The effect of intraduodenal glucose on muscle sympathetic nerve activity in healthy young and older subjects

Objective The cardiovascular response to a meal is modulated by gastric distension and the interaction of nutrients, particularly carbohydrate, within the small intestine. We tested the hypothesis that the depressor effect of small intestinal glucose is greater in older than in young subjects, because the reflex increase in muscle sympathetic nerve activity (MSNA) is blunted by age. Methods The effects of intraduodenal glucose infusion (IDGI) on blood pressure, heart rate and MSNA were evaluated in eight healthy young subjects (4 women; mean age ± SEM: 28.8 ± 3.4 years), eight healthy elderly (4 women; 75.3 ± 1.6 years) and in two patients with symptomatic postprandial hypotension (PPH), one young (21 years), and one old (90 years). Results In both young and elderly healthy subjects, IDGI decreased blood pressure (P < 0.05), but the fall in systolic blood pressure was greater in the older subjects (−17.0 ± 4.1 vs. −6.5 ± 1.6 mmHg, P < 0.03). MSNA increased similarly, after infusion in both young (9.0 ± 3.4 bursts/min) and elderly (7.8 ± 1.0 bursts/min) subjects. Baroreflex sensitivity for number of sympathetic bursts was attenuated in the elderly (P < 0.03). The increase in burst area in the young patient with PPH was attenuated (18 vs. 63% in the healthy young group). Interpretation The fall in BP induced by IDGI was greater in healthy elderly compared to healthy young subjects. The reason for this is unclear, as they have similar increases in MSNA.     

Cardiac sympathetic nerve activity during kainic acid–induced limbic cortical seizures in rats

We sought to define changes in cardiac sympathetic nerve activity that occur during seizures. We studied kainic acid–induced limbic cortical seizures in urethane-anesthetized rats using cardiac sympathetic nerve, blood pressure, and electrocardiography (ECG) recordings. We studied changes in ventilation rate before and during seizures. Cardiac sympathetic nerve activity was increased during limbic cortical seizures. The modest increases were similar to changes induced by nitroprusside infusion. The normal relation of cardiac sympathetic nerve activity to ventilation rate was lost during seizure activity. Changes in cardiac sympathetic nerve activity caused by changes in ventilation rate became unpredictable, and could be extreme. We conclude that the modest changes in cardiac sympathetic nerve activity contribute to the predominantly parasympathetic effects on the heart during limbic cortical seizures and periods of asphyxia. Further, ventilation rate changes might be associated with large sudden increases or decreases in cardiac sympathetic outflow during seizures.     

Inhibition of muscle sympathetic nerve activity during yawning

Yawning is a complex event that depends largely on the autonomic nervous system. Microneurographic techniques were used to study the mechanism involved in yawning. A series of spontaneous yawns displayed by a healthy 39-year-old male offered us the opportunity to study the muscle sympathetic nerve activity (MSNA) during this phenomenon. It was found that 2 s of yawning inhibited the MSNA recorded at the right peroneal nerve in the lateral knee area, while 3 s of slow expiration succeeding a yawn provoked an MSNA discharge. Blood pressure decreased with each slow expiration by 5–6 mmHg, and increased again with the renewed MSNA discharge. We conclude that yawning is associated with a sympathetic suppression that favours a parasympathetic dominance, as indicated by the MSNA and the decrease in blood pressure. The slow expiration following a yawn is associated with a sympathetic activation marked by an MSNA discharge and an increase in blood pressure.     

