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PubMed1990

Cardiovascular autonomic function in anthracycline-treated breast cancer patients.

Preclinical studies suggest that in addition to the well-known direct damage to the myocardium, anthracycline antineoplastic drugs exert toxic effects on the cardiovascular autonomic system as well. To investigate whether this phenomenon occurs in the clinic, we carried out noninvasive, widely used tests of cardiovascular autonomic physiology in 55 women with stage II or III breast cancer. In all, 31 were being treated with anthracycline-containing chemotherapy regimens, and 24 who were receiving CMF (cyclophosphamide, Methotrexate, and fluorouracil) served as controls. Of 279 tests conducted in anthracycline (A)-treated patients, 123 were abnormal, vs 54 of 216 tests carried out in 24 controls (44% vs 25%; P less than 0.005). Abnormal variations in heart rate on standing and in diastolic blood pressure during handgrip was found in 25 (81%) and 17 patients receiving A, vs 9 (37%; P less than 0.005) and 5 (21%; P less than 0.0001), respectively, in controls. The incidence of abnormal tests was significantly higher in A-treated patients greater than 60 years of age (41%) vs 67%; P less than 0.05). Radionuclide ventriculography was carried out in 19 patients who showed abnormal tests of cardiovascular autonomic function after greater than or equal to 6 courses of a-containing chemotherapy; only 1 of them had abnormal cardiac contractility (global hypokinesia), suggesting that abnormal tests of cardiovascular autonomic function may occur in the absence of a detectable deterioration in left ventricular ejection fraction. A large number of factors may alter cardiovascular autonomic function in cancer patients, including age, radiation therapy to the chest, and multidrug treatment. Even after correcting for the most obvious of these, chemotherapy with anthracyclines is associated with a significantly higher percentage of abnormal tests for cardiovascular autonomic function. Although indirect and semi-quantitative, our results are compatible with the idea of A-induced cardiac autonomic dysfunction.

Antibiotics, Antineoplastic↗

PubMed2000

Altered baroreflex responses in alpha7 deficient mice.

The autonomic nervous system controls and coordinates several cardiovascular functions, including heart rate, arterial pressure, blood flow and vasomotor tone. Neuronal nicotinic acetylcholine receptors (nAChRs) are the interface between the nervous system and the cardiovascular system, but it is not known which nAChR subtypes regulate autonomic function in vivo. Nicotinic AChRs containing the alpha7 subunit are a candidate subtype in autonomic ganglia. Stimulation of these nAChRs can increase neurotransmitter release via presynaptic mechanisms, as well as mediate fast synaptic transmission via postsynaptic mechanisms. To investigate the role of the alpha7 nAChR subunit in cardiac autonomic function, we measured baroreflex-mediated responses in alpha7 null mice. Here we show that the alpha7 null mice have impaired sympathetic responses to vasodilatation, as sodium nitroprusside infusion triggered a 48% heart rate increase in wild type mice but only a 21% increase in the alpha7 nulls (P < 0.001). The mutant mice developed supersensitivity to adrenergic agonists, although norepinephrine release from sympathetic nerve terminals could be elicited through mechanisms alternative to nAChR stimulation. Baroreflex-mediated parasympathetic responses were normal in alpha7 null mice. The decreased baroreflex-mediated tachycardia in alpha7 mutant mice indicates that alpha7-containing nAChRs participate in the autonomic reflex that maintains blood pressure homeostasis. The alpha7 mutant mice may serve as a model of baroreflex impairment arising from autonomic dysfunction.

Animals↗

PubMed2002

Current issues in Sjögren's syndrome.

Sjögren's syndrome is a chronic autoimmune and rheumatic disorder with prominent sicca complaints from the mucous membranes because of lack of proper exocrine secretions. There is no straightforward and simple diagnostic test for Sjögren's syndrome, although several classification criteria have been designed including several oral diagnostic tests. A new set of classification criteria in a joint effort by research groups in Europe and USA has recently been presented. A large number of autoantibodies have been reported in Sjögren's syndrome where, in some cases, the antibodies are correlated with the extent and severity of disease. The finding of serum autoantibodies directed against the muscarinic M3 receptor is an important advance in understanding the pathogenesis of not only the impaired glandular function but also associated features of autonomic dysfunction in some patients. The treatment of primary Sjögren's syndrome is still mainly symptomatic.

Animals↗

PubMed1982

Pancreatic polypeptide responses to hypoglycemia in chronic autonomic failure.

