Comparison of buffer and red blood cell perfusion of guinea pig heart oxygenation

Myocardial mean myoglobin oxygen saturation was determined spectroscopically from isolated guinea pig hearts perfused with red blood cells during increasing hypoxia. These experiments were undertaken to compare intracellular myoglobin oxygen saturation in isolated hearts perfused with a modest concentration of red blood cells (5% hematocrit) with intracellular myoglobin saturation previously reported from traditional buffer-perfused hearts. Studies were performed at 37 degrees C with hearts paced at 240 beats/min and a constant perfusion pressure of 80 cmH2O. It was found that during perfusion with a hematocrit of 5%, baseline mean myoglobin saturation was 93% compared with 72% during buffer perfusion. Mean myoglobin saturation, ventricular function, and oxygen consumption remained fairly constant for arterial perfusate oxygen tensions above 100 mmHg and then decreased precipitously below 100 mmHg. In contrast, mean myoglobin saturation, ventricular function, and oxygen consumption began to decrease even at high oxygen tension with buffer perfusion. The present results demonstrate that perfusion with 5% red blood cells in the perfusate increases the baseline mean myoglobin saturation and better preserves cardiac function at low oxygen tension relative to buffer perfusion. These results suggest that caution should be used in extrapolating intracellular oxygen dynamics from buffer-perfused to blood-perfused hearts.     

Activity and respiration in the anemone, Metridium senile (L.) exposed to salinity fluctuations

Activity and respiration in the anemone, Metridium senile (L.), were monitored under both constant and fluctuating salinity conditions. During constant exposure to 50% sea water it was found that the animals retracted the tentacles and that the rate of oxygen consumption decreased by ≈50%. The same response was elicited from animals in 100% sea water in a contracted state. Animals exposed to continually fluctuating salinities were found to retract the tentacles, contract the body wall, and produce amounts of mucus during periods of decreasing salinities. These reactions were reversed during exposure to increasing salinity. Oxygen consumption never ceased entirely in animals exposed to dilute sea water and it was found that during declining oxygen tension M. senile regulated its oxygen consumption until the environmental oxygen tension fell to ≈30% saturation.     

The effect of carbon monoxide on haem-facilitated oxygen diffusion

The aim of this paper is to quantify the effect of small quantities of carbon monoxide on the facilitated diffusion of oxygen by haemoglobin in the steady state. It is the first phase in the study of a mathematical model for carbon monoxide poisoning. Here we extend the Wyman model for facilitated diffusion to the case in which there are two ligands. The equations are solved using an asymptotic technique developed by Murray. We obtain accurate analytic approximations for the biologically important quantities of the problem for various percentages of carbon monoxide. These are the concentrations of free oxygen, haemoglobin, oxyhaemoglobin and carboxyhaemoglobin, and hence the saturation of the protein and the facilitated oxygen flux. The major effect of very small quantities of carbon monoxide on the oxygen flux is shown.     

A model study of intracellular oxygen gradients in a myoglobin-containing skeletal muscle fiber.

A theoretical two-dimensional model is used to investigate oxygen gradients in a red skeletal muscle fiber. The model describes the steady state, free and myoglobin-facilitated diffusion of oxygen into a respiring cylindrical muscle fiber cross section. The oxygen tension at the sarcolemma is assumed to vary along the sarcolemma as an approximation to the discrete capillary oxygen supply around the fiber. Maximal oxygen gradients are studied by considering parameters relevant to a maximally-respiring red muscle fiber. The model predicts that angular variations in the oxygen tension imposed at the sarcolemma due to the discrete capillary sources do not penetrate deeply into the fiber over a range of physiological values for myoglobin concentration, diffusion coefficients, number of surrounding capillaries, and oxygen tension level at the sarcolemma. Also, the oxygen tension in the core of the fiber is determined by the average oxygen tension at the sarcolemma. The drop in oxygen tension from fiber periphery to core, however, does depend significantly on the myoglobin concentration, the oxygen tension level at the sarcolemma, and the oxygen and myoglobin diffusivities. This dependence is summarized by calculating the minimum average sarcolemmal oxygen tension for maximal respiration without the development of an intracellular anoxic region. For a myoglobin-rich muscle fiber (0.5 mM myoglobin), the model predicts that maximal oxygen consumption can proceed with a relatively flat (less than 5 mm Hg) oxygen tension drop from fiber periphery to core over a large range for diffusion coefficients.     

