Showing papers in "Clinical Autonomic Research in 1999"

Autonomic nervous system disorders in stroke

Abstract: Disturbances of the autonomic nervous system are common in patients with various cerebrovascular diseases. They are attributed to damage of the central autonomic network, particularly in the frontoparietal cortical areas and in the brain stem, or to a disruption of the autonomic pathways descending from the hypothalamus via the mesencephalon, pons, and medulla to the spinal cord. The most common clinical problems include abnormalities in heart rate and blood pressure regulation, reflecting cardiovascular autonomic dysfunction, and asymmetric sweating with cold hemiplegic limbs, reflecting changes in the sudomotor and vasomotor regulatory systems. Bladder and bowel dysfunction and impotence are also frequent complaints after stroke, but the present knowledge concerning their prevalence and clinical significance is still limited. Cardiovascular autonomic dysfunction, which is mainly related to increased sympathetic activity, is most evident in the acute phase of stroke, whereas other autonomic disorders, such as abnormal sweating, are long-standing or even irreversible. In addition to the well-established sympathetic hyperfunction, abnormalities of the parasympathetic nervous system may also contribute to the autonomic imbalance after stroke. Reliable recognition of autonomic dysfunction using quantitative analysis methods is important, because these disturbances are not only subjectively disabling and uncomfortable, but they may also be prognostically unfavorable. Moreover, quantitative measurements also form the ground for successive treatment of various stroke-related autonomic disorders.

Autonomic cardiovascular control in children with obstructive sleep apnea

Abstract: Autonomic cardiorespiratory control changes with sleep-wake states and is influenced by sleep-related breathing disorders. Power spectrum (PS) analysis of instantaneous fluctuations in heart rate (HR) is used to investigate the role of the autonomic nervous system (ANS) in cardiorespiratory control. The two spectral regions of interest are the low frequency component (LF) and high frequency component (HF). The aim of the present study was to investigate the autonomic cardiorespiratory control in children with obstructive sleep apnea (OSA) syndrome. We studied 10 children with OSA versus 10 normal children. All subjects underwent whole night polysomnography. Spectral analysis of the HR and breathing signals was performed for 256 second long, artifact-free epochs in each sleep-wake state. The LF power was higher in the OSA group compared with control subjects for all states, reflecting enhanced sympathetic activity in OSA subjects. The results indicated sympathetic predominance during REM sleep in all subjects and parasympathetic predominance in slow wave sleep only in controls. The autonomic balance (LF/HF) was significantly higher in OSA patients than in control subjects, at all stages during night sleep, and while awake before sleep onset. An index of overall autonomic balance (ABI) was computed for each subject and correlated well with the measured respiratory disturbance index (RDI).

Clinical and physiological characteristics of autonomic failure with Parkinson's disease

Abstract: We analyzed the clinical and physiological features of autonomic failure with Parkinson's disease (AF-PD) in seven patients and compared them with those of autonomic failure with multiple system atrophy (AF-MSA) In AF-PD, parkinsonism was more gradually progressive than in AF-MSA, and symptoms were responsive to L-dopa All seven patients with AF-PD had orthostatic hypotension, postprandial hypotension, and constipation, but no urinary retention Of these, three had hypohidrosis and five had frequent urination; five patients had subnormal plasma norepinephrine (NE) concentrations Supersensitivity to NE infusion was observed in all patients Head-up tilting (HUT) test resulted in no increase of plasma NE concentrations in both groups, but a significant increase of the plasma arginine vasopressin (AVP) concentrations in the patients with AF-PD Urodynamic studies revealed that urinary bladder function was relatively well preserved in AF-PD in contrast to AF-MSA In conclusion, there exists some clinical and physiological differences in autonomic features between AF-PD and AF-MSA, and postganglionic involvement predominates in AF-PD

Assessment of capillary fluid shifts during orthostatic stress in normal subjects and subjects with orthostatic intolerance.

