Marc Labrunee

Peripheral chemoreflex activation contributes to sympathetic baroreflex impairment in chronic heart failure.

Background: Chemoreflex-mediated sympathetic activation contributes to both initiation and progression of chronic heart failure (CHF). Method: To study the direct role of increased peripheral chemosensitivity in reducing sympathetic baroreflex function in CHF patients, we compared sympathetic baroreflex function, assessed by the slope of the relationship between muscle sympathetic nerve activity (MSNA) and DBP, in CHF patients with augmented (n = 18) and normal (n = 20) peripheral chemosensitivity. Using a double-blind, randomized, vehicle-controlled study, we examined the effect of chemoreflex deactivation (by breathing 100% oxygen for 15 min) on sympathetic baroreflex function in CHF patients with elevated and with normal chemosensitivity. Results: Baseline MSNA was elevated (60.6 ± 3.2 vs. 48.9 ± 3.7 bursts/min, P < 0.05) and sympathetic baroreflex function impaired (3.06 ± 0.55 vs. 5.51 ± 0.69 %bursts/mmHg, P < 0.05) in CHF patients with augmented peripheral chemosensitivity compared with controls. Administration of 100% oxygen led to a significant decrease in MSNA (from 60.5 ± 3.2 to 52.6 ± 3.2 bursts/min, P < 0.001) and increase in sympathetic baroreflex (from 2.95 ± 0.56 to 6.18 ± 0.77, P < 0.001) in CHF patients with enhanced chemoreflex sensitivity. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamics or sympathetic baroreflex function in CHF patients with normal chemosensitivity. Conclusion: We report for the first time that increased peripheral chemoreflex sensitivity directly decreases sympathetic baroreflex function in CHF patients. This interaction contributes to sympathetic overactivity and blunted sympathetic baroreflex function of CHF patients and may explain how chemoreceptors contribute to the bad prognosis of CHF patients.

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

Objective 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.

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

Background The exact pathophysiology of Tako-Tsubo cardiomyopathy (TTC) remains unknown but a role for sympathetic hyperactivity has been suggested. Up to now, no direct evidence of sympathetic nerve hyperactivity has been established nor involvement of sympathetic baroreflex identified. The aim of our study was to determine, by direct sympathetic nerve activity (SNS) recording if sympathetic nervous system activity is increased and spontaneous baroreflex control of sympathetic activity reduced in patients with TTC. Methods We included 13 patients who presented with TTC and compared their SNS activity and spontaneous baroreflex control of sympathetic activity with that of 13 control patients with acutely decompensated chronic heart failure. SNS activity was evaluated by microneurography, a technique assessing muscle sympathetic nerve activity (MSNA). Spontaneous baroreflex control of sympathetic activity was evaluated as the absolute value of the slope of the regression line representing the relationship between spontaneous diastolic blood pressure values and concomitant SNS activity. Control patients were matched for age, sex, left ventricular ejection fraction and creatinine clearance. Results The mean age of the patients with TTC was 80 years, all patients were women. There were no significant differences between the two groups of patients for blood pressure, heart rate or oxygen saturation level. TTC patients presented a significant increase in sympathetic nerve activity (MSNA median 63.3 bursts/min [interquartile range 61.3 to 66.0] vs median 55.7 bursts/min [interquartile range 51.0 to 61.7]; p = 0.0089) and a decrease in spontaneous baroreflex control of sympathetic activity compared to matched control patients (spontaneous baroreflex control of sympathetic activity median 0.7%burst/mmHg [interquartile range 0.4 to 1.9] vs median 2.4%burst/mmHg [interquartile range 1.8 to 2.9]; p = 0.005). Conclusions We report for the first time, through direct measurement of sympathetic nerve activity, that patients with TTC exhibit elevated SNS activity associated with a decrease in spontaneous baroreflex control of sympathetic activity. These data may explain the pathophysiology and clinical presentation of patient with TTC.

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

Sympathetic activation contributes to both the initiation and progression of heart failure. The role of anemia in determining sympathetic overactivity in chronic heart failure (CHF) patients is unknown. We tested the hypothesis that, in CHF patients, anemia could lead to increased sympathetic activity through tonic activation of excitatory chemoreceptor afferents. 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 and without anemia. We compared the effect of breathing 100% oxygen for 15 minutes in 18 stable CHF patients with anemia and 18 control CHF patients matched for age, sex, blood pressure, and body mass index. Baseline muscle sympathetic nerve activity was significantly elevated in CHF patients with anemia compared with patients with CHF alone (56.0±3.2 versus 45.5±3.1 bursts per minute; P<0.0237). Administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity in CHF patients with anemia (from 56.0±3.4 to 50.9±3.2 bursts per minute; P<0.0019). In contrast, neither room air nor 100% oxygen changed muscle sympathetic nerve activity or hemodynamics in patients with CHF alone. We report for the first time direct evidence of increased sympathetic nerve traffic in patients with CHF-related anemia. Sympathetic hyperactivity in patients with CHF and anemia is partially chemoreflex mediated and could explain how anemia contributes to the progression of CHF and increases morbidity and mortality in these patients.

