Muscle Blood Flow Research Articles

EXPLORING THE ROLE OF SKELETAL MUSCLE MICROVASCULAR BLOOD FLOW IN EXERCISE CAPACITY AMONG INDIVIDUALS WITH CONTROLLED TYPE 2 DIABETES

INTRODUCTION & AIMS The cardiac and macrovascular system is vital for human exercise capacity, yet the microvascular network is primarily responsible for delivering nutrients and oxygen to metabolically active tissues like skeletal muscle. Due to methodological limitations, few studies have investigated the role of muscle microvascular blood flow in determining exercise capacity or intolerance in individuals with chronic conditions such as type 2 diabetes. Our aim was to use modern contrast-enhanced ultrasound to directly measure microvascular blood flow in skeletal muscle at rest and after a maximal treadmill exercise test in individuals with controlled type 2 diabetes. METHODS Fifteen adults with controlled type 2 diabetes (age: 62.5 ± 8.0 years [M ± SD]; BMI: 31.6 ± 6.9 kg/m2; HbA1c: 6.7 ± 0.9%; 13 females and 2 male) attended the laboratory after a 2-hour fast and completed a Modified Bruce treadmill exercise test until exhaustion. Microvascular blood velocity, volume, and flow in the vastus lateralis muscle was assessed at rest, immediately post-exercise, and 30 minutes post-exercise via contrast-enhanced ultrasound during a constant-rate intravenous contrast agent infusion (DEFINITY®). Participants also completed a whole-body dual x-ray absorptiometry scan and a six-minute walk test (6MWT). RESULTS Microvascular blood velocity, volume, and flow increased immediately after exercise (∼230%, ∼79%, and ∼529%, respectively; all p<0.001), and remained elevated above baseline levels 30 minutes post-exercise (∼79%, ∼25%, and ∼139%, respectively; all p≤0.003). Resting and post-exercise skeletal muscle microvascular blood flow measures were not associated with VO2peak (ml/min/kg), time to exhaustion, or six-minute walk distance (all p>0.05). CONCLUSION Muscle microvascular blood flow remains elevated for up to 30 minutes following maximal aerobic exercise in individuals with controlled type 2 diabetes. The lack of association between muscle microvascular blood flow and exercise capacity is not clear but may indicate considerable blood flow redundancy or reserve within the vascular network.

BLUNTED SKELETAL MUSCLE MICROVASCULAR BLOOD FLOW IS A POTENTIAL UNDERLYING MECHANISM FOR EXERCISE INTOLERANCE IN ADULTS WITH ATRIAL FIBRILLATION

INTRODUCTION & AIMS Approximately 45% of adults living with atrial fibrillation (AF) experience exercise intolerance (EI). However, the mechanisms of EI in AF are not well understood. We aimed to determine whether impaired skeletal muscle microvascular blood flow (MBF), not macrovascular, responses to peak exercise is a plausible explanation for EI in adults with AF. METHODS Adults with AF and healthy controls completed a Modified Bruce treadmill protocol to obtain peak oxygen uptake (V̇O2peak). Skeletal muscle microvascular blood volume, velocity, and flow in the vastus lateralis muscle was assessed using contrast enhanced ultrasound. Superficial femoral artery diameter, blood velocity and flow were assessed using 2D and Doppler ultrasound. Vascular measurements were collected at rest, immediately post-exercise, and 30 minutes post-exercise. RESULTS Nine adults with AF (age: 62±5 years, 66% females, BMI: 29.7±4.2 kg/m2, V̇O2peak: 24.3±6.1 mL/kg/min) and seven controls (age: 63±10 years, 57% females, BMI: 26.7±1.7 kg/m2, V̇O2peak: 31.0±7.5 mL/kg/min) participated. One participant was in AF during testing. A significant group x time interaction in skeletal muscle MBF (p=0.04) and near significant interaction in blood volume (capillary recruitment, p=0.08) was observed. Post-hoc analysis revealed adults with AF had a significantly blunted MBF at 30 minutes post-exercise (-1.3 fold versus control, p=0.01) and reduced microvascular blood volume (i.e. capillary recruitment) pre- and 30 minutes post-exercise (-6.6 fold [p=0.01] and -9.4 fold [p=0.01] versus controls). No differences were observed for changes in skeletal muscle microvascular blood velocity, or femoral artery diameter, blood velocity or flow. CONCLUSION Despite similar femoral artery blood flow responses, adults with AF have lower skeletal muscle MBF responses to peak exercise which may be driven by a reduced capillary recruitment in the skeletal muscle. Our findings provide new insight into vascular complications which may partially explain EI in those with AF.