Compensatory but not anticipatory adjustments are altered in older adults during lateral postural perturbations

ObjectiveThis study investigated anticipatory postural adjustments (APAs) and compensatory postural adjustments (CPAs) and their relationship in older adults during lateral postural perturbations.MethodsUnpredictable and predictable postural disturbances were induced by a swinging pendulum that impacted at the shoulder level of two groups of older adults, non-fallers (20) and fallers (20), and in a group of young control subjects (20). The electromyographic (EMG) activity of the postural muscles and the center of pressure (COP) displacement were recorded and quantified within the time intervals typical for APAs and CPAs.ResultsBoth groups of older adults (non-fallers and fallers) showed higher magnitude of EMG activity in the lateral muscles and increased COP displacement, particularly, during the CPAs time interval when compared to the young group. Older adults, however, were able to change the electrical activity of the muscles during the predictable task by generating APAs with similar magnitudes of those found in young subjects.ConclusionsCompensatory but not anticipatory adjustments are altered in older adults during predictable lateral postural perturbations.Significance: These findings provide new data on the role of APAs and CPAs in their relationship in older adults during external lateral perturbations and may advance current rehabilitative management strategies to improve balance control in older individuals.     

Muscle sympathetic nerve activity during central,mixed and obstructive apnea: Are there any differences?

Abstract  We recorded muscle sympathetic nerve activity (MSNA) from the peroneal nerve during sleep in three OSAS patients who showed three kinds of apnea. During central apneas and central component of mixed apnea, bursts of MSNA appeared in high probability with almost each heart beat. During obstructive apneas and the obstructive component of mixed apneas, bursts of MSNA appeared in a cluster after the end of each inspiratory effort. Burst rate of MSNA during apnea were higher in central apneas and the central component of mixed apnea than in obstructive apneas and the obstructive component of mixed apneas. These findings indicate that activity in the sympathetic nervous system is enhanced not only in obstructive apnea but also in central and mixed apnea.     

Evaluation of sympathetic skin response in Parkinson's disease

There is no clear definition on the role of sympathetic skin response (SSR) in the evaluation of patients with Parkinson's disease (PD). We recorded the SSR of the palms of 64 controls and 46 patients with PD to electrical stimulation of the median nerve at the wrist. We analyzed onset latency and peak-to-peak amplitude. A study of parasympathetic function (R–R interval analysis) was also undertaken. We found that patients with PD had more absent SSRs than controls. The mean amplitude of the SSR was significantly reduced in both lower and upper limbs of PD patients in comparison with control subjects (p<0.001). The onset latency was longer in the lower limbs of these patients in respect to the control group (p<0.003). There was a significant inverse correlation between SSR amplitudes and age, severity and late onset of the disease. There was no association of these parameters with dysautonomic symptoms or R–R interval variation. In conclusion, there is a significant association between altered SSR and PD and an inverse correlation in this group of patients between SSR values and older age, greater severity and later onset of disease. Therefore, the study of SSR may provide valuable information on cholinergic sympathetic function in patients with PD.     

The relation between habitual physical activity and sympathetic vascular transduction in healthy young adults

Clinical Autonomic Research -     

Brain activity during sympathetic response in anticipation and experience of pain

Pain is a multidimensional phenomenon with sensory, affective, and autonomic components. Here, we used parametric functional magnetic resonance imaging (fMRI) to correlate regional brain activity with autonomic responses to (i) painful stimuli and to (ii) anticipation of pain. The autonomic parameters used for correlation were (i) skin blood flow (SBF) and (ii) skin conductance response (SCR). During (i) experience of pain and (ii) anticipation of pain, activity in the insular cortex, anterior cingulate cortex (ACC), prefrontal cortex (PFC), posterior parietal cortex (PPC), secondary somatosensory cortex (S2), thalamus, and midbrain correlated with sympathetic outflow. A conjunction analysis revealed a common central sympathetic network for (i) pain experience and (ii) pain anticipation with similar correlations between brain activity and sympathetic parameters in the anterior insula, prefrontal cortex, thalamus, midbrain, and temporoparietal junction. Therefore, we here describe shared central neural networks involved in the central autonomic processing of the experience and anticipation of pain. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults

