Real-Time Contrast-Enhanced Ultrasound for the Assessment of Perfusion Dynamics in Skeletal Muscle

We developed a real-time low-MI contrast-enhanced ultrasound method (CEUS), compared it with venous occlusion plethysmography (VOP) and evaluated its robustness in the quantification of skeletal muscle perfusion during exercise. Contrast pulse sequencing (7 MHz) during continuous intravenous infusion of SonoVue (4.8 mL/300s) was used repeatedly in eight healthy volunteers to monitor changes of the muscle perfusion before, during and after isometric exercises (10 to 50% of individual maximum strength for 20 to 30 s) of the gastrocnemius muscle in real time. CEUS was correlated with VOP at different time points, and the exactness of several CEUS parameters obtained from ultrasound-signal-intensity-time curves was evaluated. Real-time CEUS depicted a large variability of the skeletal muscle blood volume at rest (mean, 3.48; range, 0.60 to 9.92 [mL]), with a significant reproducibility (r = 0.72, p < 0.05) and correlation with VOP (r = 0.59, p < 0.001). Mean blood volume during exercise was 1.58(mL), increased to a mean maximum after exercise of 8.88(mL), the mean change of the local blood volume during and directly after the exercise was –0.10 and +1.57(mL/s). The average CEUS signal during exercise decreased (mean area under the curve, –50.4[mL·s]) and subsequently increased post exercise (mean 118.6[mL·s]). CEUS parameters could be calculated with mean relative errors between 6 and 36%. Continuous assessment of local muscle microcirculation during exercise is possible with real-time CEUS with an acceptable robustness. Its application may be of particular interest in a better understanding of the role of perfusion during muscle training, and the monitoring of pathological vascular response, such as in diabetic microvessel diseases. (E-mail: martin.krix@kabelbw.de)     

Relationship of skeletal muscle perfusion measured by contrast-enhanced ultrasonography to histologic microvascular density.

OBJECTIVE: The purpose of this study was to compare skeletal muscle perfusion measured by contrast-enhanced ultrasonography (CEUS) with microvascular density in muscle biopsies. METHODS: Power Doppler sonography after intravenous bolus injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by analyzing replenishment kinetics. CEUS perfusion was compared with vascularization of biopsy samples from vastus lateralis muscle. Subjects were selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per body weight ranged between 23 and 66 mL . min(-1) . kg(-1) to render a large variability of skeletal muscle capillarization. Moreover, subjects' venous blood hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume fraction (1-Hkt=PVF) in which the microbubbles can distribute. RESULTS: Median capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO(2)max (r=0.59; P<.01). Among CEUS parameters, B showed the closest correlation to CFC (r=0.53; P<.01). When CFC was normalized for PVF, correlation of B to CFC was r=0.64 (P<.01). CEUS could depict the physiologic large variability of vastus lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3] approximately mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] approximately mL . min(-1) . 100 g tissue(-1)). CONCLUSIONS: B is significantly related to fiber-adjacent capillarization and may represent physiologic capillary recruitment (eg, through metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion quantification.     

Brain blood flow patterns after the development of congestive heart failure: effects of treadmill exercise

OBJECTIVE: Congestive heart failure (CHF) is associated with left ventricular (LV) failure, neurohormonal system activation, and diminished exercise capacity. Although alterations in systemic vascular resistive properties have been recognized to occur with CHF, whether and to what degree perfusion abnormalities occur within the brain after the development of CHF remain poorly understood. Accordingly, the present study measured brain blood flow patterns in pigs after the development of pacing-induced CHF at rest and after treadmill-induced exercise. MEASUREMENTS AND MAIN RESULTS: Adult pigs (n = 6) were studied before and after the development of pacing-induced CHF (240 beats/min, 3 wks) at rest and with treadmill exercise (3 mph, 15 degrees incline, 10 mins). At rest, LV stroke volume was reduced nearly 45% with CHF compared with normal (20+/-2 vs. 36+/-3 mL; p<.05) and was associated with a more than four-fold increase in plasma catecholamines, renin activity, and endothelin concentration. At rest, global brain blood flow was reduced with CHF compared with the normal state (1.06+/-0.13 vs. 0.81+/-0.06 mL/min/g; p<.05). At rest, blood flow to the frontal lobe, cerebellum, and medullary regions was reduced by approximately 30% in the CHF group (p<.05). With treadmill exercise, LV stroke volume remained lower and neurohormonal concentrations remained higher in the pacing CHF state. Global brain blood flow increased significantly with treadmill exercise in both the normal and CHF states (4.58+/-1.36 and 2.01+/-0.29 mL/min/g; p<.05) but remained reduced in the CHF state compared with normal values (p<.05). In the CHF group, the relative increase in blood flow with exercise was significantly blunted in the parietal and occipital regions of the cerebrum and the suprapyramidal region of the medulla. CONCLUSIONS: The development of pacing-induced CHF was associated with diminished brain perfusion under resting conditions and with treadmill exercise. These perfusion abnormalities with pacing CHF were pronounced in specific regions of the brain. The defects in brain perfusion with the development of CHF may contribute to abnormalities in centrally mediated processes of cardiovascular regulation.     

