Muscle Perfusion In Patients Research Articles

Application of contrast-enhanced ultrasound to evaluate skeletal muscle perfusion in lower extremity arteriosclerotic obliterans of type 2 diabetes mellitus

To evaluate the value of contrast-enhanced ultrasound in evaluating skeletal muscle perfusion in Type 2 diabetic patients with lower extremity arteriosclerosis occlusion. 80 patients with type 2 diabetes were prospectively studied and divided into two groups: 40 patients with lower extremity arteriosclerosis obliterans(observation group)and 40 diabetic volunteers with normal lower extremity arteries(control group).All subjects were subjected to the same contrast-enhanced ultrasound(CEUS) technique before and after exercise to observe the changes of skeletal muscle blood perfusion in the calf, and the time to peak(TTP)of skeletal muscle blood perfusion parameters in the two groups were compared. The time-intensity curve established by mathematical model showed that TTP in the observation group was significantly longer than TTP in the control group in the resting state and after exercise, with statistical significance(P<0.05). TTP had no significant correlation with age, hypertension and other factors(P>0.05). TTP was correlated with ankle-brachial index (ABI)(P<0.05). In conclusion, CEUS can objectively reflect the changes of skeletal muscle perfusion in patients with lower extremity arteriosclerosis obliteration before and after exercise, and it is a new diagnostic method and evaluation index to observe the changes of skeletal muscle perfusion in patients with type 2 diabetes.

An exercise stress test for contrast-enhanced duplex ultrasound assessment of lower limb muscle perfusion in patients with peripheral arterial disease

ObjectiveThe aim of the present study was to develop a standardized contrast-enhanced duplex ultrasound (CE-DUS) protocol to assess lower-extremity muscle perfusion before and after exercise and determine relationships of perfusion with clinical and functional measures. MethodsCE-DUS (EPIQ 5G, Philips) was used before and immediately after a 10-minute, standardized bout of treadmill walking to compare microvascular perfusion of the gastrocnemius muscle in older (55-82 years) patients with peripheral arterial disease (PAD) (n = 15, mean ankle-brachial index, 0.78 ± 0.04) and controls (n = 13). Microvascular blood volume (MBV) and microvascular flow velocity (MFV) were measured at rest and immediately following treadmill exercise, and the Modified Physical Performance Test (MPPT) was used to assess mobility function. ResultsIn the resting state (pre-exercise), MBV in patients with PAD was not significantly different than normal controls (5.17 ± 0.71 vs 6.20 ± 0.83 arbitrary units (AU) respectively; P = .36); however, after exercise, MBV was ∼40% lower in patients with PAD compared with normal controls (5.85 ± 1.13 vs 9.53 ± 1.31 AU, respectively; P = .04). Conversely, MFV was ∼60% higher in patients with PAD compared with normal controls after exercise (0.180 ± 0.016 vs 0.113 ± 0.018 AU, respectively; P = .01). There was a significant between-group difference in the exercise-induced changes in both MBV and MFV (P ≤ .05). Both basal and exercise MBV directly correlated with MPPT score in the patients with PAD (r = 0.56-0.62; P < .05). ConclusionsThis standardized protocol for exercise stress testing of the lower extremities quantifies calf muscle perfusion and elicits perfusion deficits in patients with PAD. This technique objectively quantifies microvascular perfusion deficits that are related to reduced mobility function and could be used to assess therapeutic efficacy in patients with PAD.

Evaluation of skeletal muscle perfusion changes in patients with peripheral artery disease before and after percutaneous transluminal angioplasty using multiparametric MR imaging