Facilitated diffusion: The problem of boundary conditions

Summary The model equations suggested by Wyman (1966) to explain Wittenberg's (1966) experiments on oxygen diffusion facilitated by haemoglobin have been studied by various authors. Kreuzer and Hoofd (1970) use a semi-analytical and numerical approach; Kutchaiet al. (1970) use a purely numerical approach; and Murray (1971) solved the equations analytically. Although the results they obtain are in good agreement with experiment, Kreuzer and Hoofd (1970) and Kutchaiet al. (1970) on the one hand and Murray (1971) and Murray and Wyman (1971) on the other use fundamentally different boundary conditions. This paper reconsiders the problem and proves that these different boundary conditions are equivalent for practically all situations of biological interest. The conclusion is that the simple algebraic result of Murray (1971) suffices for most experimental situations. In the extreme situations where his procedure is not applicable, which are distinguished in the text, the numerical scheme of Kutchaiet al. (1970) is recommended.P. J. M. would like to thank the Science Research Council for their financial support.     

Oxygen diffusion in large single-celled organisms

The functional relationship between the oxygen uptake rate of a spherical, single cell organism and the external oxygen tension is shown to be related to the dependence of the specific oxygen consumption rate, that is, the consumption rate of an infinitesimal volume element of cellular material, on the external oxygen tension. Analytical solutions of the governing steady state diffusion equation are obtained by dividing the system into three regions, an inner region of the sphere in which oxygen consumption rate depends upon oxygen tension, an outer region of the sphere in which oxygen consumption rate is constant (independent of oxygen tension), a nonconsuming membrane over the sphere that offers only resistance to oxygen diffusion, and an infinite region outside the sphere and membrane supplying oxygen to the system. The solutions show the oxygen tension as a function of position inside the spherical cell for a variety of system parameters.     

On the role of myoglobin in muscle respiration

The presence of myoglobin in red muscle tissue has a marked effect on its respiration because it combines reversibly with oxygen and hence gives rise to facilitated diffusion. In this paper we consider the role of myoglobin in facilitating oxygen diffusion and give quantitative results for the oxygen concentration within a typical muscle fibre. Simple expressions are derived for the critical metabolism for the onset of oxygen debt and the growth and size of the region in oxygen debt when the muscle metabolism exceeds this critical value.The general principle, enunciated by Murray &; Wyman (1971), that the macromolecule, myoglobin here, can only function as a carrier if it is unsaturated in some region of the system is again shown to hold.A singular perturbation procedure is used to analyze the model, the effect of which is to reduce the mathematical problem to that of trivially solving a quadratic algebraic equation for the oxygen concentration in the muscle fibre. Physically one condition which causes this phenomenon to be singular in the mathematical sense is that the relaxation times of the myoglobin-oxygen reaction are small compared with the diffusion time of the myoglobin-oxygen complex.     

The effects of dynamic tension and reduced graft size on muscle regeneration in rabbit free muscle grafts.

In a study of 28 adult New Zealand White rabbits, the influence of tension and size on muscle regeneration in tibialis anterior free muscle grafts (without vascular anastomoses) was examined 6 months after transplantation. Three laboratory models were studied: (1) whole dynamic (WD) graft (allowing ankle excursion and, therefore, variable dynamic physiologic tension), (2) whole static (WS) graft (constant, fixed length and, thus, only isometric tension), and (3) longitudinally sliced (reduced radius) dynamic (SD) model. Bilateral orthotopic grafts of the tibialis anterior muscle were performed in 24 rabbits (eight animals in each of the three different model groups). Controls consisted of normal tibialis anterior muscle from four age-matched rabbits. All tibialis anterior muscle grafts were examined histologically (fiber counts) and functionally (determined by in situ contractile properties under maximal stimulation conditions). The WD grafts demonstrated a significantly higher number of regenerated fibers per muscle cross section (4819 +/- 589) than the WS (2221 +/- 603) or SD (1919 +/- 732) grafts. The amount of tetanic tension in the WD grafts was 35 percent of the control and twice as much as that of the WS grafts (WD 1.0 +/- 0.2 kg versus WS 0.5 +/- 0.4 kg; p less than 0.05). The SD grafts produced approximately one-third as much maximum tetanic tension as the WD grafts (0.3 +/- 0.1 kg versus 1.0 +/- 0.2 kg), demonstrating that the amount of recovery was similar in these two dynamic models, since only the longitudinal middle third of the muscle was grafted in the SD model. Free muscle grafts under dynamic tension, which allows excursion, have shown a greater amount of muscle-fiber regeneration and restoration of function compared with a graft with fixed length. The positive effect of dynamic mechanical tension on small autogenous free muscle grafts (without vascular anastomoses) is clinically significant in the reconstruction of facial and hand neuromuscular deficits when blood vessels are not available for reanastomosis. Future studies using the tibialis anterior WD and SD transplant models will strengthen our understanding of the events of spontaneous revascularization and skeletal muscle regeneration.     