THE ‘OSTEOSTASIS’ AND ITS FIVE PRINCIPLES: APPLICATION IN LIMB LENGTHENING

IntroductionHumans Functions (locomotion, protection of organs, reproduction) require a strong support system (bones). The ‘Osteostasis’ is the ability of maintaining the bone structure, its mechanical characteristics and function. Five principles are required for an efficient bone system:Basic Requirements:1) Stability and 2) Function. Repair System (like house building in desert or sea):3) Roads (vessels), 4) Materials (calories, proteins), 5) Workers (bone cells).Analysis of bone problems through these principles bring to optimised treatments.Materials & MethodsMeasurements (>700 lengthening, 32-year follow-up, Full WB Albizzia/G-Nails FWBAG): Bone-DEXA, WB conditions, muscle, fat, etc.Principle-1. Solid bone replacement with a 100% biocompatible and reliable FWBAG with sports (POD0).Principle-2. Bone, Muscle & neural integrity for function Principle-3. Vascular flow lesions induce non-healing (arteriography). Muscle activity accounts for 90% of bone blood flow, ×10 by sports. Required: Checks (arteriography) and treatments (training)Principle-4. Food (NRV Kcal × 2–3, 20–25% proteins).Principle-5. Maintain bone cells and increase them. Suppress ‘opening’, ‘venting’, ‘drainages’.ResultsPrinciple1. Nail fracture (1.2%), nail dysfunction (0%) with FWBAG.Principle2. Intensive sports preop and from POD0 - Principle3. Increased preop vascular supply & muscle force, postop resistance sports fasten recovery. Wheel-chair or low activity decreases healing.Principle4. 6–9 cm circumference loss (non WB-nails or no proper training); 0 cm circumference loss (gain <10 cm) with intense resistance training + high calory intake. - Principle5. Bone cells preservation (no opening, IM saw, increasing bone cells) allow Healing Index down to 8D/cm.ConclusionsThe ‘5P’ allow reaching treatment targets by optimisation of problem solving, maintaining Osteostasis. What would I like or tolerate for me? How can I reach it? Full WB and sports from POD0 was a target 38 years-ago, still not enforced by most of us. Resistance sports, high-calory intake suppress muscle loss and fasten healing, thanks to muscle blood flow and the ‘5P’.

Aerobic Exercise Training Combined with Local Strength Exercise Restores Muscle Blood Flow and Maximal Aerobic Capacity in Long-Term Hodgkin Lymphoma Survivors.

It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin Lymphoma (HL) survivors. We test the hypothesis that: 1) MBF response during mental stress (MS) is impaired in long-term HL survivors; 2) Aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: Exercise-trained (HLT, n=10) and untrained (HLUT, n=10). Maximal aerobic capacity was evaluated by a cardiopulmonary exercise test and forearm blood flow (FBF) by venous occlusion plethysmography. MS was elicited by Stroop Color Word Test. ET was conducted for four months, three/week for 60 minutes each session. The aerobic exercise intensity corresponded to anaerobic threshold up to 10% below the respiratory compensation point. The strength exercises consisted of 2-3 sets of chest press, pulley and squat exercises, 12-15 repetitions each exercise at 30-50% of the maximal voluntary contraction. Baseline was similar in HL survivors and HC, except peak oxygen consumption (peak VO2, p=0.013) and FBF (p=0.006) that were lower in the HL survivors. FBF responses during MS were lower in HL survivors (p<0.001). ET increased peak VO2 (11.59±3.07%, p=0.002), and FBF at rest (33.74±5.13%, p<0.001) and during MS (24±5.31%, p=0.001). Further analysis showed correlation between the changes in peak VO2 and the changes in FBF during MS (r=0.711, p=0.001). Long-term HL survivors have impaired MBF responses during MS. ET restores MBF responses during MS.