Skeletal muscle response to exercise training in congestive heart failure.

To examine the ability of the skeletal muscle of congestive heart failure (CHF) patients to adapt to chronic exercise, five patients performed localized nondominant wrist flexor training for 28 d. Inorganic phosphate (Pi) and phosphocreatine (PCr) were monitored by magnetic resonance spectroscopy in both forearms at rest and during submaximal wrist flexion exercise at 6, 12, 24, and 36 J.min-1 before and after exercise training. Simultaneous measurements of limb blood flow were made by plethysmography at 12, 24, and 36 J.min-1. Forearm muscle mass and endurance were measured by magnetic resonance imaging and wrist flexion exercise before and after training. The Pi/PCr ratio and pH were calculated from the measured Pi and PCr. Exercise cardiac output, heart rate, plasma norepinephrine, and lactate measured during training were not elevated above resting values, confirming that training was localized to the forearm flexor muscles. After training, muscle bioenergetics, as assessed by the slope of the regression line relating Pi/PCr to submaximal workloads, were improved in the trained forearm of each patient, although muscle mass, limb blood flow, and pH were unchanged. Forearm endurance increased by greater than 260% after training. In the dominant untrained forearm, none of the measured indices were affected. We conclude that localized forearm exercise training in CHF patients improves muscle energetics at submaximal workloads in the trained muscle, an effect which is independent of muscle mass, limb blood flow, or a central cardiovascular response during training. These findings indicate that peripheral muscle metabolic and functional abnormalities in CHF can be improved without altering cardiac performance.     

Does handgrip exercise training increase forearm ischemic vasodilator responses in patients receiving hemodialysis?

In patients receiving hemodialysis, exercise capacity is extremely limited. Although vasodilation is one of the key phenomena for blood perfusion into working skeletal muscles during exercise, it is not clear whether the vasodilator capacity is increased after physical training in this population. We attempted to clarify whether handgrip exercise training increases forearm vasodilator responses to arterial occlusion, and to determine the relationship between muscle contraction function and the vasodilator responses in patients receiving hemodialysis. Eight patients and 7 age-matched healthy controls were tested. The patients participated in handgrip training four times a week for 6 weeks. Before and after the training the maximum muscle strength and endurance were measured with a handgrip dynamometer, and the forearm vasodilator responses to 3-minute arterial occlusion were measured by the near infrared spectroscopy technique. Maximum strength and endurance were significantly lower in the patients than in the controls. Maximum strength (from 183+/-84 to 228+/-92 Newtons, p<0.05) and endurance (from 19+/-6 to 31+/-8 sec, p<0.05) were both increased after the training in the patients. Vasodilator responses estimated by the ratio of the maximum value of oxyhemoglobin after relief of arterial occlusion to its minimum value before the relief were significantly smaller in the patients compared with those in the controls (132+/-20 vs 161+/-27%, p<0.05). In contrast to the findings in muscle function, the decreased vasodilator responses were not improved after the training (141+/-17%). Additionally, no improvement in the vasodilator responses was observed in the parameters estimated by oxygen saturation. These data suggest that exercise capacity increased by physical training is produced by the functional improvement of skeletal muscles per se, but not by alterations in blood perfusion for oxygenation of the muscles in patients receiving hemodialysis.     