PurposeTo evaluate muscle perfusion in patients with peripheral artery disease (PAD) before and after percutaneous transluminal angioplasty (PTA) of the limb by means of MR arterial spin labeling (ASL) and intravoxel incoherent motion (IVIM) under the resting state. MethodsTwenty-eight patients with lower extremity PAD were enrolled. Skeletal muscles in lower extremities were examined at rest by using ASL and IVIM at 3.0 T. Imaging metrics, including blood flow (BF), perfusion fraction f, diffusion coefficient D, and pseudodiffusion coefficient D⁎, were measured in the anterior, lateral, soleus, and gastrocnemius muscle groups. Paired t-test was used to compare the imaging parameters before and after PTA. Pearson correlation analysis was conducted between imaging parameter changes and ankle brachial index (ABI) changes after PTA. ResultsABI was significantly improved after PTA (P < 0.001). For ASL and IVIM imaging, significant changes were noted in ASL-BF and IVIM-D values in the lateral, soleus, and gastrocnemius muscle groups (all P < 0.0125) when comparing pre- and postoperative measurements. Changes in ASL-BF and IVIM-f values in the anterior muscle group, and in IVIM-D⁎ value in the anterior and soleus muscle groups after PTA, were found to be significantly correlated with ABI improvement (all P < 0.05). ConclusionMultiparametric MR techniques including ASL and IVIM can detect the perfusion changes of lower limb tissue before and after PTA in patients with PAD under resting state.

High-intensity exercise impairs extradiaphragmatic respiratory muscle perfusion in patients with COPD.

The study investigated whether high-intensity exercise impairs inspiratory and expiratory muscle perfusion in patients with chronic obstructive pulmonary disease (COPD). We compared respiratory local muscle perfusion between constant-load cycling[sustained at 80% peak work rate (WRpeak)] and voluntary normocapnic hyperpnea reproducing similar work of breathing (WoB) in 18 patients [forced expiratory volume in the first second (FEV1): 58 ± 24% predicted]. Local muscle blood flow index (BFI), using indocyanine green dye, and fractional oxygen saturation (%StiO2) were simultaneously assessed by near-infrared spectroscopy (NIRS) over the intercostal, scalene, rectus abdominis, and vastus lateralis muscles. Cardiac output (impedance cardiography), WoB (esophageal/gastric balloon catheter), and diaphragmatic and extradiaphragmatic respiratory muscle electromyographic activity (EMG) were also assessed throughout cycling and hyperpnea. Minute ventilation, breathing pattern, WoB, and respiratory muscle EMG were comparable between cycling and hyperpnea. During cycling, cardiac output and vastus lateralis BFI were significantly greater compared with hyperpnea [by +4.2 (2.6-5.9) L/min and +4.9 (2.2-7.8) nmol/s, respectively] (P < 0.01). Muscle BFI and %StiO2 were, respectively, lower during cycling compared with hyperpnea in scalene [by -3.8 (-6.4 to -1.2) nmol/s and -6.6 (-8.2 to -5.1)%], intercostal [by -1.4 (-2.4 to -0.4) nmol/s and -6.0 (-8.6 to -3.3)%], and abdominal muscles [by -1.9 (-2.9 to -0.8) nmol/s and -6.3 (-9.1 to -3.4)%] (P < 0.001). The difference in respiratory (scalene and intercostal) muscle BFI between cycling and hyperpnea was associated with greater dyspnea (Borg CR10) scores (r = -0.54 and r = -0.49, respectively, P < 0.05). These results suggest that in patients with COPD, 1) locomotor muscle work during high-intensity exercise impairs extradiaphragmatic respiratory muscle perfusion and 2) insufficient adjustment in extradiaphragmatic respiratory muscle perfusion during high-intensity exercise may partly explain the increased sensations of dyspnea.NEW & NOTEWORTHY We simultaneously assessed the blood flow index (BFI) in three respiratory muscles during hyperpnea and high-intensity constant-load cycling sustained at comparable levels of work of breathing and respiratory neural drive in patients with COPD. We demonstrated that high-intensity exercise impairs respiratory muscle perfusion, as intercostal, scalene, and abdominal BFI increased during hyperpnea but not during cycling. Insufficient adjustment in respiratory muscle perfusion during exercise was associated with greater dyspnea sensations in patients with COPD.

Beet the Best?

