Muscle Sympathetic Nerve Activity Total Activity Research Articles

Evidence for a physiological role of pulmonary arterial baroreceptors in sympathetic neural activation in healthy humans.

In an anaesthetised animal model, independent stimulation of baroreceptors in the pulmonary artery elicits reflex sympathoexcitation. In humans, pulmonary arterial pressure is positively related to basal muscle sympathetic nerve activity (MSNA) under conditions where elevated pulmonary pressure is evident (e.g. high altitude); however, a causal link is not established. Using a novel experimental approach, we demonstrate that reducing pulmonary arterial pressure lowers basal MSNA in healthy humans. This response is distinct from the negative feedback reflex mediated by aortic and carotid sinus baroreceptors when systemic arterial pressure is lowered. Afferent input from pulmonary arterial baroreceptors may contribute to sympathetic neural activation in healthy lowland natives exposed to high altitude. In animal models, distension of baroreceptors located in the pulmonary artery induces a reflex increase in sympathetic outflow; however, this has not been examined in humans. Therefore, we investigated whether reductions in pulmonary arterial pressure influenced sympathetic outflow and baroreflex control of muscle sympathetic nerve activity (MSNA). Healthy lowlanders (n=13; 5 females) were studied 4-8days following arrival at high altitude (4383m; Cerro de Pasco, Peru), a setting that increases both pulmonary arterial pressure and sympathetic outflow. MSNA (microneurography) and blood pressure (BP; photoplethysmography) were measured continuously during ambient air breathing (Amb) and a 6min inhalation of the vasodilator nitric oxide (iNO; 40ppm in 21% O2 ), to selectively lower pulmonary arterial pressure. A modified Oxford test was performed under both conditions. Pulmonary artery systolic pressure (PASP) was determined using Doppler echocardiography. iNO reduced PASP (24±3 vs. 32±5mmHg; P<0.001) compared to Amb, with a similar reduction in MSNA total activity (1369±576 to 994±474a.umin-1 ; P=0.01). iNO also reduced the MSNA operating point (burst incidence; 39±16 to 33±17 bursts·100Hb-1 ; P=0.01) and diastolic operating pressure (82±8 to 80±8mmHg; P<0.001) compared to Amb, without changing heart rate (P=0.6) or vascular-sympathetic baroreflex gain (P=0.85). In conclusion, unloading of pulmonary arterial baroreceptors reduced basal sympathetic outflow to the skeletal muscle vasculature and reset vascular-sympathetic baroreflex control of MSNA downward and leftward in healthy humans at high altitude. These data suggest the existence of a lesser-known reflex input involved in sympathetic activation in humans.

Epidural Spinal Cord Stimulation Acutely Reduces Efferent Postganglionic Sympathetic Nerve Activity in Humans

