Measurement Of Muscle Blood Flow Research Articles

Novel Method to Assess Treatment Effcacy in Preclinical Peripheral Arterial Disease Studies

Background: Peripheral arterial disease (PAD), a condition caused by atherosclerotic narrowing or occlusion of blood vessels in the lower extremities, affects ~200 million adults globally and lacks effective treatment options to improve limb function. Cilostazol is the only approved pharmacological treatment option for PAD patients, but its effect on walking performance is modest and the drug is not widely used clinically. Over the past several decades, numerous therapies (drug, gene, and cell-based) have shown promise in the preclinical setting but failed to achieve primary outcomes in clinical trials. While the failure of therapeutic translation is complex, most preclinical studies have employed perfusion recovery as a primary outcome variable whereas most clinical trials in PAD patients employ the six-minute walk test. Although perfusion is an important contributor to limb function and walking performance, assessing preclinical therapeutics solely via perfusion recovery may be a flawed approach. Objective: To address the need for a more comprehensive method to assess the effcacy of preclinical PAD therapeutics, we aimed to develop a protocol to assess hindlimb function that incorporates assessment of muscle power and perfusion across a six-minute testing period. Methods: To assess muscle contractile performance, the tibialis anterior or plantarflexor muscles were carefully exposed and the distal tendon mounted to the force-length controller (Aurora Scientific) and the muscles were stimulated via the sciatic nerve in anesthetized C57BL6 mice. After obtaining isometric forces, a six-minute functional test was performed using repeated isotonic (shortening) contractions against a submaximal load (30% or 45% of the reference force). Muscle fatigue was measured as a change in power across the testing period. Throughout the test, laser Doppler flowmetry was used to measure muscle blood flow. Hindlimb ischemia was used as an experimental model of PAD. Results: In healthy mice without PAD, the test produced the expected dose-dependent relationship between fatigue and workload with contractions performed at 30% of the reference force having less fatigue compared to 45% of the reference force ( P=0.0051), without a significant difference in muscle blood flow between the conditions. Compared the mice that received a sham surgery, those subjected to hindlimb ischemia displayed significantly lower maximal isometric forces (1514 ± 118 mN vs. 880 ± 85 mN, P=0.0001) and power at 35% maximal force (280 ± 12 vs. 105 ± 46 watts/kg, P=0.0002). Whereas sham mice lost ~25% power across the six-minute test, HLI mice displayed a ~70% loss of power. Regarding muscle blood flow, sham mice increased blood flow ~250% whereas HLI mice were only able to increase blood flow to ~105% ( P<0.001). Conclusions: This newly developed protocol successfully combines isotonic muscle function and limb perfusion assessments in the hindlimb of mice and can detect differences between healthy and PAD mice. Future work is needed to fully evaluate the accuracy and sensitivity of this method to select therapeutics in preclinical PAD models. This study was supported by National Institutes of Health (NIH) grant R01-HL149704 (T.E.R.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Respiratory and locomotor muscle blood flow measurements using near-infrared spectroscopy and indocyanine green dye in health and disease.

Measuring respiratory and locomotor muscle blood flow during exercise is pivotal for understanding the factors limiting exercise tolerance in health and disease. Traditional methods to measure muscle blood flow present limitations for exercise testing. This article reviews a method utilising near-infrared spectroscopy (NIRS) in combination with the light-absorbing tracer indocyanine green dye (ICG) to simultaneously assess respiratory and locomotor muscle blood flow during exercise in health and disease. NIRS provides high spatiotemporal resolution and can detect chromophore concentrations. Intravenously administered ICG binds to albumin and undergoes rapid metabolism, making it suitable for repeated measurements. NIRS-ICG allows calculation of local muscle blood flow based on the rate of ICG accumulation in the muscle over time. Studies presented in this review provide evidence of the technical and clinical validity of the NIRS-ICG method in quantifying respiratory and locomotor muscle blood flow. Over the past decade, use of this method during exercise has provided insights into respiratory and locomotor muscle blood flow competition theory and the effect of ergogenic aids and pharmacological agents on local muscle blood flow distribution in COPD. Originally, arterial blood sampling was required via a photodensitometer, though the method has subsequently been adapted to provide a local muscle blood flow index using venous cannulation. In summary, the significance of the NIRS-ICG method is that it provides a minimally invasive tool to simultaneously assess respiratory and locomotor muscle blood flow at rest and during exercise in health and disease to better appreciate the impact of ergogenic aids or pharmacological treatments.

