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PubMed2004

Autonomic nervous function, arterial stiffness and blood pressure in patients with Type I diabetes mellitus and normal urinary albumin excretion.

Type I diabetic patients (DM-1) with an elevated urinary albumin excretion (UAE>30 mg/24 h) have a high cardiovascular risk. However, DM-1 patients with normal UAE have incipient abnormalities of the cardiovascular and nervous systems, such as elevations of blood pressures, increases in arterial stiffness and deterioration of autonomic nervous function. We studied the interrelationships of these abnormalities in normoalbuminuric DM-1 patients. In 76 patients, we performed two cardiovascular reflex tests (deep in- and expiration test (IE test) and lying-to-standing test (LS test)), and determined aortic pulse wave velocity (PWV), local arterial compliances of the common carotid, femoral and brachial arteries, and 24-h blood pressures. The DeltaRRmax value of the LS test was associated with aortic PWV (negatively) and the compliance coefficients of the carotid, femoral and brachial arteries. Per 100-ms increase in DeltaRRmax, pulse wave velocity decreased by 0.39 m/s, compliance coefficients of the carotid, femoral and brachial arteries increased by 0.06, 0.08 and 0.05 mm2/kPa, respectively. These associations were independent of age, 24-h mean arterial pressure and 24-h heart rate. Increases in arterial stiffness were associated with increases in 24-h systolic and pulse pressure (per 1 m/s increase in PWV, systolic and pulse pressure increased by 2.1 and 1.7 mmHg, respectively). In normoalbuminuric DM-1 patients, deterioration of autonomic nervous function is associated with an increase in arterial stiffness, which, in turn, was associated with, and may cause, increased systolic and pulse pressure. These findings suggest that preventive strategies targeting autonomic dysfunction may reduce cardiovascular morbidity in diabetes.

Adult↗

PubMed1992

Cardiovascular reflexes in patients with vascular headache.

We have investigated the autonomic function of 75 patients with migraine by examining cardiovascular reflex function. The results were compared with those of 78 healthy volunteers. Measurements were made between attacks. Patients with migraine showed a smaller heart-rate response to deep breathing but a greater heart-rate response and higher blood pressure to standing when compared to controls. Migraine patients had a higher percentage of established sympathetic lesions (51% vs 17%) and severe (25% vs 5%) or atypical (24% vs 11.5%) global autonomic dysfunction. No significant differences were found among patients with migraine with aura, migraine without aura, and migraine with prolonged aura. Our findings indicate that patients with migraine have sympathetic hypofunction.

Adolescent↗

PubMed1999

Alterations of heart rate variability after radiofrequency catheter ablation of focal atrial fibrillation originating from pulmonary veins.

BACKGROUND: Transient sinus bradycardia and hypotension have been reported as complications during radiofrequency (RF) ablation of focal atrial fibrillation (AF) originating from pulmonary veins (PVs). This study used heart rate variability (HRV) to evaluate the effects of focal PVs ablation on autonomic function. METHODS AND RESULTS: Thirty-seven patients with paroxysmal AF were referred for ablation. The study group included 30 patients who underwent transseptal ablation of PVs, and the control group included 7 patients who underwent the transseptal procedure without ablation. The mean sinus rate and time-domain (standard deviation of RR intervals and root-mean-square of differences of adjacent RR intervals) and frequency-domain (low frequency, high frequency, and low-frequency/high-frequency ratio) analyses of HRV were obtained by use of 24-hour Holter monitoring before and 1 week, 1 month, and 6 months after ablation. All the triggering points of AF were from PVs, and they were successfully ablated. Severe bradycardia and hypotension were noted during ablation of PVs in 6 patients (group IA); 24 patients without the above complication belonged to group IB. Compared with preablation values, a significant increase in mean sinus rate and low-frequency/high-frequency ratio and a significant decrease in standard deviation of RR intervals, root-mean-square of differences of adjacent RR intervals, low frequency, and high frequency were noted in groups IA and IB patients 1 week after ablation. The changes in HR and HRV recovered spontaneously in the 2 subgroups by 1 month later. These parameters of HRV did not change in the control group after the transseptal procedure. CONCLUSIONS: Transient autonomic dysfunction with alterations in HR and HRV occurred after ablation of focal AF originating from PVs.

