scholarly journals Theoretical comparison of wall-derived and erythrocyte-derived mechanisms for metabolic flow regulation in heterogeneous microvascular networks

2012 ◽  
Vol 302 (10) ◽  
pp. H1945-H1952 ◽  
Author(s):  
Tuhin K. Roy ◽  
Axel R. Pries ◽  
Timothy W. Secomb
Keyword(s):  
Blood Flow ◽  
Metabolic Regulation ◽  
Muscle Mechanics ◽  
Oxygen Demand ◽  
Flow Regulation ◽  
Oxygen Deficit ◽  
Low Flow ◽  
Microvascular Networks ◽  
Metabolic Signal ◽  
Arteriolar Tone

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.

scholarly journals Theoretical model of metabolic blood flow regulation: roles of ATP release by red blood cells and conducted responses

2008 ◽  
Vol 295 (4) ◽  
pp. H1562-H1571 ◽  
Author(s):  
Julia C. Arciero ◽  
Brian E. Carlson ◽  
Timothy W. Secomb
Keyword(s):  
Theoretical Model ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Muscle Mechanics ◽  
Atp Release ◽  
Oxygen Demand ◽  
Flow Regulation ◽  
Response Signal ◽  
Arteriolar Tone ◽  
Conducted Response

A proposed mechanism for metabolic flow regulation involves the saturation-dependent release of ATP by red blood cells, which triggers an upstream conducted response signal and arteriolar vasodilation. To analyze this mechanism, a theoretical model is used to simulate the variation of oxygen and ATP levels along a flow pathway of seven representative segments, including two vasoactive arteriolar segments. The conducted response signal is defined by integrating the ATP concentration along the vascular pathway, assuming exponential decay of the signal in the upstream direction with a length constant of ∼1 cm. Arteriolar tone depends on the conducted metabolic signal and on local wall shear stress and wall tension. Arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model predicts that conducted responses stimulated by ATP release in venules and propagated to arterioles can account for increases in perfusion in response to increased oxygen demand that are consistent with experimental findings at low to moderate oxygen consumption rates. Myogenic and shear-dependent responses are found to act in opposition to this mechanism of metabolic flow regulation.

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 ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Demand ◽  
Ocular Blood Flow ◽  
Network Location ◽  
Oxygen Levels ◽  
Wide Range ◽  
In Series ◽  
Retinal Microcirculation ◽  
Metabolic Signal ◽  
High Oxygen Demand

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.

scholarly journals Theoretical predictions of metabolic flow regulation in the retina

2016 ◽  
Vol 1 (2) ◽  
pp. 70-78
Author(s):  
Simone Cassani ◽  
Julia Arciero ◽  
Giovanna Guidoboni ◽  
Brent Siesky ◽  
Alon Harris
Keyword(s):  
Blood Flow ◽  
Oxygen Demand ◽  
Flow Regulation ◽  
Retinal Blood Flow ◽  
Regulatory Mechanisms ◽  
Tissue Oxygen ◽  
Theoretical Predictions ◽  
Health And Disease ◽  
Experimental Findings ◽  
Different Levels

Purpose: This study uses a theoretical model to investigate the response of retinal blood flow to changes in tissue oxygen demand. The study is motivated by the need for a better understanding of metabolic flow regulation mechanisms in health and disease.Methods: A mathematical model is used to calculate retinal blood flow for different levels of tissue oxygen demand in the presence or absence of regulatory mechanisms. The model combines a compartmental view of the retinal vasculature and a Krogh cylinder description for oxygen delivery to retinal tissue.Results: The model predicts asymmetric behavior in response to changes in tissue oxygen demand. When all regulatory mechanisms are active, the model predicts a 6% decrease in perfusion when tissue oxygen demand is decreased by 50% and a 23% increase in perfusion when tissue oxygen demand is increased by 50%. In the absence of metabolic and carbon dioxide responses, the model predicts a constant level of blood flow that does not respond to changes in oxygen demand, suggesting the importance of these two response mechanisms. The model is not able to replicate the increase in oxygen venous saturation that has been observed in some flicker stimulation studies.Conclusions: The increase in blood flow predicted by the model due to an increase in oxygen demand is not in the same proportion as the change in blood flow observed with the same decrease in oxygen demand, suggesting that vascular regulatory mechanisms may respond differently to different levels of oxygen demand. These results might be useful for interpreting clinical and experimental findings in health and disease.