Acute effect of resistance exercise at different velocities on stiffness and vascularity of the biceps brachii muscle: a preliminary study.

Resistance exercise can be defined as the percentage of maximal strength (%1 repetition maximum) used for a particular exercise. Shear wave elastography (SWE) is a robust and novelty imaging technique that provides information regarding tissue stiffness. Superb microvascular imaging (SMI) is a non-irradiating technique that can provide quantitative measurement of muscle blood flow non-invasively. To compare the acute effects of low- and high-velocity resistance exercise on stiffness and blood flow in the biceps brachii muscle (BBM) using SWE and SMI. This prospective study included 60 healthy men (mean age=28.9 years; age range=26-34 years). BBM stiffness was measured by using SWE at rest, after low- and high-velocity resistance exercise, and muscle blood flow was also evaluated by SMI. Resistance exercise was performed using a dumbbell with a mass adjusted to 70%-80% of one-repetition maximum. The stiffness values increased significantly from resting to high- and low-velocity resistance exercises. There was no significant difference between the elastography values of the BBM after the high- and low-velocity resistance exercise. The blood flow increased significantly from resting to high- and low-velocity resistance exercises. Blood flow increase after low-velocity exercise was significantly higher compared to high-velocity exercise. While muscle stiffness parameters and blood flow significantly increased from resting after both high- and low-velocity resistance exercises, blood flow significantly increased after low-velocity exercise compared to high-velocity exercise. This can mean that metabolic stress, an important trigger for muscle development, is more likely to occur in low-velocity exercise.

Exercise Training Increases Resting Calf Muscle Oxygen Metabolism in Patients with Peripheral Artery Disease.

Exercise training can mitigate symptoms of claudication (walking-induced muscle pain) in patients with peripheral artery disease (PAD). One adaptive response enabling this improvement is enhanced muscle oxygen metabolism. To explore this issue, we used arterial-occlusion diffuse optical spectroscopy (AO-DOS) to measure the effects of exercise training on the metabolic rate of oxygen (MRO2) in resting calf muscle. Additionally, venous-occlusion DOS (VO-DOS) and frequency-domain DOS (FD-DOS) were used to measure muscle blood flow (F) and tissue oxygen saturation (StO2), and resting calf muscle oxygen extraction fraction (OEF) was calculated from MRO2, F, and blood hemoglobin. Lastly, the venous/arterial ratio (γ) of blood monitored by FD-DOS was calculated from OEF and StO2. PAD patients who experience claudication (n = 28) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 months of supervised exercise training. Optical measurements were obtained at baseline and at 3 months in both groups. Resting MRO2, OEF, and F, respectively, increased by 30% (12%, 44%) (p < 0.001), 17% (6%, 45%) (p = 0.003), and 7% (0%, 16%) (p = 0.11), after exercise training (median (interquartile range)). The pre-exercise γ was 0.76 (0.61, 0.89); it decreased by 12% (35%, 6%) after exercise training (p = 0.011). Improvement in exercise performance was associated with a correlative increase in resting OEF (R = 0.45, p = 0.02).

Intra-rater reliability of leg blood flow during dynamic exercise using Doppler ultrasound.

Developing an exercise model that resembles a traditional form of aerobic exercise and facilitates a complete simultaneous assessment of multiple parameters within the oxygen cascade is critically for understanding exercise intolerances in diseased populations. Measurement of muscle blood flow is a crucial component of such a model and previous studies have used invasive procedures to determine blood flow kinetics; however, this may not be appropriate in certain populations. Furthermore, current models utilizing Doppler ultrasound use isolated limb exercise and while these studies have provided useful data, the exercise model does not mimic the whole‐body physiological response to continuous dynamic exercise. Therefore, we aimed to measure common femoral artery blood flow using Doppler ultrasound during continuous dynamic stepping exercise performed at three independent workloads to assess the within day and between‐day reliability for such an exercise modality. We report a within‐session coefficient of variation of 5.8% from three combined workloads and a between‐day coefficient of variation of 12.7%. These values demonstrate acceptable measurement accuracy and support our intention of utilizing this noninvasive exercise model for an integrative assessment of the whole‐body physiological response to exercise in a range of populations.

