Single-unit Muscle Sympathetic Nerve Activity Research Articles

Muscle sympathetic single-unit responses during rhythmic handgrip exercise and isocapnic hypoxia in males: the role of sympathoexcitation magnitude.

A small proportion of postganglionic muscle sympathetic single units can be inhibited during sympathoexcitatory stressors in humans. However, whether these responses are dependent on the specific stressor or the level of sympathoexcitation remains unclear. We hypothesize that, when matched by sympathoexcitatory magnitude, different stressors can evoke similar proportions of inhibited single units. Multiunit and single-unit muscle sympathetic nerve activity (MSNA) were recorded in seven healthy young males at baseline and during 1) rhythmic handgrip exercise (40% of maximum voluntary contraction) and 2) acute isocapnic hypoxia (partial pressure of end-tidal O2 47 ± 3 mmHg). Single units were classified as activated, nonresponsive, or inhibited if the spike frequency was above, within, or below the baseline variability, respectively. By design, rhythmic handgrip and isocapnic hypoxia similarly increased multiunit total MSNA [Δ273 ± 208 vs. Δ254 ± 193 arbitrary units (AU), P = 0.84] and single-unit spike frequency (Δ8 ± 10 vs. Δ12 ± 13 spikes/min, P = 0.12). Among 19 identified single units, the proportions of activated (47% vs. 68%), nonresponsive (32% vs. 16%), and inhibited (21% vs. 16%) single units were not different between rhythmic handgrip and isocapnic hypoxia (P = 0.42). However, only 9 (47%) single units behaved with concordant response patterns across both stressors (7 activated, 1 nonresponsive, and 1 inhibited during both stressors). During the 1-min epoch with the highest increase in total MSNA during hypoxia (Δ595 ± 282 AU, P < 0.01) only one single unit was inhibited. These findings suggest that the proportions of muscle sympathetic single units inhibited during stress are associated with the level of sympathoexcitation and not the stressor per se in healthy young males.NEW & NOTEWORTHY Subpopulations of muscle sympathetic single units can be inhibited during mild sympathoexcitatory stress. We demonstrate that rhythmic handgrip exercise and isocapnic hypoxia, when matched by multiunit sympathoexcitation, induce similar proportions of single-unit inhibition, highlighting that heterogeneous single-unit response patterns are related to the level of sympathoexcitation independent of the stressor type. Interestingly, only 47% of single units behaved with concordant response patterns between stressors, suggesting the potential for functional specificity within the postganglionic neuronal pool.

Muscle sympathetic single‐unit responses during rhythmic handgrip exercise and isocapnic hypoxia in males: The role of sympathoexcitation magnitude

A small proportion of postganglionic muscle sympathetic single units can be inhibited during sympathoexcitatory stressors in humans. However, whether these responses are dependent on the specific stressor or the level of sympathoexcitation remains unclear. We hypothesize that, when matched by sympathoexcitatory magnitude, different stressors can evoke similar proportions of inhibited single units. Multiunit and single-unit muscle sympathetic nerve activity (MSNA) were recorded in seven healthy, young males at baseline and during: 1) rhythmic handgrip exercise (40% of maximum voluntary contraction) and 2) acute isocapnic hypoxia (partial pressure of end-tidal O2 of 47±3 mmHg). Single units were classified as activated, nonresponsive, or inhibited if the spike frequency was above, within, or below the baseline variability, respectively. By design, rhythmic handgrip and isocapnic hypoxia similarly increased multiunit total MSNA (delta 273±208 vs. 254±193 AU, P=0.84) and single-unit spike frequency (delta 7±9 vs. 11±15 spikes/min, P=0.29). Among 19 identified single units, the proportion of activated (58% vs. 74%) non-responsive (21% vs. 16%) and inhibited (21% vs. 10%) single units were not different between rhythmic handgrip and isocapnic hypoxia (P=0.57). However, only 9 (47%) single units behaved with concordant response patterns across both stressors (8 activated and 1 non-responsive during both stressors). During the 1-min epoch with the highest increase in total MSNA during hypoxia (delta 595±282 AU, P<0.01) none of the single units were inhibited. These findings suggest that the proportion of muscle sympathetic single units inhibited during stress are associated with the level of sympathoexcitation and not the stressor per se in healthy young males.