Pancreatic polypeptide (PP) and catecholamine responses to insulin-induced hypoglycemia have been measured in 15 patients with neurogenic orthostatic hypotension. Eight of the patients had idiopathic orthostatic hypotension, and 7 had multiple system atrophy, a condition characterized by the presence of central nervous system lesions in addition to the orthostatic hypotension common to both diseases. Eleven healthy subjects exhibited rapid and substantial elevations in plasma epinephrine, norepinephrine, and PP concentrations in response to insulin hypoglycemia. In contrast, patients with neurogenic orthostatic hypotension exhibited impaired catecholamine and PP responses to insulin hypoglycemia. There was no correlation between the catecholamine and PP responses in either the normal subjects or the patients, suggesting that PP release during hypoglycemia is independent of the sympathoadrenal medullary response. As PP release in response to insulin hypoglycemia is abolished by truncal vagotomy and unaffected by splanchnic nerve section, our results suggest that patients with chronic autonomic failure may have a diffuse autonomic dysfunction involving the parasympathetic as well as the sympathetic nervous system.

Adult↗

PubMed1991

[A case of acute polyradiculoneuritis associated with autonomic involvement of the pupils].

Acute polyradiculoneuritis relapses rarely, and autonomic nerve involvement is less frequent than motor cranial nerve involvement. An 11-year-old boy exhibited acute relapsing polyradiculoneuritis associated with two types of autonomic dysfunction of pupils 6 months after the onset of the disease. Parasympathetic dysfunction of pupils with ocular palsies preceded neuropathy of limbs at the onset. Thereafter, sympathetic dysfunction of pupils without ocular palsies was revealed by pupillography at the 2nd attack of limb palsies.

Autonomic Nervous System Diseases↗

PubMed1977

Postganglionic cholinergic dysautonomia.

A 9-year-old boy presented with symptoms and signs of marked postganglionic cholinergic autonomic dysfunction manifested by bilateral internal ophthalmoplegia, impaired secretion of tears and saliva, lack of gastrointestinal motility, atony of the bladder, generalized absence of sweating, and hypertension. Clinical and pharmacological studies confirmed that the abnormalities were restricted mainly to the postganglionic cholinergic autonomic system and showed evidence of postdenervation supersensitivity to parasympathomimetic drugs. The patient was treated in the early phase of his illness by the administration of carbachol, and eventually he made a slow and partial spontaneous recovery. Histoimmunofluorescent studies on a skin biopsy specimen suggested an autoimmune origin for his disease, with IgG antibodies being produced against postganglionic cholinergic autonomic fibers.

Autoimmune Diseases↗

PubMed2005

P wave signal averaged ECG and chemoreflexsensitivity in paroxysmal atrial fibrillation.

Detailed analysis of the QRS-complex and autonomic dysfunction can identify patients at risk to suffer from ventricular arrhythmias. To determine whether patients at risk for paroxysmal atrial fibrillation (PAF) could be identified while in sinus rhythm, a P wave triggered signal averaged ECG and an analysis of the autonomic function by chemoreflexsensitivity (CHRS) were examined. The ratio between the difference of RR intervals in the ECG and the venous partial pressure of oxygen before and after 5-min oxygen inhalation was measured for the determination of CHRS. We examined 224 patients (group A) who suffered from PAF, 250 patients (group B) without arrhythmic history and 30 young volunteers (group C). The filtered P wave duration (FPD) was significantly longer in group A than in group B (140.9+/-21.0 vs. 118.2+/-9.4 ms, p<0.0001) or C (105.2+/-14.1 ms, p<0.0001) while the root mean square voltage of the last 20 ms of the P wave (RMS 20) was significantly lower in group A than in group B (2.68+/-1.12 vs. 4.06+/-1.57 microV, p<0.0001) or C (3.97+/-1.36 microV, p<0.0001). Atrial late potentials (ALP) were defined as a FPD>120 ms and a RMS 20< or =3.5 microV. ALP could identify patients of group A with a specificity of 78% and a sensitivity of 83%. Patients with PAF (2.32+/-1.15 ms/mm Hg) showed a significantly lower CHRS than group B (4.14+/-1.58 ms/mm Hg, p<0.0001) or group C (4.98+/-1.51 ms/mm Hg, p<0.0001). The sensitivity for the presence of atrial fibrillation was 71% for a CHRS below 3.0 ms/mm Hg with a specificity of 70%. A combination of both methods showed a specificity of 85% and a sensitivity of 65% when ALP and pathological CHRS were present. The results of our study suggest that risk of atrial fibrillation could be detected by P wave signal averaged ECG and CHRS. An analysis of CHRS seems to be an appropriate method to demonstrate a neurovegetative imbalance, which might be one possible trigger mechanism.