Measurement of muscle blood flow and O2 uptake via near-infrared spectroscopy using a novel occlusion protocol

We describe here a novel protocol that sequentially combines venous followed by arterial occlusions to determine muscle blood flow and O2 uptake from a single measurement point using near-infrared spectroscopy (NIRS) during handgrip exercise. NIRS data were obtained from the flexor digitorum superficialis (FDS) muscle on the dominant arm of 15 young, healthy adults (3 women; 26 ± 7 years; 78.6 ± 9.1 kg). Participants completed a series of 15-s static handgrip contractions at 20, 40 and 60% of maximal voluntary contraction (MVC) immediately followed by either a: (i) venous occlusion (VO); (ii); arterial occlusion (AO); or venous then arterial occlusion (COMBO). Each condition was repeated 3 times for each exercise-intensity. The concordance correlation coefficient (CCC) and robust linear mixed effects modeling were used to determine measurement agreement between vascular occlusion conditions. FDS muscle blood flow ({dot{text{Q}}}_{{{text{FDS}}}}) and conductance ({text{C}}_{{{text{FDS}}}}) demonstrated strong absolute agreement between VO and COMBO trials from rest up to 60%MVC, as evidenced by high values for CCC (> 0.82) and a linear relationship between conditions that closely approximated the line-of-identity (perfect agreement). Conversely, although FDS muscle O2 uptake ({{dot {text{V}}}}{{text{O}}_{2{text{FDS}}}}) displayed “substantial” to “near perfect” agreement between methods across exercise intensities (i.e., CCC > 0.80), there was a tendency for COMBO trials to underestimate {{dot {text{V}}}}{{text{O}}_{2{text{FDS}}}} by up to 7%. These findings indicate that the COMBO method provides valid estimates of {dot {text{Q}}}_{{text{FDS}}} and, to a slightly lesser extent, {{dot {text{V}}}}{{text{O}}_{2{text{FDS}}}} at rest and during static handgrip exercise up to 60%MVC. Practical implications and suggested improvements of the method are discussed.

Respiratory and locomotor muscle blood flow during exercise in health and chronic obstructive pulmonary disease.

What is the topic of this review? The work presented here focuses mostly on testing the theory of blood flow redistribution from the locomotor to the respiratory muscles during heavy exercise in healthy participants and in patients with COPD. What advances does it highlight? Studies presented and the direct experimental approach to measure muscle blood flow by indocyanine green dye detected by near infrared spectroscopy, show that exercise interferes with respiratory muscle blood flow especially in COPD, but even in healthy. We have developed an indicator-dilution method to measure muscle blood flow at rest and during exercise using the light absorbing tracer indocyanine green dye (ICG) injected as an intravenous bolus, with surface optodes placed over muscles of interest to record the ICG signal by near-infrared spectroscopy. Here we review findings for both quadriceps and intercostal muscle blood flow (measured simultaneously) in trained cyclists and in patients with chronic obstructive pulmonary disease (COPD). During resting hyperpnoea in both athletes and patients, intercostal muscle blood flow increased with ventilation, correlating closely and linearly with the work of breathing, with no change in quadriceps flow. During graded exercise in athletes, intercostal flow at first increased, but then began to fall approaching peak effort. Unexpectedly, in COPD, intercostal muscle blood flow during exercise fell progressively from resting values, contrasting sharply with the response to resting hyperpnoea. During exercise at peak intensity, we found no quadriceps blood flow reduction in favour of the respiratory muscles in either athletes or patients. In COPD at peak exercise, when patients breathed 21% oxygen in helium or 100% oxygen, there was no redistribution of blood flow observed between legs and respiratory muscles in either direction. Evidence of decrease in leg blood flow and increase in respiratory muscle flow was found only when imposing expiratory flow limitation (EFL) during exercise in healthy individuals. However, because EFL caused substantial physiological derangement, lowering arterial oxygen saturation and raising end-tidal and heart rate, these results cannot be projected onto normal exercise.

