The efficacy of transcutaneous electrical nerve stimulation on the improvement of walking distance in patients with peripheral arterial disease with intermittent claudication: study protocol for a randomised controlled trial: the TENS-PAD study

International audienceBackground: In patients with peripheral arterial disease (PAD), walking improvements are often limited by early pain onset due to vascular claudication. It would thus appear interesting to develop noninvasive therapeutic strategies, such as transcutaneous electrical nerve stimulation (TENS), to improve the participation of PAD patients in rehabilitation programmes, and thus improve their quality of life. Our team recently tested the efficacy of a single 45-min session of 10-Hz TENS prior to walking. TENS significantly delayed pain onset and increased the pain-free walking distance in patients with class-II PAD. We now seek to assess the efficacy of a chronic intervention that includes the daily use of TENS for 3 weeks (5 days a week) on walking distance in Leriche-Fontaine stage-II PAD patients.Methods/design: This is a prospective, double-blind, multicentre, randomised, placebo-controlled trial. One hundred subjects with unilateral PAD (Leriche-Fontaine stage II) will be randomised into two groups (1:1). For the experimental group (TENS group): the treatment will consist of stimulation of the affected leg (at a biphasic frequency of 10 Hz, with a pulse width of 200 mu s, maximal intensity below the motor threshold) for 45 min per day, in the morning before the exercise rehabilitation programme, for 3 weeks, 5 days per week. For the control group (SHAM group): the placebo stimulation will be delivered according to the same modalities as for the TENS group but with a voltage level automatically falling to zero after 10 s of stimulation. First outcome: walking distance without pain. Secondary outcomes: transcutaneous oxygen pressure (TcPO2) measured during a Strandness exercise test, peak oxygen uptake (VO2 peak), endothelial function (EndoPAT (R)), Ankle-brachial Pressure Index, Body Mass Index, lipid profile (LDL-C, HDL-C, triglycerides), fasting glycaemia, HbA1c level, and the WELCH questionnaire.Discussion: TENS-PAD is the first randomised controlled trial that uses transcutaneous electrical therapy as an adjuvant technique to improve vascular function in the treatment of PAD. If the results are confirmed, this technique could be incorporated into the routine care in cardiovascular rehabilitation centers and used in the long term by patients to improve their walking capacity

Levosimedan improves hemodynamics functions without sympathetic activation in severe heart failure patients: direct evidence from sympathetic neural recording.

International audienceLevosimendan is a new inodilatory agent with calcium sensitizing activity. A major concern regarding the use of inotropic agent in heart failure is their effect on the sympathetic tone. This effect could explain increase in short term mortality with other inotropes. We aimed to assess the effect of levosimendan on sympathetic tone measured directly by microneurogra-phy. In a group of acute decompensated heart failure patients, we assessed cardiac performance by digital plethysmography measurement. Sympathetic tone was assessed through recording of muscle sympathetic nerve activity (MSNA) by micro-neurography. Recording were done blindly, for each patient after dobutamine perfusion was stopped (baseline) and 48 h after levosimendan infusion. Clinical, biological and morphological data were collected. We compared cardiac parameters and MSNA before and after administration of levosimendan. 13 patients were recruited (48 +/- 3.6 years). Systolic blood pressure and rate pressure product (mmHg x Beat/min) decreased significantly after levosimendan infusion (P< 0.05). Cardiac output and stroke volume were significantly increased after levosimendan infusion (P< 0.05). A significant decrease of MSNA activity is observed after levosimendan infusion (P< 0.01). Levosimendan induced improvement of cardiac performance, associated with a decreased in MSNA. This study show for the first time that levosimendan has no direct detrimental effect on the sympathetic nervous system

Between and within-day reliability of spatiotemporal gait parameters following stroke: Why measurement at maximal gait speed is required?