BackgroundDysfunctional neutrophils with advanced age are a hallmark of immunosenescence. Reduced migration and bactericidal activity increase the risk of infection. It remains unclear why neutrophil dysfunction occurs with age. Physical activity and structured exercise have been suggested to improve immune function in the elderly. The aim of this study was to assess a comprehensive range of neutrophil functions and determine their association with habitual physical activity.MethodPhysical activity levels were determined in 211 elderly (67 ± 5 years) individuals by 7-days of accelerometry wear. Twenty of the most physically active men and women were matched for age and gender to twenty of the least physically active individuals. Groups were compared for neutrophil migration, phagocytosis, oxidative burst, cell surface receptor expression, metabolic health parameters and systemic inflammation. Groups were also compared against ten young participants (23 ± 4 years).ResultsThe most active group completed over twice as many steps/day as the least active group (p < 0.001), had lower BMI’s (p = 0.007) and body fat percentages (p = 0.029). Neutrophils migrated towards IL-8 better in the most active group compared to the least active (p < 0.05) and was comparable to that of the young (p > 0.05). These differences remained after adjusting for BMI, body fat and plasma metabolic markers which were different between groups. Correlations revealed that steps/day, higher adiponectin and lower insulin were positively associated with migratory ability (p < 0.05). There was no difference in expression of the chemokine receptors CXCR1 or CXCR2 (p > 0.05 for both). CD11b was higher in the most active group compared to the least active (p = 0.048). No differences between activity groups or young controls were observed for neutrophil phagocytosis or oxidative burst in response to Escherichia coli (p > 0.05). The young group had lower concentrations of IL-6, IL-8, MCP-1, CRP, IL-10 and IL-13 (p < 0.05 for all) with no differences between the two older groups.ConclusionThese data suggest that impaired neutrophil migration, but not bactericidal function, in older adults may be, in part, the result of reduced physical activity. A 2-fold difference in physical activity is associated with better preserved neutrophil migratory dynamics in healthy older people. As a consequence increasing habitual physical activity may be beneficial for neutrophil mediated immunity.     

Reflex control of sympathetic outflow and depressed baroreflex sensitivity following myocardial infarction

Reflex control of heart rate is frequently impaired following myocardial infarction. This is referred to as depressed baroreflex sensitivity. The aim of these experiments was to assess the function of other autonomic reflexes in dogs with depressed baroreflex sensitivity. Comparisons were made to dogs in whom baroreflex sensitivity was preserved or unchanged after myocardial infarction. Under chloralose-barbiturate anesthesia, reflex control of sympathetic outflow by the sinoaortic baroreceptors was determined by measurement of changes in systolic arterial pressure and efferent renal sympathetic nerve activity during infusion of phenylephrine. Following sinoaortic denervation, reflex control of sympathetic outflow by cardiac receptors with vagal afferent fibers was determined by measurement of changes in pulmonary capillary wedge pressure and renal nerve activity during blood volume expansion. Reflex decreases in renal nerve activity in response to increases in arterial pressure were similar in the two groups of dogs. In contrast, elevation of pulmonary capillary wedge pressure elicited significantly greater reflex decreases in renal nerve activity in dogs with depressed baroreflex sensitivity following myocardial infarction compared to dogs with preserved baroreflex sensitivity. Hemodynamic parameters and infarct sizes were similar in each group. In conclusion, activation of cardiac receptors with vagal afferent fibers elicited greater reflex inhibition of sympathetic outflow in dogs with depressed baroreflex sensitivity following myocardial infarction. These data suggest that these receptors are "sensitized". These results provide additional support for the hypothesis that depressed reflex control of heart rate following myocardial infarction is related to augmented afferent input from the left ventricle.     

Effects of immediate feedback and errorless learning on recognition memory processing in young and older adults

Age-related memory decline appears to be due to impaired recollection whereas familiarity may be intact. An intervention was therefore designed with the aim of optimising use of this intact sense of familiarity. A continuous face recognition paradigm was used which required detection of repeats in a long series. The experimental intervention consisted of immediate feedback on response accuracy and avoidance of errors by discouraging guessing.