PL - 031 Skeletal muscle blood flow determination using gold standard invasive arterial input function and non-invasive image-based input function by positron emission tomography (PET)

Objective Skeletal muscle is unique among organs in that its blood flow, thus oxygen supply that is critical for muscular function, can change over a remarkably large range. Compared to the rest, muscle blood flow can increase over 20-fold during intense exercise. Positron emission tomography (PET) and [15O]-H2O tracer provide a unique tool for the direct measurement of muscle blood flow in specific muscle regions. Quantification of PET blood flow requires knowledge of the arterial input function, which is usually provided by arterial blood sampling. However, arterial sampling is an invasive approach requiring arterial cannulation. In the current study, we aimed to explore the analysis and error estimation based on non-invasive, PET image-based input function for skeletal muscle blood flow in PET [15O]-labeled radiowater study.&#x0D; Methods Thirty healthy untrained men volunteered to participate in this study. [15O]-labeled radio water PET perfusion scans were performed at rest and right after cycling exercise. GE Discovery PET-CT scanner was used for image acquisition. The 15O isotope was produced with a Cyclone 3 cyclotron (IBA Molecular, Belgium). After 455 MBq of 15O-H2O was injected intravenously and after 20 seconds, dynamic scanning images were performed in following frames: 6x5 seconds, 12x10 seconds, 7x30 seconds and 12x10 seconds. Arterial blood was sampled continuously from radial artery during imaging for radioactivity with a detector during PET scanning. All the data analysis was performed using all in-house developed programs. Arterial input function was preprocessed with delay correction. Image-based input function was defined based on sum image of dynamic images. Blood flow was calculated using the 1-tissue compartment model, k1 is considered as blood flow without any further correction. All data analysis was performed by Carimas software (http://www.turkupetcentre.fi/carimas).&#x0D; Data analysis was performed in five parts: 1) Modelling data using input function from artery. 2) By defining femoral artery Volume Of Interest (VOI) on PET images. 3) Modelling data using image-based input function. 4) Calculating the correlation for blood flow between artery (blood) input function and image-based input function. 5) Predicted true blood flow was calculated based on correlation based on the initial linear relationship between blood and image-based input functions.&#x0D; Results Skeletal muscle blood flow had a good linear relationship calculated by femoral artery VOI and by arterial (blood) input function (y = 2,9587x - 0,096, R² = 0,8852, p&lt;0.0001).&#x0D; Further, by using the prediction equation obtained by the linear relationship between VOI-determined (femoral) artery blood flow and direct gold standard (radial) artery input function determined blood flow, image-based input function determined blood flow was well predicted using this non-invasive approach (y = 1,1812x + 0,1219, R² = 0,9259, p&lt;0.0001).&#x0D; Conclusions It is concluded that there is a strong linear correlation between gold standard invasive approach and non-invasive image-based approach to measure skeletal muscle blood flow by PET, but if no further corrections are made, image-based approach overestimates correct blood flow. However, this can be corrected by linear prediction equation, suggesting that invasive arterial input function may not always be needed in the future when measuring skeletal muscle blood flow by PET. This will be of benefit particularly for exercise studies.

Reliability of muscle blood flow measurements in orbicularis oculi.

Orbicularis oculi muscle tension and muscle blood flow have been shown to be objective measures of eyestrain during visually demanding activities, such as computer work. In line with this, positive associations between eye-related pain and muscle blood flow in orbicularis oculi have been observed. A hypothesis regarding work situations with cognitive tasks and low-level muscle activity, such as computer work, proposes that muscle pain originates from the blood vessel-nociceptor interactions of the connective tissue of the muscle. Noninvasive muscle blood flow measurements in the orbicularis oculi muscle are preferable to using an invasive technique. The aim of this study was to test reproducibility and stability of muscle blood recordings in orbicularis oculi using photoplethysmography. In the reproducibility tests, 12 subjects were tested twice within 1 to 5 weeks. To study the stability of the method, six of the subjects were randomly selected and tested four more times within 2 to 6 weeks. Test subjects were doing identical visually demanding computer work for 10 minutes in each test. The short-term repeatability of muscle blood flow measurements was considered good, but the stability of blood flow recordings over time in orbicularis oculi was low because of a greater within-subject maximum variability compared with between-subject average variability. Investigators should be aware of the effect of time, possibly attributed to confounding factors such as environmental changes and mental stress, when comparing photoplethysmography muscle blood flow recordings.