Adult↗

PubMed2005

Clinical benefits of hydration and volume expansion in a wide range of illnesses may be attributable to reduction of sympatho-vagal ratio.

Hydration and volume expansion regimens are widely thought to offer symptomatic benefit in many human ailments. Many varied theories for the phenomenon exists such as decreased blood viscocity in cardiac disease, dilution of toxins in cancer, and cleansing effect on airways in asthma. While it is plausible that disparate mechanisms are involved in different conditions, we propose an alternative, unifying hypothesis that many of the clinical benefits of hydration and volume expansion are partly related to reduced sympatho-vagal ratio. Hypovolemia triggers baroreceptor-mediated sympathetic response and neurohormonal activation to promote fluid retention. Emerging evidence suggests that many diseases including cardiovascular, neurologic, gastrointestinal, metabolic, inflammatory, thrombotic, viral, and oncologic conditions are manifestations of abnormal sympathetic bias and associated T helper 2 bias. Hypovolemia-induced sympathetic activation, especially if baroreceptor dysfunction is involved, can worsen these conditions. Hydration and volume expansion may lower sympatho-vagal ratio, thereby tempering a wide variety of clinical conditions linked directly or indirectly to adrenergia including, but not limited to, acute coronary syndromes, asthma, cancer, and stroke. Interestingly, isotonic or hypertonic hydration, rather than a low-salt diet, may be a counterintuitive potential strategy to treat some cases of hypertension associated with dehydration and autonomic dysfunction. In contrast to the putative causal relationship between them, perhaps hypertension and end-organ damage represent independent consequences of dysfunctional sympathetic and neurohormonal activation. Venipuncture enables faster volume expansion but may also be a source of sympathetic hyperactivity. Oral hydration may additionally promote vagal tone by triggering gastric distension, a benefit not offered by intravenous fluids. The empiric benefits of hydration and volume expansion portend novel methods to treat a wide range of clinical conditions through pharmacologic or electrical modulation of cardiovascular or gastrointestinal baroreceptors.

Asthma↗

PubMed1997

Transfer function analysis of cerebral autoregulation dynamics in autonomic failure patients.

BACKGROUND AND PURPOSE: Autonomic nervous system diseases affect systemic blood pressure regulation. Patients with autonomic nervous system diseases have consistently larger drops in blood pressure associated with standing than the normal population. Autonomic dysfunction and/or these changes in blood pressure may affect dynamic cerebral autoregulation. METHODS: Heart rate, mean blood flow velocity (MBFV) of the middle cerebral artery via transcranial Doppler ultrasound, mean arterial blood pressure adjusted to brain level (MABPbrain) via Finapres, and end tidal CO2 were measured continuously during graded tilt (after 5 minutes in supine position as baseline, -10 degrees, +10 degrees, +30 degrees, +60 degrees, -10 degrees, and supine recovery) in autonomic failure patients and their age- and sex-matched control subjects. The dynamic response of MBFV to spontaneous variations in MABPbrain was investigated by cross-spectral analysis. The transfer gain and phase relationships between MBFV and MABPbrain were determined from the final 256 beats of each 5-minute-tilt segment. The transfer gain was normalized to mean MABPbrain and MBFV and then converted to decibels (dB). RESULTS: MBFV variation (0.03 to 0.14 Hz) preceded MABPbrain by similar phase angles in patients and control subjects and in all tilt conditions (patients: 31 +/- 5 degrees; control subjects: 30 +/- 5 degrees; mean +/- SEM). Patients had a higher supine gain than control subjects (P < .05). Both patients and control subjects showed a significant decrease in gain with tilt and by 60 degrees the patients were not different from the control subjects (supine to 60 degrees: patients = 5.23 +/- 0.77 to -1.65 +/- 0.89 dB; control subjects = 1.74 +/- 0.82 to -1.80 +/- 0.62 dB). CONCLUSIONS: These data indicate an altered, yet present, autoregulatory response with autonomic failure.