Measuring Absolute Blood Perfusion in Mice Using Dynamic Contrast-Enhanced Ultrasound

We investigated the feasibility of estimating absolute tissue blood perfusion using dynamic contrast-enhanced ultrasound (CEUS) imaging in mice. We developed a novel method of microbubble administration and a model-free approach to estimate absolute kidney perfusion, and explored the kidney as a reference organ to estimate absolute perfusion of a neuroblastoma tumor. We performed CEUS on the kidneys of CD1 nude mice using the VisualSonics VEVO 2100 imaging system. We estimated individual kidney blood perfusion using the burst–replenishment (BR) technique. We repeated the kidney imaging on the mice after a week. We performed CEUS imaging of a neuroblastoma mouse xenograft tumor along with its right kidney using two sets of microbubble administration parameters to estimate absolute tumor blood perfusion. We performed statistical tests at a significance level of 0.05. Our estimated absolute kidney perfusion (425 ± 123 mL/min/100 g) was within the range of previously reported values. There was no statistical difference between the estimated absolute kidney blood perfusions from the 2 wk of imaging (paired t-test, p = 0.09). We estimated the absolute blood perfusion in the neuroblastoma tumor to be 16.49 and 16.9 mL/min/100 g for the two sets of microbubble administration parameters (Wilcoxon rank-sum test, p = 0.6). We have established the kidney as a reliable reference organ in which to estimate absolute perfusion of other tissues. Using a neuroblastoma tumor, we have determined the feasibility of estimating absolute blood perfusion in tissues using contrast-enhanced ultrasound imaging.     

Reduced forearm blood flow in children and adolescents with type 1 diabetes (measured by near-infrared spectroscopy)

OBJECTIVE: The aim of this study was to measure forearm blood flow (FBF) to detect any possible changes that might indicate vascular disorders in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: FBF was measured by near-infrared spectroscopy (NIRS), venous occlusion at rest, and after handgrip exercise. A total of 40 children and adolescents with type 1 diabetes and 40 healthy children and adolescents (6-18 years) were matched for age and sex for comparison. RESULTS: In the diabetic group (age 12.79 +/- 2.9 years, duration of diabetes 51.5 +/- 36 months), FBF at rest was significantly lower (1.39 +/- 0.76 ml x 100 g muscle(-1) x min(-1)) than in control subjects (age 12.66 +/- 2.9 years, FBF at rest 1.90 +/- 1.19 ml x 100 g muscle(-1) x min(-1)). After exercise, FBF increased significantly less in the diabetic group (0.70 +/- 0.82 ml. 100 g muscle(-1) x min(-1)) compared with the control subjects (1.15 +/- 1.05 ml. 100 g muscle(-1) x min(-1)). FBF at rest decreased with increasing age in both groups. The change in FBF after exercise was independent of age in the diabetic group and increased with increasing age in control subjects. FBF is reduced with impaired hyperemic response after exercise in children and adolescents with type 1 diabetes. CONCLUSIONS: These data suggest that vascular disorders in childhood are detectable noninvasively by NIRS.     

Contribution of intramuscular oxidative metabolism to total ATP production during forearm isometric exercise at varying intensities

It is not fully clear whether intramuscular oxidative metabolism contributes to total adenosine triphosphate (ATP) production during forearm isometric exercise at varying intensities. We tested hypothesis that oxidative metabolism with intramuscular O2 contributes to lessen the dependence on anaerobic metabolism, in particular phosphocreatine (PCr) breakdown. Seven male subjects were tested for changes in muscle oxygenation (MO2) and high-energy phosphates in forearm flexor muscles at rest and during exercise under arterial occlusion by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and near infrared spectroscopy (NIRS). Isometric wrist flexion exercise was performed for 1 min or until exhaustion at intensities corresponding to 30%, 50% and 70% of maximal voluntary contraction (MVC) under intramuscular O2 (Intramuscular O2-Ex) and anaerobic (Anaero-Ex) conditions. Oxidative ATP production in Intramuscular O2-Ex was calculated as 0.05 +/- 0.01 mM/s for 30%MVC, 0.08 +/- 0.01 mM/s for 50%MVC and 0.11 +/- 0.01 mM/s for 70%MVC. At a lower intensity (30%MVC), PCr breakdown rate (0.17 +/- 0.02 mM/s) of Anaero-Ex was significantly higher than the rate (0.13 +/- 0.01 mM/s) of Intramuscular O2-Ex (p < 0.05). There was no significant difference in ATP production rates through PCr breakdown and glycolysis between Intramuscular O2-Ex and Anaero-Ex at the higher intensities (50% and 70%MVC). In conclusion, intramuscular oxidative metabolism plays a significant role in reducing the dependence on PCr breakdown during isometric exercise at a lower intensity (30%MVC).     

Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation

Non-invasive ultrasound techniques to assess flow-mediated vasodilation (FMD) are frequently used to assess arterial endothelial vasodilator function. However, the range of normal values varies considerably, possibly due to differences in methodological factors. We sought to determine the effect of occlusion cuff position on the time course and magnitude of brachial artery blood flow and flow-mediated dilation. Twelve healthy subjects underwent measurements of forearm blood flow using venous occlusion plethysmography (VOP) before and after 5 min of susprasystolic cuff inflation, using two randomly assigned occlusion cuff positions (upper arm and forearm). An additional 16 subjects underwent two brachial ultrasound studies, using the two cuff positions, to assess the extent and time course of changes in brachial artery diameter and blood flow. Maximum increase in blood flow (peak reactive hyperaemia), measured by VOP, occurred immediately upon each cuff deflation, but was greater after upper arm compared with forearm arterial occlusion (33.1+/-3.1 versus 22.8+/-2.2 ml/min per forearm tissue, P=0.001). Maximal brachial artery FMD was significantly greater following upper arm occlusion (9.0+/-1.2%, mean +/- S.E.M.) compared with forearm occlusion (5.9+/-0.7%, P=0.01). The time course of the change in brachial artery diameter was affected differently in response to each protocol. The time to peak dilation following upper arm occlusion was delayed by 22 s compared with forearm occlusion. Occlusion cuff position is thus a powerful determinant of peak reactive hyperaemia, volume repaid and the extent and time course of brachial artery FMD. Positioning the cuff on the upper arm produces a greater FMD. These results highlight the need for comparisons between FMD studies to be made with care.     

Myocardial insulin resistance in patients with syndrome X.

Insulin resistance is common in patients with angina pectoris, a positive exercise electrocardiogram, and normal coronary angiograms (syndrome X). It is still not known whether insulin resistance affects the cardiac muscle itself and, if so, whether insulin resistance involves myocardial hemodynamics and energy metabolism. We investigated hemodynamics as well as metabolite exchanges across the heart and the forearm in eight patients with syndrome X and eight control subjects during a baseline period after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Myocardial hemodynamics and metabolism were studied at rest, during pace stress, and in the recovery period after pacing. Neither coronary sinus blood flow nor forearm blood flow differed between the groups before and during the clamp. Whole body insulin-stimulated glucose uptake was decreased in the patients (15.6+/-2.1 vs. 23.1+/-2.0 micromol x kg-1 x min-1). Insulin-stimulated glucose uptake in the forearm and the cardiac muscle was equally reduced in the patients (46+/-5 and 48+/-5%). Myocardial glucose uptake correlated with total arterial delivery in the control subjects (r = 0.63, P < 0.01), but not in patients (r = 0.22, P = 0.13). Carbohydrate and lipid oxidation was similar in the two groups at rest, and changes during the clamp were not different in control subjects and patients either at rest, during pacing, or in the recovery period. Patients with syndrome X exhibit myocardial insulin resistance, but cardiac energy metabolism remains unaffected. In patients with syndrome X, insulin-stimulated glucose uptake is independent from myocardial blood flow.     

The Effects of Elbow Joint Angle Change on the Elbow Flexor Muscle Activation in Pulley with Weight Exercise

[Purpose] This research investigated the effect of angular variation of flexion of the elbow joint on the muscle activation of elbow flexor muscles. [Subjects] The research subjects were 24 male college students with a dominant right hand who had no surgical or neurological disorders and gave their prior written consent to participation with full knowledge of the method and purpose of this study. [Methods] The subjects'' shoulder joints stayed in the resting position, and the elbow joint was positioned at angles of 55°, 70°, and 90°. The angle between the pulley with weights and forearm stayed at 90°. Surface electromyography was used to measure muscle activities. Three measurements were made at each elbow angle, and every time the angle changed, two minutes rest was given. [Result] The muscle activities of the elbow flexors showed significant changes with change in the elbow joint angle, except for the biceps brachii activities between the angles of 55° and 70° of elbow flexion. The muscle activities of the biceps brachii and brachioradialis showed angle-related changes in the order of 55°, which showed the biggest value, followed by 70° and 90°. [Conclusion] In order to improve muscle strength of the elbow flexor using a pulley system, it seems more effective to have a 90° angle between the pulley with weights and the forearm when the muscle is stretched to a length 20% greater than its resting position.Key words: Pulley with weight exercise, Joint angle, Muscle activation     

Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans

BACKGROUND: Adenosine receptor stimulation induces several effects that could limit ischemia-reperfusion injury. We hypothesize that treatment with the nucleoside uptake inhibitor dipyridamole increases endogenous adenosine and limits ischemia-reperfusion injury in humans. METHODS: Ischemia-reperfusion injury was studied in forearm skeletal muscle by technetium Tc 99m-labeled annexin A5 scintigraphy. Ischemia-reperfusion injury was induced by unilateral forearm ischemic exercise. Immediately on reperfusion, annexin A5 labeled with technetium Tc 99m was administered intravenously, and ischemia-reperfusion injury was expressed as the percentage difference in radioactivity between the experimental arm and the control arm 1 and 4 hours after reperfusion. Targeting was quantified in the region of the thenar muscle and forearm flexor muscles. This approach was used in 9 healthy male volunteers after a 1-week treatment with dipyridamole (200 mg, slow release, twice daily) and in 23 control subjects. RESULTS: Dipyridamole treatment significantly reduced annexin A5 targeting in skeletal muscle compared with the control group (thenar region, 13% +/- 7% versus 22% +/- 15% at 1 hour after reperfusion and 9% +/- 6% versus 27% +/- 13% at 4 hours for dipyridamole and control groups, respectively [P = .01]; flexor region, 4% +/- 8% versus 7% +/- 6% at 1 hour after reperfusion and 1% +/- 4% versus 10% +/- 9% at 4 hours for dipyridamole and control groups, respectively [P = .01]). CONCLUSIONS: One week of oral treatment with the nucleoside uptake inhibitor dipyridamole (200 mg, slow release, twice daily) significantly limits ischemia-reperfusion injury in humans in vivo, as assessed by technetium Tc 99m-labeled annexin A5 scintigraphy of forearm skeletal muscle.     

Myocardial perfusion measurements by spin-labeling under different vasodynamic states.

In this study absolute myocardial perfusion was determined using a spin-labeling magnetic resonance imaging (MRI) technique at 2 Tesla. The technique was applied to 16 healthy volunteers at resting conditions, adenosine-induced stress, and oxygen breathing. Overall myocardial quantitative perfusion was determined as 2.3 +/- 0.8 mL/g/min (rest), 4.2 +/- 1.0 mL/g/min (adenosine), and 1.6 +/- 0.6 mL/g/min (oxygen), respectively. T1 of left ventricular blood pool decreased from 1709 +/- 101 ms (rest) to 1423 +/- 61 ms (oxygen), whereas T1 of right ventricular blood did not change significantly (1586 +/- 126 ms and 1558 +/- 150 ms). In conclusion, the presented technique for quantification of myocardial perfusion is an alternative to contrast agent-based methods. The spin labeling method is noninvasive and easily repeatable and it could therefore become an important tool to study changes in myocardial perfusion under different vasodynamic states.     

Forearm elevation augments sympathetic activation during handgrip exercise in humans

Although angina pectoris in patients with coronary heart disease often occurs when their forearms are in an elevated position for a prolonged period, and sympathetic activation is a major cause of this condition, little is known about the physiological effects of forearm elevation on sympathetic activity during forearm exercise. We hypothesized that forearm elevation augments sympathetic activation during the static handgrip exercise in humans. A total of 10 healthy male volunteers performed 2 min of static handgrip exercise at 30% of maximal voluntary contraction followed by 2 min of post-exercise muscle ischaemia (PEMI; specific activation of the muscle metaboreflex) with two forearm positions: the exercising forearm was elevated 50 cm above the heart (forearm-elevated trial) or fixed at the level of the heart (heart-level trial). Muscle sympathetic nerve activity (MSNA), blood pressure and heart rate were monitored. MSNA increased during handgrip exercise in both forearm positions (P<0.001); the increase was 51% greater in the forearm-elevated trial (516+/-99 arbitrary units) than in the heart-level trial (346+/-44 units; P<0.05). The increase in mean blood pressure was 8.4 mmHg greater during exercise in the forearm-elevated trial (P<0.05), while changes in heart rate were similar in both forearm positions. The increase in MSNA during PEMI was 71% greater in the forearm-elevated trial (393+/-71 arbitrary units/min) than in the heart-level trial (229+/-29 units/min; P<0.05). These results support the hypothesis that forearm elevation augments sympathetic activation during handgrip exercise. The excitatory effect of forearm elevation on exercising MSNA may be mediated primarily by increased activation of the muscle metaboreflex.     