Adolescent↗

PubMed2001

Autonomic dysreflexia in a mouse model of spinal cord injury.

Most experimental studies of spinal cord injury have centered on the rat as an experimental model. A shift toward a mouse model has occurred in recent years because of its usefulness as a genetic tool. While many studies have concentrated on motor function and the inflammatory response following spinal cord injury in the mouse, the development of autonomic dysreflexia after injury has yet to be described. Autonomic dysreflexia is a condition in which episodic hypertension develops after injuries above the mid-thoracic segment of the spinal cord. In this study 129Sv mice received a spinal cord transection at the second thoracic segment. The presence of autonomic dysreflexia was assessed 2 weeks later. Blood pressure responses to stimulation were as follows: moderate cutaneous pinch caudal to the injury (35+/-6 mm Hg), tail pinch (25+/-7 mm Hg), and a 0.3 ml balloon distension of the colon (37+/-4 mm Hg). Previous reports have suggested that small diameter primary afferent fiber sprouting after spinal cord injury may be responsible for the development of autonomic dysreflexia. In order to determine whether autonomic dysreflexia in the mouse may be caused by a similar mechanism, the size of the small diameter primary afferent arbor in spinal cord-injured and sham-operated animals was assessed by measuring the area occupied by calcitonin gene-related peptide-immunoreactive fibers. The percentage increase in the area of the small diameter primary afferent arbor in transected over sham-operated spinal cords was 46%, 45% and 80% at spinal segments thoracic T5-8, thoracic T9-12 and thoracic T13-lumbar L2 respectively. This study demonstrates the development of autonomic dysfunction in a mouse model of spinal cord injury that is associated with sprouting of calcitonin gene-related peptide fibers. These results provide strong support for the use of this mouse model of spinal cord injury in the study of autonomic dysreflexia.

Animals↗

PubMed1992

Violent visual hallucinations and aggression in frontal lobe dysfunction: clinical manifestations of deep orbitofrontal foci.

Three patients from different racial, social, and economic backgrounds were studied because of sudden intrusive thoughts: visions or intrusions of threatening scenes--violent, aggressive, and sometimes horrifying--that lasted from seconds to minutes. Apart from the association with intense anxiety, fear, and aggression, there was no association with oculomotor, motor, sensory, or autonomic dysfunction or altered conscious state. Patients had abnormal intermittent discharges that arose from frontal areas and probably did not spread further. Carbamazepine was useful in two cases. The authors suggest that violent, brief hallucinations with no other epileptic sign may be manifestations of frontal lobe seizures.

Adult↗

PubMed2006

Altered expression of neurotransmitter receptors and neuromediators in vernal keratoconjunctivitis.

BACKGROUND: There is growing evidence that autonomic innervation is involved in the pathogenesis of mucus hypersecretion, goblet cell hyperplasia, and conjunctival hyperreactivity. OBJECTIVE: To determine the expression of neurotransmitters and neurotransmitter receptors in vernal keratoconjunctivitis (VKC) tissues to evaluate whether neurogenic inflammation plays a role in this ocular atopic-related disorder. METHODS: Biopsy specimens of upper tarsal conjunctiva from 8 VKC patients with active inflammation and from 4 healthy subjects were processed for immunohistochemistry using anti-M1, anti-M2, and anti-M3 muscarinic receptors; beta1-adrenergic receptor; vasoactive intestinal peptide; nerve growth factor; and protein gene product 9.5, a marker of nerve fibers. RESULTS: In the conjunctival epithelium of VKC patients, M1 muscarinic receptor, nerve growth factor, and protein gene product 9.5 expression were decreased, whereas M2 and M3 muscarinic receptors and beta1-adrenergic receptor were irregularly distributed, compared with control subjects. Neurotransmitter receptors and vasoactive intestinal peptide expression were increased in the substantia propria-localized infiltrate of VKC compared with healthy tissue. Nerve growth factor and protein gene product 9.5 staining was also enhanced in the conjunctival stroma of VKC vs healthy conjunctiva. CONCLUSIONS: The inflamed conjunctiva of VKC patients demonstrated an obvious alteration in muscarinic and beta1-adrenergic receptor, vasoactive intestinal peptide, protein gene product 9.5, and nerve growth factor expression. These results substantiate the involvement of an autonomic dysfunction in the pathogenesis of VKC.