Different prognosis between severe and very severe obstructive sleep apnea patients; Five year outcomes

BackgroundObstructive sleep apnea (OSA) is characterized by augmented sympathetic nerve activity. In our previous study, patients with OSA and an apnea-hyperpnea index (AHI)>55events/h showed increased single-unit muscle sympathetic nerve activity compared to patients with OSA and AHI of 30–55events/h. However, the prognostic impact in these patients remains unclear. MethodsNinety-one OSA patients were included. All patients who had indication for continuous positive airway pressure (CPAP) were treated with CPAP. Patients were divided into three groups: mild/moderate OSA (S), AHI<30events/h (n=44); severe OSA (SS), AHI 30–55events/h (n=29); and very severe OSA (VSS), AHI>55events/h (n=18). The primary endpoint was a composite outcome composed of death, cardiovascular events, stroke, and heart failure with hospitalization. ResultsIn the 5-year follow-up, the primary event rate in the SS group [3 events (7%)] was the same as that in the S group [3 events (10%)]. However, the VSS group showed a significantly higher primary event rate among the three groups [6 events (33%), p<0.05]. In Cox regression analysis, the VSS group had the highest hazard ratio compared to other risk factors. ConclusionsCPAP was effective for preventing cardiovascular disease in patients with severe OSA, however patients with very severe OSA still had a high event rate, indicating that CPAP treatment might be insufficient to reduce the OSA-related risk burden in patients with very severe OSA. Additional systemic medical treatment for CPAP might be needed in patients with very severe OSA.

Single-unit muscle sympathetic nerve activity (MSNA) is more powerful predictor of sleep apnea syndrome patient’s severity than multiunit MSNA

syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), associated with obesity and metabolic syndrome. Aim of the study is to assess the prevalence of OSAS in patients with NAFLD without severe obesity. Methods. Thirty-five patients with histological NAFLD and body mass index (BMI) b35 kg/m2 underwent a complete polysomnographic (PSG) study, analyzed by a sleep expert according to the American Academy Sleep Medicine criteria. Results. PSG analysis showed that out of the 35 patients (28 males, mean age 53 ± 13.7 years, BMI 28 ± 3.3 kg/m2, neck circumference 40.6 ± 3.3 cm, waist-to-hip ratio 0.94). 23 patients (66%) had a sleep study positive for OSAS, as detected by an apnea-hypopnea index (AHI) N 5. Out of these, 13 (37%) had mild OSAS (AHI 5-15), 8 (23%) moderate OSAS (AHI 1530) and 2 (6%) severe OSAS (AHI N 30). Lowest oxygen saturation in patients without OSAS was 84 ± 8%, 82 ± 7% in those with mild OSAS, 80 ± 7% and 73 ± 9.9% respectively in thosewithmoderate and severe disease. Conclusions. In non-severely obese patients with NAFLD high risk of OSAS with sleepiness, as detected by BQ and ESS positivity, is independently associated with more severe liver damage; furthermore, a high prevalence of OSAS has been confirmed by PSG.

Paradoxical muscle sympathetic reflex activation in human heart failure.

Muscle sympathetic activation in heart failure with reduced ejection fraction (HFrEF) has been attributed, on the basis of multiunit recordings, to attenuated inhibitory feedback from stretch-sensitive cardiopulmonary mechanoreceptors. However, such preparations integrate 2 populations of single units exhibiting directionally opposite firing when atrial pressure is perturbed. We tested the hypothesis that the proportion of single units firing paradoxically when filling pressure increases is augmented in HFrEF. Muscle sympathetic nerve activity and estimated central venous pressure were recorded during nonhypotensive lower body negative pressure (LBNP; -10 mm Hg) and nonhypertensive positive pressure (LBPP; +10 mm Hg) in 11 treated HFrEF (left ventricular ejection fraction 25 ± 6% [mean ± standard deviation]) patients and 14 similarly aged controls. Single-unit muscle sympathetic nerve activity discharge was termed either anticipated, if firing frequency exhibited classic negative-feedback responses, or paradoxical. LBNP and LBPP had no heart rate, stroke volume, or blood pressure effects (P>0.05). Estimated central venous pressure decreased with LBNP (P<0.05), increased with LBPP (P<0.05), and was consistently higher in HFrEF (P<0.05). During LBNP, the ratio of single units with anticipated and paradoxical discharge was similar in HFrEF (18:7) and controls (27:5), whereas LBPP elicited paradoxical reflex excitation in a greater proportion of HFrEF single units (7:18 versus 24:6; P=0.0001). Consequently, LBPP increased mean single-unit firing frequency (P<0.05) and did not inhibit multiunit muscle sympathetic nerve activity of HFrEF subjects (P<0.05 versus controls). Firing of 12/18 HFrEF (but no control) single units increased during both LBPP and LBNP. These findings provide the first evidence in human HFrEF for an augmented excitatory cardiopulmonary-muscle sympathetic nerve activity reflex response to increased preload, incorporating 2 distinct single-unit populations with differing firing properties.

