Changes In Autonomic Function Research Articles

Otolith stimulation induces c-Fos expression in vestibular and precerebellar nuclei in cats and squirrel monkeys

Vestibular information is critical for the control of balance, posture, and eye movements. Signals from the receptors, the semicircular canals and otoliths, are carried by the eighth nerve and distributed to the four nuclei of the vestibular nuclear complex, the VNC. However, anatomical and physiological data suggest that many additional brainstem nuclei are engaged in the processing of vestibular signals and generation of motor responses. To assess the role of these structures in vestibular functions, we have used the expression of the immediate early gene c-Fos as a marker for neurons activated by stimulation of the otoliths or the semicircular canals. Excitation of the otolith organs resulted in widespread c-Fos expression in the VNC, but also in other nuclei, including the external cuneate nucleus, the postpyramidal nucleus of the raphé, the nucleus prepositus hypoglossi, the subtrigeminal nucleus, the pontine nuclei, the dorsal tegmental nucleus, the locus coeruleus, and the reticular formation. Rotations that excited the semicircular canals were much less effective in inducing c-Fos expression. The large number of brainstem nuclei that showed c-Fos expression may reflect the multiple functions of the vestibular system. Some of these neurons may be involved in sensory processing of the vestibular signals, while others provide input to the vestibulo-ocular, vestibulocollic, and vestibulospinal reflexes or mediate changes in autonomic function. The data show that otolith stimulation engages brainstem structures both within and outside of the VNC, many of which project to the cerebellum.

Aging of the autonomic nervous system and possible improvements in autonomic activity using somatic afferent stimulation

There are significant age-related changes in autonomic nervous system function that are responsible for an impaired ability to adapt to environmental or intrinsic visceral stimuli in the elderly. We review data on changes in autonomic nervous system regulation of cardiovascular and urinary function, as well as data on strategies to improve function. There are data showing alterations in peripheral and central autonomic nerve activity, and decreases in neurotransmitter receptor action that lead to diminished autonomic reactivity (e.g. blood pressure and cerebral blood flow regulation) and poorly coordinated autonomic discharge (e.g. bladder function). Simple strategies for autonomic function improvement and increasing cortical blood flow include walking and somatic afferent stimulation (e.g. stroking skin or acupuncture) to increase sympathetic, parasympathetic and central cholinergic activity.

Prolonged duration of craving, mood, and autonomic responses elicited by cues and imagery in smokers: Effects of tobacco deprivation and sex.

Increases in self-reported craving and changes in autonomic functioning are reliably elicited when smokers are exposed to tobacco-related stimuli compared with neutral stimuli. However, few studies have reported the time course of cue-elicited craving or have directly compared the effectiveness of smoking cues versus imagery to evoke a craving response. In addition to these two issues, we investigated the influence of tobacco deprivation and sex on craving, mood, and autonomic responses. Sixty cigarette smokers (30 men, 30 women) were tested in two counterbalanced sessions, one after overnight tobacco deprivation and one during ad libitum smoking. At each session, participants were exposed to four randomized experimental trials: smoking imagery, neutral imagery, smoking cues, and neutral cues. Tobacco craving and mood were assessed repeatedly and physiological measures were recorded continuously for 30 min after imagery or cue exposure. Compared with neutral trials, smoking cues and smoking imagery reliably increased tobacco craving, negative mood, heart rate, and blood pressure and decreased positive mood ratings. Changes were observed immediately after cue and imagery presentation and remained unchanged for 30 min. Responding was greater in the nondeprived condition, and cues elicited more robust responding than imagery for most measures. Women responded more robustly to smoking cues only in the nondeprived condition, whereas imagery evoked greater responses in men during both conditions. These findings provide new data on the time course, magnitude, and tobacco deprivation effects on elicited craving. Sex differences were dependent on stimulus type and deprivation condition.

