Muscle Blood Flow Research Articles

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.

Changes in Arterial Stiffness in Response to Blood Flow Restriction Resistance Training: A Narrative Review.

Arterial stiffness naturally increases with age and is a known predictor of cardiovascular morbimortality. Blood flow restriction (BFR) training involves decreasing muscle blood flow by applying a strap or a pneumatic cuff during exercise. BFR induces muscle hypertrophy even at low intensities, making it an appealing option for older, untrained individuals. However, BFR use in patients with cardiovascular comorbidities is limited by the increased pressor and chronotropic response observed in hypertensive elderly patients. Furthermore, the impact of BFR on vascular function remains unclear. We conducted a comprehensive literature review according to PRISMA guidelines, summarizing available data on the acute and long-term consequences of BFR training on vascular function. Although evidence is still scarce, it seems that BFR has a mild or neutral long-term impact on arterial stiffness. However, current research shows that BFR can cause an abrupt, albeit transient, increase in PWV and central blood pressure. BFR and, preferably, lower-body BFR, should be prescribed with caution in older populations, especially in hypertensive patients who have an exacerbated muscle metaboreflex pressor response. Longer follow-up studies are required to assess the chronic effect of BFR training on arterial stiffness, especially in elderly patients who are usually unable to tolerate high-intensity resistance exercises.

Cyclooxygenase inhibition does not blunt thermal hyperemia in skeletal muscle of humans.

Acute heat exposure increases skeletal muscle blood flow in humans. However, the mechanisms mediating this hyperemic response remain unknown. The cyclooxygenase pathway is active in skeletal muscle, is heat sensitive, and contributes to cutaneous thermal hyperemia in young healthy humans. Therefore, the purpose of this study was to test the hypothesis that cyclooxygenase inhibition would attenuate blood flow in the vastus lateralis muscle during localized heating. Twelve participants (6 women) were studied on two separate occasions: 1) time control (i.e., no ibuprofen); and 2) ingestion of 800 mg ibuprofen, a nonselective cyclooxygenase inhibitor. Experiments were randomized, counter-balanced, and separated by at least 10 days. Pulsed short-wave diathermy was used to induce unilateral deep heating of the vastus lateralis for 90 min, whereas the contralateral leg served as a thermoneutral control. Microdialysis was utilized to bypass the cutaneous circulation and directly measure local blood flow in the vastus lateralis muscle of each leg via the ethanol washout technique. Heat exposure increased muscle temperature and local blood flow (both P < 0.01 vs. baseline). However, the thermal hyperemic response did not differ between control and ibuprofen conditions (P ≥ 0.2). Muscle temperature slightly decreased for the thermoneutral leg (P < 0.01 vs. baseline), yet local blood flow remained relatively unchanged across time for control and ibuprofen conditions (both P ≥ 0.7). Taken together, our data suggest that inhibition of cyclooxygenase-derived vasodilator prostanoids does not blunt thermal hyperemia in skeletal muscle of young healthy humans.NEW & NOTEWORTHY Acute heat exposure increases skeletal muscle blood flow in humans. However, the mechanisms mediating this hyperemic response remain unknown. Using a pharmacological approach combined with microdialysis, we found that thermal hyperemia in the vastus lateralis muscle was well maintained despite the successful inhibition of cyclooxygenase. Our results suggest that cyclooxygenase-derived vasodilator prostanoids do not contribute to thermal hyperemia in skeletal muscle of young healthy humans.

Advances in Dynamic Light Scattering Imaging of Blood Flow

AbstractDynamic light scattering (DLS) is a well known experimental approach uniquely suited for the characterization of small particles undergoing Brownian motion in randomly inhomogeneous turbid scattering medium, including water suspension, polymers in solutions, cells cultures, and so on. DLS is based on the illuminating of turbid medium with a coherent laser light and further analyzes the intensity fluctuations caused by the motion of the scattering particles. The DLS‐based spin‐off derivative techniques, such laser Doppler flowmetry (LDF), diffusing wave spectroscopy (DWS), laser speckle contrast imaging (LSCI), and Doppler optical coherence tomography (DOCT), are exploited widely for non‐invasive imaging of blood flow in brain, skin, muscles, and other biological tissues. The recent advancements in the DLS‐based imaging technologies in frame of their application for brain blood flow monitoring, skin perfusion measurements, and non‐invasive blood micro‐circulation characterization are overviewed. The fundamentals, breakthrough potential, and practical findings revealed by DLS‐based blood flow imaging studies, including the limitations and challenges of the approach such as movement artifacts, non‐ergodicity, and overcoming high scattering properties of studied medium, are also discussed. It is concluded that continued research and further technological advancements in DLS‐based imaging will pave the way for new exciting developments and insights into blood flow diagnostic imaging.

