Human Muscle Nerve Research Articles

Recruiting "clean" chronic insomnia participants: the unicorn of sleep research.

Recruiting "clean" chronic insomnia participants: the unicorn of sleep research.

Reply to Willie and Tzeng

### Interindividual Heterogeneity in Integrative Physiology to the editor: We were very pleased to read the letter from Willie and Tzeng ([12][1]) regarding our recent publication in this Journal and our focus on the importance of interindividual variability in hemodynamic variables in the control

Not so fast: intrinsic heart rate vs. β-adrenergic responsiveness in the aging human heart

two of the fundamental observations associated with the cardiovascular responses to exercise are that heart rate increases with exercise but that maximum heart rate declines with aging. This decline in maximum heart rate with aging has a number of important consequences, including its major

Regulation of sympathetic nerve traffic to skeletal muscle in resting humans

An overview is given of microneurographic studies of resting vasoconstrictor traffic in human muscle nerves (muscle sympathetic nerve activity = MSNA). In multiunit recordings, the activity consists of synchronized bursts of vasoconstrictor impulses, the outflow of which is under potent arterial baroreflex control. In agreement with this, the bursts always display cardiac rhythmicity and occur during temporary reductions of blood pressure. Burst occurrence shows a close inverse correlation to variations of diastolic blood pressure whereas the correlation to the strength of the bursts is weak or absent, suggesting that the mechanisms controlling the two parameters are not identical. These dynamic characteristics are similar in all subjects despite large, reproducible, interindividual differences in number of bursts. Such interindividual differences probably have a genetic origin, and since discharge frequencies in single vasoconstrictor fibers are similar in subjects with few and many bursts, the differences in multiunit activity are likely to be due to a higher number of active fibers in subjects with many bursts. The interindividual differences in multiunit activity are not associated with differences in resting blood pressure levels. Recent studies have revealed (a) an inverse relationship between resting levels of cardiac output and MSNA and (b) evidence of reduced vascular responsiveness to noradrenaline in subject with many sympathetic bursts at rest. These findings suggest that the vasoconstriction induced by the sympathetic impulses is balanced or reduced by these factors, which thereby contribute to the poor relationship between the mean number of sympathetic bursts and the blood pressure level.

Treating Hypertension

What do we really know about sympathetic outflow and blood pressure in humans? For example, in healthy normotensive young subjects, baseline sympathetic outflow can vary 2-fold to 3-fold.1,2 We also know that in healthy aging subjects, baseline sympathetic outflow can be increased dramatically with only a modest impact on vascular resistance and little or no impact on blood pressure.1 Additionally, there is no clear evidence for dramatic increases in baseline sympathetic outflow in “garden variety” essential hypertension.1 If we stop here, a position of “nihilism” about sympathetic outflow and blood pressure seems reasonable. However, when the sympathetic nervous system is destroyed by disease or surgery, blood pressure is highly labile.3 We also know that many “stressors” that evoke a pressor response also evoke marked sympathetic activation, and that the magnitude of these pressor responses can be a harbinger of future hypertension.4,5 Finally, in disease states like congestive heart failure, excessive sympathetic activation is a “bad thing.”6,7 If we emphasize these points, sympathetic vasoconstriction seems more important to blood pressure and perhaps survival. …

Interindividual differences in sympathetic and effector responses to arousal in humans.

Surprising sensory stimuli have been found to attenuate one or two sympathetic discharges in human muscle nerves of some, but not all subjects, an effect suggested to be due to arousal. The aims of the present study were: (1) to provide evidence for or against an arousal mechanism by searching for evidence of habituation, and (2) to investigate if the presence or absence of inhibitory response is reproducible. To this end we recorded peroneal muscle sympathetic nerve activity (MSNA), electrocardiogram (ECG), finger blood pressure and changes of skin electrical resistance in 17 awake healthy subjects, while sensory stimuli consisting of five electrical pulses were delivered to a finger. The electrical pulses were triggered on five consecutive R waves of the ECG after a delay of 200 ms. Dummy stimuli, consisting of five trigger pulses without electrical pulses were used as controls, and the interval between two successive stimuli (real or dummy) was 30 s. On a group basis, the stimuli attenuated two initial and one late MSNA bursts. On an individual basis, significant attenuation of one or two initial bursts occurred in eight subjects, whereas in nine subjects there was no significant inhibition. In nine subjects the experiments were repeated once and in three subjects they were repeated twice. The effects on MSNA were reproducible in 11 of the12 subjects. In the group of subjects without significant MSNA inhibition the stimuli induced a small, transient increase in mean blood pressure, which was not present in the group with significant MSNA inhibition. Heart rate did not change in either group. In conclusion, the inhibitory effect on MSNA of five repeated electrical pulses to a finger is largely similar to that previously shown for one pulse, i.e. there is rapid habituation of the response, compatible with an arousal-induced effect. The inhibitory responsiveness shows marked interindividual differences, which are reproducible over several months and associated with different effects on blood pressure.