Evidence in clinical and animal studies demonstrates that epidural spinal cord stimulation (SCS) mimics the effects of sympathetic block or sympathectomy and increases peripheral blood flow. However, the extent to which SCS lowers sympathetic nerve activity in humans remains unclear because no studies have directly assessed muscle sympathetic nerve activity (MSNA) responses to SCS. We tested the hypothesis that acute SCS (60 min) at the lower thoracic spine would 1) lead to reduced MSNA in the peroneal nerve, and 2) increase blood flow in the legs, but not the arms. Twelve patients (54 ± 3 yrs, 5 men/7 women) that previously underwent surgical implantation of a SCS device for management of neuropathic pain were studied. Following 48 hours of no SCS, femoral and brachial artery blood flow was assessed using Doppler ultrasound at baseline and at 15, 30, 45, 60 min of SCS, and 15 min post SCS. MSNA was assessed using microneurography under the same conditions during a second visit (n=5). Femoral artery blood flow was significantly increased throughout SCS and 15 min post SCS (15 min: 26 ± 1%, 30 min: 32 ± 14%, 45 min: 30 ± 13%, 60 min: 26 ± 13%, 15 min post SCS: 40 ± 14% ml/min, P=0.02), but no change in brachial artery blood flow was observed (15 min: 4 ± 6%, 30 min: 5 ± 8%, 45 min: 5 ± 7%, 60 min: 7 ± 7% ml/min, 15 min post SCS: 6 ± 11% ml/min, P=0.86). MSNA was progressively reduced during SCS, reaching significance at 45 and 60 min, and returned toward baseline following SCS (15 min: −1 ± 6%, 30 min: −13 ± 4%, 45 min: −17 ± 6%, 60 min: −21 ± 7%, 15 min post SCS: −4 ± 5% bursts/100heartbeats, P=0.01). Similar results were observed for MSNA total activity (AU/min) (P&lt;0.042). During measures of MSNA, self‐reported neuropathic pain was low at baseline and not significantly changed by SCS (scale 0–10; BL: 2.8 ± 0.8, 15 min: 1.7 ± 0.9, 30 min: 1.5 ± 1, 45 min: 1.7 ± 1, 60 min: 1.5 ± 1, P=0.07), suggesting that reductions in MSNA were SCS‐mediated and not primarily a result of pain relief. These preliminary results demonstrate proof of principle that acute lower thoracic SCS significantly reduces peroneal MSNA in humans.Support or Funding InformationAHA 17POST33440101, T32 HL07121, NHLBI (P01HL014388), U54 TR001356 and AHA (13DG143400012)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sympathetic Neural and Hemodynamic Responses to Painful Stimuli are Related to Perception of Pain

Painful stimuli cause activation of the sympathetic nervous system, increasing efferent muscle sympathetic nerve activity (MSNA) and altering downstream hemodynamic responses. However, there is considerable inter-individual variability in the perception of pain to a given painful stimulus; how this magnitude of perceived pain relates to sympathetic neural and hemodynamic responses remains to be fully elucidated. PURPOSE: Thus, the purpose of this study was to evaluate the relationship between the perception of pain and the corresponding sympathetic neural and hemodynamic responses to a painful stimulus in healthy normotensive men and women. METHODS: Heart rate (HR), MSNA, and blood pressure (BP) were measured at baseline (supine, rest) and during a two-minute cold pressor test (CPT) in 15 subjects (6 female, 9 male; age: 31.5 ± 7.5 years, body mass index (BMI): 25.1 ± 3.4 kg/m2, mean ± SD). Stroke volume (SV), cardiac output (Qc), and total peripheral resistance (TPR) were calculated using the model flow method. Immediately following the CPT subjects rated their pain on a verbal descriptor scale (Numerical Rating Scale, range 0-10). Statistical significance was set at p < 0.05. RESULTS: Subjects were grouped according to pain ratings given following the CPT (Pain ≥7, i.e., “severe” pain, n=9; and Pain ≤ 6, i.e. “none” to “mild-to-moderate” pain, n=6). The two groups were similar with regards to gender, age, and BMI. Subjects who rated their Pain >6 had significantly larger increases during the CPT in MSNA total activity (1208 ± 631 vs. 173 ± 87 a.u./min), burst frequency (24 ± 15 vs. 9 ± 6 bursts/min), burst incidence (38 ± 18 vs. 13 ± 5 bursts/100 heartbeats,), TPR (223 ± 178 vs.79 ± 107 dynes/s/cm-5), Qc (1.26 ± 0.63 vs. 0.54 ± 0.39 L/min) and mean BP (15 ± 6 vs. 6 ± 7 mmHg) compared to individuals who rated their Pain ≤6 (n=6). Changes in HR and SV in response to the CPT were not related to pain ratings. CONCLUSION: In healthy, normotensive men and women, the sympathetic neural, BP, & vasoconstrictor responses to a fixed painful stimulus are positively related to the magnitude of pain perception. These findings may have important clinical implications, as hypoalgesia (i.e., decreased sensitivity to pain) is a common characteristic of many cardiovascular disease states.