Experimental and control interventions were compared by recruiting 40 people aged under 30 years or over 60 years for six 45-minute training sessions. The elderly participants initially showed a more lax response criterion than young people but the experimental intervention reversed this effect so that by the end of training the elderly participants were less prone to false alarms than the younger participants. However, there was only limited evidence of generalisation of this training effect to other memory tasks and no effect on recognition sensitivity.

This study demonstrates that combined feedback and errorless learning allow elderly people to adjust their response criterion during recognition memory tasks. Taken together with previous encouraging studies, it seems that this training approach might have potential as a therapy for age-related memory impairment. However this would require development of additional methods to enhance generalisation beyond trained tasks and to elicit improvements in sensitivity as well as reduction of false alarms. The separate contributions of feedback and errorless learning also need to be investigated.     

Thermographic assessment of impaired sympathetic function in peripheral nerve injuries

Summary Twenty-three patients with focal, strictly unilateral lesions of the peripheral nervous system were examined by infrared-thermography. The Minor sweat test was used to determine if sympathetic outflow was disturbed.In fifteen patients without a concomitant sympathetic lesion (controls) thermosymmetry was not disturbed.Eight patients had evidence of abnormal sweat secretion. In these patients thermoregulation was severely disturbed. During the first 5 to 8 months, affected skin areas were hyperthermic, whereas later only hypothermia was observed. Cold stimuli increased temperature differences in patients with disturbed sympathetic function, but not in controls.Thermography is a reliable, non-invasive technique to detect a lesion of sympathetic outflow and permits an estimation of the time-course of the lesion.

---

Zusammenfassung Dreiundzwanzig Patienten mit monotopen, streng einseitigen Schädigungen des peripheren Nervensystems wurden mittels der Infrarot-Thermographie untersucht. Durch den Schweißtest nach Minor wurde festgestellt, ob eine Sympathikusläsion vorlag.Bei fünfzehn Patienten (Kontrollpatienten) ohne eine begleitende Sympathikusschädigung war die Thermosymmetrie nicht gestört.Bei acht Patienten war die Schweißsekretion vermindert oder erloschen. Diese Patienten hatten eine schwere Störung der Thermoregulation. Während der ersten 5 bis 8 Monate waren die betroffenen Hautareale hypertherm, wohingegen später nur Hypothermien beobachtet wurden. Durch Kältereize vergrößerten sich die Temperaturdifferenzen bei Patienten mit einer Sympathikusschädigung, nicht jedoch bei den Kontrollpatienten.Die Thermographie ist eine verläßliche, nicht-invasive Methode zur Aufdeckung einer Sympathikusschädigung und erlaubt eine Abschätzung des Alters der Schädigung.

     

Influences of neck afferents on sympathetic and respiratory nerve activity

It is well established that the vestibular system influences the sympathetic nervous system and the respiratory system; presumably, vestibulosympathetic and vestibulorespiratory responses participate in maintaining stable blood pressure and blood oxygenation during movement and changes in posture. Many brainstem neurons that generate vestibulospinal reflexes integrate signals from the labyrinth and neck muscles to distinguish between head movements on a stable body and whole body movements. In the present study, responses were recorded from the splanchnic (sympathetic), hypoglossal (inspiratory) and abdominal (expiratory) nerves during stimulation of the C2 dorsal root ganglion or C2 or C3 nerve branches innervating dorsal neck muscles. Stimulation of neck afferents using low current intensities, in many cases less than twice the threshold for producing an afferent volley recordable from the cord dorsum, elicited changes in sympathetic and respiratory nerve activity. These data suggest that head rotation on a stable body would elicit both cervical and vestibular inputs to respiratory motoneurons and sympathetic preganglionic neurons. The effects of cervical afferent stimulation on abdominal, splanchnic and hypoglossal nerve activity were not abolished by transection of the brainstem caudal to the vestibular nuclei; thus, pathways in addition to those involving the vestibular nuclei are involved in relaying cervical inputs to sympathetic preganglionic neurons and respiratory motoneurons. Transection of the C1-3 dorsal roots enhanced responses of the splanchnic and abdominal nerves to pitch head rotations on a fixed body but diminished responses of the hypoglossal nerve. Thus, neck and vestibular afferent influences on activity of respiratory pump muscles and sympathetic outflow appear to be antagonistic, so that responses will occur during whole body movements but not head movements on a stationary trunk. In contrast, neck and vestibular influences on tongue musculature are complementary, presumably to produce tongue protrusion either during movements of the head alone or of the whole body.     

