Calculations of intracapillary oxygen tension distributions in muscle

Eggleton, Charles D.; Vadapalli, Arjun; Roy, Tuhin K.; Popel, Aleksander S.

doi:10.1016/s0025-5564(00)00038-9

Cited by 56 publications

(66 citation statements)

References 32 publications

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“…The model includes both dissolved and hemoglobin-bound oxygen in the capillaries. Transport between the blood and tissue is described using a flux boundary condition with mass transfer coefficients calculated previously using a discrete erythrocyte model (7). For all O2 transport simulations, an array of 19 parallel capillaries was used to represent a typical capillary network (14,15) with the placement of capillaries and relative distribution of hemodynamic parameters (erythrocyte velocity and hematocrit) determined from in vivo measurements in the rat extensor digitorum longus muscle (8).…”

Section: Methodsmentioning

confidence: 99%

Divergent effects of low-O₂tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O₂supply to skeletal muscle

Sprague

Goldman

Bowles

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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ML. Divergent effects of low-O 2 tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O 2 supply to skeletal muscle. Am J Physiol Heart Circ Physiol 299: H566 -H573, 2010. First published May 28, 2010 doi:10.1152/ajpheart.00430.2010.-Erythrocytes release both O 2 and a vasodilator, ATP, when exposed to reduced O2 tension. We investigated the hypothesis that ATP release is impaired in erythrocytes of humans with type 2 diabetes (DM2) and that this defect compromises the ability of these cells to stimulate dilation of resistance vessels. We also determined whether a general vasodilator, the prostacyclin analog iloprost (ILO), stimulates ATP release from healthy human (HH) and DM2 erythrocytes. Finally, we used a computational model to compare the effect on tissue O 2 levels of increases in blood flow directed to areas of increased O2 demand (erythrocyte ATP release) with nondirected increases in flow (ILO). HH erythrocytes, but not DM2 cells, released increased amounts of ATP when exposed to reduced O2 tension (PO2 Ͻ 30 mmHg). In addition, isolated hamster skeletal muscle arterioles dilated in response to similar decreases in extraluminal O 2 when perfused with HH erythrocytes, but not when perfused with DM2 erythrocytes. In contrast, both HH and DM2 erythrocytes released ATP in response to ILO. In the case of DM2 erythrocytes, amounts of ATP released correlated inversely with glycemic control. Modeling revealed that a functional regulatory system that directs blood flow to areas of need (low O2-induced ATP release) provides appropriate levels of tissue oxygenation and that this level of the matching of O2 delivery with demand in skeletal muscle cannot be achieved with a general vasodilator. These results suggest that the inability of erythrocytes to release ATP in response to exposure to low-O2 tension could contribute to the peripheral vascular disease of DM2. muscle blood flow; red blood cells; oxygen delivery; prostacyclin CARDIOVASCULAR DISEASE ACCOUNTS for nearly half of deaths in humans with type 2 diabetes (DM2) (31, 41). It is estimated that in 2010 there will be in excess of 300 million cases of DM2 worldwide making this disease a major public health challenge (4). A significant complication of DM2 is impaired vascular function that contributes to a fourfold increased risk for claudication (4) and as much as a 16-fold increased risk for lower limb amputation (12,30,43). Although individuals with DM2 have an increased incidence of atherosclerosis in largeconduit vessels (4, 30), there is extensive evidence that microvascular circulatory control is also abnormal in humans with DM2 (23,24,27,35). Although direct studies of the skeletal muscle microcirculation are not possible in humans, such studies have been performed in several animal models of diabetes and reveal reduced convective O 2 delivery and diffusive O 2 transport that could contribute to a failure of the skeletal muscle vasculature to deliver appropriate amounts of O 2 to meet metabolic need bot...

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Section: Methodsmentioning

confidence: 99%

Divergent effects of low-O₂tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O₂supply to skeletal muscle

Sprague

Goldman

Bowles

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Intravascular mass transfer coefficients were estimated using a previously developed finite element method (FEM) model of oxygen transport around discrete RBCs flowing single file through a capillary (Eggleton et al, 2000;Vadapalli et al, 2002). Briefly, O 2 transport in and around capillaries containing discrete parachute shaped RBC flowing in the lumen of the capillary was investigated using a FEM.…”

Section: Intravascular Mass Transfer Coefficientsmentioning

confidence: 99%

“…k o and k cell depend on a number of parameters including Hct, O 2 saturation of Hb, and RBC geometry. Expressions for the mass transfer coefficients as a function of Hct and O 2 saturation are acquired using FEM analysis described in detail in previous studies (Eggleton et al, 2000;Vadapalli et al, 2002). When free hemoglobin is present in the plasma the intravascular resistance in O 2 transport will decrease (i.e.…”