Abstract: Orthostatic stress causes, in addition to venous pooling, a loss of plasma fluid from capillaries to the dependent tissues. The rate of this loss may be one of the factors determining orthostatic tolerance. In this study we assessed the use of a multichannel impedance plethysmograph for determining changes in volume in the calf, thigh, and abdominal segments, in asymptomatic volunteers and in patients shown to have poor tolerance to orthostatic stress. Impedance plethysmography showed, for leg segments, that following head-up tilt there was an initial rapid change in volume followed after 2 to 4 minutes by an almost linear change. Results from the abdominal segment were more variable. The rate of change of leg (thigh + calf) volume was significantly correlated with the estimated loss of plasma volume derived from the changes in the concentration of plasma protein, using Evans Blue dye as the marker. Comparison of results of leg filtration rates between patients and volunteers indicated that some of the patients had abnormally high filtration rates and suggests that impedance plethysmography may have a role in assessing the possible reasons for orthostatic intolerance.

Estimation of beat-to-beat changes in stroke volume from arterial pressure: a comparison of two pressure wave analysis techniques during head-up tilt testing in young, healthy men.

Abstract: Objective: The aim of this study was to compare beat-to-beat changes in stroke volume (SV) estimated by two different pressure wave analysis techniques during orthostatic stress testing: pulse contour analysis and Modelflow, ie, simulation of a three-element model of aortic input impedance. Methods: A reduction in SV was introduced in eight healthy young men (mean age, 25; range, 19-32 y) by a 30-minute head-up tilt maneuver. Intrabrachial and noninvasive finger pressure were monitored simultaneously. Beat-to-beat changes in SV were estimated from intrabrachial pressure by pulse contour analysis and Modelflow. In addition, the relative differences in Modelflow SV obtained from intrabrachial pressure and noninvasive finger pressure were assessed. Results: Beat-to-beat changes in Modelflow SV from intrabrachial pressure were comparable with pulse contour measures. The relative difference between the two methods amounted to 0.1 ± 1% (mean ± SEM) and was not dependent on the duration of tilt. The difference between Modelflow applied to intrabrachial pressure and finger pressure amounted to -2.7 ± 1.3% (p = 0.04). This difference was not dependent on the duration of tilt or level of arterial pressure. Conclusions: Based on different mathematical models of the human arterial system, pulse contour and Modelflow compute similar changes in SV from intrabrachial pressure during orthostatic stress testing in young healthy men. The magnitude of the difference in SV derived from intrabrachial and finger pressure may vary among subjects; Modelflow SV from noninvasive finger pressure tracks fast and brisk changes in SV derived from intrabrachial pressure.

Autonomic function in patients with chronic fatigue syndrome.

Abstract: Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in 37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be lower in CFS patients (28.4 +/- 10.5 beats) than in healthy controls (32.2 +/- 9.5) (p = 0.11). The maximal increase in HR during standing up was not significantly different between the CFS group (37.6 +/-8.9 beats) and the control group (40.2 +/- 8.9 beats). There were no significant differences between both groups with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva maneuver. The HR response to MA was significantly less in the CFS group (22.6 +/- 9.9) than in the control group (29.5 +/- 16.7) (p < 0.05), suggesting impaired cardiac sympathetic responsiveness to mental stress. The lower HR responses could not be explained by the level of concentration in the CFS group. During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group, but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant differences between CFS patients with and without symptoms of autonomic dysfunction regarding the hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are no gross alterations in cardiovascular autonomic function in patients with CFS.

The effects of exposure to moderate altitude on cardiovascular autonomic function in normal subjects.

Abstract: Cardiovascular responses to altitude have been studied on well-trained young subjects, generally at high altitudes (>4000 m). Less known are the effects of exposure to lower altitudes, easily reached by the general population. The aim of the study was to evaluate the effects of exposure to a moderate altitude (2950 m) on heart rate (HR), blood pressure (BP) profile, and cardiovascular autonomic function, and their correlation with hemoglobin oxygen saturation (HbO2S), in untrained subjects of a wide age range. Twenty-seven healthy normotensive subjects (age range 6–83; 8 children, 9 adults, and 10 elderly subjects) underwent a battery of noninvasive cardiovascular reflex tests and 24-h ambulatory BP monitoring. Corrected QT interval was also calculated. HbO2S was measured with a transcutaneous oxymeter. All measurements were performed at about 200 m (s.l.) and repeated at 2950 m. 24-h HR and systolic/diastolic BP mean values increased at 2950 m in children (% change respectively: 6.4±6.4, p<0.05; 6.5±4.0/13.5±6.9, p<0.05), adults (4.9±8.1, NS; 6.0±5.1/8.1±5.8, p<0.05), and elderly subjects (7.2±4.8, p<0.05; 5.1±2.3/2.8±4.1, p<0.05 for systolic BP only). Standard deviation of BP mean values increased during night-time in the adult group (p<0.05). All subjects scored normal cardiovascular test results and no differences were observed after exposure to 2950m, at both 1 hour and 24 hours from arrival. After exposure to altitude, HbO2S decreased significantly in the three groups, both on arrival and after 24 hours. No correlation was found between changes in HbO2S and BP/HR responses, and cardiovascular test results. In conclusion, exposure to moderate altitudes, easily and often reached by the general population, causes a small but significant increase in BP and HR in healthy untrained subjects of a wide age range (6–83 years). Some physiological factors (eg, lower environmental temperature and lifestyle modification) together with hypoxia, possibly more than altered cardiovascular reactivity, seem responsible for this cardiovascular change. In terms of end-organ damage, the clinical relevance of this increase in BP and BP variability for repeated exposure is not known.

