Maximal Voluntary Contraction Handgrip Research Articles

Rapid Onset Vasodilation: Impact of Cardiorespiratory Fitness

IntroductionHigher cardiorespiratory fitness is associated with greater vascular function that leads to improved regulation of skeletal muscle blood flow during exercise. Rapid onset vasodilation (ROV) describes the immediate increase in blood flow following a single contraction, which is integral to support greater blood flow during exercise. As such, blood flow regulation during exercise hyperemia is important. However, it is unclear if cardiorespiratory fitness plays a role in ROV of small muscle mass in young, healthy individuals.PurposeTo investigate the relationship of cardiorespiratory fitness on ROV following a single handgrip (HG) contraction in young, healthy adults.MethodsCardiorespiratory fitness (VO2peak) was assessed during a maximal cycle ergometer test in 14 volunteers (M/F, 6/8; 28 ± 5yrs; 24.8 ± 4.1kg/m2). Brachial velocity and diameter were measured using duplex Doppler ultrasound for 10 cardiac cycles prior to and 20 cardiac cycles following the first cardiac cycle after a single 30% of maximal voluntary handgrip contraction. Brachial artery blood flow (FBF) was calculated for each cardiac cycle: (diameter2/2)*π*velocity*60. Peak forearm (brachial) blood flow (FBFpeak) was determined as the maximal FBF from baseline following the first cardiac cycle after the single HG contraction. Time to peak blood flow response was determined as the time to reach FBFpeak and heart rate was measured using a three‐lead ECG. The relationship between FBFpeak and time to peak blood flow was tested using a multivariate regression analysis with cardiorespiratory fitness and sex as independent variables.ResultsCardiorespiratory fitness (VO2peak: 30.6 ± 8.0mL/kg/min); β for VO2peak= 0.162 [0.003, 0.327]) was the only predictor of time to peak blood flow response, F(1,12)= 4.602, p= 0.05, R2= 0.217, r= 0.526, while sex (β for time to peak= ‐106.5 [‐156.9, ‐56.2]) was the only predictor of FBFpeak, F(1,12)= 21.245, p<0.001, R2= 0.609, r= 0.799, indicating that females had a lower FBFpeakoverall.ConclusionOur data suggests blood flow responsiveness (e.g., time to peak) is positively associated with cardiorespiratory fitness and these data contribute to our understanding of potential mechanisms between improved blood flow regulation commonly associated with greater cardiorespiratory fitness. More research is necessary to fully elucidate the role biological sex has on these relationships, but our data suggest there may be sex differences in certain blood flow responses.

Time course of interlimb strength transfer after unilateral handgrip training

"Cross-education" is the increase in strength or functional performance of an untrained limb after unilateral training. A major limitation for clinical translation from unilateral injury includes knowledge on the minimum time for the emergence of crossed effects. Therefore, the primary purpose was to characterize the time course of bilateral strength changes during both "traditional" ( n = 11) and "daily" ( n = 8) unilateral handgrip training in neurologically intact participants. Traditional training included five sets of five maximal voluntary handgrip contractions 3 times/wk for 6 wk whereas daily training included the same number of sessions and contractions but over 18 consecutive days. Three pre- and one posttest session evaluated strength, muscle activation, and reflex excitability bilaterally. Time course information was assessed by recording handgrip force for every contraction in the trained limb and from a single contraction on every third training session in the untrained limb. Six weeks of traditional training increased handgrip strength in the trained limb after the 9th session whereas the untrained limb was stronger after the 12th session. This was accompanied by increased peak muscle activation and bilateral alterations in Hoffmann reflex excitability. Daily training revealed a similar number of sessions (15) were required to induce significant strength gains in the untrained limb (7.8% compared with 12.5%) in approximately half the duration of traditional training. Therefore, minimizing rest days may improve the efficiency of unilateral training when the trained limb is not the focus. Establishing a "dose" for the time course of adaptation to strength training is paramount for effective translation to rehabilitative interventions. NEW & NOTEWORTHY Unilateral handgrip training using a "traditional" protocol (3 times/wk; 6 wk) increased strength bilaterally after 9 (trained arm) and 12 (untrained arm) sessions. "Daily" training (18 consecutive days) increased strength in the untrained limb in a similar number of training sessions, which was accomplished in approximately half the time. Within clinical populations when the focus is on the untrained limb, reducing rest days may optimize the recovery of strength.