Autonomic Nervous System Diseases↗

PubMed2003

The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis.

OBJECTIVE: To examine by meta-analysis the relationship between cardiovascular autonomic neuropathy (CAN) and risk of mortality in individuals with diabetes. RESEARCH DESIGN AND METHODS: We searched Medline for English-language articles published from 1966 to 2001. Fifteen studies having a baseline assessment of cardiovascular autonomic function and mortality follow-up were identified. The analyses were stratified according to whether a single abnormality or two or more measures of cardiovascular autonomic function were used to define CAN. A global measure of association (i.e., relative risk) was generated for each group by pooling estimates across the studies using the Mantel-Haenszel procedure. RESULTS: CAN was significantly associated with subsequent mortality in both groups, although the magnitude of the association was stronger for those studies for which two or more measures were used to define CAN. The pooled relative risk for studies that defined CAN with the presence of two or more abnormalities was 3.45 (95% CI 2.66-4.47; P < 0.001) compared with 1.20 (1.02-1.41; P = 0.03) for studies that used one measure. CONCLUSIONS: These results support an association between CAN and increased risk of mortality. The stronger association observed in studies defining CAN by the presence of two or more abnormalities may be due to more severe autonomic dysfunction in these subjects or a higher frequency of other comorbid complications that contributed to their higher mortality risk. Future studies should evaluate whether early identification of subjects with CAN can lead to a reduction in mortality.

Autonomic Nervous System Diseases↗

PubMed2005

Determinants of mortality in stroke patients with right brain damage.

Stroke is the world's second leading cause of mortality and long-term disability. Damage to the nondominant right brain has distinct clinical characteristics. The resultant cardiovascular and autonomic dysfunction peculiar to right hemispheric stroke can adversely affect the short- and long-term outcome of stroke victims. Blood flow characteristics to the right hemisphere may also put the right brain at more risk for embolic and silent infarcts.

Autonomic Nervous System↗

PubMed1997

Diabetic neuropathy.

The most common form of diabetic neuropathy is chronic, distal symmetrical sensorimotor, or predominantly sensory neuropathy; the latter is invariably associated with some degree of autonomic dysfunction. There are, however, other neuropathic patterns in diabetes mellitus that are uncommon but are important to recognize, since they may mimic many other non-neurologic diseases. This article discusses a variety of forms of mononeuropathies and diabetic proximal motor neuropathy, commonly known as diabetic amyotropy.

Autonomic Nervous System Diseases↗

PubMed2001

Depression, heart rate variability, and acute myocardial infarction.

BACKGROUND: Clinical depression is associated with an increased risk for mortality in patients with a recent myocardial infarction (MI). Reduced heart rate variability (HRV) has been suggested as a possible explanation for this association. The purpose of this study was to determine if depression is associated with reduced HRV in patients with a recent MI. METHODS AND RESULTS: Three hundred eighty acute MI patients with depression and 424 acute MI patients without depression were recruited. All underwent 24-hour ambulatory electrocardiographic monitoring after hospital discharge. In univariate analyses, 4 indices of HRV were significantly lower in patients with depression than in patients without depression. Variables associated with HRV were then compared between patients with and without depression, and potential confounds were identified. These variables (age, sex, diabetes, and present cigarette smoking) were entered into an analysis of covariance model, followed by depression status. In the final model, all but one HRV index (high-frequency power) remained significantly lower in patients with depression than in patients without depression. CONCLUSIONS: We conclude that greater autonomic dysfunction, as reflected by decreased HRV, is a plausible mechanism linking depression to increased cardiac mortality in post-MI patients.

Autonomic Nervous System↗

PubMed1999

Lupus carditis: evaluation with technetium-99m MIBI myocardial SPECT and heart rate variability.