Adolescent↗

PubMed2003

Effects of sleep position, sleep state and age on heart rate responses following provoked arousal in term infants.

Previous studies have suggested that autonomic dysfunction may be involved in Sudden Infant Death Syndrome (SIDS). The major risk factors for SIDS are the prone sleeping position and maternal smoking. Our aim was to examine the effects of sleeping position and maternal smoking on the postnatal maturation of autonomic function by examining heart rate responses following arousal in healthy term infants. Twenty-four infants (11 born to mothers who smoked during pregnancy and 13 to mother who did not smoke) were studied using daytime polysomnography and multiple measurements of arousal threshold (cm H(2)O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep (AS) and quiet sleep (QS). We demonstrated no difference between smoking and non-smoking groups of infants in any of our measurements, and thus combined data from the groups. Baseline (BHR) was elevated in the prone compared to the supine position in quiet sleep (QS) at 2-3 weeks (p<0.001) and 5-6 months (p<0.001), and in active sleep (AS) at 2-3 and 5-6 months (p<0.05). BHR was significantly elevated in AS compared to QS in the supine position at all ages (p<0.01) and in the prone position at 2-3 (p<0.001) and 5-6 months (p<0.05). Increases in heart rate (deltaHR%) following arousal were significantly greater in the supine compared to the prone position in QS at 2-3 weeks (p<0.05) and in AS at both 2-3 (p<0.01) and 5-6 months (p<0.05). DeltaHR% was significantly greater in AS compared to QS in both supine (p<0.05) and prone (p<0.001) positions at 2-3 weeks and in the supine position at 2-3 months (p<0.001). We conclude that sleep state, sleep position and postnatal age affect the cardiac responses following arousal from sleep in healthy term infants. Impairment of heart rate control in the prone position may be important in understanding the increased risk for SIDS in this position.

Adolescent↗

PubMedDate not supplied

Cardiovascular reflex responses in cluster headache patients: basal autonomic alterations.

To investigate the involvement of the autonomic nervous system in Cluster Headache (CH) patients, we compared the cardiovascular reflex responses in a group of CH subjects and a group of controls. We considered five tests: 1) deep breathing test (DB); 2) lying to standing test; 3) heart rate response to Valsalva manoeuvre; 4) blood pressure response to standing; 5) blood pressure response to sustained handgrip. Our data confirm an autonomic dysfunction in CH, particularly regarding the parasympathetic system. Alternative interpretations of these results are discussed.

Adult↗

PubMed1982

Acquired postganglionic cholinergic dysautonomia: case report and review of the literature.

An 8-year-old girl with acute abdominal pain had cholinergic autonomic dysfunction. There have been only four patients with acquired postganglionic cholinergic dysautonomia described in the literature. The characteristic clinical features are atony of the bowel and bladder, lack of tears, saliva, and sweat, internal ophthalmoplegia, and normal adrenergic functions. Special studies for autonomic nervous function help in confirming this diagnosis. The exact pathogenesis of the disorder is still not clear. This case demonstrates successful treatment with bethanechol chloride.

Autonomic Nervous System Diseases↗

PubMedDate not supplied

Complex regional pain syndrome type I associated with amyotrophic lateral sclerosis.

BACKGROUND: (CRPS I [formerly called reflex sympathetic dystrophy]) is a syndrome with pain and signs of autonomic dysfunction after trauma or immobilization; the pathophysiologic mechanisms of CRPS I, however, remain unknown. DESIGN: The authors present a case of CRPS I associated with amyotrophic lateral sclerosis. Along with the motor paresis due to amyotrophic lateral sclerosis, pain, swelling, and signs of autonomic disturbance occurred. CONCLUSIONS: This case supports the hypothesis that immobilization is one of the major contributing factors for CRPS I.

Aged↗

PubMed2006

Long-term effects of cardiac resynchronization therapy on heart rate and heart rate variability.