Transcranial magnetic stimulation for auditory hallucination in severe schizophrenia: Partial efficacy and acute elevation of sympathetic modulation

Repetitive transcranial magnetic stimulation (rTMS) has been reported to be an effective treatment for auditory hallucination (AH) in schizophrenia patients. The efficacy of rTMS and immediate changes in cardiac autonomic function (CAF) after rTMS in severe schizophrenia patients with AH (n = 8) were investigated. Three patients reported a >or=50% reduction of AH after rTMS. The ratio of low-frequency power to high-frequency power, an index of sympathetic modulation, increased significantly after rTMS. Further replication studies with larger sample sizes are indicated.

Conditioning of an autonomic response in Crustacea

Reports on experience-dependent changes in invertebrate autonomic function are few. In the crab Chasmagnathus, repeated presentations of a visual danger stimulus (VDS) elicit long-term cardiac adjustments. Although these changes can be explained in terms of an associative process, they do not necessarily indicate an anticipatory conditioned response. In the present work, we investigated anticipation of the cardio-inhibitory response (CIR) after classical conditioning. We found that an initially seemingly neutral stimulus, which could trigger only a brief CIR as part of an arousal/orienting response, following pairing with the unconditioned stimulus, 24 h after a second exposure, triggered a significantly stronger CIR response compared to controls. We propose that, as a result of training, the conditioned stimulus acquires a different biological meaning, allowing the crab to anticipate the aversive stimulus.

Altered Cardiac Autonomic Function May Precede Insulin Resistance in Metabolic Syndrome

Background Previous studies on the change of cardiac autonomic function and insulin resistance in metabolic syndrome recruited subjects with cardiovascular-related disease and defined metabolic abnormality with a more severe cutoff. We explored the alteration of cardiac autonomic function and insulin resistance in predisease community dwellers with different numbers of metabolic abnormalities. Methods A total of 1298 subjects were classified as none (n = 539), one (n = 378), 2 (n = 218), and 3 or more metabolic abnormalities (n = 154). Insulin resistance was calculated by homeostatic model assessment. Cardiac autonomic function included 5-minute standard deviation of R-R interval, low- and high-frequency power spectrum, and low-/high-frequency power spectrum ratio, the ratio of the longest R-R interval around the 30th beat and the shortest R-R interval around the 15th beat after standing, and the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing. Results Subjects with a single metabolic abnormality or more had a lower standard deviation of R-R interval and expiratory/inspiratory ratio than subjects without metabolic abnormality in multivariate analysis. Subjects with 3 or more metabolic abnormalities had a higher low-/high-frequency power spectrum ratio, but a lower high-frequency power. Insulin resistance was higher in groups with 2 metabolic abnormalities or more, but not in the group with one metabolic abnormality, than those without metabolic abnormality. Conclusions Cardiac autonomic function altered in predisease subjects with one or more metabolic abnormalities, while insulin resistance existed in subjects with 2 or more metabolic abnormalities. Thus, autonomic function change may precede insulin resistance in the initiation of metabolic syndrome.

Cardiac autonomic function associated with treatment adherence after a brief intervention in chronic pain

Multidisciplinary approaches to pain management often include training in self-regulatory techniques such as diaphragmatic breathing. However, there is a paucity of quantitative evidence in the literature regarding the psychological and physiological changes associated with the use of diaphragmatic breathing. The main objectives of this study were to determine if training and practice in a brief focused breathing technique was associated with changes in pain symptoms and cardiac autonomic function.

Neurophysiological, histological and immunohistochemical characterization of bortezomib-induced neuropathy in mice