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Clinical Implications

HomeHypertensionVol. 61, No. 2Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Feb 2013https://doi.org/10.1161/HYP.0b013e318284b8b8Hypertension. 2013;61:267Autoantibodies in Primary Aldosteronism (page 526)Primary aldosteronism (PA) is the most frequent endocrine cause of hypertension. The differential diagnosis between its 2 main subtypes, for example—aldosterone-producing adenoma and idiopathic hyperaldosteronism, is the key for selecting surgical or medical treatment, but challenging.In this study, we detected autoantibodies against the AT1 receptor (AT1AA) at a raised titer in serum of PA patients, and particularly in those with an aldosterone-producing adenoma as compared with those with idiopathic hyperaldosteronism or essential hypertension with similar blood pressure (BP) elevation. Of clinical relevance, the AT1AA titer provided a discrimination of aldosterone-producing adenoma from idiopathic hyperaldosteronism, thus suggesting that the AT1AA titer can help in selecting the PA patients to be submitted to adrenal vein sampling. The latter test, which is expensive, invasive, and not widely available, is recommended by the Endocrine Society Guidelines in all patients who are candidates for adrenalectomy.Finally, the mechanisms underlying PA have eluded identification thus far notwithstanding a long quest. As these AT1AA are suggested to play an agonistic effect, including stimulation of aldosterone secretion, their presence in aldosterone-producing adenoma patients could explain the persistent over-secretion of aldosterone in spite of the high BP, the suppression of the renin-angiotensin system and the hypokalemia, all factors that would be expected to blunt aldosterone secretion. Hence our data might shed a new light on the pathophysiology of PA.Download figureDownload PowerPointRenal Denervation and Sympathetic Activity (page title>Autoantibodies in Primary Aldosteronism (page 457)Catheter-based renal denervation has emerged as a novel treatment option for patients with resistant hypertension. The limited number of studies available thus far suggest that the procedure is safe and results in a significant and sustained BP reduction in the majority of treated patients with resistant hypertension. Although ablation of efferent renal nerves, as evident form a mean reduction in renal noradrenaline spillover of 47%, is likely to contribute to the BP lowering effects via alteration of renin release, renal blood flow, and tubular sodium retention, inhibition of central sympathetic outflow has also been documented by applying multiunit muscle sympathetic nerve activity recordings.Here, we examined whether renal denervation may differentially influence the sympathetic discharge pattern of single vasoconstrictor neurons in patients with resistant hypertension and found that all properties of single-unit muscle sympathetic nerve activity, including firing rates of individual vasoconstrictor fibers, firing probability, and multiple firing incidence of single units within a cardiac cycle, were substantially reduced. These findings indicate that renal denervation may restrain abnormal patterns of sympathetic nerve firing commonly evident in patients with resistant hypertension and exhibit renal signaling via afferent nerves projecting to certain brain stem nuclei as a likely contributor to the BP rise in resistant hypertension.Download figureDownload PowerPointCombination Therapy, CV Events, and BP Control (page Sympathetic Activity (page title>Autoantibodies in Primary Aldosteronism (page 309)Combination therapy is required to achieve current BP targets in ≈75% of hypertensive patients. Previous studies indicate that initial use of a combination accelerates the time course over which BP control is attained. However, the optimal time frame for achieving BP control in clinical practice has never been defined, and criteria for using initial combination therapy remain uncertain. In a retrospective, matched cohort study, the impact of initial versus delayed combination therapy on the risk of developing a cardiovascular (CV) event was assessed in a community practice setting. The mean baseline BP was ≈150/85 mm Hg, and two thirds had stage I hypertension. Initial combination treatment led to more rapid and more effective BP control and was associated with a 34% risk reduction for CV events or death relative to patients initiated on monotherapy and subsequently uptitrated to combination treatment by their practicing physicians. Fewer patients who experienced a CV event achieved target BP, and on-treatment BP parameters accounted for most of the difference in CV event rates.Initial combination therapy was also associated with a significant reduction in healthcare resource utilization. These results suggest that combination therapy should be initiated routinely in most patients likely to require multiple agents to reach goal BP, and that initial combination therapy is a superior treatment strategy for a large segment of the hypertensive population including many patients with mild hypertension.Download figureDownload PowerPoint Previous Back to top Next FiguresReferencesRelatedDetails February 2013Vol 61, Issue 2 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/HYP.0b013e318284b8b8 Originally publishedFebruary 1, 2013 PDF download Advertisement