The effect of myoglobin-facilitated oxygen transport on the basal metabolism of papillary muscle.

A mathematical model of oxygen diffusion into cylindrical papillary muscles is presented. The model partitions total oxygen flux into its simple and myoglobin-facilitated components. The model includes variable sigmoidal, exponential, or hyperbolic functions relating oxygen partial pressure to both fractional myoglobin saturation and rate of oxygen consumption. The behavior of the model was explored for a variety of saturation- and consumption-concentration relations. Facilitation of oxygen transport by myoglobin was considerable as indexed both by the elevation of oxygen partial pressure on the longitudinal axis of the muscle and by the fraction of total oxygen flux at the muscle center contributed by oxymyoglobin. Despite its facilitation of oxygen flux at the muscle center, myoglobin made only a negligible contribution to the total oxygen consumption averaged over the muscle cross-section. Hence the presence of myoglobin fails to explain either the experimentally determined basal metabolism-muscle radius relation or the stretch effect observed in isolated papillary muscle.     

A computational model of oxygen transport in skeletal muscle for sprouting and splitting modes of angiogenesis

Oxygen transport from capillary networks in muscle at a high oxygen consumption rate was simulated using a computational model to assess the relative efficacies of sprouting and splitting modes of angiogenesis. Efficacy was characterized by the volumetric fraction of hypoxic tissue and overall heterogeneity of oxygen distribution at steady state. Oxygen transport was simulated for a three-dimensional vascular network using parameters for rat extensor digitorum longus (EDL) muscle when oxygen consumption by tissue reached 6, 12, and 18 times basal consumption. First, a control network was generated by using straight non-anastomosed capillaries to establish baseline capillarity. Two networks were then constructed simulating either abluminal lateral sprouting or intraluminal splitting angiogenesis such that capillary surface area was equal in both networks. The sprouting network was constructed by placing anastomosed capillaries between straight capillaries of the control network with a higher probability of placement near hypoxic tissue. The splitting network was constructed by splitting capillaries from the control network into two branches at randomly chosen branching points. Under conditions of moderate oxygen consumption (6 times basal), only minor differences in oxygen delivery resulted between the sprouting and splitting networks. At higher consumption levels (12 and 18 times basal), the splitting network had the lowest volume of hypoxic tissue of the three networks. However, when total blood flow in all three networks was made equal, the sprouting network had the lowest volume of hypoxic tissue. This study also shows that under the steady-state conditions the effect of myoglobin (Mb) on oxygen transport was small.     

Effect of convection in capillaries on oxygen removal from arterioles in striated muscle

