimulation

NASA Astrophysics Data System (ADS)

Akgoren, Nuran; Fabricius, Martin; Lauritzen, Martin

1994-06-01

The endothelium-derived relaxing factor, probably nitric oxide (NO), is a potent vasodilator that regulates the vascular tone in several vascular beds, including the brain. We explored the possibility that NO might be of importance for the increase of cerebral blood flow (CBF) associated with activity of the well-defined neuronal circuits of the rat cerebellar cortex. Laser-Doppler flowmetry was used to measure increases of cerebellar blood flow evoked by trains of electrical stimulations of the dorsal surface. The evoked increases of CBF were frequency-dependent, being larger on than off the parallel fiber tracts, suggesting that conduction along parallel fibers and synaptic activation of target cells were important for the increase of CBF. This was verified experimentally since the evoked CBF increases were abolished by tetrodotoxin and reduced by 10 mM Mg2+ and selective antagonists for non-N-methyl-D-aspartate receptors. The cerebellar cortex contains high levels of NO synthase. This raised the possibility that NO was involved in the increase of CBF associated with neuronal activation. NO synthase inhibition by topical application of N^G-nitro-L-arginine attenuated the evoked CBF increase by about 50%. This effect was partially reversed by pretreatment with L-arginine, the natural substrate for the enzyme, while N^G-nitro-D-arginine, the inactive enantiomer, had no effect on the evoked CBF increases. Simultaneous blockade of non-N-methyl-D-aspartate receptors and NO synthase had no further suppressing effect on the blood flow increase than either substance alone, suggesting that the NO-dependent flow rise was dependent on postsynaptic mechanisms. These findings are consistent with the idea that local synthesis of NO is involved in the transduction mechanism between neuronal activity and increased CBF.

Blood flow/pump rotation ratio as an artificial lung performance monitoring tool during extracorporeal respiratory support using centrifugal pumps.

PubMed

Park, Marcelo; Mendes, Pedro Vitale; Hirota, Adriana Sayuri; dos Santos, Edzangela Vasconcelos; Costa, Eduardo Leite Vieira; Azevedo, Luciano Cesar Pontes

2015-01-01

To analyze the correlations of the blood flow/pump rotation ratio and the transmembrane pressure, CO2 and O2 transfer during the extracorporeal respiratory support. Five animals were instrumented and submitted to extracorporeal membrane oxygenation in a five-step protocol, including abdominal sepsis and lung injury. This study showed that blood flow/pump rotations ratio variations are dependent on extracorporeal membrane oxygenation blood flow in a positive logarithmic fashion. Blood flow/pump rotation ratio variations are negatively associated with transmembrane pressure (R2 = 0.5 for blood flow = 1500mL/minute and R2 = 0.4 for blood flow = 3500mL/minute, both with p < 0.001) and positively associated with CO2 transfer variations (R2 = 0.2 for sweep gas flow ≤ 6L/minute, p < 0.001, and R2 = 0.1 for sweep gas flow > 6L/minute, p = 0.006), and the blood flow/pump rotation ratio is not associated with O2 transfer variations (R2 = 0.01 for blood flow = 1500mL/minute, p = 0.19, and R2 = - 0.01 for blood flow = 3500 mL/minute, p = 0.46). Blood flow/pump rotation ratio variation is negatively associated with transmembrane pressure and positively associated with CO2 transfer in this animal model. According to the clinical situation, a decrease in the blood flow/pump rotation ratio can indicate artificial lung dysfunction without the occurrence of hypoxemia.

CD8 down-regulation on cytotoxic T lymphocytes of patients with endometrioid endometrial carcinomas.

PubMed

Pascual-García, Mónica; Bértolo, Cristina; Nieto, Juan C; Serrat, Neus; Espinosa, Íñigo; D'Angelo, Emanuela; Muñoz, Raquel; Rovira, Ramón; Vidal, Silvia; Prat, Jaime

2016-10-01

Carcinogenesis is a multistep process in which cancer cells and tumor stroma cells play important roles. T lymphocytes are immune constituents of tumor stroma and play a crucial function in anti-tumor response. By immunohistochemistry and flow cytometry, we studied T cytotoxic (CTLs) and T helper lymphocyte distribution and percentage in the tumor microenvironment and peripheral blood from 35 patients with endometrioid endometrial carcinomas (EEC). We also studied 23 healthy donors' blood samples as a control group. Tumor and non-tumoral endometrium samples were obtained. Immunohistochemistry revealed a high number of CTLs and T helper lymphocytes in the tumor stroma of myoinvasive EECs. T lymphocytes were mostly located in the invasive front. By flow cytometry, the percentages of CTLs and T helper lymphocytes were significantly higher in the tumor compared with the non-neoplastic endometrium (P = .0492 and P = .002). The mean fluorescence intensity of CD8 staining was lower in the tumor compared to the non-neoplastic endometrium (P = .001). There was also reduction of the mean fluorescence intensity of CD8 staining on peripheral blood from patients with grade 3 EECs compare to the peripheral blood from healthy donors (P = .0093). No alterations in the expression of granzymes A and B were found in the CTLs from the EEC cases. Finally, in a proteome profiler cytokine array we found that the growth differentiation factor 15 (GDF15) increased in blood in parallel to the tumor grade. EECs are capable of down-regulating CD8 expression of CTLs. Most likely, this effect is mediated by a soluble molecule present in plasma and is not a result of anergy or exhaustion state. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal nerves dynamically regulate renal blood flow in conscious, healthy rabbits.

PubMed

Schiller, Alicia M; Pellegrino, Peter R; Zucker, Irving H

2016-01-15

Despite significant clinical interest in renal denervation as a therapy, the role of the renal nerves in the physiological regulation of renal blood flow (RBF) remains debated. We hypothesized that the renal nerves physiologically regulate beat-to-beat RBF variability (RBFV). This was tested in chronically instrumented, healthy rabbits that underwent either bilateral surgical renal denervation (DDNx) or a sham denervation procedure (INV). Artifact-free segments of RBF and arterial pressure (AP) from calmly resting, conscious rabbits were used to extract RBFV and AP variability for time-domain, frequency-domain, and nonlinear analysis. Whereas steady-state measures of RBF, AP, and heart rate did not statistically differ between groups, DDNx rabbits had greater RBFV than INV rabbits. AP-RBF transfer function analysis showed greater admittance gain in DDNx rabbits than in INV rabbits, particularly in the low-frequency (LF) range where systemic sympathetic vasomotion gives rise to AP oscillations. In the LF range, INV rabbits exhibited a negative AP-RBF phase shift and low coherence, consistent with the presence of an active control system. Neither of these features were present in the LF range of DDNx rabbits, which showed no phase shift and high coherence, consistent with a passive, Ohm's law pressure-flow relationship. Renal denervation did not significantly affect nonlinear RBFV measures of chaos, self-affinity, or complexity, nor did it significantly affect glomerular filtration rate or extracellular fluid volume. Cumulatively, these data suggest that the renal nerves mediate LF renal sympathetic vasomotion, which buffers RBF from LF AP oscillations in conscious, healthy rabbits. Copyright © 2016 the American Physiological Society.

Clinical Investigation Program.

DTIC Science & Technology

1979-10-01

It has been established by a series of dog experiments using the-e-e-ctromagnetic flow meter that the blood flow in the inferior vena cava between...by thermodilution. Hepatic vein blood flow could be estimated by subtraction of the blood flow in the vena cava at the level of the renal veins from...the vena cava blood flow at the level of the diaphragm. This should be liver blood flow. It should be possible to sample pure hepatic vein blood by

Brachial blood flow under relative levels of blood flow restriction is decreased in a nonlinear fashion.

PubMed

Mouser, J Grant; Ade, Carl J; Black, Christopher D; Bemben, Debra A; Bemben, Michael G

2018-05-01

Blood flow restriction (BFR), the application of external pressure to occlude venous return and restrict arterial inflow, has been shown to increase muscular size and strength when combined with low-load resistance exercise. BFR in the research setting uses a wide range of pressures, applying a pressure based upon an individual's systolic pressure or a percentage of occlusion pressure; not a directly determined reduction in blood flow. The relationship between relative pressure and blood flow has not been established. To measure blood flow in the arm under relative levels of BFR. Forty-five people (18-40 years old) participated. Arterial occlusion pressure in the right arm was measured using a 5-cm pneumatic cuff. Blood flow in the brachial artery was measured at rest and at pressures between 10% and 90% of occlusion using ultrasound. Blood flow decreased in a nonlinear, stepped fashion. Blood flow decreased at 10% of occlusion and remained constant until decreasing again at 40%, where it remained until 90% of occlusion. The decrease in brachial blood flow is not proportional to the applied relative pressure. The prescription of blood flow restriction should take into account the stimulus provided at each relative level of blood flow. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Bridging macroscopic and microscopic methods for the measurements of cerebral blood flow: Toward finding the determinants in maintaining the CBF homeostasis.

PubMed

Kanno, I; Masamoto, K

Methods exist to evaluate the cerebral blood flow (CBF) at both the macroscopic and microscopic spatial scales. These methods provide complementary information for understanding the mechanism in maintaining an adequate blood supply in response to neural demand. The macroscopic CBF assesses perfusion flow, which is usually measured using radioactive tracers, such as diffusible, nondiffusible, or microsphere. Each of them determines CBF based on indicator dilution principle or particle fraction principle under the assumption that CBF is steady state during the measurement. Macroscopic CBF therefore represents averaged CBF over a certain space and time domains. On the other hand, the microscopic CBF assesses bulk flow, usually measures using real-time microscopy. The method assesses hemodynamics of microvessels, ie, vascular dimensions and flow velocities of fluorescently labeled or nonlabeled RBC and plasma markers. The microscopic CBF continuously fluctuates in time and space. Smoothing out this heterogeneity may lead to underestimation in the macroscopic CBF. To link the two measurements, it is needed to introduce a common parameter which is measurable for the both methods, such as mean transit time. Additionally, applying the defined physiological and/or pharmacological perturbation may provide a good exercise to determine how the specific perturbations interfere the quantitative relationships between the macroscopic and microscopic CBF. Finally, bridging these two-scale methods potentially gives a further indication how the absolute CBF is regulated with respect to a specific type of the cerebrovascular tones or capillary flow velocities in the brain. © 2016 Elsevier B.V. All rights reserved.

Live dynamic analysis of the developing cardiovascular system in mice

NASA Astrophysics Data System (ADS)

Lopez, Andrew L.; Wang, Shang; Larin, Kirill V.; Larina, Irina V.

2017-02-01

The study of the developing cardiovascular system in mice is important for understanding human cardiogenesis and congenital heart defects. Our research focuses on imaging early development in the mouse embryo to specifically understand cardiovascular development under the regulation of dynamic factors like contractile force and blood flow using optical coherence tomography (OCT). We have previously developed an OCT based approach that combines static embryo culture and advanced image processing with computational modeling to live-image mouse embryos and obtain 4D (3D+time) cardiodynamic datasets. Here we present live 4D dynamic blood flow imaging of the early embryonic mouse heart in correlation with heart wall movement. We are using this approach to understand how specific mutations impact heart wall dynamics, and how this influences flow patterns and cardiogenesis. We perform studies in mutant embryos with cardiac phenotypes such as myosin regulatory light chain 2, atrial isoform (Mlc2a). This work is brings us closer to understanding the connections between dynamic mechanical factors and gene programs responsible for early cardiovascular development.

Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise.

PubMed

Dominelli, Paolo B; Archiza, Bruno; Ramsook, Andrew H; Mitchell, Reid A; Peters, Carli M; Molgat-Seon, Yannick; Henderson, William R; Koehle, Michael S; Boushel, Robert; Sheel, A William

2017-11-01

What is the central question of this study? Does manipulation of the work of breathing during high-intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant-load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 versus 3.7 ± 0.8 l min -1 , P > 0.05), but was lower on the proportional assist ventilator trial (3.4 ± 0.7 l min -1 , P < 0.05) compared with control. Our findings support the concept that respiratory muscle work significantly influences the distribution of blood flow to both respiratory and locomotor muscles. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Leg blood flow is impaired during small muscle mass exercise in patients with COPD.

PubMed

Iepsen, U W; Munch, G W; Rugbjerg, M; Ryrsø, C K; Secher, N H; Hellsten, Y; Lange, P; Pedersen, B K; Thaning, P; Mortensen, S P

2017-09-01

Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee-extensor exercise, and during arterial infusions of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. Ten patients with moderate to severe COPD and eight age- and sex-matched healthy controls were studied. During knee-extensor exercise (10 W), leg blood flow was lower in the patients compared with the controls (1.82 ± 0.11 vs. 2.36 ± 0.14 l/min, respectively; P < 0.05), which compromised leg oxygen delivery (372 ± 26 vs. 453 ± 32 ml O 2 /min, respectively; P < 0.05). At rest, plasma endothelin-1 (vasoconstrictor) was higher in the patients with COPD ( P < 0.05) and also tended to be higher during exercise ( P = 0.07), whereas the formation of interstitial prostacyclin (vasodilator) was only increased in the controls. There was no difference between groups in the nitrite/nitrate levels (vasodilator) in plasma or interstitial fluid during exercise. Moreover, patients and controls showed similar vasodilatory capacity in response to both endothelium-independent (SNP) and endothelium-dependent (ACh) stimulation. The results suggest that leg muscle blood flow is impaired during small muscle mass exercise in patients with COPD possibly due to impaired formation of prostacyclin and increased levels of endothelin-1. NEW & NOTEWORTHY This study demonstrates that chronic obstructive pulmonary disease (COPD) is associated with a reduced blood flow to skeletal muscle during small muscle mass exercise. In contrast to healthy individuals, interstitial prostacyclin levels did not increase during exercise and plasma endothelin-1 levels were higher in the patients with COPD. Copyright © 2017 the American Physiological Society.

Transcutaneous Electrical Nerve Stimulation Regulates Organ Blood Flow and Apoptosis during Controlled Hypotension in Dogs

PubMed Central

Zhang, Lele; Shao, Xiaomei; Zhou, Chuanlong; Guo, Xiaoqing; Jin, Ling; Lian, Linli; Yu, Xiaojing; Dong, Zhenhua; Mo, Yadi; Fang, Jianqiao

2014-01-01

Transcutaneous electrical nerve stimulation (TENS) is commonly used in clinical practice for alleviating pains and physiological disorders. It has been reported that TENS could counteract the ischemic injury happened in some vital organs. To determine the protective effect of TENS on internal organs during CH in dogs, target hypotension was maintained for 60 min at 50% of the baseline mean arterial pressure (MAP). The perfusion to the brain, liver, stomach, and kidney was recorded and apoptosis within these organs was observed. Results showed that when arriving at the target MAP, and during the maintaining stage for 10 min, perfusion to the stomach and liver in the CH+TENS group was much higher than in the CH group (P<0.05). Perfusion to the cerebral cortex greatly declined in both the controlled pressure groups when compared with the general anesthesia (GA) group (P<0.05). After withdrawing CH, the hepatic blood flow in both the CH and CH+TENS groups, and the gastric and cerebral cortical blood flow in the CH+TENS group, were rapidly increased. By the end of MAP restoration, gastric blood flow in the CH group was still low. At 72 h after applying CH, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in stomach and kidney tissue from the CH group were significantly increased compared with those in the GA group (P<0.05). There was no significant difference in TUNEL-positive cells in the liver and hippocampus among the three groups. Our results demonstrated that CH with a 50% MAP level could cause lower perfusion to the liver, stomach, cerebral cortex, and kidney, with apoptosis subsequently occurring in the stomach and kidney. TENS combined GA is able to improve the blood flow to the liver, stomach, and reduce the apoptosis in the stomach and kidney. PMID:24732970

Cerebral blood perfusion after treatment with zolpidem and flumazenil in the baboon.

PubMed

Clauss, Ralf P; Dormehl, Irene C; Kilian, Elmaré; Louw, Werner K A; Nel, Wally H; Oliver, Douglas W

2002-01-01

Previous studies have shown that zolpidem (CAS 82626-48-0) can lead to improved perfusion in damaged brain tissue. Zolpidem belongs to the imidazopyridine chemical class and it illicits its pharmacological action via the gamma-aminobutyric acid (GABA) receptor system through stimulation of particularly the omega 1 receptors and to a lesser extent omega 2 receptors. Previously it was reported that no cerebral blood flow effects were observed in normal baboons after treatment with zolpidem, whereas an asymmetric regional increase in cerebral blood flow was observed in a neurologically abnormal baboon. In this study, the effect of a combination of the benzodiazepine receptor antagonist flumazenil (CAS 78755-81-4) and zolpidem on brain perfusion was examined by the 99mTc-hexamethyl-propylene amine oxime (99mTc-HMPAO) split dose brain single photon emission computed tomography (SPECT). Four normal baboons and the neurologically abnormal baboon from the previous zolpidem study were examined. In the current study the asymmetric changes observed after zolpidem--only treatment in the abnormal baboon was attenuated by flumazenil intervention. A decreased brain blood flow was observed after combination treatment of zolpidem and flumazenil in the normal baboons. The involvement of the omega receptors is suggested by these results. Up- or down-regulation of omega receptors may also contribute to the observed responses in the abnormal baboon and a brain injured patient.

An H-infinity approach to optimal control of oxygen and carbon dioxide contents in blood

NASA Astrophysics Data System (ADS)

Rigatos, Gerasimos; Siano, Pierluigi; Selisteanu, Dan; Precup, Radu

2016-12-01

Nonlinear H-infinity control is proposed for the regulation of the levels of oxygen and carbon dioxide in the blood of patients undergoing heart surgery and extracorporeal blood circulation. The levels of blood gases are administered through a membrane oxygenator and the control inputs are the externally supplied oxygen, the aggregate gas supply (oxygen plus nitrogen), and the blood flow which is regulated by a blood pump. The proposed control method is based on linearization of the oxygenator's dynamical model through Taylor series expansion and the computation of Jacobian matrices. The local linearization points are defined by the present value of the oxygenator's state vector and the last value of the control input that was exerted on this system. The modelling errors due to linearization are considered as disturbances which are compensated by the robustness of the control loop. Next, for the linearized model of the oxygenator an H-infinity control input is computed at each iteration of the control algorithm through the solution of an algebraic Riccati equation. With the use of Lyapunov stability analysis it is demonstrated that the control scheme satisfies the H-infinity tracking performance criterion, which signifies improved robustness against modelling uncertainty and external disturbances. Moreover, under moderate conditions the asymptotic stability of the control loop is also proven.

Acetazolamide-induced vasodilation does not inhibit the visually evoked flow response

PubMed Central

Yonai, Yaniv; Boms, Neta; Molnar, Sandor; Rosengarten, Bernhard; Bornstein, Natan M; Csiba, Laszlo; Olah, Laszlo

2010-01-01

Different methods are used to assess the vasodilator ability of cerebral blood vessels; however, the exact mechanism of cerebral vasodilation, induced by different stimuli, is not entirely known. Our aim was to investigate whether the potent vasodilator agent, acetazolamide (AZ), inhibits the neurovascular coupling, which also requires vasodilation. Therefore, visually evoked flow parameters were examined by transcranial Doppler in ten healthy subjects before and after AZ administration. Pulsatility index and peak systolic flow velocity changes, evoked by visual stimulus, were recorded in the posterior cerebral arteries before and after intravenous administration of 15 mg/kg AZ. Repeated-measures ANOVA did not show significant group main effect between the visually evoked relative flow velocity time courses before and after AZ provocation (P=0.43). Visual stimulation induced significant increase of relative flow velocity and decrease of pulsatility index not only before but also at the maximal effect of AZ. These results suggest that maximal cerebral vasodilation cannot be determined by the clinically accepted dose of AZ (15 mg/kg) and prove that neurovascular coupling remains preserved despite AZ-induced vasodilation. Our observation indicates independent regulation of vasodilation during neurovascular coupling, allowing the adaptation of cerebral blood flow according to neuronal activity even if other processes require significant vasodilation. PMID:19809468

[THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS].

PubMed

Titov, V N

2015-11-01

The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism-microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension.

Blood flow/pump rotation ratio as an artificial lung performance monitoring tool during extracorporeal respiratory support using centrifugal pumps

PubMed Central

Park, Marcelo; Mendes, Pedro Vitale; Hirota, Adriana Sayuri; dos Santos, Edzangela Vasconcelos; Costa, Eduardo Leite Vieira; Azevedo, Luciano Cesar Pontes

2015-01-01

Objective To analyze the correlations of the blood flow/pump rotation ratio and the transmembrane pressure, CO2 and O2 transfer during the extracorporeal respiratory support. Methods Five animals were instrumented and submitted to extracorporeal membrane oxygenation in a five-step protocol, including abdominal sepsis and lung injury. Results This study showed that blood flow/pump rotations ratio variations are dependent on extracorporeal membrane oxygenation blood flow in a positive logarithmic fashion. Blood flow/pump rotation ratio variations are negatively associated with transmembrane pressure (R2 = 0.5 for blood flow = 1500mL/minute and R2 = 0.4 for blood flow = 3500mL/minute, both with p < 0.001) and positively associated with CO2 transfer variations (R2 = 0.2 for sweep gas flow ≤ 6L/minute, p < 0.001, and R2 = 0.1 for sweep gas flow > 6L/minute, p = 0.006), and the blood flow/pump rotation ratio is not associated with O2 transfer variations (R2 = 0.01 for blood flow = 1500mL/minute, p = 0.19, and R2 = - 0.01 for blood flow = 3500 mL/minute, p = 0.46). Conclusion Blood flow/pump rotation ratio variation is negatively associated with transmembrane pressure and positively associated with CO2 transfer in this animal model. According to the clinical situation, a decrease in the blood flow/pump rotation ratio can indicate artificial lung dysfunction without the occurrence of hypoxemia. PMID:26340159

Enhanced Perfusion During Advanced Life Support Improves Survival With Favorable Neurologic Function in a Porcine Model of Refractory Cardiac Arrest

PubMed Central

Debaty, Guillaume; Metzger, Anja; Rees, Jennifer; McKnite, Scott; Puertas, Laura; Yannopoulos, Demetris; Lurie, Keith

2016-01-01

Objective To improve the likelihood for survival with favorable neurologic function after cardiac arrest, we assessed a new advanced life support approach using active compression-decompression cardiopulmonary resuscitation plus an intrathoracic pressure regulator. Design Prospective animal investigation. Setting Animal laboratory. Subjects Female farm pigs (n = 25) (39 ± 3 kg). Interventions Protocol A: After 12 minutes of untreated ventricular fibrillation, 18 pigs were randomized to group A—3 minutes of basic life support with standard cardiopulmonary resuscitation, defibrillation, and if needed 2 minutes of advanced life support with standard cardiopulmonary resuscitation; group B—3 minutes of basic life support with standard cardiopulmonary resuscitation, defibrillation, and if needed 2 minutes of advanced life support with active compression-decompression plus intrathoracic pressure regulator; and group C—3 minutes of basic life support with active compression-decompression cardiopulmonary resuscitation plus an impedance threshold device, defibrillation, and if needed 2 minutes of advanced life support with active compression-decompression plus intrathoracic pressure regulator. Advanced life support always included IV epinephrine (0.05 μg/kg). The primary endpoint was the 24-hour Cerebral Performance Category score. Protocol B: Myocardial and cerebral blood flow were measured in seven pigs before ventricular fibrillation and then following 6 minutes of untreated ventricular fibrillation during sequential 5 minutes treatments with active compression-decompression plus impedance threshold device, active compression-decompression plus intrathoracic pressure regulator, and active compression-decompression plus intrathoracic pressure regulator plus epinephrine. Measurements and Main Results Protocol A: One of six pigs survived for 24 hours in group A versus six of six in groups B and C (p = 0.002) and Cerebral Performance Category scores were 4.7 ± 0.8, 1.7 ± 0.8, and 1.0 ± 0, respectively (p = 0.001). Protocol B: Brain blood flow was significantly higher with active compression-decompression plus intrathoracic pressure regulator compared with active compression-decompression plus impedance threshold device (0.39 ± 0.23 vs 0.27 ± 0.14 mL/min/g; p = 0.03), whereas differences in myocardial perfusion were not statistically significant (0.65 ± 0.81 vs 0.42 ± 0.36 mL/min/g; p = 0.23). Brain and myocardial blood flow with active compression-decompression plus intrathoracic pressure regulator plus epinephrine were significantly increased versus active compression-decompression plus impedance threshold device (0.40 ± 0.22 and 0.84 ± 0.60 mL/min/g; p = 0.02 for both). Conclusion Advanced life support with active compression-decompression plus intrathoracic pressure regulator significantly improved cerebral perfusion and 24-hour survival with favorable neurologic function. These findings support further evaluation of this new advanced life support methodology in humans. PMID:25756411

Metabolic dynamics in skeletal muscle during acute reduction in blood flow and oxygen supply to mitochondria: in-silico studies using a multi-scale, top-down integrated model.

PubMed

Dash, Ranjan K; Li, Yanjun; Kim, Jaeyeon; Beard, Daniel A; Saidel, Gerald M; Cabrera, Marco E

2008-09-09

Control mechanisms of cellular metabolism and energetics in skeletal muscle that may become evident in response to physiological stresses such as reduction in blood flow and oxygen supply to mitochondria can be quantitatively understood using a multi-scale computational model. The analysis of dynamic responses from such a model can provide insights into mechanisms of metabolic regulation that may not be evident from experimental studies. For the purpose, a physiologically-based, multi-scale computational model of skeletal muscle cellular metabolism and energetics was developed to describe dynamic responses of key chemical species and reaction fluxes to muscle ischemia. The model, which incorporates key transport and metabolic processes and subcellular compartmentalization, is based on dynamic mass balances of 30 chemical species in both capillary blood and tissue cells (cytosol and mitochondria) domains. The reaction fluxes in cytosol and mitochondria are expressed in terms of a general phenomenological Michaelis-Menten equation involving the compartmentalized energy controller ratios ATP/ADP and NADH/NAD(+). The unknown transport and reaction parameters in the model are estimated simultaneously by minimizing the differences between available in vivo experimental data on muscle ischemia and corresponding model outputs in coupled with the resting linear flux balance constraints using a robust, nonlinear, constrained-based, reduced gradient optimization algorithm. With the optimal parameter values, the model is able to simulate dynamic responses to reduced blood flow and oxygen supply to mitochondria associated with muscle ischemia of several key metabolite concentrations and metabolic fluxes in the subcellular cytosolic and mitochondrial compartments, some that can be measured and others that can not be measured with the current experimental techniques. The model can be applied to test complex hypotheses involving dynamic regulation of cellular metabolism and energetics in skeletal muscle during physiological stresses such as ischemia, hypoxia, and exercise.

Effect of continuous negative-pressure breathing on skin blood flow during exercise in a hot environment.

PubMed

Nagashima, K; Nose, H; Takamata, A; Morimoto, T

1998-06-01

To assess the impact of continuous negative-pressure breathing (CNPB) on the regulation of skin blood flow, we measured forearm blood flow (FBF) by venous-occlusion plethysmography and laser-Doppler flow (LDF) at the anterior chest during exercise in a hot environment (ambient temperature = 30 degreesC, relative humidity = approximately 30%). Seven male subjects exercised in the upright position at an intensity of 60% peak oxygen consumption rate for 40 min with and without CNPB after 20 min of exercise. The esophageal temperature (Tes) in both conditions increased to 38.1 degreesC by the end of exercise, without any significant differences between the two trials. Mean arterial pressure (MAP) increased by approximately 15 mmHg by 8 min of exercise, without any significant difference between the two trials before CNPB. However, CNPB reduced MAP by approximately 10 mmHg after 24 min of exercise (P < 0.05). The increase in FBF and LDF in the control condition leveled off after 18 min of exercise above a Tes of 37.7 degreesC, whereas in the CNPB trial the increase continued, with a rise in Tes despite the decrease in MAP. These results suggest that CNPB enhances vasodilation of skin above a Tes of approximately 38 degrees C by stretching intrathoracic baroreceptors such as cardiopulmonary baroreceptors.

In vivo determination of cerebral hemodynamics and bioenergetics using spin-echo magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Oja, Joni Marcus Eric

1999-08-01

It is well known that the transverse relaxation time, T 2, is dependent on the oxygenation state of blood. Two biophysical mechanisms have been proposed to explain this interdependency. In the diffusion model, oxygenation effects are accounted for by water diffusion through field gradients inside and outside, of the erythrocytes, whereas in the exchange model, the oxygenation effect is thought to be due to the exchange of water between erythrocytes and plasma. Careful in vitro studies with blood have shown that the exchange model fits best to the obtained data in preference to the diffusion model. During brain activation, local increases in blood flow exceed the oxygen demand, resulting in less deoxygenated blood in the capillary and venous compartments. Due to this, blood is less paramagnetic in these activated brain regions, lengthening T2, which in turn increases the signal intensities of the corresponding voxels in the MR image. Thus the measured blood-oxygen-level-dependent (BOLD) image contrast is a complex function of many physiological parameters, such as tissue morphometry, blood volume, blood flow, oxygenation and oxygen metabolism. All of these parameters contribute to the tissue magnetization influencing the transverse relaxation rate. Until now, no exact equations have been available which would relate these hemodynamic variables to a single MRI observable parameter, namely T 2, in a manner in which absolute units can be used. A fundamental theory was developed to explain measured spin-echo BOLD effects, and it was tested in animals and humans. In animal studies, blood oxygenation was altered by regulating arterial oxygen or carbon dioxide tension. This resulted in changes in blood volume, flow and blood magnetization, which in turn was reflected in T2. Using analytical expressions derived from the theory, the transverse relaxation rate was related to the oxygen saturation and extraction and quantification of microvascular cerebral blood volume was achieved. Additionally, visual activation studies in humans were performed at different spatial resolutions to reveal the origin of the measured fMRI effects. The effect increased with spatial resolution indicating partial voluming with draining veins, which was correctly described by the theory. Also the relationship between oxygen demand and delivery ( OER = oxygen extraction ratio) was quantified from extraction ratio) was quantified from venous blood draining from the activated tissue. The measured OER indicated unmatched physiological alteration in oxygen consumption and blood flow, emphasizing that oxygenation effects dominate the changes seen in the measured fMRI signal changes.

Aryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells Is Required for Optimal Peripheral Perfusion Recovery.

PubMed

Borton, Anna Henry; Benson, Bryan L; Neilson, Lee E; Saunders, Ashley; Alaiti, M Amer; Huang, Alex Y; Jain, Mukesh K; Proweller, Aaron; Ramirez-Bergeron, Diana L

2018-06-01

Limb ischemia resulting from peripheral vascular disease is a common cause of morbidity. Vessel occlusion limits blood flow, creating a hypoxic environment that damages distal tissue, requiring therapeutic revascularization. Hypoxia-inducible factors (HIFs) are key transcriptional regulators of hypoxic vascular responses, including angiogenesis and arteriogenesis. Despite vascular smooth muscle cells' (VSMCs') importance in vessel integrity, little is known about their functional responses to hypoxia in peripheral vascular disease. This study investigated the role of VSMC HIF in mediating peripheral ischemic responses. We used Arnt SMKO mice with smooth muscle-specific deletion of aryl hydrocarbon receptor nuclear translocator (ARNT, HIF-1β), required for HIF transcriptional activity, in a femoral artery ligation model of peripheral vascular disease. Arnt SMKO mice exhibit impaired perfusion recovery despite normal collateral vessel dilation and angiogenic capillary responses. Decreased blood flow manifests in extensive tissue damage and hypoxia in ligated limbs of Arnt SMKO mice. Furthermore, loss of aryl hydrocarbon receptor nuclear translocator changes the proliferation, migration, and transcriptional profile of cultured VSMCs. Arnt SMKO mice display disrupted VSMC morphologic features and wrapping around arterioles and increased vascular permeability linked to decreased local blood flow. Our data demonstrate that traditional vascular remodeling responses are insufficient to provide robust peripheral tissue reperfusion in Arnt SMKO mice. In all, this study highlights HIF responses to hypoxia in arteriole VSMCs critical for the phenotypic and functional stability of vessels that aid in the recovery of blood flow in ischemic peripheral tissues. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Blood flow and blood cell interactions and migration in microvessels

NASA Astrophysics Data System (ADS)

Fedosov, Dmitry; Fornleitner, Julia; Gompper, Gerhard

2011-11-01

Blood flow in microcirculation plays a fundamental role in a wide range of physiological processes and pathologies in the organism. To understand and, if necessary, manipulate the course of these processes it is essential to investigate blood flow under realistic conditions including deformability of blood cells, their interactions, and behavior in the complex microvascular network which is characteristic for the microcirculation. We employ the Dissipative Particle Dynamics method to model blood as a suspension of deformable cells represented by a viscoelastic spring-network which incorporates appropriate mechanical and rheological cell-membrane properties. Blood flow is investigated in idealized geometries. In particular, migration of blood cells and their distribution in blood flow are studied with respect to various conditions such as hematocrit, flow rate, red blood cell aggregation. Physical mechanisms which govern cell migration in microcirculation and, in particular, margination of white blood cells towards the vessel wall, will be discussed. In addition, we characterize blood flow dynamics and quantify hemodynamic resistance. D.F. acknowledges the Humboldt Foundation for financial support.

The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation.

PubMed

Nishi, Erika E; Bergamaschi, Cássia T; Campos, Ruy R

2015-04-20

What is the topic of this review? This review describes the role of renal nerves as the key carrier of signals from the kidneys to the CNS and vice versa; the brain and kidneys communicate through this carrier to maintain homeostasis in the body. What advances does it highlight? Whether renal or autonomic dysfunction is the predominant contributor to systemic hypertension is still debated. In this review, we focus on the role of the renal nerves in a model of renovascular hypertension. The sympathetic nervous system influences the renal regulation of arterial pressure and body fluid composition. Anatomical and physiological evidence has shown that sympathetic nerves mediate changes in urinary sodium and water excretion by regulating the renal tubular water and sodium reabsorption throughout the nephron, changes in the renal blood flow and the glomerular filtration rate by regulating the constriction of renal vasculature, and changes in the activity of the renin-angiotensin system by regulating the renin release from juxtaglomerular cells. Additionally, renal sensory afferent fibres project to the autonomic central nuclei that regulate blood pressure. Hence, renal nerves play a key role in the crosstalk between the kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased sympathetic nerve activity to the kidney and the renal afferent nerve activity to the CNS may contribute to the outcome of diseases, such as hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Effect of Vestibular Impairment on Cerebral Blood Flow Response to Dynamic Roll Tilt

NASA Technical Reports Server (NTRS)

Serrador, J. M.; Black, F. O.; Schlgel, Todd T.; Lipsitz, L. A.; Wood, S. J.

2008-01-01

Change to upright posture results in reductions in cerebral perfusion pressure due to hydrostatic pressure changes related to gravity. Since vestibular organs, specifically the otoliths, provide information on position relative to gravity, vestibular inputs may assist in adaptation to the upright posture. The goal of this study was to examine the effect of direct vestibular stimulation on cerebral blood flow (CBF). To examine the role of otolith inputs we screened 165 subjects for vestibular function and classified subjects as either normal or impaired based on ocular torsion. Ocular torsion, an indication of otolith function, was assessed during sinusoidal roll tilt of 20 degrees at 0.01 Hz (100 sec per cycle). Subjects with torsion one SD below the mean were classified as impaired while subjects one SD above the mean were considered normal. During one session subjects were placed in a chair that was sinusoidally rotated 25 degrees in the roll plane at five frequencies: 0.25 & 0.125 Hz for 80 sec, 0.0625 Hz for 160 sec and 0.03125 Hz and 0.015625 Hz for 320 sec. During testing, CBF (transcranial Doppler), blood pressure (Finapres), and end tidal CO2 (Puritan Bennet) were measured continuously. Ocular torsion was assessed from infrared images of the eyes. All rotations were done in the dark with subjects fixated on a red LED directly at the center of rotation. In the normal group, dynamic tilt resulted in significant changes in both blood pressure and cerebral blood flow velocity that was related to the frequency of stimulus. In contrast the impaired group did not show similar patterns. As expected normal subjects demonstrated significant ocular torsion that was related to stimulus frequency while impaired subjects had minimal changes. These data suggest that vestibular inputs have direct effects on cerebral blood flow regulation during dynamic tilt. Supported by NASA.