Effects of static lung inflation on sympathetic activity in human muscle nerves at rest and during asphyxia

Muscle sympathetic activity is inhibited during the second half of phasic lung inflation associated with normal (negative pressure) breathing or artificial ventilation with intermittent positive-pressure, and this inspiratory inhibition appears unrelated to the associated changes in arterial pressure. In the present study we tested the hypothesis that a static inflation of the lungs would cause a sustained inhibition of muscle sympathetic activity. Microneurographic techniques were used to record muscle sympathetic activity from the peroneal nerve, and arterial pressure was monitored continuously by finger-pulse photoplethysmography (Finapres). In nine subjects static lung inflation, brought about either actively or passively, caused a pronounced and sustained increase in sympathetic activity (not the predicted decrease) that could not be explained by changes in arterial pressure. When delivered at the end of a voluntary end-expiratory apnoea, static lung inflation caused an initial inhibition of the large chemoreceptor-induced sympathetic bursts and a subsequent excitation that was sustained for the duration of the lung inflation. These observations indicate that respiration can affect muscle sympathetic activity in humans in two opposing ways: inhibition during phasic increases in lung volume, and excitation during large static increases in lung volume. Neither phenomenon depends on changes in arterial pressure, and hence influences of carotid arterial and aortic (high-pressure) baroreceptors can be excluded. We suggest that the initial inhibition is evoked from lung or chest-wall receptors and the static exitation from unloading of cardiopulmonary (low pressure) baroreceptors.

Coupling between variations in strength and baroreflex latency of sympathetic discharges in human muscle nerves.

1. Pulse-synchronous multiunit muscle nerve sympathetic activity was recorded simultaneously from two nerves together with ECG in eleven healthy subjects; seven recordings were made from the two peroneal nerves during prolonged expiratory apnoeas and four from a radial and a peroneal nerve during lower body negative pressure of 10-40 mmHg. The neural records were displayed in mean voltage neurograms (time constant 0.1 s) and for each mean voltage burst the following measures were taken and related to each other: amplitude, duration, rise time, decay time and baroreflex latency (from the appropriate R-wave of the ECG to the peak of the burst). 2. Average baroreflex latencies were 1.3 s in the peroneal nerves and 0.9 s in the radial nerve. There were significant positive correlations between both the amplitudes and the baroreflex latencies of corresponding bursts in peroneal-peroneal recordings and in radial-peroneal recordings. 3. In all nerves baroreflex latency shortened significantly when burst amplitude increased. The correlation between burst amplitude and baroreflex latency was weaker in the radial than in the peroneal nerve. The average variation of baroreflex latency in peroneal-peroneal recordings was 0.20 +/- 0.02 s in both legs, and in radial-peroneal recordings the variation was 0.09 +/- 0.01 s in the radial nerve and 0.12 +/- 0.02 s in the peroneal nerve. 4. When peroneal burst amplitudes increased, burst duration increased. This was due to increases of both the rise time and the decay time of the burst, the latter being the greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible genetic influence on the strength of human muscle nerve sympathetic activity at rest.