Muscle Strength, Power, and Torque Deficits in Children With Type SS Sickle Cell Disease.

In African-American children aged 5 to 17 years with and without type SS sickle cell disease (SCD-SS), dominant hand maximal handgrip strength, peak power, and plantar flexion isometric maximal voluntary contraction (MVC) torque were compared with adjustments for body size and composition. Children with SCD-SS (n=21; age, 11±1 y) compared with healthy control children (n=23; 10±1 y) did not differ by age, sex, or maturation stage, but had significantly lower Z scores for height, weight, body mass index, arm circumference, upper arm muscle area, and lean mass-for-height. Children with SCD-SS had significantly lower unadjusted handgrip strength (16±2 vs. 23±2 kg, P<0.01), peak power (1054±107 vs. 1488±169 W, P<0.04) and MVC torques at 2 angles (10 degrees: 27±3 vs. 42±5 Nm; 20 degrees: 21±3 vs. 34±4 Nm; all P<0.05). Performance decrements persisted when handgrip strength was adjusted for lean body mass and fat mass explaining 66% of the variance; peak power adjusted for age, lean body mass, fat mass, and height explaining 91% of the variance; and the highest MVC torque (10-degree angle) adjusted for left leg length, lean mass-for-height, and fat mass-for-height Z scores explaining 65% of the variance. This suggests additional factors contribute to the attenuated anaerobic performance.

Skeletal Muscle Oxygenation During Plantarflexion Exercise In Young-old And Older-old Adults

The aging process is associated with a gradual decrease in exercise performance, leg muscle blood flow and oxygenation, and endothelial vascular reactivity. PURPOSE: To examine potential differences in femoral artery flow-mediated dilation (fa-FMD) and calf muscle oxygenation (HbO2) during low-intensity plantarflexion exercise in older adults. METHODS: 43 young-old (YO; n=24, 67 ± 1 years) and older-old (OO: n=19, 70 ± 1 years) individuals were included in this study. We measured body fat % and leg lean mass (LLM) by DEXA and handgrip maximal voluntary contraction (MVC) using a dynamometer. VO2max was estimated using a submaximal treadmill test. fa-FMD was assessed by Doppler ultrasound, measuring the relative change in diameter from baseline to peak hyperemic response following 5 min of muscle ischemia. After a 10-min semi-recumbent rest, participants performed three sets (3-min each) of rhythmic plantar-flexion exercise at increasing intensity (20, 30 and 40 pounds) separated by 1-min of rest. Percent changes (%[INCREMENT]) in muscle HbO from baseline to the 3rd min of each set was monitored by near-infrared spectroscopy (NIRS) on the medial gastrocnemius muscle. RESULTS: There were no between-group differences in VO2max, MVC, LLM, body fat %, and fa-BF (P= .07). The OO group had significantly lower fa-FMD compared to the YO group (5.7 ± 1.4 vs 6.7 ± 1.6%, p < .05). During exercise, the OO group exhibited a higher %[INCREMENT] in HbO2 compared to the YO in sets 2 (-60.0 ± 21.2 vs. -44.7 ± 17.2%, p < .05) and 3 (-66.7 ± 18.8 vs. -52.6 ± 18.2%, p < .05). CONCLUSIONS: There was a lower calf muscle oxygenation during low-intensity plantar-flexion exercise performed at the same absolute intensity in OO compared to YO adults. Exercising at a greater relative intensity may explain the lower calf muscle oxygenation in OO adults.