Bortezomib, a proteasome inhibitor, is an antineoplastic drug to treat multiple myeloma and mantle cell lymphoma. Its most clinically significant adverse event is peripheral sensory neuropathy. Our objective was to characterize the neuropathy induced by bortezomib in a mouse model. Two groups were used; one group received vehicle solution and another bortezomib (1 mg/kg/twice/week) for 6 weeks (total dose as human schedule). Tests were performed during treatment and for 4 weeks post dosing to evaluate electrophysiological, autonomic, pain sensibility and sensory-motor function changes. At the end of treatment and after washout, sciatic and tibial nerves, dorsal ganglia and intraepidermal innervation were analyzed. Bortezomib induced progressive significant decrease of sensory action potential amplitude, mild reduction of sensory velocities without effect in motor conductions. Moreover, it significantly increased pain threshold and sensory-motor impairment at 6 weeks. According to these data, histopathological findings shown a mild reduction of myelinated (−10%; p = 0.001) and unmyelinated fibers (−27%; p = 0.04), mostly involving large and C fibers, with abnormal vesicular inclusion body in unmyelinated axons. Neurons were also involved as shown by immunohistochemical phenotypic switch. After washout, partial recovery was observed in functional, electrophysiological and histological analyses. These results suggest that axon and myelin changes might be secondary to an initial dysfunctional neuronopathy.

Chronotropic incompetence and autonomic dysfunction in patients without structural heart disease

An attenuated heart rate response to exercise, termed chronotropic incompetence (CI), has been reported to be an independent predictor of cardiovascular mortality. We examined the change in autonomic function during exercise testing and correlated the results with CI. Exercise testing using a bicycle ergometer was performed in 172 patients who had no evidence of cardiac disease. Chronotropic incompetence was defined as the failure to achieve 85% of the age-predicted maximum heart rate, heart rate reserve <80%, or chronotropic response index <0.80. We analysed the relationship between CI and the change in two components of heart rate variability during exercise testing: high-frequency (HF) component (0.15-0.40 Hz) as an index of vagal modulation and the ratio of low-frequency (LF) component (0.04-0.15 Hz) to HF component as an index of sympathovagal balance. Heart rate variability indexes before exercise were similar in patients with and without CI. Percentage changes after exercise in the ratio of LF to HF component were higher in patients with CI than in those without CI (84 +/- 15 vs. 41 +/- 16%, P < 0.05), whereas percentage changes in an HF component were similar in the two groups. Our data suggested that CI in patients without structural heart disease was mainly caused by a pathophysiological condition in which sympathetic activation was not well translated into heart rate increase. Further study is needed to determine the post-synaptic sensitivity of the beta-adrenergic receptor pathway in relation to CI.

Autonomic function and change in insulin for exercising postmenopausal women

Purpose Obesity, physical inactivity and altered estrogen metabolism play an integrated role contributing to the disease risk profiles of postmenopausal women. These same risk factors also affect modulation of the autonomic nervous system (ANS). Methods We examined 332 postmenopausal, overweight, previously sedentary women (mean ± SD; age, 57.6 ± 6.3 years; weight, 84.3 ± 11.9 kg; BMI, 31.7 ± 3.7 kg/m 2) participating in a 6-month, moderate intensity, aerobic exercise training intervention to determine the relationship between heart rate variability (HRV) derived autonomic function and fasting insulin. We analyzed quartiles of change in time and frequency domain indices of ANS activity and changes in insulin for between and within group differences using ANCOVA and Tukey post hoc tests adjusted for age, ethnicity, randomization group, change in fitness, and change in weight. Results We observed at baseline that insulin was positively correlated with body anthropometry (body weight, r 2 = 0.34; BMI, r 2 = 0.39; waist circumference, r 2 = 0.29; all, P < 0.001), and inversely associated with rMSSD ( r 2 = −0.12) and SDNN ( r 2 = −0.18; all, P < 0.01). After the intervention, changes in rMSSD ( r 2 = −0.21, P < 0.002) and SDNN r 2 −0.19, P < 0.0001) were inversely correlated to insulin change. Further ANCOVA analysis revealed that rMSSD and SDNN were both significant ( P < 0.0001); however, only rMSSD exhibited a step-wise pattern of improvement when quartiles of rMSSD were compared to corresponding insulin reductions: Q1 (referent group, 8.41 ± 3.2 uIU/ml), Q2 (−3.30 ± −3.2 uIU/ml), Q3 (−5.66 ± −3.2 uIU/ml; P < 0.02), and Q4 (−9.60 ± −3.2 uIU/ml; P < 0.006). Conclusion Our study shows that changes in autonomic function are associated with changes in insulin and that exercise training may influence this relationship in postmenopausal women.