Large reproducible interindividual differences in the strength of human muscle nerve sympathetic activity have been demonstrated previously without satisfactory explanation. We undertook the present study to investigate whether a genetic influence may be a factor of importance. Microneurographic recordings of sympathetic impulse traffic were made in the peroneal nerve in nine pairs of monozygotic male twins and eight pairs of age-matched male subjects without family relationship. The strength of the sympathetic activity was quantitated as number of sympathetic bursts per 100 heart beats and bursts per minute. Group mean values of muscle sympathetic activity, heart rate, and blood pressure were similar in the two groups. Intrapair differences (mean +/- SEM) of sympathetic activity were 5.4 +/- 1.7 bursts per 100 heart beats (1.7 +/- 0.5 bursts per minute) for the twins and 19.4 +/- 3.2 bursts per 100 heart beats (11.8 +/- 2.5 bursts per minute) for the control subjects (P < .01 for both). The degree of reproducibility between twins is similar to that reported previously between repeated recordings in the same subject. The finding may indicate that the strength of sympathetic outflow to muscle is controlled genetically. If so, we speculate that this may contribute to the heritability of blood pressure in both normotensive and hypertensive subjects.

Baroreflex and respiratory modulation of single and multi-unit sympathetic activity in human muscle nerves

Baroreflex and respiratory modulation of single and multi-unit sympathetic activity in human muscle nerves

Rapid resetting of human baroreflex working range: insights from sympathetic recordings during acute hypoglycaemia.

1. Human muscle nerve sympathetic activity (MSA), which is governed by baroreflexes and involved in blood pressure homeostasis, is increased during acute insulin-induced hypoglycaemia. 2. To elucidate the detailed relationship between MSA and blood pressure during hypoglycaemia, 0.15 i.u. (kg body weight)-1 regular human insulin was given intravenously to eight fasting, healthy volunteers. Microneurographic recording of MSA in the peroneal nerve was made with simultaneous monitoring of arterial blood pressure by a finger cuff (Finapres). The course of MSA and blood pressure was monitored for 30 min before and 60 min after insulin injection. In three subjects control recording without insulin injection was made for the same duration. 3. Stimulus-response regression lines were constructed by plotting diastolic blood pressure against the occurrence frequency of MSA for the period of initial rest, the period of maximal MSA outflow during hypoglycaemia and the period of glucose counter-regulation. The control experiments were analysed for the corresponding periods. 4. The stimulus-response line was stable throughout the control experiments, whereas it was shifted either to the left or to the right during hypoglycaemia, and regularly shifted to the left (i.e. towards a lower blood pressure) during glucose counter-regulation, without change of slope. 5. It is concluded that the changes in MSA during acute hypoglycaemia are not secondary to baroreflex regulation but instead are characterized by acute resetting of the baroreflex working range without change of sensitivity.

Sympathetic response to oral carbohydrate administration. Evidence from microelectrode nerve recordings.

Microneurography was used to measure sympathetic outflow in human muscle nerves (MSA) for up to 90 min after the ingestion of 100 g D-glucose, 75.8 g D-xylose, intravenous D-glucose (0.35 g/kg), and 300 ml water. 19 healthy subjects were examined using a microelectrode positioned in the right peroneal nerve. MSA increased from 21 +/- 0.9 bursts/min at rest to 36.9 +/- 4.3 bursts/min 30 min after ingestion of D-glucose and from 18.9 +/- 2.9 to 26.3 +/- 3.4 bursts/min 30 min after D-xylose. The increase in MSA was already significant by 15 min. MSA had not returned to the basal level after 90 min. Neither intravenous D-glucose nor water intake enhanced MSA. MSA increased in parallel with plasma norepinephrine, and a significant correlation (r = 0.55; P less than 0.001) was observed between the plasma insulin concentration and MSA after D-glucose ingestion. In three subjects the outflow of sympathetic nerve activity to the skin was examined after oral D-glucose and no change was observed, emphasizing the differentiated nature of the sympathetic nerve response to carbohydrate. Multiple factors such as insulin alone, hemodynamic adjustment to splanchnic vasodilation, and gastrointestinal distension are probably involved in the increased muscle nerve sympathetic outflow after carbohydrate ingestion.