Effect of pimobendan on cardiopulmonary baroreflex control of sympathetic nerve activity in healthy young men

In order to determine the effect of pimobendan on sympathetic nerve activity and cardiopulmonary baroreflex (CPB), electrocardiogram, direct arterial pressure, central venous pressure (CVP) and cardiac output were recorded along with muscle sympathetic nerve activity (MSNA) in 8 healthy young men. CPB function was evaluated before and 60 min after oral administration of 5 mg pimobendan using the response of MSNA to lower body negative pressure (LBNP) of -5 and -10 mm Hg. The same protocol also was performed during handgrip exercise. Cardiac index, MSNA increased and CVP decreased significantly (p<0.01, respectively), but arterial pressure and heart rate unchanged after pimobendan administration. During LBNP, CVP decreased and MSNA increased significantly. CPB sensitivity was augmented from 5.53+/-0.75 to 8.59+/-0.78 burst incidence/mm Hg after pimobendan administration (p<0.01). Pimobendan did not alter the percentage increase of MSNA during handgrip exercise. In conclusion, pimobendan induces an increase in basal sympathetic nerve activity by decreasing CVP and augmenting CPB sensitivity without changing arterial pressure in healthy young men.     

Stress-induced changes in human salivary alpha-amylase activity -- associations with adrenergic activity

The salivary enzyme alpha-amylase has been proposed to indicate stress-reactive bodily changes. A previous study by the authors revealed marked increases in salivary alpha-amylase following psychosocial stress, indicating a stress-dependent activation of salivary alpha-amylase. Salivary alpha-amylase has been suggested to reflect catecholaminergic reactivity. Our aim was to assess/evaluate a possible relationship between salivary alpha-amylase and adrenergic parameters, i.e. catecholamines, as well as other stress markers. Using an intra-individual repeated measures design, 30 healthy young men underwent the Trier Social Stress Test (TSST), which consists of a mental arithmetic task and free speech in front of an audience and a control condition in randomized order. Salivary alpha-amylase and salivary cortisol as well as plasma catecholamines and cardiovascular activity were repeatedly measured before, during, and after both conditions. Significant differences were found between the stress and the rest condition in salivary alpha-amylase, salivary cortisol, plasma catecholamines, and cardiovascular parameters (heart rate, LF, HF, LF/HF). However, general alpha-amylase responses (area under the curve) were not associated with general responses in catecholamines and cortisol in the stress condition (r smaller than 0.25 for all analyses). Analysis of cardiovascular parameters indicates a positive relationship between amylase and sympathetic tone (LF/HF) during stress. Salivary alpha-amylase is sensitive to psychosocial stress. Since it does not seem to be closely related to other biological stress markers such as catecholamines and cortisol, salivary alpha-amylase may be a useful additional parameter for the measurement of stress.     

Central representation of the sympathetic nervous system in the cerebral cortex

The sympathetic-related regions of the cerebral cortex were identified in rats after pseudorabies virus injections were made in functionally different targets: adrenal gland, stellate ganglion which regulates the heart, or celiac ganglion which innervates the gastrointestinal tract. Extensive transneuronal labeling was found in limbic system areas: (1) extended amygdaloid complex, (2) lateral septum, and (3) infralimbic, insular, and ventromedial temporal cortical regions (viz., ectorhinal CORTEX=Brodmann’s area 36, perirhinal CORTEX=area 35, lateral ENTORHINAL=area 28, and ventral temporal association CORTEX=Te3 region). Deep temporal lobe structures were prominently labeled, including the amygdalopiriform and amygdalohippocampal transition areas, ventral hippocampus and ventral subiculum. The cortical circuits mediating emotional–autonomic changes (i.e., mind–body control) are discussed.     