Muscle Strength Influences Pressor Responses to Static Handgrip in Men and Women.

Whether differences in absolute muscle strength affect blood pressure (BP) responses to relative intensity static exercise remains controversial but could contribute to known sex-based differences and influence the interpretation of cross-sectional data. One hundred thirty-two healthy participants (66 men and 66 women; age, 22 ± 3 yr) underwent continuous seated measurements of BP (Finometer) and heart rate (electrocardiography) during baseline rest and 2 min of static handgrip (30% maximal voluntary contraction (MVC)). BP and heart rate responses were quantified in 30-s epochs during exercise and compared between men and women with and without statistical adjustment (ANCOVA) for differences in baseline BP (or heart rate), forearm girth, and handgrip MVC. Within each sex, BP and heart rate responses were compared also between tertiles of handgrip MVC (n = 22 per group). Men had larger systolic, diastolic, and mean arterial pressure responses during static handgrip than did women (interaction term, all P < 0.0005), although heart rates responses were similar (interaction term, P = 0.25). These sex-based BP differences persisted after statistical adjustment for differences in baseline BP or forearm girth; however, controlling for handgrip MVC abolished differences in BP responses during static handgrip exercise between men and women (interaction term, all P > 0.35). In men, BP responses were smaller within the lowest tertile of handgrip MVC (interaction term, all P < 0.006), whereas in women, BP responses were larger within the highest tertile of handgrip MVC (interaction term, all P < 0.04). Our findings suggest an important between- and within-sex role of absolute handgrip strength in mediating the BP response to static handgrip exercise and highlight the importance of controlling for interindividual differences in future work.

Performance and physiological analysis of 500 km non-stop cycling: a case study

ABSTRACTUltra-endurance sports have gained popularity over the last years. In this case, a well-trained cyclist completed 503.5 km non-stop (33.3 km.h−1). Speed and power output were reduced during the trial, being the reduction of power attributable to changes in pedal velocity rather than pedal forces. Heart rate (HR) showed an initial cardiovascular drift and progressively decreased independently of power. A decreased HR variability, a marked inflammatory response, signs of muscle damage and alterations of the haematological profile were observed after the trial. These adverse physiological effects were still present 24–48 h after exercise. A reduction in handgrip maximal voluntary contraction was observed immediately after the trial and 24 h later despite these muscles being minimally active during exercise. These findings show the high levels of stress to which the organism is subjected during ultra-endurance exercise even in the case of a trained cyclist.

Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients.

Previous studies have reported exaggerated increases in arterial blood pressure during exercise in type 2 diabetes (T2D) patients. However, little is known regarding the underlying neural mechanism(s) involved. We hypothesized that T2D patients would exhibit an augmented muscle metaboreflex activation and this contributes to greater pressor and sympathetic responses during exercise. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured in 16 patients with T2D (8 normotensive and 8 hypertensive) and 10 healthy controls. Graded isolation of the muscle metaboreflex was achieved by postexercise ischemia (PEI) following static handgrip performed at 30% and 40% maximal voluntary contraction (MVC). A cold pressor test (CPT) was also performed as a generalized sympathoexcitatory stimulus. Increases in MAP and MSNA during 30 and 40% MVC handgrip were augmented in T2D patients compared with controls (P < 0.05), and these differences were maintained during PEI (MAP: 30% MVC PEI: T2D, Δ16 ± 2 mmHg vs. controls, Δ8 ± 1 mmHg; 40% MVC PEI: T2D, Δ26 ± 3 mmHg vs. controls, Δ16 ± 2 mmHg, both P < 0.05). MAP and MSNA responses to handgrip and PEI were not different between normotensive and hypertensive T2D patients (P > 0.05). Interestingly, MSNA responses were also greater in T2D patients compared with controls during the CPT (P < 0.05). Collectively, these findings indicate that muscle metaboreflex activation is augmented in T2D patients and this contributes, in part, to augmented pressor and sympathetic responses to exercise in this patient group. Greater CPT responses suggest that a heightened central sympathetic reactivity may be involved.