Relationship between Fatigability and Skeletal Muscle Blood Flow in Patients with Type 2 Diabetes

Relationship between Fatigability and Skeletal Muscle Blood Flow in Patients with Type 2 Diabetes

Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice.

Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance; however, the underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) is a small GTPase that plays a critical role in endothelial cell function. Here, we tested the hypothesis that the deletion of endothelial Arf6 will result in systemic insulin resistance. We used mouse models of constitutive endothelial cell-specific Arf6 deletion (Arf6f/- Tie2Cre) and tamoxifen-inducible Arf6 knockout (Arf6f/f Cdh5CreER+). Endothelium-dependent vasodilation was assessed using pressure myography. Metabolic function was assessed using a battery of metabolic assessments including glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamps. We used a fluorescence microsphere-based technique to measure tissue blood flow. Skeletal muscle capillary density was assessed using intravital microscopy. Endothelial Arf6 deletion impaired insulin-stimulated vasodilation in white adipose tissue and skeletal muscle feed arteries. The impairment in vasodilation was primarily due to attenuated insulin-stimulated NO bioavailability but independent of altered acetylcholine-mediated or sodium nitroprusside-mediated vasodilation. Endothelial cell-specific deletion of Arf6 also resulted in systematic insulin resistance in normal chow-fed mice and glucose intolerance in high-fat diet-fed obese mice. The underlying mechanisms of glucose intolerance were reductions in insulin-stimulated blood flow and glucose uptake in the skeletal muscle and were independent of changes in capillary density or vascular permeability. Results from this study support the conclusion that endothelial Arf6 signaling is essential for maintaining insulin sensitivity. Reduced expression of endothelial Arf6 impairs insulin-mediated vasodilation and results in systemic insulin resistance. These results have therapeutic implications for diseases that are associated with endothelial cell dysfunction and insulin resistance such as diabetes.

Impaired muscle oxygenation despite normal pulmonary function in type 2 diabetes without complications.

Long-term hyperglycemia in individuals with type 2 diabetes (T2D) can detrimentally impact pulmonary function and muscle oxygenation. As a result, these factors can impede the body's adaptation to physical exertion. We aimed to evaluate the oxygen pathway during maximal exercise among overweight/obese individuals with type 2 diabetes free from complications, in comparison with a group of matched overweight/obese individuals without diabetes, specifically concentrating on the effects on pulmonary function and muscle oxygenation. Fifteen overweight/obese adults with type 2 diabetes [glycated hemoglobin (HbA1c) = 8.3 ± 1.2%] and 15 matched overweight/obese adults without diabetes underwent pre- and post exercise lung function assessment. A maximal incremental exercise test was conducted, monitoring muscle oxygenation using near-infrared spectroscopy and collecting arterial blood gas samples. Both groups exhibited normal lung volumes at rest and after exercise. Spirometric lung function did not significantly differ pre- and post exercise in either group. During maximal exercise, the type 2 diabetes group showed significantly lower augmentation in total hemoglobin and deoxygenated hemoglobin compared with the control group. Despite comparable usual physical activity levels and comparable heart rates at exhaustion, the type 2 diabetes group had a lower peak oxygen consumption than controls. No significant differences were found in arterial blood gas analyses ([Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]) between the groups. Individuals with type 2 diabetes free from complications displayed normal pulmonary function at rest and post exercise. However, impaired skeletal muscle oxygenation during exercise, resulting from reduced limb blood volume and altered muscle deoxygenation, may contribute to the lower V̇o2peak observed in this population.NEW & NOTEWORTHY Individuals with type 2 diabetes free from micro- and macrovascular complications have normal resting pulmonary function, but their V̇o2peak is impaired due to poor skeletal muscle oxygenation during exercise. Tailoring exercise regimes for this population should prioritize interventions aimed at enhancing muscle oxygenation and blood flow improvement.

Blood oxygen transport and depletion in diving emperor penguins.