scholarly journals Overview of mathematical modeling of myocardial blood flow regulation

2020 ◽  
Vol 318 (4) ◽  
pp. H966-H975
Author(s):  
Ravi Namani ◽  
Yoram Lanir ◽  
Lik Chuan Lee ◽  
Ghassan S. Kassab
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Oxygen Demand ◽  
Flow Regulation ◽  
Flow Reserve ◽  
Arterial Blood ◽  
Blood Flow Regulation ◽  
Highly Nonlinear ◽  
Coronary Flow Regulation

The oxygen consumption by the heart and its extraction from the coronary arterial blood are the highest among all organs. Any increase in oxygen demand due to a change in heart metabolic activity requires an increase in coronary blood flow. This functional requirement of adjustment of coronary blood flow is mediated by coronary flow regulation to meet the oxygen demand without any discomfort, even under strenuous exercise conditions. The goal of this article is to provide an overview of the theoretical and computational models of coronary flow regulation and to reveal insights into the functioning of a complex physiological system that affects the perfusion requirements of the myocardium. Models for three major control mechanisms of myogenic, flow, and metabolic control are presented. These explain how the flow regulation mechanisms operating over multiple spatial scales from the precapillaries to the large coronary arteries yield the myocardial perfusion characteristics of flow reserve, autoregulation, flow dispersion, and self-similarity. The review not only introduces concepts of coronary blood flow regulation but also presents state-of-the-art advances and their potential to impact the assessment of coronary microvascular dysfunction (CMD), cardiac-coronary coupling in metabolic diseases, and therapies for angina and heart failure. Experimentalists and modelers not trained in these models will have exposure through this review such that the nonintuitive and highly nonlinear behavior of coronary physiology can be understood from a different perspective. This survey highlights knowledge gaps, key challenges, future research directions, and novel paradigms in the modeling of coronary flow regulation.

Microvascular blood flow resistance: role of endothelial surface layer

1997 ◽  
Vol 273 (5) ◽  
pp. H2272-H2279 ◽  
Author(s):  
Axel R. Pries ◽  
Timothy W. Secomb ◽  
Helfried Jacobs ◽  
Markus Sperandio ◽  
Kurt Osterloh ◽  
...  
Keyword(s):  
Blood Flow ◽  
Flow Resistance ◽  
Capillary Flow ◽  
Vessel Diameter ◽  
Low Flow ◽  
Microvascular Blood Flow ◽  
Microvascular Networks ◽  
Flow Rates ◽  
Rat Mesentery ◽  
Endothelial Surface

Observations of blood flow in microvascular networks have shown that the resistance to blood flow is about twice that expected from studies using narrow glass tubes. The goal of the present study was to test the hypothesis that a macromolecular layer (glycocalyx) lining the endothelial surface contributes to blood flow resistance. Changes in flow resistance in microvascular networks of the rat mesentery were observed with microinfusion of enzymes targeted at oligosaccharide side chains in the glycocalyx. Infusion of heparinase resulted in a sustained decrease in estimated flow resistance of 14–21%, hydrodynamically equivalent to a uniform increase of vessel diameter by ∼1 μm. Infusion of neuraminidase led to accumulation of platelets on the endothelium and doubled flow resistance. Additional experiments in untreated vascular networks in which microvascular blood flow was reduced by partial microocclusion of the feeding arteriole showed a substantial increase of flow resistance at low flow rates (average capillary flow velocities < 100 diameters/s). These observations indicate that the glycocalyx has significant hemodynamic relevance that may increase at low flow rates, possibly because of a shear-dependent variation in glycocalyx thickness.

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