Role of adenosine in the sympathetic activation produced by isometric exercise in humans.

Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate increased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 96 +/- 25% (n = 6, P < 0.01) and MABP by 12 +/- 3 mmHg (P < 0.01). Adenosine produced forearm discomfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adenosine. Furthermore, adenosine receptor antagonism with intrabrachial theophylline (1 microgram/ml forearm per min) blocked the increase in MSNA (92 +/- 15% vs. 28 +/- 6%, n = 7, P < 0.01) and MABP (38 +/- 6 vs. 27 +/- 4 mmHg, P = 0.01) produced by isometric handgrip (30% of maximal voluntary contraction) in the infused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle afferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans.     

Changes in flexed posture, musculoskeletal impairments, and physical performance after group exercise in community-dwelling older women

OBJECTIVE: To determine whether improvements in flexed posture, strength, range of motion (ROM), and physical performance would be observed after 12 weeks of group exercise in older women who because of age are prone to flexed posture and impaired physical function. DESIGN: Pretest-posttest of outcome measures. SETTING: Outpatient academic medical center. PARTICIPANTS: Twenty-one women with thoracic kyphosis of 50 degrees or greater. INTERVENTION: Multidimensional group exercise performed 2 times a week for 12 weeks. MAIN OUTCOME MEASURES: Primary dependent measures of flexed posture included kyphosis, forward head, and height. Other dependent measures included spinal extensor muscle strength; shoulder, hip, and knee ROM; balance; modified Physical Performance Test (PPT); jug test; and gait speed. RESULTS: Baseline kyphosis was 57 degrees +/-5.0 degrees , and age was 72.0+/-4.2 years. There were significant improvements in usual (-6 degrees +/-3 degrees ) and best kyphosis (-5 degrees +/-3 degrees ) (P<.001), spinal extensor muscle strength (21%+/-13% of peak torque/body weight, P<.001), popliteal angle (right, 7 degrees +/-7 degrees ; left, 9 degrees +/-10 degrees ; P<.001), modified PPT (2+/-2 points, P<.001), and jug test (-1.4+/-1.3s, P<.001). Age and modified PPT at baseline correlated with change in kyphosis (r=0.5, P=.02; r=.42, P=.055, respectively). CONCLUSIONS: Multidimensional group exercise reduced measured kyphosis and improved strength, ROM, and physical performance. This study provides a promising exercise intervention that may improve posture and physical performance in older women with flexed posture.     

Muscular Echovariation: A New Biomarker in Amyotrophic Lateral Sclerosis

The purpose of the work described here was to assess the characteristics of echovariation in amyotrophic lateral sclerosis (ALS) compared with other muscle ultrasonography parameters. Twenty-six ALS patients (8 women, mean age 58.9 y, standard deviation 12.02 y) and 26 healthy controls (17 women, mean age 59.6 y, standard deviation 6.41 y) were included in this observational study. They underwent bilateral and transverse ultrasound of the biceps/brachialis, forearm flexor group, quadriceps femoris and tibialis anterior. Muscular thickness, echo-intensity and echovariation were analyzed. Muscles affected by ALS had increased echo-intensity, decreased thickness and decreased echovariation. Echovariation in all muscles except the quadriceps femoris strongly correlated with muscle strength (explained variance between 21.8% in the biceps/brachialis and 37.5% in the tibialis anterior) and the ALS Functional Rating Scale Revised score (explained variance between 26% in the biceps/brachialis and 36.7% in the forearm flexor group). Echovariation is an easy-to-obtain quantitative muscle ultrasonography parameter that could distinguish ALS patients from healthy controls more accurately than previous described biomarkers.     