Oxygen store management underlies dive performance and is dependent on the slow heart rate and peripheral vasoconstriction of the dive response to control tissue blood flow and oxygen uptake. Prior research has revealed two major patterns of muscle myoglobin saturation profiles during dives of emperor penguins. In Type A profiles, myoglobin desaturated rapidly, consistent with minimal muscle blood flow and low tissue oxygen uptake. Type B profiles, with fluctuating and slower declines in myoglobin saturation, were consistent with variable tissue blood flow patterns and tissue oxygen uptake during dives. We examined arterial and venous blood oxygen profiles to evaluate blood oxygen extraction and found two primary patterns of venous hemoglobin desaturation that complemented corresponding myoglobin saturation profiles. Type A venous profiles had a hemoglobin saturation that (a) increased/plateaued for most of a dive's duration, (b) only declined during the latter stages of ascent, and (c) often became arterialized [arterio-venous (a-v) shunting]. In Type B venous profiles, variable but progressive hemoglobin desaturation profiles were interrupted by inflections in the profile that were consistent with fluctuating tissue blood flow and oxygen uptake. End-of-dive saturation of arterial and Type A venous hemoglobin saturation profiles were not significantly different, but did differ from those of Type B venous profiles. These findings provide further support that the dive response of emperor penguins is a spectrum of cardiac and vascular components (including a-v shunting) that are dependent on the nature and demands of a given dive and even of a given segment of a dive.

Differential changes in blood flow and oxygen utilization in active muscles between voluntary exercise and electrical muscle stimulation in young adults.

The physiological effects on blood flow and oxygen utilization in active muscles during and after involuntary contraction triggered by electrical muscle stimulation (EMS) remain unclear, particularly compared with those elicited by voluntary (VOL) contractions. Therefore, we used diffuse correlation and near-infrared spectroscopy (DCS-NIRS) to compare changes in local muscle blood flow and oxygen consumption during and after these two types of muscle contractions in humans. Overall, 24 healthy young adults participated in the study, and data were successfully obtained from 17 of them. Intermittent (2-s contraction, 2-s relaxation) isometric ankle dorsiflexion with a target tension of 20% of maximal VOL contraction was performed by EMS or VOL for 2 min, followed by a 6-min recovery period. DCS-NIRS probes were placed on the tibialis anterior muscle, and relative changes in local tissue blood flow index (rBFI), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rMRO2) were continuously derived. EMS induced more significant increases in rOEF and rMRO2 than VOL exercise but a comparable increase in rBFI. After EMS, rBFI and rMRO2 decreased more slowly than after VOL and remained significantly higher until the end of the recovery period. We concluded that EMS augments oxygen consumption in contracting muscles by enhancing oxygen extraction while increasing oxygen delivery at a rate similar to the VOL exercise. Under the conditions examined in this study, EMS demonstrated a more pronounced and/or prolonged enhancement in local muscle perfusion and aerobic metabolism compared with VOL exercise in healthy participants.

Association between peripheral and respiratory muscle strength and gait speed in the elderly is not mediated by peripheral muscle blood flow

BackgroundThe aging process affects different systems, including the musculoskeletal and respiratory systems. Both systems seem to be interconnected in relation to functional capacity deterioration in the elderly. Therefore, this study aimed to evaluate the association between peripheral and respiratory muscle strength with gait speed and its possible mediation by leg muscle blood flow (LBF) in the elderly. MethodsPeople aged over 65 years, of both sexes and clinically stable were evaluated. Gait speed was evaluated by the 4.6 m walking test. Maximal inspiratory pressure (MIP) and expiratory pressure (MEP) by manuvacuometry, Handgrip strength by a dynamometer (Jamar®) and LBF by venous occlusion plethysmography. ResultsWe included 110 patients with mean age 76.9 ± 7.2 years, 56 (50.9 %) were women, 72 (67.9 %) were classified as frail by Fried criteria and 22 (20.0 %) reported the regular practice of exercise. Baseline mean values of MIP was 59.5 ± 23.8 and MEP 68.2 ± 23.8. The median gait speed was 0.88 m/s, handgrip strength 19.5 Kg/f and LBF 2.7 ml/min/100 ml. Further analysis showed a significant association between gait speed and handgrip strength with MIP (p = 0.005, p = 0.013, respectively). However, no mediation by LBF were found. ConclusionThere is a strong association between gait speed and handgrip strength with MIP without mediation by LBF.

DCS blood flow index underestimates skeletal muscle perfusion in vivo: rationale and early evidence for the NIRS-DCS perfusion index.

