scholarly journals Metabolic Signaling in a Theoretical Model of the Human Retinal Microcirculation

Photonics ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 409
Author(s):  
Julia Arciero ◽  
Brendan Fry ◽  
Amanda Albright ◽  
Grace Mattingly ◽  
Hannah Scanlon ◽  
...  

Impaired blood flow and oxygenation contribute to many ocular pathologies, including glaucoma. Here, a mathematical model is presented that combines an image-based heterogeneous representation of retinal arterioles with a compartmental description of capillaries and venules. The arteriolar model of the human retina is extrapolated from a previous mouse model based on confocal microscopy images. Every terminal arteriole is connected in series to compartments for capillaries and venules, yielding a hybrid model for predicting blood flow and oxygenation throughout the retinal microcirculation. A metabolic wall signal is calculated in each vessel according to blood and tissue oxygen levels. As expected, a higher average metabolic signal is generated in pathways with a lower average oxygen level. The model also predicts a wide range of metabolic signals dependent on oxygen levels and specific network location. For example, for high oxygen demand, a threefold range in metabolic signal is predicted despite nearly identical PO2 levels. This whole-network approach, including a spatially nonuniform structure, is needed to describe the metabolic status of the retina. This model provides the geometric and hemodynamic framework necessary to predict ocular blood flow regulation and will ultimately facilitate early detection and treatment of ischemic and metabolic disorders of the eye.

2020 ◽  
pp. 0271678X2092710
Author(s):  
Jose T Celaya-Alcala ◽  
Grace V Lee ◽  
Amy F Smith ◽  
Bohan Li ◽  
Sava Sakadžić ◽  
...  

Advanced imaging techniques have made available extensive three-dimensional microvascular network structures. Simulation of oxygen transport by such networks requires information on blood flow rates and oxygen levels in vessels crossing boundaries of the imaged region, which is difficult to obtain experimentally. Here, a computational method is presented for estimating blood flow rates, oxygen levels, tissue perfusion and oxygen extraction, based on incomplete boundary conditions. Flow rates in all segments are estimated using a previously published method. Vessels crossing the region boundary are classified as arterioles, capillaries or venules. Oxygen levels in inflowing capillaries are assigned based on values in outflowing capillaries, and similarly for venules. Convective and diffusive oxygen transport is simulated. Contributions of each vessel to perfusion are computed in proportion to the decline in oxygen concentration along that vessel. For a vascular network in the mouse cerebral cortex, predicted tissue oxygen levels show a broad distribution, with 99% of tissue in the range of 20 to 80 mmHg under reference conditions, and steep gradients near arterioles. Perfusion and extraction estimates are consistent with experimental values. A 30% reduction in perfusion or a 30% increase in oxygen demand, relative to reference levels, is predicted to result in tissue hypoxia.


2012 ◽  
Vol 302 (10) ◽  
pp. H1945-H1952 ◽  
Author(s):  
Tuhin K. Roy ◽  
Axel R. Pries ◽  
Timothy W. Secomb

The objective of this study is to compare the effectiveness of metabolic signals derived from erythrocytes and derived from the vessel wall for regulating blood flow in heterogeneous microvascular networks. A theoretical model is used to simulate blood flow, mass transport, and vascular responses. The model accounts for myogenic, shear-dependent, and metabolic flow regulation. Metabolic signals are assumed to be propagated upstream along vessel walls via a conducted response. Arteriolar tone is assumed to depend on the conducted metabolic signal as well as local wall shear stress and wall tension, and arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model shows that under certain conditions metabolic regulation based on wall-derived signals can be more effective in matching perfusion to local oxygen demand relative to regulation based on erythrocyte-derived signals, resulting in higher extraction and lower oxygen deficit. The lower effectiveness of the erythrocyte-derived signal is shown to result in part from the unequal partition of hematocrit at diverging bifurcations, such that low-flow vessels tend to receive a reduced hematocrit and thereby experience a reduced erythrocyte-derived metabolic signal. The model simulations predict that metabolic signals independent of erythrocytes may play an important role in local metabolic regulation of vascular tone and flow distribution in heterogeneous microvessel networks.