Abstract 19395: Increased Multiple Firing of Single Muscle Vasoconstrictor Neurons during Lower Body Positive Pressure in Human Heart Failure

Introduction: Functionally specific efferent renal sympathetic nerves fire selectively in response to distinct hemodynamic afferent inputs. Using norepinephrine spillover, our group detected a heart failure (HF)-specific cardio-cardiac sympathoexcitatory reflex stimulated by high atrial pressure. Efferent discharge directed at other vascular beds similarly activated by atrial stretch might not be detected by multi-unit sympathetic recordings. Hypothesis: In contrast to healthy controls (CON), in HF some muscle sympathetic fibers respond paradoxically (i.e. increase firing) to increases in filling pressure. Methods: Single-unit muscle sympathetic nerve activity (sMSNA; microneurography) and peripheral venous pressure (PVP; forearm catheter) were recorded from 11 CON and 10 treated HF (LVEF 27±6%) patients at baseline and during non-hypotensive lower body negative pressure (LBNP; -10mmHg) and non-hypertensive lower body positive pressure (LBPP; +10mmHg). sMSNA firing frequency and incidence, and the percentage of multiple within-burst firing was calculated for each condition. Results: PVP was reduced with LBNP (p&lt;0.05) and increased with LBPP (p&lt;0.05) in both groups, with PVP greater in HF across each condition (p&lt;0.05). Blood pressure and heart rate were unchanged by LBNP or LBPP in both groups (p&gt;0.05). We identified 26 and 22 single-units in CON and HF patients, respectively. sMSNA firing frequency was similar (p&gt;0.05) in CON and HF at baseline (30±18 vs. 35±15 spikes/min) and during LBNP (45±24 vs. 42±23 spikes/min) but higher in HF during LBPP (28±17 vs. 40±22 spikes/min, p=0.05). sMSNA firing incidence was similar (p&gt;0.05) in both groups across each condition. The percentage of within-burst multiple spike firing was similar (p&gt;0.05) in CON and HF during baseline (24±9% vs. 24±7%) and LBNP (25±11% vs. 28±14%) but higher in HF during LBPP (17±8% vs. 34±16%, p&lt;0.001). Conclusions: In HF, increases in PVP with non-hypertensive LBPP cause a paradoxical increase in muscle sympathetic single-unit firing frequency and multiple within-burst firing, compared to CON. This provides evidence of a sympathoexcitatory cardiac-skeletal muscle vasoconstrictor reflex in human HF that may be attenuated by normalizing filling pressures.

Substantial Reduction in Single Sympathetic Nerve Firing After Renal Denervation in Patients With Resistant Hypertension

Renal denervation (RDN) has been shown to reduce blood pressure (BP) and muscle sympathetic nerve activity (MSNA) in patients with resistant hypertension. The mechanisms underlying sympathetic neural inhibition are unknown. We examined whether RDN differentially influences the sympathetic discharge pattern of vasoconstrictor neurons in patients with resistant hypertension. Standardized office BP, single-unit MSNA, and multi-unit MSNA were obtained at baseline and at 3-month follow-up in 35 patients with resistant hypertension. Twenty-five patients underwent RDN, and 10 patients underwent repeated measurements without RDN (non-RDN). Baseline BP averaged 164/93 mm Hg (RDN) and 164/87 mm Hg (non-RDN) despite use of an average of 4.8 ± 0.4 and 4.4 ± 0.5 antihypertensive drugs, respectively. Mean office BP decreased significantly by -13/-6 mm Hg for systolic BP (P<0.001) and diastolic BP (P<0.05) with RDN but not in non-RDN at 3-month follow-up. RDN moderately decreased multi-unit MSNA (79 ± 3 versus 73 ± 4 bursts/100 heartbeats; P<0.05), whereas all properties of single-unit MSNA including firing rates of individual vasoconstrictor fibers (43 ± 5 versus 27 ± 3 spikes/100 heartbeats; P<0.01), firing probability (30 ± 2 versus 22 ± 2% per heartbeat; P<0.02), and multiple firing incidence of single units within a cardiac cycle (8 ± 1 versus 4 ± 1% per heartbeat; P<0.05) were substantially reduced at follow-up. BP, single-unit MSNA, and multi-unit MSNA remained unaltered in the non-RDN cohort at follow-up. RDN results in the substantial and rapid reduction in firing properties of single sympathetic vasoconstrictor fibers, this being more pronounced than multi-unit MSNA inhibition. Whether the earlier changes in single-unit firing patterns may predict long-term BP response to RDN warrants further exploration.