Augmented Skeletal Muscle Metaboreflex Activation in Patients with Type 2 Diabetes Mellitus

Previous reports demonstrate augmented blood pressure responses to exercise in patients with type 2 diabetes mellitus (T2D). However, the underlying neural mechanisms involved remain unknown. We tested the hypothesis that T2D patients would exhibit an augmented activation of the muscle metaboreflex, which contributes to greater pressor and sympathetic responses during exercise. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured in T2D patients (n=13) and age- and sex-matched healthy controls (CON, n=6) during static handgrip performed at 30 and 40% maximal voluntary contraction (MVC) followed by a period of postexercise ischemia (PEI) to isolate the muscle metaboreflex. Peak 30s average increases in MAP from baseline were augmented in T2D patients compared to controls during both 30 and 40% MVC handgrip (40%: T2D, +32 ± 3 vs. CON, +20 ± 5 mmHg, P<0.05), and these differences were maintained during PEI (40%: T2D, +29 ± 4 vs. CON, +15 ± 4 mmHg, P<0.05). Similarly, peak 30s average increases in MSNA from baseline were augmented in T2D subjects compared to controls during both 30 and 40% MVC handgrip (40%: T2D, +190 ± 38 vs. CON, +87 ± 51 AU·min, P<0.05), and these differences were also maintained during PEI (40%: T2D, +180 ± 41 vs. CON, +29 ± 7 AU·min, P<0.05). HR increased similarly in both groups during handgrip and returned toward baseline with PEI. These preliminary findings suggest T2D patients exhibit augmented pressor and sympathetic responses to handgrip exercise, which are in part attributable to heightened metaboreflex activation.

Peripheral chemoreceptor control of cardiovascular function at rest and during exercise in heart failure patients.

Peripheral chemoreceptor activity/sensitivity is enhanced in chronic heart failure (HF), and sensitivity is linked to greater mortality. This study aimed to determine the role of the peripheral chemoreceptor in cardiovascular control at rest and during exercise in HF patients and controls. Clinically stable HF patients (n = 11; ejection fraction: 39 ± 5%) and risk-matched controls (n = 10; ejection fraction: 65 ± 2%) performed randomized trials with or without dopamine infusion (2 μg·min(-1)·kg(-1)) at rest and during 40% maximal voluntary contraction handgrip (HG) exercise, and a resting trial of 2 min of inspired 100% oxygen. Both dopamine and hyperoxia were used to inhibit the peripheral chemoreceptor. At rest in HF patients, dopamine decreased ventilation (P = 0.02), decreased total peripheral resistance index (P = 0.003), and increased cardiac and stroke indexes (P ≤ 0.01), yet there was no effect of dopamine on these variables in controls (P ≥ 0.7). Hyperoxia lowered ventilation in HF (P = 0.01), but not in controls (P = 0.9), indicating suppression of the peripheral chemoreceptors in HF. However, no decrease of total peripheral resistance index was observed in HF. As expected, HG increased heart rate, ventilation, and brachial conductance of the nonexercising arm in controls and HF patients. During dopamine infusion, there were no changes in mean arterial pressure, heart rate, or ventilation responses to HG in either group (P ≥ 0.26); however, brachial conductance increased with dopamine in the control group (P = 0.004), but decreased in HF (P = 0.02). Our findings indicate that the peripheral chemoreceptor contributes to cardiovascular control at rest in HF patients and during exercise in risk-matched controls.

Rapid onset pressor and sympathetic responses to static handgrip in older hypertensive adults.