The objective of this paper was to investigate the incidence of myocardial perfusion defects in patients with systemic lupus erythematosus (SLE) associated with dysautonomic alterations. Twenty patients without any sign or symptoms of heart disease, selected from a larger population of patients with SLE, underwent technetium-99m sestamibi (Tc-99m MIBI) single photon emission computed tomography (SPECT), at rest and after dipyridamole infusion; they also underwent heart rate variability (HRV) examination by a 24 hour ambulatory electrocardiography, analyzing in the time domain the standard deviation of the R-R intervals average (SDNN) and the percentage of R-R adjacent intervals differing from each other more than 50 msec (pNN50); in the frequency domain the low (LF) and high frequencies (HF) were analyzed. Twenty healthy volunteers served as control group for heart rate variability. At MIBI-SPECT examination, the scan was found abnormal in 15 patients and normal in five: three patients demonstrated reversible defects in the anteroseptal region, four had irreversible defects in a region (two in the anteroseptal region and two in the lateral region), two had rest defects in two different regions (lateral and inferior, lateral and anteroseptal) that improved during dipyridamole scan, and six had both reversible and irreversible defects: four in a single segment (three anteroseptal and one lateral, and two in two different regions, particularly anteroseptal and lateral, lateral and inferior). All 20 patients showed significantly lower HRV parameters in comparison with the control group, except for pNN50, which indicates decreased physiologic periodic fluctuations of the autonomic nervous system. In six patients who underwent coronary angiography, the epicardial vessels were found completely normal. In view of the high incidence of myocardial hypoperfusion in patients with HRV alterations, the authors hypothesize that autonomic dysfunction may be associated with microvascular disease or metabolic alteration. They also believe that MIBI scintigraphy is a suitable technique in detecting myocardial damage in SLE patients free of clinical manifestation.

Adolescent↗

PubMed2002

Electrocardiographic findings in mdx mice: a cardiac phenotype of Duchenne muscular dystrophy.

The mdx mouse is a model of Duchenne muscular dystrophy (DMD). As many DMD patients die of cardiac failure, we investigated whether mdx mice exhibited clinically relevant cardiac phenotypes. We applied a recently developed method for noninvasively recording electrocardiograms (ECGs) to study male mdx mice (n = 15) and control mice (n = 15). The mdx mice had significant tachycardia and decreased heart rate variability, consistent with observations in DMD patients. Heart rate was nearly 15% faster in mdx mice than control mice (P < 0.05). The rate-corrected QT interval duration and PR interval were shorter in mdx compared to control mice (P < 0.05). The muscarinic antagonist atropine significantly increased heart rate and decreased PR interval in C57 mice. In contrast, atropine significantly decreased heart rate and increased PR interval in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. Baseline ECGs and contrary responses to muscarinic blockade by atropine in mice deficient in neuronal nitric oxide synthase (nNOS) suggest that the autonomic dysfunction in mdx mice may be independent of decreased myocardial nNOS. These electrocardiographic findings in dystrophin-deficient mice may provide new bases for diagnosing, understanding, and treating DMD patients.

Animals↗

PubMed2007

Dementia with Lewy bodies.

Synucleinopathies, with and without dementia, encompass a wide range of diseases including Parkinson's disease, multiple system atrophy, rapid eye movement (REM) sleep behavior disorder, and dementia with Lewy bodies (DLB). DLB is a neurodegenerative disorder resulting in slowly progressive and unrelenting dementia until death. Prevalence studies suggest that it is the second most common dementing illness in the elderly. The neuropathologic findings of DLB show a wide anatomic range. Lewy bodies and Lewy-related pathology are found from the brain stem to the cortex and, in many cases, associated with concurrent Alzheimer's disease pathology. A recent international consortium on DLB has resulted in revised criteria for the clinical and pathological diagnosis of DLB incorporating new information about the core clinical features and improved methods for their assessment. The presentation of DLB is typically one of cortical and subcortical cognitive impairments, with worse visuospatial and executive dysfunction than Alzheimer's disease. There may be relative sparing of memory especially in the early stages. Core clinical features of DLB include fluctuating attention, recurrent visual hallucinations, and parkinsonism. Suggestive features include REM sleep behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in the basal ganglia on functional neuroimaging. Additional supportive features that commonly occur in DLB, but with lower specificity, include repeated falls and syncope, transient, unexplained loss of consciousness, severe autonomic dysfunction, hallucinations in other modalities, systematized delusions, depression, relative preservation of medial temporal lobe structures on structural neuroimaging, reduced occipital activity on functional neuroimaging, prominent slow wave activity on electroencephalogram, and low uptake myocardial scintigraphy. Management of DLB includes pharmacological and nonpharmacological interventions for its cognitive, neuropsychiatric, motor, and sleep disturbances.