2006 ◽  
Vol 41 (3) ◽  
pp. 325-332 ◽  
Author(s):  
Wendong Tao ◽  
Ken J. Hall ◽  
Sheldon J.B. Duff

Abstract Woodwaste leachate is usually acidic, of high oxygen demand, and toxic. To prevent potential adverse impacts of the raw leachate on heterotrophic bacteria and aquatic plants, woodwaste leachate was diluted before discharge to constructed wetlands. This study compared treatment performance among four vegetated surface flow mesocosm wetlands fed with different dilutions of woodwaste leachate over a period of 12 weeks. During another period of 13 weeks, the effluent of a vegetated wetland fed with the raw leachate was further treated in a vegetated wetland and an open wetland. The highest reduction rates for chemical oxygen demand as well as tannin and lignin were achieved in the wetland fed with the raw leachate. The most diluted (6x) woodwaste leachate yielded the lowest reduction rates and highest reduction efficiencies. Up to 47 mg L-1 volatile fatty acids in influent were depleted through wetlands with a hydraulic retention time of 13 d. Vegetation made insignificant performance differences for treatment of woodwaste leachate. Chemical oxygen demand as well as tannin and lignin were further removed through the wetlands in series, though at lower reduction rates. Wetland performance for treatment of woodwaste leachate was likely regulated by dissolved oxygen concentration and availability of bacterial substrates.


2019 ◽  
Vol 89 (1-2) ◽  
pp. 5-12
Author(s):  
Alon Harris ◽  
Brent Siesky ◽  
Amelia Huang ◽  
Thai Do ◽  
Sunu Mathew ◽  
...  

Abstract. Introduction: To investigate the effects of a lutein complex supplementation on ocular blood flow in healthy subjects. Materials and Methods: Sixteen healthy female patients (mean age 36.8 ± 12.1 years) were enrolled in this randomized, placebo-controlled, double-blinded, two-period crossover study. Subjects received daily an oral dose of the lutein with synergistic phytochemicals complex (lutein (10 mg), ascorbic acid (500 mg), tocopherols (364 mg), carnosic acid (2.5 mg), zeaxanthin (2 mg), copper (2 mg), with synergistic effects in reducing pro-inflammatory mediators and cytokines when administered together in combination) and placebo during administration periods. Measurements were taken before and after three-week supplementation periods, with crossover visits separated by a three-week washout period. Data analysis included blood pressure, heart rate, intraocular pressure, visual acuity, contrast sensitivity detection, ocular perfusion pressure, confocal scanning laser Doppler imaging of retinal capillary blood flow, and Doppler imaging of the retrobulbar blood vessels. Results: Lutein complex supplementation produced a statistically significant increase in mean superior retinal capillary blood flow, measured in arbitrary units (60, p = 0.0466) and a decrease in the percentage of avascular area in the superior (−0.029, p = 0.0491) and inferior (−0.023, p = 0.0477) retina, as well as reduced systolic (−4.06, p = 0.0295) and diastolic (−3.69, p = 0.0441) blood pressure measured in mmHg from baseline. Data comparison between the two supplement groups revealed a significant decrease in systemic diastolic blood pressure (change from pre- to post-treatment with lutein supplement (mean (SE)): −3.69 (1.68); change from pre- to post-treatment with placebo: 0.31 (2.57); p = 0.0357) and a significant increase in the peak systolic velocity (measured in cm/sec) in the central retinal artery (change from pre- to post-treatment with lutein supplement: 0.36 (0.19); change from pre- to post-treatment with placebo: −0.33 (0.21); p = 0.0384) with lutein complex supplement; data analyses from the placebo group were all non-significant. Discussion: In healthy participants, oral administration of a lutein phytochemicals complex for three weeks produced increased ocular blood flow biomarkers within retinal vascular beds and reduced diastolic blood pressure compared to placebo.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaku Itoh ◽  
Masato Furuhashi ◽  
Yosuke Ida ◽  
Hiroshi Ohguro ◽  
Megumi Watanabe ◽  
...  