Evaluating the methods used for measuring cerebral blood flow at rest and during exercise in humans.

PubMed

Tymko, Michael M; Ainslie, Philip N; Smith, Kurt J

2018-05-16

The first accounts of measuring cerebral blood flow (CBF) in humans were made by Angelo Mosso in ~1880, who recorded brain pulsations in patients with skull defects. In 1890, Charles Roy and Charles Sherrington determined in animals that brain pulsations-assessed via a similar method used by Mosso-were altered during a variety of stimuli including sensory nerve stimulation, asphyxia, and pharmacological interventions. Between 1880 and 1944, measurements for CBF were typically relied on skull abnormalities in humans. Thereafter, Kety and Schmidt introduced a new methodological approach in 1945 that involved nitrous oxide dilution combined with serial arterial and jugular venous blood sampling. Less than a decade later (1950's), several research groups employed the Kety-Schmidt technique to assess the effects of exercise on global CBF and metabolism; these studies demonstrated an uncoupling of CBF and metabolism during exercise, which was contrary to early hypotheses. However, there were several limitations to this technique related to low temporal resolution and the inability to measure regional CBF. These limitations were overcome in the 1960's when transcranial Doppler ultrasound (TCD) was developed as a method to measure beat-by-beat cerebral blood velocity. Between 1990 and 2010, TCD further progressed our understanding of CBF regulation and allowed for insight into other mechanistic factors, independent of local metabolism, involved in regulating CBF during exercise. Recently, it was discovered that TCD may not be accurate under several physiological conditions. Other measures of indexing CBF such as Duplex ultrasound and magnetic resonance imaging, although not without some limitations, may be more applicable for future investigations.

Thermography-based blood flow imaging in human skin of the hands and feet: a spectral filtering approach.

PubMed

Sagaidachnyi, A A; Fomin, A V; Usanov, D A; Skripal, A V

2017-02-01

The determination of the relationship between skin blood flow and skin temperature dynamics is the main problem in thermography-based blood flow imaging. Oscillations in skin blood flow are the source of thermal waves propagating from micro-vessels toward the skin's surface, as assumed in this study. This hypothesis allows us to use equations for the attenuation and dispersion of thermal waves for converting the temperature signal into the blood flow signal, and vice versa. We developed a spectral filtering approach (SFA), which is a new technique for thermography-based blood flow imaging. In contrast to other processing techniques, the SFA implies calculations in the spectral domain rather than in the time domain. Therefore, it eliminates the need to solve differential equations. The developed technique was verified within 0.005-0.1 Hz, including the endothelial, neurogenic and myogenic frequency bands of blood flow oscillations. The algorithm for an inverse conversion of the blood flow signal into the skin temperature signal is addressed. The examples of blood flow imaging of hands during cuff occlusion and feet during heating of the back are illustrated. The processing of infrared (IR) thermograms using the SFA allowed us to restore the blood flow signals and achieve correlations of about 0.8 with a waveform of a photoplethysmographic signal. The prospective applications of the thermography-based blood flow imaging technique include non-contact monitoring of the blood supply during engraftment of skin flaps and burns healing, as well the use of contact temperature sensors to monitor low-frequency oscillations of peripheral blood flow.

Flicker-induced retinal vasodilatation is not dependent on complement factor H polymorphism in healthy young subjects.

PubMed

Told, Reinhard; Palkovits, Stefan; Boltz, Agnes; Schmidl, Doreen; Napora, Katarzyna J; Werkmeister, René M; Haslacher, Helmuth; Frantal, Sophie; Popa-Cherecheanu, Alina; Schmetterer, Leopold; Garhöfer, Gerhard

2014-11-01

The complement factor H (CFH) tyrosine 402 histidine (Y402H, rs1061170) variant is known to be significantly associated with age-related macular degeneration (AMD). Whether this genetic variant may impact retinal blood flow regulation is largely unknown. This study investigated whether flicker-induced vasodilation, an indicator for the coupling between neural activity and blood flow, is altered in subjects carrying the rs1061170 risk allele. One hundred healthy subjects (aged between 18 and 45 years) were included in this study. Retinal blood flow regulation was tested by assessing retinal vessel calibres in response to stimulation with diffuse flicker light. Retinal vascular flicker responses were determined with a Dynamic Vessel Analyzer (DVA). In addition, genotyping for rs1061170 was performed. Eighteen subjects were homozygous for the risk allele C, 50 were homozygous for the ancestral allele T, and 31 subjects were heterozygous (CT). One subject had to be excluded from data evaluation, as no genetic analysis could be performed due to technical difficulties. Baseline diameters of retinal arteries (p = 0.39) and veins (p = 0.64) were comparable between the three groups. Flicker-induced vasodilation in both retinal arteries (p = 0.38) and retinal veins (p = 0.62) was also comparable between the three studied groups. Our data indicate that homozygous healthy young carriers of the C risk allele at rs1061170 do not show abnormal flicker-induced vasodilation in the retina. This suggests that the high-risk genetic variant of CFH polymorphism does not impact neuro-vascular coupling in healthy subjects. © 2014 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.

Treatment with a nitric oxide-donating NSAID alleviates functional muscle ischemia in the mouse model of Duchenne muscular dystrophy.

PubMed

Thomas, Gail D; Ye, Jianfeng; De Nardi, Claudio; Monopoli, Angela; Ongini, Ennio; Victor, Ronald G

2012-01-01

In patients with Duchenne muscular dystrophy (DMD) and the standard mdx mouse model of DMD, dystrophin deficiency causes loss of neuronal nitric oxide synthase (nNOSμ) from the sarcolemma, producing functional ischemia when the muscles are exercised. We asked if functional muscle ischemia would be eliminated and normal blood flow regulation restored by treatment with an exogenous nitric oxide (NO)-donating drug. Beginning at 8 weeks of age, mdx mice were fed a standard diet supplemented with 1% soybean oil alone or in combination with a low (15 mg/kg) or high (45 mg/kg) dose of HCT 1026, a NO-donating nonsteroidal anti-inflammatory agent which has previously been shown to slow disease progression in the mdx model. After 1 month of treatment, vasoconstrictor responses to intra-arterial norepinephrine (NE) were compared in resting and contracting hindlimbs. In untreated mdx mice, the usual effect of muscle contraction to attenuate NE-mediated vasoconstriction was impaired, resulting in functional ischemia: NE evoked similar decreases in femoral blood flow velocity and femoral vascular conductance (FVC) in the contracting compared to resting hindlimbs (ΔFVC contraction/ΔFVC rest=0.88 ± 0.03). NE-induced functional ischemia was unaffected by low dose HCT 1026 (ΔFVC ratio=0.92 ± 0.04; P>0.05 vs untreated), but was alleviated by the high dose of the drug (ΔFVC ratio=0.22 ± 0.03; P<0.05 vs untreated or low dose). The beneficial effect of high dose HCT 1026 was maintained with treatment up to 3 months. The effect of the NO-donating drug HCT 1026 to normalize blood flow regulation in contracting mdx mouse hindlimb muscles suggests a putative novel treatment for DMD. Further translational research is warranted.

Functional optical coherence tomography for live dynamic analysis of mouse embryonic cardiogenesis

NASA Astrophysics Data System (ADS)

Wang, Shang; Lopez, Andrew L.; Larina, Irina V.

2018-02-01

Blood flow, heart contraction, and tissue stiffness are important regulators of cardiac morphogenesis and function during embryonic development. Defining how these factors are integrated is critically important to advance prevention, diagnostics, and treatment of congenital heart defects. Mammalian embryonic development is taking place deep within the female body, which makes cardiodynamic imaging and analysis during early developmental stages in humans inaccessible. With thousands of mutant lines available and well-established genetic manipulation tools, mouse is a great model to understand how biomechanical factors are integrated with molecular pathways to regulate cardiac function and development. Dynamic imaging and quantitative analysis of the biomechanics of live mouse embryos have become increasingly important, which demands continuous advancements in imaging techniques and live assessment approaches. This has been one of the major drives to keep pushing the frontier of embryonic imaging for better resolution, higher speed, deeper penetration, and more diverse and effective contrasts. Optical coherence tomography (OCT) has played a significant role in addressing such demands, and its features in non-labeling imaging, 3D capability, a large working distance, and various functional derivatives allow OCT to cover a number of specific applications in embryonic imaging. Recently, our group has made several technical improvements in using OCT to probe the biomechanical aspects of live developing mouse embryos at early stages. These include the direct volumetric structural and functional imaging of the cardiodynamics, four-dimensional quantitative Doppler imaging and analysis of the cardiac blood flow, and fourdimensional blood flow separation from the cardiac wall tissue in the beating embryonic heart. Here, we present a short review of these studies together with brief descriptions of the previous work that demonstrate OCT as a valuable and useful imaging tool for the research in developmental cardiology.

Effect of Processing and Storage on RBC function in vivo

PubMed Central

Doctor, Allan; Spinella, Phil

2012-01-01

Red Blood Cell (RBC) transfusion is indicated to improve oxygen delivery to tissue, and for no other purpose. We have come to appreciate that donor RBCs are fundamentally altered during processing and storage, in a fashion that both impairs oxygen transport efficacy and introduces additional risk by perturbing both immune and coagulation systems. The protean biophysical and physiologic changes in RBC function arising from storage are termed the ‘storage lesion’; many have been understood for some time; for example, we know that the oxygen affinity of stored blood rises during the storage period1 and that intracellular allosteric regulators, notably 2,3-bisphosphoglyceric acid (DPG) and ATP, are depleted during storage. Our appreciation of other storage lesion features has emerged with improved understanding of coagulation, immune and vascular signaling systems. Herein we review key features of the ‘storage lesion’. Additionally, we call particular attention to the newly appreciated role of RBCs in regulating linkage between regional blood flow and regional O2 consumption by regulating the bioavailability of key vasoactive mediators in plasma, as well as discuss how processing and storage disturbs this key signaling function and impairs transfusion efficacy. PMID:22818545

Experimental Study of Isothermal Plate Uniformity for Blood Warmer Development using Geothermal Energy

NASA Astrophysics Data System (ADS)

Hendrarsakti, J.; Ichsan, Y.

2016-09-01

This research was conducted to assess the direct use of geothermal energy for blood warmer. The heating plate was made form aluminium plates with dimensions of 100 x 200 mm and then fed from the hot water heater. Tests were conducted in the laboratory where geothermal source water is replaced with the heat generated from the heater. The hot water from the heater in the temperature range 55°C - 60°C flowed into vertical chamber. Setting the temperature of the hot water heater is done by changing the flow of hot water coming out of the heater. Results showed that the value of a standard deviation of plate temperature was about 0.42 °C, so it can be said isothermal accordance with design requirement and objective. The test data used for the analysis of the manufacture of the heating plate in the blood warmer to regulate the discharge of hot water at intervals of 21.47 mL/s to 24.8 mL/s to obtain a temperature of 37.20 °C - 40.15 °C. Geothermal energy has the potential for blood warmer because blood warmer is part of the energy cascade in a temperature range of 40°C to 60°C

Modeling microcirculatory blood flow: current state and future perspectives.

PubMed

Gompper, Gerhard; Fedosov, Dmitry A

2016-01-01

Microvascular blood flow determines a number of important physiological processes of an organism in health and disease. Therefore, a detailed understanding of microvascular blood flow would significantly advance biophysical and biomedical research and its applications. Current developments in modeling of microcirculatory blood flow already allow to go beyond available experimental measurements and have a large potential to elucidate blood flow behavior in normal and diseased microvascular networks. There exist detailed models of blood flow on a single cell level as well as simplified models of the flow through microcirculatory networks, which are reviewed and discussed here. The combination of these models provides promising prospects for better understanding of blood flow behavior and transport properties locally as well as globally within large microvascular networks. © 2015 Wiley Periodicals, Inc.

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase.

PubMed

Khan, Sitara G; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R; Martin, Katherine; Khan, Faisal; O'Gallagher, Kevin; Chowienczyk, Philip J; Shah, Ajay M

2017-09-01

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion ( P < 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S -methyl-l-thiocitrulline (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% ( P = 0.02) and 0.5 ± 2.8% ( P = 0.51) in the presence of S -methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress ( r 2 = -0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. Copyright © 2017 the American Physiological Society.

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

PubMed Central

Khan, Sitara G.; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R.; Martin, Katherine; Khan, Faisal; O’Gallagher, Kevin; Chowienczyk, Philip J.

2017-01-01

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion (P < 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S-methyl-l-thiocitrulline (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% (P = 0.02) and 0.5 ± 2.8% (P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress (r2 = −0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. PMID:28646032

Non-invasive determination of instantaneous brachial blood flow using the oscillometric method.

PubMed

Liu, Shing-Hong; Wang, Jia-Jung; Cheng, Da-Chuan

2009-08-01

The oscillometric method has been widely used to measure arterial systolic and diastolic blood pressures, but its potential for arterial blood flow measurements still remains to be explored. The aim of this study was to non-invasively determine arterial blood flow using an oscillometric blood flow measurement system. The system consists of a pneumatic elastic cuff, an air-pumping motor, a releaser valve, a pressure transducer, and an airflow meter. To build a non-linear cuff model, we measured airflow pumped into the pneumatic cuff and cuff pressure using an airflow meter and pressure transducer during the inflation period, respectively. During the deflation period, only the pressure transducer was used to record cuff pressure. Based on the cuff model, the oscillometric blood flow waveform was obtained by integrating the oscillometric pressure waveform. We compared arterial blood flow derived from the maximum amplitude of the oscillometric blood flow waveform with Doppler-measured blood flow calculated with the diameters and blood velocities of the brachial arteries in 32 subjects who underwent diagnostic evaluations for peripheral arterial embolism. A linear correlation coefficient of r = 0.716 was found between the oscillometry- and Doppler-based blood flow measurements in the 32 subjects. These results suggest that blood flow passing through the brachial artery can be quantified non-invasively using the oscillometric approach after appropriate calibration.

Acute effect of coffee drinking on dynamic cerebral autoregulation.

PubMed

Sasaki, Hiroyuki; Hirasawa, Ai; Washio, Takuro; Ogoh, Shigehiko

2016-05-01

Drinking coffee causes caffeine-induced physiological alterations such as increases in arterial blood pressure, sympathetic nerve activity, cerebral vasoconstriction, etc., and these physiological alterations may be associated with a reduced risk of cerebral vascular disease. However, the effect of coffee drinking on dynamic cerebral blood flow (CBF) regulation remains unclear. The aim of this study was to test our hypothesis that coffee drinking enhances dynamic cerebral autoregulation. Twelve healthy young subjects participated in the present study. After a 5 min baseline measurement in a semi-recumbent position on the hospital bed, each subject drank water (CON) as a placebo condition or coffee beverage (Coffee INT). Arterial blood pressure and middle cerebral artery blood velocity (MCAv) were measured continuously throughout the experiment. At 30 min after the intake of either water or coffee, dynamic cerebral autoregulation was examined using a thigh cuffs occlusion and release technique. Each condition was randomly performed on a different day. Under Coffee INT condition, mean arterial blood pressure was increased (P = 0.01) and mean MCAv was decreased (P = 0.01) from the baseline. The rate of regulation (RoR), as an index of dynamic cerebral autoregulation, during coffee condition was significantly higher than that during CON (P = 0.0009). The findings of the present study suggest that coffee drinking augments dynamic CBF regulation with cerebral vasoconstriction. This phenomenon may be associated with a reduction in the risk of cerebral vascular disease.

Cardiovascular Responses to Skeletal Muscle Stretching: "Stretching" the Truth or a New Exercise Paradigm for Cardiovascular Medicine?

PubMed

Kruse, Nicholas T; Scheuermann, Barry W

2017-12-01

Stretching is commonly prescribed with the intended purpose of increasing range of motion, enhancing muscular coordination, and preventing prolonged immobilization induced by aging or a sedentary lifestyle. Emerging evidence suggests that acute or long-term stretching exercise may modulate a variety of cardiovascular responses. Specifically, at the onset of stretch, the mechanical deformation of the vascular bed coupled with stimulation of group III muscle afferent fibers initiates a cascade of events resulting in both peripheral vasodilation and a heart rate-driven increase in cardiac output, blood pressure, and muscle blood flow. This potential to increase shear stress and blood flow without the use of excessive muscle energy expenditure may hold important implications for future therapeutic vascular medicine and cardiac health. However, the idea that a cardiovascular component may be involved in human skeletal muscle stretching is relatively new. Therefore, the primary intent of this review is to highlight topics related to skeletal muscle stretching and cardiovascular regulation and function. The current evidence suggests that acute stretching causes a significant macro- and microcirculatory event that alters blood flow and the relationship between oxygen availability and oxygen utilization. These acute vascular changes if performed chronically may result in improved endothelial function, improved arterial blood vessel stiffness, and/or reduced blood pressure. Although several mechanisms have been postulated, an increased nitric oxide bioavailability has been highlighted as one promising candidate for the improvement in vessel function with stretching. Collectively, the evidence provided in this review suggests that stretching acutely or long term may serve as a novel and alternative low intensity therapeutic intervention capable of improving several parameters of vascular function.

[The value of the thermocouple in the measurement of the gastric mucosal blood-flow. The influence of the occlusion of the celiac artery and prostaglandin E1 on the gastric mucosal blood flow. An experimental study in animals (author's transl)].

PubMed

Koch, H; Demling, L

1976-02-27

The study has been carried out to ensure the positive evidence of the measurement of the gastric mucosal blood-flow with the aid of the thermocouple (heat-clearance technique). The experiments have shown that the suction pressure of 600 mm mercury column which was used to fix the Thermocouple to the mucosa was indispensable in order to assess the blood-flow in the entire depth of the mucosa. Changes in the mucosal blood-flow are measuured at the same rate in all quadrants of the gastric corpus. The measuring of the blood-flow of a well circumscribed area of the mucosa is therefore representative for the entire corpus. Vasopressin led to a significant reduction of the gastric mucosal blood-flow measured with heat-clearance as well aminopyrine-clearance. There was a linear correlation between the results of both methods. Vasopressin selectively reduces the blood-flow of the gastric mucosa but not of the submucosa, the muscular layer and the serosa. Therefore it seems to be probable that changes in mucosal blood-flow selectively can be measured with the aid of the thermocouple. After previous stimulation with pentagastrin neither mucosal blood-flow nor acid secretion of the stomach were influenced by the occlusion of the celiac artery by 25 %. The occlusion of the celiac artery by 50 % reduced significantly the pentagastrin-stimulated gastric mucosal blood-flow whereas the acid secretion was not influenced. Prostaglandin E1 at a dose rate of 2 mug/kg-h increased significantly arterial and mucosal blood-flow as well as acid secretion of the stomach. In comparison PGE1 administered at a dose rate of 4 mug/kg-h reduced significantly gastric mucosal blood-flow and gastric secretion. PGE1 at a dose rate of 8 mug/kg-h did not produce any significant changes in blood-flow and secretion. The results suggested that the changes of gastric secretion observed with PGE1 were the consequence of primary changes in the gastric mucosal blood-flow.

Cell-cell interaction in blood flow in patients with coronary heart disease (in vitro study)

NASA Astrophysics Data System (ADS)

Malinova, Lidia I.; Simonenko, Georgy V.; Denisova, Tatyana P.; Tuchin, Valery V.

2007-02-01

Blood cell-cell and cell-vessel wall interactions are one of the key patterns in blood and vascular pathophysiology. We have chosen the method of reconstruction of pulsative blood flow in vitro in the experimental set. Blood flow structure was studied by PC integrated video camera with following slide by slide analysis. Studied flow was of constant volumetric blood flow velocity (1 ml/h). Diameter of tube in use was comparable with coronary arteries diameter. Glucose solution and unfractured heparin were used as the nonspecial irritants of studied flow. Erythrocytes space structure in flow differs in all groups of patients in our study (men with stable angina pectoris (SAP), myocardial infarction (MI) and practically healthy men (PHM). Intensity of erythrocytes aggregate formation was maximal in patients with SAP, but time of their "construction/deconstruction" at glucose injection was minimal. Phenomena of primary clotting formation in patients with SAP of high function class was reconstructed under experimental conditions. Heparin injection (10 000 ED) increased linear blood flow velocity both in patients with SAP, MI and PHP but modulated the cell profile in the flow. Received data correspond with results of animal model studies and noninvasive blood flow studies in human. Results of our study reveal differences in blood flow structure in patients with coronary heart disease and PHP under irritating conditions as the possible framework of metabolic model of coronary blood flow destabilization.

Effects of Omega-3 Fatty Acids on Resting Cerebral Perfusion in Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

PubMed

Schwarz, C; Wirth, M; Gerischer, L; Grittner, U; Witte, A V; Köbe, T; Flöel, A

2018-01-01

Alteration of cerebral perfusion can be considered as a possible therapeutic target in mild cognitive impairment. This randomized, placebo-controlled, double-blind proof-of-concept study assessed effects of omega-3 fatty acids on cerebral perfusion in patients with mild cognitive impairment. In thirteen patients (omega:n=5; placebo:n=8) cerebral perfusion was measured before and after 26-weeks intervention within posterior cortical regions using magnetic resonance imaging. There was a medium effect of intervention on cerebral blood flow (η2=0.122) and blood volume (η2=0.098). The omega group showed an increase in blood flow (mean difference: 0.02 [corresponds to 26.1%], 95% confidence interval:0.00-0.05) and blood volume (mean difference: 0.08 [corresponds to 18.5%], 95% confidence interval:0.01-0.15), which was not observed in the placebo group. These preliminary findings suggest that omega-3 fatty acids supplementation may improve perfusion in cerebral regions typically affected in mild cognitive impairment.Regulation of perfusion may help to maintain brain structure and function and potentially delay conversion to dementia.

Three-dimensional imaging of absolute blood flow velocity and blood vessel position under low blood flow velocity based on Doppler signal information included in scattered light from red blood cells

NASA Astrophysics Data System (ADS)

Kyoden, Tomoaki; Akiguchi, Shunsuke; Tajiri, Tomoki; Andoh, Tsugunobu; Hachiga, Tadashi

2017-11-01

The development of a system for in vivo visualization of occluded distal blood vessels for diabetic patients is the main target of our research. We herein describe two-beam multipoint laser Doppler velocimetry (MLDV), which measures the instantaneous multipoint flow velocity and can be used to observe the blood flow velocity in peripheral blood vessels. By including a motorized stage to shift the measurement points horizontally and in the depth direction while measuring the velocity, the path of the blood vessel in the skin could be observed using blood flow velocity in three-dimensional space. The relationship of the signal power density between the blood vessel and the surrounding tissues was shown and helped us identify the position of the blood vessel. Two-beam MLDV can be used to simultaneously determine the absolute blood flow velocity distribution and identify the blood vessel position in skin.

Sex-dependent alterations in resting-state cerebral blood flow, amplitude of low-frequency fluctuations and their coupling relationship in schizophrenia.

PubMed

Ma, Xiaomei; Wang, Di; Zhou, Yujing; Zhuo, Chuanjun; Qin, Wen; Zhu, Jiajia; Yu, Chunshui

2016-04-01

We aimed to investigate sex-dependent alterations in resting-state relative cerebral blood flow, amplitude of low-frequency fluctuations and relative cerebral blood flow-amplitude of low-frequency fluctuations coupling in patients with schizophrenia. Resting-state functional magnetic resonance imaging and three-dimensional pseudo-continuous arterial spin labeling imaging were performed to obtain resting-state amplitude of low-frequency fluctuations and relative cerebral blood flow in 95 schizophrenia patients and 99 healthy controls. Sex differences in relative cerebral blood flow and amplitude of low-frequency fluctuations were compared in both groups. Diagnostic group differences in relative cerebral blood flow, amplitude of low-frequency fluctuations and relative cerebral blood flow-amplitude of low-frequency fluctuations coupling were compared in male and female subjects, respectively. In both healthy controls and schizophrenia patients, the males had higher relative cerebral blood flow in anterior brain regions and lower relative cerebral blood flow in posterior brain regions than did the females. Compared with multiple regions exhibiting sex differences in relative cerebral blood flow, only the left middle frontal gyrus had a significant sex difference in amplitude of low-frequency fluctuations. In the females, schizophrenia patients exhibited increased relative cerebral blood flow and amplitude of low-frequency fluctuations in the basal ganglia, thalamus and hippocampus and reduced relative cerebral blood flow and amplitude of low-frequency fluctuations in the frontal, parietal and occipital regions compared with those of healthy controls. However, there were fewer brain regions with diagnostic group differences in the males than in the females. Brain regions with diagnostic group differences in relative cerebral blood flow and amplitude of low-frequency fluctuations only partially overlapped. Only the female patients exhibited increased relative cerebral blood flow-amplitude of low-frequency fluctuations couplings compared with those of healthy females. The alterations in the relative cerebral blood flow and amplitude of low-frequency fluctuations in schizophrenia are sex-specific, which should be considered in future neuroimaging studies. The relative cerebral blood flow and amplitude of low-frequency fluctuations have different sensitivity in detecting changes in neuronal activity in schizophrenia and can provide complementary information. © The Royal Australian and New Zealand College of Psychiatrists 2015.

A novel method to measure regional muscle blood flow continuously using NIRS kinetics information

PubMed Central

Nioka, Shoko; Kime, Ryotaro; Sunar, Ulas; Im, Joohee; Izzetoglu, Meltem; Zhang, Jun; Alacam, Burak; Chance, Britton

2006-01-01

Background This article introduces a novel method to continuously monitor regional muscle blood flow by using Near Infrared Spectroscopy (NIRS). We demonstrate the feasibility of the new method in two ways: (1) by applying this new method of determining blood flow to experimental NIRS data during exercise and ischemia; and, (2) by simulating muscle oxygenation and blood flow values using these newly developed equations during recovery from exercise and ischemia. Methods Deoxy (Hb) and oxyhemoglobin (HbO2), located in the blood ofthe skeletal muscle, carry two internal relationships between blood flow and oxygen consumption. One is a mass transfer principle and the other describes a relationship between oxygen consumption and Hb kinetics in a two-compartment model. To monitor blood flow continuously, we transfer these two relationships into two equations and calculate the blood flow with the differential information of HbO2 and Hb. In addition, these equations are used to simulate the relationship between blood flow and reoxygenation kinetics after cuff ischemia and a light exercise. Nine healthy subjects volunteered for the cuff ischemia, light arm exercise and arm exercise with cuff ischemia for the experimental study. Results Analysis of experimental data of both cuff ischemia and light exercise using the new equations show greater blood flow (four to six times more than resting values) during recovery, agreeing with previous findings. Further, the simulation and experimental studies of cuff ischemia and light exercise agree with each other. Conclusion We demonstrate the accuracy of this new method by showing that the blood flow obtained from the method agrees with previous data as well as with simulated data. We conclude that this novel continuous blood flow monitoring method can provide blood flow information non-invasively with NIRS. PMID:16704736

Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis.

PubMed

Mittal, Rahul; Debs, Luca H; Patel, Amit P; Nguyen, Desiree; Patel, Kunal; O'Connor, Gregory; Grati, M'hamed; Mittal, Jeenu; Yan, Denise; Eshraghi, Adrien A; Deo, Sapna K; Daunert, Sylvia; Liu, Xue Zhong

2017-09-01

Neurotransmitters, including catecholamines and serotonin, play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the "fight or flight" response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in GI and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, GI innate immune system, and the microbiome. Furthermore, in pathological states, such as inflammatory bowel disease (IBD) and Parkinson's disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of GI symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal GI physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology. J. Cell. Physiol. 232: 2359-2372, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Useful method to monitor the physiological effects of alcohol ingestion by combination of micro-integrated laser Doppler blood flow meter and arm-raising test.

PubMed

Iwasaki, Wataru; Nogami, Hirofumi; Ito, Hiroki; Gotanda, Takeshi; Peng, Yao; Takeuchi, Satoshi; Furue, Masutaka; Higurashi, Eiji; Sawada, Renshi

2012-10-01

Alcohol has a variety of effects on the human body, affecting both the sympathetic and parasympathetic nervous system. We examined the peripheral blood flow of alcohol drinkers using a micro-integrated laser Doppler blood flow meter (micro-electromechanical system blood flow sensor). An increased heart rate and blood flow was recorded at the earlobe after alcohol ingestion, and we observed strong correlation between blood flow, heart rate, and breath alcohol content in light drinkers; but not heavy drinkers. We also found that the amplitude of pulse waves measured at the fingertip during an arm-raising test significantly decreased on alcohol consumption, regardless of the individual's alcohol tolerance. Our micro-electromechanical system blood flow sensor successfully detected various physiological changes in peripheral blood circulation induced by alcohol consumption.

Modulation of apelin and APJ receptor in normal and preeclampsia-complicated placentas.

PubMed

Cobellis, L; De Falco, M; Mastrogiacomo, A; Giraldi, D; Dattilo, D; Scaffa, C; Colacurci, N; De Luca, A

2007-01-01

Apelin is an endogenous ligand of the human orphan receptor APJ. This peptide is produced through processing from the C-terminal portion in the pre-pro-protein consisting of 77 amino acid residues and exists in multiple molecular forms. Although the main physiological functions of apelin have not yet been clarified, it is known that apelin is involved in the regulation of blood pressure, blood flow and central control of body fluid homeostasis in different organs. Since human placenta is a tissue where vasculogenesis, blood pressure and flow are dramatically important to allow a normal embryonic and fetal growth and development, the aim of the present study was to investigate the immunohistochemical distribution of apelin and APJ in normal placentas throughout pregnancy and in preeclampsia-complicated placentas. Specifically, we observed that in normal placentas the expression levels of apelin decreased from the first to the third trimester of gestation in both cytotrophoblast and syncytiotrophoblast cells and in the stroma of placental villi, in contrast with increased expression levels of APJ in the cytoplasm of cytotrophoblast cells and in the cytoplasm of endothelial cells of normal placenta samples. In contrast, in preeclampsia-complicated pregnancies, we observed a very strong increase of expression levels of both apelin and APJ receptor in all the placental compartments, cytotrophoblast, syncytiotrophoblast and stroma with a particular increase in endothelial cells inside preeclamptic placental villi. Our data seem to indicate an important role of apelin and APJ in the regulation of fetal development through a correct regulation of human placenta formation during pregnancy. Moreover, the strong expression levels of apelin and APJ in preeclamptic placentas, suggest their possible involvement in the onset of this pathology.

European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease-the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow.

PubMed

Meulenbroek, Olga; O'Dwyer, Sarah; de Jong, Daan; van Spijker, Gerrita; Kennelly, Sean; Cregg, Fiona; Olde Rikkert, Marcel; Abdullah, Laila; Wallin, Anders; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Daly, Leslie; Segurado, Ricardo; Borjesson-Hanson, Anne; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Molloy, William; Tsolaki, Magda; Howard, Robert; Adams, Jessica; Gaynor, Siobhan; Lawlor, Brian

2016-07-19

In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers. All participants who fulfil criteria for the main NILVAD study are eligible for participation in the NILVAD substudies. Participation is subject to informed consent and whether the substudy is available at a particular NILVAD study site. Each substudy entails extra measurements during the course of the main NILVAD study. For example, in the blood and genetic biomarkers substudy, extra blood (30 mL) will be collected at week 0, week 13, week 52 and week 78, while in the cerebral blood flow substudy, participants will receive an MRI and transcranial Doppler measurements at week 0, week 26 and week 78. In the CSF substudy, 10 mL CSF is collected at week 0 and week 78. All NILVAD substudies and all subsequent amendments have received ethical approval within each participating country, according to national regulations. Each participant provides written consent to participate. All participants remain anonymised throughout and the results of each substudy will be published in an international peer reviewed journal. EUDRACT 2012-002764-27; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Detection of Site-Specific Blood Flow Variation in Humans during Running by a Wearable Laser Doppler Flowmeter.

PubMed

Iwasaki, Wataru; Nogami, Hirofumi; Takeuchi, Satoshi; Furue, Masutaka; Higurashi, Eiji; Sawada, Renshi

2015-10-05

Wearable wireless physiological sensors are helpful for monitoring and maintaining human health. Blood flow contains abundant physiological information but it is hard to measure blood flow during exercise using conventional blood flowmeters because of their size, weight, and use of optic fibers. To resolve these disadvantages, we previously developed a micro integrated laser Doppler blood flowmeter using microelectromechanical systems technology. This micro blood flowmeter is wearable and capable of stable measurement signals even during movement. Therefore, we attempted to measure skin blood flow at the forehead, fingertip, and earlobe of seven young men while running as a pilot experiment to extend the utility of the micro blood flowmeter. We measured blood flow in each subject at velocities of 6, 8, and 10 km/h. We succeeded in obtaining stable measurements of blood flow, with few motion artifacts, using the micro blood flowmeter, and the pulse wave signal and motion artifacts were clearly separated by conducting frequency analysis. Furthermore, the results showed that the extent of the changes in blood flow depended on the intensity of exercise as well as previous work with an ergometer. Thus, we demonstrated the capability of this wearable blood flow sensor for measurement during exercise.

Visualization and contractile activity of cochlear pericytes in the capillaries of the spiral ligament.

PubMed

Dai, Min; Nuttall, Alfred; Yang, Yue; Shi, Xiaorui

2009-08-01

Pericytes, mural cells located on microvessels, are considered to play an important role in the formation of the vasculature and the regulation of local blood flow in some organs. Little is known about the physiology of cochlear pericytes. In order to investigate the function of cochlear pericytes, we developed a method to visualize cochlear pericytes using diaminofluorescein-2 diacetate (DAF-2DA) and intravital fluorescence microscopy. This method can permit the study of the effect of vasoactive agents on pericytes under the in vivo and normal physiological condition. The specificity of the labeling method was verified by the immunofluorescence labeling of pericyte maker proteins such as desmin, neural proteoglycan (NG2), and thymocyte differentiation antigen 1 (Thy-1). Superfused K(+) and Ca(2+) to the cochlear lateral wall resulted in localized constriction of capillaries at pericyte locations both in vivo and in vitro, while there was no obvious change in cochlear capillary diameters with application of the adrenergic neurotransmitter noradrenaline. The method could be an effective way to visualize cochlear pericytes and microvessels and study lateral wall vascular physiology. Moreover, we demonstrate for the first time that cochlear pericytes have contractility, which may be important for regulation of cochlear blood flow.