Hemodynamic changes in the temporalis and masseter muscles during acute stress in healthy humans.

Autonomic control of orofacial areas is an integral part of the stress response, controlling functions such as pupil dilatation, salivation, and skin blood flow. However, the specific control of blood flow in head muscles during stress is unknown. This study aims to investigate the hemodynamic response of temporalis and masseter muscles in response to five different stressors. Sixteen healthy individuals were subjected to a randomized series of stressors, including cold pressor test, mental arithmetic test, apnea, isometric handgrip, and post-handgrip muscle ischemia, while in the sitting posture. Finger-pulse photoplethysmography was used to measure arterial blood pressure, heart rate, and cardiac output. Near-infrared spectroscopy was used to measure changes in tissue oxygenation and hemoglobin indices from the temporalis and masseter muscles. All stressors effectively and significantly increased arterial blood pressure. Tissue oxygenation index significantly increased in both investigated head muscles during mental arithmetic test (temporalis: 4.22 ± 3.52%; masseter: 3.43 ± 3.63%) and isometric handgrip (temporalis: 3.45 ± 3.09%; masseter: 3.26 ± 3.07%), suggesting increased muscle blood flow. Neither the masseter nor the temporalis muscles evidenced a vasoconstrictive response to any of the stressors tested. In the different conditions, temporalis and masseter muscles exhibited similar hemodynamic patterns of response, which do not include the marked vasoconstriction generally observed in limb muscles. The peculiar sympathetic control of head muscles is possibly related to the involvement of these muscles in aggressive/defensive reactions and/or to their unfavorable position with regard to hydrostatic blood levels.

Abstract 13886: Impaired Locomotor Muscle Blood Flow During Cycling Exercise in Heart Failure With Preserved Ejection Fraction

Introduction: Obesity and hypertension (HTN) are highly prevalent comorbid risk factors for heart failure with preserved ejection fraction (HFpEF). Obesity and HTN independently increase sympathetic nervous activity and impair muscle blood flow during exercise. Previous work has reported attenuated limb blood flow in patients with HFpEF; however, these findings were compared to controls with dissimilar comorbidities and during small muscle mass exercise. It is unclear if HFpEF alters muscle blood flow responses independent of the obesity- and HTN-mediated alterations. Hypothesis: We hypothesized the muscle blood flow response during cycling would be lower in HFpEF patients than age, sex, BMI, and HTN matched controls (CTL). Methods: HFpEF patients (n=14, 9M/5W, 71±7yrs, 32±4 kg/m 2 ) and CTL (n=12, 8M/4W, 69±7yrs, 31±4 kg/m 2 ) performed an incremental cycling test. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) by open-circuit acetylene wash-in technique, and systemic vascular resistance (SVR) was calculated. Vastus lateralis blood flow index (BFI) was measured by near-infrared spectroscopy and indocyanine green dye injections and venous norepinephrine concentration was measured. Changes from rest to 40 W of the incremental test are reported. Results: Resting Q, mean arterial pressure, SVR, and venous norepinephrine concentration were not statistically different between groups (p&gt;0.18). From rest to 40 W, the increases in Q (CTL: 3.9±0.8 vs. HFpEF: 3.6±0.7 L/min), mean arterial pressure (CTL: 5.7±2.7 vs. HFpEF: 6.6±6.1 mmHg), and SVR (CTL: -7.3±2.1 vs. HFpEF: -6.0±2.0 mmHg/L/min) were not statistically different between groups (all, p&gt;0.13). The HFpEF group had smaller increases in vastus lateralis BFI at 40 W compared to CTL (CTL: 7.2±3.6 vs. HFpEF: 4.2±2.6 fold-increase from rest) (p=0.02). The HFpEF group had greater increases in venous norepinephrine concentration from rest to 40 W than CTL (CTL: 164±216 vs. HFpEF: 377±247 pg/mL) (p=0.05). Conclusions: Our findings suggest that, compared to age, sex, BMI, and HTN matched controls, patients with HFpEF have an impaired locomotor muscle blood flow response during submaximal cycling exercise likely due to higher locomotor muscle vascular resistance.