Diffuse correlation spectroscopy (DCS) permits non-invasive assessment of skeletal muscle blood flow but may misestimate changes in muscle perfusion. We aimed to highlight recent evidence that DCS blood flow index (BFI) misestimates changes in muscle blood flow during physiological perturbation and to introduce a novel approach that adjusts BFI for estimated changes in vasodilation. We measured changes in muscle BFI during quadriceps and forearm exercises using DCS, the latter of which were adjusted for estimated changes in microvascular flow area and then compared to Doppler ultrasound in the brachial artery. Then, we compared adjusted BFI- and arterial spin labeling (ASL) MRI measures of gastrocnemius blood flow during reactive hyperemia and plantar flexion exercise. We observed little-to-no change in quadriceps BFI during maximal-effort exercise. Similarly, forearm BFI was modestly increased during handgrip exercise, but the magnitude was significantly lower than measured by Doppler ultrasound in the brachial artery. However, this difference was ameliorated after adjusting BFI for estimated changes in microvascular flow area. Similar observations were also observed in the gastrocnemius when directly comparing the adjusted BFI values to ASL-MRI. Adjusting BFI for estimated changes in microvascular flow area may improve DCS estimates of muscle blood flow, but further study is needed to validate these methods moving forward.

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.

2019 Association of Bradykinin receptor 2 variants with physical performance and muscle mass: findings from the LACE sarcopenia trial

Abstract Introduction The kinin-kallikrein system has been implicated in muscle performance: bradykinin promotes glucose uptake and blood flow in muscle through bradykinin receptor 2 (BDKRB2). BDKRB2 variants include rs1799722 and rs5810761, where the T and -9 alleles respectively have associated with increased transcriptional rates and were overrepresented in endurance athletes. However, these variants have rarely been studied among older people or those with sarcopenia. Methods The Leucine and ACE inhibitor (ACE) trial enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants’ blood samples had DNA extracted and were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq (and visualised through 4% agarose gel electrophoresis). The differences in genotypes for each variant against physical performance measures (e.g. six-minute walk distance [6MWD]) was calculated using t-tests or Mann-Whitney tests where appropriate. Genotypes were also tested for Hardy-Weinberg equilibrium (HWE) using Chi-squared test. Results Data from 136 individuals were included in the analysis. For rs1799722, the genotype frequency (TT: 17, CC: 48, CT: 71) remained in HWE (p=0.248). No difference between TT and CC/CT group was seen for 6MWD, grip strength or SPPB. Among men, the TT genotype had greater 6MWD compared to CC/CT (400m vs 312m, p=0.007), and also greater leg muscle mass (17.6kg vs 15.3kg, p =0.005), but no difference was noted in women. For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) also remained in HWE (p=0.269). No difference between -9-9 and +9+9/+9-9 was seen for 6MWD, grip strength or SPPB. In men, but not women, -9-9 genotype had reduced arm fat baseline (1.85kg vs 2.72kg; p=0.005). Conclusion Among men, the TT genotype was associated with longer 6MW distance and higher leg muscle mass. The -9-9 genotype was associated with lower regional fat mass in men.

Altered locomotor muscle metaboreflex control of ventilation in patients with COPD.