Understanding Muscle Energetics in Locomotion

Recent estimates of muscle energy consumption during locomotion, based on computational models and muscle blood flow measurements, demonstrate complex patterns of energy use across the gait cycle, which are further complicated when task demands change. A deeper understanding of muscle energetics in locomotion will benefit from efforts to more tightly integrate muscle-specific approaches with organismal measurements.

Near-infrared spectroscopy and indocyanine green derived blood flow index for noninvasive measurement of muscle perfusion during exercise

Near-infrared spectroscopy (NIRS) with the tracer indocyanine green (ICG) may be used for measuring muscle blood flow (MBF) during exercise, if arterial ICG concentration is measured simultaneously. Although pulse dye densitometry allows for noninvasive measurement of arterial dye concentration, this technique is sensitive to motion and may not be applicable during exercise. The aim of this study was to evaluate a noninvasive blood flow index (BFI), which is derived solely from the muscle ICG concentration curve. In 10 male cyclists 5 mg ICG were injected into an antecubital vein at rest and during cycling at 30, 60, 70, 80, 90, and 100% of previously determined maximal work load. Simultaneously blood was withdrawn through a photodensitometer at 20 ml/min from the radial artery to measure arterial ICG concentration. To measure muscle tissue ICG concentrations, two sets of NIRS optodes were positioned on the skin, one over the left seventh intercostal space and the other over the left vastus lateralis muscle. MBF was calculated from the arterial and muscle concentration data according to Fick's principle. BFI was calculated solely from the muscle concentration curve as ICG concentration difference divided by rise time between 10 and 90% of peak. During exercise mean BFI values changed similarly to MBF in both intercostal and quadriceps muscles and showed excellent correlations with MBF: r = 0.98 and 0.96, respectively. Individual data showed some scattering among BFI and MBF values but still reasonable correlations of BFI with MBF: r = 0.73 and 0.72 for intercostal and quadriceps muscles, respectively. Interobserver variability, as analyzed by Bland-Altman plots, was considerably less for BFI than MBF. These data suggest that BFI can be used for measuring changes in muscle perfusion from rest to maximal exercise. Although absolute blood flow cannot be determined, BFI has the advantages of being essentially noninvasive and having low interobserver variability.

Measuring muscle blood flow: a key link between systemic and regional metabolism

To provide a brief overview of the main techniques to measure muscle blood flow in humans and highlight some of the strengths and weaknesses associated with each technique. Peak muscle blood flow values of 300 ml/min per 100 g are possible in humans during heavy exercise performed with small muscle mass. This value is far higher than that which appears in most textbooks. Accurate and reliable techniques are therefore essential in measuring muscle blood flow. Current invasive techniques commonly used include indicator dilution (thermodilution and dye dilution) and radiolabel tracer washout (e.g. 133Xe washout) methods. Although invasive techniques have provided valuable insight into tissue blood flow, noninvasive techniques such as venous occlusion plethysmography and Doppler ultrasound are frequently used and provide accurate measurements of blood flow. Newer imaging techniques (MRI, positron emission tomography, and contrast-enhanced ultrasonography) promise increased resolution of measurements of local blood flow, including in discrete tissues in which more classical techniques are not able to be used. Muscle blood flow is a key link in the interplay and regulation of systemic and local muscle metabolism. Recognizing the advantages and limitations of each technique is essential to translational researchers studying the effects of nutrition and metabolism on muscle blood flow.

Gender Differences in Brachial Blood Flow during Fatiguing Intermittent Handgrip

Females have been reported to have greater resistance to skeletal muscle fatigue than males. Blood flow, which plays an important role in supplying oxygen and nutrients to working muscles, may play an important role in the mechanisms of gender difference. We hypothesized that females would have greater conduit artery blood flow supplying working muscles than males during intermittent maximal handgrip exercise. Healthy adult (22-31 yr old) males (N = 8) and females (N = 8), lying in a supine position, repeated static maximal voluntary contractions (MVC) with a handgrip device in an intermittent pattern. Mean brachial arterial blood flow (MBABF) was continuously monitored using Doppler ultrasonography during the 5-s muscle-relaxation phase, when intramuscular pressure does not impede measurement of muscle blood flow during the 4-min exercise period, and continuously during the 10-min recovery period. Vascular conductance (VC) was calculated from the MBABF normalized by forearm volume and mean blood pressure (MBP). Females achieved higher relative muscle force (%MVC) than males throughout both the exercise and the recovery periods (P < 0.05); females tended to exhibit smaller declines in muscle force (i.e., less fatigue). Exercise-induced increases in MBABF normalized to forearm volume were greater in females compared with males during the relaxation phases (P < 0.05), during which females also exhibited greater VC than males (P < 0.05). Our findings suggest that the normalized MBABF and VC in females, who experience less muscle fatigue, are greater during intermittent maximal voluntary handgrip exercise.