The Effects of Acupuncture Stimulation on Human Muscle Nerve Sympathetic Activity and Clinical Effects

The Effects of Acupuncture Stimulation on Human Muscle Nerve Sympathetic Activity and Clinical Effects

Microneurographic analysis of thyrotropin-releasing hormone effects on sympathetic outflow in human muscle nerves

In order to clarify the human sympathetic response to thyrotropin-releasing hormone (TRH), microneurographic analysis was performed in 12 healthy subjects. Multi-unit vasoconstrictive impulses of muscle nerve sympathetic activity (MSA) were directly recorded from tibial nerve fascicles together with ECG and blood pressure. Subcutaneous injection of saline (1 ml) had no effect on blood pressure and neurograms of MSA. Following s.c. injection of TRH (0.5 mg, 1 ml), however, a significant increase in heart rate and blood pressure occurred 2 min after injection; the change was statistically correlated with increased MSA, and disappeared after about 10 min. The observation suggests that TRH-activated vasoconstrictive impulses of MSA increase the peripheral vascular resistance and elevate blood pressure. We speculate that TRH directly activates vasomotor centers or higher autonomic centers rather than peripheral organs, because the parallel increase of blood pressure and MSA after TRH injection counteracts the effect of baroreflex mechanism.

Sympathetic outflow in human muscle nerves increases during hypoglycemia.

The normal response to insulin-induced hypoglycemia bears many characteristics of activation of the sympathetic nervous system. In this study, the impulse pattern of muscle nerve sympathetic activity (MSA) involved in cardiovascular homeostasis was identified by microneurography in the peroneal nerve of seven healthy and two adrenalectomized subjects. After recordings at rest and an intravenous injection of 0.15 IU insulin/kg body wt (0.10 IU insulin/kg body wt in adrenalectomized subjects), MSA was followed for 90 min. Nadir of hypoglycemia (2.0 +/- 0.1 mM) was reached at 30 min. All subjects, including the two adrenalectomized subjects, exhibited an increase of MSA, which peaked at the glucose nadir. The time course of MSA increase was a mirror image of the blood glucose curve. This directly measured increase of MSA may be part of the hemodynamic adjustment to the fall in plasma volume known to occur in hypoglycemia. Another possible cause is direct stimulation of central sympathetic motoneurons.

Sympathetic outflow in human muscle nerves increases during hypoglycemia

Sympathetic outflow in human muscle nerves increases during hypoglycemia

Effect of lower body negative pressure on human muscle nerve sympathetic activity.

1. Recordings of multi-unit sympathetic activity were made from muscle branches of the median nerve in five healthy subjects during application of lower body negative pressure (l.b.n.p.). Simultaneous recordings of arterial blood pressure were made in four subjects. The strength of the neural activity was quantitated by counting the number of pulse synchronous sympathetic bursts and their amplitudes in the mean voltage neurogram.2. The general appearance of the sympathetic activity in pulse synchronous bursts was similar during control periods and during l.b.n.p., but during l.b.n.p. there was always an increase in the number of sympathetic bursts and usually also in the mean voltage amplitude of the bursts.3. The probability of occurrence of a burst was correlated to different blood pressure parameters of individual heart beats and both during control periods and during l.b.n.p. there was regularly a close negative correlation to diastolic, a low correlation to systolic, an intermediate negative correlation to mean and a positive correlation to pulse pressures.4. The changes in arterial blood pressure during l.b.n.p. were small and in most cases statistically insignificant. The observed increases in the number of sympathetic bursts during l.b.n.p. were significantly greater than what could be expected on the basis of the blood pressure changes.5. The findings suggest that the reflex control from the arterial baroreceptors is maintained during l.b.n.p. but, since the increase of sympathetic activity during l.b.n.p. could not be explained by a change in stimulation of the arterial baroreceptors, influence from other receptor groups (presumably intrathoracic volume receptors) must also have occurred.

Human muscle nerve sympathetic activity at rest. Relationship to blood pressure and age.