Baroreflex failure following radiation therapy for nasopharyngeal carcinoma.

Abstract: The authors present a 51-year-old man with right-sided nasopharyngeal carcinoma who was treated for regional lymph node involvement by bilateral radiation therapy of the neck. Six years later he presented with episodic complaints of headache, flushing, and palpitations accompanied by elevations of blood pressure. Examination of arterial baroreflex function indicated selective afferent carotid sinus denervation. Cross spectral analysis of spontaneous heart rate and blood pressure variability showed decreased arterial baroreflex sensitivity (6.5 ms/mm Hg). Twenty-four hour measurements of blood pressure and heart rate variability showed labile hypertension during normal daytime activities. Baroreflex failure in this patient probably represents a late complication of bilateral radiation therapy of the neck.

One hundred years of adrenaline: the discovery of autoreceptors.

Abstract: The active principle of suprenal extract that produces its pressor effects was isolated by the joint research of John Abel in 1899 and Jokichi Takamine in 1901. Within three years Elliott, working in Langley's laboratory, suggested that this active principle, referred to by British physiologists as “adrenaline” and named “Adrenalin” by Takamine, was released from sympathetic nerve terminals to act on smooth muscle cells. However, it was not until 1946 that von Euler showed that demythelated adrenaline (noradrenaline) rather than adrenaline is a sympathetic transmitter. The possibility that this sympathetic transmitter could also act on nerve terminals was not developed until 1971. Research on autoreceptors culminated in the identification of adrenergic receptors on nerve terminals different to those on muscle cells. This paper assesses the contributions that established the idea of the adrenergic autoreceptor, 100 years after the discovery of adrenaline.

Exercise test in Parkinson's disease.

Abstract: In this study we assessed cardiovascular performance and metabolic response after an exercise test in Parkinsonian patients (PD patients). Methods: 15 PD patients (10 male, 5 female; mean age;63±6.17 y; mean weight: 72.2±9.5 kg) and 15 sex, age (mean: 63.8±5.38 y), and weight-(mean: 72.2±8.69 kg) matched controls performed an exercise test using a cycle ergometer and a ramp protocol. All patients and control subjects underwent a heart rate variability test prior to the exercise test. At rest and at the end of each interval blood pressure (BP) and capillary lactate samples were taken. Heart rate was monitored continuously. Results: The heart rate variability tests were abnormal in Parkinson's patients. All patients and control subjects achieved an intensity level of 75 watts, 12/15 PD patients managed 100 watts, and 7/15 PD patients managed 150 watts. 12/15 control subjects performed at an intensity level of 125 Watts and 9/15 at an intensity level of 150 Watts. There was no statistically significant difference in heart rate increase but there was a tendency to lower lactate levels at high intensity levels in PD patients. PD patients had a statistically lower systolic BP at 75, 100, 125, and 150 watts. Conclusion: We did not find striking differences in cardiovascular adaptation to physical work in PD patients and we propose, therefore, that it should be possible to improve cardiovascular endurance in PD patients. Previously, reports have suggested respiratory chain impairment in Parkinson's disease and poor endurance performance. However, our results do not support a clinically relevant impairment of the respiratory chain.

Cholinergic stimulation with pyridostigmine blunts the cardiac responses to mental stress.

