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PubMed1997

Baroreflex and chemoreflex dysfunction in streptozotocin-diabetic rats.

Several investigators have demonstrated that streptozotocin (STZ) diabetes induces changes in the autonomic control of the cardiovascular system. Changes in cardiovascular function may be related to peripheral neuropathy. The aim of the present study was to analyze changes in heart rate (HR) and arterial pressure (AP) as well as baroreflex and chemoreflex sensitivity in STZ-induced diabetic male Wistar rats (STZ, 50 mg/kg, i.v., 15 days). Intra-arterial blood pressure signals were obtained for control and diabetic rats (N = 9, each group). Data were processed in a data acquisition system (CODAS, 1 kHz). Baroreflex sensitivity was evaluated by measuring heart rate changes induced by arterial pressure variation produced by phenylephrine and sodium nitroprusside injection. Increasing doses of potassium cyanide (KCN) were used to evaluate bradycardic and pressor responses evoked by chemoreflex activation. STZ induced hyperglycemia (447 +/- 49 vs 126 +/- 3 mg/dl), and a reduction in AP (99 +/- 3 vs 118 +/- 2 mmHg), resting HR (296 +/- 11 vs 355 +/- 16 bpm) and plasma insulin levels (16 +/- 1 vs 57 +/- 11 microU/ml). We also observed that the reflex bradycardia (-16.8 +/- 0.1 vs -12.5 +/- 0.1 bpm/mmHg, in the diabetic group) and tachycardia (-3.68 +/- 0.5 vs -1.75 +/- 0.3 bpm/mmHg, in the diabetic group) produced by vasopressor and depressor agents were impaired in the diabetic group. Bradycardia evoked by chemoreflex activation was attenuated in diabetic rats (control: -17 +/- 1, -86 +/- 19, -185 +/- 18, -208 +/- 17 vs diabetic: -7 +/- 1, -23 +/- 5, -95 +/- 13, -140 +/- 13 bpm), as also was the pressor response (control: 6 +/- 1, 30 +/- 7, 54 +/- 4, 59 +/- 5 vs diabetic: 6 +/- 1, 8 +/- 2, 33 +/- 4, 42 +/- 5 mmHg). In conclusion, the cardiovascular response evoked by baroreflex and chemoreflex activation are impaired in diabetic rats. The alterations of cardiovascular responses may be secondary to the autonomic dysfunction of cardiovascular control.

Animals↗

PubMed1984

Autonomic sinus node dysfunction and its treatment.

The clinical, electrocardiographic, pharmacologic, electrophysiologic and Holter monitoring findings are described in four patients with autonomic sinus node dysfunction and one patient with autonomic binodal disease. All showed cerebral symptoms, and had attacks of dizziness, weakness, near-syncope or syncope. After a pharmacologic autonomic blockade with propranolol and atropine, all patients had normal intrinsic heart rates. Electrophysiological studies revealed normal corrected intrinsic node recovery time (less than or equal to 240 msec) a gradual return to the basic cycle length in the secondary postpacing cycles after autonomic blockade, and no intrinsic paroxysmal atrioventricular block. Continuous ECG monitoring (1-3 X 24 hours) revealed severe sinus bradycardia, SA-block, severe sinus arrest, cardiac standstill, atrial fibrillation and in two patients associated AV-block. Autonomic blockade with electrophysiological studies exclude the intrinsic involvement of the sinoatrial and atrioventricular node. Holter monitoring is the best method for assessing the autonomic neurovegetative component of dysrhythmias. Therapy regarding isolated autonomic sinus node dysfunction depended on the pathomechanisms of rhythm disorders: two patients received permanent pacemakers, antiarrhythmic drugs were applied in the case of two patients, and etiological treatment in the case of one. During the follow-up, all patients became symptom-free.

Adult↗

PubMed1989

Autonomic nervous system dysfunction in severe tetanus: current perspectives.

The enigma of autonomic nervous system dysfunction in severe tetanus is discussed in the light of recent and older evidence concerning the nature and action of tetanus toxin, its clinical effects, and therapy. Some suggestions for the pathogenesis and management of the cardiovascular disturbances are made.

Autonomic Nervous System Diseases↗

PubMed2000

Effects of exercise training on autonomic and myocardial dysfunction in streptozotocin-diabetic rats.