Congestive heart failure is characterized by significant autonomic dysfunction. Development of left bundle branch block in congestive heart failure is a predictor of worse outcome. There are several lines of evidence that cardiac resynchronization therapy (CRT), by biventricular stimulation in patients with severe heart failure and left bundle branch block, improves autonomic functions which can be quantified by measuring heart rate variability. The aim of the present study was to assess the effect of CRT on autonomic functions quantified by heart rate variability and mean heart rate (HR) in patients with advanced heart failure and left bundle branch block in short and long-term follow-up. A total of 35 patients with systolic heart failure and left bundle branch block (mean-age 60 +/- 11 years; 24 male and 11 female; mean left ventricular ejection fraction [EF]: 22.3 +/- 3%) were enrolled. Clinical assessment and echocardiographic examination were performed at baseline and every three months. Continuous electrocardiographic monitorization by 24-hour Holter recordings was performed pre-implantation, 3 months and 2 years after implantation. Mean HR and one of the time-domain parameters of heart rate variability, standard deviation of the R-R intervals (SDNN) were measured. CRT was associated with a decrease in the mean duration of QRS, and an increase in diastolic filling time, the rate with which the left ventricular pressure rises (dP/dt), and left ventricular ejection fraction. Decrease in mean heart rate and increase in SDNN were statistically significant in the third month and second year recordings when compared to baseline recording (p values were < 0.001 for both). In conclusion, CRT with biventricular pacing provides sustained improvement in autonomic function in patients with advanced heart failure and left bundle branch block.

Female↗

PubMed1993

Is the corrected QT interval a reliable indicator of the severity of diabetic autonomic neuropathy?

OBJECTIVE: We investigated whether the corrected QT interval correlated with two other tests for diagnosing autonomic dysfunction in 60 type I diabetic patients with proven peripheral neuropathy. The mean age +/- SD was 48.3 +/- 11.2 yr, the mean duration of diabetes was 24.9 +/- 11.4 yr, and the mean HbA1 was 9.3 +/- 2.4%. RESEARCH DESIGN AND METHODS: All patients underwent three autonomic function tests: 1) the standard five cardiovascular Ewing tests, each scored 0 (normal), 0.5 (borderline), or 1.0 (abnormal). We used the sum of the abnormal findings for the analysis, the cardiovascular autonomic score; 2) measurement of the corrected QT interval taken from a routine electrocardiogram recording; and 3) static and dynamic pupillometry: measurement of dark adapted pupil diameter as percentage of total iris diameter and of pupil constriction latency using an infrared light reflex technique. RESULTS: No significant correlation was found between age, duration of diabetes, or HbA1 and any of the autonomic function tests, except for one between age and cardiovascular autonomic score (r = 0.3202, P = 0.0126). Corrected QT interval did not correlate with cardiovascular autonomic score, pupil diameter, or constriction latency. A significant inverse correlation was found between cardiovascular autonomic score and pupil diameter (r = -0.4861, P < 0.001) and constriction latency (r = 0.3783, P < 0.001). Pupil diameter and constriction latency correlated well (r = -0.4276, P < 0.001). CONCLUSIONS: The corrected QT interval did not correlate with cardiovascular autonomic tests nor pupillometry results. The corrected QT interval therefore should not be used for the diagnosis of the severity of diabetic autonomic neuropathy.

Autonomic Nervous System↗

PubMed1967

Shear injuries of the brain.

A blow to the head will impart rotational velocity to the brain and, depending on its magnitude, will produce effects ranging from concussion to profound neurological dysfunction. Resultant shear strains distort and rupture axons, blood vessels and major fibre tracts. Thirty-seven patients with head injury that was not complicated by significant hemorrhage or superficial laceration of the brain had coma or severe dementia, spastic quadriparesis, incontinence and autonomic dysfunction. These patients survived 24 hours to 243 days. Gross pathological examination revealed little, but there was microscopic evidence of axonal and small vessel injury in all; this was localized to the basal and midsagittal areas of the diencephalon and mesencephalon, particularly in those less severely injured. Such changes represent the basic pathology of all head injury. Data from this study suggest that concussion depends upon varying degrees of damage to the axon as well as the neuron. The current definition of concussion-immediate loss of consciousness with rapid and complete recovery of cerebral function-should not exclude the fact that a small number of neurons may have been permanently disconnected or have perished.

Axons↗

PubMed1993

Investigation and treatment of autonomic circulatory failure.

Investigation and treatment of patients suffering from autonomic circulatory failure should be based on the application of knowledge of basic physiology to the problem of a particular patient. For an overall evaluation of cardiovascular autonomic dysfunction, an analysis of the heart rate and blood pressure responses to standing usually is sufficient. Instruction in physical maneuvers such as squatting and leg crossing should be part of the treatment programs to reduce disabilities from orthostatic hypotension in patients with circulatory autonomic failure.

Autonomic Nervous System↗