Based on experimental data that show the presence of significant oxygen saturation gradients in precapillary arterioles, it has been suggested that the in vivo permeability to oxygen of resting striated muscle may be significantly higher than the corresponding in vitro value obtained in unperfused tissue samples (Popel et al., 1989b, Adv. expl. Med. Biol. 247, 215). The present study performs two analyses to further compare theoretical predictions with experimental data obtained under control conditions and during hemodilution and hemoconcentration. First, it is shown that, in principle, a capillary-perfused tissue layer with a thickness of a few hundred microns is necessary to convectively carry the experimentally determined amount of oxygen released by precapillary arterioles under control and hemodiluted conditions. This capacity to convect oxygen depends strongly on the resting tissue oxygen tension. Second, a more general version of a previous model (Weerappuli & Popel, 1989, J. Biomech. Eng. 111, 24) is used to examine whether changes made in the model parameters within the physiological range of values can explain the experimentally measured flux. The results show that the theoretical predictions can be made compatible with experimental observations if the in vivo permeability of perfused tissue to oxygen is assumed to be one to two orders of magnitude higher than the in vitro value. Furthermore, the predicted in vivo permeability for perfused tissue surrounding an arteriole varies with the arteriolar luminal oxygen tension and flow. This may be due to simplifying approximations made in the model or possible experimental artifacts. Alternatively, it could also be speculated that this variability indicates the flow dependency of the permeability of perfused tissue to oxygen.     

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

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 approximately 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.     

Spatial Variations in Vitreous Oxygen Consumption

We investigated the spatial variation of vitreous oxygen consumption in enucleated porcine eyes. A custom made oxygen source was fabricated that could be localized to either the mid or posterior vitreous cavity and steady state vitreous oxygen tension was measured as a function of distance from the source using a commercially available probe. The reaction rate constant of ascorbate oxidation was estimated ex vivo by measuring the change in oxygen tension over time using vitreous harvested from porcine eyes. Vitreous ascorbate from mid and posterior vitreous was measured spectrophotometrically. When the oxygen source was placed in either the mid-vitreous (N = 6) or the posterior vitreous (N = 6), we measured a statistically significant decrease in vitreous oxygen tension as a function of distance from the oxygen source when compared to control experiments without an oxygen source; (p<0.005 for mid-vitreous and p<0.018 for posterior vitreous at all distances). The mid-vitreous oxygen tension change was significantly different from the posterior vitreous oxygen tension change at 2 and 3mm distances from the respective oxygen source (p<0.001). We also found a statistically significant lower concentration of ascorbate in the mid-vitreous as compared to posterior vitreous (p = 0.02). We determined the reaction rate constant, k = 1.61 M^-1s^-1 ± 0.708 M^-1s^-1 (SE), of the oxidation of ascorbate which was modeled following a second order rate equation. Our data demonstrates that vitreous oxygen consumption is higher in the posterior vitreous compared to the mid-vitreous. We also show spatial variations in vitreous ascorbate concentration.     

Effect of ceruloplasmin on the oxygen tension in muscular tissue of experimental animals]

The polarographic method using platinum electrode has been applied to study the effect of ceruloplasmin (CP) on the oxygen tension (pO2), oxygen saturation rate and rate of oxygen utilization in the muscular tissue of high-leukemic AKR mice, C57BL/6 mice with transplanted Lewis lung carcinoma (3LL) and rats after gamma-irradiation in a dose of 7 Gr. It has been shown that CP in AKR mice improves oxygen saturation of the muscular tissue. This effect is also evident in the case of the marked pO2 decrease in the muscle and its oxygen saturation rate (animals with Lewis lung carcinoma and after gamma-irradiation).     