Control of microvascular oxygen pressures during recovery in rat fast‐twitch muscle of differing oxidative capacity

Whether the speed of recovery of microvascular O(2) pressures (Pmvo(2) ) differs within muscles composed primarily of type II fibres with contrasting oxidative capacity has not been determined. We tested the hypothesis that, following contractions, the recovery of Pmvo(2) would be slower in the white (WG; low oxidative capacity) versus the mixed gastrocnemius (MG; comparatively high oxidative capacity). Radiolabelled microsphere and phosphorescence quenching techniques were used to measure muscle blood flow ( Q, hence O(2) delivery, Q(O2)) and during contractions (1 Hz twitch) at low (LO, 2.5 V) and high intensities (HI, 4.5 V) in rat (n = 15) MG and WG muscle and during subsequent recovery. Following the LO protocol, end-contraction Pmvo(2) was lower in WG (11.6 +/- 0.5 mmHg) than in MG (16.2 +/- 0.6 mmHg; P < 0.05) while, contrary to our hypothesis, the initial rate of change in during recovery ( d P(O2)/dt; MG 0.11 +/- 0.01 mmHg s(-1) and WG 0.06 +/- 0.03 mmHg s(-1)) and mean response time (MRT; MG 110.3 +/- 5.1 s and WG 113.5 +/- 8.4 s, P > 0.05) were not different. In contrast, end-contraction baseline Pmvo(2) was not different following the HI protocol (MG 10.3 +/- 0.6 mmHg and WG 9.2 +/- 0.6 mmHg; P > 0.05) but, in agreement with our hypothesis, d P(O2)/dt was slower (MG 0.07 +/- 0.01 mmHg s(-1) and WG 0.03 +/- 0.003 mmHg s(-1); P < 0.05) and MRT longer (WG 180.8 +/- 4.5 s and MG 115.4 +/- 6.7 s; P < 0.05) in WG versus MG following the HI protocol. These data suggest that following high-intensity, though submaximal, muscle contractions, Pmvo(2) recovers much faster in the more oxidative mixed gastrocnemius than in the less oxidative white gastrocnemius.

Muscle Blood-Flow Dynamics at Exercise Onset

Common approaches to understanding control of muscle blood flow in exercise focus on the contributions of various putative vasoregulatory mechanisms to the magnitude of the steady-state response. The application of systems-control principles offers a unique approach to characterizing and quantifying the non-steady-state adaptation of muscle blood flow with exercise onset. Information gained from this approach provides novel insight into the nature of control mechanisms governing physiological responses to exercise. This review is intended to provide the reader with an understanding of 1) exercise models, methodology for measuring muscle blood flow, and analysis approaches for quantifying muscle blood-flow dynamics; 2) what is currently known about the dynamic response of muscle blood-flow control mechanisms in humans; and 3) the similarities and differences in exercising muscle blood-flow control in the upper versus the lower limbs in humans.

The cost of running uphill: linking organismal and muscle energy use in guinea fowl (Numida meleagris)