Interactive effects of trigeminal nerve stimulation and muscle metaboreflex activation on muscle sympathetic nerve activity in healthy humans (1170.5)

We investigated the independent and interactive effects of trigeminal cutaneous receptor stimulation and activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) on muscle sympathetic nerve activity (MSNA). Heart rate (HR; ECG), blood pressure (BP; Finometer) and MSNA (microneurography) were continuously recorded in eight healthy men (29±2 yr) during three experimental conditions; 1) facial cooling [0°C, trigeminal stimulation, TGS], 2) muscle metaboreflex activation by post‐exercise ischemia [PEI] following isometric handgrip at 30% maximum voluntary contraction, and 3) simultaneous TGS and PEI. Trials were counterbalanced and respiratory rate and tidal volume controlled at baseline, TGS, PEI and TGS+PEI. TGS produced a significant decrease in HR (Δ‐5±2 bpm; mean±SE), and increase in mean BP (Δ14±3 mmHg) and MSNA total activity (Δ353±118% AU). During PEI, HR remained at resting levels (Δ3±2 bpm; mean±SE), while mean BP (Δ25±3 mmHg) and MSNA total activity (Δ234±83% AU) increased. Finally, during combined TGS and PEI, HR was unchanged (Δ0±2 bpm; mean±SE), while mean BP (Δ30±3 mmHg) and MSNA total activity (Δ331±100% AU) were increased. Thus, excitatory inputs from the trigeminal nerve and metabolically sensitive skeletal muscle afferents do not appear to summate algebraically in determining a MSNA response, but rather exhibit neural occlusion.Grant Funding Source: Supported by CAPES, CNPq, FAPERJ.

Resting sympathetic baroreflex sensitivity in subjects with low and high tolerance to simulated hemorrhage with lower body negative pressure

Central hypovolemia elicited by hemorrhage or lower body negative pressure (LBNP) triggers autonomic reflexes to maintain organ perfusion; these reflexes fail with severe blood loss resulting in cardiovascular collapse. The ability to tolerate LBNP is variable and factors contributing to tolerance are unclear. We tested the hypothesis that resting sympathetic baroreflex sensitivity (BRS) is attenuated in subjects who have a low tolerance (LT) to LBNP. Muscle sympathetic nerve activity (MSNA) and diastolic arterial pressure (DAP) were recorded in 48 human subjects who subsequently underwent LBNP to presyncope. LT subjects reached presyncope prior to completing −60 mmHg LBNP, and high tolerant (HT) subjects experienced presyncope after −60 mmHg LBNP. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/ DAP correlations were strong (r&gt;0.5) in 36 subjects (LT: n= 8; HT: n=28), and BRS was not different between LT and HT (−1.91 ± 0.31 vs. −2.24 ± 0.22 bursts·(100 beats)−1·mmHg−1, p=0.45). MSNA total activity/ DAP correlations were strong (r&gt;0.5) in 34 subjects (LT: n= 8; HT: n=26), and BRS was not different between LT and HT (−592 ± 69 vs. −666 ± 70 arbitrary units·(beats)−1·mmHg−1, p=0.58). We conclude that resting MSNA BRS does not influence tolerance to LBNP. Funded by the US Army Medical Research and Materiel Command.

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.

Respiratory influences on sympathetic vasomotor outflow in humans.

We have attempted to synthesize findings dealing with four types of respiratory system influences on sympathetic outflow in the human. First, a powerful lung volume-dependent modulation of muscle sympathetic nerve activity (MSNA) occurs within each respiratory cycle showing late-inspiratory inhibition and late-expiratory excitation. Secondly, in the intact human, neither reductions in spontaneous respiratory motor output nor voluntary near-maximum increases in central respiratory motor output and inspiratory effort, per sec, influence MSNA modulation within a breath, MSNA total activity or limb vascular conductance. Thirdly, carotid chemoreceptor stimuli markedly increase total MSNA; but most of the MSNA response to chemoreceptor activation appears to be mediated independently of increased central respiratory motor output. Fourthly, repeated fatiguing contractions of the diaphragm or expiratory muscles in the human show a metaboreflex mediated time-dependent increase in MSNA and reduced vascular conductance and blood flow in the resting limb. Recent evidence suggests that these respiratory influences contribute significantly to sympathetic vasomotor outflow and to the distribution of systemic vascular conductances and blood flow in the exercising human.