Oxygen and the Spatial Structure of Microbial Communities

Oxygen has two faces. On one side it is the terminal electron acceptor of aerobic respiration – the most efficient engine of energy metabolism. On the other hand, oxygen is toxic because the reduction of molecular O₂ creates reactive oxygen species such as the superoxide anion, peroxide, and the hydroxyl radical. Probably most prokaryotes, and virtually all eukaryotes, depend on oxygen respiration, and we show that the ambiguous relation to oxygen is both an evolutionary force and a dominating factor driving functional interactions and the spatial structure of microbial communities.We focus on microbial communities that are specialised for life in concentration gradients of oxygen, where they acquire the full panoply of specific requirements from limited ranges of PO₂ , which also support the spatial organisation of microbial communities. Marine and lake sediments provide examples of steep O₂ gradients, which arise because consumption or production of oxygen exceeds transport rates of molecular diffusion. Deep lakes undergo thermal stratification in warm waters, resulting in seasonal anaerobiosis below the thermocline, and lakes with a permanent pycnocline often have permanent anoxic deep water. The oxycline is here biologically similar to sediments, and it harbours similar microbial biota, the main difference being the spatial scale. In sediments, transport is dominated by molecular diffusion, and in the water column, turbulent mixing dominates vertical transport.Cell size determines the minimum requirement of aerobic organisms. For bacteria (and mitochondria), the half‐saturation constant for oxygen uptake ranges within 0.05 – 0.1% atmospheric saturation; for the amoeba Acanthamoeba castellanii it is 0.2%, and for two ciliate species measuring around 150 μm, it is 1‐2 % atmospheric saturation. Protection against O₂ toxicity has an energetic cost that increases with increasing ambient O₂ tension. Oxygen sensing seems universal in aquatic organisms. Many aspects of oxygen sensing are incompletely understood, but the mechanisms seem to be evolutionarily conserved. A simple method of studying oxygen preference in microbes is to identify the preferred oxygen tension accumulating in O₂ gradients. Microorganisms cannot sense the direction of a chemical gradient directly, so they use other devices to orient themselves. Different mechanisms in different prokaryotic and eukaryotic microbes are described. In O₂ gradients, many bacteria and protozoa are vertically distributed according to oxygen tension and they show a very limited range of preferred PO₂. In some pigmented protists the required PO₂ is contingent on light due to photochemically generated reactive oxygen species. In protists that harbour endosymbiotic phototrophs, orientation towards light is mediated through the oxygen production of their photosynthetic symbionts. Oxygen plays a similar role for the distribution of small metazoans (meiofauna) in sediments, but there is little experimental evidence for this. Thus the oxygenated sediments surrounding ventilated animal burrows provide a special habitat for metazoan meiofauna as well as unicellular organisms.     

Oxygen delivery by blood determines the maximal VO2 and work rate during whole body exercise in humans: in silico studies

It has been proposed by Saltin (J Exp Biol 115: 345-354, 1985) that oxygen delivery by blood is limiting for maximal work and oxygen consumption in humans during whole body exercise but not during single-muscle exercise. To test this prediction quantitatively, we developed a static (steady-state) computer model of oxygen transport to and within human skeletal muscle during single-muscle (quadriceps) exercise and whole body (cycling) exercise. The main system fluxes, namely cardiac output and oxygen consumption by muscle, are described as a function of the "primary" parameter: work rate. The model is broadly validated by comparison of computer simulations with various experimental data. In silico studies show that, when all other parameters and system properties are kept constant, an increase in the working muscle mass from 2.5 kg (single quadriceps) to 15 kg (two legs) causes, at some critical work intensity, a drop in oxygen concentration in muscle cells to (very near) zero, and therefore oxygen supply by blood limits maximal oxygen consumption and oxidative ATP production. Therefore, the maximal oxygen consumption per muscle mass is significantly higher during single-muscle exercise than during whole body exercise. The effect is brought about by a distribution of a limited amount of oxygen transported by blood in a greater working muscle mass during whole body exercise.     

Oxygen requirements and mass transfer in hairy-root culture

Oxygen mass transfer in clumps of Atropa belladonna hairy roots was investigated as a function of root density and external flow conditions. Convection was the dominant mechanism for mass transfer into root clumps 3.5 to 5.0 cm in diameter; Peclet numbers inside the clumps ranged from 1.4 x 10(3) to 7.1 x 10(4) for external superficial flow velocities between 0.4 and 1.4 cm s(-1). Local dissolved-oxygen levels and rates of oxygen uptake were measured in aflow chamber and in bubble column and stirred bioreactors. When air was used as oxygen source, intraclump dissolved-oxygen tensions ranged from90% to 100% air saturation at high external flow velocity andlow root density, to less than 20% air saturation in dense root clumps. Specific oxygen-uptake rate declined with increasing root density. When external boundary layers around individual roots were eliminated byforcing liquid through the clumps at superficial velocities between 0.2 and1.0 cm s(-1), internal dissolved-oxygen tension was maintained at 95% to 100% air saturation and rate of oxygen uptake at 1.6 x 10(-6) g g(-1) s(-1) dry weight. Liquid culture of single A. belladonna hairy roots was used to investigate the effect of dissolved-oxygen tensionon root growth and morphology. Total root length and number of root tips increased exponentially at oxygen tensions between 70% and 100%air saturation. Specific growth rate increased with oxygen tension up to 100% air saturation; this result demonstrates that hairy roots aeratedwithout oxygen supplementation are likely to be oxygenlimited. No growth occurred at 50% air saturation. Growth of hairy roots proceeded with an average length per tip of about 1 cm; this value was essentially independent of dissolved-oxygen tension between 70% and 100% air saturation. (c) 1994 John Wiley & Sons, Inc.     