Effect of pioglitazone on systemic inflammation is independent of metabolic control and cardiac autonomic function in patients with type 2 diabetes

The aim of this article is to investigate the relation of the anti-inflammatory effect of pioglitazone with cardiac autonomic function and metabolic control in diabetic patients. In this prospective open label trial, 36 type 2 diabetic patients (age 60 ± 10, 20 M) without overt cardiovascular disease were randomized to add pioglitazone (30 mg) to their therapy or to continue standard therapy. C-reactive protein (CRP) serum levels, metabolic parameters and cardiac autonomic function (assessed by heart rate variability [HRV] on 24-h ECG Holter monitoring) were measured at baseline and after 3 months. Clinical and laboratory variables were similar in the two groups. No significant changes were observed after 3 months for metabolic and anthropometric parameters, except for a mild increase in HDL levels in the pioglitazone group only (P = 0.04 vs. controls). CRP levels decreased significantly at follow-up in the pioglitazone group (3.2 ± 1.97 vs. 2.37 ± 1.56 mg/l) but not in the control group (3.0 ± 1.92 vs. 3.93 ± 2.14 mg/l; P = 0.003). No differences were found in basal and follow-up HRV variables between the two groups. In type 2 diabetic patients pioglitazone exerts favourable effects on inflammation even after short-term therapy. This effect precedes those on metabolic and anthropometric parameters and is not associated with changes in cardiac autonomic function.

Diagnostic Manual–Intellectual Disability: A Textbook of Diagnosis of Mental Disorders in Persons With Intellectual Disability, by R. Fletcher, E. Loschen, C. Stavrakaki, and M. First

Diagnostic Manual–Intellectual Disability: A Textbook of Diagnosis of Mental Disorders in Persons With Intellectual Disability, by R. Fletcher, E. Loschen, C. Stavrakaki, and M. First

Epileptic seizure-induced hypertension and its prevention by calcium channel blockers: a real-time study in conscious telemetered rats

Epileptic seizures are accompanied by changes in autonomic function that in turn influence the cardiovascular system (hypertension and bradyarrhythmia). We have studied possible cardioprotective activity (during the ictal state in conscious animals) of valproic acid, nifedipine, and verapamil, alone and in combination, during pentylenetetrazole (PTZ)-induced seizures. Telemetry system was used for recording EEG, blood pressure, and heart rate in conscious, freely moving rats during seizures. We observed that PTZ-induced seizures were accompanied by hypertension and bradyarrhythmia. Pretreatment with valproic acid did not block seizure-induced hypertension and bradyarrhythmia. Nifedipine alone and in combination with valproic acid blocked seizure-induced hypertension and bradyarrhythmia significantly. We also observed that pretreatment with verapamil alone and in combination with valproic acid did not block seizure-induced hypertension and bradyarrhythmia significantly. Our results suggest that pretreatment with nifedipine alone or in combination with valproic acid provides protection against seizure-induced hypertension and bradyarrhythmia.

Exposure to environmental carbon monoxide may have a greater negative effect on cardiac autonomic function in people with metabolic syndrome

Carbon monoxide (CO) has been recognized as a risk factor for adverse cardiovascular outcomes. We investigated the effects of CO on cardiac autonomic function by measuring the heart rate variability (HRV) in patients with and without metabolic syndrome (MetS). We also explored the relationship between CO exposure and specific components of MetS. Data were obtained from air pollution measurements and from health examinations on a total of 986 subjects, from a Korean community. Measurements of the 5-min HRV and examinations for MetS were conducted, and a linear regression model with a time lag was evaluated for any association. The group with MetS showed a significant reduction in the standard deviation of the normal-to-normal intervals (SDNN) and in the high frequency domain of HRV. After adjusting for age, sex, smoking status, day of the week effect, month effect, temperature, and relative humidity, these declines were significantly associated with exposure to CO for 25 to 48 h prior to the HRV measurement. Evidence for effect-modification by two specific MetS components, fasting blood glucose and triglycerides, was also observed in relation to CO exposure. These results suggest that CO exposure may trigger changes in cardiac autonomic function, and that subjects at high risk for heart disease may be more susceptible to CO effects.