Abstract publiéObjectiveAssessment of the metrological properties of the spatiotemporal gait parameters is a key point because they are used as a monitoring criterion of post-stroke recovery and as outcome in interventional studies. The objective of the study was to explore the relevance of gait assessment at maximal gait speed (MGS) rather than spontaneous gait speed (SGS) for post-stroke subjects through (1) the study of between and within-day reliability data of spatiotemporal gait parameters at SGS and MGS; and (2) a comparison of the direct measurement of velocity at MGS versus its estimate. It was also designed to (3) highlight the importance of considering the distribution of the random error to use an adequate expression of the measurement error (MErr).Material/patients and methodsSpatiotemporal gait parameters – velocity, walk ratio, span acceleration, and spatiotemporal asymmetries indexes – from 30 post-stroke subjects (mean ± SD age, 51.6 ± 16.2 years; median [range] time since stroke, 4.4 [1 to 101] months; 60% of male; 70% using a walking assistive device) were collected using the Locometer (Satel, Blagnac, France) on three times, about 7 days (between-day) and 30 minutes (within-day) apart, at SGS and MGS. The minimal metrically detectable change with a 95% confidence interval was computed in original unit, or in percentage (MDCp) if the distribution of random error was heteroscedastic.ResultsReliability was better at MGS than at SGS, and for within than for between-day test-retest. MDCp for velocity were equal to 36.2%/16.2% at SGS for between/within-day test–retest, and 21.2% at MGS for between-day test-retest. Gait velocity at MGS should be measured and not estimated because of unacceptable error of prediction in 70% of cases. An inappropriate expression of MErr without taking into account the random error distribution leads to over-/underestimate of the significant modifications of gait parameters.Discussion – conclusionData from the present study allow for a suitable interpretation of spatiotemporal gait parameters modification for post-stroke subjects. We highlighted the necessary gait assessment at MGS, being the most likely to show differences related to therapeutic intervention for post-stroke subjects and showed that the velocity at MGS should be measured and not predicted

Effects of Resistance Exercise and Nutritional Supplementation on Dynamic Cerebral Autoregulation in Head-Down Bed Rest

International audienceHead-down bed rest (HDBR) is commonly considered as ground-based analog to spaceflight and simulates the headward fluid shift and cardiovascular deconditioning associated with spaceflight. We investigated in healthy volunteers whether HDBR, with or without countermeasures, affect cerebral autoregulation (CA). Twelve men (at selection: 34 ± 7 years; 176 ± 7 cm; 70 ± 7 kg) underwent three interventions of a 21-day HDBR: a control condition without countermeasure (CON), a condition with resistance vibration exercise (RVE) comprising of squats, single leg heel, and bilateral heel raises and a condition using also RVE associated with nutritional supplementation (NeX). Cerebral blood flow velocity was assessed using transcranial Doppler ultrasonography. CA was evaluated by transfer function analysis and by the autoregulatory index (Mxa) in order to determine the relationship between mean cerebral blood flow velocity and mean arterial blood pressure. In RVE condition, coherence was increased after HDBR. In CON condition, Mxa index was significantly reduced after HDBR. In contrast, in RVE and NeX conditions, Mxa were increased after HBDR. Our results indicate that HDBR without countermeasures may improve dynamic CA, but this adaptation may be dampened with RVE. Furthermore, nutritional supplementation did not enhance or worsen the negative effects of RVE. These findings should be carefully considered and could not be applied in spaceflight. Indeed, the subjects spent their time in supine position during bed rest, unlike the astronauts who perform normal daily activities

Cardiorenal anemia syndrome in chronic heart failure contributes to increased sympathetic nerve activity.

International audienceBACKGROUND: We sought to assess whether cardiorenal anemia syndrome (CRAS) in chronic heart failure (CHF) patients contributes to sympathetic overactivity through modulation of sympathetic reflexes. METHODS AND RESULTS: We prospectively studied 15 patients with CRAS and CHF and 15 control CHF patients, matched for age, gender distribution, type of cardiomyopathy, left ventricular ejection fraction (LVEF) and BMI. We compared muscle sympathetic nerve activity (MSNA) and the effect of peripheral chemoreflex deactivation on MSNA in both groups. We also compared sympathetic baroreflex function, assessed by the slope of the relationship between MSNA and diastolic blood pressure in both groups and while peripheral chemoreflexes were (by breathing 100% oxygen for 15min) or not deactivated. Baseline MSNA was significantly elevated in CHF patients with CRAS compared with control CHF patients (83.1±4.6 versus 64.9±2.9bursts/100 heart beats; P<0.05) and sympathetic baroreflex impaired (2.69±0.44 vs 5.25±0.60%bursts/mmHg; P<0.01). Chemoreflex deactivation with administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity (77.8±4.7 versus 82.1±4.9bursts/100 heart beats; P<0.01) and to an increase in sympathetic baroreflex function (2.77±0.45 vs 5.63±0.73%bursts/mmHg; P<0.01) in patients with CRAS and CHF. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamic or sympathetic baroreflex function in control CHF patients. CONCLUSIONS: CRAS in CHF patients is associated with elevated sympathetic activity mediated by both tonic activation of peripheral chemoreflex and baroreflex impairment

Excessive sympathetic activation in heart failure with chronic renal failure: role of chemoreflex activation.