788 PROFOUND REDUCTION IN SYMPATEHTIC NERVE FIRING PATTERN AFTER RENAL DENERVATION IN RESISTANT HYPERTENSION

Objective: Renal denervation (RDN) has been shown to reduce blood pressure (BP) and sympathetic activation in resistant hypertension (RH). The underlying mechanisms involved in sympathetic neural inhibition are unknown. We examined whether RDN may influence differentially sympathetic discharge of vasoconstrictor neurons in patients with RH. Design and method: Standardized office BP, multi-unit and single-unit muscle sympathetic nerve activity (MSNA) measured by microneurography were obtained in 23 patients with RH (57 ± 12yrs) before and 3 months after RDN. Results: Baseline BP averaged 166/74 ± 18/20mmHg despite the use of 4.8 ± 2.0 antihypertensive drugs. RDN was performed with an average of 9.4 ± 1.8 total ablations. SBP decreased significantly by -11 ± 18 mmHg (p < 0.01) and DBP by -5 ± 10 mmHg (p < 0.05). While multi-unit MSNA was only moderately reduced (78 ± 17 vs 71 ± 17bursts/100 heart beats (hb); p < 0.05), all properties of single-unit MSNA including firing rates of individual vasoconstrictor fibers (44 ± 25 vs 27 ± 17 spikes/100hb; p < 0.01), firing probability (31 ± 12 vs 22 ± 12% of hb; p < 0.02), and the multiple firing incidence of single units (9 ± 8 vs 4 ± 4% of hb; p < 0.05) were substantially reduced at 3 month follow up. The DBP reduction was significantly related to multi-unit MSNA decrease (r = 0.54; p < 0.01), but not to single-unit firing pattern. Conclusions: In patients with RH, RDN results in a marked and rapid reduction in the single-unit sympathetic firing discharge pattern of active vasoconstrictor fibres that appears to be more pronounced than multi-unit MSNA reduction. Whether early assessment of the changes in single-unit firing characteristics may be useful to predict the BP response to RDN warrants further investigation.

Augmented single‐unit muscle sympathetic nerve activity in heart failure with chronic atrial fibrillation

Atrial fibrillation (AF) is a common complication in heart failure (HF) patients. However, it remains unclear whether irregular ventricular response patterns induced by AF increase sympathetic nerve activity. We measured resting multi- and single-unit muscle sympathetic nerve activity (MSNA) in 21 age-matched HF patients with chronic AF (n = 11) rhythm or sinus rhythm (SR, n = 10). The multi-unit MSNA, which was expressed as total activity, was similar between HF + AF patients and HF + SR patients. However, the single-unit MSNA in HF + AF patients was significantly greater than that in HF + SR patients (62 ± 9 spikes min(-1) vs. 42 ± 4 spikes min(-1), P < 0.05). Moreover, the incidence of multiple firing of single-unit MSNA within a given burst was augmented in HF + AF patients as compared with HF + SR patients (48 ± 8% vs. 26 ± 3%, P < 0.01). A significant negative relationship was observed between the reduced diastolic pressure induced by a prolonged cardiac interval in AF subjects and single-unit MSNA frequency within one cardiac interval in each HF + AF subject. The firing characteristics of single-unit MSNA were different between HF patients with AF and HF patients with SR; particularly, those with a prolonged long RR interval showed multiple firings of single-unit MSNA. These findings suggest that AF per se leads to the instantaneous augmentation of single-unit MSNA induced by decreased diastolic pressure, which might partially contribute to disease progression in HF patients.