Changes of autonomic and sensory function during 24 weeks of antiviral treatment in patients with chronic HCV infection

Changes of autonomic and sensory function during 24 weeks of antiviral treatment in patients with chronic HCV infection

Analysis of cardiovascular autonomic function from telemetric blood pressure recordings: effects of age, high fat diet and angiotensin II

Assessments of sympathetic/parasympathetic nervous activity and baroreceptor reflex gain (BRG) are important for understanding neural mechanisms of cardiovascular diseases, and evaluation of heart rate variability (HRV) as well as spontaneous BRG from telemetric blood pressure recordings provides a useful tool in experimental rat models. We analyzed changes in these parameters in response to 60% high fat diet feeding and to central infusion of angiotensin II (AngII, 10nmol/h) or losartan (LOS, 15µg/h) in young (5 mo) and old (27mo) F344xBN rats that were equipped with telemetric BP transmitters. Spontaneous BRG was significantly higher in young rats vs. old. High fat feeding, as well as central infusions of both AngII and LOS, reduced BRG in young rats, but were ineffective in old animals. Both low frequency power (LF) of pulse interval data, which reflects sympathetic tone to the heart, and high frequency power (HF), which reflects parasympathetic tone, were significantly lower in old rats compared with young. AngII increased LF in young, but not in old rats, whereas HF remained unchanged in both groups. In contrast, LOS had no effect on either parameter. In response to high fat feeding, LF increased in young, but decreased in old rats, while HF decreased both in young and old animals. These data show that analysis of BRG and HRV can be used to detect age‐, diet‐ and AngII‐induced changes in autonomic function, and that age has a significant effect on how the autonomic nervous system reacts to these stimuli.

Nutritional influences on maternal autonomic function during pregnancy

The objective of this study was to identify influences on longitudinal changes in autonomic function during pregnancy. We studied 195 low-income Peruvian women who were subjects in a randomized controlled trial of zinc supplementation and fetal neurobehavioral development. Maternal cardiorespiratory status and electrodermal activity were assessed at 20, 24, 28, 32, 36, and 38 weeks' gestation over a 50-min session. At baseline (10-16 weeks), and at 28 and 36 weeks' gestation, mass and height, arm and calf circumferences, and skinfold thicknesses were assessed, and blood was taken to measure hemoglobin, hematocrit, and plasma zinc concentration. Measures of heart period (HP), respiratory period (RP), respiratory sinus arrhythmia (RSA), skin conductance level (SCL), and mean arterial pressure (MAP) were analyzed using longitudinal models. Having a hemoglobin concentration <10.5 g.dL-1 at 28 weeks was associated with shorter HP and RP and lower RSA, and change in hemoglobin from baseline to 36 weeks was associated with decreased SCL. Further, 3 measures were associated with variation in fat or fat-free mass in the calf; RSA was negatively associated with changes in calf muscle area over pregnancy, while changes in calf fat area were positively associated with MAP and SCL. Variability in autonomic function during the second half of pregnancy is associated with hematologic status and changes in lower limb body composition across pregnancy.