Early skeletal muscle loss in adolescent and young adult cancer patients treated with anthracycline chemotherapy.

Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status. Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time points during the first year of treatment. In parallel, we used translational juvenile mouse models to assess the impact of doxorubicin (DOX) in the soleus and gastrocnemius on muscle wasting. Significant reductions in total skeletal muscle index and density were seen after chemotherapy in AYA cancer patients (p < 0.01 & p = 0.04, respectively). The severity of skeletal muscle loss varied by subgroup (i.e., cancer type, sex, and treatment). Murine models demonstrated a reduction in skeletal muscle fiber cross-sectional area, increased apoptosis and collagen volume for both the soleus and gastrocnemius after DOX treatment (all p < 0.05). After DOX, hindlimb skeletal muscle blood flow was significantly reduced (p < 0.01). Significant skeletal muscle loss is experienced early during treatment in AYA cancer patients. Reductions in skeletal muscle blood flow may be a key contributing factor to anthracycline doxorubicin induced skeletal muscle loss.

Vascular deficits contributing to skeletal fragility in type 1 diabetes.

Over 1 million Americans are currently living with T1D and improvements in diabetes management have increased the number of adults with T1D living into later decades of life. This growing population of older adults with diabetes is more susceptible to aging comorbidities, including both vascular disease and osteoporosis. Indeed, adults with T1D have a 2- to 3- fold higher risk of any fracture and up to 7-fold higher risk of hip fracture compared to those without diabetes. Recently, diabetes-related vascular deficits have emerged as potential risks factors for impaired bone blood flow and poor bone health and it has been hypothesized that there is a direct pathophysiologic link between vascular disease and skeletal outcomes in T1D. Indeed, microvascular disease (MVD), one of the most serious consequences of diabetes, has been linked to worse bone microarchitecture in older adults with T1D compared to their counterparts without MVD. The association between the presence of microvascular complications and compromised bone microarchitecture indicates the potential direct deleterious effect of vascular compromise, leading to abnormal skeletal blood flow, altered bone remodeling, and deficits in bone structure. In addition, vascular diabetic complications are characterized by increased vascular calcification, decreased arterial distensibility, and vascular remodeling with increased arterial stiffness and thickness of the vessel walls. These extensive alterations in vascular structure lead to impaired myogenic control and reduced nitric-oxide mediated vasodilation, compromising regulation of blood flow across almost all vascular beds and significantly restricting skeletal muscle blood flow seen in those with T1D. Vascular deficits in T1D may very well extend to bone, compromising skeletal blood flow control, and resulting in reduced blood flow to bone, thus negatively impacting bone health. Indeed, several animal and ex vivo human studies report that diabetes induces microvascular damage within bone are strongly correlated with diabetes disease severity and duration. In this review article, we will discuss the contribution of diabetes-induced vascular deficits to bone density, bone microarchitecture, and bone blood flow regulation, and review the potential contribution of vascular disease to skeletal fragility in T1D.

An Examination of the Acute Effects of Static Stretching Duration on Gastrocnemius Muscle Blood Flow by Superb Microvascular Imaging Method

AIM: Static stretching (SS) exercises are frequently used to increase muscle flexibility, improve physical performance, and reduce musculoskeletal injuries. The purpose of this study was to examine the acute effects of different SS duration applied to the gastrocnemius muscle on muscle blood flow by superb microvascular imaging (SMI) method and compare the impact of stretching at different duration immediately after stretching and 10 minutes later.&#x0D; MATERIAL AND METHOD: 30 healthy volunteers aged between 18-35 years were included in this study. The individuals were divided into two groups randomly. 2-minute SS was applied to the gastrocnemius muscle of the first group, and 5-minute SS was performed to the gastrocnemius muscle of the second group. Blood flow in the muscle after stretching was evaluated by the SMI method.&#x0D; RESULTS: It was obtained that muscle blood flow raised as a result of stretching applications for 2 minutes and 5 minutes, stretching application for 5 minutes increased blood flow more than stretching application for 2 minutes (p0.05).&#x0D; CONCLUSION: It was thought that 2 or 5 minutes of stretching applications to increase circulation in healthy individuals might be sufficient.