Exaggerated pressor and muscle sympathetic nerve activity (MSNA) responses have been reported during static handgrip in hypertensive (HTN) adults. Recent work suggests that such responses may occur much more rapidly in HTN patients; however, this has not been extensively studied. Thus, we examined the blood pressure (BP) and MSNA responses at the immediate onset of muscle contraction and tested the hypothesis that older HTN adults would exhibit rapid onset pressor and sympathetic responses compared with normotensive (NTN) adults. Heart rate (HR), BP (Finometer) and MSNA (peroneal microneurography) were retrospectively analyzed in 15 HTN (62 ± 1 years; resting BP 153 ± 3/91 ± 5 mm Hg) and 23 age-matched NTN (60 ± 1 years; resting BP 112 ± 1/67 ± 2 mm Hg) subjects during the first 30 s of static handgrip at 30 and 40% of maximal voluntary contraction (MVC). HTN adults demonstrated exaggerated increases in mean BP during the first 10 s of both 30% (NTN: Δ1 ± 1 vs HTN: Δ7 ± 2 mm Hg; P < 0.05) and 40% (NTN: Δ2 ± 1 vs HTN: Δ8 ± 2 mm Hg; P < 0.05) intensity handgrip. Likewise, HTN adults exhibited atypical increases in MSNA within 10 s. Increases in HR were also greater in HTN adults at 10 s of 30% MVC handgrip, although not at 40% MVC. There were no group differences in 10 s pressor or sympathetic responses to a cold pressor test, suggesting no differences in generalized sympathetic responsiveness. Thus, static handgrip evokes rapid onset pressor and sympathetic responses in older HTN adults. These findings suggest that older HTN adults likely have greater cardiovascular risk even during short duration activities of daily living that contain an isometric component.

Accuracy of Force Exertion in Response to Demanded Forces Based on Subjective Information and Laterality

The strength required for motor activities should be exerted effectively according to the type of activity and the load size. This study examined the relationship between the accuracy of handgrip exertion for demanded forces of 20%–80% of the maximal voluntary contraction (MVC) and laterality. Subjects were 100 healthy young males (mean age, 22.4 ± 2.8 years). After the handgrip MVC was measured, subjects attempted to exert a handgrip at demanded forces of 20, 40, 60, and 80% of the MVC. All tests were performed twice and with dominant and non-dominant hands, and mean values were used for statistical analysis. Differences between demanded forces and exerted forces were converted into relative values based on each subject’s MVC. Two-way repeated measures ANOVA showed significant interaction between demanded forces and laterality. In multiple comparison tests, smaller demanded forces were associated with larger errors only in the non-dominant hand. For demanded forces of 20% and 40% MVC errors were smaller for the dominant hand than for the non-dominant hand. The non-dominant hand is used less than the dominant hand in daily life and in sport activities. It is therefore not unexpected that a laterality-based difference in the accuracy of exerted force for each demanded force is found, and the accuracy of exerted force at low demanded forces was inferior for the non-dominant hand. In conclusion, there was a difference in the accuracy of exerted force for each demanded force for the non-dominant hand with a larger error at lower demanded forces. In particular, the accuracy of exerted force in response to demanded forces of 40% MVC or less was inferior in the non-dominant hand compared with that in the dominant hand. Laterality is therefore a significant factor in force response to lower demanded force values.

Medical Equipment to Make Colonoscopy Procedures Safer for Physicians: Control Head Holder and Splatter Shield1

Medical Equipment to Make Colonoscopy Procedures Safer for Physicians: Control Head Holder and Splatter Shield1

Effects of Caffeine on Anaerobic Exercise in Boys

The effects of caffeine on anaerobic exercise in young boys was investigated. Twenty-four healthy 8-10 year old boys participated in a randomized double-blind, double-crossover, counter-balanced study. Each subject received the caffeinated drink (CAF--5 mg · kg(-1)) or placebo (PL) twice each on four separate visits. Sixty minutes following ingestion of either CAF or PL boys performed a static hand-grip test and then a Wingate test. Reliability was moderately high for the Wingate test (R = .70-0.95). Hand-grip reliability was higher for CAF (R = .88) than PL (R = .52). Mean power (180 ± 36 vs 173 ± 28 W) was significantly higher (p < .05) in CAF versus PL, respectively. There were no differences in peak power or static hand-grip maximal voluntary contraction with CAF. Further, peak HR (190 ± 10 vs 185 ± 10 beats · min(-1)) was significantly higher in CAF versus PL, respectively. Thus, in this study a moderately high dose of CAF significantly increased the average power during a Wingate test, yet it does not affect peak power or static hand-grip strength.