Advantage of Recording Single-Unit Muscle Sympathetic Nerve Activity in Heart Failure

Elevated sympathetic activation is a characteristic feature of heart failure (HF). Excessive sympathetic activation under resting conditions has been shown to increase from the early stages of the disease, and is related to prognosis. Direct recording of multiunit efferent muscle sympathetic nerve activity (MSNA) by microneurography is the best method for quantifying sympathetic nerve activity in humans. To date, this technique has been used to evaluate the actual central sympathetic outflow to the periphery in HF patients at rest and during exercise; however, because the firing occurrence of sympathetic activation is mainly synchronized by pulse pressure, multiunit MSNA, expressed as burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats), may have limitations for the quantification of sympathetic nerve activity. In HF, multiunit MSNA is near the maximum level, and cannot increase further than the heartbeat. Single-unit MSNA analysis in humans is technically demanding, but provides more detailed information regarding central sympathetic firing. Although a great deal is known about the response of multiunit MSNA to stress, little information is available regarding the responses of single-unit MSNA to physiological stress and disease. The purposes of this review are to describe the differences between multiunit and single-unit MSNA during stress and to discuss the advantages of single-unit MSNA recording in improving our understanding the pathology of increased sympathetic activity in HF.

Change in sympathetic nerve firing pattern associated with dietary weight loss in the metabolic syndrome

Sympathetic activation in subjects with the metabolic syndrome (MS) plays a role in the pathogenesis of cardiovascular disease development. Diet-induced weight loss decreases sympathetic outflow. However the mechanisms that account for sympathetic inhibition are not known. We sought to provide a detailed description of the sympathetic response to diet by analyzing the firing behavior of single-unit sympathetic nerve fibers. Fourteen subjects (57 ± 2 years, nine men, five females) fulfilling ATP III criteria for the MS underwent a 3-month low calorie diet. Metabolic profile, hemodynamic parameters, and multi-unit and single-unit muscle sympathetic nerve activity (MSNA, microneurography) were assessed prior to and at the end of the diet. Patients’ weight dropped from 96 ± 4 to 88 ± 3 kg (P < 0.001). This was associated with a decrease in systolic and diastolic blood pressure (−12 ± 3 and −5 ± 2 mmHg, P < 0.05), and in heart rate (−7 ± 2 bpm, P < 0.01) and an improvement in all metabolic parameters (fasting glucose: −0.302.1 ± 0.118 mmol/l, total cholesterol: −0.564 ± 0.164 mmol/l, triglycerides: −0.414 ± 0.137 mmol/l, P < 0.05). Multi-unit MSNA decreased from 68 ± 4 to 59 ± 5 bursts/100 heartbeats (P < 0.05). Single-unit MSNA indicated that the firing rate of individual vasoconstrictor fibers decreased from 59 ± 10 to 32 ± 4 spikes/100 heart beats (P < 0.05). The probability of firing decreased from 34 ± 5 to 23 ± 3% of heartbeats (P < 0.05), and the incidence of multiple firing decreased from 14 ± 4 to 6 ± 1% of heartbeats (P < 0.05). Cardiac and sympathetic baroreflex function were significantly improved (cardiac slope: 6.57 ± 0.69 to 9.57 ± 1.20 ms·mmHg−1; sympathetic slope: −3.86 ± 0.34 to −5.05 ± 0.47 bursts/100 heartbeats·mmHg−1, P < 0.05 for both). Hypocaloric diet decreased sympathetic activity and improved hemodynamic and metabolic parameters. The sympathoinhibition associated with weight loss involves marked changes, not only in the rate but also in the firing pattern of active vasoconstrictive fibers.