Mechanisms for the control of local tissue blood flow during thermal interventions: influence of temperature‐dependent ATP release from human blood and endothelial cells

PubMed Central

Chiesa, Scott T.; Trangmar, Steven J.; Ali, Leena; Lotlikar, Makrand D.; González‐Alonso, José

2017-01-01

New Findings What is the central question of this study? Skin and muscle blood flow increases with heating and decreases with cooling, but the temperature‐sensitive mechanisms underlying these responses are not fully elucidated. What is the main finding and its importance? We found that local tissue hyperaemia was related to elevations in ATP release from erythrocytes. Increasing intravascular ATP augmented skin and tissue perfusion to levels equal or above thermal hyperaemia. ATP release from isolated erythrocytes was altered by heating and cooling. Our findings suggest that erythrocytes are involved in thermal regulation of blood flow via modulation of ATP release. Local tissue perfusion changes with alterations in temperature during heating and cooling, but the thermosensitivity of the vascular ATP signalling mechanisms for control of blood flow during thermal interventions remains unknown. Here, we tested the hypotheses that the release of the vasodilator mediator ATP from human erythrocytes, but not from endothelial cells or other blood constituents, is sensitive to both increases and reductions in temperature and that increasing intravascular ATP availability with ATP infusion would potentiate thermal hyperaemia in limb tissues. We first measured blood temperature, brachial artery blood flow and plasma [ATP] during passive arm heating and cooling in healthy men and found that they increased by 3.0 ± 1.2°C, 105 ± 25 ml min−1 °C−1 and twofold, respectively, (all P < 0.05) with heating, but decreased or remained unchanged with cooling. In additional men, infusion of ATP into the brachial artery increased skin and deep tissue perfusion to levels equal or above thermal hyperaemia. In isolated erythrocyte samples exposed to different temperatures, ATP release increased 1.9‐fold from 33 to 39°C (P < 0.05) and declined by ∼50% at 20°C (P < 0.05), but no changes were observed in cultured human endothelial cells, plasma or serum samples. In conclusion, increases in plasma [ATP] and skin and deep tissue perfusion with limb heating are associated with elevations in ATP release from erythrocytes, but not from endothelial cells or other blood constituents. Erythrocyte ATP release is also sensitive to temperature reductions, suggesting that erythrocytes may function as thermal sensors and ATP signalling generators for control of tissue perfusion during thermal interventions. PMID:27859767

Relationship between preoperative radial artery and postoperative arteriovenous fistula blood flow in hemodialysis patients.

PubMed

Sato, Michiko; Io, Hiroaki; Tanimoto, Mitsuo; Shimizu, Yoshio; Fukui, Mitsumine; Hamada, Chieko; Horikoshi, Satoshi; Tomino, Yasuhiko

2012-01-01

It is recommended that arteriovenous fistula (AVF) blood flow should be more than 425 ml/min before cannulation. However, the relationship between preoperative radial artery flow (RAF) and postoperative AVF blood flow has still not been examined. Sixty-one patients with end-stage kidney disease (ESKD) were examined. They had an AVF prepared at Juntendo University Hospital from July 2006 through August 2007. Preoperative RAF and postoperative AVF blood flows were measured by ultrasonography. AVF blood flow gradually increased after the operation. AVF blood flow was significantly correlated with preoperative RAF. When preoperative RAF exceeded 21.4 ml/min, AVF blood flow rose to more than 425 ml/min. The postoperative AVF blood flow in the group with RAF of more than 20 ml/min was significantly higher than that in those with less than 20 ml/min. Preoperative RAF of less than 20 ml/min had a significantly high risk of primary AVF failure within 8 months compared with that of more than 20 ml/min. It appears that measurement of RAF by ultrasonography is useful for estimating AVF blood flow postoperatively and can predict the risk of complications in ESKD patients.

Functional Divergence of Platelet Protein Kinase C (PKC) Isoforms in Thrombus Formation on Collagen*

PubMed Central

Gilio, Karen; Harper, Matthew T.; Cosemans, Judith M. E. M.; Konopatskaya, Olga; Munnix, Imke C. A.; Prinzen, Lenneke; Leitges, Michael; Liu, Qinghang; Molkentin, Jeffery D.; Heemskerk, Johan W. M.; Poole, Alastair W.

2010-01-01

Arterial thrombosis, a major cause of myocardial infarction and stroke, is initiated by activation of blood platelets by subendothelial collagen. The protein kinase C (PKC) family centrally regulates platelet activation, and it is becoming clear that the individual PKC isoforms play distinct roles, some of which oppose each other. Here, for the first time, we address all four of the major platelet-expressed PKC isoforms, determining their comparative roles in regulating platelet adhesion to collagen and their subsequent activation under physiological flow conditions. Using mouse gene knock-out and pharmacological approaches in human platelets, we show that collagen-dependent α-granule secretion and thrombus formation are mediated by the conventional PKC isoforms, PKCα and PKCβ, whereas the novel isoform, PKCθ, negatively regulates these events. PKCδ also negatively regulates thrombus formation but not α-granule secretion. In addition, we demonstrate for the first time that individual PKC isoforms differentially regulate platelet calcium signaling and exposure of phosphatidylserine under flow. Although platelet deficient in PKCα or PKCβ showed reduced calcium signaling and phosphatidylserine exposure, these responses were enhanced in the absence of PKCθ. In summary therefore, this direct comparison between individual subtypes of PKC, by standardized methodology under flow conditions, reveals that the four major PKCs expressed in platelets play distinct non-redundant roles, where conventional PKCs promote and novel PKCs inhibit thrombus formation on collagen. PMID:20479008

Functional divergence of platelet protein kinase C (PKC) isoforms in thrombus formation on collagen.

PubMed

Gilio, Karen; Harper, Matthew T; Cosemans, Judith M E M; Konopatskaya, Olga; Munnix, Imke C A; Prinzen, Lenneke; Leitges, Michael; Liu, Qinghang; Molkentin, Jeffery D; Heemskerk, Johan W M; Poole, Alastair W

2010-07-23

Arterial thrombosis, a major cause of myocardial infarction and stroke, is initiated by activation of blood platelets by subendothelial collagen. The protein kinase C (PKC) family centrally regulates platelet activation, and it is becoming clear that the individual PKC isoforms play distinct roles, some of which oppose each other. Here, for the first time, we address all four of the major platelet-expressed PKC isoforms, determining their comparative roles in regulating platelet adhesion to collagen and their subsequent activation under physiological flow conditions. Using mouse gene knock-out and pharmacological approaches in human platelets, we show that collagen-dependent alpha-granule secretion and thrombus formation are mediated by the conventional PKC isoforms, PKCalpha and PKCbeta, whereas the novel isoform, PKC, negatively regulates these events. PKCdelta also negatively regulates thrombus formation but not alpha-granule secretion. In addition, we demonstrate for the first time that individual PKC isoforms differentially regulate platelet calcium signaling and exposure of phosphatidylserine under flow. Although platelet deficient in PKCalpha or PKCbeta showed reduced calcium signaling and phosphatidylserine exposure, these responses were enhanced in the absence of PKC. In summary therefore, this direct comparison between individual subtypes of PKC, by standardized methodology under flow conditions, reveals that the four major PKCs expressed in platelets play distinct non-redundant roles, where conventional PKCs promote and novel PKCs inhibit thrombus formation on collagen.

Effects of endothelium-derived nitric oxide on skin and digital blood flow in humans.

PubMed

Coffman, J D

1994-12-01

The effects of NG-monomethyl-L-arginine (L-NMMA) on total finger and forearm, and dorsal finger and forearm skin, blood flows were studied in the basal state and during reflex sympathetic vasoconstriction in normal subjects. Total flows were measured by venous occlusion plethysmography and skin flows by laser-Doppler flowmetry (LDF). L-NMMA in doses of 2, 4, and 8 microM/min given by constant infusion via a brachial artery catheter significantly decreased finger blood flow, forearm blood flow, and vascular conductances. At 8 microM/min, total finger blood flow decreased 38.4% and forearm blood flow decreased 24.8%. Dorsal finger and forearm skin LDF were also significantly decreased (25 and 37% at 8 microM/min). Body cooling significantly decreased finger blood flow (73.6%), vascular conductance, and finger LDF (59.7%). L-NMMA had no effect on total finger blood flow or dorsal finger LDF during body cooling. Nitric oxide or related compounds contribute to the basal dilator tone of the dorsal finger and forearm skin but not during reflex sympathetic vasoconstriction.

Methods of blood flow measurement in the arterial circulatory system.

PubMed

Tabrizchi, R; Pugsley, M K

2000-01-01

The most commonly employed techniques for the in vivo measurement of arterial blood flow to individual organs involve the use of flow probes or sensors. Commercially available systems for the measurement of in vivo blood flow can be divided into two categories: ultrasonic and electromagnetic. Two types of ultrasonic probes are used. The first type of flow probe measures blood flow-mediated Doppler shifts (Doppler flowmetry) in a vessel. The second type of flow probe measures the "transit time" required by an emitted ultrasound wave to traverse the vessel and are transit-time volume flow sensors. Measurement of blood flow in any vessel requires that the flow probe or sensor be highly accurate and exhibit signal linearity over the flow range in the vessel of interest. Moreover, additional desirable features include compact design, size, and weight. An additional important feature for flow probes is that they exhibit good biocompatability; it is imperative for the sensor to behave in an inert manner towards the biological system. A sensitive and reliable method to assess blood flow in individual organs in the body, other than by the use of probes/sensors, is the reference sample method that utilizes hematogeneously delivered microspheres. This method has been utilized to a large extend to assess regional blood flow in the entire body. Obviously, the purpose of measuring blood flow is to determine the amount of blood delivered to a given region per unit time (milliliters per minute) and it is desirable to achieve this goal by noninvasive methodologies. This, however, is not always possible. This review attempts to offer an overview of some of the techniques available for the assessment of regional blood flow in the arterial circulatory system and discusses advantages and disadvantages of these common techniques.

Brain blood flow and blood pressure during hypoxia in the epaulette shark Hemiscyllium ocellatum, a hypoxia-tolerant elasmobranch.

PubMed

Söderström, V; Renshaw, G M; Nilsson, G E

1999-04-01

The key to surviving hypoxia is to protect the brain from energy depletion. The epaulette shark (Hemiscyllium ocellatum) is an elasmobranch able to resist energy depletion and to survive hypoxia. Using epi-illumination microscopy in vivo to observe cerebral blood flow velocity on the brain surface, we show that cerebral blood flow in the epaulette shark is unaffected by 2 h of severe hypoxia (0.35 mg O2 l-1 in the respiratory water, 24 C). Thus, the epaulette shark differs from other hypoxia- and anoxia-tolerant species studied: there is no adenosine-mediated increase in cerebral blood flow such as that occurring in freshwater turtles and cyprinid fish. However, blood pressure showed a 50 % decrease in the epaulette shark during hypoxia, indicating that a compensatory cerebral vasodilatation occurs to maintain cerebral blood flow. We observed an increase in cerebral blood flow velocity when superfusing the normoxic brain with adenosine (making sharks the oldest vertebrate group in which this mechanism has been found). The adenosine-induced increase in cerebral blood flow velocity was reduced by the adenosine receptor antagonist aminophylline. Aminophylline had no effect upon the maintenance of cerebral blood flow during hypoxia, however, indicating that adenosine is not involved in maintaining cerebral blood flow in the epaulette shark during hypoxic hypotension.

Doppler ultrasonography and single-fiber laser Doppler flowmetry for measurement of hind limb blood flow in anesthetized horses.

PubMed

Raisis, A L; Young, L E; Taylor, P M; Walsh, K P; Lekeux, P

2000-03-01

To use Doppler ultrasonography and single-fiber laser Doppler flowmetry (LDF) to evaluate blood flow in the dependent and nondependent hind limbs of anesthetized horses and to evaluate changes in femoral arterial blood flow and microvascular skeletal muscle perfusion in response to administration of phenylephrine hydrochloride or dobutamine hydrochloride. 6 healthy adult horses. Horses were anesthetized and positioned in left lateral recumbency. Doppler ultrasonography was used to measure velocity and volumetric flow in the femoral vessels. Single-fiber LDF was used to measure relative microvascular perfusion at a single site in the semimembranosus muscles. Phenylephrine or dobutamine was then administered to decrease or increase femoral arterial blood flow, and changes in blood flow and microvascular perfusion were recorded. Administration of phenylephrine resulted in significant decreases in femoral arterial and venous blood flows and cardiac output and significant increases in mean aortic blood pressure, systemic vascular resistance, and PCV. Administration of dobutamine resulted in significant increases in femoral arterial blood flow, mean aortic blood pressure, and PCV. Significant changes in microvascular perfusion were not detected. Results suggest that Doppler ultrasonography and single-fiber LDF can be used to study blood flows in the hind limbs of anesthetized horses. However, further studies are required to determine why changes in femoral arterial blood flows were not associated with changes in microvascular perfusion.

MUSCLE METABOLISM WITH BLOOD FLOW RESTRICTION IN CHRONIC FATIGUE SYNDROME

PubMed Central

McCully, Kevin K.; Smith, Sinclair; Rajaei, Sheeva; Leigh, John S.; Natelson, Benjamin H.

2009-01-01

The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced blood flow and muscle oxidative metabolism. Patients with CFS according to CDC criteria (n=19) were compared to normal sedentary subjects (n = 11). Muscle blood flow was measured in the femoral artery with Doppler ultrasound after exercise. Muscle metabolism was measured in the medial gastrocnemius muscle using 31P magnetic resonance spectroscopy (MRS). Muscle oxygen saturation and blood volume were measured using near-infrared spectroscopy. CFS and controls were not different in hyperemic blood flow or phosphocreatine recovery rate. Cuff pressures of 50,60,70,80,and 90 mmHg were used to partially restrict blood flow during recovery. All pressures reduced blood flow and oxidative metabolism, with 90 mmHg reducing blood flow by 46% and oxidative metabolism by 30.7% in CFS patients. Hyperemic blood flow during partial cuff occlusion was significantly reduced in CFS patients (P < 0.01), and recovery of oxygen saturation was slower (P < 0.05). No differences were seen in the amount of reduction in metabolism with partially reduced blood flow. In conclusion, CFS patients showed evidence of reduced hyperemic flow and reduced oxygen delivery, but no evidence that this impaired muscle metabolism. Thus, CFS patients might have altered control of blood flow, but this is unlikely to influence muscle metabolism. Further, abnormalities in muscle metabolism do not appear to be responsible for the CFS symptoms. PMID:14578362

Biofluid mechanics of special organs and the issue of system control. Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28-30, 2008 Pasadena, California.

PubMed

Zamir, Mair; Moore, James E; Fujioka, Hideki; Gaver, Donald P

2010-03-01

In the field of fluid flow within the human body, focus has been placed on the transportation of blood in the systemic circulation since the discovery of that system; but, other fluids and fluid flow phenomena pervade the body. Some of the most fascinating fluid flow phenomena within the human body involve fluids other than blood and a service other than transport--the lymphatic and pulmonary systems are two striking examples. While transport is still involved in both cases, this is not the only service which they provide and blood is not the only fluid involved. In both systems, filtration, extraction, enrichment, and in general some "treatment" of the fluid itself is the primary function. The study of the systemic circulation has also been conventionally limited to treating the system as if it were an open-loop system governed by the laws of fluid mechanics alone, independent of physiological controls and regulations. This implies that system failures can be explained fully in terms of the laws of fluid mechanics, which of course is not the case. In this paper we examine the clinical implications of these issues and of the special biofluid mechanics issues involved in the lymphatic and pulmonary systems.

Structural (CT) and functional imaging (PET/SPECT) for the investigation of dolphin bioacoustics

NASA Astrophysics Data System (ADS)

Houser, Dorian S.; Finneran, James J.; Mattrey, Robert; Hoh, Carl; Ridgway, Sam

2003-10-01

A combination of imaging modalities was used to address physiological and anatomical questions relevant to dolphin bioacoustics. Three dolphins (Tursiops truncatus) were scanned with CT to investigate in vivo dolphin cranial anatomy. One dolphin underwent SPECT and PET scanning to investigate blood flow and metabolic activity of the cranial tissues. Air spaces were mostly contiguous and covered the periotic bone and auditory bulla dorsally and medially. Cranial air was compartmentalized by the nasal plug and constriction of the palatopharyngeus muscle. Blood flow, determined from SPECT imaging of 99Tc-bicisate distribution, was greatest in the brain, melon, and posterior fats of the lower jaw. Metabolic activity of tissues, assessed by monitoring the uptake of 18F-deoxyglucose via PET, indicated that melon and jaw fats were metabolically inert compared to the brain. Nasal cavity and sinus air volume that is reduced during diving may be replenished with lung air via the palatopharyngeus and Eustachian tube. Air covering the bulla may protect the ears from outgoing echolocation pulses and contribute to spectral and time of arrival cues. Blood flow to the melon and lower jaw fats may serve to either regulate the temperature of acoustic lipids or act as a site of counter-current heat exchange.

Age-related Changes in the Hepatic Microcirculation in Mice

PubMed Central

Ito, Yoshiya; Sørensen, Karen K.; Bethea, Nancy W.; Svistounov, Dmitri; McCuskey, Margaret K.; Smedsrød, Bård H.; McCuskey, Robert S.

2007-01-01

Aging of the liver is associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins. Since reduced hepatic blood flow is suspected to contribute this impairment, we examined age-related alterations in hepatic microcirculation.. Livers of C57Bl/6 mice were examined at 0.8 (pre-pubertal), 3 (young adult), 14 (middle-aged) and 27 (senescent) months of age using in vivo and electron microscopic methods. The results demonstrated a 14% reduction in the numbers of perfused sinusoids between 0.8 and 27 month mice associated with 35% reduction in sinusoidal blood flow. This was accompanied by an inflammatory response evidenced by a 5-fold increase in leukocyte adhesion in 27 month mice, up-regulated expression of ICAM-1, and increases in intrahepatic macrophages. Sinusoidal diameter decreased 6-10%. Liver sinusoidal endothelial cell (LSEC) dysfunction was seen as early as 14 months when there was a 3-fold increase in the numbers of swollen LSEC. The endocytotic capacity of LSEC also was found to be reduced in older animals. The sinusoidal endothelium in 27 month old mice exhibited pseudocapillarization. In conclusion, the results suggest that leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarization and dysfunction of LSEC reduce sinusoidal blood flow in aged livers. PMID:17582718

In vivo effects of CB2 receptor-selective cannabinoids on the vasculature of normal and arthritic rat knee joints

PubMed Central

McDougall, J J; Yu, V; Thomson, J

2007-01-01

Background and purpose: Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor-mediated responses was also tested. Experimental approach: Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees. Key results: In normal animals, JWH015 and JWH133 caused a concentration-dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid-1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow. Conclusion and implications: In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated. PMID:17982474

Passive restriction of blood flow and counter-current heat exchange via lingual retia in the tongue of a neonatal gray whale Eschrichtius robustus (Cetacea, Mysticeti).

PubMed

Ekdale, Eric G; Kienle, Sarah S

2015-04-01

Retia mirabilia play broad roles in cetacean physiology, including thermoregulation during feeding and pressure regulations during diving. Vascular bundles of lingual retia are described within the base of the tongue of a neonatal female gray whale (Eschrichtius robustus). Each rete consists of a central artery surrounded by four to six smaller veins. The retia and constituent vessels decrease in diameter as they extend anteriorly within the hyoglossus muscle from a position anterior to the basihyal cartilage toward the apex of the tongue. The position of the retia embedded in the hyoglossus and the anterior constriction of the vessels differs from reports of similar vascular bundles that were previously identified in gray whales. The retia likely serve as a counter-current heat exchange system to control body temperature during feeding. Cold blood flowing toward the body center within the periarterial veins would accept heat from warm blood in the central artery flowing toward the anterior end of the tongue. Although thermoregulatory systems have been identified within the mouths of a few mysticete species, the distribution of such vascular structures likely is more widespread among baleen whales than has previously been described. © 2015 Wiley Periodicals, Inc.

Evaluating anesthetic protocols for functional blood flow imaging in the rat eye

NASA Astrophysics Data System (ADS)

Moult, Eric M.; Choi, WooJhon; Boas, David A.; Baumann, Bernhard; Clermont, Allen C.; Feener, Edward P.; Fujimoto, James G.

2017-01-01

The purpose of this study is to evaluate the suitability of five different anesthetic protocols (isoflurane, isoflurane-xylazine, pentobarbital, ketamine-xylazine, and ketamine-xylazine-vecuronium) for functional blood flow imaging in the rat eye. Total retinal blood flow was measured at a series of time points using an ultrahigh-speed Doppler OCT system. Additionally, each anesthetic protocol was qualitatively evaluated according to the following criteria: (1) time-stability of blood flow, (2) overall rate of blood flow, (3) ocular immobilization, and (4) simplicity. We observed that different anesthetic protocols produced markedly different blood flows. Different anesthetic protocols also varied with respect to the four evaluated criteria. These findings suggest that the choice of anesthetic protocol should be carefully considered when designing and interpreting functional blood flow studies in the rat eye.

Effect of Hindlimb Unweighting on Tissue Blood Flow in the Rat

NASA Technical Reports Server (NTRS)

McDonald, K. S.; Delp, M. D.; Fitts, R. H.

1992-01-01

The purpose of this study was to characterize the distribution of blood flow in the rat during hindlimb unweighting (HU) and post-HU standing and exercise and examine whether the previously reported elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was caused by a reduced hindlimb blood flow. After either 15 days of HU or cage control, blood flow was measured with radioactive microspheres during unweighting, normal standing, and running on a treadmill (15 m/min). In another group of control and experimental animals, blood flow was measured during preexercise (PE) treadmill standing and treadmill running (15 m/min). Soleus muscle blood flow was not different between groups during unweighting, PE standing, and running at 15 m/min. Chronic unweighting resulted in the tendency for greater blood flow to muscles composed of predominantly fast-twitch glycolytic fibers. With exercise, blood flow to visceral organs was reduced compared with PE values in the control rats, whereas flow to visceral organs in 15-day HU animals was unaltered by exercise. These higher flows to the viscera and to muscles composed of predominantly fast-twitch glycolytic fibers suggest an apparent reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. In conclusion, because 15 days of HU did not affect blood flow to the soleus during exercise, the increased dependence of the atrophied soleus on anerobic energy production during contractile activity cannot be explained by a reduced muscle blood flow.

Some potential blood flow experiments for space

NASA Technical Reports Server (NTRS)

Cokelet, G. R.; Meiselman, H. J.; Goldsmith, H. L.

1979-01-01

Blood is a colloidal suspension of cells, predominantly erythrocytes, (red cells) in an aqueous solution called plasma. Because the red cells are more dense than the plasma, and because they tend to aggregate, erythrocyte sedimentation can be significant when the shear stresses in flowing blood are small. This behavior, coupled with equipment restrictions, has prevented certain definitive fluid mechanical studies from being performed with blood in ground-based experiments. Among such experiments, which could be satisfactorily performed in a microgravity environment, are the following: (1) studies of blood flow in small tubes, to obtain pressure-flow rate relationships, to determine if increased red cell aggregation can be an aid to blood circulation, and to determine vessel entrance lengths, and (2) studies of blood flow through vessel junctions (bifurcations), to obtain information on cell distribution in downstream vessels of (arterial) bifurcations, and to test flow models of stratified convergent blood flows downstream from (venous) bifurcations.

A study of the action of amlodipine on adrenergically regulated sodium handling by the kidney in normotensive and hypertensive rats.

PubMed Central

Johns, E. J.

1988-01-01

1. An investigation was undertaken to examine the effect of calcium channel blockade, induced by amlodipine, on the ability of the renal sympathetic nerves to cause an antidiuresis and anti-natriuresis in normotensive Sprague Dawley and spontaneously hypertensive rats anaesthetized with pentobarbitone. 2. Low frequency renal nerve stimulation in normotensive rats, which did not change renal blood flow, caused a 15% reduction in glomerular filtration rate and was associated with falls in urine flow of 37%, absolute sodium excretion of 47%, and fractional sodium excretion of 38%. The magnitude of these renal excretory changes was unaffected by prior administration of amlodipine at either 200 micrograms kg-1 plus 50 micrograms kg-1 h-1 or 400 micrograms kg-1 plus 100 micrograms kg-1 h-1. Amlodipine given in the higher dose, decreased basal levels of blood pressure and increased basal urine flow and sodium excretion. 3. In spontaneously hypertensive rats, renal nerve stimulation minimally affected renal haemodynamics but decreased urine flow, absolute and fractional sodium excretion by 29%, 31% and 24%, respectively. 4. Similar renal nerve stimulation in spontaneously hypertensive rats given amlodipine at 200 micrograms kg-1 plus 50 micrograms kg-1 h-1 or 400 micrograms kg-1 plus 100 micrograms kg-1 h-1 caused minimal changes in renal haemodynamics and in the excretion of water and sodium. The higher dose of drug resulted in decreased blood pressure and increased basal rates of urine flow and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2967097

An investigation into the blood-flow characteristics of telangiectatic skin lesions in systemic sclerosis using dual-wavelength laser Doppler imaging.

PubMed

Murray, A K; Moore, T L; Griffiths, C E M; Herrick, A L

2009-07-01

Superficial telangiectases associated with systemic sclerosis may be more responsive to treatment than those deeper in the dermis. We investigated whether dual-wavelength laser Doppler imaging (LDI) is sufficiently sensitive to ascertain the distribution of blood flow within telangiectases and whether blood flow relates to telangiectatic diameter. The perfusion and diameter of 20 telangiectases were measured in superficial and deeper layers of the skin using dual-wavelength LDI. Of 20 telangiectases, 18 had higher blood flow in the red (representing deeper blood flow), rather than the green (representing superficial blood flow) wavelength images. Clinically apparent diameters correlated with those of the superficial (r = 0.61, P = 0.01), but not with the deeper blood flow images. Hence, the apparent size of telangiectases at the skin surface does not predict blood flow through the microvessel(s) at deeper levels, and thus clinically apparent size is unlikely to predict treatment response. Dual-wavelength LDI may help predict treatment response.

Optic nerve head blood flow response to reduced ocular perfusion pressure by alteration of either the blood pressure or intraocular pressure.

PubMed

Wang, Lin; Cull, Grant A; Fortune, Brad

2015-04-01

To test the hypothesis that blood flow autoregulation in the optic nerve head has less reserve to maintain normal blood flow in the face of blood pressure-induced ocular perfusion pressure decrease than a similar magnitude intraocular pressure-induced ocular perfusion pressure decrease. Twelve normal non-human primates were anesthetized by continuous intravenous infusion of pentobarbital. Optic nerve blood flow was monitored by laser speckle flowgraphy. In the first group of animals (n = 6), the experimental eye intraocular pressure was maintained at 10 mmHg using a saline reservoir connected to the anterior chamber. The blood pressure was gradually reduced by a slow injection of pentobarbital. In the second group (n = 6), the intraocular pressure was slowly increased from 10 mmHg to 50 mmHg by raising the reservoir. In both experimental groups, optic nerve head blood flow was measured continuously. The blood pressure and intraocular pressure were simultaneously recorded in all experiments. The optic nerve head blood flow showed significant difference between the two groups (p = 0.021, repeat measures analysis of variance). It declined significantly more in the blood pressure group compared to the intraocular pressure group when the ocular perfusion pressure was reduced to 35 mmHg (p < 0.045) and below. There was also a significant interaction between blood flow changes and the ocular perfusion pressure treatment (p = 0.004, adjusted Greenhouse & Geisser univariate test), indicating the gradually enlarged blood flow difference between the two groups was due to the ocular perfusion pressure decrease. The results show that optic nerve head blood flow is more susceptible to an ocular perfusion pressure decrease induced by lowering the blood pressure compared with that induced by increasing the intraocular pressure. This blood flow autoregulation capacity vulnerability to low blood pressure may provide experimental evidence related to the hemodynamic pathophysiology in glaucoma.

Endothelial C-Type Natriuretic Peptide Acts on Pericytes to Regulate Microcirculatory Flow and Blood Pressure.

PubMed

Špiranec, Katarina; Chen, Wen; Werner, Franziska; Nikolaev, Viacheslav O; Naruke, Takashi; Koch, Franziska; Werner, Andrea; Eder-Negrin, Petra; Diéguez-Hurtado, Rodrigo; Adams, Ralf H; Baba, Hideo A; Schmidt, Hannes; Schuh, Kai; Skryabin, Boris V; Movahedi, Kiavash; Schweda, Frank; Kuhn, Michaela

2018-04-06

Background -Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular tone but the target cells remain controversial. The cGMP-producing guanylyl cyclase-B (GC-B) receptor for CNP is expressed in vascular smooth muscle cells (VSMC). However, whereas endothelial cell-specific CNP knockout mice are hypertensive, mice with deletion of GC-B in VSMC have unaltered blood pressure. Methods -We analyzed whether the vasodilating response to CNP changes along the vascular tree, i.e. whether the GC-B receptor is expressed in microvascular types of cells. Mice with a floxed GC-B ( Npr2 ) gene were interbred with Tie2-Cre or PDGF-Rβ-Cre ERT2 lines to develop mice lacking GC-B in endothelial cells or in precapillary arteriolar SMC and capillary pericytes. Intravital microscopy, (non)invasive hemodynamics, fluorescence energy transfer studies of pericyte's cAMP levels in situ and renal physiology were combined to dissect whether and how CNP/GC-B/cGMP signaling modulates microcirculatory tone and blood pressure. Results -Intravital microscopy studies revealed that the vasodilatatory effect of CNP increases towards small-diameter arterioles and capillaries. Consistently, CNP did not prevent endothelin-1-induced acute constrictions of proximal arterioles but fully reversed endothelin effects in precapillary arterioles and capillaries. Here, the GC-B receptor is expressed both in endothelial and mural cells, i.e. in pericytes. Notably, the vasodilatatory effects of CNP were preserved in mice with endothelial GC-B deletion but abolished in mice lacking GC-B in microcirculatory SMC and pericytes. CNP, via GC-B/cGMP signaling modulates two signaling cascades in pericytes: it activates cGMP-dependent protein kinase I to phosphorylate downstream targets such as the cytoskeleton-associated vasodilator activated phosphoprotein; and it inhibits phosphodiesterase 3A, thereby enhancing pericyte's cAMP levels. Ultimately these pathways prevent endothelin-induced increases of pericyte calcium levels and pericyte contraction. Mice with deletion of GC-B in microcirculatory SMC and pericytes have elevated peripheral resistance and chronic arterial hypertension without a change in renal function. Conclusions -Our studies indicate that endothelial CNP regulates distal arteriolar and capillary blood flow. CNP-induced GC-B/cGMP signaling in microvascular SMC and pericytes is essential for the maintenance of normal microvascular resistance and blood pressure.

Effect of hindlimb unweighting on tissue blood flow in the rat

NASA Technical Reports Server (NTRS)

Mcdonald, K. S.; Delp, M. D.; Fitts, R. H.

1992-01-01

This study characterized distribution of blood flow in the rat during hindlimb unweighting (HU), and post-HU standing and exercise. The relationship between reduced hindlimb blood flow and the previously observed elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was examined (Witzmann et al., 1992). Blood flow was measured during unweighting, normal standing, and running on a treadmill (15 m/min), after 15 days of HU or cage control. For another group blood flow was measured during preexercise treadmill standing and treadmill running. During unweighting, PE standing, and running no difference in soleus blood flow was observed between groups. Muscles composed mainly of fast twitch glycolytic fibers received greater blood flow during chronic unweighting. With exercise blood flow to visceral organs was reduced in control animals, a similar change was not seen in 15 day HU rats. These changes suggest a reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. A reduction in blood flow to the soleus during exercise was not observed after HU and so does not explain the increased dependence of the atrophied soleus on anerobic energy production during contractile activity.

Modified Beer-Lambert law for blood flow.

PubMed

Baker, Wesley B; Parthasarathy, Ashwin B; Busch, David R; Mesquita, Rickson C; Greenberg, Joel H; Yodh, A G

2014-11-01

We develop and validate a Modified Beer-Lambert law for blood flow based on diffuse correlation spectroscopy (DCS) measurements. The new formulation enables blood flow monitoring from temporal intensity autocorrelation function data taken at single or multiple delay-times. Consequentially, the speed of the optical blood flow measurement can be substantially increased. The scheme facilitates blood flow monitoring of highly scattering tissues in geometries wherein light propagation is diffusive or non-diffusive, and it is particularly well-suited for utilization with pressure measurement paradigms that employ differential flow signals to reduce contributions of superficial tissues.

Pharmacological characteristics of endothelin receptors on sheep rectal blood vessels.

PubMed

Lohsiriwat, Varut; Scholefield, John H; Dashwood, Michael R; Wilson, Vincent G

2011-06-01

Haemorrhoids is associated with high blood flow of the anorectal region. The question of whether pharmacological manipulation of vascular supply can relieve the symptoms of haemorrhoids has been raised. In order to undertake this type of clinical investigation, it is first essential to gain a better understanding of the properties of vascular receptors that may regulate blood flow into anal cushions and haemorrhoids. Due to the limited availability of human anorectal specimens and the good reliability of sheep tissue as an experimental model of human anorectal diseases, we studied the properties of endothelin receptors in sheep rectal artery (SRA) and vein (SRV), the vessels contributing to the blood flow of haemorrhoidal plexus, using isometric tension recordings. We found that endothelin-1 and sarafotoxin 6a were very potent constrictor agents in both SRA and SRV. The selective ET(A) receptor antagonist PD156707 (100 nM) produced a parallel rightward displacement of ET-1-induced contractions in both vessels and abolished sarafotoxin 6a-induced contractions in the SRA. PD156707 (3 μM) practically abolished contractions to ET-1 in the SRA, suggesting that the response is entirely mediated by ET(A) receptors. While, the selective ET(B) receptor antagonist BQ788 (100 nM) caused no significant change in ET-1-induced contractions in both vessels, a minor role for ET(B) receptor subtype to responses to sarafotoxin 6a in the artery was suggested. Copyright © 2011 Elsevier Ltd. All rights reserved.

Endothelium-dependent control of cerebrovascular functions through age: exercise for healthy cerebrovascular aging.

PubMed

Bolduc, Virginie; Thorin-Trescases, Nathalie; Thorin, Eric

2013-09-01

Cognitive performances are tightly associated with the maximal aerobic exercise capacity, both of which decline with age. The benefits on mental health of regular exercise, which slows the age-dependent decline in maximal aerobic exercise capacity, have been established for centuries. In addition, the maintenance of an optimal cerebrovascular endothelial function through regular exercise, part of a healthy lifestyle, emerges as one of the key and primary elements of successful brain aging. Physical exercise requires the activation of specific brain areas that trigger a local increase in cerebral blood flow to match neuronal metabolic needs. In this review, we propose three ways by which exercise could maintain the cerebrovascular endothelial function, a premise to a healthy cerebrovascular function and an optimal regulation of cerebral blood flow. First, exercise increases blood flow locally and increases shear stress temporarily, a known stimulus for endothelial cell maintenance of Akt-dependent expression of endothelial nitric oxide synthase, nitric oxide generation, and the expression of antioxidant defenses. Second, the rise in circulating catecholamines during exercise not only facilitates adequate blood and nutrient delivery by stimulating heart function and mobilizing energy supplies but also enhances endothelial repair mechanisms and angiogenesis. Third, in the long term, regular exercise sustains a low resting heart rate that reduces the mechanical stress imposed to the endothelium of cerebral arteries by the cardiac cycle. Any chronic variation from a healthy environment will perturb metabolism and thus hasten endothelial damage, favoring hypoperfusion and neuronal stress.

Prostaglandins and nonsteroidal anti-inflammatory drugs. Effects on renal hemodynamics.

PubMed

DiBona, G F

1986-01-17

Renal prostaglandins are important modulators of renal hemodynamic function. Their synthesis from arachidonic acid precursor is regulated by neurohumoral vasoactive substances as well as by intrarenal factors. Endogenous renal prostaglandins exert little influence on renal blood flow and glomerular filtration rate in the basal state. In contrast, inhibition of cyclooxygenase-dependent arachidonic acid metabolism with nonsteroidal anti-inflammatory drugs in states of decreased renal perfusion causes marked alterations in these variables. Thus, clinical states characterized by decreased intravascular volume (decreased effective blood volume) with decreased renal perfusion augment the activity of various neurohumoral vasoactive systems and result in an increased dependence of renal hemodynamics on endogenous renal prostaglandin synthesis, which is stimulated, in a compensatory manner, by these same systems. The development of newer drugs that undergo biotransformation in the kidney between active and inactive forms may permit a lesser degree of renal cyclooxygenase inhibition, with the possibility of a reduction in the adverse effects on renal blood flow and glomerular filtration rate. Appropriate clinical use of nonsteroidal anti-inflammatory drugs requires careful consideration of the potential deleterious consequences of prostaglandin synthesis inhibition. Prostaglandins are considered to be autacoids and, as such, they exert their physiologic actions close to or at the site of synthesis. Therefore, production of prostaglandins, thromboxanes, and, possibly, leukotrienes in the renal cortex by the constituent cells of the glomeruli and the arterioles would be anticipated to influence their hemodynamic functions, that is, glomerular filtration rate, renal blood flow, renal vascular resistance, and juxtaglomerular granular cell renin release.