Effect of a cold pressor test (CPT) on the cardiovascular (CV) responses to static handgrip exercise and peak force production

The transition from an inverted to upright position results in greater maximal voluntary contraction (MVC) force and greater CV response to exercise. It is unclear whether these results are due to the postural change per se or the heightened sympathetic state associated with the upright posture. We tested the hypothesis that elevated baseline sympathetic activity, elicited using a CPT, produces greater MVC handgrip force and a larger CV response to isometric handgrip exercise (IHG). 13 (8F/5M) normotensive subjects (22 ± 2 years) were randomized between cold (~10ºC) and thermoneutral (~24ºC) conditions. During each condition, their foot was submerged for 6 minutes. Non‐dominant MVC handgrip force (kg) was recorded then followed by a 150s rest period, 90s of IHG (40% MVC), and 120s of post‐exercise ischemia (no exercise). Heart rate (HR), mean arterial pressure (MAP) and calf blood flow (CBF) were measured throughout. Calf vascular resistance (CVR) was calculated. At rest, MAP (+4 ± 1 mmHg) and CVR (+5 ± 3 PRU) were increased in the cold condition. Handgrip MVC was greater (24 ± 10 vs. 22 ± 8 kg) in the thermoneutral condition. MAP during IHG was higher in the cold condition (93 ± 12 vs. 86 ± 7 mmHg). Application of a cold stimulus augmented resting MAP and CVR. This heightened sympathetic state resulted in a lower handgrip MVC force but an exaggerated MAP response to IHG

Changes in eccrine sweating on the glabrous skin of the palm and finger during isometric exercise

The goals of this study were to investigate changes in the sweating and cutaneous vascular responses on the palm and the volar aspect of the index finger during sustained static exercise of increasing intensity and to determine whether the former can be attributed to altered sweat gland activity. Five male and five female subjects performed maximal voluntary handgrip contractions (MVC: right hand) for 60 s at 20, 35 and 50% MVC (ambient temperature 25 °C, relative humidity 50%). The sweat rate and the number of activated sweat glands on the non-exercised hand showed intensity-dependent increases (P < 0.05). At 35 and 50% MVC, finger sweat secretion was significantly higher than on the palm, which was primarily associated with the number of activated sweat glands (P < 0.05). In addition, there was a marked simultaneous decrease in the cutaneous vascular conductance for the finger at 35 and 50% MVC (P < 0.05), but not for the palm. Our results suggest that a difference exists between intensity-dependent increases of sudomotor responses within more than one glabrous skin site. Specifically, markedly greater sweating occurs on the volar finger than on the palmar surface during sustained static exercise. These differences in sweat rate mainly resulted from changes in the number of activated sweat glands. In addition, intra-segment variations in cutaneous blood flow on the glabrous hand are shown.

Exaggerated sympathetic and pressor responses to handgrip exercise in older hypertensive humans: role of the muscle metaboreflex