Measuring mitochondrial respiration in intact single muscle fibers

Measurement of mitochondrial function in skeletal muscle is a vital tool for understanding regulation of cellular bioenergetics. Currently, a number of different experimental approaches are employed to quantify mitochondrial function, with each involving either mechanically or chemically induced disruption of cellular membranes. Here, we describe a novel approach that allows for the quantification of substrate-induced mitochondria-driven oxygen consumption in intact single skeletal muscle fibers isolated from adult mice. Specifically, we isolated intact muscle fibers from the flexor digitorum brevis muscle and placed the fibers in culture conditions overnight. We then quantified oxygen consumption rates using a highly sensitive microplate format. Peak oxygen consumption rates were significantly increased by 3.4-fold and 2.9-fold by simultaneous stimulation with the uncoupling agent, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), and/or pyruvate or palmitate exposure, respectively. However, when calculating the total oxygen consumed over the entire treatment, palmitate exposure resulted in significantly more oxygen consumption compared with pyruvate. Further, as proof of principle for the procedure, we isolated fibers from the mdx mouse model, which has known mitochondrial deficits. We found significant reductions in initial and peak oxygen consumption of 51% and 61% compared with fibers isolated from the wild-type (WT) animals, respectively. In addition, we determined that fibers isolated from mdx mice exhibited less total oxygen consumption in response to the FCCP + pyruvate stimulation compared with the WT mice. This novel approach allows the user to make mitochondria-specific measures in a nondisrupted muscle fiber that has been isolated from a whole muscle.     

CHO cell responses to low oxygen: regulation of oxygen consumption and sensitization to oxidative stress

We have investigated the regulation of oxygen consumption and modulation of glutathione levels in CHO-K1 cells under oxygen-limiting conditions. We report here suppression of oxygen consumption and alteration of the supply-dependent relationship as a consequence of prolonged hypoxic or anoxic exposure. The suppression is characterized by an increase in the value of P(o(2)/50) (the oxygen tension at which oxygen consumption is half maximal). Under prolonged anoxia there is also a decrease in the cells' potential to use oxygen. Elevated glucose consumption under low oxygen conditions may contribute to the suppression in respiration. The glutathione concentration remains constant throughout hypoxic exposure but may decrease by as much as 40% under anoxia. The glutathione level in hypoxic and anoxic cells increases by two- and four-fold, respectively, over that of the control cells when exposed to a cytotoxic level of oxygen (93%). This suggests that anoxic and hypoxic exposure sensitizes CHO cells to oxidative stress. (c) 1992 John Wiley & Sons, Inc.     

A computational study of the effect of capillary network anastomoses and tortuosity on oxygen transport

The objective of this study was to investigate the effects of capillary network anastomoses and tortuosity on oxygen transport in skeletal muscle, as well as the importance of muscle fibers in determining the arrangement of parallel capillaries. Countercurrent flow and random capillary blockage (e.g. by white blood cells) were also studied. A general computational model was constructed to simulate oxygen transport from a network of blood vessels within a rectangular volume of tissue. A geometric model of the capillary network structure, based on hexagonally packed muscle fibers, was constructed to produce networks of straight unbranched capillaries, capillaries with anastomoses, and capillaries with tortuosity, in order to examine the effects of these geometric properties. Quantities examined included the tissue oxygen tension and the capillary oxyhemoglobin saturation. The computational model included a two-phase simulation of blood flow. Appropriate parameters were chosen for working hamster cheek-pouch retractor muscle. Our calculations showed that the muscle-fiber geometry was important in reducing oxygen transport heterogeneity, as was countercurrent flow. Tortuosity was found to increase tissue oxygenation, especially when combined with anastomoses. In the absence of tortuosity, anastomoses had little effect on oxygen transport under normal conditions, but significantly improved transport when vessel blockages were present.