A primary goal of therapy for patients with peripheral artery disease (PAD) and intermittent claudication is increased ambulatory function. Supervised exercise rehabilitation was recently shown to confer superior walking benefits to pharmacological or surgical interventions. Increases in plasma inorganic nitrite, via oral nitrate, have been shown to increase exercise performance in both human and animal models, especially in hypoxic conditions. To determine whether a 36-session exercise rehabilitation program while consuming oral inorganic nitrate (4.2 mmol concentrated beetroot juice) would produce superior benefits over exercise plus placebo in pain-free walking and markers of increased skeletal muscle perfusion in patients with PAD and intermittent claudication. This was a randomized, double-blind, per-protocol study design. After the 12-week protocol, claudication onset time on a maximal treadmill test increased by 59.2±57.3 s for the exercise plus placebo group (n=13) and by 180.3±46.6 s for the exercise plus beetroot juice group (n=11; P≤0.05). This produced a between treatment medium to large standardized effect size (Cohen d) of 0.62 (95% CI, -0.23 to +1.44). The data for 6-minute walk distance showed a similar pattern with increases of 24.6±12.1 and 53.3±19.6 m ( P≤0.05) in the exercise plus placebo and exercise plus beetroot juice groups, respectively. Measures of gastrocnemius perfusion, including ankle-brachial index, peak reactive hyperemic blood flow, and tissue deoxygenation characteristics, during exercise (assessed my near-infrared spectroscopy) all changed significantly for the exercise plus beetroot juice group with moderate-to-large effect sizes over exercise plus placebo changes. Although it is premature to speculate on overall clinical utility of a nitrate-based therapy for PAD, this early pilot study evidence is encouraging. Specifically, our data suggests that increasing plasma nitrite before exercise may allow PAD subjects to train with less pain, at higher workloads for longer durations at each training session, thereby maximizing the beneficial peripheral vascular and skeletal muscle adaptations. URL: http://www.clinicaltrials.gov . Unique identifier: NCT01684930 and NCT01785524.

Augmentation of Muscle Blood Flow by Ultrasound Cavitation Is Mediated by ATP and Purinergic Signaling.

Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signaling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1.3 MHz, mechanical index 1.3) was performed for 10 minutes after intravenous injection of 2×108 lipid microbubbles. Microvascular perfusion was evaluated by low-power contrast ultrasound perfusion imaging. In vivo muscle ATP release and in vitro ATP release from endothelial cells or erythrocytes were assessed by a luciferin-luciferase assay. Purinergic signaling pathways were assessed by studying interventions that (1) accelerated ATP degradation; (2) inhibited P2Y receptors, adenosine receptors, or KATP channels; or (3) inhibited downstream signaling pathways involving endothelial nitric oxide synthase or prostanoid production (indomethacin). Augmentation in muscle perfusion by ultrasound cavitation was assessed in a proof-of-concept clinical trial in 12 subjects with stable sickle cell disease. Therapeutic ultrasound cavitation increased muscle perfusion by 7-fold in normal mice, reversed tissue ischemia for up to 24 hours in the murine model of peripheral artery disease, and doubled muscle perfusion in patients with sickle cell disease. Augmentation in flow extended well beyond the region of ultrasound exposure. Ultrasound cavitation produced an ≈40-fold focal and sustained increase in ATP, the source of which included both endothelial cells and erythrocytes. Inhibitory studies indicated that ATP was a critical mediator of flow augmentation that acts primarily through either P2Y receptors or adenosine produced by ectonucleotidase activity. Combined indomethacin and inhibition of endothelial nitric oxide synthase abolished the effects of therapeutic ultrasound, indicating downstream signaling through both nitric oxide and prostaglandins. Therapeutic ultrasound using microbubble cavitation to increase muscle perfusion relies on shear-dependent increases in ATP, which can act through a diverse portfolio of purinergic signaling pathways. These events can reverse hindlimb ischemia in mice for >24 hours and increase muscle blood flow in patients with sickle cell disease. URL: http://clinicaltrials.gov. Unique identifier: NCT01566890.