Several investigators have demonstrated that diabetes is associated with autonomic and myocardial dysfunction. Exercise training is an efficient non-pharmacological treatment for cardiac and metabolic diseases. The aim of the present study was to investigate the effects of exercise training on hemodynamic and autonomic diabetic dysfunction. After 1 week of diabetes induction (streptozotocin, 50 mg/kg, iv), male Wistar rats (222 +/- 5 g, N = 18) were submitted to exercise training for 10 weeks on a treadmill. Arterial pressure signals were obtained and processed with a data acquisition system. Autonomic function and intrinsic heart rate were studied by injecting methylatropine and propranolol. Left ventricular function was assessed in hearts perfused in vitro by the Langendorff technique. Diabetes (D) bradycardia and hypotension (D: 279 +/- 9 bpm and 91 +/- 4 mmHg vs 315 +/- 11 bpm and 111 +/- 4 mmHg in controls, C) were attenuated by training (TD: 305 +/- 7 bpm and 100 +/- 4 mmHg). Vagal tonus was decreased in the diabetic groups and sympathetic tonus was similar in all animals. Intrinsic heart rate was lower in D (284 +/- 11 bpm) compared to C and TD (390 +/- 8 and 342 +/- 14 bpm, respectively). Peak systolic pressure developed at different pressures was similar for all groups, but +dP/dt max was decreased and -dP/dt max was increased in D. In conclusion, exercise training reversed hypotension and bradycardia and improved myocardial function in diabetic rats. These changes represent an adaptive response to the demands of training, supporting a positive role of physical activity in the management of diabetes.

Animals↗

PubMed1993

Physiological assessment of aspects of autonomic function in patients with secondary progressive multiple sclerosis.

A detailed non-invasive study of systemic and regional haemodynamic responses to a range of autonomic tests which assess sympathetic and parasympathetic pathways (mental arithmetic, cutaneous cold, isometric exercise, deep breathing, Valsalva manoeuvre and head-up tilt) were performed in ten patients with secondary progressive multiple sclerosis and ten age- and sex-matched healthy normal subjects (controls). Blood pressure rose in controls during the pressor tests and was maintained during tilt. In six out of ten patients with multiple sclerosis blood pressure was unchanged during one or more of the three pressor tests, but was maintained in all during tilt. In the controls, superior mesenteric artery blood flow fell during pressor tests and head-up tilt. In multiple sclerosis patients, superior mesenteric artery blood flow did not change during pressor tests but fell during tilt. Cardiac index rose during isometric exercise and fell during head-up tilt in controls. Forearm blood flow rose during mental arithmetic in the controls only, but fell during tilt in both groups. Individual analysis indicated that of the ten multiple sclerosis patients, four had responses during the pressor tests similar to controls. Responses to deep breathing and to the Valsalva manoeuvre in controls and multiple sclerosis patients were similar. We conclude that some patients with an aggressive and disabling form of multiple sclerosis have selective autonomic dysfunction, in particular involving pressor responses, despite the lack of postural hypotension. The autonomic abnormality is likely to involve central autonomic interconnections rather than afferent or sympathetic efferent pathways. Further clarification of the nature, site and progression of these lesions is needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Impaired autoregulation of the retinal vasculature and microalbuminuria in diabetes mellitus.

The relationship between microalbuminuria and retinal vessel responses to sustained handgrip contraction was studied in a group of 20 diabetic patients. The diabetics were divided into two groups based on their albumin excretion rates (AER): Group 1 (AER less than or equal to 10 mcg/min) consisted of ten diabetic patients, mean age 55.8 +/- 3.9 years (mean +/- SEM); five IDDM and five NIDDM. Group 2 (AER greater than 10 mcg/min) comprised ten diabetic patients: mean age 56.8 +/- 3.04 years; six IDDM and four NIDDM. Both groups were similar in that there were no significant differences between mean age, type of diabetes, mean duration of diabetes, glycaemic control or mean resting blood pressures. Group 2 diabetics had a higher incidence of autonomic dysfunction than Group 1, based on the results of four standard tests of autonomic nerve function. There were significantly decreased retinal vessel responses to sustained handgrip contraction in Group 2 diabetics (mean arteriolar constriction 0.1 +/- 0.32%, and mean venule constriction 1.0% +/- 0.99%) compared with Group 1 diabetics (mean arteriolar constriction 6.9 +/- 1.69%, and mean venule constriction 4.2 +/- 0.05%). Retinopathy was slightly worse in Group 2. The implications of the association of microalbuminuria (AER greater than 10 mcg/min) and loss of retinal vessel reactivity to sustained handgrip contraction are discussed.

Adult↗

PubMed1992

[The Shy-Drager syndrome].