Effect of beta-adrenergic blockade with timolol on myocardial blood flow during exercise after myocardial infarction in the dog.

PubMed

Herzog, C A; Aeppli, D P; Bache, R J

1984-12-01

The effect of beta-adrenergic blockade with timolol (40 micrograms/kg) on myocardial blood flow during rest and graded treadmill exercise was assessed in 12 chronically instrumented dogs 10 to 14 days after myocardial infarction was produced by acute left circumflex coronary artery occlusion. During exercise at comparable external work loads, the heart rate-systolic blood pressure product was significantly decreased after timilol, with concomitant reductions of myocardial blood flow in normal, border and central ischemic areas (p less than 0.001) and increases in subendocardial/subepicardial blood flow ratios (p less than 0.05). In addition to the blunted chronotropic response to exercise, timolol exerted an effect on myocardial blood flow that was not explained by changes in heart rate or blood pressure. At comparable rate-pressure products during exercise, total myocardial blood flow was 24% lower after timolol (p less than 0.02) and flow was redistributed from subepicardium to subendocardium in all myocardial regions. Thus, timolol altered myocardial blood flow during exercise by two separate mechanisms: a negative chronotropic effect, and a significant selective reduction of subepicardial perfusion independent of changes in heart rate or blood pressure with transmural redistribution of flow toward the subendocardium.

Influence of exercise induced hyperlactatemia on retinal blood flow during normo- and hyperglycemia.

PubMed

Garhöfer, Gerhard; Kopf, Andreas; Polska, Elzbieta; Malec, Magdalena; Dorner, Guido T; Wolzt, Michael; Schmetterer, Leopold

2004-05-01

Short term hyperglycemia has previously been shown to induce a blood flow increase in the retina. The mechanism behind this effect is poorly understood. We set out to investigate whether exercise-induced hyperlactatemia may alter the response of retinal blood flow to hyperglycemia. We performed a randomized, controlled two-way cross over study comprising 12 healthy subjects, performed a 6-minutes period of dynamic exercise during an euglcaemic or hyperglycaemic insulin clamp. Retinal blood flow was assessed by combined vessel size measurement with the Zeiss retinal vessel analyzer and measurement of red blood cell velocities using bi-directional laser Doppler velocimetry. Retinal and systemic hemodynamic parameters were measured before, immediately after and 10 and 20 minutes after isometric exercise. On the euglycemic study day retinal blood flow increased after dynamic exercise. The maximum increase in retinal blood flow was observed 10 minutes after the end of exercise when lactate plasma concentration peaked. Hyperglycemia increased retinal blood flow under basal conditions, but had no incremental effect during exercise induced hyperlactatemia. Our results indicate that both lactate and glucose induce an increase in retinal blood flow in healthy humans. This may indicate a common pathway between glucose and lactate induced blood flow changes in the human retina.

Effects of thermal stimulation, applied to the hindpaw via a hot water bath, upon ovarian blood flow in anesthetized nonpregnant rats.

PubMed

Uchida, Sae; Hotta, Harumi; Hanada, Tomoko; Okuno, Yuka; Aikawa, Yoshihiro

2007-08-01

The effects of thermal stimulation, applied to the hindpaw via a hot bath set to either 40 degrees C (non-noxious) or 49 degrees C (noxious), upon ovarian blood flow were examined in nonpregnant anesthetized rats. Ovarian blood flow was measured using a laser Doppler flowmeter. Blood pressure was markedly increased following 49 degrees C stimulation. Ovarian blood flow, however, showed no obvious change during stimulation, although a small increase was observed after stimulation. Ovarian blood flow and blood pressure responses to 49 degrees C stimulation were abolished after hindlimb somatic nerves proximal to the stimuli were cut. Heat stimulation (49 degrees C) resulted in remarkable increases in both ovarian blood flow and blood pressure in rats in which the sympathetic nerves supplying the ovary were cut but the hindlimb somatic nerves remained intact. The efferent activity of the ovarian plexus nerve was increased during stimulation at 49 degrees C. Stimulation at 40 degrees C had no effect upon ovarian blood flow, blood pressure or ovarian plexus nerve activity. Electrical stimulation of the distal part of the severed ovarian plexus nerve resulted in a decrease in both the diameter of ovarian arterioles, observed using a digital video microscope, and ovarian blood flow.The present results demonstrate that noxious heat, but not non-noxious warm, stimulation of the hindpaw skin in anesthetized rats influences ovarian blood flow in a manner that is attributed to reflex responses in ovarian sympathetic nerve activity and blood pressure.

Histaminergic H3-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow.

PubMed

Bertlich, Mattis; Ihler, Friedrich; Freytag, Saskia; Weiss, Bernhard G; Strupp, Michael; Canis, Martin

2015-01-01

Betahistine is a histamine-like drug that is considered beneficial in Ménière's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H1-receptor and as an inverse agonist at the H3-receptor, these receptors as well as the adrenergic α2-receptor were investigated for betahistine effects on cochlear blood flow. A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H1-, H3- or α2-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. Blockage of the H3- or α2-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H3-receptors caused a drop in cochlear blood flow and blood pressure. H1-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. Betahistine most likely affects cochlear blood flow through histaminergic H3-heteroreceptors. © 2015 S. Karger AG, Basel.

Steroid Hormones and Uterine Vascular Adaptation to Pregnancy

PubMed Central

Chang, Katherine; Zhang, Lubo

2008-01-01

Pregnancy is a physiological state that involves a significant decrease in uterine vascular tone and an increase in uterine blood flow, which is mediated in part by steroid hormones, including estrogen, progesterone, and cortisol. Previous studies have demonstrated the involvement of these hormones in the regulation of uterine artery contractility through signaling pathways specific to the endothelium and the vascular smooth muscle. Alterations in endothelial nitric oxide synthase expression and activity, nitric oxide production, and expression of enzymes involved in PGI2 production contribute to the uterine artery endothelium-specific responses. Steroid hormones also have an effect on calcium-activated potassium channel activity, PKC signaling pathway and myogenic tone, and alterations in pharmacomechanical coupling in the uterine artery smooth muscle. This review addresses current understanding of the molecular mechanisms by which steroid hormones including estrogen, progesterone, and cortisol modulate uterine artery contractility to alter uterine blood flow during pregnancy with an emphasis on the pregnant ewe model. PMID:18497342

[Microcirculation in patients with paranoid schizophrenia].

PubMed

Sakharov, A V; Ozornin, A S; Golygina, S E; Vinogradova, A O; Shvets, M S

2018-01-01

To study microcirculation in patients with paranoid schizophrenia by laser Doppler flowmetry. Fifty-three patients at the age from 18 to 38 years with a diagnosis of 'paranoid schizophrenia' (F20.0) were examined in the acute psychotic state and after 3 weeks of therapy. The control group consisted of 20 healthy volunteers. To assess microcirculation, the noninvasive technique of laser Doppler flowmetry using a laser blood flow analyzer was used. Significant changes in the microcirculation persisting even over three weeks of therapy in patients were identified. The total microcirculation index was increased by 1.4 times which indicated the acceleration of blood flow. An increase in the average fluctuations of perfusion by 3.7 times and in the coefficient of variation by 1.9 times, which reflect the excessive strengthening of local mechanisms of regulation of microcirculation, were found. There were an increase in the myogenic tone and neurogenic tone of metarteriole and precapillary sphincters as well as bypass index.

A computer-controlled scintiscanning system and associated computer graphic techniques for study of regional distribution of blood flow.

NASA Technical Reports Server (NTRS)

Coulam, C. M.; Dunnette, W. H.; Wood, E. H.

1970-01-01

Two methods whereby a digital computer may be used to regulate a scintiscanning process are discussed from the viewpoint of computer input-output software. The computer's function, in this case, is to govern the data acquisition and storage, and to display the results to the investigator in a meaningful manner, both during and subsequent to the scanning process. Several methods (such as three-dimensional maps, contour plots, and wall-reflection maps) have been developed by means of which the computer can graphically display the data on-line, for real-time monitoring purposes, during the scanning procedure and subsequently for detailed analysis of the data obtained. A computer-governed method for converting scintiscan data recorded over the dorsal or ventral surfaces of the thorax into fractions of pulmonary blood flow traversing the right and left lungs is presented.

Cerebral vasomotor reactivity in neurodegenerative diseases.

PubMed

Smoliński, Łukasz; Członkowska, Anna

Small-caliber cerebral vessels change their diameters in response to alterations of key metabolite concentrations such as carbon dioxide or oxygen. This phenomenon, termed the cerebral vasomotor reactivity (CVMR), is the basis for blood flow regulation in the brain in accordance with its metabolic status. Typically, CVMR is determined as the amount of change in cerebral blood flow in response to a vasodilating stimulus, which can be measured by various neuroimaging methods or by transcranial Doppler. It has been shown that CVMR is impaired in cerebrovascular diseases, but there is also evidence of a similar dysfunction in neurodegenerative disorders. Here, we review studies that have investigated CVMR in the common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. Moreover, we discuss potential neurodegenerative mechanisms responsible for the impairment of CVMR. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effects of chewing rate and reactive hyperemia on blood flow in denture-supporting mucosa during simulated chewing.

PubMed

Ogino, Takamichi; Ueda, Takayuki; Ogami, Koichiro; Koike, Takashi; Sakurai, Kaoru

2017-01-01

We examined how chewing rate and the extent of reactive hyperemia affect the blood flow in denture-supporting mucosa during chewing. The left palatal mucosa was loaded under conditions of simulated chewing or simulated clenching for 30s, and the blood flow during loading was recorded. We compared the relative blood flow during loading under conditions that recreated different chewing rates by combining duration of chewing cycle (DCC) and occlusal time (OT): fast chewing group, typical chewing group, slow chewing group and clenching group. The relationship between relative blood flow during simulated chewing and the extent of reactive hyperemia was also analyzed. When comparing the different chewing rate, the relative blood flow was highest in fast chewing rate, followed by typical chewing rate and slow chewing rate. Accordingly, we suggest that fast chewing increases the blood flow more than typical chewing or slow chewing. There was a significant correlation between the amount of blood flow during simulated chewing and the extent of reactive hyperemia. Within the limitations of this study, we concluded that slow chewing induced less blood flow than typical or fast chewing in denture-supporting mucosa and that people with less reactive hyperemia had less blood flow in denture-supporting mucosa during chewing. Copyright © 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Abnormal resting state corticolimbic blood flow in depressed unmedicated patients with major depression: a (15)O-H(2)O PET study.

PubMed

Monkul, E Serap; Silva, Leandro A P; Narayana, Shalini; Peluso, Marco A M; Zamarripa, Frank; Nery, Fabiano G; Najt, Pablo; Li, John; Lancaster, Jack L; Fox, Peter T; Lafer, Beny; Soares, Jair C

2012-02-01

We investigated the differences in the resting state corticolimbic blood flow between 20 unmedicated depressed patients and 21 healthy comparisons. Resting state cerebral blood flow (CBF) was measured with H(2)(15)O PET. Anatomical MRI scans were performed on an Elscint 1.9 T Prestige system for PET-MRI coregistration. Significant changes in cerebral blood flow indicating neural activity were detected using an ROI-free image subtraction strategy. In addition, the resting blood flow in patients was correlated with the severity of depression as measured by HAM-D scores. Depressed patients showed decreases in blood flow in right anterior cingulate (Brodmann areas 24 and 32) and increased blood flow in left and right posterior cingulate (Brodmann areas 23, 29, 30), left parahippocampal gyrus (Brodmann area 36), and right caudate compared with healthy volunteers. The severity of depression was inversely correlated with the left middle and inferior frontal gyri (Brodmann areas 9 and 47) and right medial frontal gyrus (Brodmann area 10) and right anterior cingulate (Brodmann areas 24, 32) blood flow, and directly correlated with the right thalamus blood flow. These findings support previous reports of abnormalities in the resting state blood flow in the limbic-frontal structures in depressed patients compared to healthy volunteers. Copyright © 2011 Wiley Periodicals, Inc.

Skeletal muscle contractions uncoupled from gravitational loading directly increase cortical bone blood flow rates in vivo.

PubMed

Caulkins, Carrie; Ebramzadeh, Edward; Winet, Howard

2009-05-01

The direct and indirect effects of muscle contraction on bone microcirculation and fluid flow are neither well documented nor explained. However, skeletal muscle contractions may affect the acquisition and maintenance of bone via stimulation of bone circulatory and interstitial fluid flow parameters. The purposes of this study were to assess the effects of transcutaneous electrical neuromuscular stimulation (TENS)-induced muscle contractions on cortical bone blood flow and bone mineral content, and to demonstrate that alterations in blood flow could occur independently of mechanical loading and systemic circulatory mechanisms. Bone chamber implants were used in a rabbit model to observe real-time blood flow rates and TENS-induced muscle contractions. Video recording of fluorescent microspheres injected into the blood circulation was used to calculate changes in cortical blood flow rates. TENS-induced repetitive muscle contractions uncoupled from mechanical loading instantaneously increased cortical microcirculatory flow, directly increased bone blood flow rates by 130%, and significantly increased bone mineral content over 7 weeks. Heart rates and blood pressure did not significantly increase due to TENS treatment. Our findings suggest that muscle contraction therapies have potential clinical applications for improving blood flow to cortical bone in the appendicular skeleton. Copyright 2008 Orthopaedic Research Society

Quantitative analysis of optical properties of flowing blood using a photon-cell interactive Monte Carlo code: effects of red blood cells' orientation on light scattering.

PubMed

Sakota, Daisuke; Takatani, Setsuo

2012-05-01

Optical properties of flowing blood were analyzed using a photon-cell interactive Monte Carlo (pciMC) model with the physical properties of the flowing red blood cells (RBCs) such as cell size, shape, refractive index, distribution, and orientation as the parameters. The scattering of light by flowing blood at the He-Ne laser wavelength of 632.8 nm was significantly affected by the shear rate. The light was scattered more in the direction of flow as the flow rate increased. Therefore, the light intensity transmitted forward in the direction perpendicular to flow axis decreased. The pciMC model can duplicate the changes in the photon propagation due to moving RBCs with various orientations. The resulting RBC's orientation that best simulated the experimental results was with their long axis perpendicular to the direction of blood flow. Moreover, the scattering probability was dependent on the orientation of the RBCs. Finally, the pciMC code was used to predict the hematocrit of flowing blood with accuracy of approximately 1.0 HCT%. The photon-cell interactive Monte Carlo (pciMC) model can provide optical properties of flowing blood and will facilitate the development of the non-invasive monitoring of blood in extra corporeal circulatory systems.

Effects of hypoxia on cochlear blood flow in mice evaluated using Doppler optical microangiography.

PubMed

Dziennis, Suzan; Reif, Roberto; Zhi, Zhongwei; Nuttall, Alfred L; Wang, Ruikang K

2012-10-01

Reduced cochlear blood flow (CoBF) is a main contributor to hearing loss. Studying CoBF has remained a challenge due to the lack of available tools. Doppler optical microangiography (DOMAG), a method to quantify single-vessel absolute blood flow, and laser Doppler flowmetry (LDF), a method for measuring the relative blood flow within a large volume of tissue, were used for determining the changes in CoBF due to systemic hypoxia in mice. DOMAG determined the change in blood flow in the apical turn (AT) with single-vessel resolution, while LDF averaged the change in the blood flow within a large volume of the cochlea (hemisphere with ∼1 to 1.5 mm radius). Hypoxia was induced by decreasing the concentration of oxygen-inspired gas, so that the oxygen saturation was reduced from >95% to ∼80%. DOMAG determined that during hypoxia the blood flow in two areas of the AT near and far from the helicotrema were increased and decreased, respectively. The LDF detected a decrease in blood flow within a larger volume of the cochlea (several turns averaged together). Therefore, the use of DOMAG as a tool for studying cochlear blood flow due to its ability to determine absolute flow values with single-vessel resolution was proposed.

Effects of hypoxia on cochlear blood flow in mice evaluated using Doppler optical microangiography

NASA Astrophysics Data System (ADS)

Dziennis, Suzan; Reif, Roberto; Zhi, Zhongwei; Nuttall, Alfred L.; Wang, Ruikang K.

2012-10-01

Reduced cochlear blood flow (CoBF) is a main contributor to hearing loss. Studying CoBF has remained a challenge due to the lack of available tools. Doppler optical microangiography (DOMAG), a method to quantify single-vessel absolute blood flow, and laser Doppler flowmetry (LDF), a method for measuring the relative blood flow within a large volume of tissue, were used for determining the changes in CoBF due to systemic hypoxia in mice. DOMAG determined the change in blood flow in the apical turn (AT) with single-vessel resolution, while LDF averaged the change in the blood flow within a large volume of the cochlea (hemisphere with ˜1 to 1.5 mm radius). Hypoxia was induced by decreasing the concentration of oxygen-inspired gas, so that the oxygen saturation was reduced from >95% to ˜80%. DOMAG determined that during hypoxia the blood flow in two areas of the AT near and far from the helicotrema were increased and decreased, respectively. The LDF detected a decrease in blood flow within a larger volume of the cochlea (several turns averaged together). Therefore, the use of DOMAG as a tool for studying cochlear blood flow due to its ability to determine absolute flow values with single-vessel resolution was proposed.

Central command generated prior to arbitrary motor execution induces muscle vasodilatation at the beginning of dynamic exercise.

PubMed

Ishii, Kei; Matsukawa, Kanji; Liang, Nan; Endo, Kana; Idesako, Mitsuhiro; Asahara, Ryota; Kadowaki, Akito; Wakasugi, Rie; Takahashi, Makoto

2016-06-15

The purpose of this study was to examine the role of central command, generated prior to arbitrary motor execution, in cardiovascular and muscle blood flow regulation during exercise. Thirty two subjects performed 30 s of two-legged cycling or 1 min of one-legged cycling (66 ± 4% and 35% of the maximal exercise intensity, respectively), which was started arbitrarily or abruptly by a verbal cue (arbitrary vs. cued start). We measured the cardiovascular variables during both exercises and the relative changes in oxygenated-hemoglobin concentration (Oxy-Hb) of noncontracting vastus lateralis muscles as index of tissue blood flow and femoral blood flow to nonexercising leg during one-legged cycling. Two-legged cycling with arbitrary start caused a decrease in total peripheral resistance (TPR), which was smaller during the exercise with cued start. The greater reduction of TPR with arbitrary start was also recognized at the beginning of one-legged cycling. Oxy-Hb of noncontracting muscle increased by 3.6 ± 1% (P < 0.05) during one-legged cycling with arbitrary start, whereas such increase in Oxy-Hb was absent with cued start. The increases in femoral blood flow and vascular conductance of nonexercising leg were evident (P < 0.05) at 10 s from the onset of one-legged cycling with arbitrary start, whereas those were smaller or absent with cued start. It is likely that when voluntary exercise is started arbitrarily, central command is generated prior to motor execution and then contributes to muscle vasodilatation at the beginning of exercise. Such centrally induced muscle vasodilatation may be weakened and/or masked in the case of exercise with cued start. Copyright © 2016 the American Physiological Society.

Cerebral pressure–flow relationship in lowlanders and natives at high altitude

PubMed Central

Smirl, Jonathan D; Lucas, Samuel J E; Lewis, Nia C S; duManior, Gregory R; Smith, Kurt J; Bakker, Akke; Basnyat, Aperna S; Ainslie, Philip N

2014-01-01

We investigated if dynamic cerebral pressure–flow relationships in lowlanders are altered at high altitude (HA), differ in HA natives and after return to sea level (SL). Lowlanders were tested at SL (n=16), arrival to 5,050 m, after 2-week acclimatization (with and without end-tidal PO2 normalization), and upon SL return. High-altitude natives (n=16) were tested at 5,050 m. Testing sessions involved resting spontaneous and driven (squat–stand maneuvers at very low (VLF, 0.05 Hz) and low (LF, 0.10 Hz) frequencies) measures to maximize blood pressure (BP) variability and improve assessment of the pressure–flow relationship using transfer function analysis (TFA). Blood flow velocity was assessed in the middle (MCAv) and posterior (PCAv) cerebral arteries. Spontaneous VLF and LF phases were reduced and coherence was elevated with acclimatization to HA (P<0.05), indicating impaired pressure–flow coupling. However, when BP was driven, both the frequency- and time-domain metrics were unaltered and comparable with HA natives. Acute mountain sickness was unrelated to TFA metrics. In conclusion, the driven cerebral pressure–flow relationship (in both frequency and time domains) is unaltered at 5,050 m in lowlanders and HA natives. Our findings indicate that spontaneous changes in TFA metrics do not necessarily reflect physiologically important alterations in the capacity of the brain to regulate BP. PMID:24169852

Cerebral pressure-flow relationship in lowlanders and natives at high altitude.

PubMed

Smirl, Jonathan D; Lucas, Samuel J E; Lewis, Nia C S; duManoir, Gregory R; Dumanior, Gregory R; Smith, Kurt J; Bakker, Akke; Basnyat, Aperna S; Ainslie, Philip N

2014-02-01

We investigated if dynamic cerebral pressure-flow relationships in lowlanders are altered at high altitude (HA), differ in HA natives and after return to sea level (SL). Lowlanders were tested at SL (n=16), arrival to 5,050 m, after 2-week acclimatization (with and without end-tidal PO2 normalization), and upon SL return. High-altitude natives (n=16) were tested at 5,050 m. Testing sessions involved resting spontaneous and driven (squat-stand maneuvers at very low (VLF, 0.05 Hz) and low (LF, 0.10 Hz) frequencies) measures to maximize blood pressure (BP) variability and improve assessment of the pressure-flow relationship using transfer function analysis (TFA). Blood flow velocity was assessed in the middle (MCAv) and posterior (PCAv) cerebral arteries. Spontaneous VLF and LF phases were reduced and coherence was elevated with acclimatization to HA (P<0.05), indicating impaired pressure-flow coupling. However, when BP was driven, both the frequency- and time-domain metrics were unaltered and comparable with HA natives. Acute mountain sickness was unrelated to TFA metrics. In conclusion, the driven cerebral pressure-flow relationship (in both frequency and time domains) is unaltered at 5,050 m in lowlanders and HA natives. Our findings indicate that spontaneous changes in TFA metrics do not necessarily reflect physiologically important alterations in the capacity of the brain to regulate BP.

Retinal blood flow in type 1 diabetic patients with no or mild diabetic retinopathy during euglycemic clamp.

PubMed

Pemp, Berthold; Polska, Elzbieta; Garhofer, Gerhard; Bayerle-Eder, Michaela; Kautzky-Willer, Alexandra; Schmetterer, Leopold

2010-09-01

To compare total retinal blood flow in diabetic patients with no or mild nonproliferative diabetic retinopathy and healthy control subjects and to investigate in patients whether there is a difference between retinal blood flow before morning insulin and under normoglycemic conditions using a glucose clamp. Twenty patients with type 1 diabetes with no or mild diabetic retinopathy were included in this open parallel-group study, and 20 healthy age- and sex-matched subjects were included as control subjects. Retinal blood flow was assessed by combining velocity measurements using laser Doppler velocimetry and diameter measurements using a commercially available dynamic vessel analyzer. Measurements were performed before and during a euglycemic clamp. Total retinal blood flow was higher in diabetic patients (53 +/- 16 microl/min) than in healthy subjects (43 +/- 16 microl/min; P = 0.034 between groups). When plasma glucose in diabetic patients was reduced from 9.3 +/- 1.7 to 5.3 +/- 0.5 mmol/l (P < 0.001) retinal blood flow decreased to 49 +/- 15 microl/min (P = 0.0003 vs. baseline). Total retinal blood flow during the glucose clamp was not significantly different from blood flow in normal control subjects (P = 0.161). Type 1 diabetic patients with no or only mild diabetic retinopathy have increased retinal blood flow before their morning insulin dosage. Blood flow is reduced toward normal during euglycemic conditions. Retinal blood flow may fluctuate significantly with fluctuating plasma glucose levels, which may contribute to the microvascular changes seen in diabetic retinopathy.

Relationship among visual field, blood flow, and neural structure measurements in glaucoma.

PubMed

Hwang, John C; Konduru, Ranjith; Zhang, Xinbo; Tan, Ou; Francis, Brian A; Varma, Rohit; Sehi, Mitra; Greenfield, David S; Sadda, Srinivas R; Huang, David

2012-05-17

To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma. Case-control study. Forty-seven eyes of 42 patients with perimetric glaucoma were age-matched with 27 normal eyes of 27 patients. All patients underwent Doppler Fourier-domain optical coherence tomography to measure retinal blood flow and standard glaucoma evaluation with visual field testing and quantitative structural imaging. Linear regression analysis was performed to analyze the relationship among visual field, blood flow, and structure, after all variables were converted to logarithmic decibel scale. Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P < 0.001). Visual field loss was correlated with both reduced retinal blood flow and structural loss of rim area and retinal nerve fiber layer (RNFL). There was no correlation or paradoxical correlation between blood flow and structure. Multivariate regression analysis revealed that reduced blood flow and structural loss are independent predictors of visual field loss. Each dB decrease in blood flow was associated with at least 1.62 dB loss in mean deviation (P ≤ 0.001), whereas each dB decrease in rim area and RNFL was associated with 1.15 dB and 2.56 dB loss in mean deviation, respectively (P ≤ 0.03). There is a close link between reduced retinal blood flow and visual field loss in glaucoma that is largely independent of structural loss. Further studies are needed to elucidate the causes of the vascular dysfunction and potential avenues for therapeutic intervention. Blood flow measurement may be useful as an independent assessment of glaucoma severity.

Hypoxemia, oxygen content, and the regulation of cerebral blood flow

PubMed Central

Bain, Anthony R.; Rieger, Mathew G.; Bailey, Damian M; Ainslie, Philip N.

2015-01-01

This review highlights the influence of oxygen (O2) availability on cerebral blood flow (CBF). Evidence for reductions in O2 content (CaO2) rather than arterial O2 tension (PaO2) as the chief regulator of cerebral vasodilation, with deoxyhemoglobin as the primary O2 sensor and upstream response effector, is discussed. We review in vitro and in vivo data to summarize the molecular mechanisms underpinning CBF responses during changes in CaO2. We surmise that 1) during hypoxemic hypoxia in healthy humans (e.g., conditions of acute and chronic exposure to normobaric and hypobaric hypoxia), elevations in CBF compensate for reductions in CaO2 and thus maintain cerebral O2 delivery; 2) evidence from studies implementing iso- and hypervolumic hemodilution, anemia, and polycythemia indicate that CaO2 has an independent influence on CBF; however, the increase in CBF does not fully compensate for the lower CaO2 during hemodilution, and delivery is reduced; and 3) the mechanisms underpinning CBF regulation during changes in O2 content are multifactorial, involving deoxyhemoglobin-mediated release of nitric oxide metabolites and ATP, deoxyhemoglobin nitrite reductase activity, and the downstream interplay of several vasoactive factors including adenosine and epoxyeicosatrienoic acids. The emerging picture supports the role of deoxyhemoglobin (associated with changes in CaO2) as the primary biological regulator of CBF. The mechanisms for vasodilation therefore appear more robust during hypoxemic hypoxia than during changes in CaO2 via hemodilution. Clinical implications (e.g., disorders associated with anemia and polycythemia) and future study directions are considered. PMID:26676248

Analysis of blood flow in the long posterior ciliary artery of the cat.

PubMed

Koss, M C

1999-03-01

Experiments were undertaken to use a new technique for direct on-line measurement of blood flow in the long posterior ciliary artery (LPCA) in cats and to evaluate possible physiological mechanisms controlling blood flow in the vascular beds perfused by this artery. Blood flow in the temporal LPCA was measured on a continuous basis using ultrasonic flowmetry in anesthetized cats. Effects of acute sectioning of the sympathetic nerve and changes in LPCA and cerebral blood flows in response to altered levels of inspired CO2 and O2 were tested in some animals. In others, the presence of vascular autoregulatory mechanisms in response to stepwise elevations of intraocular pressure was studied. Blood flow in the temporal LPCA averaged 0.58+/-0.03 ml/min in 45 cats anesthetized with pentobarbital. Basal LPCA blood flow was not altered by acute sectioning of the sympathetic nerve or by changes in low levels of inspired CO2 and O2, although 10% CO2 caused a modest increase. Stepwise elevations of intraocular pressure resulted in comparable stepwise decreases of LPCA blood flow, with perfusion pressure declining in a linear manner throughout the perfusion-pressure range. Ultrasonic flowmetry seems to be a useful tool for continuous on-line measurement of LPCA blood flow in the cat eye. Blood flow to vascular beds perfused by this artery does not seem to be under sympathetic neural control and is refractory to modest alterations of blood gas levels of CO2 and O2. Blood vessels perfused by the LPCA show no clear autoregulatory mechanisms.

Hydrostatic pressure and shear stress affect endothelin-1 and nitric oxide release by endothelial cells in bioreactors.

PubMed

Vozzi, Federico; Bianchi, Francesca; Ahluwalia, Arti; Domenici, Claudio

2014-01-01

Abundant experimental evidence demonstrates that endothelial cells are sensitive to flow; however, the effect of fluid pressure or pressure gradients that are used to drive viscous flow is not well understood. There are two principal physical forces exerted on the blood vessel wall by the passage of intra-luminal blood: pressure and shear. To analyze the effects of pressure and shear independently, these two stresses were applied to cultured cells in two different types of bioreactors: a pressure-controlled bioreactor and a laminar flow bioreactor, in which controlled levels of pressure or shear stress, respectively, can be generated. Using these bioreactor systems, endothelin-1 (ET-1) and nitric oxide (NO) release from human umbilical vein endothelial cells were measured under various shear stress and pressure conditions. Compared to the controls, a decrease of ET-1 production by the cells cultured in both bioreactors was observed, whereas NO synthesis was up-regulated in cells under shear stress, but was not modulated by hydrostatic pressure. These results show that the two hemodynamic forces acting on blood vessels affect endothelial cell function in different ways, and that both should be considered when planning in vitro experiments in the presence of flow. Understanding the individual and synergic effects of the two forces could provide important insights into physiological and pathological processes involved in vascular remodeling and adaptation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of Adaptive Starling-Like Controller to Total Artificial Heart Using Dual Rotary Blood Pumps.

PubMed

Ng, Boon C; Smith, Peter A; Nestler, Frank; Timms, Daniel; Cohn, William E; Lim, Einly

2017-03-01

The successful clinical applicability of rotary left ventricular assist devices (LVADs) has led to research interest in devising a total artificial heart (TAH) using two rotary blood pumps (RBPs). The major challenge when using two separately controlled LVADs for TAH support is the difficulty in maintaining the balance between pulmonary and systemic blood flows. In this study, a starling-like controller (SLC) hybridized with an adaptive mechanism was developed for a dual rotary LVAD TAH. The incorporation of the adaptive mechanism was intended not only to minimize the risk of pulmonary congestion and atrial suction but also to match cardiac demand. A comparative assessment was performed between the proposed adaptive starling-like controller (A-SLC) and a conventional SLC as well as a constant speed controller. The performance of all controllers was evaluated by subjecting them to three simulated scenarios [rest, exercise, head up tilt (HUT)] using a mock circulation loop. The overall results showed that A-SLC was superior in matching pump flow to cardiac demand without causing hemodynamic instabilities. In contrast, improper flow regulation by the SLC resulted in pulmonary congestion during exercise. From resting supine to HUT, overpumping of the RBPs at fixed speed (FS) caused atrial suction, whereas implementation of SLC resulted in insufficient flow. The comparative study signified the potential of the proposed A-SLC for future TAH implementation particularly among outpatients, who are susceptible to variety of clinical scenarios.

The effects of recirculation flows on mass transfer from the arterial wall to flowing blood.

PubMed

Zhang, Zhiguo; Deng, Xiaoyan; Fan, Yubo; Guidoin, Robert

2008-01-01

Using a sudden tubular expansion as a model of an arterial stenosis, the effect of disturbed flow on mass transfer from the arterial wall to flowing blood was studied theoretically and tested experimentally by measuring the dissolution rate of benzoic acid disks forming the outer tube of a sudden tubular expansion. The study revealed that mass transfer from vessel wall to flowing fluid in regions of disturbed flow is independent of wall shear rates. The rate of mass transfer is significantly higher in regions of disturbed flow with a local maximum around the reattachment point where the wall shear rate is zero. The experimental study also revealed that the rate of mass transfer from the vessel wall to a flowing fluid is much higher in the presence of microspheres (as models of blood cells) in the flowing fluid and under the condition of pulsatile flow than in steady flow. These results imply that flow disturbance may enhance the transport of biochemicals and macromolecules, such as plasma proteins and lipoproteins synthesized within the blood vessel wall, from the blood vessel wall to flowing blood.

The effect of partial portal decompression on portal blood flow and effective hepatic blood flow in man: a prospective study.

PubMed

Rosemurgy, A S; McAllister, E W; Godellas, C V; Goode, S E; Albrink, M H; Fabri, P J

1995-12-01

With the advent of transjugular intrahepatic porta-systemic stent shunt and the wider application of the surgically placed small diameter prosthetic H-graft portacaval shunt (HGPCS), partial portal decompression in the treatment of portal hypertension has received increased attention. The clinical results supporting the use of partial portal decompression are its low incidence of variceal rehemorrhage due to decreased portal pressures and its low rate of hepatic failure, possibly due to maintenance of blood flow to the liver. Surprisingly, nothing is known about changes in portal hemodynamics and effective hepatic blood flow following partial portal decompression. To prospectively evaluate changes in portal hemodynamics and effective hepatic blood flow brought about by partial portal decompression, the following were determined in seven patients undergoing HGPCS: intraoperative pre- and postshunt portal vein pressures and portal vein-inferior vena cava pressure gradients, intraoperative pre- and postshunt portal vein flow, and pre- and postoperative effective hepatic blood flow. With HGPCS, portal vein pressures and portal vein-inferior vena cava pressure gradients decreased significantly, although portal pressures remained above normal. In contrast to the significant decreases in portal pressures, portal vein blood flow and effective hepatic blood flow do not decrease significantly. Changes in portal vein pressures and portal vein-inferior vena cava pressure gradients are great when compared to changes in portal vein flow and effective hepatic blood flow. Reduction of portal hypertension with concomitant maintenance of hepatic blood flow may explain why hepatic dysfunction is avoided following partial portal decompression.

Effect of age on cerebral blood flow during hypothermic cardiopulmonary bypass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brusino, F.G.; Reves, J.G.; Smith, L.R.