Infant botulism intoxication and autonomic nervous system dysfunction

Three infants presenting with severe cases of infantile botulism, occurring at 17, 30, and 180 days of life, respectively, are described in this report. All three infants presented with areflexive flaccid coma or apnoeas requiring prolonged ventilation. In serum, type B botulinum neurotoxin (BoNT/B) was detected in two cases and BoNT/A in the third case, confirming the diagnosis of infantile botulism. Despite constant nursing and monitoring, the recovery of motility was progressive, but finally complete. Dysautonomia, measured by recording heart rate variability (HRV), persisted beyond observable physical recovery. Dysautonomia was assessed using a time-domain analysis of the continuous electrocardiogram response (via non-invasive weekly 24 h Holters), which included sympathetic (SDNN) and parasympathetic indices (RMS-SD, pNN50). In all three of our patients, we observed an initial hypotonic period and a major decrease in all HRV indices. Despite observable recovery shortly after extubation, HRV time domain indices remained altered for many weeks. Because of the close monitoring afforded by hospitalization, this change in autonomic function was not accompanied by syncope, complications arising from ventricular arrhythmia, or sudden death. Our observations have important clinical implications since they emphasize the importance of pursuing cardiopulmonary monitoring following apparent functional recovery from the BoNTs.

Fruit, vegetable, and fish consumption and heart rate variability: the Veterans Administration Normative Aging Study

Background: Higher intakes of fruit, vegetables, and dark fish may prevent sudden cardiac death and arrhythmias, but the exact mechanisms are not fully understood.Objective: We examined whether high consumption of fruit, vegetables, and dark fish would be associated with beneficial changes in heart rate variability (HRV).Design: HRV variables were measured among 586 older men with 928 total observations from November 2000 to June 2007 in the Normative Aging Study, a community-based longitudinal study of aging. Dietary intake was evaluated with a self-administered semiquantitative food-frequency questionnaire and categorized into quartiles.Results: After controlling for potential confounders, intake of green leafy vegetables was positively associated with normalized high-frequency power and inversely associated with normalized low-frequency power (P for trend < 0.05). These significant associations were retained after further adjustment for healthy lifestyle factors, such as physical activity and use of multivitamins. No significant association was seen between HRV measures and intakes of other fruit and vegetables, vitamin C, carotenoids, tuna and dark-meat fish, or n–3 (omega-3) fatty acids. An effect modification of intake of noncitrus fruit by obesity and of total vegetables and cruciferous vegetables by cigarette smoking was seen, which warrants further investigation.Conclusion: These findings suggest that higher intake of green leafy vegetables may reduce the risk of cardiovascular disease through favorable changes in cardiac autonomic function.

Autonomic function in patients with Duchenne muscular dystrophy

Assessing autonomic function is important for patients with chronic heart failure, but the way that autonomic function changes in patients with Duchenne muscular dystrophy (DMD) and correlates with other clinical parameters during their young age is not clearly known. Heart rate variability (HRV) during ambulatory electrocardiogram (ECG) was performed in 57 DMD patients (130 recordings) who were not receiving medication (mean age 15.3 +/- 4.5 years). The data were compared with the serum levels of brain natriuretic peptide (BNP), the shortening fraction (SF) of the left ventricle on echocardiography, and simple parameters of heart rate from 24 h ambulatory ECG. Among four parameters of HRV measurements (high frequency [HF]; percentage of adjacent normal R-R intervals that were >50 ms different for the entire 24 h recording [%RR50]; ratio of low to high frequency [LF/HF]; and standard deviation for all normal R-R intervals for the entire 24 h recording [SDNN]), SDNN was most frequently abnormal. Even when SF was normal, a significant percentage of patients exhibited, abnormal parasympathetic activity (HF, %RR50: 74%, 78%, respectively), sympathetic activity (LF/HF, 43%), and SDNN (96%). Similarly, even if serum BNP levels were normal, 86%, 89%, 59%, and 97% of the patients displayed abnormal autonomic function on these measurements, respectively. Mean heart rate at night most accurately predicted abnormality of SDNN. When the cut-off point for mean heart rate at night was 71 beats/min, the sensitivity and specificity of this parameter for predicting abnormal SDNN was 94% and 85%, respectively (P < 0.0001). In DMD, autonomic function, especially SDNN, was frequently abnormal, although conventional clinical examinations of cardiac function (BNP levels and SF) were normal. It is proposed that mean heart rate during night could be used as a simple measurement for evaluation of autonomic function.