For 15 years a now 70-year-old woman had been having occasional episodes of circulatory collapse which 7 years ago were diagnosed as being caused by severe idiopathic orthostatic hypotension. These episodes had recently become much more frequent and she was hardly able to be upright for more than one minute. In the Schellong test the blood pressure fell from 80/50 mm Hg when lying to 70/30 mm Hg on standing, the pulse rate remaining unchanged at 60/min. The standing test had to be abandoned after 90 seconds. Serum catecholamine concentrations (epinephrine 65 ng/l, norepinephrine 100 ng/l) did not rise on standing (epinephrine 25 ng/l, norepinephrine 105 ng/l). 24-hour urinary excretion of vanillyl mandelic acid was at the lower limit of normal (2.2 mg). The autonomic dysfunction of circulatory control suggested a Shy-Drager syndrome. Other signs of autonomic failure included gastroparesis, decreased tear and sweat secretion and transitory urinary incontinence. Symptomatic treatment with elastic stockings, fludrocortisone, etilefrine, dihydroergotamine, L-dopa, yohimbine and amezinium methylsulfate gave the patient greater mobility without achieving normal blood pressure responses.

Aged↗

PubMed2004

Association between cardiovascular autonomic neuropathy and left ventricular hypertrophy in diabetic haemodialysis patients.

BACKGROUND: Patients with diabetic nephropathy are likely to have neurological complications including cardiovascular autonomic dysfunction, which is related to increased risk of mortality. We investigated whether cardiovascular autonomic neuropathy is associated with left ventricular hypertrophy (LVH) in diabetic haemodialysis patients. METHODS: Holter electrocardiography was carried out for 24 h with time and frequency domain analyses of heart rate variability in 154 diabetic (age 62+/-11 years) and 63 non-diabetic haemodialysis patients (62+/-10 years). The left ventricular mass index (LVMI) was determined by echocardiography. We used the percentage of differences exceeding 50 ms between adjacent normal RR intervals (pNN50) in time domain analysis and the power in the high-frequency range (HF: 0.15-0.40 Hz) in frequency domain analysis as indicators of parasympathetic activity. RESULTS: The mean LVMI was greater in diabetic than in non-diabetic patients (168+/-63 vs 144+/-54 g/m(2), P<0.01). LVMI inversely correlated with pNN50 (r = -0.270, P = 0.0007, n = 154) and HF (r = -0.277, P = 0.0005, n = 154) in diabetic patients, but not in non-diabetic patients. By multiple logistic analysis, LVH was strongly associated with pNN50 (odds ratio 0.088; 0, <2%; 1, >/=2%) and HF (odds ratio 0.058; 0, <500 ms(2); 1, >/=500 ms(2)) in diabetic patients. CONCLUSIONS: Impaired parasympathetic activity, which indicates cardiovascular autonomic neuropathy, was associated with the presence of LVH in diabetic haemodialysis patients. The co-existence of cardiovascular autonomic neuropathy and LVH may be one of the key factors for the high incidence of cardiovascular events in diabetic haemodialysis patients.

Aged↗

PubMed2004

Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects.

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23-77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70 degrees HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component (r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV (r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.

Adult↗

PubMed2002

Incidence of cardiac autonomic neuropathy and its correlation with retinopathy, micro-albuminuria and glycated haemoglobin in non-insulin dependent diabetes mellitus.

Forty non-insulin dependent diabetes mellitus (NIDDM patients were subjected to bedside evaluation of cardiovascular autonomic reflexes. Autonomic neuropathy was detected in 23 patients (57.5%); orthostatic hypotension in 6 (15%), abnormal blood pressure response to sustained handgrip in 8 (20%), abnormal Valsalva ratio in 10 (25%), abnormal heart rate response to deep breathing in 12 (30%) and abnormal heart rate response to standing in 11 patients (27.5%). Incidence of parasympathetic neuropathy was 57.5% in comparison to 20% sympathetic neuropathy One abnormal cardiac reflex was seen in 6 (15%), 2 in 13 (32.5%) and 3 or more in 4 patients (10%). Raised glycated haemoglobin was seen in 17 patients,retinopathy in 3 and micro-albuminuria in 11 patients with autonomic dysfunction and in 13, 0 and 3 patients respectively in NIDDM patients without autonomic neuropathy. Positive correlation of cardiac autonomic neuropathy was seen with retinopathy and micro-albuminuria.

Adult↗

PubMed2006

Sudden cardiac arrest in an intubated premature infant with cerebellar and brainstem injury: is there a link?