1989-04-01

Cerebral blood flow was measured in 20 patients by xenon 133 clearance methodology during nonpulsatile hypothermic cardiopulmonary bypass to determine the effect of age on regional cerebral blood flow during these conditions. Measurements of cerebral blood flow at varying perfusion pressures were made in patients arbitrarily divided into two age groups at nearly identical nasopharyngeal temperature, hematocrit value, and carbon dioxide tension and with equal cardiopulmonary bypass flows of 1.6 L/min/m2. The range of mean arterial pressure was 30 to 110 mm Hg for group I (less than or equal to 50 years of age) and 20 to 90 mmmore » Hg for group II (greater than or equal to 65 years of age). There was no significant difference (p = 0.32) between the mean arterial pressure in group I (54 +/- 28 mm Hg) and that in group II (43 +/- 21 mm Hg). The range of cerebral blood flow was 14.8 to 29.2 ml/100 gm/min for group I and 13.8 to 37.5 ml/100 gm/min for group II. There was no significant difference (p = 0.37) between the mean cerebral blood flow in group I (21.5 +/- 4.6 ml/100 gm/min) and group II (24.3 +/- 8.1 ml/100 gm/min). There was a poor correlation between mean arterial pressure and cerebral blood flow in both groups: group I, r = 0.16 (p = 0.67); group II, r = 0.5 (p = 0.12). In 12 patients, a second cerebral blood flow measurements was taken to determine the effect of mean arterial pressure on cerebral blood flow in the individual patient. Changes in mean arterial pressure did not correlate with changes in cerebral blood flow (p less than 0.90). We conclude that age does not alter cerebral blood flow and that cerebral blood flow autoregulation is preserved in elderly patients during nonpulsatile hypothermic cardiopulmonary bypass.« less

Relationship between regional myocardial blood flow and thallium-201 distribution in the presence of coronary artery stenosis and dipyridamole-induced vasodilation.

PubMed Central

Mays, A E; Cobb, F R

1984-01-01

This study assesses the relationship between the distribution of thallium-201 and myocardial blood flow during coronary vasodilation induced by intravenous dipyridamole in canine models of partial and complete coronary artery stenosis. 10 dogs were chronically instrumented with catheters in the left atrium and aorta and with a balloon occluder and electromagnetic flow probe on the proximal left circumflex coronary artery. Regional myocardial blood flow was measured during control conditions with radioisotope-labeled microspheres, and the phasic reactive hyperemic response to a 20-s transient occlusion was then recorded. Dipyridamole was then infused intravenously until phasic coronary blood flow increased to match peak hyperemic values. The left circumflex coronary artery was either partially occluded to reduce phasic blood flow to control values (group 1) or it was completely occluded (group 2), and thallium-201 and a second microsphere label were injected. 5 min later, the animals were sacrificed, the left ventricle was sectioned into 1-2-g samples, and thallium-201 activity and regional myocardial blood flow were measured. Curvilinear regression analyses between thallium-201 localization and myocardial blood flow during dipyridamole infusion demonstrated a slightly better fit to a second- as compared with a first-order model, indicating a slight roll-off of thallium activity as myocardial blood flow increases. During the dipyridamole infusion, the increases in phasic blood flow, the distributions of regional myocardial blood flow, and the relationships between thallium-201 localization and regional blood flow were comparable to values previously observed in exercising dogs with similar occlusions. These data provide basic validation that supports the use of intravenous dipyridamole and thallium-201 as an alternative to exercise stress and thallium-201 for evaluating the effects of coronary occlusive lesions on the distribution of regional myocardial blood flow. PMID:6715540

Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis.

PubMed

Zhang, Zenan; Zheng, Wenjiao; Xie, Hua; Chai, Ruonan; Wang, Junling; Zhang, Huiyun; He, Shaoheng

2017-05-01

Large numbers of CD8 + T cells were observed in atopic dermatitis (AD) skin, and monocytes from AD patients showed increased prostaglandin E2 production. However, little is known about the expression of substance P (SP) and its receptor NK1R in blood leukocytes of patients with AD. To explore the expression of SP and NK1R in leukocytes of AD and the influence of allergens on SP and NK1R expression. The expression levels of SP and NK1R in patients with AD were examined by flow cytometry, ELISA and a mouse AD model. The plasma SP level was 4.9-fold higher in patients with AD than in HC subjects. Both the percentage of SP expression in the population and mean fluorescence intensity (MFI) of SP expression were elevated in CD8 + T cells in the blood of AD patients. However, both the CD14 + NK1R + population and MFI of NK1R expression on CD14 + cells were enhanced in the blood of AD patients. Allergens ASWE, HDME and PPE failed to up-regulate SP expression in CD8 + T cells. However, allergens ASWE and HDME both enhanced NK1R expression on CD14 + blood leukocytes regardless of AD or HC subjects. OVA-sensitized AD mice showed an elevated proportion and MFI of SP-expressing CD8 + T cells in the blood, which agrees with the SP expression situation in human AD blood. Injection of SP into mouse skin did not up-regulate NK1R expression on monocytes. An elevated plasma SP level, up-regulated expression of SP and NK1R indicate that the SP/NK1R complex is important in the development of AD. Therefore, SP and NK1R antagonist or blocker agents may help to treat patients with AD. Trial registration Registration number: ChiCTR-BOC-16010279; Registration date: Dec., 28, 2016; retrospectively registered.

A close look at brain dynamics: cells and vessels seen by in vivo two-photon microscopy.

PubMed

Fumagalli, Stefano; Ortolano, Fabrizio; De Simoni, Maria-Grazia

2014-10-01

The cerebral vasculature has a unique role in providing a constant supply of oxygen and nutrients to ensure normal brain functions. Blood vessels that feed the brain are far from being simply channels for passive transportation of fluids. They form complex structures made up of different cell types. These structures regulate blood supply, local concentrations of O2 and CO2, transport of small molecules, trafficking of plasma cells and fine cerebral functions in normal and diseased brains. Until few years ago, analysis of these functions has been typically based on post mortem techniques, whose interpretation is limited by the need for tissue processing at specific times. For a reliable and effective picture of the dynamic processes in the central nervous system, real-time information in vivo is required. There are now few in vivo systems, among which two-photon microscopy (2-PM) is a truly innovative tool for studying the brain. 2-PM has been used to dissect specific aspects of vascular and immune cell dynamics in the context of neurological diseases, providing exciting results that could not have been obtained with conventional methods. This review summarizes the latest findings on vascular and immune system action in the brain, with particular focus on the dynamic responses after ischemic brain injury. 2-PM has helped define the hierarchical architecture of the brain vasculature, the dynamic interaction between the vasculature and immune cells recruited to lesion sites, the effects of blood flow on neuronal and microglial activity and the ability of cells of the neurovascular unit to regulate blood flow. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impaired cerebral microcirculation induced by ammonium chloride in rats is due to cortical adenosine release.

PubMed

Bjerring, Peter Nissen; Bjerrum, Esben Jannik; Larsen, Fin Stolze

2018-06-01

Liver failure results in hyperammonaemia, impaired regulation of cerebral microcirculation, encephalopathy, and death. However, the key mediator that alters cerebral microcirculation remains unidentified. In this study we show that topically applied ammonium significantly increases periarteriolar adenosine tone on the brain surface of healthy rats and is associated with a disturbed microcirculation. Cranial windows were prepared in anaesthetized Wistar rats. The flow velocities were measured by speckle contrast imaging and compared before and after 30 min of exposure to 10 mM ammonium chloride applied on the brain surface. These flow velocities were compared with those for control groups exposed to artificial cerebrospinal fluid or ammonium plus an adenosine receptor antagonist. A flow preservation curve was obtained by analysis of flow responses to a haemorrhagic hypotensive challenge and during stepwise exsanguination. The periarteriolar adenosine concentration was measured with enzymatic biosensors inserted in the cortex. After ammonium exposure the arteriolar flow velocity increased by a median (interquartile range) of 21.7% (23.4%) vs. 7.2% (10.2%) in controls (n = 10 and n = 6, respectively, p <0.05), and the arteriolar surface area increased. There was a profound rise in the periarteriolar adenosine concentration. During the hypotensive challenge the flow decreased by 27.8% (14.9%) vs. 9.2% (14.9%) in controls (p <0.05). The lower limit of flow preservation remained unaffected, 27.7 (3.9) mmHg vs. 27.6 (6.4) mmHg, whereas the autoregulatory index increased, 0.29 (0.33) flow units per millimetre of mercury vs. 0.03 (0.21) flow units per millimetre of mercury (p <0.05). When ammonium exposure was combined with topical application of an adenosine receptor antagonist, the autoregulatory index was normalized. Vasodilation of the cerebral microcirculation during exposure to ammonium chloride is associated with an increase in the adenosine tone. Application of a specific adenosine receptor antagonist restores the regulation of the microcirculation. This indicates that adenosine could be a key mediator of the brain dysfunction seen during hyperammonaemia and is a potential therapeutic target. In patients with liver failure, disturbances in brain function are caused in part by ammonium toxicity. In our project we studied how ammonia, through adenosine release, affects the blood flow in the brain of rats. In our experimental model we demonstrated that the detrimental effect of ammonia on blood flow regulation was counteracted by blocking the adenosine receptors in the brain. With this observation we identified a novel potential treatment target. If we can confirm our findings in a future clinical study, this might help patients with liver failure and the severe condition called hepatic encephalopathy. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Self-separation of blood plasma from whole blood during the capillary flow in microchannel

NASA Astrophysics Data System (ADS)

Nunna, Bharath Babu; Zhuang, Shiqiang; Lee, Eon Soo

2017-11-01

Self-separation of blood plasma from whole blood in microchannels is of great importance due to the enormous range of applications in healthcare and diagnostics. Blood is a multiphase complex fluid, composed of cells suspended in blood plasma. RBCs are the suspended particles whose shape changes during the flow of blood. The primary constituents of blood are erythrocytes or red blood cells (RBCs), leukocytes or white blood cells (WBCs), thrombocytes or platelets and blood plasma. The existence of RBCs in blood makes the blood a non-Newtonian fluid. The current study of separation of blood plasma from whole blood during self-driven flows in a single microchannel without bifurcation, by enhancing the capillary effects. The change in the capillary effect results in a change in contact angle which directly influences the capillary flow. The flow velocity directly influences the net force acting on the RBCs and influence the separation process. The experiments are performed on the PDMS microchannels with different contact angles by altering the surface characteristics using plasma treatment. The change in the separation length is studied during the capillary flow of blood in microchannel. Bharath Babu Nunna is a researcher in mechanical engineering and implementing the novel and innovative technologies in the biomedical devices to enhance the sensitivity of the disease diagnosis.

Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

NASA Technical Reports Server (NTRS)

Meehan, R. T.

1986-01-01

Understanding the role of circulating peptide hormones in the pathogenesis of space-flight induced disorders would be greatly facilitated by a method which monitors chronic levels of hormones and their effects upon in vivo cell physiology. Single and simultaneous multiparameter flow cytometry analysis was employed to identify subpopulations of mononuclear cells bearing receptors for ACTH, Endorphin, and Somatomedin-C using monoclonal antibodies and monospecific antisera with indirect immunofluorescence. Blood samples were obtained from normal donors and subjects participating in decompression chamber studies (acute stress), medical student academic examination (chronic stress), and a drug study (Dexamethasone). Preliminary results indicate most ACTH and Endorphin receptor positive cells are monocytes and B-cells, exhibit little diurnal variation but the relative percentages of receptor positive cells are influenced by exposure to various stressors and ACTH inhibition. This study demonstrates the capability of flow cytometry analysis to study cell surface hormone receptor regulation which should allow insight into neuroendocrine modulation of the immune and other cellular systems during exposure to stress or microgravity.

Effects of dorzolamide on choroidal blood flow, ciliary blood flow, and aqueous production in rabbits.

PubMed

Reitsamer, Herbert A; Bogner, Barbara; Tockner, Birgit; Kiel, Jeffrey W

2009-05-01

To determine the effects of topical dorzolamide (a carbonic anhydrase inhibitor) on choroidal and ciliary blood flow and the relationship between ciliary blood flow and aqueous flow. The experiments were performed in four groups of pentobarbital-anesthetized rabbits treated with topical dorzolamide (2%, 50 microL). In all groups, intraocular pressure (IOP) and mean arterial pressure (MAP) at the eye level were measured continuously by direct cannulation. In group 1, aqueous flow was measured by fluorophotometry before and after dorzolamide treatment. In group 2, aqueous flow was measured after dorzolamide at normal MAP and while MAP was held constant at 80, 55, or 40 mm Hg with occluders on the aorta and vena cava. In group 3, the same MAP levels were used, and ciliary blood flow was measured transsclerally by laser Doppler flowmetry (LDF). In group 4, choroidal blood flow was measured by LDF with the probe tip positioned in the vitreous over the posterior pole during ramp increases and decreases in MAP before and after dorzolamide. Dorzolamide lowered IOP by 19% (P < 0.01) and aqueous flow by 17% (P < 0.01), and increased ciliary blood flow by 18% (P < 0.01), which was associated with a significant reduction in ciliary vasculature resistance (-7%, P < 0.01). Dorzolamide shifted the relationship between ciliary blood flow and aqueous flow downward relative to the previously determined control relationship in the rabbit. Dorzolamide did not alter choroidal blood flow, choroidal vascular resistance, or the choroidal pressure flow relationship. Acute topical dorzolamide is a ciliary vasodilator and has a direct inhibitory effect on aqueous production, but it does not have a detectable effect on choroidal hemodynamics at the posterior pole in the rabbit.

Cerebral blood flow in humans following resuscitation from cardiac arrest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohan, S.L.; Mun, S.K.; Petite, J.

1989-06-01

Cerebral blood flow was measured by xenon-133 washout in 13 patients 6-46 hours after being resuscitated from cardiac arrest. Patients regaining consciousness had relatively normal cerebral blood flow before regaining consciousness, but all patients who died without regaining consciousness had increased cerebral blood flow that appeared within 24 hours after resuscitation (except in one patient in whom the first measurement was delayed until 28 hours after resuscitation, by which time cerebral blood flow was increased). The cause of the delayed-onset increase in cerebral blood flow is not known, but the increase may have adverse effects on brain function and maymore » indicate the onset of irreversible brain damage.« less

Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy

PubMed Central

Ramirez, Gabriel; Proctor, Ashley R.; Jung, Ki Won; Wu, Tong Tong; Han, Songfeng; Adams, Russell R.; Ren, Jingxuan; Byun, Daniel K.; Madden, Kelley S.; Brown, Edward B.; Foster, Thomas H.; Farzam, Parisa; Durduran, Turgut; Choe, Regine

2016-01-01

The non-invasive, in vivo measurement of microvascular blood flow has the potential to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clinically relevant doses were investigated. Treatments with cyclophosphamide increased blood flow as early as 3 days after administration, whereas paclitaxel induced a transient blood flow decrease at 1 day after administration. Early blood flow changes correlated strongly with the treatment outcome and distinguished treated from untreated mice individually for effective treatments. PMID:27699124

Effect of pyrrolidone-pyroglutamic acid composition on blood flow in rat middle cerebral artery.

PubMed

Semkina, G A; Matsievskii, D D; Mirzoyan, N R

2006-01-01

We compared the effects of a pyrrolidone-pyroglutamic acid composition and nimodipine on blood circulation in the middle cerebral artery in rats. The composition produced a strong effect on blood supply to the brain, stimulated blood flow in the middle cerebral artery (by 60 +/- 9%) and decreased blood pressure (by 25.0 +/- 2.7%). The cerebrovascular effects of this composition differed from those of nimodipine. Nimodipine not only increased middle cerebral artery blood flow, but also decreased cerebral blood flow in the early period after treatment.

Modified Beer-Lambert law for blood flow

PubMed Central

Baker, Wesley B.; Parthasarathy, Ashwin B.; Busch, David R.; Mesquita, Rickson C.; Greenberg, Joel H.; Yodh, A. G.

2014-01-01

We develop and validate a Modified Beer-Lambert law for blood flow based on diffuse correlation spectroscopy (DCS) measurements. The new formulation enables blood flow monitoring from temporal intensity autocorrelation function data taken at single or multiple delay-times. Consequentially, the speed of the optical blood flow measurement can be substantially increased. The scheme facilitates blood flow monitoring of highly scattering tissues in geometries wherein light propagation is diffusive or non-diffusive, and it is particularly well-suited for utilization with pressure measurement paradigms that employ differential flow signals to reduce contributions of superficial tissues. PMID:25426330

Redistribution of blood within the body is important for thermoregulation in an ectothermic vertebrate (Crocodylus porosus).

PubMed

Seebacher, Frank; Franklin, Craig E

2007-11-01

Changes in blood flow are a principal mechanism of thermoregulation in vertebrates. Changes in heart rate will alter blood flow, although multiple demands for limited cardiac output may compromise effective thermoregulation. We tested the hypothesis that regional differences in blood flow during heating and cooling can occur independently from changes in heart rate. We measured heart rate and blood pressure concurrently with blood flow in the crocodile, Crocodylus porosus. We measured changes in blood flow by laser Doppler flowmetry, and by injecting coloured microspheres. All measurements were made under different heat loads, with and without blocking cholinergic and beta-adrenergic receptors (autonomic blockade). Heart rates were significantly faster during heating than cooling in the control animals, but not when autonomic receptors were blocked. There were no significant differences in blood flow distribution between the control and autonomic blockade treatments. In both treatments, blood flow was directed to the dorsal skin and muscle and away from the tail and duodenum during heating. When the heat source was switched off, there was a redistribution of blood from the dorsal surface to the duodenum. Blood flow to the leg skin and muscle, and to the liver did not change significantly with thermal state. Blood pressure was significantly higher during the autonomic blockade than during the control. Thermal time constants of heating and cooling were unaffected by the blockade of autonomic receptors. We concluded that animals partially compensated for a lack of differential heart rates during heating and cooling by redistributing blood within the body, and by increasing blood pressure to increase flow. Hence, measures of heart rate alone are insufficient to assess physiological thermoregulation in reptiles.

Evaluation of (/sup 18/F)-4-fluoroantipyrine as a new blood flow tracer for multiradionuclide autoradiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sako, K.; Diksic, M.; Kato, A.

This article reports the evaluation of (/sup 18/F)-4-fluoroantipyrine (FAP) as a quantitative blood flow tracer by comparing blood flow measured with (/sup 18/F)FAP to that determined simultaneously with (/sup 14/C)-4-iodoantipyrine (IAP), a standard blood flow tracer, by means of double-tracer autoradiography. The single-pass extraction value (m), which indicates diffusibility of a tracer, was determined according to the procedure described by Crone. The diffusibility of FAP was essentially the same as that of IAP. The brain-blood partition coefficient for FAP was found to be similar to that for IAP, 0.89 +/- 0.01. Values of local cerebral blood flow obtained with FAPmore » agree with those determined with IAP. From these results, we concluded that FAP is indeed as good a blood flow tracer as IAP. Since /sup 18/F is a positron-emitting radionuclide, it might be a useful tracer for blood flow measurement by positron emission tomography.« less

Effect of sumatriptan on cerebral blood flow in the baboon model.

PubMed

Oliver, D W; Dormehl, I C; Hugo, N

1994-08-01

Changes in cerebral blood flow are implicated to be important in the pathophysiology of migraine. Furthermore, serotonin (5-HT) is known to be the most important substance in the etiology of migraine. Sumatriptan (CAS 103628-46-2), a 5-HTID receptor agonist was recently introduced in the treatment of migraine. In the present study a baboon model was used to investigate the changes in cerebral blood flow due to anaesthesia and pharmacological interventions using 99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) and single photon emission computed tomography (SPECT). The effect of sumatriptan on cerebral blood flow was investigated after 10 min and again after 23 min, with the animal under anaesthesia, i.e. induction with ketamine and maintenance on thiopental. Sumatriptan did not alter the cerebral blood flow during the 10 min procedure. However, sumatriptan reversed the increased cerebral blood flow due to the prolonged anaesthesia (23 min), lowering the cerebral blood flow by more than 20%. No significant changes in the biochemical parameters (blood pressure, heart rate, pO2 and pCO2) were observed. These results also suggest that sumatriptan reverses the increased cerebral blood flow most likely via 5-HTID receptor stimulation.

Influence of Dai-kenchu-to (DKT) on human portal blood flow.

PubMed

Ogasawara, Takashi; Morine, Yuji; Ikemoto, Tetsuya; Imura, Satoru; Fujii, Masahiko; Soejima, Yuji; Shimada, Mitsuo

2008-01-01

Dai-kenchu-to (DKT) is known as an herbal medicine used for postoperative ileus. However, no report exists about the effect of DKT on portal blood flow. The aim of this study is to clarify the influence of DKT on portal blood flow. To healthy volunteers (Healthy; n = 6), cirrhotic patients (Cirrhosis; n = 7) and liver-transplant patients (LTx; n = 3), DKT (2.5g) with 100mL of warm water was orally administrated in the DKT group, and only warm water was administrated in the control group. The portal blood flow rate (M-VEL: cm/sec.) and portal blood flow (Flow volume: mL/min.) was measured each time after administration using an ultrasonic Doppler method. Furthermore, the arterial blood pressure and heart rate was measured at the same time points. In the DKT group, a significant increase of M-VEL (120%) and flow volume (150%) 30 minutes after administration was observed in both Healthy and Cirrhosis in comparison with the control group. In LTx, there was also a significant increase of flow volume (128%) 30 minutes after administration. However, there was no change in average blood pressure and heart rate in all groups. DKT increases portal blood flow in early phase after oral administration without any significant changes in the blood pressure and heart rate.

Measurement of bronchial blood flow in the sheep by video dilution technique.

PubMed Central

Link, D P; Parsons, G H; Lantz, B M; Gunther, R A; Green, J F; Cross, C E

1985-01-01

Bronchial blood flow was determined in five adult anaesthetised sheep by the video dilution technique. This is a new fluoroscopic technique for measuring blood flow that requires only arterial catheterisation. Catheters were placed into the broncho-oesophageal artery and ascending aorta from the femoral arteries for contrast injections and subsequent videotape recording. The technique yields bronchial blood flow as a percentage of cardiac output. The average bronchial artery blood flow was 0.6% (SD 0.20%) of cardiac output. In one sheep histamine (90 micrograms) injected directly into the bronchial artery increased bronchial blood flow by a factor of 6 and histamine (90 micrograms) plus methacholine (4.5 micrograms) augmented flow by a factor of 7.5 while leaving cardiac output unchanged. This study confirms the high degree of reactivity of the bronchial circulation and demonstrates the feasibility of using the video dilution technique to investigate the determinants of total bronchial artery blood flow in a stable animal model avoiding thoracotomy. Images PMID:3883564

Relation of retinal blood flow and retinal oxygen extraction during stimulation with diffuse luminance flicker

PubMed Central

Palkovits, Stefan; Lasta, Michael; Told, Reinhard; Schmidl, Doreen; Werkmeister, René; Cherecheanu, Alina Popa; Garhöfer, Gerhard; Schmetterer, Leopold

2015-01-01

Cerebral and retinal blood flow are dependent on local neuronal activity. Several studies quantified the increase in cerebral blood flow and oxygen consumption during activity. In the present study we investigated the relation between changes in retinal blood flow and oxygen extraction during stimulation with diffuse luminance flicker and the influence of breathing gas mixtures with different fractions of O2 (FiO2; 100% 15% and 12%). Twenty-four healthy subjects were included. Retinal blood flow was studied by combining measurement of vessel diameters using the Dynamic Vessel Analyser with measurements of blood velocity using laser Doppler velocimetry. Oxygen saturation was measured using spectroscopic reflectometry and oxygen extraction was calculated. Flicker stimulation increased retinal blood flow (57.7 ± 17.8%) and oxygen extraction (34.6 ± 24.1%; p < 0.001 each). During 100% oxygen breathing the response of retinal blood flow and oxygen extraction was increased (p < 0.01 each). By contrast, breathing gas mixtures with 12% and 15% FiO2 did not alter flicker–induced retinal haemodynamic changes. The present study indicates that at a comparable increase in blood flow the increase in oxygen extraction in the retina is larger than in the brain. During systemic hyperoxia the blood flow and oxygen extraction responses to neural stimulation are augmented. The underlying mechanism is unknown. PMID:26672758

The feasibility of measuring renal blood flow using transesophageal echocardiography in patients undergoing cardiac surgery.

PubMed

Yang, Ping-Liang; Wong, David T; Dai, Shuang-Bo; Song, Hai-Bo; Ye, Ling; Liu, Jin; Liu, Bin

2009-05-01

There is no reliable method to monitor renal blood flow intraoperatively. In this study, we evaluated the feasibility and reproducibility of left renal blood flow measurements using transesophageal echocardiography during cardiac surgery. In this prospective noninterventional study, left renal blood flow was measured with transesophageal echocardiography during three time points (pre-, intra-, and postcardiopulmonary bypass) in 60 patients undergoing cardiac surgery. Sonograms from 6 subjects were interpreted by 2 blinded independent assessors at the time of acquisition and 6 mo later. Interobserver and intraobserver reproducibility were quantified by calculating variability and intraclass correlation coefficients. Patients with Doppler angles of >30 degrees (20 of 60 subjects) were eliminated from renal blood flow measurements. Left renal blood flow was successfully measured and analyzed in 36 of 60 (60%) subjects. Both interobserver and intraobserver variability were <10%. Interobserver and intraobserver reproducibility in left renal blood flow measurements were good to excellent (intraclass correlation coefficients 0.604-0.999). Left renal arterial luminal diameter for the pre, intra, and postcardiopulmonary bypass phases, ranged from 3.8 to 4.1 mm, renal arterial velocity from 25 to 35 cm/s, and left renal blood flow from 192 to 299 mL/min. In patients undergoing cardiac surgery, it was feasible in 60% of the subjects to measure left renal blood flow using intraoperative transesophageal echocardiography. The interobserver and intraobserver reproducibility of renal blood flow measurements was good to excellent.

Cerebral blood flow response to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kern, F.H.; Ungerleider, R.M.; Quill, T.J.

1991-04-01

We examined the relationship of changes in partial pressure of carbon dioxide on cerebral blood flow responsiveness in 20 pediatric patients undergoing hypothermic cardiopulmonary bypass. Cerebral blood flow was measured during steady-state hypothermic cardiopulmonary bypass with the use of xenon 133 clearance methodology at two different arterial carbon dioxide tensions. During these measurements there was no significant change in mean arterial pressure, nasopharyngeal temperature, pump flow rate, or hematocrit value. Cerebral blood flow was found to be significantly greater at higher arterial carbon dioxide tensions (p less than 0.01), so that for every millimeter of mercury rise in arterial carbonmore » dioxide tension there was a 1.2 ml.100 gm-1.min-1 increase in cerebral blood flow. Two factors, deep hypothermia (18 degrees to 22 degrees C) and reduced age (less than 1 year), diminished the effect carbon dioxide had on cerebral blood flow responsiveness but did not eliminate it. We conclude that cerebral blood flow remains responsive to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in infants and children; that is, increasing arterial carbon dioxide tension will independently increase cerebral blood flow.« less

Parameterizing the Morse Potential for Coarse-Grained Modeling of Blood Plasma

PubMed Central

Zhang, Na; Zhang, Peng; Kang, Wei; Bluestein, Danny; Deng, Yuefan

2014-01-01

Multiscale simulations of fluids such as blood represent a major computational challenge of coupling the disparate spatiotemporal scales between molecular and macroscopic transport phenomena characterizing such complex fluids. In this paper, a coarse-grained (CG) particle model is developed for simulating blood flow by modifying the Morse potential, traditionally used in Molecular Dynamics for modeling vibrating structures. The modified Morse potential is parameterized with effective mass scales for reproducing blood viscous flow properties, including density, pressure, viscosity, compressibility and characteristic flow dynamics of human blood plasma fluid. The parameterization follows a standard inverse-problem approach in which the optimal micro parameters are systematically searched, by gradually decoupling loosely correlated parameter spaces, to match the macro physical quantities of viscous blood flow. The predictions of this particle based multiscale model compare favorably to classic viscous flow solutions such as Counter-Poiseuille and Couette flows. It demonstrates that such coarse grained particle model can be applied to replicate the dynamics of viscous blood flow, with the advantage of bridging the gap between macroscopic flow scales and the cellular scales characterizing blood flow that continuum based models fail to handle adequately. PMID:24910470

Distribution of intrarenal blood flow consequent to left atrial balloon inflation.

PubMed

Passmore, J C; Stremel, R W; Hock, C E; Allen, R L; Bradford, W B

1985-01-01

The effects of inflation of a balloon within, and consequent distension of, the left atrium (LABI, left atrial balloon inflation) on total renal blood flow (RBF) and intrarenal blood flow distribution were measured and compared to values obtained from another group of dogs that were hemorrhaged (HEM) to the same level of hypotension as that produced by LABI, a mean systemic arterial pressure of 88 mm Hg. Kidney wt/kg, RBF/kg body wt, and urine flow were markedly reduced during the hemorrhage period in the HEM group when compared to values obtained during the experimental period for the LABI group. Data from the freeze-dissection (133Xe) analysis revealed that the percentage distribution of blood flow as renal outer cortical (OC) blood flow was less (26%) in the HEM group than in the LABI group (50%), this latter value being very similar to that of control dogs that experienced no hypotension (49%). LABI better maintains OC blood flow and urine flow when compared to HEM at the same systemic blood pressure, suggesting a role for cardiopulmonary receptors in reflex sympathetic control of renal blood flow distribution during hypotension.

Blood cell interactions and segregation in flow.

PubMed

Munn, Lance L; Dupin, Michael M

2008-04-01

For more than a century, pioneering researchers have been using novel experimental and computational approaches to probe the mysteries of blood flow. Thanks to their efforts, we know that blood cells generally prefer to migrate to the axis of flow, that red and white cells segregate in flow, and that cell deformability and their tendency to reversibly aggregate contribute to the non-Newtonian nature of this unique fluid. All of these properties have beneficial physiological consequences, allowing blood to perform a variety of critical functions. Our current understanding of these unusual flow properties of blood have been made possible by the ingenuity and diligence of a number of researchers, including Harry Goldsmith, who developed novel technologies to visualize and quantify the flow of blood at the level of individual cells. Here we summarize efforts in our lab to continue this tradition and to further our understanding of how blood cells interact with each other and with the blood vessel wall.

Hemodilution increases cerebral blood flow in acute ischemic stroke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vorstrup, S.; Andersen, A.; Juhler, M.

1989-07-01

We measured cerebral blood flow in 10 consecutive, but selected, patients with acute ischemic stroke (less than 48 hours after onset) before and after hemodilution. Cerebral blood flow was measured by xenon-133 inhalation and emission tomography, and only patients with focal hypoperfusion in clinically relevant areas were included. Hemodilution was done according to the hematocrit level: for a hematocrit greater than or equal to 42%, 500 ml whole blood was drawn and replaced by the same volume of dextran 40; for a hematocrit between 37% and 42%, only 250 ml whole blood was drawn and replaced by 500 cc ofmore » dextran 40. Mean hematocrit was reduced by 16%, from 46 +/- 5% (SD) to 39 +/- 5% (SD) (p less than 0.001). Cerebral blood flow increased in both hemispheres by an average of 20.9% (p less than 0.001). Regional cerebral blood flow increased in the ischemic areas in all cases, on an average of 21.4 +/- 12.0% (SD) (p less than 0.001). In three patients, a significant redistribution of flow in favor of the hypoperfused areas was observed, and in six patients, the fractional cerebral blood flow increase in the hypoperfused areas was of the same magnitude as in the remainder of the brain. In the last patient, cerebral blood flow increased relatively less in the ischemic areas. Our findings show that cerebral blood flow increases in the ischemic areas after hemodilution therapy in stroke patients. The marked regional cerebral blood flow increase seen in some patients could imply an improved oxygen delivery to the ischemic tissue.« less

Non-invasive pulmonary blood flow analysis and blood pressure mapping derived from 4D flow MRI

NASA Astrophysics Data System (ADS)

Delles, Michael; Rengier, Fabian; Azad, Yoo-Jin; Bodenstedt, Sebastian; von Tengg-Kobligk, Hendrik; Ley, Sebastian; Unterhinninghofen, Roland; Kauczor, Hans-Ulrich; Dillmann, Rüdiger

2015-03-01

In diagnostics and therapy control of cardiovascular diseases, detailed knowledge about the patient-specific behavior of blood flow and pressure can be essential. The only method capable of measuring complete time-resolved three-dimensional vector fields of the blood flow velocities is velocity-encoded magnetic resonance imaging (MRI), often denoted as 4D flow MRI. Furthermore, relative pressure maps can be computed from this data source, as presented by different groups in recent years. Hence, analysis of blood flow and pressure using 4D flow MRI can be a valuable technique in management of cardiovascular diseases. In order to perform these tasks, all necessary steps in the corresponding process chain can be carried out in our in-house developed software framework MEDIFRAME. In this article, we apply MEDIFRAME for a study of hemodynamics in the pulmonary arteries of five healthy volunteers. The study included measuring vector fields of blood flow velocities by phase-contrast MRI and subsequently computing relative blood pressure maps. We visualized blood flow by streamline depictions and computed characteristic values for the left and the right pulmonary artery (LPA and RPA). In all volunteers, we observed a lower amount of blood flow in the LPA compared to the RPA. Furthermore, we visualized blood pressure maps using volume rendering and generated graphs of pressure differences between the LPA, the RPA and the main pulmonary artery. In most volunteers, blood pressure was increased near to the bifurcation and in the proximal LPA, leading to higher average pressure values in the LPA compared to the RPA.

Retinal Blood Flow in Type 1 Diabetic Patients With No or Mild Diabetic Retinopathy During Euglycemic Clamp

PubMed Central

Pemp, Berthold; Polska, Elżbieta; Garhofer, Gerhard; Bayerle-Eder, Michaela; Kautzky-Willer, Alexandra; Schmetterer, Leopold

2010-01-01

OBJECTIVE To compare total retinal blood flow in diabetic patients with no or mild nonproliferative diabetic retinopathy and healthy control subjects and to investigate in patients whether there is a difference between retinal blood flow before morning insulin and under normoglycemic conditions using a glucose clamp. RESEARCH DESIGN AND METHODS Twenty patients with type 1 diabetes with no or mild diabetic retinopathy were included in this open parallel-group study, and 20 healthy age- and sex-matched subjects were included as control subjects. Retinal blood flow was assessed by combining velocity measurements using laser Doppler velocimetry and diameter measurements using a commercially available dynamic vessel analyzer. Measurements were performed before and during a euglycemic clamp. RESULTS Total retinal blood flow was higher in diabetic patients (53 ± 16 μl/min) than in healthy subjects (43 ± 16 μl/min; P = 0.034 between groups). When plasma glucose in diabetic patients was reduced from 9.3 ± 1.7 to 5.3 ± 0.5 mmol/l (P < 0.001) retinal blood flow decreased to 49 ± 15 μl/min (P = 0.0003 vs. baseline). Total retinal blood flow during the glucose clamp was not significantly different from blood flow in normal control subjects (P = 0.161). CONCLUSIONS Type 1 diabetic patients with no or only mild diabetic retinopathy have increased retinal blood flow before their morning insulin dosage. Blood flow is reduced toward normal during euglycemic conditions. Retinal blood flow may fluctuate significantly with fluctuating plasma glucose levels, which may contribute to the microvascular changes seen in diabetic retinopathy. PMID:20585003

Blood in the gastric lumen increases splanchnic blood flow and portal pressure in portal-hypertensive rats.

PubMed

Chen, L; Groszmann, R J

1996-10-01

In portal-hypertensive humans, portal blood flow and pressure increase after a meal. These hemodynamic changes may increase variceal rupture risk. The aim of this study was to determine whether blood in the stomach lumen increases splanchnic flow and portal pressure (PP) in portal-hypertensive rats. superior mesenteric artery flow and PP were measured in conscious, unrestrained, fasted partial portal vein-ligated rats with chronically implanted Doppler flow probes or portal vein catheters before and after gavage with heparinized, warmed blood from donor rats, air, standard meal, or empty tube. Percentage of changes in flow and pressure from baseline were significantly greater after gavage with blood (an increase of 22.6% +/- 3.5% and an increase of 16.4% +/- 3.1%, respectively) than empty tube (an increase of 3.4% +/- 0.6% and a decrease of 5.4% +/- 3.5%, respectively) (P < 0.005). Percentage of changes in flow and pressure were slightly but insignificantly greater after gavage with air vs. empty tube (P < 0.005). In portal-hypertensive rats, blood in the stomach lumen significantly increases splanchnic blood flow and PP. Splanchnic hyperemia from absorption of blood's calories probably contributes to these hemodynamic changes. In patients with variceal hemorrhage, blood in the stomach may increase the risk of persistent variceal bleeding or rebleeding.