Muscle Blood Flow and Vasodilation are Blunted at the Onset of Exercise Following an Acute Bout of Ischemia-Reperfusion.

Ischemia-reperfusion injury (I/R) can inhibit endothelial function and impair nitric oxide bioavailability. We tested the hypothesis that I/R also blunts the rapid and steady-state hyperemic and vasodilatory response to handgrip exercise. Ten subjects (8M/2F; 24±4yr) performed handgrip exercises before and after I/R (20 min of ischemia/20 min of reperfusion) and time control (40 min supine rest) trials. Forearm blood flow (FBF) and vascular conductance (FVC) were assessed with Doppler ultrasound during single forearm contractions and 3 min of rhythmic handgrip exercise. Venous blood samples were drawn at rest and during exercise to assess plasma [nitrite]. Peak ΔFBF (from baseline) and ΔFVC following single contractions were attenuated following I/R (134±48 vs. 103±42 ml·min-1; 160±55 vs. 118±48 ml·min-1·100 mmHg-1, P<0.05 for both) but not following time control (115±63 vs. 124±57 ml·min-1; 150±80 vs. 148±64 ml·min-1·100 mmHg-1, P=0.16 and P=0.95, respectively). Steady-state ΔFBF and ΔFVC during rhythmic exercise were unchanged in both I/R (192 ± 52 vs. 190±53 ml·min-1; 208±56 vs. 193±60 ml·min-1·100 mmHg-1) and time control (188±54 vs. 196±48 ml·min-1; 206±60 vs. 207±49 ml·min-1·100 mmHg-1) trials (group x time interactions P=0.34 and 0.21, respectively). Plasma [nitrite] under resting conditions and during steady-steady state rhythmic exercise was attenuated following I/R (P<0.05 for both) but not time control (P=0.54 and 0.93). These data indicate I/R blunts hyperemia and vasodilation at the onset of muscle contractions but does not attenuate these responses during steady-state exercise.

Effect of CO2 and H2 gas mixture in cold water immersion on recovery after eccentric loading

BackgroundThe findings of previous studies support the efficacy of cold water immersion (CWI) with carbon dioxide (CO2) in enhancing muscle blood flow and maintaining aerobic performance efficiency. We hypothesize that the addition of hydrogen gas (H2), known for its antioxidant properties and role in inflammation regulation, to C-CWI can enhance recovery after eccentric exercise. Subjectsand Methods: Thirty-four healthy subjects performed a knee-extensor eccentric exercise. They were randomly allocated into four groups: control, CWI, CO2-rich CWI (C-CWI), and CO2 + H2 gas mixture CWI (CH-CWI). In the three CWI groups, all subjects were immersed in the appropriate bath at 20 °C for 20 min immediately after 60 repetitions of eccentric exercise. Before exercise and after 48 h of recovery, the subjects' maximal voluntary isometric contraction torque (MVC-ISO), maximal voluntary concentric (MVC-CON) contraction torque, countermovement jump (CMJ) height, knee flexion range of motion (ROM), muscle soreness, and muscle thickness were measured. ResultsIn the CH-CWI group only, the MVC-ISO, CMJ height, and ROM did not decrease significantly post-exercise, whereas all of these decreased in the other three groups. Muscle soreness at palpation, contraction, and stretching significantly increased post-exercise in all groups. Echo intensity and tissue hardness did not increase significantly in the CH-CWI group. ConclusionsCH-CWI stimulated recovery from impairments in MVC-ISO torque, CMJ height, knee-flexion ROM, tissue hardness, and echo intensity. These findings indicate that CH-CWI can promote recovery after eccentric exercise.