Brain↗

PubMed1988

Dizziness due to dysautonomia: response to specific therapy.

We have reported a case of hypervagal dysautonomia in which there was improvement in the results of autonomic nervous system tests (ANSTs) as well as in the patient's symptoms. This patient is one of more than 200 patients who have had our testing protocol. Although a high percentage of autonomic dysfunction was detected in this group of patients, we do not suggest that these tests be applied routinely to every patient complaining of dizziness. Rather, ANSTs should be selectively administered after otologic disease has been excluded and when dizziness is accompanied by various other symptoms.

Autonomic Nervous System Diseases↗

PubMed2004

Botulinum toxin in clinical practice.

Botulinum toxin, the most potent biological toxin, has become a powerful therapeutic tool for a growing number of clinical applications. This review draws attention to new findings about the mechanism of action of botulinum toxin and briefly reviews some of its most frequent uses, focusing on evidence based data. Double blind, placebo controlled studies, as well as open label clinical trials, provide evidence that, when appropriate targets and doses are selected, botulinum toxin temporarily ameliorates disorders associated with excessive muscle contraction or autonomic dysfunction. When injected not more often than every three months, the risk of blocking antibodies is slight. Long term experience with this agent suggests that it is an effective and safe treatment not only for approved indications but also for an increasing number of off-label indications.

Autonomic Nervous System Diseases↗

PubMed1983

Hypergastrinemia in obese noninsulin-dependent diabetes: a possible reflection of high prevalence of vagal dysfunction.

To elucidate the relation of noninsulin-dependent (type II) diabetes mellitus to plasma levels of gastrin, pepsinogen I, and pepsinogen II, gastric acid secretion, and gastric emptying, we studied diabetic and nondiabetic obese Pima Indian subjects. Fasting and postprandial plasma gastrin concentrations were significantly higher (P less than 0.02) in diabetic than in nondiabetic subjects, but gastric acid outputs basally, after an acaloric liquid meal, and in response to betazole were similar in the two groups. Plasma pepsinogen I and pepsinogen II levels were also similar in both groups. A significant negative relation (r = -0.84; P less than 0.01) was found between basal gastrin levels and gastric acid production in nondiabetic Indians, but not in diabetic Pimas. The fractional gastric emptying rate of an acaloric liquid meal was significantly decreased in diabetic Pimas (P less than 0.01); and at least one test showing abnormal vagal function, as estimated by the Valsalva maneuver, heart rate changes between deep expiration and inspiration, and postural hypotension, was found in every diabetic subject. These findings suggest that hypergastrinemia in type II diabetes is not related to hypochlorhydria, but, instead, results from autonomic dysfunction with slow gastric emptying.

Adult↗

PubMed1995

Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria.