The relationship between exercise‐induced muscle fatigue,arterial blood flow and muscle perfusion after 56 days local muscle unloading

In the light of the dynamic nature of habitual plantar flexor activity, we utilized an incremental isokinetic exercise test (IIET) to assess the work‐related power deficit (WoRPD) as a measure for exercise‐induced muscle fatigue before and after prolonged calf muscle unloading and in relation to arterial blood flow and muscle perfusion. Eleven male subjects (31 ± 6 years) wore the HEPHAISTOS unloading orthosis unilaterally for 56 days. It allows habitual ambulation while greatly reducing plantar flexor activity and torque production. Endpoint measurements encompassed arterial blood flow, measured in the femoral artery using Doppler ultrasound, oxygenation of the soleus muscle assessed by near‐infrared spectroscopy, lactate concentrations determined in capillary blood and muscle activity using soleus muscle surface electromyography. Furthermore, soleus muscle biopsies were taken to investigate morphological muscle changes. After the intervention, maximal isokinetic torque was reduced by 23·4 ± 8·2% (P<0·001) and soleus fibre size was reduced by 8·5 ± 13% (P = 0·016). However, WoRPD remained unaffected as indicated by an unchanged loss of relative plantar flexor power between pre‐ and postexperiments (P = 0·88). Blood flow, tissue oxygenation, lactate concentrations and EMG median frequency kinematics during the exercise test were comparable before and after the intervention, whereas the increase of RMS in response to IIET was less following the intervention (P = 0·03). In conclusion, following submaximal isokinetic muscle work exercise‐induced muscle fatigue is unaffected after prolonged local muscle unloading. The observation that arterial blood flow was maintained may underlie the unchanged fatigability.     

Limb congestion and sympathoexcitation during exercise. Implications for congestive heart failure.

During static exercise, heart failure (HF) subjects activate the sympathetic nervous system differently than normal controls. HF causes metaboreceptor desensitization with either enhanced mechanoreceptor activity or central command. In this report, we examined whether increased muscle interstitial pressure, as seen in HF, augments other neural systems. We measured muscle sympathetic nerve activity (MSNA; peroneal nerve) in 10 normals during static exercise (40% maximal voluntary grip) and posthandgrip circulatory arrest (PHG-CA). This was repeated after venous congestion (VC; cuff inflation to 90 mmHg). VC increased forearm volume (plethysmography) by 4.7%. MSNA responses to exercise were greater after VC (150.5 +/- 41.8 vs. 317.3 +/- 69.9 arbitrary units; P < 0.01). However, MSNA responses during PHG-CA were not affected by VC, and 31P nuclear magnetic resonance (n = 5) demonstrated no effect of VC on pH or H2PO4-. Similar effects of VC on MSNA were noted after ischemic exercise (n = 7), excluding flow alterations as the explantation. VC probably sensitized mechanically sensitive afferents since MSNA during involuntary biceps contractions increased after VC (n = 6), and skin sympathetic nerve responses during handgrip, an index of central command, were not increased by VC (n = 6).     

Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm

Experimental data suggest that vascular ATP-sensitive potassium (K(ATP)) channels may be an important determinant of functional hyperaemia, but the contribution of K(ATP) channels to exercise-induced hyperaemia in humans is unknown. Forearm blood flow was assessed in 39 healthy subjects (23 males/16 females; age 22+/-4 years) using the technique of venous occlusion plethysmography. Resting forearm blood flow and functional hyperaemic blood flow (FHBF) were measured before and after brachial artery infusion of the K(ATP) channel inhibitors glibenclamide (at two different doses: 15 and 100 microg/min) and gliclazide (at 300 microg/min). FHBF was induced by 2 min of non-ischaemic wrist flexion-extension exercise at 45 cycles/min. Compared with vehicle (isotonic saline), glibenclamide at either 15 microg/min or 100 microg/min did not significantly alter resting forearm blood flow or peak FHBF. The blood volume repaid at 1 and 5 min after exercise was not diminished by glibenclamide. Serum glucose was unchanged after glibenclamide, but plasma insulin rose by 36% (from 7.2+/-0.8 to 9.8+/-1.3 m-units/l; P =0.02) and 150% (from 9.1+/-1.3 to 22.9+/-3.5 m-units/l; P =0.002) after the 15 and 100 microg/min infusions respectively. Gliclazide also did not affect resting forearm blood flow, peak FHBF, or the blood volume repaid at 1 and 5 min after exercise, compared with vehicle (isotonic glucose). Gliclazide induced a 12% fall in serum glucose (P =0.009) and a 38% increase in plasma insulin (P =0.001). Thus inhibition of vascular K(ATP) channels with glibenclamide or gliclazide does not appear to affect resting forearm blood flow or FHBF in healthy humans. These findings suggest that vascular K(ATP) channels may not play an important role in regulating basal vascular tone or skeletal muscle metabolic vasodilation in the forearm of healthy human subjects.