Quantitative Assessment of Peripheral Oxidative Metabolism With a New Dynamic 1H MRI Technique: A Pilot Study in People With and Without Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is linked to impaired mitochondrial function. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a gadolinium-contrast-free 1H method to assess mitochondrial function by measuring low-concentration metabolites. A CEST MRI-based technique may serve as a non-invasive proxy for assessing mitochondrial health. A 1H CEST MRI technique may detect significant differences in in vivo skeletal muscle phosphocreatine (SMPCr) kinetics between healthy volunteers and T2DM patients undergoing standardized isometric exercise. Cross-sectional study. Seven subjects without T2DM (T2DM-) and seven age, sex, and BMI-matched subjects with T2DM (T2DM+). Single-shot rapid acquisition with refocusing echoes (RARE) and single-shot gradient-echo sequences, 3 T. Subjects underwent a rest-exercise-recovery imaging protocol to dynamically acquire SMPCr maps in calf musculature. Medial gastrocnemius (MG) and soleus SMPCr concentrations were plotted over time, and SMPCr recovery time, , was determined. Mitochondrial function index was calculated as the ratio of resting SMPCr to . Participants underwent a second exercise protocol for imaging of skeletal muscle blood flow (SMBF), and its association with SMPCr was assessed. Unpaired t-tests and Pearson correlation coefficient. A P value <0.05 was considered statistically significant. SMPCr concentrations in MG and soleus displayed expected declines during exercise and returns to baseline during recovery. was significantly longer in the T2DM+ cohort (MG 83.5 ± 25.8 vs. 54.0 ± 21.1, soleus 90.5 ± 18.9 vs. 51.2 ± 14.5). The mitochondrial function index in the soleus was significantly lower in the T2DM+ cohort (0.33 ± 0.08 vs. 0.66 ± 0.19). SMBF was moderately correlated with the SMPCr in T2DM-; this correlation was not significant in T2DM+ (r = -0.23, P = 0.269). The CEST MRI method is feasible for quantifying SMPCr in peripheral muscle tissue. T2DM+ individuals had significantly lower oxidative capacities than T2DM- individuals. In T2DM, skeletal muscle metabolism appeared to be decoupled from perfusion. 1 TECHNICAL EFFICACY: Stage 1.

Neural control of the circulation during exercise in heart failure with reduced and preserved ejection fraction.

Patients with heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) exhibit severe exercise intolerance that may be due, in part, to inappropriate cardiovascular and hemodynamic adjustments to exercise. Several neural mechanisms and locally released vasoactive substances work in concert through complex interactions to ensure proper adjustments to meet the metabolic demands of the contracting skeletal muscle. Specifically, accumulating evidence suggests that disease-related alterations in neural mechanisms (e.g., central command, exercise pressor reflex, arterial baroreflex, and cardiopulmonary baroreflex) contribute to heightened sympathetic activation and impaired ability to attenuate sympathetic vasoconstrictor responsiveness that may contribute to reduced skeletal muscle blood flow and severe exercise intolerance in patients with HFrEF. In contrast, little is known regarding these important aspects of physiology in patients with HFpEF, though emerging data reveal heightened sympathetic activation and attenuated skeletal muscle blood flow during exercise in this patient population that may be attributable to dysregulated neural control of the circulation. The overall goal of this review is to provide a brief overview of the current understanding of disease-related alterations in the integrative neural cardiovascular responses to exercise in both HFrEF and HFpEF phenotypes, with a focus on sympathetic nervous system regulation during exercise.

Critical limb-threatening ischaemia and microvascular transformation: clinical implications.

Clinical management of critical limb-threatening ischaemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified and more importantly not utilized for treatment. The aim of this explorative study was to characterize the role of the microvasculature in CLTI pathology. Clinical high-resolution imaging of CLTI patients (n = 50) and muscle samples from amputated CLTI limbs (n = 40) were used to describe microvascular pathology of CLTI at the level of resting muscle blood flow and microvascular structure, respectively. Furthermore, a chronic, low arterial driving pressure-simulating ischaemia model in rabbits (n = 24) was used together with adenoviral vascular endothelial growth factor A gene transfers to study the effect of microvascular alterations on muscle outcome. Resting microvascular blood flow was not depleted but displayed decreased capillary transit time (P < .01) in CLTI muscles. Critical limb-threatening ischaemia muscle microvasculature also exhibited capillary enlargement (P < .001) and further arterialization along worsening of myofibre atrophy and detaching of capillaries from myofibres. Furthermore, CLTI-like capillary transformation was shown to worsen calf muscle force production (P < .05) and tissue outcome (P < .01) under chronic ischaemia in rabbits and in healthy, normal rabbit muscle. These findings depict a progressive, hypoxia-driven transformation of the microvasculature in CLTI muscles, which pathologically alters blood flow dynamics and aggravates tissue damage under low arterial driving pressure. Hypoxia-driven capillary enlargement can be highly important for CLTI outcomes and should therefore be considered in further development of diagnostics and treatment of CLTI.