Higher Myocardial and Skeletal Muscle Microvascular Flow in Sickle Cell Disease Patients on Hydroxyurea

Individuals with SCD have recurrent episodes of ischemia-reperfusion in vital organs, and abnormal microcirculation is considered a major determinant of end organ damage. Hydroxyurea (HU) treatment has been shown to produce ATP- and nitric oxide-mediated vasodilation, and to improve red cells deformability Few tools are available to quantitatively measure microvascular blood flow in vivo. The purpose of this study was to assess the ability of a novel ECHO based imaging modality to assess the effect of hydroxyurea on cardiac and skeletal muscle perfusion in patients with sickle cell anemia.Methods and Results: Twenty-one HBSS/B0 patients, of whom 15 were treated with HU(average daily dose of 18 ± 8 mg/kg/day), underwent brachial artery ultrasound, echocardiography and contrast enhanced ultrasound (CEU) perfusion imaging of deep flexor muscles of the forearm as well as the myocardium at rest and during vasodilator stress with regadenoson ( ClinicalTrials.gov NCT016028090). Quantitative image analysis was performed to obtain microvascular blood volume and flow velocity measurements. Patients on HU had a lower white blood cell count (6.7±2.1 K/uL vs 10.0±2.1 K/uL, p<0.05), higher mean corpuscular volume (103.6±11.5 fL vs 82.5±8.6 fL, p<0.05) , and lower reticulocyte count (9.3±3.4% vs 15.7±5.6%, p<0.05) as well as a trend towards higher hemoglobin (9.4±1.4g/dL vs 7.9±1.1g/dL , p=NS). Table 1. Cardiac output and total myocardial work was not affected by HU treatment and macrovascular flow in the brachial artery was not affected (Figure 1A). In contrast, both skeletal muscle microvascular flow and myocardial microvascular flow was significantly higher in the SCD patients on HU therapy (Figure 1B, 1C).Conclusions: The beneficial effects of HU therapy in SCD are varied, and clinical effects are often seen prior to a rise in fetal hemoglobin. Other effects, such as lower hemolysis, improved red cell deformability, and inhibition of adhesive properties in the microvasculature have been reported. Some of the beneficial effects of HU may be due to stimulation of nitric oxide synthase, induction of cyclic GMP dependent signaling and improved NO bioavailability. Our study indicates that SCD patients on chronic HU therapy have higher levels of myocardial and skeletal muscle microvascular blood flow. Long term studies are necessary to evaluate whether HU reduces end organ damage in SCA.Skeletal muscle and myocardial microvascular blood flow.Each panel shows blood flow in all SCD patients (red filled diamonds), SCD patients not on HU (red open triangles) and SCD patients on HU (red open inverted triangles).Panel A. Skeletal muscle perfusion normalized to hemoglobin (A x β x hemoglobin)Panel B. Myocardial perfusion normalized to hemoglobin level and total myocardial work. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Blood Oxygenation Level-Dependent CMR-Derived Measures in Critical Limb Ischemia and Changes With Revascularization

BackgroundUse of blood oxygenation level-dependent cardiovascular magnetic resonance (BOLD-CMR) to assess perfusion in the lower limb has been hampered by poor reproducibility and a failure to reliably detect post-revascularization improvements in patients with critical limb ischemia (CLI). ObjectivesThis study sought to develop BOLD-CMR as an objective, reliable clinical tool for measuring calf muscle perfusion in patients with CLI. MethodsThe calf was imaged at 3-T in young healthy control subjects (n = 12), age-matched control subjects (n = 10), and patients with CLI (n = 34). Signal intensity time curves were generated for each muscle group and curve parameters, including signal reduction during ischemia (SRi) and gradient during reactive hyperemia (Grad). BOLD-CMR was used to assess changes in perfusion following revascularization in 12 CLI patients. Muscle biopsies (n = 28), obtained at the level of BOLD-CMR measurement and from healthy proximal muscle of patients undergoing lower limb amputation (n = 3), were analyzed for capillary-fiber ratio. ResultsThere was good interuser and interscan reproducibility for Grad and SRi (all p < 0.0001). The ischemic limb had lower Grad and SRi compared with the contralateral asymptomatic limb, age-matched control subjects, and young control subjects (p < 0.001 for all comparisons). Successful revascularization resulted in improvement in Grad (p < 0.0001) and SRi (p < 0.0005). There was a significant correlation between capillary-fiber ratio (p < 0.01) in muscle biopsies from amputated limbs and Grad measured pre-operatively at the corresponding level. ConclusionsBOLD-CMR showed promise as a reliable tool for assessing perfusion in the lower limb musculature and merits further investigation in a clinical trial.