Recent animal studies have reported that exercise pressor reflex (EPR)-mediated increases in blood pressure are exaggerated in hypertensive (HTN) rodents. Whether these findings can be extended to human hypertension remains unclear. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and venous metabolites were measured in normotensive (NTN; n = 23; 60 ± 1 yr) and HTN (n = 15; 63 ± 1 yr) subjects at baseline, and during static handgrip at 30 and 40% maximal voluntary contraction (MVC) followed by a period of postexercise ischemia (PEI) to isolate the metabolic component of the EPR. Changes in MAP from baseline were augmented in HTN subjects during both 30 and 40% MVC handgrip (P < 0.05 for both), and these group differences were maintained during PEI (30% PEI trial: Δ15 ± 2 NTN vs. Δ19 ± 2 HTN mmHg; 40% PEI trial: Δ16 ± 1 NTN vs. Δ23 ± 2 HTN mmHg; P < 0.05 for both). Similarly, in HTN subjects, MSNA burst frequency was greater during 30 and 40% MVC handgrip (P < 0.05 for both), and these differences were maintained during PEI [30% PEI trial: 35 ± 2 (NTN) vs. 44 ± 2 (HTN) bursts/min; 40% PEI trial: 36 ± 2 (NTN) vs. 48 ± 2 (HTN) bursts/min; P < 0.05 for both]. No group differences in metabolites were observed. MAP and MSNA responses to a cold pressor test were not different between groups, suggesting no group differences in generalized sympathetic responsiveness. In summary, compared with NTN subjects, HTN adults exhibit exaggerated sympathetic and pressor responses to handgrip exercise that are maintained during PEI, indicating that activation of the metabolic component of the EPR is augmented in older HTN humans.

Effects of rituximab in two patients with dysferlin-deficient muscular dystrophy

BackgroundThe administration of rituximab (RTX) in vivo results in B-cell depletion, but evidence for multiple mechanisms of action have been reported. Surprisingly, B cell depletion produced a response in patients with polymyositis, which is characterized as a T cell-mediated autoimmune disorder with biopsy findings similar to Miyoshi myopathy (MM). Indeed, in dysferlinopathies, there is evidence of immune system involvement including the presence of muscle inflammation and a down regulation of the complement inhibitory factor, CD55.MethodsTwo patients were treated with four weekly infusions of RTX 375 mg/m2. To measure the improvement in muscle strength after treatment, the isometric hand grip maximal voluntary contraction (MVC) was measured by load cell four times during treatment, and again after one year. In order to assess the reproducibility of our grip assessment, we determined the hand MVC analysis in 16 healthy subjects. Moreover, we measured the number of B cells present in patients by flow cytometric analysis during the course of treatment.ResultsThe analysis of B cell number during the course of treatment showed that CD20- and CD19-positive cells were depleted to 0-0.01%. The decrease in B cells was followed by an improvement in the mobility of the pelvic and shoulder girdles as shown by the MRC%. The MVC values of both patients began at values lower than normal whereas during treatment patients had improved percentage of muscle strength. The strength peak in both patients coincided with the minimum B cell values. There were no severe adverse events associated with an infusion of RTX.ConclusionWe consider the increase in muscle strength observed in both treated patients to be a consequence of their treatment with RTX. To our knowledge, these are the first cases of increased muscle strength in patients with MM. Furthermore, the results of this study indicate that B cell depletion with RTX may be useful in the treatment of patients affected by MM, suggesting a possible role for B cells in the pathophysiology of this muscle disorder.

Indication for cholinergically mediated cerebral vasodilatation during static exercise in humans

Cholinergically mediated vasodilatation is reported in humans, but its importance for cerebral perfusion during exercise is unknown. The increase in middle cerebral artery blood flow velocity (MCA Vmean) during static handgrip exercise was evaluated by blockade of acetylcholine receptors as well as with beta‐adrenergic blockade, in nine males in separate, randomized and counterbalanced trials over two minutes. Mean arterial pressure (MAP) increased during both 25 % and 40 % maximal voluntary contraction (MVC) handgrip (P &lt; 0.01) with no effect of treatment. Resting cardiac output was reduced by ~20% with beta‐adrenergic blockade (P &lt; 0.05) and increased by ~40% with vagal‐blockade (P &lt; 0.05). Compared to control, exercise‐induced increases in cardiac output were attenuated with beta‐adrenergic blockade (P &lt; 0.01) and abolished with cholinergic blockade. MCA Vmean increased ~16% during control exercise (independent of intensity; P &lt; 0.01). During 25% MVC handgrip, both cholinergic and beta‐adrenergic blockade abolished the exercise‐induced increase in MCA Vmean (~3 % and ~7 %, respectively), whereas at 40 % MVC only cholinergic blockade abolished the increase. These findings suggest that the increase in cerebral perfusion during exercise is dependent upon cardiac output, but that a cholinergically mediated vasodilatatory mechanism may also be important.