Insulin Resistance Is Associated With Reduced Capillary Permeability of Thigh Muscles in Patients With Type 2 Diabetes.

Insulin-mediated microvascular permeability and blood flow of skeletal muscle appears to be altered in the condition of insulin resistance. Previous studies on this effect used invasive procedures in humans or animals. The aim of this study was to demonstrate the feasibility of a noninvasive assessment of human muscle microcirculation via dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) of skeletal muscle in patients with type 2 diabetes (T2D). A total of 56 participants (46 with T2D, 10 healthy controls [HC]) underwent DCE-MRI of the right thigh at 3 Tesla. The constant of the musculature's microvascular permeability (Ktrans), extravascular extracellular volume fraction (ve), and plasma volume fraction (vp) were calculated. In T2D patients, skeletal muscle Ktrans was lower (HC 0.0677 ± 0.002 min-1, T2D 0.0664 ± 0.002 min-1; P = 0.042) while the homeostasis model assessment (HOMA) index was higher in patients with T2D compared to HC (HC 2.72 ± 2.2, T2D 6.11 ± 6.2; P = .011). In T2D, Ktrans correlated negatively with insulin (r = -0.39, P = .018) and HOMA index (r = -0.38, P = .020). The results signify that skeletal muscle DCE-MRI can be employed as a noninvasive technique for the assessment of muscle microcirculation in T2D. Our findings suggest that microvascular permeability of skeletal muscle is lowered in patients with T2D and that a decrease in microvascular permeability is associated with insulin resistance. These results are of interest with regard to the impact of muscle perfusion on diabetic complications such as diabetic sarcopenia.

Evidence of impaired functional sympatholysis in patients with heart failure with preserved ejection fraction.

Exercising muscle blood flow is reduced in patients with heart failure with a preserved ejection fraction (HFpEF), which may be related to disease-related changes in the ability to overcome sympathetic nervous system (SNS)-mediated vasoconstriction during exercise, (i.e., "functional sympatholysis"). Thus, in 12 patients with HFpEF (69 ± 7 yr) and 11 healthy controls (Con, 69 ± 4 yr), we examined forearm blood flow (FBF), mean arterial pressure (MAP), and forearm vascular conductance (FVC) during rhythmic handgrip exercise (HG) at 30% of maximum voluntary contraction with or without lower-body negative pressure (LBNP, -20 mmHg) to increase SNS activity and elicit peripheral vasoconstriction. SNS-mediated vasoconstrictor responses were determined as LBNP-induced changes (%Δ) in FVC, and the "magnitude of sympatholysis" was calculated as the difference between responses at rest and during exercise. At rest, the LBNP-induced change in FVC was significantly lesser in HFpEF compared with Con (HFpEF: -9.5 ± 5.5 vs. Con: -21.0 ± 8.0%; P < 0.01). During exercise, LBNP-induced %ΔFVC was significantly attenuated in Con compared with rest (HG: -5.8 ± 6.0%; P < 0.05) but not in HFpEF (HG: -9.9 ± 2.5%; P = 0.88). Thus, the magnitude of sympatholysis was lesser in HFpEF compared with Con (HFpEF: 0.4 ± 4.7 vs. Con: -15.2 ± 11.8%; P < 0.01). These data demonstrate a diminished ability to attenuate SNS-mediated vasoconstriction in HFpEF and provide new evidence suggesting impaired functional sympatholysis in this patient group.NEW & NOTEWORTHY Data from the current study suggest that functional sympatholysis, or the ability to adequately attenuate sympathetic nervous system (SNS)-mediated vasoconstriction during exercise, is impaired in patients with heart failure with preserved ejection fraction (HFpEF). These observations extend the current understanding of HFpEF pathophysiology by implicating inadequate functional sympatholysis as an important contributor to reduced exercising muscle blood flow in this patient group.

Effects of an arteriovenous fistula stenosis prevention program in patients receiving hemodialysis.