Computational Network Model Prediction of Hemodynamic Alterations Due to Arteriolar Rarefaction and Estimation of Skeletal Muscle Perfusion in Peripheral Arterial Disease.

To estimate the relative influence of input pressure and arteriole rarefaction on gastrocnemius muscle perfusion in patients with PAD after exercise and/or percutaneous interventions. A computational network model of the gastrocnemius muscle microcirculation was adapted to reflect rarefaction based on arteriolar density measurements from PAD patients, with and without exercise. A normalized input pressure was applied at the feeder artery to simulate both reduced and restored ABI in the PAD condition. In simulations of arteriolar rarefaction, resistance increased non-linearly with rarefaction, leading to a disproportionally large drop in perfusion. In addition, perfusion was less sensitive to changes in input pressure as the degree of rarefaction increased. Reduced arteriolar density was observed in PAD patients and improved 33.8% after three months of exercise. In model simulations of PAD, ABI restoration yielded perfusion recovery to only 66% of baseline. When exercise training was simulated by reducing rarefaction, ABI restoration increased perfusion to 80% of baseline. Microvascular resistance increases non-linearly with increasing arteriole rarefaction. Therefore, muscle perfusion becomes disproportionally less sensitive to ABI restoration as arteriole rarefaction increases. These results highlight the importance of restoring both microvascular structure and upstream input pressure in PAD therapy.

Perfusion measurements of the calf in patients with peripheral arterial occlusive disease before and after percutaneous transluminal angioplasty using Mr arterial spin labeling

To evaluate muscle perfusion in patients with peripheral arterial occlusive disease (PAOD) before and after percutaneous transluminal angioplasty (PTA) of the limb by means of MR arterial spin labeling (ASL) perfusion measurements during reactive hyperemia. Ten patients with symptomatic PAOD affecting the iliac or femoral vessels were investigated before and after PTA. A pseudo-continuous arterial spin labeling (PCASL) MR technique was applied. Perfusion was measured in soleus and tibialis anterior muscle during reactive hyperemia. Key parameters such as mean perfusion value (Phyp ), time-to-peak (TTP) and duration of hyperemia (Thyp ) describing the perfusion signal curve were examined. Between baseline and post-PTA, Phyp increased in both muscle groups. At the same time, TTP and Thyp decreased in both muscle groups. At the same time the clinically assessed ankle brachial index (ABI) increased from 0.56 ± 0.10 to 0.83 ± 0.15. The impaired pain-free walking distance improved in all patients. PCASL MRI can detect changes of the key perfusion parameters Phyp , TTP, and Thyp after successful PTA of the calf muscles during reactive hyperemia and seems to be a promising tool for monitoring of interventional treatments.

Correlation of the severity of diabetic retinopathy and the heart muscle perfusion in patients with type 2 diabetes

ObjectiveThe objective was to investigate whether microvascular disturbances in patients with type 2 diabetes (DM) as defined by retinal examination predict the existence of macrovascular disturbances found on radioisotopic perfusion examinations of the heart muscle. Materials and methodsA total of 100 patients with type 2 DM and an additional cardiovascular risk factor were enrolled in the study. All patients underwent comprehensive ophthalmologic examination, including fundus color photography and fluorescein angiography, and were divided into three groups: group 1 (NoDR): met the inclusion criteria but had no diabetic retinopathy; group 2 (NPDR): had signs of nonproliferative diabetic retinopathy; group 3 (PDR): had signs of preproliferative or proliferative diabetic retinopathy. After collecting general medical history and clinical data, patients underwent heart muscle perfusion studies. All patients followed a 48-h protocol heart muscle perfusion examination in the rest state as well as after the standardized exercise test. Single photon emission computed tomography examination was performed. ResultsIn the PDR group, the impairment of the heart muscle perfusion at stress and rest was more frequent than in the NPDR and NoDR groups. Analysis of the heart muscle perfusion results for the three groups showed a significant relationship with the severity of microvascular complications observed in eye fundus examinations. ConclusionsComprehensive ophthalmologic assessment of the progression of diabetic retinopathy in patients with type 2 DM may be an indicator of heart muscle perfusion disturbance.