Impact of increased muscle sympathetic nerve activity on conduit artery shear rate patterns

Disturbed flow patterns induce a proatherogenic endothelial cell phenotype; however, the factors accountable for the oscillatory shear profiles in peripheral conduit arteries are not fully understood. We tested the hypothesis that acute elevations in muscle sympathetic nerve activity (MSNA) are accompanied by increases in conduit artery retrograde shear and oscillatory shear index (OSI). Fourteen healthy men (25±1 yrs) performed three sympatho‐excitatory maneuvers: progressive lower body negative pressure (LBNP) from −10 to −40 Torr, cold pressor test (CPT), and 35% maximal voluntary contraction handgrip followed by postexercise ischemia (PEI). MSNA, arterial blood pressure (BP), and brachial artery velocity and diameter were recorded continuously. All maneuvers elicited significant increases in MSNA total activity from baseline; whereas mean BP was only increased during CPT and PEI (p&lt;0.05). Interestingly, retrograde shear (−3.96±1.2 baseline vs. −8.15±1.8 s−1 −40 LBNP, p&lt;0.05) and OSI (0.09±0.02 baseline vs. 0.20±0.02 a.u. −40 LBNP, p&lt;0.05) were primarily increased during LBNP in which elevated MSNA was not accompanied by increases in BP. Together, these data suggest that elevated MSNA may promote an increase in retrograde and oscillatory shear; however, these effects may be influenced by concomitant changes in BP. Support: NIH RO1HL093167, HL52490

Increased muscle sympathetic nerve activity acutely alters conduit artery shear rate patterns

Escalating evidence indicates that disturbed flow patterns, characterized by the presence of retrograde and oscillatory shear stress, induce a proatherogenic endothelial cell phenotype; however, the mechanisms underlying oscillatory shear profiles in peripheral conduit arteries are not fully understood. We tested the hypothesis that acute elevations in muscle sympathetic nerve activity (MSNA) are accompanied by increases in conduit artery retrograde and oscillatory shear. Fourteen healthy men (25 +/- 1 yr) performed three sympathoexcitatory maneuvers: graded lower body negative pressure (LBNP) from 0 to -40 Torr, cold pressor test (CPT), and 35% maximal voluntary contraction handgrip followed by postexercise ischemia (PEI). MSNA (microneurography; peroneal nerve), arterial blood pressure (finger photoplethysmography), and brachial artery velocity and diameter (duplex Doppler ultrasound) in the contralateral arm were recorded continuously. All maneuvers elicited significant increases in MSNA total activity from baseline (P < 0.05). Retrograde shear (-3.96 +/- 1.2 baseline vs. -8.15 +/- 1.8 s(-1), -40 LBNP, P < 0.05) and oscillatory shear index (0.09 +/- 0.02 baseline vs. 0.20 +/- 0.02 arbitrary units, -40 LBNP, P < 0.05) were progressively augmented during graded LBNP. In contrast, during CPT and PEI, in which MSNA and blood pressure were concomitantly increased (P < 0.05), minimal or no changes in retrograde and oscillatory shear were noted. These data suggest that acute elevations in MSNA are associated with an increase in conduit artery retrograde and oscillatory shear, an effect that may be influenced by concurrent increases in arterial blood pressure. Future studies should examine the complex interaction between MSNA, arterial blood pressure, and other potential modulatory factors of shear rate patterns.