We investigated the locomotor muscle metaboreflex control of ventilation, circulation, and dyspnea in patients with chronic obstructive pulmonary disease (COPD). Ten patients [forced expiratory volume in 1 second (FEV1; means ± SD) = 43 ± 17% predicted] and nine age- and sex-matched controls underwent 1) cycling exercise followed by postexercise circulatory occlusion (PECO) to activate the metaboreflex or free circulatory flow to inactivate it, 2) cold pressor test to interpret whether any altered reflex response was specific to the metaboreflex arc, and 3) muscle biopsy to explore the metaboreflex arc afferent side. We measured airflow, dyspnea, heart rate, arterial pressure, muscle blood flow, and vascular conductance during reflexes activation. In addition, we measured fiber types, glutathione redox balance, and metaboreceptor-related mRNAs in the vastus lateralis. Metaboreflex activation increased ventilation versus free flow in patients (∼15%, P < 0.020) but not in controls (P > 0.450). In contrast, metaboreflex activation did not change dyspnea in patients (P = 1.000) but increased it in controls (∼100%, P < 0.001). Other metaboreflex-induced responses were similar between groups. Cold receptor activation increased ventilation similarly in both groups (P = 0.46). Patients had greater type II skeletal myocyte percentage (14%, P = 0.010), lower glutathione ratio (-34%, P = 0.015), and lower nerve growth factor (NGF) mRNA expression (-60%, P = 0.031) than controls. Therefore, COPD altered the locomotor muscle metaboreflex control of ventilation. It increased type II myocyte percentage and elicited redox imbalance, potentially producing more muscle metaboreceptor stimuli. Moreover, it decreased NGF expression, suggesting a downregulation of metabolically sensitive muscle afferents.NEW & NOTEWORTHY This study's integrative physiology approach provides evidence for a specific alteration in locomotor muscle metaboreflex control of ventilation in patients with COPD. Furthermore, molecular analyses of a skeletal muscle biopsy suggest that the amount of muscle metaboreceptor stimuli derived from type II skeletal myocytes and redox imbalance overcame a downregulation of metabolically sensitive muscle afferents.

Blood Pressure Regulation in Persons with a Transfemoral Amputation: Effects of Wearing a Prosthesis

ABSTRACT INTRODUCTION The purpose of this study was to investigate the effect of wearing a transfemoral prosthesis (FP) on blood pressure regulation in response to postural change. METHODS We enrolled seven persons with a transfemoral amputation who underwent a head-up tilt test while wearing an FP (PROS test) and without wearing an FP (control [CON] test). Systolic blood pressure (SBP), heart rate variability, and muscle blood flow using near-infrared spectroscopy were measured continuously. RESULTS In the CON (no FP) test, SBP decreased from supine to standing positions in all participants (P = 0.001). In contrast, in the PROS (wearing an FP) test, SBP increased (P = 0.001) during the postural change. CONCLUSIONS The findings suggest that a transfemoral prosthesis increases peripheral vascular resistance in the lower limbs and stimulates the baroreflex, helping to stabilize the circulatory dynamics upon postural change. CLINICAL RELEVANCE Because circulatory dynamics may be hampered in persons with a transfemoral amputation, wearing a prosthesis not only assists in ambulation but can also play a significant role in blood pressure regulation during activities of daily living.

Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation.

Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.

Effect of One Session of Muscle Blood Flow Restriction Training Versus Normal Training on Blood Lactate Level.

Blood flow restriction training (BFRT) is useful for improving muscle strength. However, it involves a long training time and is unsuitable for vigorous exercise. Muscle blood flow restriction training (MBFRT), which uses multiple parallel pneumatic cuffs (MPCs) to compress large areas of the extremities and restrict blood flow, was subsequently developed to address these issues. This study compared the effects of MBFRT with normal training (NT). Ten healthy adults underwent low-intensity MBFRT. MPC pressure was increased to 200 mmHg just before training. The exercise was a bodyweight half-squat. Three sets of 30 squats were performed. Two weeks later, the participants underwent NT with the same exercise. Blood lactate levels were measured before the start of training and at 1 and 5 min after training. The Borg index was also measured at the end of the training. The blood lactate level was elevated at 1 min after MBFRT and NT. The elevated blood lactate level was maintained at 5 min after MBFRT, whereas the lactate level was significantly decreased at 5 min after NT. The Borg index at the end of the training was significantly higher in MBFRT than in NT. Lactic acid accumulates in the muscles during low-intensity MBFRT, thereby initiating type II fiber activity.

Short-term cutaneous vasodilatory and thermosensory effects of topical methyl salicylate.