The ventilated premature infant frequently exhibits unprovoked desaturation episodes accompanied by bradycardia. In most instances, these episodes are short-lived and recover spontaneously or with minimal interventions. However, in some infants these episodes may be more profound and require substantial interventions to restore cardiorespiratory status. Here we present the case of a ventilated premature infant who had experienced prolonged, multiple daily desaturation episodes accompanied by bradycardia that required significant interventions. Postoperatively, after placement of a tracheotomy and despite a patent airway, the infant developed acute bradycardia that progressed rapidly to sudden death. At autopsy, significant cerebellar and brainstem injury was noted. We hypothesize that the specific cerebellum and brainstem injury may have contributed to autonomic dysfunction and sudden death.

Autonomic Nervous System↗

PubMed2006

[Introduction of Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University].

Pathologic informatics is an analysis of mechanism of pathogenesis using various medical information. Biologic reactions by many reactants are studied on molecules, cells, organs, and individuals by using various methods. Themes of our laboratory are as follows: 1) to analyze of the pathogenesis of various diseases by using novel diagnostic methods, 2) to elucidate amyloid formation mechanism in amyloidosis and to develop novel therapies, 3) to develop the methods for tests and diagnosis for DIC, 4) to study on activation mechanism of ribosomal proteins in the tissues by the blood cell function, 5) to study on the expression and suppression of neogenesis of blood vessels by physical invasion in the organ failure, and 6) to develop the diagnostic methods for autonomic dysfunction and to analyze the pathogenesis.

Amyloidosis↗

PubMed1987

Sympathetic skin response in diabetic neuropathy.

The sympathetic skin response (SSR) was studied in 47 diabetic patients selected for the presence of symptoms and clinical signs of peripheral neuropathy and in 24 normal control subjects. The SSR was present in all controls but was absent at the foot in 66% and at the hand in 27.7% of the diabetic patients. Absence of the SSR failed to correlate with other electrophysiologic parameters on routine nerve conduction and electromyographic studies. Although absent SSR was more often found in patients with symptoms of autonomic dysfunction (P less than 0.05), there was no correlation with any specific symptoms of autonomic involvement. The SSR was frequently absent, at least in the foot, in those patients with abnormal cardiac beat-to-beat variability (expiratory: inspiratory, E:I, ratio) and pupil cycle time (PCT). In addition there was a good correlation between the amplitude of the SSR and the value of the E:I ratio (r = 0.81, P less than 0.001). The SSR may be a valuable adjunct in the assessment of autonomic involvement in diabetic neuropathy, but its sensitivity requires further evaluation.

Adult↗

PubMed1994

Predictors of the pressor response to the clinic visit in essential hypertensives with and without diabetes mellitus.

Predictive models for the pressor response to the outpatient clinic visit (PRC) in essential hypertensives with and without diabetes are proposed. The hypotheses are derived from previous studies about the univariate correlates of this response. PRC was measured with ambulatory monitors. Twenty-four hour blood pressures and average PRCs were similar in the two groups. Diabetics had faster 24-h heart rates, decreased heart rate variability, a broader range of PRCs and more depressor responders. PRC of nondiabetics correlated with duration of hypertension and was dependent on race; the predictive model had R2 of 0.19. In contrast, PRC of diabetics exhibited correlations with age, weight, BP and blood glucose and the model had R2 of 0.71. The data suggest that: diabetics had autonomic dysfunction, that their PRC can be modelled with predictors that are accepted correlates of autonomic neuropathy, and that these predictors attenuated PRC or its buffering. If these results were confirmed by prospective application of the model to a larger group of patients, 'true' blood pressures could be estimated by subtraction of predicted PRC from office blood pressures in diabetic, but not in nondiabetic, hypertensive patients.

Age Factors↗

PubMed1995

Autonomic function in type I diabetes mellitus complicated by nephropathy. A cross-sectional analysis in the presymptomatic phase.

The purpose of this study was to determine the prevalence of parasympathetic and sympathetic autonomic dysfunction in long-standing type I diabetics with established nephropathy and to correlate autonomic function with cardiac risk factors. We used prospective analysis of heart rate variations to standardized testing and 24-hour blood pressure control prior to enrollment in a study utilizing various methods of intense diabetic control to prevent deterioration of kidney function. The settings were outpatient clinical research units. The patients were 42 type I diabetics with proteinuria (total urinary protein > or = 300 mg/day or urinary albumin > or = 100 mg/day) and creatinine clearance > or = 30 mL/min. Heart rate variation during respiratory cycles with change in posture from supine to upright, and during the Valsalva maneuver was recorded by a computerized method. Mean arterial blood pressure was recorded for 24 h by a computerized method. Heart rate variations in this group were abnormal during timed respiratory cycles in 26 of 40 patients (56%), during changes in posture in 15 of 40 patients (38%), and during Valsalva maneuver in 13 of 34 patients (38%) whose retinal disease permitted Valsalva testing. Blunted day/night mean arterial pressure ratios occurred in 18 of 41 (44%) patients and were more severe in men than in women (1.00 v 1.06, P < or = .05). Absence of deep tendon reflexes was associated with an increased incidence of both parasympathetic (respiratory rate variation) and sympathetic (postural rate variation) abnormalities (both P < or = .05). Loss of vibration sensation was not associated with autonomic functional abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2000

Familial mydriasis, cardiac arrhythmia, respiratory failure, muscular weakness and hypohidrosis.