High-Intensity Interval Exercise Improves Vagal Tone and Decreases Arrhythmias in Chronic Heart Failure

PURPOSE Autonomic dysfunction including sympathetic activation and vagal withdrawal has been reported in patients with chronic heart failure (CHF). We tested the hypotheses that high-intensity interval exercise (HIIE) in CHF patients would enhance vagal modulation and thus decrease arrhythmic events. METHODS Eighteen CHF patients underwent a baseline assessment (CON) and were then randomized to a single session of HIIE and to an isocaloric moderate-intensity continuous exercise (MICE). We evaluated the HR, HR variability parameters, and arrhythmic events by 24-h Holter ECG recordings after HIIE, MICE, and CON sessions. RESULTS We found that HR was significantly decreased after HIIE (68 ± 3 bpm, P < 0.01) when compared with CON and MICE values (71.1 ± 2 and 69 ± 3 bpm, respectively). HIIE led to a significant increase in normalized high-frequency power (35.95% ± 2.83% vs 31.56% ± 1.93% and 24.61% ± 2.62% for CON and MICE, respectively, P < 0.01). Both exercise conditions were associated with an increase in very low frequency power comparative to CON. After HIIE, premature ventricular contractions were significantly decreased (531 ± 338 vs 1007 ± 693 and 1671 ± 1604 for CON and MICE, respectively, P < 0.01). An association was found between the changes in premature ventricular contraction and the changes in low-frequency/high-frequency ratio (r = 0.66, P < 0.01) in patients exposed to HIIE. CONCLUSION We demonstrate that a single session of HIIE improves autonomic profile of CHF patients, leading to significant reductions of HR and arrhythmic events in a 24-h posttraining period. Cardioprotective effects of HIIE in CHF patients need to be confirmed in a larger study population and on a long-term basis.

Acute electromyostimulation Decreases Muscle Sympathetic Nerve Activity in Patients with Advanced Chronic Heart Failure (EMSICA Study)

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. However, Transcutaneous Electrical Nerve Stimulation (TENS) is able to improve baroreflex in CHF. The primary aim of the present study was to investigate the acute effect of TENS and NMES compared to Sham stimulation on sympathetic overactivity as assessed by Muscle Sympathetic Nerve Activity (MSNA). Methods We performed a serie of two parallel, randomized, double blinded and sham controlled protocols in twenty-two CHF patients in New York Heart Association (NYHA) Class III. Half of them performed stimulation by TENS, and the others tested NMES. Results Compare to Sham stimulation, both TENS and NMES are able to reduce MSNA (63.5 ± 3.5 vs 69.7 ± 3.1 bursts / min, p < 0.01 after TENS and 51.6 ± 3.3 vs 56.7 ± 3.3 bursts / min, p < 0, 01 after NMES). No variation of blood pressure, heart rate or 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.

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

Abstract Levosimendan 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 × 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.

Improved Walking Claudication Distance with Transcutaneous Electrical Nerve Stimulation: An Old Treatment with a New Indication in Patients with Peripheral Artery Disease.

ObjectiveThe aim of this study was to determine whether 45 mins of transcutaneous electrical nerve stimulation before exercise could delay pain onset and increase walking distance in peripheral artery disease patients. DesignAfter a baseline assessment of the walking velocity that led to pain after 300 m, 15 peripheral artery disease patients underwent four exercise sessions in a random order. The patients had a 45-min transcutaneous electrical nerve stimulation session with different experimental conditions: 80 Hz, 10 Hz, sham (presence of electrodes without stimulation), or control with no electrodes, immediately followed by five walking bouts on a treadmill until pain occurred. The patients were allowed to rest for 10 mins between each bout and had no feedback concerning the walking distance achieved. ResultsTotal walking distance was significantly different between T10, T80, sham, and control (P < 0.0003). No difference was observed between T10 and T80, but T10 was different from sham and control. Sham, T10, and T80 were all different from control (P < 0.001). There was no difference between each condition for heart rate and blood pressure. ConclusionsTranscutaneous electrical nerve stimulation immediately before walking can delay pain onset and increase walking distance in patients with class II peripheral artery disease, with transcutaneous electrical nerve stimulation of 10 Hz being the most effective.

Whole-Body Strength Training Using a Huber Motion Lab in Coronary Heart Disease Patients: Safety, Tolerance, Fuel Selection, and Energy Expenditure Aspects and Optimization

Objective The aim of this study was to investigate safety, tolerance, relative exercise intensity, and muscle substrate oxidation during sessions performed on a Huber Motion Lab in coronary heart disease patients. Design After an assessment of V˙o2 peak, 20 coronary heart disease patients participated in two different exercises performed in random order at 40% and 70% (W40 and W70) of the maximal isometric voluntary contraction. Results No significant arrhythmia or abnormal blood pressure responses occurred during either session, and no muscle soreness was reported within 48 hrs posttest. The authors found a difference between W40 and W70 sessions for mean (standard deviation) ventilation (25.1% [8%] and 32.1% [9%] of maximal ventilation, respectively; P = 0.04) and a small difference for mean (standard deviation) heart rate (73 [7] and 79 [8] beats/min, respectively; P < 0.01). When compared with the W40, the W70 was associated with higher active energy expenditure (2.4 [0.6] and 3.1 [0.9] Kcal/min, respectively; P < 0.0001) and a similar mean (standard deviation) oxygen uptake (5.5 [1] and 6.6 [1] ml/min per kilogram, respectively; P = 0.07). The qualitative percentages of carbohydrates and lipids oxidized were 71% and 29%, respectively, at W40 and 91% and 9%, respectively, at W70. Conclusions Both protocols, which consisted of repeating 6-sec phases of contractions with 10 secs of passive recovery on the Huber Motion Lab, seemed to be well tolerated, safe, and feasible in this group of coronary heart disease patients.

300 The cardiorenal anaemia syndrome in chronic heart failure: Focus on sympathetic activity

Purpose: In Hypertension, left ventricle (LV) hypertrophy (LVH) is a potent prognostic factor to predict outcome. Proton Nuclear Magnetic Resonance (H NMR) spectroscopy, a new technique for analyzing blood metabolites profiles has proved to be one of the most powerful technologies in metabonomic studies of biofluids. We investigated for plasma LVH biomarkers of human Hypertensive Heart Disease.