To evaluate the possibility that parkinsonian signs may be the only presenting feature of multiple system atrophy (MSA), parkinsonian patients were studied who had no atypical clinical signs and had no symptoms of autonomic dysfunction, but who reported that they had not experienced the anticipated good response to dopaminergic treatment. These stringent criteria identified 20 patients from a series of 298 consecutive parkinsonian outpatients. The following clinical pointers were analysed: (a) rate of disease progression; (b) symmetry of parkinsonian symptoms and signs; (c) occurrence of resting tremor during the first three years from onset. In addition, all patients underwent (d) acute and chronic challenge with dopaminergic drugs; (e) cardiovascular reflex autonomic function tests; (f) high field MRI. Rapid progression of disease was seen in 45% of patients, onset was symmetric in 25%, tremor was absent at onset in 70%, response to dopaminergic drug challenges was inadequate in 40%, abnormal cardiovascular reflexes occurred in 50%, and some abnormal MRI finding occurred in 35% of cases. Each of these features was equally weighted by giving to each patient a 0 to 6 point score corresponding to the number of abnormal findings. Fifteen patients scoring higher than 1 were considered at risk for having MSA: five of them were classified as clinically possible (score 2), six as clinically probable (score 3-4), and four patients were classified as clinically definite multiple system atrophy (score 5). The six pointers considered were variably combined in each patient, none of them being universally abnormal in patients with high scores. The patients were followed up for a mean 2.1 (SEM 0.65) years. All but one of the 10 patients prospectively classified as probable or definite MSA developed unequivocal clinical signs of fully symptomatic MSA. A receiver operator characteristic cure was plotted for the prospective score based on follow up diagnosis. The best compromise for trade off between sensitivity and specificity was a cut off value at a score of 3. The sensitivity and specificity of the individual pointers considered to predict fully symptomatic MSA varied considerably, and no single item could predict whether patients presenting with just parkinsonian signs went on during the two year follow up period to develop fully symptomatic MSA. Instead, the number of abnormalities offered a predictive value for the clinical prognosis of these parkinsonian patients.

Adult↗

PubMed1996

Symptomatic improvement with one-year cisapride treatment in neuropathic chronic intestinal dysmotility.

AIM: To assess the efficacy of a prokinetic agent in the long-term treatment of chronic intestinal dysmotility and the influence of extrinsic denervation. METHODS: We assessed symptoms, compliance and untoward effects in an open, 1-year trial of cisapride, 20 mg t.d.s., in 37 patients with neuropathic forms of chronic intestinal dysmotility. Patients' autonomic function had previously been characterized; effects of cisapride at 12 weeks in a placebo-controlled trial were previously reported. RESULTS: Seventeen patients had idiopathic dysmotility, 11 had diabetes mellitus with autonomic dysfunction, five had had previous gastric surgery and four had neurological syndromes. Median medication compliance was 98.9% for the study period completed by each individual. Median duration of follow-up was 9.5 months; 20 patients completed 1 year of treatment, and 27 of 37 at least 6 months of treatment; seven dropped out because of lack of benefit. Mean total symptom score was significantly reduced at the last observation relative to the entry into the trial; this was particularly the case in those patients without abdominal vagal dysfunction. One patient withdrew because of aggravation of abdominal pain. CONCLUSIONS: During an open, long-term trial, cisapride, 20 mg t.d.s., provided continued symptomatic relief to patients with chronic intestinal dysmotility, particularly those without vagal neuropathy.

Adult↗

PubMed1995

Circadian blood pressure variation versus renal function.

Several published reports describe an abnormal circadian blood pressure profile in chronic renal failure subjects. Factors other than renal failure, including age, diagnosis of diabetes mellitus, autonomic dysfunction, and race, also may affect circadian blood pressure profiles. To further elucidate the relationship between renal function and circadian blood pressure variation, we compared day/night circadian blood pressure changes in three groups of male veteran hypertensive patients: group A, creatinine clearance (CC) > 80 mL/min, n = 20; group B, CC 20 to 80 mL/min, n = 19; and group C, CC < 20 mL/min, n = 14. We use postural changes in catecholamines, renin, and aldosterone as a measure of autonomic function. No significant difference in day/night percent change in systolic, diastolic, mean arterial pressure (MAP), or heart rate was seen by renal function group. Regression analysis using age, diagnosis of diabetes mellitus, postural hormonal changes, and creatinine clearance found race to be the only significant predictor of the day/night percent change in MAP (P < 0.05). Compared with whites, black subjects had higher nocturnal heart rates (P = 0.01); smaller day/night heart rate changes (P = 0.03); significantly higher diastolic blood pressure (P = 0.01); and a trend toward smaller day/night change in diastolic blood pressure (P = 0.06). In conclusion, renal function level does not influence day/night blood pressure changes. The blunting or reversal of the normal circadian blood pressure pattern seen in some chronic renal failure hypertensive subjects may be attributable to the association between chronic renal failure and cofactors associated with abnormal circadian blood pressure, including black race and possibly severity of atherosclerosis.

Aldosterone↗