AbstractThe fatty acid-binding protein4 (FABP4) and vascular endothelial growth factor A (VEGFA) play key roles in the metabolic and cardiovascular diseases, and proliferative diabetic retinopathy (PDR), respectively. To identify FABP4 in vitreous fluid in PDR, vitreous concentrations of FABP4 (V-FABP4) and VEGFA (V-VEGFA) from PDR (n = 20) and non-PDR (n = 20) patients were determined by Enzyme-Linked ImmunoSorbent Assays. The data, which included height and weight, systemic blood pressures, several blood biochemical parameters and blood flow at the optic nerve head (ONH) by laser speckle flowgraphy (LSFG) were collected. The levels of V-FABP4 and V-VEGFA were significantly higher in PDR patients than in non-PDR patients (P < 0.001) with a high positive correlation (r = 0.72, P < 0.001) between them. The findings were not affected by body mass index values and the presence of vitreous hemorrhaging. Among the clinical parameters, V-FABP4 correlated positively with creatinine and negatively with age and aspartate transaminase (AST) levels, while V-VEGFA correlated positively with fasting plasma glucose and hemoglobin A1c (HbA1c) levels but negatively with AST. Multiple regression analyses indicated that V-VEGFA, or V-FABP4, AST and HbA1c were independent predictors of V-FABP4 or V-VEGFA, respectively. Both were negatively correlated, but more evident in V-FABP4, with the ONH ocular blood flow.


Author(s):  
David Kuerten ◽  
Matthias Fuest ◽  
Peter Walter ◽  
Babac Mazinani ◽  
Niklas Plange

Abstract Purpose To investigate the relationship of ocular blood flow (via arteriovenous passage time, AVP) and contrast sensitivity (CS) in healthy as well as normal tension glaucoma (NTG) subjects. Design Mono-center comparative prospective trial Methods Twenty-five NTG patients without medication and 25 healthy test participants were recruited. AVP as a measure of retinal blood flow was recorded via fluorescein angiography after CS measurement using digital image analysis. Association of AVP and CS at 4 spatial frequencies (3, 6, 12, and 18 cycles per degree, cpd) was explored with correlation analysis. Results Significant differences regarding AVP, visual field defect, intraocular pressure, and CS measurement were recorded in-between the control group and NTG patients. In NTG patients, AVP was significantly correlated to CS at all investigated cpd (3 cpd: r =  − 0.432, p< 0.03; 6 cpd: r =  − 0.629, p< 0.0005; 12 cpd: r =  − 0.535, p< 0.005; and 18 cpd: r =  − 0.58, p< 0.001), whereas no significant correlations were found in the control group. Visual acuity was significantly correlated to CS at 6, 12, and 18 cpd in NTG patients (r =  − 0.68, p< 0.002; r =  − 0.54, p< .02, and r =  − 0.88, p< 0.0001 respectively), however not in healthy control patients. Age, visual field defect MD, and PSD were not significantly correlated to CS in in the NTG group. MD and PSD were significantly correlated to CS at 3 cpd in healthy eyes (r = 0.55, p< 0.02; r =  − 0.47, p< 0.03). Conclusion Retinal blood flow alterations show a relationship with contrast sensitivity loss in NTG patients. This might reflect a disease-related link between retinal blood flow and visual function. This association was not recorded in healthy volunteers.


1965 ◽  
Vol 209 (4) ◽  
pp. 705-710 ◽  
Author(s):  
Michael D. Klein ◽  
Lawrence S. Cohen ◽  
Richard Gorlin

Myocardial blood flow in human subjects was assessed by comparative simultaneous measurement of krypton 85 radioactive decay from coronary sinus and precordial scintillation. Empirical correction of postclearance background from precordial curves yielded a high degree of correlation between flows derived from the two sampling sites (r = .889, P < .001). Comparison of left and right coronary flows in nine subjects revealed similarity in flow through the two vessels over a wide range of actual flow values (r = .945, P < .001).


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