Multimodal Pressure Flow Analysis: Application of Hilbert Huang Transform in Cerebral Blood Flow Regulation

PubMed Central

Lo, Men-Tzung; Hu, Kun; Liu, Yanhui; Peng, C.-K.; Novak, Vera

2008-01-01

Quantification of nonlinear interactions between two nonstationary signals presents a computational challenge in different research fields, especially for assessments of physiological systems. Traditional approaches that are based on theories of stationary signals cannot resolve nonstationarity-related issues and, thus, cannot reliably assess nonlinear interactions in physiological systems. In this review we discuss a new technique “Multi-Modal Pressure Flow method (MMPF)” that utilizes Hilbert-Huang transformation to quantify dynamic cerebral autoregulation (CA) by studying interaction between nonstationary cerebral blood flow velocity (BFV) and blood pressure (BP). CA is an important mechanism responsible for controlling cerebral blood flow in responses to fluctuations in systemic BP within a few heart-beats. The influence of CA is traditionally assessed from the relationship between the well-pronounced systemic BP and BFV oscillations induced by clinical tests. Reliable noninvasive assessment of dynamic CA, however, remains a challenge in clinical and diagnostic medicine. In this brief review we: 1) present an overview of transfer function analysis (TFA) that is traditionally used to quantify CA; 2) describe the a MMPF method and its modifications; 3) introduce a newly developed automatic algorithm and engineering aspects of the improved MMPF method; and 4) review clinical applications of MMPF and its sensitivity for detection of CA abnormalities in clinical studies. The MMPF analysis decomposes complex nonstationary BP and BFV signals into multiple empirical modes adaptively so that the fluctuations caused by a specific physiologic process can be represented in a corresponding empirical mode. Using this technique, we recently showed that dynamic CA can be characterized by specific phase delays between the decomposed BP and BFV oscillations, and that the phase shifts are significantly reduced in hypertensive, diabetics and stroke subjects with impaired CA. In addition, the new technique enables reliable assessment of CA using both data collected during clinical test and spontaneous BP/BFV fluctuations during baseline resting conditions. PMID:18725996

Sodium nitroprusside increases human skeletal muscle blood flow, but does not change flow distribution or glucose uptake.

PubMed

Pitkanen, O P; Laine, H; Kemppainen, J; Eronen, E; Alanen, A; Raitakari, M; Kirvela, O; Ruotsalainen, U; Knuuti, J; Koivisto, V A; Nuutila, P

1999-12-15

1. The role of blood flow as a determinant of skeletal muscle glucose uptake is at present controversial and results of previous studies are confounded by possible direct effects of vasoactive agents on glucose uptake. Since increase in muscle blood flow can be due to increased flow velocity or recruitment of new capillaries, or both, it would be ideal to determine whether the vasoactive agent affects flow distribution or only increases the mean flow. 2. In the present study blood flow, flow distribution and glucose uptake were measured simultaneously in both legs of 10 healthy men (aged 29 +/- 1 years, body mass index 24 +/- 1 kg m-2) using positron emission tomography (PET) combined with [15O]H2O and [18F]fluoro-2-deoxy-D-glucose (FDG). The role of blood flow in muscle glucose uptake was studied by increasing blood flow in one leg with sodium nitroprusside (SNP) and measuring glucose uptake simultaneously in both legs during euglycaemic hyperinsulinaemia (insulin infusion 6 pmol kg-1 min-1). 3. SNP infusion increased skeletal muscle blood flow by 86 % (P < 0.01), but skeletal muscle flow distribution and insulin-stimulated glucose uptake (61.4 +/- 7. 5 vs. 67.0 +/- 7.5 micromol kg-1 min-1, control vs. SNP infused leg, not significant), as well as flow distribution between different tissues of the femoral region, remained unchanged. The effect of SNP infusion on blood flow and distribution were unchanged during infusion of physiological levels of insulin (duration, 150 min). 4. Despite a significant increase in mean blood flow induced by an intra-arterial infusion of SNP, glucose uptake and flow distribution remained unchanged in resting muscles of healthy subjects. These findings suggest that SNP, an endothelium-independent vasodilator, increases non-nutritive, but not nutritive flow or capillary recruitment.

Blood flow patterns during incremental and steady-state aerobic exercise.

PubMed

Coovert, Daniel; Evans, LeVisa D; Jarrett, Steven; Lima, Carla; Lima, Natalia; Gurovich, Alvaro N

2017-05-30

Endothelial shear stress (ESS) is a physiological stimulus for vascular homeostasis, highly dependent on blood flow patterns. Exercise-induced ESS might be beneficial on vascular health. However, it is unclear what type of ESS aerobic exercise (AX) produces. The aims of this study are to characterize exercise-induced blood flow patterns during incremental and steady-state AX. We expect blood flow pattern during exercise will be intensity-dependent and bidirectional. Six college-aged students (2 males and 4 females) were recruited to perform 2 exercise tests on cycleergometer. First, an 8-12-min incremental test (Test 1) where oxygen uptake (VO2), heart rate (HR), blood pressure (BP), and blood lactate (La) were measured at rest and after each 2-min step. Then, at least 48-hr. after the first test, a 3-step steady state exercise test (Test 2) was performed measuring VO2, HR, BP, and La. The three steps were performed at the following exercise intensities according to La: 0-2 mmol/L, 2-4 mmol/L, and 4-6 mmol/L. During both tests, blood flow patterns were determined by high-definition ultrasound and Doppler on the brachial artery. These measurements allowed to determine blood flow velocities and directions during exercise. On Test 1 VO2, HR, BP, La, and antegrade blood flow velocity significantly increased in an intensity-dependent manner (repeated measures ANOVA, p<0.05). Retrograde blood flow velocity did not significantly change during Test 1. On Test 2 all the previous variables significantly increased in an intensity-dependent manner (repeated measures ANOVA, p<0.05). These results support the hypothesis that exercise induced ESS might be increased in an intensity-dependent way and blood flow patterns during incremental and steady-state exercises include both antegrade and retrograde blood flows.

Mechanical performance comparison between RotaFlow and CentriMag centrifugal blood pumps in an adult ECLS model.

PubMed

Yulong Guan; Xiaowei Su; McCoach, Robert; Kunselman, Allen; El-Banayosy, Aly; Undar, Akif

2010-03-01

Centrifugal blood pumps have been widely adopted in conventional adult cardiopulmonary bypass and circulatory assist procedures. Different brands of centrifugal blood pumps incorporate distinct designs which affect pump performance. In this adult extracorporeal life support (ECLS) model, the performances of two brands of centrifugal blood pump (RotaFlow blood pump and CentriMag blood pump) were compared. The simulated adult ECLS circuit used in this study included a centrifugal blood pump, Quadrox D membrane oxygenator and Sorin adult ECLS tubing package. A Sorin Cardiovascular(R) VVR(R) 4000i venous reservoir (Sorin S.p.A., Milan, Italy) with a Hoffman clamp served as a pseudo-patient. The circuit was primed with 900ml heparinized human packed red blood cells and 300ml lactated Ringer's solution (total volume 1200 ml, corrected hematocrit 40%). Trials were conducted at normothermia (36 degrees C). Performance, including circuit pressure and flow rate, was measured for every setting analyzed. The shut-off pressure of the RotaFlow was higher than the CentriMag at all measurement points given the same rotation speed (p < 0.0001). The shut-off pressure differential between the two centrifugal blood pumps was significant and increased given higher rotation speeds (p < 0.0001). The RotaFlow blood pump has higher maximal flow rate (9.08 +/- 0.01L/min) compared with the CentriMag blood pump (8.37 +/- 0.02L/min) (p < 0.0001). The blood flow rate differential between the two pumps when measured at the same revolutions per minute (RPM) ranged from 1.64L/min to 1.73L/min. The results obtained in this experiment demonstrate that the RotaFlow has a higher shut-off pressure (less retrograde flow) and maximal blood flow rate than the CentriMag blood pump. Findings support the conclusion that the RotaFlow disposable pump head has a better mechanical performance than the CentriMag. In addition, the RotaFlow disposable pump is 20-30 times less expensive than the CentriMag.

Reduced expression of mitochondrial electron transport chain proteins from hibernating hearts relative to ischemic preconditioned hearts in the second window of protection.

PubMed

Cabrera, Jesús A; Butterick, Tammy A; Long, Eric K; Ziemba, Elizabeth A; Anderson, Lorraine B; Duffy, Cayla M; Sluiter, Willem; Duncker, Dirk J; Zhang, Jianyi; Chen, Yingjie; Ward, Herbert B; Kelly, Rosemary F; McFalls, Edward O

2013-07-01

Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12 weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2 min, each separated by 2 min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (P<0.05). Despite reduced regional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport. Published by Elsevier Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Na; Zhang, Peng; Kang, Wei

Multiscale simulations of fluids such as blood represent a major computational challenge of coupling the disparate spatiotemporal scales between molecular and macroscopic transport phenomena characterizing such complex fluids. In this paper, a coarse-grained (CG) particle model is developed for simulating blood flow by modifying the Morse potential, traditionally used in Molecular Dynamics for modeling vibrating structures. The modified Morse potential is parameterized with effective mass scales for reproducing blood viscous flow properties, including density, pressure, viscosity, compressibility and characteristic flow dynamics of human blood plasma fluid. The parameterization follows a standard inverse-problem approach in which the optimal micro parameters aremore » systematically searched, by gradually decoupling loosely correlated parameter spaces, to match the macro physical quantities of viscous blood flow. The predictions of this particle based multiscale model compare favorably to classic viscous flow solutions such as Counter-Poiseuille and Couette flows. It demonstrates that such coarse grained particle model can be applied to replicate the dynamics of viscous blood flow, with the advantage of bridging the gap between macroscopic flow scales and the cellular scales characterizing blood flow that continuum based models fail to handle adequately.« less

Ischemia may be the primary cause of the neurologic deficits in classic migraine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skyhoj Olsen, T.; Friberg, L.; Lassen, N.A.

1987-02-01

This study investigates whether the cerebral blood flow reduction occurring in attacks of classic migraine is sufficient to cause neurologic deficits. Regional cerebral blood flow measured with the xenon 133 intracarotid injection technique was analyzed in 11 patients in whom a low-flow area developed during attacks of classic migraine. When measured with this technique, regional cerebral blood flow in focal low-flow areas will be overestimated because of the effect of scattered radiation (Compton scatter) on the recordings. In this study, this effect was particularly taken into account when evaluating the degree of blood flow reduction. During attacks of classic migraine,more » cerebral blood flow reductions averaging 52% were observed focally in the 11 patients. Cerebral blood flow levels known to be insufficient for normal cortical function (less than 16 to 23 mL/100 g/min) were measured in seven patients during the attacks. This was probably also the case in the remaining four patients, but the effect of scattered radiation made a reliable evaluation of blood flow impossible. It is concluded that the blood flow reduction that occurs during attacks of classic migraine is sufficient to cause ischemia and neurologic deficits. Hence, this study suggests a vascular origin of the prodromal neurologic deficits that may accompany attacks of classic migraine.« less

Effect of blood flow on near-the-wall mass transport of drugs and other bioactive agents: a simple formula to estimate boundary layer concentrations.

PubMed

Rugonyi, Sandra

2008-04-01

Transport of bioactive agents through the blood is essential for cardiovascular regulatory processes and drug delivery. Bioactive agents and other solutes infused into the blood through the wall of a blood vessel or released into the blood from an area in the vessel wall spread downstream of the infusion/release region and form a thin boundary layer in which solute concentration is higher than in the rest of the blood. Bioactive agents distributed along the vessel wall affect endothelial cells and regulate biological processes, such as thrombus formation, atherogenesis, and vascular remodeling. To calculate the concentration of solutes in the boundary layer, researchers have generally used numerical simulations. However, to investigate the effect of blood flow, infusion rate, and vessel geometry on the concentration of different solutes, many simulations are needed, leading to a time-consuming effort. In this paper, a relatively simple formula to quantify concentrations in a tube downstream of an infusion/release region is presented. Given known blood-flow rates, tube radius, solute diffusivity, and the length of the infusion region, this formula can be used to quickly estimate solute concentrations when infusion rates are known or to estimate infusion rates when solute concentrations at a point downstream of the infusion region are known. The developed formula is based on boundary layer theory and physical principles. The formula is an approximate solution of the advection-diffusion equations in the boundary layer region when solute concentration is small (dilute solution), infusion rate is modeled as a mass flux, and there is no transport of solute through the wall or chemical reactions downstream of the infusion region. Wall concentrations calculated using the formula developed in this paper were compared to the results from finite element models. Agreement between the results was within 10%. The developed formula could be used in experimental procedures to evaluate drug efficacy, in the design of drug-eluting stents, and to calculate rates of release of bioactive substances at active surfaces using downstream concentration measurements. In addition to being simple and fast to use, the formula gives accurate quantifications of concentrations and infusion rates under steady-state and oscillatory flow conditions, and therefore can be used to estimate boundary layer concentrations under physiological conditions.

Preserved arterial flow secures hepatic oxygenation during haemorrhage in the pig

PubMed Central

Rasmussen, Allan; Skak, Claus; Kristensen, Michael; Ott, Peter; Kirkegaard, Preben; Secher, Niels H

1999-01-01

This study examined the extent of liver perfusion and its oxygenation during progressive haemorrhage. We examined hepatic arterial flow and hepatic oxygenation following the reduced portal flow during haemorrhage in 18 pigs. The hepatic surface oxygenation was assessed by near-infrared spectroscopy and the hepatic metabolism of oxygen, lactate and catecholamines determined the adequacy of the hepatic flow. Stepwise haemorrhage until circulatory collapse resulted in proportional reductions in cardiac output and in arterial, central venous and pulmonary wedge pressures. While heart rate increased, pulmonary arterial pressure remained stable. In addition, renal blood flow decreased, renal vascular resistance increased and there was elevated noradrenaline spill-over. Further, renal surface oxygenation was lowered from the onset of haemorrhage. Similarly, the portal blood flow was reduced in response to haemorrhage, and, as for the renal flow, the reduced splanchnic blood flow was associated with an elevated noradrenaline spill-over. In contrast, hepatic arterial blood flow was only slightly reduced by haemorrhage, and surface oxygenation did not change. The hepatic oxygen uptake was maintained until the blood loss represented more than 30 % of the estimated blood volume. At 30 % reduced blood volume, hepatic catecholamine uptake was reduced, and the lactate uptake approached zero. Subsequent reduction of cardiac output and portal blood flow elicited a selective dilatation of the hepatic arterial vascular bed. Due to this dilatation liver blood flow and hepatic cell oxygenation and metabolism were preserved prior to circulatory collapse. PMID:10087351

A microfluidic device for simultaneous measurement of viscosity and flow rate of blood in a complex fluidic network

PubMed Central

Jun Kang, Yang; Yeom, Eunseop; Lee, Sang-Joon

2013-01-01

Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T < 10 s). For performance demonstrations, the proposed method was applied to evaluate blood viscosity with respect to varying flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity and flow rate of whole blood circulating in the complex fluid network, with sensorless and label-free detection. Furthermore, the proposed method will be used in evaluating variations in the viscosity of human blood during cardiopulmonary bypass procedures or hemodialysis. PMID:24404074

A microfluidic device for simultaneous measurement of viscosity and flow rate of blood in a complex fluidic network.

PubMed

Jun Kang, Yang; Yeom, Eunseop; Lee, Sang-Joon

2013-01-01

Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T < 10 s). For performance demonstrations, the proposed method was applied to evaluate blood viscosity with respect to varying flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity and flow rate of whole blood circulating in the complex fluid network, with sensorless and label-free detection. Furthermore, the proposed method will be used in evaluating variations in the viscosity of human blood during cardiopulmonary bypass procedures or hemodialysis.

Cerebral blood flow in patients with congestive heart failure treated with captopril.

PubMed

Paulson, O B; Jarden, J O; Godtfredsen, J; Vorstrup, S

1984-05-31

The effect of captopril on cerebral blood flow was studied in five patients with severe congestive heart failure and in five control subjects. Cerebral blood flow was measured by inhalation of 133xenon and registration of its uptake and washout from the brain by single photon emission computer tomography. In addition, cerebral (internal jugular) venous oxygen tension was determined in the controls. The measurements were made before and 15, 60, and 180 minutes after a single oral dose of captopril (6.25 mg in patients with congestive heart failure and 25 mg in controls). Despite a marked decrease in blood pressure, cerebral blood flow increased slightly in the patients with severe congestive heart failure. When a correction was applied to take account of a change in arterial carbon dioxide tension, however, cerebral blood flow was unchanged after captopril administration even in patients with the greatest decrease in blood pressure, in whom a decrease in cerebral blood flow might have been expected. In the controls, blood pressure was little affected by captopril, whereas a slight, but not statistically significant, decrease in cerebral blood flow was observed. The cerebral venous oxygen tension decreased concomitantly.

Renal dopaminergic system: Pathophysiological implications and clinical perspectives

PubMed Central

Choi, Marcelo Roberto; Kouyoumdzian, Nicolás Martín; Rukavina Mikusic, Natalia Lucía; Kravetz, María Cecilia; Rosón, María Inés; Rodríguez Fermepin, Martín; Fernández, Belisario Enrique

2015-01-01

Fluid homeostasis, blood pressure and redox balance in the kidney are regulated by an intricate interaction between local and systemic anti-natriuretic and natriuretic systems. Intrarenal dopamine plays a central role on this interactive network. By activating specific receptors, dopamine promotes sodium excretion and stimulates anti-oxidant and anti-inflammatory pathways. Different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome, hypertension and renal inflammation, can be associated with impaired action of renal dopamine including alteration in biosynthesis, dopamine receptor expression and signal transduction. Given its properties on the regulation of renal blood flow and sodium excretion, exogenous dopamine has been postulated as a potential therapeutic strategy to prevent renal failure in critically ill patients. The aim of this review is to update and discuss on the most recent findings about renal dopaminergic system and its role in several diseases involving the kidneys and the potential use of dopamine as a nephroprotective agent. PMID:25949933

Diastolic coronary artery pressure-flow velocity relationships in conscious man.

PubMed

Dole, W P; Richards, K L; Hartley, C J; Alexander, G M; Campbell, A B; Bishop, V S

1984-09-01

We characterised the diastolic pressure-flow velocity relationship in the normal left coronary artery of conscious man before and after vasodilatation with angiographic contrast medium. Phasic coronary artery pressure and flow velocity were measured in ten patients during individual diastoles (0.5 to 1.0 s) using a 20 MHz catheter-tipped, pulsed Doppler transducer. All pressure-flow velocity curves were linear over the diastolic pressure range of 110 +/- 15 (SD) mmHg to 71 +/- 7 mmHg (r = 0.97 +/- 0.01). In the basal state, values for slope and extrapolated zero flow pressure intercept averaged 0.35 +/- 0.12 cm X s-1 X mmHg-1 and 51.7 +/- 8.6 mmHg, respectively. Vasodilatation resulted in a 2.5 +/- 0.5 fold increase in mean flow velocity. The diastolic pressure-flow velocity relationship obtained during peak vasodilatation compared to that during basal conditions was characterised by a steeper slope (0.80 +/- 0.48 cm X s-1 X mmHg-1, p less than 0.001) and lower extrapolated zero flow pressure intercept (37.9 +/- 9.8 mmHg, p less than 0.05). Mean right atrial pressure for the group averaged 4.4 +/- 1.7 mmHg, while left ventricular end-diastolic pressure averaged 8.7 +/- 2.8 mmHg. These observations in man are similar to data reported in the canine coronary circulation which are consistent with a vascular waterfall model of diastolic flow regulation. In this model, coronary blood flow may be regulated by changes in diastolic zero flow pressure as well as in coronary resistance.

Confinement regulates complex biochemical networks: initiation of blood clotting by "diffusion acting".

PubMed

Shen, Feng; Pompano, Rebecca R; Kastrup, Christian J; Ismagilov, Rustem F

2009-10-21

This study shows that environmental confinement strongly affects the activation of nonlinear reaction networks, such as blood coagulation (clotting), by small quantities of activators. Blood coagulation is sensitive to the local concentration of soluble activators, initiating only when the activators surpass a threshold concentration, and therefore is regulated by mass transport phenomena such as flow and diffusion. Here, diffusion was limited by decreasing the size of microfluidic chambers, and it was found that microparticles carrying either the classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus, initiated coagulation of human platelet-poor plasma only when confined. A simple analytical argument and numerical model were used to describe the mechanism for this phenomenon: confinement causes diffusible activators to accumulate locally and surpass the threshold concentration. To interpret the results, a dimensionless confinement number, Cn, was used to describe whether a stimulus was confined, and a Damköhler number, Da(2), was used to describe whether a subthreshold stimulus could initiate coagulation. In the context of initiation of coagulation by bacteria, this mechanism can be thought of as "diffusion acting", which is distinct from "diffusion sensing". The ability of confinement and diffusion acting to change the outcome of coagulation suggests that confinement should also regulate other biological "on" and "off" processes that are controlled by thresholds.

Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise.

PubMed

Washio, Takuro; Sasaki, Hiroyuki; Ogoh, Shigehiko

2017-04-01

We examined whether a change in posterior cerebral artery flow velocity (PCAv) reflected the posterior cerebral blood flow in healthy subjects during both static and dynamic exercise. PCAv and vertebral artery (VA) blood flow, as an index of posterior cerebral blood flow, were continuously measured during an exercise trial using transcranial Doppler (TCD) ultrasonography and Doppler ultrasound, respectively. Static handgrip exercise significantly increased both PCAv and VA blood flow. Increasing intensity of dynamic exercise further increased VA blood flow from moderate exercise, while PCAv decreased to almost resting level. During both static and dynamic exercise, the PCA cerebrovascular conductance (CVC) index significantly decreased from rest (static and high-intensity dynamic exercise, -11.5 ± 12.2% and -18.0 ± 16.8%, means ± SD, respectively) despite no change in the CVC of VA. These results indicate that vasoconstriction occurred at PCA but not VA during exercise-induced hypertension. This discrepancy in vascular response to exercise between PCA and VA may be due to different cerebral arterial characteristics. Therefore, to determine the effect of exercise on posterior cerebral circulation, at least, we need to carefully consider which cerebral artery to measure, regardless of exercise mode. NEW & NOTEWORTHY We examined whether transcranial Doppler-determined flow velocity in the posterior cerebral artery can be used as an index of cerebral blood flow during exercise. However, the changes in posterior cerebral artery flow velocity during exercise do not reflect vertebral artery blood flow. Copyright © 2017 the American Physiological Society.

Neurovascular signaling in the brain and the pathological consequences of hypertension

PubMed Central

Dunn, Kathryn M.

2013-01-01

The execution and maintenance of all brain functions are dependent on a continuous flow of blood to meet the metabolic needs of the tissue. To ensure the delivery of resources required for neural processing and the maintenance of neural homeostasis, the cerebral vasculature is elaborately and extensively regulated by signaling from neurons, glia, interneurons, and perivascular nerves. Hypertension is associated with impaired neurovascular regulation of the cerebral circulation and culminates in neurodegeneration and cognitive dysfunction. Here, we review the physiological processes of neurovascular signaling in the brain and discuss mechanisms of hypertensive neurovascular dysfunction. PMID:24163077

[The effects of carbogen inhalation on microvascular within lateral wall of cochlear following acute acoustic trauma].

PubMed

Zhao, Jing; Sun, Jianjun; Kong, Weijia

2008-11-01

To explore the influence of carbogen on lateral wall microvascular of cochlear after acute acoustic trauma. Forty guinea pigs were divided into 4 groups: group A (noise damage), group B (carbogen inhalation), group C (noise damage + carbogen inhalation), and the control group without any treatment. The diameter of the column of RBCs (RBC column diameter, RBCCD), blood flow velocity (BFV) and blood flow states(BFS) in microvasculature were measured and described under microscope. The microvascular in group A demonstrated a blood flow in contrary direction, granuliform flow, and granular slow flow. The erythrocytes aggregated in the microvascular of the cochlea. The RBCCD decreased 12.1% compared with the control group (P < 0.05). The blood flow in group B showed a laminar flow or laminar granular flow, and the RBCCD increased 20.7% compared with the control group. The blood condition in group C was the same as the control group-laminar granular blood flow; the blood flow with contrary direction was less than group A, and the RBCCD was 17.4% lager than that of group A. Carbogen can dilate the RBCCD and increase the BFV in stria vascular. So carbogen can alleviate the harm from noise.

Phasic changes in human right coronary blood flow before and after repair of aortic insufficiency.

PubMed

Folts, J D; Rowe, G G; Kahn, D R; Young, W P

1979-02-01

We have shown previously that acute aortic insufficiency in chronically instrumented dogs reverses the normally high ratio of diastolic to systolic coronary blood flow. Phasic blood flow in the dominant right coronary artery was measured directly with an electromagnetic flow meter during surgery in eight patients with severe aortic insufficiency before and after relacement of the aortic valve. Before the insufficiency was eliminated, right coronary flow average 116 +/- 37 ml./minute and the diastolic to systolic flow ratio was 0.88 +/- 17. Mean arterial blood pressure averaged 106 +/- 17 mm. Hg, heart rate 84 +/- 19 beats/minute, and mean diastolic pressure averaged 67 +/- 10 mm. Hg. After the aortic valve was replaced with an average heart rate of 90 +/- 15 and mean blood pressure of 103 +/- 13 mm. Hg, the average right coronary blood flow increased to 180 +/- 40 ml./minute with a D/S ratio of 2.18 +/- 0.8. In all cases the right coronary blood flow increased after the aortic insufficiency was eliminated surgically. Right coronary flow probably increased because of the improved diastolic perfusion pressure and the change from predominantly systolic to diastolic coronary flow.

Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO/sub 2/

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murkin, J.M.; Farrar, J.K.; Tweed, W.A.

Measurement of /sup 133/Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO/sub 2/ at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBFmore » was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO/sub 2/ of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.« less

Blood pressure regulation V: in vivo mechanical properties of precapillary vessels as affected by long-term pressure loading and unloading.

PubMed

Eiken, Ola; Mekjavic, Igor B; Kölegård, Roger

2014-03-01

Recent studies are reviewed, concerning the in vivo wall stiffness of arteries and arterioles in healthy humans, and how these properties adapt to iterative increments or sustained reductions in local intravascular pressure. A novel technique was used, by which arterial and arteriolar stiffness was determined as changes in arterial diameter and flow, respectively, during graded increments in distending pressure in the blood vessels of an arm or a leg. Pressure-induced increases in diameter and flow were smaller in the lower leg than in the arm, indicating greater stiffness in the arteries/arterioles of the leg. A 5-week period of intermittent intravascular pressure elevations in one arm reduced pressure distension and pressure-induced flow in the brachial artery by about 50%. Conversely, prolonged reduction of arterial/arteriolar pressure in the lower body by 5 weeks of sustained horizontal bedrest, induced threefold increases of the pressure-distension and pressure-flow responses in a tibial artery. Thus, the wall stiffness of arteries and arterioles are plastic properties that readily adapt to changes in the prevailing local intravascular pressure. The discussion concerns mechanisms underlying changes in local arterial/arteriolar stiffness as well as whether stiffness is altered by changes in myogenic tone and/or wall structure. As regards implications, regulation of local arterial/arteriolar stiffness may facilitate control of arterial pressure in erect posture and conditions of exaggerated intravascular pressure gradients. That increased intravascular pressure leads to increased arteriolar wall stiffness also supports the notion that local pressure loading may constitute a prime mover in the development of vascular changes in hypertension.

Segmental Blood Flow and Hemodynamic State of Lymphedematous and Nonlymphedematous Arms

PubMed Central

Montgomery, Leslie D.; Dietrich, Mary S.; Armer, Jane M.; Stewart, B. R.

2011-01-01

Abstract Background Findings regarding the influence hemodynamic factors, such as increased arterial blood flow or venous abnormalities, on breast cancer treatment-related lymphedema are mixed. The purpose of this study was to compare segmental arterial blood flow, venous blood return, and blood volumes between breast cancer survivors with treatment-related lymphedema and healthy normal individuals without lymphedema. Methods and Results A Tetrapolar High Resolution Impedance Monitor and Cardiotachometer were used to compare segmental arterial blood flow, venous blood return, and blood volumes between breast cancer survivors with treatment-related lymphedema and healthy normal volunteers. Average arterial blood flow in lymphedema-affected arms was higher than that in arms of healthy normal volunteers or in contralateral nonlymphedema affected arms. Time of venous outflow period of blood flow pulse was lower in lymphedema-affected arms than in healthy normal or lymphedema nonaffected arms. Amplitude of the venous component of blood flow pulse signal was lower in lymphedema-affected arms than in healthy or lymphedema nonaffected arms. Index of venular tone was also lower in lymphedema-affected arms than healthy or lymphedema nonaffected arms. Conclusions Both arterial and venous components may be altered in the lymphedema-affected arms when compared to healthy normal arms and contralateral arms in the breast cancer survivors. PMID:21417765

Physiological and biochemical principles underlying volume-targeted therapy--the "Lund concept".

PubMed

Nordström, Carl-Henrik

2005-01-01

The optimal therapy of sustained increase in intracranial pressure (ICP) remains controversial. The volume-targeted therapy ("Lund concept") discussed in this article focuses on the physiological volume regulation of the intracranial compartments. The balance between effective transcapillary hydrostatic and osmotic pressures constitutes the driving force for transcapillary fluid exchange. The low permeability for sodium and chloride combined with the high crystalloid osmotic pressure (approximately 5700 mmHg) on both sides of the blood-brain barrier (BBB) counteracts fluid exchange across the intact BBB. Additionally, variations in systemic blood pressure generally are not transmitted to these capillaries because cerebral intracapillary hydrostatic pressure (and blood flow) is physio-logically tightly autoregulated. Under pathophysiological conditions, the BBB may be partially disrupted. Transcapillary water exchange is then determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Pressure autoregulation of cerebral blood flow is likely to be impaired in these conditions. A high cerebral perfusion pressure accordingly increases intracapillary hydrostatic pressure and leads to increased intracerebral water content and an increase in ICP. The volume-targeted "Lund concept" has been evaluated in experimental and clinical studies to examine the physiological and biochemical (utilizing intracerebral microdialysis) effects, and the clinical experiences have been favorable.

Regional cerebral blood flow measurement with intravenous ( sup 15 O)water bolus and ( sup 18 F)fluoromethane inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herholz, K.; Pietrzyk, U.; Wienhard, K.

1989-09-01

In 20 patients with ischemic cerebrovascular disease, classic migraine, or angiomas, we compared paired dynamic positron emission tomographic measurements of regional cerebral blood flow using both ({sup 15}O)water and ({sup 18}F)fluoromethane as tracers. Cerebral blood flow was also determined according to the autoradiographic technique with a bolus injection of ({sup 15}O)water. There were reasonable overall correlations between dynamic ({sup 15}O)water and ({sup 18}F)fluoromethane values for cerebral blood flow (r = 0.82) and between dynamic and autoradiographic ({sup 15}O)water values for cerebral blood flow (r = 0.83). We found a close correspondence between abnormal pathologic findings and visually evaluated cerebral bloodmore » flow tomograms obtained with the two tracers. On average, dynamic ({sup 15}O)water cerebral blood flow was 6% lower than that measured with ({sup 18}F)fluoromethane. There also was a general trend toward a greater underestimation with ({sup 15}O)water in high-flow areas, particularly in hyperemic areas, probably due to incomplete first-pass extraction of ({sup 15}O)water. Underestimation was not detected in low-flow areas or in the cerebellum. Absolute cerebral blood flow values were less closely correlated between tracers and techniques than cerebral blood flow patterns. The variability of the relation between absolute flow values was probably caused by confounding effects of the variation in the circulatory delay time. The autoradiographic technique was most sensitive to this type error.« less

Skin cooling on contact with cold materials: the effect of blood flow during short-term exposures.

PubMed

Jay, Ollie; Havenith, George

2004-03-01

This study investigates the effect of blood flow upon the short-term (<180 s) skin contact cooling response in order to ascertain whether sufferers of circulatory disorders, such as the vasospastic disorder Raynaud's disease, are at a greater risk of cold injury than people with a normal rate of blood flow. Eight female volunteers participated, touching blocks of stainless steel and nylon with a finger contact force of 2.9 N at a surface temperature of -5 degrees C under occluded and vasodilated conditions. Contact temperature (Tc) of the finger pad was measured over time using a T-type thermocouple. Forearm blood flow was measured using strain gauge plethysmography. Contact cooling responses were analysed by fitting a modified Newtonian cooling curve. A significant difference was found between the starting skin temperatures for the two blood flow conditions (P<0.001). However, no effect of blood flow was found upon any of the derived cooling curve parameters characterizing the skin cooling response (P>0.05). It is hypothesized that the finger contact force used (2.9 N) and the resultant pressure upon the tissue of the contact finger pad restricted the blood supply to the contact area under both blood flow conditions; therefore, no effect of blood flow was found upon the parameters describing the contact cooling response. Whilst the findings of this study are sufficient to draw a conclusion for those in a working environment, i.e. contact forces below 2.9 N will seldom be encountered, a further study will be required to ascertain conclusively whether blood flow does affect the contact cooling response at a finger contact force low enough to allow unrestricted blood flow to the finger pad. Further protocol improvements are also recommended.

Comparison of non-invasive MRI measurements of cerebral blood flow in a large multisite cohort.

PubMed

Dolui, Sudipto; Wang, Ze; Wang, Danny Jj; Mattay, Raghav; Finkel, Mack; Elliott, Mark; Desiderio, Lisa; Inglis, Ben; Mueller, Bryon; Stafford, Randall B; Launer, Lenore J; Jacobs, David R; Bryan, R Nick; Detre, John A

2016-07-01

Arterial spin labeling and phase contrast magnetic resonance imaging provide independent non-invasive methods for measuring cerebral blood flow. We compared global cerebral blood flow measurements obtained using pseudo-continuous arterial spin labeling and phase contrast in 436 middle-aged subjects acquired at two sites in the NHLBI CARDIA multisite study. Cerebral blood flow measured by phase contrast (CBFPC: 55.76 ± 12.05 ml/100 g/min) was systematically higher (p < 0.001) and more variable than cerebral blood flow measured by pseudo-continuous arterial spin labeling (CBFPCASL: 47.70 ± 9.75). The correlation between global cerebral blood flow values obtained from the two modalities was 0.59 (p < 0.001), explaining less than half of the observed variance in cerebral blood flow estimates. Well-established correlations of global cerebral blood flow with age and sex were similarly observed in both CBFPCASL and CBFPC CBFPC also demonstrated statistically significant site differences, whereas no such differences were observed in CBFPCASL No consistent velocity-dependent effects on pseudo-continuous arterial spin labeling were observed, suggesting that pseudo-continuous labeling efficiency does not vary substantially across typical adult carotid and vertebral velocities, as has previously been suggested. Although CBFPCASL and CBFPC values show substantial similarity across the entire cohort, these data do not support calibration of CBFPCASL using CBFPC in individual subjects. The wide-ranging cerebral blood flow values obtained by both methods suggest that cerebral blood flow values are highly variable in the general population. © The Author(s) 2016.

Investigation of spiral blood flow in a model of arterial stenosis.