International audienceOBJECTIVE: Sympathetic activation contributes both to the initiation and progression of heart failure. The role of chronic renal failure (CRF) in determining sympathetic overactivity in chronic heart failure (CHF) patients is unknown. We tested the hypothesis that in CHF patients, CRF could lead to increase sympathetic activity through tonic activation of excitatory chemoreceptor afferents. METHODS: We conducted a double-blind, randomized, vehicle-controlled study to examine the effect of chemoreflex deactivation on muscle sympathetic nerve activity in CHF patients with or without CRF. We compared effect of breathing 100% oxygen for 15 min in 15 stable CHF patients with CRF and 15 control CHF patients matched for age, sex, blood pressure and BMI. RESULTS: The baseline muscle sympathetic nerve activity was significantly elevated in CHF patients with CRF as compared with simple CHF patients (61 +/- 3 versus 42 +/- 4 bursts/min; P < 0.01). Administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity in CHF patients with CRF (from 61 +/- 3 to 55 +/- 4 bursts/min; P < 0.05). By contrast, neither 100% oxygen nor room air changed muscle sympathetic nerve activity or hemodynamics in patients with solely CHF. CONCLUSION: Tonic activation of excitatory chemoreflex afferents contributes to increased efferent sympathetic activity to muscle circulation and to blood pressure control in CHF patients with CRF. These findings may have important implications for understanding how CRF contributes to the progression of CHF and increases morbidity and mortality in CHF patients

Transcatheter aortic valve implantation reduces sympathetic activity and normalizes arterial spontaneous baroreflex in patients with aortic stenosis.

International audienceOBJECTIVES: This study sought to measure muscle sympathetic nerve activity (MSNA) in patients with aortic stenosis (AS) before and after transcatheter aortic valve implantation (TAVI) and to compare MSNA with that of control patients. BACKGROUND: TAVI is an emerging therapeutic option in patients with severe AS at high risk of open heart surgery. Whether patients with AS have increased sympathetic activity remains to be established, and the effects of TAVI on the sympathetic nervous system are also unknown. METHODS: We prospectively enrolled 14 patients with severe symptomatic AS treated by TAVI. Fourteen control patients matched for age, body mass index, and unscathed of AS were also included. All patients underwent MSNA and arterial baroreflex gain assessment at baseline and 1 week after TAVI for AS patients. RESULTS: Patients with AS had lower blood pressure (BP) levels, a significant increase in MSNA (61.0 ± 1.7 burst/min vs. 55.4 ± 1.4 burst/min; p < 0.05), and a decrease in arterial baroreflex gain (2.13 ± 0.14% burst/mm Hg vs. 3.32 ± 0.19% burst/mm Hg; p < 0.01) compared with matched control patients. The TAVI procedures induced an increase in BP associated with a significant decrease in MSNA (from 61.0 ± 1.7 burst/min to 54.1 ± 1.0 burst/min; p < 0.01) and was associated with a significant increase in arterial baroreflex gain (from 2.13 ± 0.14% burst/mm Hg to 3.49 ± 0.33% burst/mm Hg; p < 0.01). CONCLUSIONS: We report for the first time, through direct measurement of nerve activity, that patients with AS have increased sympathetic nervous system activity associated with a decrease in sympathetic baroreflex gain and that TAVI normalizes these parameters. This study provides evidence of a new beneficial effect of TAVI, namely, normalization of sympathetic nervous system hyperactivity

Direct evidences for sympathetic hyperactivity and baroreflex impairment in Tako Tsubo cardiopathy

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Baseline characteristics of the two groups of patients.

<p>LVEF (as assessed by echocardiography); ACEi: Angiotensin converting enzyme inhibitors; AT1: Angiotensin II type 1. Values are median (interquartile range).</p

Comparison of MSNA activity between Tako Tsubo patients and CHF control patient.

<p>In this figure we show the comparison of mean MSNA activity, expressed in burst/min, between 13 TTC patients (on the left) and 13 acutely decompensated CHF patients (on the right).</p