OBJECTIVES: To describe a family with some sort of progressive autonomic failure in one generation (2 affected of a sibship of 7 sisters). The main features were: mydriasis, cardiac arrhythmia, cardiomegaly, hypohidrosis, respiratory failure, and muscular weakness. METHODS: Pupillometry, evaporimetry, and isokinetic power measurements were carried out. RESULTS: The autonomic dysfunction pattern (mainly cardiac abnormalities, mydriasis) seems to differ somewhat from that of progressive autonomic failure (Shy-Drager syndrome). "Lewy body-like" inclusions were present, in particular in substantia nigra, but also in locus ceruleus and raphe nuclei (cell loss only in locus ceruleus). There were no oligodendroglial, cytoplasmatic inclusions, apparently a marker in multiple system atrophy. Proper Lewy bodies were also present. Differences seemed to prevail vs the Shy-Drager syndrome. Various traits: muscular weakness pattern (e.g. preferential peroneal distribution), minor elbow contractures, and arrhythmia were reminiscent of Emery-Dreifuss muscle dystrophy (E-D). Distinguishing features included: hereditary pattern, mydriasis, and hypohidrosis. CONCLUSION: Conceivably, this disorder is close to, but still not identical with E-D.

Adult↗

PubMed2001

Neurology of ciguatera.

Ciguatera is a widespread ichthyosarcotoxaemia with dramatic and clinically important neurological features. This severe form of fish poisoning may present with either acute or chronic intoxication syndromes and constitutes a global health problem. Ciguatera poisoning is little known in temperate countries as a potentially global problem associated with human ingestion of large carnivorous fish that harbour the bioaccumulated ciguatoxins of the photosynthetic dinoflagellate Gambierdiscus toxicus. This neurotoxin is stored in the viscera of fish that have eaten the dinoflagellate and concentrated it upwards throughout the food chain towards progressively larger species, including humans. Ciguatoxin accumulates in all fish tissues, especially the liver and viscera, of "at risk" species. Both Pacific (P-CTX-1) and Caribbean (C-CTX-1) ciguatoxins are heat stable polyether toxins and pose a health risk at concentrations above 0.1 ppb. The presenting signs of ciguatera are primarily neurotoxic in more than 80% of cases. Such include the pathognomonic features of postingestion paraesthesiae, dysaesthesiae, and heightened nociperception. Other sensory abnormalities include the subjective features of metallic taste, pruritus, arthralgia, myalgia, and dental pain. Cerebellar dysfunction, sometimes diphasic, and weakness due to both neuropathy and polymyositis may be encountered. Autonomic dysfunction leads to hypotension, bradycardia, and hypersalivation in severe cases. Ciguatoxins are potent, lipophilic sodium channel activator toxins which bind to the voltage sensitive (site 5) sodium channel on the cell membranes of all excitable tissues. Treatment depends on early diagnosis and the early administration of intravenous mannitol. The early identification of the neurological features in sentinel patients has the potential to reduce the number of secondary cases in cluster outbreaks.

Ciguatoxins↗

PubMed2003

Neuronal ganglionic acetylcholine receptor autoimmunity.

We have developed and validated an assay to detect serum antibodies specific for the ganglionic AChR. The assay uses ganglionic AChR solubilized from membranes of the human neuroblastoma cell line (IMR-32) as antigen. The ganglionic AChR is radiolabeled by complexing with 125I-epibatidine. Among patients with acquired dysautonomia, seropositivity is highly associated with the diagnosis of idiopathic or paraneoplastic autonomic neuropathy and can distinguish these disorders from other forms of autonomic dysfunction. Ganglionic AChR binding antibodies are detectable in 50% of patients with subacute autoimmune autonomic neuropathy (AAN). These patients often have a high antibody value (>0.2 nmol/L). Lower values (0.05-0.20 nmol/L) are found in approximately 10% of patients with limited AAN.

Antibodies↗