PubMed

Paul, Manosh C; Larman, Arkaitz

2009-11-01

The spiral component of blood flow has both beneficial and detrimental effects in human circulatory system [Stonebridge PA, Brophy CM. Spiral laminar flow in arteries? Lancet 1991; 338: 1360-1]. We investigate the effects of the spiral blood flow in a model of three-dimensional arterial stenosis with a 75% cross-sectional area reduction at the centre by means of computational fluid dynamics (CFD) techniques. The standard k-omega model is employed for simulation of the blood flow for the Reynolds number of 500 and 1000. We find that for Re=500 the spiral component of the blood flow increases both the total pressure and velocity of the blood, and some significant differences are found between the wall shear stresses of the spiral and non-spiral induced flow downstream of the stenosis. The turbulent kinetic energy is reduced by the spiral flow as it induces the rotational stabilities in the forward flow. For Re=1000 the tangential component of the blood velocity is most influenced by the spiral speed, but the effect of the spiral flow on the centreline turbulent kinetic energy and shear stress is mild. The results of the effects of the spiral flow are discussed in the paper along with the relevant pathological issues.

AltitudeOmics: effect of ascent and acclimatization to 5260 m on regional cerebral oxygen delivery.

PubMed

Subudhi, Andrew W; Fan, Jui-Lin; Evero, Oghenero; Bourdillon, Nicolas; Kayser, Bengt; Julian, Colleen G; Lovering, Andrew T; Roach, Robert C

2014-05-01

Cerebral hypoxaemia associated with rapid ascent to high altitude can be life threatening; yet, with proper acclimatization, cerebral function can be maintained well enough for humans to thrive. We investigated adjustments in global and regional cerebral oxygen delivery (DO2) as 21 healthy volunteers rapidly ascended and acclimatized to 5260 m. Ultrasound indices of cerebral blood flow in internal carotid and vertebral arteries were measured at sea level, upon arrival at 5260 m (ALT1; atmospheric pressure 409 mmHg) and after 16 days of acclimatization (ALT16). Cerebral DO2 was calculated as the product of arterial oxygen content and flow in each respective artery and summed to estimate global cerebral blood flow. Vascular resistances were calculated as the quotient of mean arterial pressure and respective flows. Global cerebral blood flow increased by ∼70% upon arrival at ALT1 (P < 0.001) and returned to sea-level values at ALT16 as a result of changes in cerebral vascular resistance. A reciprocal pattern in arterial oxygen content maintained global cerebral DO2 throughout acclimatization, although DO2 to the posterior cerebral circulation was increased by ∼25% at ALT1 (P = 0.032). We conclude that cerebral DO2 is well maintained upon acute exposure and acclimatization to hypoxia, particularly in the posterior and inferior regions of the brain associated with vital homeostatic functions. This tight regulation of cerebral DO2 was achieved through integrated adjustments in local vascular resistances to alter cerebral perfusion during both acute and chronic exposure to hypoxia. © 2013 The Authors. Experimental Physiology © 2013 The Physiological Society.

Measurement of retinal blood flow in the rat by combining Doppler Fourier-domain optical coherence tomography with fundus imaging

NASA Astrophysics Data System (ADS)

Werkmeister, René M.; Vietauer, Martin; Knopf, Corinna; Fürnsinn, Clemens; Leitgeb, Rainer A.; Reitsamer, Herbert; Gröschl, Martin; Garhöfer, Gerhard; Vilser, Walthard; Schmetterer, Leopold

2014-10-01

A wide variety of ocular diseases are associated with abnormalities in ocular circulation. As such, there is considerable interest in techniques for quantifying retinal blood flow, among which Doppler optical coherence tomography (OCT) may be the most promising. We present an approach to measure retinal blood flow in the rat using a new optical system that combines the measurement of blood flow velocities via Doppler Fourier-domain optical coherence tomography and the measurement of vessel diameters using a fundus camera-based technique. Relying on fundus images for extraction of retinal vessel diameters instead of OCT images improves the reliability of the technique. The system was operated with an 841-nm superluminescent diode and a charge-coupled device camera that could be operated at a line rate of 20 kHz. We show that the system is capable of quantifying the response of 100% oxygen breathing on the retinal blood flow. In six rats, we observed a decrease in retinal vessel diameters of 13.2% and a decrease in retinal blood velocity of 42.6%, leading to a decrease in retinal blood flow of 56.7%. Furthermore, in four rats, the response of retinal blood flow during stimulation with diffuse flicker light was assessed. Retinal vessel diameter and blood velocity increased by 3.4% and 28.1%, respectively, leading to a relative increase in blood flow of 36.2%;. The presented technique shows much promise to quantify early changes in retinal blood flow during provocation with various stimuli in rodent models of ocular diseases in rats.

Endothelin and vasopressin influence splanchnic blood flow distribution during and after cardiopulmonary bypass.

PubMed

Bomberg, Hagen; Bierbach, Benjamin; Flache, Stephan; Wagner, Isabell; Gläser, Lena; Groesdonk, Heinrich V; Menger, Michael D; Schäfers, Hans-Joachim

2013-02-01

Gastrointestinal blood flow can be compromised during and after cardiopulmonary bypass. Endothelin has been shown to be involved in the intestinal microcirculatory disturbance of sepsis. The aim of the present study was to analyze the involvement of the endothelin system on intestinal blood flow regulation during cardiopulmonary bypass and the effect of vasopressin given during cardiopulmonary bypass. A total of 24 pigs were studied in 4 groups (n = 6): group I, sham; group II, ischemia/reperfusion with 1 hour of superior mesenteric artery occlusion; group III, cardiopulmonary bypass for 1 hour; and group IV, 1 hour of cardiopulmonary bypass plus vasopressin administration, maintaining the baseline arterial pressure. All the pigs were reperfused for 90 minutes. During the experiment, the hemodynamics and jejunal microcirculation were measured continuously. The jejunal mucosal expression of endothelin-1 and its receptor subtypes A and B were determined using polymerase chain reaction. During cardiopulmonary bypass, superior mesenteric artery flow was preserved but marked jejunal microvascular impairment occurred compared with baseline (mucosal capillary density, 192.2 ± 5.4 vs 150.8 ± 5.1 cm/cm(2); P = .005; tissue blood flow, 501.7 ± 39.3 vs 332.3 ± 27.9 AU; P = .025). The expression of endothelin-1 after cardiopulmonary bypass (3.2 ± 0.4 vs 12.2 ± 0.8 RQ, P = .006) and endothelin subtype A (0.7 ± 0.2 vs 2.4 ± 0.6 RQ; P = .01) was significantly increased compared to the sham group. Vasopressin administration during cardiopulmonary bypass led to normal capillary density (189.9 ± 3.9 vs 178.0 ± 6.3; P = .1) and tissue blood flow (501.7 ± 39.3 vs 494.7 ± 44.4 AU; P = .4) compared with baseline. The expression of endothelin-1 (3.2 ± 0.4 vs 1.8 ± 0.3 RQ; P = .3) and endothelin subtype A (0.7 ± 0.2 vs 0.9 ± 0.2 RQ; P = .5) was not different from the sham group. Cardiopulmonary bypass leads to microvascular impairment of jejunal microcirculation, which is associated with the upregulation of endothelin-1 and endothelin subtype A. The administration of vasopressin minimizes these cardiopulmonary bypass-associated alterations. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms

PubMed Central

Anderson, Debra F.; Cheung, Cecilia Y.

2014-01-01

Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport. PMID:25186112

Viral infection potentiates the increase in airway blood flow produced by substance P.

PubMed

Yamawaki, I; Geppetti, P; Bertrand, C; Chan, B; Massion, P; Piedimonte, G; Nadel, J A

1995-08-01

We examined the effect of respiratory tract infection with Sendai virus on the responsiveness of airway blood flow to substance P (SP) in rats. Pathogen-free rats were inoculated with either Sendai virus suspension or sterile viral growth medium into each nostril. Five days later, we measured airway and esophageal blood flows before and immediately after injection of SP or histamine into the left ventricle of rats in both groups using a modification of the reference-sample microsphere technique. Viral infection potentiated the increase in airway blood flow evoked by SP but not by histamine. We also examined the effect of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the SP-induced increase in airway blood flow. Both phosphoramidon (NEP inhibitor) and captopril (ACE inhibitor) potentiated the increase in airway blood flow produced by SP in pathogen-free rats. In the presence of both peptidase inhibitors, a submaximal dose of SP increased blood flow to a similar level in infected and pathogen-free rats. Thus decreased activity of both ACE and NEP may be involved in the exaggerated increase in airway blood flow evoked by SP in virus-infected rats.

Changes in scalp and cortical blood flow during hyperventilation measured with diffusing-wave spectroscopy

NASA Astrophysics Data System (ADS)

Li, Jun; Ninck, Markus; Gisler, Thomas

2009-07-01

Changes in scalp and cortical blood flow induced by voluntary hyperventilation are investigated by near-infrared diffusing-wave spectroscopy. The temporal intensity autocorrelation function g(2) (τ) of multiply scattered light is recorded from the forehead of subjects during hyperventilation. Blood flow within the sampled tissue volume is estimated by the mean decay rate of g(2) (τ) . Data measured from six subjects show that the pattern of the hemodynamic response during 50 s hyperventilation is rather complicated: within the first 10 s, in three subjects an initial increase in blood flow is observed; from 10 s to 20 s, the mean blood flow is smaller than its baseline value for all six subjects; for the duration from 20 s to 30 s, the blood flow increases again. However, after 30 s the change is not consistent across subjects. Further study on one of these subjects by using two receivers probing the blood flow in the cortex and in the superficial layers simultaneously, reveals that during hyperventilation, the direction of change in blood flow within the scalp is opposite to the one in the brain. This helps to understand the complicated hemodynamic response observed in our measurements.

Effect of renal denervation on dynamic autoregulation of renal blood flow.

PubMed

DiBona, Gerald F; Sawin, Linda L

2004-06-01

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

Gingival blood flow measurement with a non-contact laser flowmeter.

PubMed

Matsuki, M; Xu, Y B; Nagasawa, T

2001-07-01

A non-contact laser flowmeter was used to measure the changing of the gingival blood flow. Five university students with healthy oral condition were selected in this study. The blood flow measurement on the extensor digitorum (above the head of third metacarpal), with the changing of distance and angle between the probe and the tissue was used as a pre-study experiment. Blood flow rate was determined in the labial gingiva (2 mm above the cervical line) of upper central incisor using a stent fixing the probe at a 3-mm distance from the tissue. A basal level of gingival blood flow was taken two times each day for 5 days. The effects of water of different temperatures on the gingival blood flow are discussed. With the changing of distance, the blood flow rate became smaller, but there was no significant effect from the angle. The reproducibility was acceptable through the 5-day measurement. After stimulating with warm and body temperature water, the blood flow first increased significantly and then went back to the basal line (faster with the body temperature water). With cold water, different reactions between the subjects were observed.

Retinal blood flow detection in diabetic patients by Doppler Fourier domain optical coherence tomography◊

PubMed Central

Wang, Yimin; Fawzi, Amani; Tan, Ou; Gil-Flamer, John; Huang, David

2010-01-01

We present human retinal blood flow investigation for diabetic patients using Doppler Fourier domain optical coherence tomography (FD-OCT). The scanning pattern consisted of two concentric circles around the optic nerve head. The blood flow in one patient with diabetes and no retinpathy and another patient with treated proliferative diabetic retinopathy were measured. The patient without retinopathy showed a total blood flow value at the lower level of the normal range. The flow distribution between superior and inferior retina was balanced. The patient with diabetic retinopathy had a flow value lower than the normal people. Our study shows that Doppler FD-OCT can be used to evaluate the total retinal blood flow in patients with retinal diseases. PMID:19259246

Using the developed cross-flow filtration chip for collecting blood plasma under high flow rate condition and applying the immunoglobulin E detection

NASA Astrophysics Data System (ADS)

Yeh, Chia-Hsien; Hung, Chia-Wei; Wu, Chun-Han; Lin, Yu-Cheng

2014-09-01

This paper presents a cross-flow filtration chip for separating blood cells (white blood cells, red blood cells, and platelets) and obtaining blood plasma from human blood. Our strategy is to flow the sample solution in parallel to the membrane, which can generate a parallel shear stress to remove the clogging microparticles on the membrane, so the pure sample solution is obtained in the reservoir. The cross-flow filtration chip includes a cross-flow layer, a Ni-Pd alloy micro-porous membrane, and a reservoir layer. The three layers are packaged in a polymethylmethacrylate (PMMA) frame to create the cross-flow filtration chip. Various dilutions of the blood sample (original, 2 × , 3 × , 5 × , and 10×), pore sizes with different diameters (1 µm, 2 µm, 4 µm, 7 µm, and 10 µm), and different flow rates (1 mL/min, 3 mL/min, 5 mL/min, 7 mL/min, and 10 mL/min) are tested to determine their effects on filtration percentage. The best filtration percentage is 96.2% when the dilution of the blood sample is 10 × , the diameter of pore size of a Ni-Pd alloy micro-porous membrane is 2 µm, and the flow rate is 10 mL/min. Finally, for the clinical tests of the immunoglobulin E (IgE) concentration, the cross-flow filtration chip is used to filter the blood of the allergy patients to obtain the blood plasma. This filtered blood plasma is compared with that obtained using the conventional centrifugation based on the enzyme-linked immunosorbent assay. The results reveal that these two blood separation methods have similar detection trends. The proposed filtration chip has the advantages of low cost, short filtration time, and easy operation and thus can be applied to the separation of microparticles, cells, bacteria, and blood.

Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

NASA Astrophysics Data System (ADS)

Cochran, J. M.; Chung, S. H.; Leproux, A.; Baker, W. B.; Busch, D. R.; DeMichele, A. M.; Tchou, J.; Tromberg, B. J.; Yodh, A. G.

2017-06-01

We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

The effects of bupivacaine, L-nitro-L-arginine-methyl ester, and phenylephrine on cardiovascular adaptations to asphyxia in the preterm fetal lamb.

PubMed

Santos, A C; Yun, E M; Bobby, P D; Noble, G; Arthur, G R; Finster, M

1997-12-01

The preterm fetal lamb that is exposed to clinically relevant plasma concentrations of lidocaine loses its cardiovascular adaptations to asphyxia, and its condition deteriorates further. Nitric oxide (NO) is an important regulator of vascular tone, and local anesthetics are known to inhibit endothelium-dependent vasodilation. The purpose of the present study was to determine whether the adverse effects of lidocaine noted in the preterm fetal lamb also occur with bupivacaine and whether the inhibition of NO results in effects similar to those of bupivacaine. Thirty-two chronically prepared pregnant sheep were studied at 117-119 days' gestation. Maternal and fetal blood pressure, heart rate, and acid-base state were evaluated. Fetal organ blood flows were determined using 15-microM diameter dye-labeled microspheres. After a control period, mild to moderate asphyxia (fetal PaO2 15 mm Hg) was induced by partial umbilical cord occlusion and maintained throughout the experiment. Ewes in Group I (n = 13) were given a two-step intravenous infusion of bupivacaine for 180 min. Fetuses in Group II (n = 12) received an intravenous injection of L-nitro-L-arginine-methyl ester (L-NAME) (25 mg/kg), and measurements were taken 10 and 30 min after the injection. A third group (Group III) of fetuses (n = 7) were given an intravenous infusion of phenylephrine to mimic the blood pressure increases noted in L-NAME-treated fetuses. At 90 min of stable asphyxia, there was a significant decrease in fetal PaO2 and pHa and an increase in PaCO2 and mean arterial blood pressure. There was also an increase in blood flow to the adrenals, myocardium, and cerebral cortex, whereas blood flow to the placenta decreased. Administration of bupivacaine during asphyxia did not affect the changes in mean arterial blood pressure and acid-base state but did abolish the increases in blood flows to the myocardium and cerebral cortex. Injection of L-NAME to the asphyxiated fetus resulted in an increase in mean arterial blood pressure above the level noted at 90 min of cord occlusion, and an increase in fetal PaO2 toward control levels. This was accompanied by a reduction in organ blood flows to preasphyxia levels. In asphyxiated Group III fetuses, titration of the phenylephrine infusion to achieve blood pressure increases similar to those noted with L-NAME were also associated with an increase in fetal PaO2. These data indicate that bupivacaine abolishes some of the circulatory adaptations to mild to moderate asphyxia induced by partial cord occlusion in the preterm fetal lamb. It is not clear whether these effects of bupivacaine are due to inhibition of NO. In the preterm fetal lamb, clinically relevant plasma concentrations of bupivacaine achieved by intravenous infusion to the pregnant ewe (80% gestation) abolished some of the fetal cardiovascular adaptations to asphyxia induced by partial umbilical cord occlusion.

Blood flow measurement of human skeletal muscle during various exercise intensity using diffuse correlation spectroscopy (DCS)

NASA Astrophysics Data System (ADS)

Murakami, Yuya; Ono, Yumie; Ichinose, Masashi

2017-02-01

We studied blood flow dynamics of active skeletal muscle using diffuse correlation spectroscopy (DCS), an emerging optical modality that is suitable for noninvasive quantification of microcirculation level in deep tissue. Seven healthy subjects conducted 0.5 Hz dynamic handgrip exercise for 3 minutes at intensities of 10, 20, 30, and 50 % of maximal voluntary contraction (MVC). DCS could detect the time-dependent increase of the blood flow response of the forearm muscle for continuous exercises, and the increase ratios of the mean blood flow through the exercise periods showed good correlation with the exercise intensities. We also compared blood flow responses detected from DCS with two different photon sampling rates and found that an appropriate photon sampling rates should be selected to follow the wide-ranged increase in the muscle blood flow with dynamic exercise. Our results demonstrate the possibility for utilizing DCS in a field of sports medicine to noninvasively evaluate the dynamics of blood flow in the active muscles.

Microfluidic measurement for blood flow and platelet adhesion around a stenotic channel: Effects of tile size on the detection of platelet adhesion in a correlation map

PubMed Central

Jung, Sung Yong; Yeom, Eunseop

2017-01-01

Platelet aggregation affects the surrounding blood flow and usually occurs where a blood vessel is narrowed as a result of atherosclerosis. The relationship between blood flow and platelet aggregation is not yet fully understood. This study proposes a microfluidic method to measure the velocity and platelet aggregation simultaneously by combining the micro-particle image velocimetry technique and a correlation mapping method. The blood flow and platelet adhesion procedure in a stenotic micro-channel with 90% severity were observed for a relatively long period of 4 min. In order to investigate the effect of tile size on the detection of platelet adhesion, 2D correlation coefficients were evaluated with binary images obtained by manual labeling and the correlation mapping method with different sizes of the square tile ranging from 3 to 50 pixels. The maximum 2D correlation coefficient occurred with the optimum tile size of 5 × 5 pixels. Since the blood flow and platelet aggregation are mutually influenced by each other, blood flow and platelet adhesion were continuously varied. When there was no platelet adhesion (t = 0 min), typical blood flow is observed. The blood flow passes through the whole channel smoothly, and jet-like flow occurs in the post-stenosis region. However, the flow pattern changes when platelet adhesion starts at the stenosis apex and after the stenosis. These adhesions induce narrow high velocity regions to become wider over a range of area from upstream to downstream of the stenosis. Separated jet-like flows with two high velocity regions are also created. The changes in flow patterns may alter the patterns of platelet adhesion. As the area of the plate adhesion increases, the platelets plug the micro-channel and there is only a small amount of blood flow, finally. The microfluidic method could provide new insights for better understanding of the interactions between platelet aggregation and blood flow in various physiological conditions. PMID:28798854

Microfluidic measurement for blood flow and platelet adhesion around a stenotic channel: Effects of tile size on the detection of platelet adhesion in a correlation map.

PubMed

Jung, Sung Yong; Yeom, Eunseop

2017-03-01

Platelet aggregation affects the surrounding blood flow and usually occurs where a blood vessel is narrowed as a result of atherosclerosis. The relationship between blood flow and platelet aggregation is not yet fully understood. This study proposes a microfluidic method to measure the velocity and platelet aggregation simultaneously by combining the micro-particle image velocimetry technique and a correlation mapping method. The blood flow and platelet adhesion procedure in a stenotic micro-channel with 90% severity were observed for a relatively long period of 4 min. In order to investigate the effect of tile size on the detection of platelet adhesion, 2D correlation coefficients were evaluated with binary images obtained by manual labeling and the correlation mapping method with different sizes of the square tile ranging from 3 to 50 pixels. The maximum 2D correlation coefficient occurred with the optimum tile size of 5 × 5 pixels. Since the blood flow and platelet aggregation are mutually influenced by each other, blood flow and platelet adhesion were continuously varied. When there was no platelet adhesion (t = 0 min), typical blood flow is observed. The blood flow passes through the whole channel smoothly, and jet-like flow occurs in the post-stenosis region. However, the flow pattern changes when platelet adhesion starts at the stenosis apex and after the stenosis. These adhesions induce narrow high velocity regions to become wider over a range of area from upstream to downstream of the stenosis. Separated jet-like flows with two high velocity regions are also created. The changes in flow patterns may alter the patterns of platelet adhesion. As the area of the plate adhesion increases, the platelets plug the micro-channel and there is only a small amount of blood flow, finally. The microfluidic method could provide new insights for better understanding of the interactions between platelet aggregation and blood flow in various physiological conditions.

Modified Beer-Lambert law for blood flow

NASA Astrophysics Data System (ADS)

Baker, Wesley B.; Parthasarathy, Ashwin B.; Busch, David R.; Mesquita, Rickson C.; Greenberg, Joel H.; Yodh, A. G.

2015-03-01

The modified Beer-Lambert law is among the most widely used approaches for analysis of near-infrared spectroscopy (NIRS) reflectance signals for measurements of tissue blood volume and oxygenation. Briefly, the modified Beer-Lambert paradigm is a scheme to derive changes in tissue optical properties based on continuous-wave (CW) diffuse optical intensity measurements. In its simplest form, the scheme relates differential changes in light transmission (in any geometry) to differential changes in tissue absorption. Here we extend this paradigm to the measurement of tissue blood flow by diffuse correlation spectroscopy (DCS). In the new approach, differential changes of the intensity temporal auto-correlation function at a single delay-time are related to differential changes in blood flow. The key theoretical results for measurement of blood flow changes in any tissue geometry are derived, and we demonstrate the new method to monitor cerebral blood flow in a pig under conditions wherein the semi-infinite geometry approximation is fairly good. Specifically, the drug dinitrophenol was injected in the pig to induce a gradual 200% increase in cerebral blood flow, as measured with MRI velocity flow mapping and by DCS. The modified Beer-Lambert law for flow accurately recovered these flow changes using only a single delay-time in the intensity auto-correlation function curve. The scheme offers increased DCS measurement speed of blood flow. Further, the same techniques using the modified Beer-Lambert law to filter out superficial tissue effects in NIRS measurements of deep tissues can be applied to the DCS modified Beer-Lambert law for blood flow monitoring of deep tissues.

[A capillary blood flow velocity detection system based on linear array charge-coupled devices].

PubMed

Zhou, Houming; Wang, Ruofeng; Dang, Qi; Yang, Li; Wang, Xiang

2017-12-01

In order to detect the flow characteristics of blood samples in the capillary, this paper introduces a blood flow velocity measurement system based on field-programmable gate array (FPGA), linear charge-coupled devices (CCD) and personal computer (PC) software structure. Based on the analysis of the TCD1703C and AD9826 device data sheets, Verilog HDL hardware description language was used to design and simulate the driver. Image signal acquisition and the extraction of the real-time edge information of the blood sample were carried out synchronously in the FPGA. Then a series of discrete displacement were performed in a differential operation to scan each of the blood samples displacement, so that the sample flow rate could be obtained. Finally, the feasibility of the blood flow velocity detection system was verified by simulation and debugging. After drawing the flow velocity curve and analyzing the velocity characteristics, the significance of measuring blood flow velocity is analyzed. The results show that the measurement of the system is less time-consuming and less complex than other flow rate monitoring schemes.

Prediction of blood pressure and blood flow in stenosed renal arteries using CFD

NASA Astrophysics Data System (ADS)

Jhunjhunwala, Pooja; Padole, P. M.; Thombre, S. B.; Sane, Atul

2018-04-01

In the present work an attempt is made to develop a diagnostive tool for renal artery stenosis (RAS) which is inexpensive and in-vitro. To analyse the effects of increase in the degree of severity of stenosis on hypertension and blood flow, haemodynamic parameters are studied by performing numerical simulations. A total of 16 stenosed models with varying degree of stenosis severity from 0-97.11% are assessed numerically. Blood is modelled as a shear-thinning, non-Newtonian fluid using the Carreau model. Computational Fluid Dynamics (CFD) analysis is carried out to compute the values of flow parameters like maximum velocity and maximum pressure attained by blood due to stenosis under pulsatile flow. These values are further used to compute the increase in blood pressure and decrease in available blood flow to kidney. The computed available blood flow and secondary hypertension for varying extent of stenosis are mapped by curve fitting technique using MATLAB and a mathematical model is developed. Based on these mathematical models, a quantification tool is developed for tentative prediction of probable availability of blood flow to the kidney and severity of stenosis if secondary hypertension is known.

Matrix-specific protein kinase A signaling regulates p21 activated kinase activation by flow in endothelial cells

PubMed Central

Funk, Steven Daniel; Yurdagul, Arif; Green, Jonette M.; Jhaveri, Krishna A.; Schwartz, Martin Alexander; Orr, A. Wayne

2010-01-01

Rationale Atherosclerosis is initiated by blood flow patterns that activate inflammatory pathways in endothelial cells. Activation of inflammatory signaling by fluid shear stress is highly dependent on the composition of the subendothelial extracellular matrix. The basement membrane proteins laminin and collagen found in normal vessels suppress flow-induced p21 activated kinase (PAK) and NF-κB activation. By contrast, the provisional matrix proteins fibronectin and fibrinogen found in wounded or inflamed vessels support flow-induced PAK and NF-κB activation. PAK mediates both flow-induced permeability and matrix-specific activation of NF-κB. Objective To elucidate the mechanisms regulating matrix-specific PAK activation. Methods and Results We now show that matrix composition does not affect the upstream pathway by which flow activates PAK (integrin activation, Rac). Instead basement membrane proteins enhance flow-induced protein kinase A (PKA) activation, which suppresses PAK. Inhibiting PKA restored flow-induced PAK and NF-κB activation in cells on basement membrane proteins, whereas stimulating PKA inhibited flow-induced activation of inflammatory signaling in cells on fibronectin. PKA suppressed inflammatory signaling through PAK inhibition. Activating PKA by injection of the PGI2 analog iloprost reduced PAK activation and inflammatory gene expression at sites of disturbed flow in vivo, whereas inhibiting PKA by PKI injection enhanced PAK activation and inflammatory gene expression. Inhibiting PAK prevented the enhancement of inflammatory gene expression by PKI. Conclusions Basement membrane proteins inhibit inflammatory signaling in endothelial cells via PKA-dependent inhibition of PAK. PMID:20224042

Disorders of cochlear blood flow.

PubMed

Nakashima, Tsutomu; Naganawa, Shinji; Sone, Michihiko; Tominaga, Mitsuo; Hayashi, Hideo; Yamamoto, Hiroshi; Liu, Xiuli; Nuttall, Alfred L

2003-09-01

The cochlea is principally supplied from the inner ear artery (labyrinthine artery), which is usually a branch of the anterior inferior cerebellar artery. Cochlear blood flow is a function of cochlear perfusion pressure, which is calculated as the difference between mean arterial blood pressure and inner ear fluid pressure. Many otologic disorders such as noise-induced hearing loss, endolymphatic hydrops and presbycusis are suspected of being related to alterations in cochlear blood flow. However, the human cochlea is not easily accessible for investigation because this delicate sensory organ is hidden deep in the temporal bone. In patients with sensorineural hearing loss, magnetic resonance imaging, laser-Doppler flowmetry and ultrasonography have been used to investigate the status of cochlear blood flow. There have been many reports of hearing loss that were considered to be caused by blood flow disturbance in the cochlea. However, direct evidence of blood flow disturbance in the cochlea is still lacking in most of the cases.

Elevated Skin Blood Flow Influences Near Infrared Spectroscopy Measurements During Supine Rest

NASA Technical Reports Server (NTRS)

Lee, Stuart M. C.; Clarke, Mark S. F.

2004-01-01

Near infrared spectroscopy is a non-invasive technique that allows determination of tissue oxygenation/blood flow based on spectrophotometric quantitation of oxy- and deoxyhemoglobin present within a tissue. This technique has gained acceptance as a means of detecting and quantifying changes in tissue blood flow due to physiological perturbation, such as that which is elicited in skeletal muscle during exercise. Since the NIRS technique requires light to penetrate the skin and subcutaneous fat in order to reach the muscle of interest, changes in skin blood flow may alter the NIRS signal in a fashion unrelated to blood flow in the muscle of interest. The aim of this study was to determine the contribution of skin blood flow to the NIRS signal obtained from resting vastus lateralis muscle of the thigh.

Numerical Simulation of Sickle Cell Blood Flow in the Microcirculation

NASA Astrophysics Data System (ADS)

Berger, Stanley A.; Carlson, Brian E.

2001-11-01

A numerical simulation of normal and sickle cell blood flow through the transverse arteriole-capillary microcirculation is carried out to model the dominant mechanisms involved in the onset of vascular stasis in sickle cell disease. The transverse arteriole-capillary network is described by Strahler's network branching method, and the oxygen and blood transport in the capillaries is modeled by a Krogh cylinder analysis utilizing Lighthill's lubrication theory, as developed by Berger and King. Poiseuille's law is used to represent blood flow in the arterioles. Applying this flow and transport model and utilizing volumetric flow continuity at each network bifurcation, a nonlinear system of equations is obtained, which is solved iteratively using a steepest descent algorithm coupled with a Newton solver. Ten different networks are generated and flow results are calculated for normal blood and sickle cell blood without and with precapillary oxygen loss. We find that total volumetric blood flow through the network is greater in the two sickle cell blood simulations than for normal blood owing to the anemia associated with sickle cell disease. The percentage of capillary blockage in the network increases dramatically with decreasing pressure drop across the network in the sickle cell cases while there is no blockage when normal blood flows through simulated networks. It is concluded that, in sickle cell disease, without any vasomotor dilation response to decreasing oxygen concentrations in the blood, capillary blockage will occur in the microvasculature even at average pressure drops across the transverse arteriole-capillary networks.

H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

PubMed Central

Kumar, Gaurav; Chhabra, Aastha; Mishra, Shalini; Kalam, Haroon; Kumar, Dhiraj; Meena, Ramniwas; Ahmad, Yasmin; Bhargava, Kalpana; Prasad, Dipti N.; Sharma, Manish

2016-01-01

Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment. PMID:27211559

Cerebellar blood flow in methylmercury poisoning (Minamata disease).

PubMed

Itoh, K; Korogi, Y; Tomiguchi, S; Takahashi, M; Okajima, T; Sato, H

2001-04-01

We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part.

Validation of thermal techniques for measurement of pelvic organ blood flows in the nonpregnant sheep: comparison with transit-time ultrasonic and microsphere measurements of blood flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Randall, N.J.; Beard, R.W.; Sutherland, I.A.

1988-03-01

Data obtained from a thermal system capable of measuring changes in organ temperature as well as tissue thermal clearance in the uterus and vagina have been compared with blood flow measured continuously with a transit-time ultrasound volume-flow sensor placed around the common internal iliac artery and intermittently with radioactive microspheres in the chronically instrumented nonpregnant sheep. Temperature changes in both the uterus and the vagina correlated well with blood flow changes measured by both techniques after intravenous administration of estradiol or norepinephrine. Thermal clearance did not correlate well with blood flow in the vagina or uterus. These methods may havemore » value in the investigation of blood flow patterns in various clinical situations such as the pelvic pain syndrome and early pregnancy.« less

Blood Cell Interactions and Segregation in Flow

PubMed Central

Munn, Lance L.; Dupin, Michael M.

2009-01-01

For more than a century, pioneering researchers have been using novel experimental and computational approaches to probe the mysteries of blood flow. Thanks to their efforts, we know that blood cells generally prefer to migrate to the axis of flow, that red and white cells segregate in flow, and that cell deformability and their tendency to reversibly aggregate contribute to the non-Newtonian nature of this unique fluid. All of these properties have beneficial physiological consequences, allowing blood to perform a variety of critical functions. Our current understanding of these unusual flow properties of blood have been made possible by the ingenuity and diligence of a number of researchers, including Harry Goldsmith, who developed novel technologies to visualize and quantify the flow of blood at the level of individual cells. Here we summarize efforts in our lab to continue this tradition and to further our understanding of how blood cells interact with each other and with the blood vessel wall. PMID:18188702

Positron emission tomography detects greater blood flow and less blood flow heterogeneity in the exercising skeletal muscles of old compared with young men during fatiguing contractions

PubMed Central

Rudroff, Thorsten; Weissman, Jessica A; Bucci, Marco; Seppänen, Marko; Kaskinoro, Kimmo; Heinonen, Ilkka; Kalliokoski, Kari K

2014-01-01

The purpose of this study was to investigate blood flow and its heterogeneity within and among the knee muscles in five young (26 ± 6 years) and five old (77 ± 6 years) healthy men with similar levels of physical activity while they performed two types of submaximal fatiguing isometric contraction that required either force or position control. Positron emission tomography (PET) and [15O]-H2O were used to determine blood flow at 2 min (beginning) and 12 min (end) after the start of the tasks. Young and old men had similar maximal forces and endurance times for the fatiguing tasks. Although muscle volumes were lower in the older subjects, total muscle blood flow was similar in both groups (young men: 25.8 ± 12.6 ml min−1; old men: 25.1 ± 15.4 ml min−1; age main effect, P = 0.77) as blood flow per unit mass of muscle in the exercising knee extensors was greater in the older (12.5 ± 6.2 ml min−1 (100 g)−1) than the younger (8.6 ± 3.6 ml min−1 (100 g)−1) men (age main effect, P = 0.001). Further, blood flow heterogeneity in the exercising knee extensors was significantly lower in the older (56 ± 27%) than the younger (67 ± 34%) men. Together, these data show that although skeletal muscles are smaller in older subjects, based on the intact neural drive to the muscle and the greater, less heterogeneous blood flow per gram of muscle, old fit muscle achieves adequate exercise hyperaemia. Key points The results of previous studies that attempted to demonstrate the effects of ageing on skeletal muscle blood flow are controversial because these studies used indirect assessments of skeletal muscle blood flow obtained via whole limb blood flow measurements that provide no information on the distribution of blood flow within particular muscles. We used positron emission tomography to measure blood flow per gram of muscle in old and young men with similar levels of physical activity. Resting muscle blood flow was similar in both groups and exercising muscle blood flow was greater and less heterogeneous in the older men. Old and young men achieved similar maximal voluntary contraction forces and endurance times during two types of fatiguing isometric task. These findings indicate that physically active old men have intact neural drive to the muscle and achieve adequate exercise hyperaemia despite the age-induced decrease in their muscle volume. PMID:24247981

Microvascular Branching as a Determinant of Blood Flow by Intravital Particle Imaging Velocimetry

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia; McKay, Terri L.; Vickerman, Mary B.; Wernet, Mark P.; Myers, Jerry G.; Radhakrishnan, Krishnan

2007-01-01

The effects of microvascular branching on blood flow were investigated in vivo by microscopic particle imaging velocimetry (micro-PIV). We use micro-PIV to measure blood flow by tracking red blood cells (RBC) as the moving particles. Velocity flow fields, including flow pulsatility, were analyzed for the first four branching orders of capillaries, postcapillary venules and small veins of the microvascular network within the developing avian yolksac at embryonic day 5 (E5). Increasing volumetric flowrates were obtained from parabolic laminar flow profiles as a function of increasing vessel diameter and branching order. Maximum flow velocities increased approximately twenty-fold as the function of increasing vessel diameter and branching order compared to flow velocities of 100 - 150 micron/sec in the capillaries. Results from our study will be useful for the increased understanding of blood flow within anastomotic, heterogeneous microvascular networks.