1. Recordings of multi-unit sympathetic activity were made from median or peroneal muscle nerve fascicles in thirty-three healthy subjects, resting in recumbent position. Simultaneous recordings of intra-arterial blood pressure were made in seventeen subjects. The neural activity, quantified by counting the number of pulse synchronous sympathetic bursts in the mean voltage neurogram (burst incidence), was plotted against the arterial blood pressure level and the age of the subjects. The effects of spontaneous temporary blood pressure fluctuations were studied by correlating different pressure parameters of individual heart beats to the probability of occurrence of a sympathetic burst and to the amplitude of the occurring burst.2. Between different subjects there were marked differences in burst incidence, from less than 10 to more than 90 bursts/100 heart beats. No correlation was found to interindividual differences in the arterial blood pressure level but there was a slight tendency for increasing burst incidence with increasing age.3. Irrespective of the magnitude of the burst incidence, the bursts always occurred more frequently during spontaneous transient blood pressure reductions than during transient increases in blood pressure. When, for each heart cycle, the occurrence of a sympathetic burst was correlated with different blood pressure parameters there was regularly a close negative correlation to diastolic pressure, a low correlation to systolic and an intermediary negative correlation to mean blood pressure. There was a positive correlation to pulse pressure and to pulse interval.4. When measured for individual heart beats, not only the occurrence but also the mean voltage amplitude of the sympathetic bursts tended to increase with decreasing diastolic pressure.5. In a given subject when comparing heart beats with the same diastolic pressure, the occurrence as well as the amplitude of the sympathetic bursts was higher for heart beats occurring during falling than for heart beats occurring during rising blood pressure. For a given change in diastolic blood pressure, sympathetic activity changed more if pressure was falling than if it was rising.6. The findings suggest that the sympathetic outflow is modulated by arterial baroreflex mechanisms and that transient variations in the strength of the activity are, to a large extent, determined by diastolic blood pressure fluctuations. The intimate correlation with ;dynamic' variations in blood pressure and the absence of correlation to the ;static' blood pressure level suggests that the sympathetic outflow to skeletal muscles is of importance for buffering acute blood pressure changes but has little influence on the long term blood pressure level. The difference in reflex sensitivity between falling and rising pressure indicates that acute blood pressure decreases may be buffered more efficiently than acute blood pressure increases.7. In twenty-seven subjects baroreflex latency was calculated from the QRS-complexes in the e.c.g. to the appropriate systolic inhibition in the sympathetic activity. When recording in the peroneal nerve, the latency ranged between 1.16 and 1.49 sec and there was a positive correlation with the height of the subjects. It is suggested that such latency measurements may be used clinically to evaluate conduction in sympathetic fibres.

General characteristics of sympathetic activity in human muscle nerves.

AbstractMulti‐unit sympathetic activity was recorded in human muscle nerves, together with measurements of intra‐arterial blood pressure and forearm or calf blood flow, during manoeuvres causing circulatory adjustments. Manoeuvres causing an increased vascular resistance in the forearm or calf were regularly associated with an increase in sympathetic outflow, proving that the neural activity was dominated by vasoconstrictor impulses. The inverse changes of blood pressure and sympathetic activity observed during Valsalva's manoeuvre and mental stress are explicable in terms of baroreflex control of the neural outflow. However, during muscle work and hyperventilation the relation between blood pressure and sympathetic activity was more complex, indicating that the baroreflex influence was superimposed or modified by other regulatory mechanisms. Some manoeuvres known to affect sympathetic outflow in skin nerves caused no appreciable change in sympathetic muscle nerve activity.

Manoeuvres affecting sympathetic outflow in human muscle nerves.

AbstractMultiunit sympathetic activity was recorded from muscle nerve fascicles in the median or peroneal nerve of resting, relaxed human subjects. The impulses, which were reversibly abolished by a Sympathetic ganglion blocking agent, were grouped in the pulse rhythm, and series of such pulse rhythmic bursts of impulses regularly appeared during spontaneously occurring blood pressure reductions, whereas temporary blood pressure elevations were associated with neural silence. The findings agree with the notion that the sympathetic muscle nerve activity recorded consists of vasoconstrictor impulses, the outflow of which is modulated by a strong phasic and tonic inhibitory baroreflex influence. The reflex delay from an arterial pulse wave to the corresponding inhibition of efferent sympathetic activity was 0.9–1.4 seconds, depending on the recording site. Several stimuli, such as sudden chest compression, a rapid deep breath or an electrical shock against the skin, caused a transient inhibition of the sympathetic discharges lasting a few seconds.