Section: Intravascular Transportmentioning

confidence: 99%

A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks

Tsoukias

Goldman

Vadapalli

et al. 2007

Journal of Theoretical Biology

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A detailed computational model is developed to simulate oxygen transport from a three-dimensional microvascular network to surrounding tissue in the presence of hemoglobin-based oxygen carriers. The model accounts for nonlinear O 2 consumption, myoglobin facilitated diffusion and nonlinear oxyhemoglobin dissociation in the RBCs and plasma. It also includes a detailed description of intravascular resistance to O 2 transport and is capable of incorporating realistic three-dimensional microvascular network geometries. Simulations in this study were performed using a computergenerated microvascular architecture that mimics morphometric parameters for the hamster cheek pouch retractor muscle. Theoretical results are presented next to corresponding experimental data. Phosphoresence quenching microscopy provided PO 2 measurements at the arteriolar and venular ends of capillaries in the hamster retractor muscle before and after isovolemic hemodilution with three different hemodilutents; a non-oxygen-carrying plasma expander and two hemoglobin solutions with different oxygen affinities. Sample results in a microvascular network show an enhancement of diffusive shunting between arterioles, venules and capillaries and a decrease in hemoglobin's effectiveness for tissue oxygenation when its affinity for O 2 is decreased. Model simulations suggest that microvascular network anatomy can affect the optimal hemoglobin affinity for reducing tissue hypoxia. O 2 transport simulations in realistic representations of microvascular networks should provide a theoretical framework for choosing optimal parameter values in the development of hemoglobin-based blood-substitutes.

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“…These factors include the myoglobin concentration, the density of lipid-rich subcellular structures (mitochondria and sarcoplasmic reticulum), and the distribution of the sites of oxygen consumption as well as the metabolic demand (Eggleton et al, 2000;Salathe and Gorman, 1997;Sidell, 1998).…”

Section: Scaling Of Maximum Fibre Diametermentioning

confidence: 99%

Rapid evolution of muscle fibre number in post-glacial populations of Arctic charrSalvelinus alpinus

Johnston

Abercromby

Vieira

et al. 2004

Journal of Experimental Biology

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SUMMARY Thingvallavatn, the largest and one of the oldest lakes in Iceland,contains four morphs of Arctic charr Salvelinus alpinus. Dwarf benthic (DB), large benthic (LB), planktivorous (PL) and piscivorous (PI)morphs can be distinguished and differ markedly in head morphology,colouration and maximum fork length (FLmax), reflecting their different resource specialisations within the lake. The four morphs in Thingvallavatn are thought to have been isolated for approximately 10 000 years, since shortly after the end of the last Ice Age. We tested the null hypothesis that the pattern of muscle fibre recruitment was the same in all morphs, reflecting their recent diversification. The cross-sectional areas of fast and slow muscle fibres were measured at 0.7 FL in 46 DB morphs, 23 LB morphs, 24 PL morphs and 22 PI morphs, and the ages of the charr were estimated using sacculus otoliths. In fish larger than 10 g, the maximum fibre diameter scaled with body mass(Mb)0.18 for both fibre types in all morphs. The number of myonuclei per cm fibre length increased with fibre diameter, but was similar between morphs. On average, at 60 μm diameter, there were 2264 nuclei cm–1 in slow fibres and 1126 nuclei cm–1 in fast fibres. The absence of fibres of diameter 4–10 μm was used to determine the FL at which muscle fibre recruitment stopped. Slow fibre number increased with body length in all morphs, scaling with Mb0.45. In contrast, the recruitment of fast muscle fibres continued until a clearly identifiable FL, corresponding to 18–19 cm in the dwarf morph, 24–26 cm in the pelagic morph, 32–33 cm in the large benthic morph and 34–35 cm in the piscivorous morph. The maximum fast fibre number(FNmax) in the dwarf morph (6.97×104) was 56.5% of that found in the LB and PI morphs combined(1.23×105) (P<0.001). Muscle fibre recruitment continued until a threshold body size and occurred at a range of ages,starting at 4+ years in the DB morph and 7+ years in the LB and PI morphs. Our null hypothesis was therefore rejected for fast muscle and it was concluded that the dwarf condition was associated with a reduction in fibre number. We then investigated whether variations in development temperature associated with different spawning sites and periods were responsible for the observed differences in muscle cellularity between morphs. Embryos from the DB, LB and PL morphs were incubated at temperature regimes simulating cold subterranean spring-fed sites (2.2–3.2°C) and the general lakebed(4–7°C). Myogenic progenitor cells (MPCs) were identified using specific antibodies to Paired box protein 7 (Pax 7), Forkhead box protein K1-α (FoxK1-α), MyoD and Myf-5. The progeny showed no evidence of developmental plasticity in the numbers of either MPCs or muscle fibres. Juveniles and adult stages of the DB and LB morphs coexist and have a similar diet. We therefore conclude that the reduction in FNmax in the dwarf morph probably has a genetic basis and that gene networks regulating myotube production are under high selection pressure. To explain these findings we propose that there is an optimal fibre size, and hence number,which varies with maximum body size and reflects a trade-off between diffusional constraints on fibre diameter and the energy costs of maintaining ionic gradients. The predictions of the optimal fibre size hypothesis and its consequences for the adaptive evolution of muscle architecture in fishes are briefly discussed.

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Calculations of intracapillary oxygen tension distributions in muscle

Cited by 56 publications

References 32 publications

Divergent effects of low-O₂tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O₂supply to skeletal muscle

Divergent effects of low-O₂tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O₂supply to skeletal muscle

A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks

Rapid evolution of muscle fibre number in post-glacial populations of Arctic charrSalvelinus alpinus

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Calculations of intracapillary oxygen tension distributions in muscle

Cited by 56 publications

References 32 publications

Divergent effects of low-O2tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O2supply to skeletal muscle

Divergent effects of low-O2tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O2supply to skeletal muscle

A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks

Rapid evolution of muscle fibre number in post-glacial populations of Arctic charrSalvelinus alpinus

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Divergent effects of low-O₂tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O₂supply to skeletal muscle

Divergent effects of low-O₂tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O₂supply to skeletal muscle