To increase the efficiency of hemodialysis, an appropriate vascular pathway must be created, and its function must be maintained. This study aimed to identify the effects of an arteriovenous fistula (AVF) stenosis prevention program on upper muscular strength, blood flow, physiological indexes, and self-efficacy among patients receiving hemodialysis. The participants were patients receiving hemodialysis at Keimyung University Dongsan Medical Center in Daegu, Republic of Korea. They were divided into experimental and control groups based on the day of the week they received hemodialysis at the outpatient department and included 25 participants each. The study was conducted for 8 weeks. The AVF stenosis prevention program was effective in improving upper extremity muscle strength (F=15.23, p<0.001) and blood flow rate (F=36.00, p<0.001). As a result of the program, the phosphorus index level, which is a physiological indicator in hemodialysis patients, decreased (F=8.64, p<0.001). Encouragement and support through text messages and practice lists also resulted in an increase in self-efficacy (F=18.62, p<0.001). The AVF stenosis prevention program in this study resulted in an increase in upper extremity muscle strength through grip strength exercises and was effective in preventing AVF stenosis by increasing the blood flow rate.

Contrast-free ultrasound imaging for blood flow assessment of the lower limb in patients with peripheral arterial disease: a feasibility study

While being a relatively prevalent condition particularly among aging patients, peripheral arterial disease (PAD) of lower extremities commonly goes undetected or misdiagnosed due to its symptoms being nonspecific. Additionally, progression of PAD in the absence of timely intervention can lead to dire consequences. Therefore, development of non-invasive and affordable diagnostic approaches can be highly beneficial in detection and treatment planning for PAD patients. In this study, we present a contrast-free ultrasound-based quantitative blood flow imaging technique for PAD diagnosis. The method involves monitoring the variations of blood flow in the calf muscle in response to thigh-pressure-cuff-induced occlusion. Four quantitative metrics are introduced for analysis of these variations. These metrics include post-occlusion to baseline flow intensity variation (PBFIV), total response region (TRR), Lag0 response region (L0RR), and Lag4 (and more) response region (L4 + RR). We examine the feasibility of this method through an in vivo study consisting of 14 PAD patients with abnormal ankle-brachial index (ABI) and 8 healthy volunteers. Ultrasound data acquired from 13 legs in the patient group and 13 legs in the healthy group are analyzed. Out of the four utilized metrics, three exhibited significantly different distributions between the two groups (p-value < 0.05). More specifically, p-values of 0.0015 for PBFIV, 0.0183 for TRR, and 0.0048 for L0RR were obtained. The results of this feasibility study indicate the diagnostic potential of the proposed method for the detection of PAD.

The Effect of Skeletal Muscle Oxygenation on Hemodynamics, Cerebral Oxygenation and Activation, and Exercise Performance during Incremental Exercise to Exhaustion in Male Cyclists.

This study aimed to elucidate whether muscle blood flow restriction during maximal exercise is associated with alterations in hemodynamics, cerebral oxygenation, cerebral activation, and deterioration of exercise performance in male participants. Thirteen healthy males, cyclists (age 33 ± 2 yrs., body mass: 78.6 ± 2.5 kg, and body mass index: 25.57 ± 0.91 kg·m-1), performed a maximal incremental exercise test on a bicycle ergometer in two experimental conditions: (a) with muscle blood flow restriction through the application of thigh cuffs inflated at 120 mmHg (with cuffs, WC) and (b) without restriction (no cuffs, NC). Exercise performance significantly deteriorated with muscle blood flow restriction, as evidenced by the reductions in V˙O2max (-17 ± 2%, p < 0.001), peak power output (-28 ± 2%, p < 0.001), and time to exhaustion (-28 ± 2%, p < 0.001). Muscle oxygenated hemoglobin (Δ[O2Hb]) during exercise declined more in the NC condition (p < 0.01); however, at exhaustion, the magnitude of muscle oxygenation and muscle deoxygenation were similar between conditions (p > 0.05). At maximal effort, lower cerebral deoxygenated hemoglobin (Δ[HHb]) and cerebral total hemoglobin (Δ[THb]) were observed in WC (p < 0.001), accompanied by a lower cardiac output, heart rate, and stroke volume vs. the NC condition (p < 0.01), whereas systolic blood pressure, rating of perceived exertion, and cerebral activation (as assessed by electroencephalography (EEG) activity) were similar (p > 0.05) between conditions at task failure, despite marked differences in exercise duration, maximal aerobic power output, and V˙O2max. In conclusion, in trained cyclists, muscle blood flow restriction during an incremental cycling exercise test significantly limited exercise performance. Exercise intolerance with muscle blood flow restriction was mainly associated with attenuated cardiac responses, despite cerebral activation reaching similar maximal levels as without muscle blood flow restriction.