Increase in muscle nerve sympathetic activity after glucose intake is blunted in the elderly

Muscle nerve sympathetic activity (MSA; involved in blood pressure regulation) was recorded by microneurography in the peroneal nerve for 90 min after ingestion of 100 gd-glucose in three groups of healthy subjects: young subjects (mean age 26 years) and 70-year-old men with normal and reduced insulin sensitivity as assessed by euglycaemic insulin clamp. Muscle nerve sympathetic activity at rest was lowest in the young and highest in the insulin-resistant subjects (burst frequencies 19.8±6.0, 47.7±7.0 and 55.1±11.5 bursts/min for the three groups, respectively). The young subjects responded to glucose intake with a pronounced increase in MSA, a response that was blunted in the elderly and weakest in the insulin-resistant subjects. A similar relationship was observed during a Valsalva manoeuvre, indicating that the blunted response in the elderly is a generalized phenomenon. Blood pressure remained stable in the young subjects but fell slightly and significantly in the elderly subjects. It is concluded that old subjects utilize their total capacity for MSA close to maximum at rest. Thus, the reserve for response to stimuli normally evoking a strong increase in MSA is restricted. This restriction may contribute to postprandial hypotension in the healthy elderly.     

Muscle sympathetic nerve activity peaks in the first trimester in healthy pregnancy: a longitudinal case study

Objective and methods

Muscle sympathetic nerve activity and baroreflex sensitivity were examined at rest before, during (weeks 6, 11, 17, 22, 25, 33 and 36) and after a normotensive pregnancy.

Results

Muscle sympathetic nerve activity is elevated during pregnancy with a large peak in the first trimester (Δ17 bursts/min) and a secondary peak in the third trimester (Δ11 bursts/min). Cardiac baroreflex sensitivity peaked in the first trimester (10 vs. 6 ms/mmHg pre-pregnancy), whereas sympathetic baroreflex sensitivity was greater throughout.

Interpretation

The increase in sympathetic outflow early in pregnancy cannot be explained by a reduction in baroreflex sensitivity, while the secondary increase in burst frequency in the third trimester may, in part, be explained by the elevated heart rate.

     

Spinal interneurons play a minor role in generating ongoing renal sympathetic nerve activity in spinally intact rats

The purpose of the present study was to determine whether spinal interneurons play a role in the regulation of sympathetic activity in spinally intact rats. In acutely spinally transected rats, we have described a population of spinal interneurons that, by virtue of correlations between their ongoing firing rates and the magnitude of ongoing renal sympathetic nerve activity (RSNA), are candidates for generators of sympathetic activity. Further evidence for a sympathetic role for these neurons comes from our observation that cervical spinal stimulation that reduces RSNA also reduces their discharge rates. In chloralose-anesthetized, spinally intact and spinally transected rats, we recorded ongoing RSNA and the ongoing activities of T₁₀ dorsal horn and intermediate zone interneurons, and we determined the incidence of sympathetically related neurons in these rats by cross-correlating their activities with RSNA. The incidence of correlated neurons was much smaller in spinally intact than in spinally transected rats. We stimulated the dorsolateral, C_2–3 spinal cord before and after acute C₁ spinal transection. Dorsolateral cervical stimulation in spinally transected rats reduced both RSNA and the activities of most T₁₀ interneurons, but stimulation in spinally intact rats increased RSNA while still reducing the activities of most T₁₀ interneurons. Both the low incidence of sympathetically correlated spinal neurons in intact rats and the dissociation between the effects of cervical stimulation on RSNA and the discharge rates of spinal interneurons argue against these neurons playing a major role in regulating sympathetic activity in intact rats.