Active nitric oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin-mediated nitrite reduction.

PubMed

Nagababu, Enika; Ramasamy, Somasundaram; Abernethy, Darrell R; Rifkind, Joseph M

2003-11-21

Recent studies have generated a great deal of interest in a possible role for red blood cells in the transport of nitric oxide (NO) to the microcirculation and the vascular effect of this nitric oxide in facilitating the flow of blood through the microcirculation. Many questions have, however, been raised regarding such a mechanism. We have instead identified a completely new mechanism to explain the role of red cells in the delivery of NO to the microcirculation. This new mechanism results in the production of NO in the microcirculation where it is needed. Nitrite produced when NO reacts with oxygen in arterial blood is reutilized in the arterioles when the partial pressure of oxygen decreases and the deoxygenated hemoglobin formed reduces the nitrite regenerating NO. Nitrite reduction by hemoglobin results in a major fraction of the NO generated retained in the intermediate state where NO is bound to Hb(III) and in equilibrium with the nitrosonium cation bound to Hb(II). This pool of NO, unlike Hb(II)NO, is weakly bound and can be released from the heme. The instability of Hb(III)NO in oxygen and its displacement when flushed with argon requires that reliable determinations of red blood cell NO must be performed on freshly lysed samples without permitting the sample to be oxygenated. In fresh blood samples Hb(III)NO accounts for 75% of the red cell NO with appreciably higher values in venous blood than arterial blood. These findings confirm that nitrite reduction at reduced oxygen pressures is a major source for red cell NO. The formation and potential release from the red cell of this NO could have a major impact in regulating the flow of blood through the microcirculation.

Regulation of coronary blood flow during exercise.

PubMed

Duncker, Dirk J; Bache, Robert J

2008-07-01

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand: heart rate, myocardial contractility, and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already 70-80% at rest) increase only modestly in most species. In contrast, in the right ventricle, oxygen extraction is lower at rest and increases substantially during exercise, similar to skeletal muscle, suggesting fundamental differences in blood flow regulation between these two cardiac chambers. The increase in heart rate also increases the relative time spent in systole, thereby increasing the net extravascular compressive forces acting on the microvasculature within the wall of the left ventricle, in particular in its subendocardial layers. Hence, appropriate adjustment of coronary vascular resistance is critical for the cardiac response to exercise. Coronary resistance vessel tone results from the culmination of myriad vasodilator and vasoconstrictors influences, including neurohormones and endothelial and myocardial factors. Unraveling of the integrative mechanisms controlling coronary vasodilation in response to exercise has been difficult, in part due to the redundancies in coronary vasomotor control and differences between animal species. Exercise training is associated with adaptations in the coronary microvasculature including increased arteriolar densities and/or diameters, which provide a morphometric basis for the observed increase in peak coronary blood flow rates in exercise-trained animals. In larger animals trained by treadmill exercise, the formation of new capillaries maintains capillary density at a level commensurate with the degree of exercise-induced physiological myocardial hypertrophy. Nevertheless, training alters the distribution of coronary vascular resistance so that more capillaries are recruited, resulting in an increase in the permeability-surface area product without a change in capillary numerical density. Maintenance of alpha- and ss-adrenergic tone in the presence of lower circulating catecholamine levels appears to be due to increased receptor responsiveness to adrenergic stimulation. Exercise training also alters local control of coronary resistance vessels. Thus arterioles exhibit increased myogenic tone, likely due to a calcium-dependent protein kinase C signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, training augments endothelium-dependent vasodilation throughout the coronary microcirculation. This enhanced responsiveness appears to result principally from an increased expression of nitric oxide (NO) synthase. Finally, physical conditioning decreases extravascular compressive forces at rest and at comparable levels of exercise, mainly because of a decrease in heart rate. Impedance to coronary inflow due to an epicardial coronary artery stenosis results in marked redistribution of myocardial blood flow during exercise away from the subendocardium towards the subepicardium. However, in contrast to the traditional view that myocardial ischemia causes maximal microvascular dilation, more recent studies have shown that the coronary microvessels retain some degree of vasodilator reserve during exercise-induced ischemia and remain responsive to vasoconstrictor stimuli. These observations have required reassessment of the principal sites of resistance to blood flow in the microcirculation. A significant fraction of resistance is located in small arteries that are outside the metabolic control of the myocardium but are sensitive to shear and nitrovasodilators. The coronary collateral system embodies a dynamic network of interarterial vessels that can undergo both long- and short-term adjustments that can modulate blood flow to the dependent myocardium. Long-term adjustments including recruitment and growth of collateral vessels in response to arterial occlusion are time dependent and determine the maximum blood flow rates available to the collateral-dependent vascular bed during exercise. Rapid short-term adjustments result from active vasomotor activity of the collateral vessels. Mature coronary collateral vessels are responsive to vasodilators such as nitroglycerin and atrial natriuretic peptide, and to vasoconstrictors such as vasopressin, angiotensin II, and the platelet products serotonin and thromboxane A(2). During exercise, ss-adrenergic activity and endothelium-derived NO and prostanoids exert vasodilator influences on coronary collateral vessels. Importantly, alterations in collateral vasomotor tone, e.g., by exogenous vasopressin, inhibition of endogenous NO or prostanoid production, or increasing local adenosine production can modify collateral conductance, thereby influencing the blood supply to the dependent myocardium. In addition, vasomotor activity in the resistance vessels of the collateral perfused vascular bed can influence the volume and distribution of blood flow within the collateral zone. Finally, there is evidence that vasomotor control of resistance vessels in the normally perfused regions of collateralized hearts is altered, indicating that the vascular adaptations in hearts with a flow-limiting coronary obstruction occur at a global as well as a regional level. Exercise training does not stimulate growth of coronary collateral vessels in the normal heart. However, if exercise produces ischemia, which would be absent or minimal under resting conditions, there is evidence that collateral growth can be enhanced. In addition to ischemia, the pressure gradient between vascular beds, which is a determinant of the flow rate and therefore the shear stress on the collateral vessel endothelium, may also be important in stimulating growth of collateral vessels.

Melanopsin mediates light-dependent relaxation in blood vessels.

PubMed

Sikka, Gautam; Hussmann, G Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K; Koehler, Raymond C; Snyder, Solomon H; Shimoda, Larissa A; Berkowitz, Dan E

2014-12-16

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

Modeling malaria infected cells in microcirculation

NASA Astrophysics Data System (ADS)

Raffiee, Amir Hossein; Dabiri, Sadegh; Motavalizadeh Ardekani, Arezoo

2016-11-01

Plasmodim (P.) falciparum is one of the deadliest types of malaria species that invades healthy red blood cells (RBC) in human blood flow. This parasite develops through 48-hour intra-RBC process leading to significant morphological and mechanical (e.g., stiffening) changes in RBC membrane. These changes have remarkable effects on blood circulation such as increase in flow resistance and obstruction in microcirculation. In this work a computational framework is developed to model RBC suspension in blood flow using front-tracking technique. The present study focuses on blood flow behavior under normal and infected circumstances and predicts changes in blood rheology for different levels of parasitemia and hematocrit. This model allows better understanding of blood flow circulation up to a single cell level and provides us with realistic and deep insight into hematologic diseases such as malaria.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paulson, O.B.; Jarden, J.O.; Godtfredsen, J.

The effect of captopril on cerebral blood flow was studied in five patients with severe congestive heart failure and in five control subjects. Cerebral blood flow was measured by inhalation of /sup 133/xenon and registration of its uptake and washout from the brain by single photon emission computer tomography. In addition, cerebral (internal jugular) venous oxygen tension was determined in the controls. The measurements were made before and 15, 60, and 180 minutes after a single oral dose of captopril (6.25 mg in patients with congestive heart failure and 25 mg in controls). Despite a marked decrease in blood pressure,more » cerebral blood flow increased slightly in the patients with severe congestive heart failure. When a correction was applied to take account of a change in arterial carbon dioxide tension, however, cerebral blood flow was unchanged after captopril administration even in patients with the greatest decrease in blood pressure, in whom a decrease in cerebral blood flow might have been expected. In the controls, blood pressure was little affected by captopril, whereas a slight, but not statistically significant, decrease in cerebral blood flow was observed. The cerebral venous oxygen tension decreased concomitantly.« less

Spiral blood flow in aorta-renal bifurcation models.

PubMed

Javadzadegan, Ashkan; Simmons, Anne; Barber, Tracie

2016-01-01

The presence of a spiral arterial blood flow pattern in humans has been widely accepted. It is believed that this spiral component of the blood flow alters arterial haemodynamics in both positive and negative ways. The purpose of this study was to determine the effect of spiral flow on haemodynamic changes in aorta-renal bifurcations. In this regard, a computational fluid dynamics analysis of pulsatile blood flow was performed in two idealised models of aorta-renal bifurcations with and without flow diverter. The results show that the spirality effect causes a substantial variation in blood velocity distribution, while causing only slight changes in fluid shear stress patterns. The dominant observed effect of spiral flow is on turbulent kinetic energy and flow recirculation zones. As spiral flow intensity increases, the rate of turbulent kinetic energy production decreases, reducing the region of potential damage to red blood cells and endothelial cells. Furthermore, the recirculation zones which form on the cranial sides of the aorta and renal artery shrink in size in the presence of spirality effect; this may lower the rate of atherosclerosis development and progression in the aorta-renal bifurcation. These results indicate that the spiral nature of blood flow has atheroprotective effects in renal arteries and should be taken into consideration in analyses of the aorta and renal arteries.

Vascular smooth muscle cell contractile protein expression is increased through protein kinase G-dependent and -independent pathways by glucose-6-phosphate dehydrogenase inhibition and deficiency.

PubMed

Chettimada, Sukrutha; Joshi, Sachindra Raj; Dhagia, Vidhi; Aiezza, Alessandro; Lincoln, Thomas M; Gupte, Rakhee; Miano, Joseph M; Gupte, Sachin A

2016-10-01

Homeostatic control of vascular smooth muscle cell (VSMC) differentiation is critical for contractile activity and regulation of blood flow. Recently, we reported that precontracted blood vessels are relaxed and the phenotype of VSMC is regulated from a synthetic to contractile state by glucose-6-phosphate dehydrogenase (G6PD) inhibition. In the current study, we investigated whether the increase in the expression of VSMC contractile proteins by inhibition and knockdown of G6PD is mediated through a protein kinase G (PKG)-dependent pathway and whether it regulates blood pressure. We found that the expression of VSMC-restricted contractile proteins, myocardin (MYOCD), and miR-1 and miR-143 are increased by G6PD inhibition or knockdown. Importantly, RNA-sequence analysis of aortic tissue from G6PD-deficient mice revealed uniform increases in VSMC-restricted genes, particularly those regulated by the MYOCD-serum response factor (SRF) switch. Conversely, expression of Krüppel-like factor 4 (KLF4) is decreased by G6PD inhibition. Interestingly, the G6PD inhibition-induced expression of miR-1 and contractile proteins was blocked by Rp-β-phenyl-1,N 2 -etheno-8-bromo-guanosine-3',5'-cyclic monophosphorothioate, a PKG inhibitor. On the other hand, MYOCD and miR-143 levels are increased by G6PD inhibition through a PKG-independent manner. Furthermore, blood pressure was lower in the G6PD-deficient compared with wild-type mice. Therefore, our results suggest that the expression of VSMC contractile proteins induced by G6PD inhibition occurs via PKG1α-dependent and -independent pathways. Copyright © 2016 the American Physiological Society.

Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth

PubMed Central

Julian, Colleen Glyde; Wilson, Megan J.; Lopez, Miriam; Yamashiro, Henry; Tellez, Wilma; Rodriguez, Armando; Bigham, Abigail W.; Shriver, Mark D.; Rodriguez, Carmelo; Vargas, Enrique; Moore, Lorna G.

2009-01-01

The effect of high altitude on reducing birth weight is markedly less in populations of high- (e.g., Andeans) relative to low-altitude origin (e.g., Europeans). Uterine artery (UA) blood flow is greater during pregnancy in Andeans than Europeans at high altitude; however, it is not clear whether such blood flow differences play a causal role in ancestry-associated variations in fetal growth. We tested the hypothesis that greater UA blood flow contributes to the protection of fetal growth afforded by Andean ancestry by comparing UA blood flow and fetal growth throughout pregnancy in 137 Andean or European residents of low (400 m; European n = 28, Andean n = 23) or high (3,100–4,100 m; European n = 51, Andean n = 35) altitude in Bolivia. Blood flow and fetal biometry were assessed by Doppler ultrasound, and maternal ancestry was confirmed, using a panel of 100 ancestry-informative genetic markers (AIMs). At low altitude, there were no ancestry-related differences in the pregnancy-associated rise in UA blood flow, fetal biometry, or birth weight. At high altitude, Andean infants weighed 253 g more than European infants after controlling for gestational age and other known influences. UA blood flow and O2 delivery were twofold greater at 20 wk in Andean than European women at high altitude, and were paralleled by greater fetal size. Moreover, variation in the proportion of Indigenous American ancestry among individual women was positively associated with UA diameter, blood flow, O2 delivery, and fetal head circumference. We concluded that greater UA blood flow protects against hypoxia-associated reductions in fetal growth, consistent with the hypothesis that genetic factors enabled Andeans to achieve a greater pregnancy-associated rise in UA blood flow and O2 delivery than European women at high altitude. PMID:19244584

The influence of gravity on regional lung blood flow in humans: SPECT in the upright and head-down posture.

PubMed

Ax, M; Sanchez-Crespo, A; Lindahl, S G E; Mure, M; Petersson, J

2017-06-01

Previous studies in humans have shown that gravity has little influence on the distribution of lung blood flow while changing posture from supine to prone. This study aimed to evaluate the maximal influence of posture by comparison of regional lung blood flow in the upright and head-down posture in 8 healthy volunteers, using a tilt table. Regional lung blood flow was marked by intravenous injection of macroaggregates of human albumin labeled with 99m Tc or 113m In, in the upright and head-down posture, respectively, during tidal breathing. Both radiotracers remain fixed in the lung after administration. The distribution of radioactivity was mapped using quantitative single photon emission computed tomography (SPECT) corrected for attenuation and scatter. All images were obtained supine during tidal breathing. A shift from upright to the head-down posture caused a clear redistribution of blood flow from basal to apical regions. We conclude that posture plays a role for the distribution of lung blood flow in upright humans, and that the influence of posture, and thereby gravity, is much greater in the upright and head-down posture than in horizontal postures. However, the results of the study demonstrate that lung structure is the main determinant of regional blood flow and gravity is a secondary contributor to the distribution of lung blood flow in the upright and head-down positions. NEW & NOTEWORTHY Using a dual-isotope quantitative SPECT method, we demonstrated that although a shift in posture redistributes blood flow in the direction of gravity, the results are also consistent with lung structure being a greater determinant of regional blood flow than gravity. To our knowledge, this is the first study to use modern imaging methods to quantify the shift in regional lung blood flow in humans at a change between the upright and head-down postures. Copyright © 2017 the American Physiological Society.

Noninvasive blood-flow meter using a curved cannula with zero compensation for an axial flow blood pump.

PubMed

Kosaka, Ryo; Fukuda, Kyohei; Nishida, Masahiro; Maruyama, Osamu; Yamane, Takashi

2013-01-01

In order to monitor the condition of a patient using a left ventricular assist system (LVAS), blood flow should be measured. However, the reliable determination of blood-flow rate has not been established. The purpose of the present study is to develop a noninvasive blood-flow meter using a curved cannula with zero compensation for an axial flow blood pump. The flow meter uses the centrifugal force generated by the flow rate in the curved cannula. Two strain gauges served as sensors. The first gauges were attached to the curved area to measure static pressure and centrifugal force, and the second gauges were attached to straight area to measure static pressure. The flow rate was determined by the differences in output from the two gauges. The zero compensation was constructed based on the consideration that the flow rate could be estimated during the initial driving condition and the ventricular suction condition without using the flow meter. A mock circulation loop was constructed in order to evaluate the measurement performance of the developed flow meter with zero compensation. As a result, the zero compensation worked effectively for the initial calibration and the zero-drift of the measured flow rate. We confirmed that the developed flow meter using a curved cannula with zero compensation was able to accurately measure the flow rate continuously and noninvasively.

Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling.

PubMed

Zhang, M-J; Gu, Y; Wang, H; Zhu, P-F; Liu, X-Y; Wu, J

2016-01-01

Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling

PubMed Central

Xu, Suowen; Ha, Chang Hoon; Wang, Weiye; Xu, Xiangbin; Yin, Meimei; Jin, Felix Q.; Mastrangelo, Michael; Koroleva, Marina; Fujiwara, Keigi; Jin, Zheng Gen

2016-01-01

Endothelial dysfunction, characterized by impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued decrease of NO production, is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Laminar blood flow-mediated specific signaling cascades modulate vascular endothelial cells (ECs) structure and functions. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation in ECs, which in part confers laminar flow atheroprotective action. However, the molecular mechanisms whereby flow regulates Gab1 tyrosine phosphorylation and its downstream signaling events remain unclear. Here we show that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation. Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in flow signaling and HGF signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K decreased flow-, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation in vivo induced by voluntary wheel running was reduced in PECAM1 knockout mice. These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs. PMID:26706435

Impact of chronic hypoxemia on blood flow to the brain, heart, and adrenal gland in the late-gestation IUGR sheep fetus.

PubMed

Poudel, Rajan; McMillen, I Caroline; Dunn, Stacey L; Zhang, Song; Morrison, Janna L

2015-02-01

In the fetus, there is a redistribution of cardiac output in response to acute hypoxemia, to maintain perfusion of key organs, including the brain, heart, and adrenal glands. There may be a similar redistribution of cardiac output in the chronically hypoxemic, intrauterine growth-restricted fetus. Surgical removal of uterine caruncles in nonpregnant ewe results in the restriction of placental growth (PR) and intrauterine growth. Vascular catheters were implanted in seven control and six PR fetal sheep, and blood flow to organs was determined using microspheres. Placental and fetal weight was significantly reduced in the PR group. Despite an increase in the relative brain weight in the PR group, there was no difference in blood flow to the brain between the groups, although PR fetuses had higher blood flow to the temporal lobe. Adrenal blood flow was significantly higher in PR fetuses, and there was a direct relationship between mean gestational PaO2 and blood flow to the adrenal gland. There was no change in blood flow, but a decrease in oxygen and glucose delivery to the heart in the PR fetuses. In another group, there was a decrease in femoral artery blood flow in the PR compared with the Control group, and this may support blood flow changes to the adrenal and temporal lobe. In contrast to the response to acute hypoxemia, these data show that there is a redistribution of blood flow to the adrenals and temporal lobe, but not the heart or whole brain, in chronically hypoxemic PR fetuses in late gestation. Copyright © 2015 the American Physiological Society.

Proteinuria in mice expressing PKB/SGK-resistant GSK3.

PubMed

Boini, Krishna M; Amann, Kerstin; Kempe, Daniela; Alessi, Dario R; Lang, Florian

2009-01-01

SGK1 is critically important for mineralocorticoid/salt-induced glomerular injury. SGK1 inactivates GSK3, which downregulates Snail, a DNA-binding molecule repressing the transcription of nephrin, a protein critically important for the integrity of the glomerular slit membrane. PKB/SGK-dependent GSK regulation is disrupted in mice carrying a mutation, in which the serine in the SGK/PKB-phosphorylation consensus sequence is replaced by alanine. The present study explored whether PKB/SGK-dependent GSK3 regulation influences glomerular proteinuria. Gene-targeted knockin mice with mutated and thus PKB/SGK-resistant GSK3alpha,beta (gsk3(KI)) were compared with their wild-type littermates (gsk3(WT)). gsk3(KI) and gsk3(WT) mice were implanted with DOCA release pellets and offered 1% saline as drinking water for 21 days. Under standard diet, tap water intake and absence of DOCA, urinary flow rate, glomerular filtration rate, and urinary albumin excretion were significantly larger and blood pressure was significantly higher in gsk3(KI) than in gsk3(WT) mice. Within 18 days, DOCA/salt treatment significantly increased fluid intake and urinary flow rate, urinary protein and albumin excretion, and blood pressure in both genotypes but the respective values were significantly higher in gsk3(KI) than in gsk3(WT) mice. Plasma albumin concentration was significantly lower in gsk3(KI) than in gsk3(WT) mice. Proteinuria was abrogated by lowering of blood pressure with alpha(1)-blocker prazosin (1 microg/g body wt) in 8-mo-old mice. According to immunofluorescence, nephrin at 3 and 8 mo and podocin expression at 3 mo were significantly lower in gsk3(KI) than in gsk3(WT) mice. After 18 days, DOCA/salt treatment renal glomerular sclerosis and tubulointerstitial damage were significantly more pronounced in gsk3(KI) than in gsk3(WT) mice. The observations reveal that disruption of PKB/SGK-dependent regulation of GSK3 leads to glomerular injury with proteinuria, which may at least partially be secondary to enhanced blood pressure.

Effects of hyperbaric oxygen on intracranial pressure and cerebral blood flow in experimental cerebral oedema1

PubMed Central

Miller, J. D.; Ledingham, I. McA.; Jennett, W. B.

1970-01-01

Increased intracranial pressure was induced in anaesthetized dogs by application of liquid nitrogen to the dura mater. Intracranial pressure and cerebral blood flow were measured, together with arterial blood pressure and arterial and cerebral venous blood gases. Carbon dioxide was administered intermittently to test the responsiveness of the cerebral circulation, and hyperbaric oxygen was delivered at intervals in a walk-in hyperbaric chamber, pressurized to two atmospheres absolute. Hyperbaric oxygen caused a 30% reduction of intracranial pressure and a 19% reduction of cerebral blood flow in the absence of changes in arterial PCO2 or blood pressure, but only as long as administration of carbon dioxide caused an increase in both intracranial pressure and cerebral blood flow. When carbon dioxide failed to influence intracranial pressure or cerebral blood flow then hyperbaric oxygen had no effect. This unresponsive state was reached at high levels of intracranial pressure. Images PMID:5497875

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burton, H.W.; Stevenson, T.R.; Dysko, R.C.

The transplantation of whole skeletal muscles is a common clinical procedure. Although atypical blood flows have been reported in small free muscle grafts, the blood flow of large neurovascular-intact (NVI) and neurovascular-anastomosed (NVA) grafts have not been measured. Because the maximum specific force (N/cm{sup 2}) of NVI and NVA grafts is 65% that of control muscles, we hypothesized that total and regional blood flows of NVI and NVA grafts at rest and during twitch contractions are significantly lower than lower flows of control muscles. In rabbits, blood flows of control rectus femoris (RFM) muscles and NVI and NVA grafts ofmore » RFM muscles were measured by the radioactive-microsphere technique. Total blood flows in grafts were not different from the control RFM muscle values, except for a higher resting flow in NVA grafts and a lower flow at 3 Hz in NVI grafts. Minor variations in regional flows were observed. We conclude that the operative procedures of grating and repair of blood vessels affect the vascular bed of muscles minimally, and the deficits observed in grafts do not arise from inadequate perfusion.« less

Blood flow dynamic improvement with aneurysm repair detected by a patient-specific model of multiple aortic aneurysms.

PubMed

Sughimoto, Koichi; Takahara, Yoshiharu; Mogi, Kenji; Yamazaki, Kenji; Tsubota, Ken'ichi; Liang, Fuyou; Liu, Hao

2014-05-01

Aortic aneurysms may cause the turbulence of blood flow and result in the energy loss of the blood flow, while grafting of the dilated aorta may ameliorate these hemodynamic disturbances, contributing to the alleviation of the energy efficiency of blood flow delivery. However, evaluating of the energy efficiency of blood flow in an aortic aneurysm has been technically difficult to estimate and not comprehensively understood yet. We devised a multiscale computational biomechanical model, introducing novel flow indices, to investigate a single male patient with multiple aortic aneurysms. Preoperative levels of wall shear stress and oscillatory shear index (OSI) were elevated but declined after staged grafting procedures: OSI decreased from 0.280 to 0.257 (first operation) and 0.221 (second operation). Graftings may strategically counter the loss of efficient blood delivery to improve hemodynamics of the aorta. The energy efficiency of blood flow also improved postoperatively. Novel indices of pulsatile pressure index (PPI) and pulsatile energy loss index (PELI) were evaluated to characterize and quantify energy loss of pulsatile blood flow. Mean PPI decreased from 0.445 to 0.423 (first operation) and 0.359 (second operation), respectively; while the preoperative PELI of 0.986 dropped to 0.820 and 0.831. Graftings contributed not only to ameliorate wall shear stress or oscillatory shear index but also to improve efficient blood flow. This patient-specific modeling will help in analyzing the mechanism of aortic aneurysm formation and may play an important role in quantifying the energy efficiency or loss in blood delivery.

Correlation between blood flow velocity in the middle cerebral artery and EEG during cognitive effort.

PubMed

Szirmai, Imre; Amrein, Ilona; Pálvölgyi, László; Debreczeni, Róbert; Kamondi, Anita

2005-06-01

Cognitive effort modifies blood flow velocity (BFV) in the middle cerebral artery (MCA) which can be recorded by transcranial Doppler sonography (TCD). EEG parameters can be used as indicators of cortical activation. To find temporal and spatial relation between circulatory and bioelectric phenomena, we used combined EEG and TCD measurements during cognitive experiments. Bilateral BFV in the MCAs and 16-channel scalp EEG were recorded during mental arithmetic (MA) and verbal fluency (VF) tests in 12 healthy volunteers. Temporal profile of BFV, heart rate (HR), EEG central frequency (CF), relative alpha power (ralphap), and laterality index (Li) for BFV and CF were statistically analysed. During mental effort, BFV changes showed a reproducible pattern, which was different in MA and VF tests. The Li(BFV) correlated with handedness in 9/12 subjects (75%) in the VF, and in 6/12 subjects (50%) in the MA test. Significant correlation was found between Li(BFV) and Li(CF) during VF (r(2) = 0.69). Li was more indicative for the hemispheric dominance in the VF than in the MA test. During VF test, correlation between HR and BFV was significant in 7/12 subjects. CF and ralphap provide real time assessment of the functional state of the brain tissue during cognition. The correlation between CF and BFV during mental activity suggests a short latency neurogenic and a long latency, supposedly chemical regulation of regional blood flow. Parallel analysis of EEG and flow parameters increases the confidence of determining hemispheric dominance and provides an alternative to study physiological consequences of cognitive processes.

Endothelial dysfunction: methods of assessment and application to hypertension.

PubMed

Nadar, Sunil; Blann, Andrew D; Lip, Gregory Y H

2004-01-01

Interest in the endothelium has been growing in recent decades and the traditional belief that it provides an inert interface between blood and the vessel wall is no longer the case. It is now clear that the endothelium produces a large number of substances that influence blood flow, and it is in turn affected by changes in the blood and the pressure of blood flow. Nitric oxide and endothelins are the major regulators of the vascular tone, and thereby the blood pressure. Historically speaking, concepts such as endothelial cell damage and injury were described in the 1960s and 1970s. More recently, terms such as endothelial cell activation and dysfunction have also been introduced. Although similar in some respects or part of a continuum, these terms differ in the actual effects on the endothelium, and hence differentiation is important. In hypertension, the delicate balance between the vasodilators and the vasoconstrictors is upset, with disturbance in the nitric oxide pathways that lead to a predominance of the vasoconstrictors. This in turn leads to many other changes that take place in the endothelium, setting up a vicious cycle that maintains the high blood pressure. Therefore, accurate assessment of vascular function is important in linking pathophysiology with clinical disease, such as hypertension. Indeed, there are several methods currently employed experimentally to assess endothelial dysfunction. However, the most widely studied and accepted tests are the estimation of plasma markers such as von Willebrand factor, E-selectin and thrombomodulin, and studies of forearm circulation in response to hypoxia induced stress ('flow mediated dilatation', FMD) or intra arterially administered drugs such as acetyl choline. The present document examines these topics. Whilst acknowledging the debt owed to animal models in the study of hypertension, we shall focus on work where primary study is in homo sapiens. A greater appreciation of how endothelial assessments are made in hypertension will have relevance for drug development and future management strategies.

Changes in cochlear blood flow in mice due to loud sound exposure measured with Doppler optical microangiography and laser Doppler flowmetry.

PubMed

Reif, Roberto; Zhi, Zhongwei; Dziennis, Suzan; Nuttall, Alfred L; Wang, Ruikang K

2013-10-01

In this work we determined the contributions of loud sound exposure (LSE) on cochlear blood flow (CoBF) in an in vivo anesthetized mouse model. A broadband noise system (20 kHz bandwidth) with an intensity of 119 dB SPL, was used for a period of one hour to produce a loud sound stimulus. Two techniques were used to study the changes in blood flow, a Doppler optical microangiography (DOMAG) system; which can measure the blood flow within individual cochlear vessels, and a laser Doppler flowmetry (LDF) system; which averages the blood flow within a volume (a hemisphere of ~1.5 mm radius) of tissue. Both systems determined that the blood flow within the cochlea is reduced due to the LSE stimulation.

Effects of hypothyroidism on the skeletal muscle blood flow response to contractions.

PubMed

Bausch, L; McAllister, R M

2003-04-01

Hypothyroidism is associated with impaired blood flow to skeletal muscle under whole body exercise conditions. It is unclear whether poor cardiac and/or vascular function account for blunted muscle blood flow. Our experiment isolated a small group of hindlimb muscles and simulated exercise via tetanic contractions. We hypothesized that muscle blood flow would be attenuated in hypothyroid rats (HYPO) compared with euthyroid rats (EUT). Rats were made hypothyroid by mixing propylthiouracil in their drinking water (2.35 x 10-3 mol/l). Treatment efficacy was evidenced by lower serum T3 concentrations and resting heart rates in HYPO (both P<0.05). In the experimental preparation, isometric contractions of the lower right hindlimb muscles at a rate of 30 tetani/min were induced via sciatic nerve stimulation. Regional blood flows were determined by the radiolabelled microsphere method at three time points: rest, 2 min of contractions and 10 min of contractions. Muscle blood flow generally increased from rest ( approximately 5-10 ml/min per 100 g) through contractions for both groups. Further, blood flow during contractions did not differ between groups for any muscle (eg. red section of gastrocnemius muscle; EUT, 59.9 +/- 14.1; HYPO, 61.1 +/- 15.0; NS between groups). These findings indicate that hypothyroidism does not significantly impair skeletal muscle blood flow when only a small muscle mass is contracting. Our findings suggest that impaired blood flow under whole body exercise is accounted for by inadequate cardiac function rather than abnormal vascular function.

Myocardial Blood Flow Distribution during Ischemia-Induced Coronary Vasodilation in the Unanesthetized Dog

PubMed Central

Bache, Robert J.; Cobb, Frederick R.; Greenfield, Joseph C.

1974-01-01

This study was designed to determine whether coronary vasodilation distal to a flow-limiting coronary artery stenosis could result in redistribution of myocardial blood flow to produce subendocardial underperfusion. Studies were performed in 10 awake dogs chronically prepared with electromagnetic flow-meters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was measured using radionuclide-labeled microspheres, 7-10 μm in diameter, injected into the left atrium. A 5-s coronary artery occlusion was followed by reactive hyperemia with excess inflow of arterial blood effecting 375±20% repayment of the blood flow debt incurred during occlusion. When, after a 5-s occlusion, the occluder was only partially released to hold arterial inflow to the preocclusion level for 20 s before complete release, the delayed reactive hyperemia was augmented (mean blood flow repayment = 610±45%, P < 0.01). This augmentation of the reactive hyperemia suggested that ischemia was continuing during the interval of coronary vasodilation when coronary inflow was at the preocclusion level. Measurements of regional myocardial blood flow demonstrated that endocardial flow slightly exceeded epicardial flow during control conditions. When arterial inflow was limited to the preocclusion rate during vasodilation after a 5-s total coronary artery occlusion, however, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium. Thus, in the presence of a flow-limiting proximal coronary artery stenosis, ischemia-induced coronary vasodilation resulted in redistribution of myocardial blood flow with production of subendocardial ischemia in the presence of a net volume of arterial inflow which, if properly distributed, would have been adequate to prevent myocardial ischemia. Images PMID:4279928

Evaluation of blood flow in human exercising muscle by diffuse correlation spectroscopy: a phantom model study

NASA Astrophysics Data System (ADS)

Nakabayashi, Mikie; Ono, Yumie; Ichinose, Masashi

2018-02-01

Diffuse correlation spectroscopy (DCS) has a potential to noninvasively and quantitatively measure the blood flow in the exercising muscle that could contribute to the fields of sports physiology and medicine. However, the blood flow index (BFI) measured from skin surface by DCS reflects hemodynamic signals from both superficial tissue and muscle layer. Thus, an appropriate calibration technology is required to quantify the absolute blood flow in the muscle layer. We therefore fabricated a realistic two-layer phantom model consisted of a static silicon layer imitating superficial tissue and a dynamic flow layer imitating the muscle blood flow and investigated the relationship between the simulated blood flow rate in the muscle layer and the BFI measured from the surface of the phantom. The absorption coefficient and the reduced scattering coefficient of the forearm were measured from 25 healthy young adults using a time-resolved nearinfrared spectroscopy. The depths of the superficial and muscle layers of forearm were also determined by ultrasound tomography images from 25 healthy young adults. The phantoms were fabricated to satisfy these optical coefficients and anatomical constraints. The simulated blood flow rate were set from 0 mL/ min to 68.7 mL/ min in ten steps, which is considered to cover a physiological range of mean blood flow of the forearm between per 100g of muscle tissue at rest to heavy dynamic handgrip exercise. We found a proportional relationship between the flow rates and BFIs with significant correlation coefficient of R = 0.986. Our results suggest that the absolute exercising muscle blood flow could be estimated by DCS with optimal calibration using phantom models.

Treatment with a Nitric Oxide-Donating NSAID Alleviates Functional Muscle Ischemia in the Mouse Model of Duchenne Muscular Dystrophy

PubMed Central

Thomas, Gail D.; Ye, Jianfeng; De Nardi, Claudio; Monopoli, Angela; Ongini, Ennio; Victor, Ronald G.

2012-01-01

In patients with Duchenne muscular dystrophy (DMD) and the standard mdx mouse model of DMD, dystrophin deficiency causes loss of neuronal nitric oxide synthase (nNOSμ) from the sarcolemma, producing functional ischemia when the muscles are exercised. We asked if functional muscle ischemia would be eliminated and normal blood flow regulation restored by treatment with an exogenous nitric oxide (NO)-donating drug. Beginning at 8 weeks of age, mdx mice were fed a standard diet supplemented with 1% soybean oil alone or in combination with a low (15 mg/kg) or high (45 mg/kg) dose of HCT 1026, a NO-donating nonsteroidal anti-inflammatory agent which has previously been shown to slow disease progression in the mdx model. After 1 month of treatment, vasoconstrictor responses to intra-arterial norepinephrine (NE) were compared in resting and contracting hindlimbs. In untreated mdx mice, the usual effect of muscle contraction to attenuate NE-mediated vasoconstriction was impaired, resulting in functional ischemia: NE evoked similar decreases in femoral blood flow velocity and femoral vascular conductance (FVC) in the contracting compared to resting hindlimbs (ΔFVC contraction/ΔFVC rest = 0.88±0.03). NE-induced functional ischemia was unaffected by low dose HCT 1026 (ΔFVC ratio = 0.92±0.04; P>0.05 vs untreated), but was alleviated by the high dose of the drug (ΔFVC ratio = 0.22±0.03; P<0.05 vs untreated or low dose). The beneficial effect of high dose HCT 1026 was maintained with treatment up to 3 months. The effect of the NO-donating drug HCT 1026 to normalize blood flow regulation in contracting mdx mouse hindlimb muscles suggests a putative novel treatment for DMD. Further translational research is warranted. PMID:23139842