Uphill running requires more energy than level running at the same speed, largely due to the additional mechanical work of elevating the body weight. We explored the distribution of energy use among the leg muscles of guinea fowl running on the level and uphill using both organismal energy expenditure (oxygen consumption) and muscle blood flow measurements. We tested each bird under four conditions: (1) rest, (2) a moderate-speed level run at 1.5 m s(-1), (3) an incline run at 1.5 m s(-1) with a 15% gradient and (4) a fast level run at a speed eliciting the same metabolic rate as did running at a 15% gradient at 1.5 m s(-1) (2.28-2.39 m s(-1)). The organismal energy expenditure increased by 30% between the moderate-speed level run and both the fast level run and the incline run, and was matched by a proportional increase in total blood flow to the leg muscles. We found that blood flow increased significantly to nearly all the leg muscles between the moderate-speed level run and the incline run. However, the increase in flow was distributed unevenly across the leg muscles, with just three muscles being responsible for over 50% of the total increase in blood flow during uphill running. Three muscles showed significant increases in blood flow with increased incline but not with an increase in speed. Increasing the volume of active muscle may explain why in a previous study a higher maximal rate of oxygen consumption was measured during uphill running. The majority of the increase in energy expenditure between level and incline running was used in stance-phase muscles. Proximal stance-phase extensor muscles with parallel fibers and short tendons, which have been considered particularly well suited for doing positive work on the center of mass, increased their mass-specific energy use during uphill running significantly more than pinnate stance-phase muscles. This finding provides some evidence for a division of labor among muscles used for mechanical work production based on their muscle-tendon architecture. Nevertheless, 33% of the total increase in energy use (40% of the increase in stance-phase energy use) during uphill running was provided by pinnate stance-phase muscles. Swing-phase muscles also increase their energy expenditure during uphill running, although to a lesser extent than that required by running faster on the level. These results suggest that neither muscle-tendon nor musculoskeletal architecture appear to greatly restrict the ability of muscles to do work during locomotor tasks such as uphill running, and that the added energy cost of running uphill is not solely due to lifting the body center of mass.

Partitioning locomotor energy use among and within muscles Muscle blood flow as a measure of muscle oxygen consumption

Linking the mechanics and energetics of locomotion in vertebrates has been hampered by a lack of information regarding the energy use of individual skeletal muscles in vivo. Here, we present a review of the available data concerning the relationship between the rates of skeletal muscle blood flow and oxygen consumption (V(O2)). In active muscle, during aerobically supported exercise, there is a linear relationship between these variables, irrespective of the muscle fiber type and intensity of exercise through most of the aerobic exercise range. We conclude that the rate of blood flow is the best available indicator of aerobic metabolic rate in multiple individual muscles or regions of muscles during locomotion. The practical considerations of using the injectable microsphere technique to measure muscle blood flow in this context are discussed.

The value of muscle blood-flow measurements in patients with clinically doubtful arterial disease.

The value of muscle blood-flow measurements in patients with clinically doubtful arterial disease.

Muscle blood-flow following insertion of a by-pass vein-graft in femoropopliteal occlusive disease.

Abstract Muscle blood-flow has been measured by the local clearance of 133Xe in 32 patients (34 limbs) following arterial replacement with a by-pass vein-graft for atherosclerotic occlusive disease affecting the femoropopliteal segment. In 27 cases (29 limbs) in which the graft was functioning satisfactorily there was a marked improvement in muscle blood-flow with a return to within normal range in most instances. In 5 patients the graft occluded within 3 months of operation and in these cases there was no significant alteration in the muscle blood-flow following operation. The measurement of muscle blood-flow therefore provided objective corroborative evidence of the success or failure of the procedure. Seventeen of the group had muscle blood-flow measurements carried out at 3-monthly intervals for a year or more after operation. The postoperative flow tended to remain stable throughout this period, and did not show any tendency to return to the preoperative levels as has previously been reported for thrombo-endarterectomy. This lends further support for the view that in reconstructive surgery for femoropopliteal occlusive disease the long-term results are better with by-pass vein-grafts than with thrombo-endarterectomy.

Muscle blood flow in response to concentric muscular activity vs passive venous compression.

To measure muscle blood flow (MBF) using photoplethysmography (PPG) following concentric muscular activity of the leg (active treatment) or passive venous compression (passive treatment) with or without venous obstruction. In study A, blood flow in the anterior tibial muscle was measured in 15 healthy subjects with a mean age of 30 years. In study B, blood flow in the gastrocnemius muscle was measured in nine healthy subjects with a mean age of 34 years. Subjects performed concentric muscular activity in one leg. Passive venous compression by a venous foot pump was applied in the contralateral leg. MBF increased significantly following concentric muscular activity, but not following passive venous compression. MBF decreased in both legs when venous obstruction, induced by a thigh tourniquet, was applied. However, MBF was significantly higher following concentric muscular activity than passive venous compression. We conclude that concentric muscular activity produces higher MBF values than passive venous compression.