Background Muscle passive contraction of lower limb by neuromuscular electrostimulation (NMES) is frequently used in chronic heart failure (CHF) patients but no data are available concerning its action on sympathetic activity. 51.6 ± 3.3 vs 56.7 ± 3.3 bursts / min p < 0 1 after NMES). No variation of blood pressure PX-866 heart rate or Gpc3 respiratory parameters was observed after stimulation. Conclusion The results suggest that sensory stimulation of lower limbs by electrical device either TENS or NMES could inhibit sympathetic outflow directed to legs in CHF patients. These properties could benefits CHF patients and pave the way for a new non-pharmacological approach of CHF. Introduction Chronic heart failure (CHF) is usually characterised by sympathetic overactivity causing direct effect on the initiation and progression of heart failure. Consequently sympathetic activity (SA) is usually a strong predictor of morbidity and mortality . Risk -related to PX-866 this feature are numerous. Among them the risk of sudden death but also muscle weakness leading to exercise intolerance are common.. Thus SA represent a direct or indirect target for most therapeutics used in CHF as beta-blockade drugs  or resynchronization therapy [4 5 It has been shown that exercise can improve symptoms morbidity and outcomes related to CHF partly due to a diminution of resting SA [6 7 Exercise techniques used in this setting are time consuming costly and cannot be well applied to severe CHF patients. Neuromuscular electrical stimulation (NMES) could be an alternative in these patients [8-10]. Indeed the repetition of NMES on lower limbs is known to improve muscular atrophy with specific increase of muscular oxidative fibres (type I) allowing better aerobic capacity [11-13]. In CHF patients some studies shows that NMES modulates immunity and improve blood flow and muscle functioning  Beside these peripheral effects due to passive muscular contraction NMES also induces a sensory stimulation. In healthy subjects cutaneous electrical stimulation has an inhibitory effect on sympathetic activity . In CHF patients it has also been shown recently that cutaneous electrical stimulation improved baroreflex sensitivity  and authors hypothesized that TENS could interact with sympathetic activity. However in this study patients were not randomized the study was not controlled (i.e no sham stimulation) and SA was not measured. We therefore decided to undertake the following study in order to demonstrate that TENS benefits (i.e. baroreflex sensitivity enhancement) could be related to a direct PX-866 effect on SA as assessed by Muscle Sympathetic Nerve Activity (MSNA). In addition since NMES unlike TENS is the electrical standard treatment used in the rehabilitation of CHF patients we sought to test whether NMES would be associated with a decrease in SA (TENS effect during NMES) or another modulation of sympathetic activity. Using a double blind randomized sham controlled design we examined successively the effects of TENS and NMES on sympathetic activity assessed directly by nerve recording (MSNA) in CHF patients. Methods Ethics statements Twenty two patients (all in New York Heart Association (NYHA) Class III) with systolic CHF were prospectively recruited. All patient received pharmacotherapy according to the current guidelines for advanced CHF corresponding to Beta-blockade drugs Angiotensin-converting enzyme inhibitors or angiotensin II type-1 receptor inhibitors diuretics and anti-aldosterone drugs. Exclusion criteria were: non PX-866 sinusal rhythm PX-866 severe cardiac arrhythmia diabetes sensibility deficiency neuropathy chronic pain on leg. Informed written consent was obtained from all participants in accordance with standards established by the latest revision of the Declaration of Helsinki. The study was approved by the local Institutional Human Subjects Review Committee named “CPP Sud-Ouest et Outre Mer II”. Measurements Heart rate (HR) was measured constantly by an electrocardiogram (ADInstruments Castle Hill New South Wales Australia). Blood Pressure was measured constantly by the Finometer system (Finometer Finapress Medical SystemBV Amsterdam The Netherlands). Multiunit postganglionic sympathetic nerve activity was recorded as previously described . Briefly a tungsten microelectrode (shaft diameter 200mm tapering.