Association between the sympathetic firing pattern and anxiety level in patients with the metabolic syndrome and elevated blood pressure

Recent evidence indicates that stress is associated with obesity, hypertension and metabolic abnormalities. Stress pathways, including both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, are activated in individuals with the metabolic syndrome. In order to gain some insight into the relation between sympathetic nervous system activation, metabolic profile and stress, we examined the pattern of sympathetic nervous firing in eight women and 17 men with the metabolic syndrome and elevated blood pressure (BP) in relation to their underlying psychological stress. Both multiunit and single-unit muscle sympathetic nerve activity (MSNA) were recorded by using the technique of microneurography and psychological stress was assessed by Spielberger's State and Trait Anxiety scores and the Beck Depression Inventory II (BDI-II). Women had higher cholesterol levels, higher depressive symptom scores and similar multiunit MSNA compared with the men but displayed a disturbed firing pattern of sympathetic activity as indicated by a higher incidence of multiple spikes per burst (P < 0.05). In all individuals, regression analysis after adjustment for sex indicated that the single-unit sympathetic nerve-firing pattern did not correlate with any aspect of the metabolic profile; however it was significantly associated with anxiety state and trait and the affective component of the BDI scores. In particular, higher incidence of multiple firing (more than two spikes) during a sympathetic neural burst was associated with higher trait anxiety score (R = 0.557, P = 0.004) and higher affective depressive symptoms (R = 0.517, P = 0.008). Somatic symptoms bore no association with the sympathetic firing pattern. These results suggest that chronic mental stress modulates the pattern of sympathetic activity, which, in turn, may confer greater cardiovascular risk on individuals with the metabolic syndrome and elevated BP.

Altered firing pattern of single‐unit muscle sympathetic nerve activity during handgrip exercise in chronic heart failure

Sympathetic activation in chronic heart failure (CHF) is greatly augmented at rest but the response to exercise remains controversial. We previously demonstrated that single-unit muscle sympathetic nerve activity (MSNA) provides a more detailed description of the sympathetic response to physiological stress than multi-unit nerve recordings. The purpose of this study was to determine whether the reflex response and discharge properties of single-unit MSNA are altered during handgrip exercise (HG, 30% of maximum voluntary contraction for 3 min) in CHF patients (New York Heart Association functional class II or III, n = 16) compared with age-matched healthy control subjects (n = 13). At rest, both single-unit and multi-unit indices of sympathetic outflow were augmented in CHF compared with controls (P < 0.05). However, the percentage of cardiac intervals that contained one, two, three or four single-unit spikes were not different between the groups. Compared to the control group, HG elicited a larger increase in multi-unit total MSNA (Delta1002 +/- 50 compared with Delta636 +/- 76 units min(-1), P < 0.05) and single-unit MSNA spike incidence (Delta27 +/- 5 compared with Delta8 +/- 2 spikes (100 heart beats)(-1)), P < 0.01) in the CHF patients. More importantly, the percentage of cardiac intervals that contained two or three single-unit spikes was increased (P < 0.05) during exercise in the CHF group only (Delta8 +/- 2% and Delta5 +/- 1% for two and three spikes, respectively). These results suggest that the larger multi-unit total MSNA response observed during HG in CHF is brought about in part by an increase in the probability of multiple firing of single-unit sympathetic neurones.

P-42 Arterial Baroreflex Control of Single-Unit Muscle Sympathetic Nerve Activity in Chronic Heart Failure with Atrial Fibrillation

P-42 Arterial Baroreflex Control of Single-Unit Muscle Sympathetic Nerve Activity in Chronic Heart Failure with Atrial Fibrillation

The activity of a single muscle sympathetic vasoconstrictor nerve unit is affected by physiological stress in humans

Recording of neural firing from single-unit muscle sympathetic nerve activity (MSNA) is a new strategy offering information about the frequency of pure sympathetic firing. However, it is uncertain whether and when single-unit MSNA would be more useful than multiunit MSNA for analysis of various physiological stresses in humans. In 15 healthy subjects, we measured single-unit and multiunit MSNA before and during handgrip exercise at 30% of maximum voluntary contraction for 3 min and during the Valsalva maneuver at 40 mmHg expiratory pressure for 15 s. Shapes of individual single-unit MSNA were proved to be consistent and suitable for further evaluation. Single-unit and multiunit MSNA exhibited similar responses during handgrip exercise. However, acceleration of neural firing determined from single-unit MSNA became steeper than multiunit MSNA during the Valsalva maneuver. During the Valsalva maneuver, unlike handgrip exercise, the distribution of multiunit burst between 0, 1, 2, 3, and 4 spikes was significantly shifted toward multiple spikes within a given burst (P < 0.05). These results indicated that evaluation of single-unit MSNA could provide more detailed and accurate information concerning the role and responses of neuronal discharges induced by various physiological stresses in humans, especially amid intense sympathetic activity.