The immediate rise in leg blood flow during calf exercise is dependent on functional venous valves

The importance of the muscle pump in exercise hyperemia is incompletely understood. We have recently shown that a large hydrostatic column induced by head up tilt (HUT) increases the effect of the leg muscle pump on muscle perfusion in healthy subjects. In this study we investigated the effect of a larger hydrostatic column on muscle perfusion in patients with insufficient venous valves.The transient and steady state rise in leg arterial blood flow (ultrasound Doppler) was investigated in 10 patients with venous insufficiency, both supine and 30º HUT.Within ~15 s of the start of exercise, the rise in femoral flow was not significantly different between supine (0.21 L/min) and HUT (0.24 L/min). After 80 s of exercise, femoral flow was stable at 0.20 L/min and 0.22 L/min above rest in supine and HUT respectively (not significantly different).These results indicate that there is no significant muscle pump effect on the immediate rise in muscle perfusion in patients with venous insufficiency.This is in contrast to the findings in healthy subjects, where the transient rise in femoral flow was considerably larger in the tilted than in the supine position. The reduced immediate rise in blood flow observed in the present study indicates that the larger transient rise in femoral flow in healthy subjects was indeed dependent on functional venous valves, and thus caused by a leg muscle pump effect.Research support: University of Oslo.

The major limitation to exercise performance in COPD is inadequate energy supply to the respiratory and locomotor muscles

No doubt dynamic hyperinflation and lack of oxidative capacity of skeletal muscles are important causes of exercise limitation in COPD. O'Donnell and Webb and Debigare and Maltais will convince the reader of this by the elegant experiments they have performed. The thesis we will put forward is that

Pathologic Skeletal Muscle Perfusion in Patients with Myositis: Detection with Quantitative Contrast-enhanced US—Initial Results

To prospectively determine whether contrast material-enhanced ultrasonography (US) can depict inflammation-induced changes in muscle perfusion for patients suspected of having dermatomyositis or polymyositis and to compare these findings with those of magnetic resonance (MR) imaging and muscle biopsy. Institutional review board approval and informed consent were obtained. Perfusion in skeletal muscles was quantified with contrast-enhanced intermittent power Doppler US by applying a modified model that analyzed the replenishment kinetics of microbubbles. In 22 patients (16 women, six men; mean age, 52 years +/- 17) who were suspected of having myositis and in 10 healthy volunteers (two women, eight men; mean age, 28 years +/- 4), contrast-enhanced US of the clinically affected right biceps muscle was performed to measure blood flow, blood volume, and blood flow velocity. Additionally, the right upper arm was examined with a 1.5-T unit by using three different MR imaging techniques. Findings were compared with the results of clinical examinations and muscle biopsy. Data for perfusion-related parameters obtained at contrast-enhanced US were analyzed by using a nonparametric Mann-Whitney U test. Eight patients had histologically confirmed myositis and showed significantly higher blood flow velocity (P = .01), blood flow (P = .001), and blood volume (P = .002) at contrast-enhanced US than did patients who did not have myositis. Blood flow velocity (P = .001) and blood flow (P = .002) were significantly higher in patients with myositis than in volunteers. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis, while contrast material enhancement on fat-suppressed T1-weighted MR images was found in only four of seven patients with myositis. Initial results show that contrast-enhanced US is a feasible method for noninvasively demonstrating increased perfusion in the involved muscle groups in patients with myositis.