The autonomic nervous system and cardiac arrhythmias

Disturbed autonomic nervous balance of the sympathetic nervous and vagal outflows to the heart potentiates the experimental development of ventricular arrhythmias in laboratory animals. For some time the best evidence for the occurrence of a similar phenomemon in humans was provided by the long QT interval syndrome, sufferers of which are very prone to develop serious ventricular arrhythmias and in whom evidence exists of abnormal anatomy and function of the cardiac sympathetic nerves. Recently the case for disturbed autonomic function causing clinical arrhythmias has become more broadly based. Reduced baroreflex sensitivity after myocardial infarction, and low heart rate variability, both of which rest largely on vagal underactivity, have been shown to be associated with substantially increased risk of subsequent sudden death. A second observation is that patients having recovered from unexpected ventricular tachycardia or ventricular fibrillation have markedly increased cardiac sympathetic activity compared with appropriate reference groups, based on measurements of the rate of spillover of the sympathetic neurotransmitter, noradrenaline, from the heart to plasma. These clinical findings support a role for cardiac autonomic dysfunction, specifically sympathetic activation and vagal withdrawal, in arrhythmogenesis. These observations are timely, given the recent demonstration that most conventional anti-arrythmics are of little benefit in preventing sudden death. A reappraisal of the anti-arrhythmic activity of -adrenergic blocking drugs, and evaluation of potential benefits of other pharmacological and non-pharmacological means of favourably altering cardiac autonomic function is now needed.     

Testing the autonomic nervous system

Noninvasive, well-validated clinical tests of autonomic function are available and are in relatively wide use. These comprise an evaluation of sudomotor, cardiovagal, and adrenergic functions. These tests are very useful and have resulted in the recognition of milder degrees of autonomic failure and the presence of orthostatic intolerance that previously were missed. An extensive normative database and commercial equipment is available. The main limitations of the tests relate to the fact that they evaluate mainly the function of target tissues so that the status of autonomic reflexes are inferred. The tests can be affected by medications. There are more invasive, more time-consuming, or less validated tests of autonomic function that can directly record from sympathetic nerve fibers (microneurography) and mesenteric bed to study cerebral vasoregulation and the status of the veins.     

A comparative study of the autonomic nervous system innervation of the thymus in the mouse and chicken

It is well-established that the thymus of rats and mice are directly innervated prenatally by neurons of the central nervous system (CNS). Evidence now suggests that this innervation is involved in determining the neuroendocrine-immune functions of the gland. In this study an analysis of CNS innervation of the chicken thymus was carried out using the horseradish peroxidase (HRP) retrograde transport method to establish the phylogenetic integrity of CNS-thymic innervation and to gain insight into its function. Day-old chicks received HRP injections into upper of lower thymic lobes. Lower injections resulted in HRP-labeled neurons in the ventral horn of the cervical spinal cord and in the dorsal and ventral brainstem complex of the nucleus of X. Injections into upper thymic lobes resulted in similar spinal cord labeling and in labeling of neurons in the nuclei of both IX and X. These injections produced more labeled neurons in the ventral complex of X than did injections into lower thymic lobes. Unilateral HRP injections into upper or lower thymic lobes produced predominantly ipsilateral labeling in the appropriate areas. The results of this study indicate that chick thymuses are innervated by the CNS during embryogenesis. Furthermore, there appears to be a topographical distribution of nerve fibers suggesting discrete functions for individual lobes.     

Roles of cardiac sympathetic neuroimaging in autonomic medicine

Clinical Autonomic Research - Sympathetic neuroimaging is based on the injection of compounds that either radiolabel sites of the cell membrane norepinephrine transporter (NET) or that are taken up...     

Progressive loss of cardiac sympathetic innervation in Parkinson's disease

This study addressed whether cardiac sympathetic denervation progresses over time in Parkinson's disease. In 9 patients without orthostatic hypotension, 6-[(18)F]fluorodopamine positron emission tomography scanning was repeated after a mean of 2 years from the first scan. 6-[(18)F]fluorodopamine-derived radioactivity was less in the second scan than in the first scan, by 31% in the left ventricular free wall and 16% in the septum. In Parkinson's disease, loss of cardiac sympathetic denervation progresses in a pattern of loss suggesting a dying-back mechanism.     

Nociception and autonomic nervous system

To observe the effects of minimally invasive procedures for the evacuation of intracerebral hematomas on perihematomal ET-1 expression and their correlation with blood–brain barrier (BBB) permeability. Forty-five rabbits (2.8–3.4 kg body weight) were randomly divided into a normal control group (NC group, 15 rabbits), a model control group (MC group, 15 rabbits) and a minimally invasive group (MI group, 15 rabbits). A model of intracerebral hemorrhage (ICH) was prepared in the MC and MI groups by infusing autologous arterial blood into the rabbits’ brains; the same procedure was also performed in the NC group but without infusing blood into the rabbits’ brains. The intracerebral hematomas were evacuated by a stereotactic procedure in the minimally invasive group 6 h after the model was established. The neurological functions, ET-1 expression and the perihematomal BBB permeability were determined and analyzed in all of the animals. The number of endothelial cells with ET-1-positive expression and the perihematomal BBB permeability significantly increased 1, 3, and 7 days after the ICH model was prepared successfully, as compared to the NC group. In the MI group, however, both measurements decreased markedly compared with the MC group at the same time point. A positive correlation between the number of endothelial cells with ET-1-positive expression and BBB permeability was observed. Increased BBB permeability might be associated with perihematomal ET-1 levels. Minimally invasive procedures for the evacuation of intracerebral hematomas could significantly decrease BBB permeability in perihematomal brain tissues, likely by reducing the production of ET-1.     

Neuroimaging and pain: a window on the autonomic nervous system

Neurological Sciences - Pain is one of the most common experiences of humans. Neuroimaging techniques can visualize the main brain areas involved in pain modulation, the pain matrix. It is...     

Neurotoxic action of 2,5-hexanedione on the autonomic nervous system: ultrastructural and functional alterations in the rat sympathetic superior cervical ganglion

In rats treated for 14 days with 2,5-hexanedione, the efficiency of ganglionic transmission was markedly reduced whereas only faint ultrastructural changes occurred in a few preganglionic fibers; evident signs of axonal pathology were observed on the 30th day of treatment. Choline acetyltransferase activity and acetylcholine formation showed no alteration at any time. The autonomic system is affected early during 2,5-hexanedione neuropathy, functional changes being more marked than morphological lesions.     

Multiple sclerosis and the autonomic nervous system

Symptoms related to alterations of the autonomic nervous system are frequent in patients with multiple sclerosis (MS). Bladder or bowel dysfunction or impairment of sexual performance is highly distressing for most MS patients,whereas the clinical relevance of other autonomic symptoms is less clear. Cardiovascular autonomic alterations might relate to clinical signs such as orthostatic intolerance; a relationship with fatigue is uncertain. However, the frequency of abnormal findings in tests for the cardiovascular autonomic system varies due to the lack of standardized test performance or differentially used cut-off values. The incidence of additional symptoms such as pupillomotor or sweating alterations and especially their relationship to overall autonomic nervous system abnormalities is not well known. Although their impact on daily life is low, they can at least serve as diagnostic tools. Beside these clinical aspects, alterations of the autonomic nervous system have also been reported to alter immunological cascades in experimental conditions. However, corresponding results have not been confirmed in clinical trials yet.