Methyl salicylate, the main compound of wintergreen oil, is widely used in topical applications. However, its vascular and thermosensory effects are not fully understood. The primary aim was to investigate the effects of topical methyl salicylate on skin temperature (Tskin), skin microcirculation (MCskin) and muscle oxygen saturation (SmO2) compared to a placebo gel. The secondary aim was to assess thermosensory responses (thermal sensation, thermal comfort) and to explore to which extent these sensations correspond to the physiological responses over time. 21 healthy women (22.2 ± 2.9years) participated in this single-blind, randomized controlled trial. Custom-made natural wintergreen oil (12.9%), containing methyl salicylate (>99%) and a placebo gel, 1 g each, were applied simultaneously to two paravertebral skin areas (5cm × 10cm, Th4-Th7). Tskin (infrared thermal imaging), MCskin (laser speckle contrast imaging) and SmO2 (deep tissue oxygenation monitoring) and thermosensation (Likert scales) were assessed at baseline (BL) and at 5-min intervals during a 45min post-application period (T0-T45). Both gels caused an initial decrease in Tskin, with Tskin(min) at T5 for both methyl salicylate (BL-T5: Δ-3.36°C) and placebo (BL-T5: Δ-3.90°C), followed by a gradual increase (p < .001). Methyl salicylate gel resulted in significantly higher Tskin than placebo between T5 and T40 (p < .05). For methyl salicylate, MCskin increased, with MCskin(max) at T5 (BL-T5: Δ88.7%). For placebo, MCskin decreased (BL-T5: Δ-17.5%), with significantly lower values compared to methyl salicylate between T0 and T45 (p < .05). Both gels had minimal effects on SmO2, with no significant differences between methyl salicylate and placebo (p > .05). Thermal sensation responses to topical methyl salicylate ranged from "cool" to "hot", with more intense sensations reported at T5. The findings indicate that topical methyl salicylate induces short-term cutaneous vasodilation, but it may not enhance skeletal muscle blood flow. This study highlights the complex sensory responses to its application, which may be based on the short-term modulation of thermosensitive transient receptor potential channels.

The heart, a secondary organ in the control of blood circulation.

Circulation of the blood is a fundamental physiological function traditionally ascribed to the pressure-generating function of the heart. However, over the past century the 'cardiocentric' view has been challenged by August Krogh, Ernst Starling, Arthur Guyton and others, based on haemodynamic data obtained from isolated heart preparations and organ perfusion. Their research brought forth experimental evidence and phenomenological observations supporting the concept that cardiac output occurs primarily in response to the metabolic demands of the tissues. The basic tenets of Guyton's venous return model are presented and juxtaposed with their critiques. Developmental biology of the cardiovascular system shows that the blood circulates before the heart has achieved functional integrity and that its movement is intricately connected with the metabolic demands of the tissues. Long discovered, but as yet overlooked, negative interstitial pressure may play a role in assisting the flow returning to the heart. Based on these phenomena, an alternative circulation model has been proposed in which the heart functions like a hydraulic ram and maintains a dynamic equilibrium between the arterial (centrifugal) and venous (centripetal) forces which define the blood's circular movement. In this focused review we introduce some of the salient arguments in support of the proposed circulation model. Finally, we present evidence that exercising muscle blood flow is subject to local metabolic control which upholds optimal perfusion in the face of a substantive rise in muscle vascular conductance, thus lending further support to the permissive role of the heart in the overall control of blood circulation.

Doppler Ultrasound-Based Leg Blood Flow Assessment During Single-Leg Knee-Extensor Exercise in an Uncontrolled Setting.

Doppler ultrasound has revolutionized the assessment of organ blood flow and is widely used in research and clinical settings. While Doppler ultrasound-based assessment of contracting leg muscle blood flow is common in human studies, the reliability of this method requires further investigation. Therefore, this study aimed to investigate the within-day test-retest, between-day test-retest, and inter-rater reliability of Doppler ultrasound for assessing leg blood flow during rest and graded single-leg knee-extensions (0 W, 6 W, 12 W, and 18 W), with the ultrasound probe being removed between measurements. The study included thirty healthy subjects (age: 33 ± 9.3, male/female: 14/16) who visited the laboratory on two different experimental days separated by 10 days. The study did not control for major confounders such as nutritional state, time of day, or hormonal status. Across different exercise intensities, the results demonstrated high within-day reliability with a coefficient of variation (CV) ranging from 4.0% to 4.3%, acceptable between-day reliability with a CV ranging from 10.1% to 20.2%, and inter-rater reliability with a CV ranging from 17.9% to 26.8%. Therefore, in a real-life clinical scenario where controlling various environmental factors is challenging, Doppler ultrasound can be used to determine leg blood flow during submaximal single-leg knee-extensor exercise with high within-day reliability and acceptable between-day reliability when performed by the same sonographer.