Abstract: Mental stress may induce myocardial ischemia and ventricular arrhythmia in patients with coronary artery disease, and cholinergic stimulation is a potential protective mechanism. The purpose of this study was to determine the effect of pyridostigmine bromide (PYR), a reversible cholinesterase inhibitor, on the cardiac responses to a mental stress challenge. Twelve healthy young volunteers were submitted to a mental stress test (arithmetic test) 2 hours after the oral administration of either placebo or PYR (45 mg) on two separate days, following a randomized crossover double-blind protocol. Heart rate was reduced after both placebo and PYR (p<0.05), but the cardiac responses to the mental stress were lower with PYR (p<0.05): mean RR interval (mean±SE)—placebo: 730±19 msec; PYR: 769±21 msec; Peak systolic pressure-placebo: 129±4 mmHg; PYR: 124±3 mmHg; Peak diastolic pressure-placebo: 92±3 mmHg; PYR: 89±4 mmHg; Mean ratepressure product-placebo: 10,496±412 bpm×mmHg; PYR: 9,746±383 bpm×mmHg. In conclusion, 45 mg of pyridostigmine blunted the pressor and chronotropic responses to mental stress in healthy young subjects.

Occurrence of depressive symptoms in Shy-Drager syndrome.

Abstract: We investigated the frequency and severity of depressive symptoms among patients with Shy-Drager Syndrome (SDS) and correlated depression with the extent of the patients' disability. Data were collected from 15 patients and their spouse caregivers through a mailed questionnaire. The patients were asked to complete the Beck Depression Inventory (BDI) questionnaire, while caregivers were asked to complete the self-assessment Parkinson's Disease Disability Scale and The Northwestern University Disability Scale for Parkinson's Disease. Data were statistically analyzed using descriptive statistics and Pearson-Product moment correlations. The prevalence of depressive symptoms was 85.7%; 28.6% of SDS patients scored in the moderately to severely depressed range. There was no significant correlation between the severity of depressive symptoms and disability (r=0.02, p=0.94) and the ability to perform activities of daily living (r=0.0, p=1.0). The prevalence of depressive symptoms in patients with SDS is common. The patient's level of depression does not correlate with physical disability. Pharmacologic management and interventions aimed at increasing active coping methods should improve quality of life.

Autonomic dysfunction and the gastrointestinal tract.

Abstract: Autonomic neuropathy of the gastrointestinal tract may represent a primary disorder, but much more often it is secondary due to systemic disorders like diabetes mellitus. This review gives an overview about the common clinical manifestations and the principles and limitations in diagnostic work-up of autonomic dysfunction of the gastrointestinal tract. Diagnostic evaluation usually includes a combination of screening tests for autonomic neuropathy and specialized diagnostic procedures for the detection of sequela of autonomic neuropathy in gastrointestinal motility.

Electrocardiographic repolarization abnormalities in familial dysautonomia: an indicator of cardiac autonomic dysfunction.

Abstract: Objective: Electrocardiographic repolarization intervals were evaluated to determine the extent of cardiac autonomic dysfunction in patients with familial dysautonomia (FD) and to determine if any of these intervals could serve as a possible predicotr of clinical symptoms.

Hyperhidrosis and sympathetic skin response in chronic alcoholic patients.

Abstract: Palmoplantar hyperhidrosis is frequently observed in patients with a clinical history of chronic abnormal alcoholic intake. It can be related to peripheral or central mechanisms such as abnormal spontaneous activity in peripheral damaged fibres; receptor hypersensitivity; compensatory incremented activity in segmentary anhidrosis; or impairment of central sweat control. With the aim of quantifying this phenomenon and of identifying its possible origin, sympathetic skin response (SSR) analysis was performed in 20 chronic alcoholic patients with clinical diffuse acral hyperhidrosis, compared with 30 normal subjects and 2 patients affected by primary palmoplantar hyperhidrosis (PPH). SSRs were recorded by disc electrodes place on the hands and feet, simultaneously. At the hand level two recording sites were selected: palm-dorsum proximally and ventral-dorsal tip of the third finger distally. Attention was paid to the number of SSR after a single endogenous or exogenous stimulus. The alcoholic patients were divided into two groups, with and without mild polyneuropathy. Both patient groups showed synchronous SSR at recording sites, with the same pattern and the normal delay between upper and lower arms. In the control group one response was generally related to a single stimulus; if more responses were elicited an evident adaptation was shown; in the two groups of patients an increase of the waves was observed in all the recording sites without any adaptation. The SSR profile described in alcoholic patients was observed also in PPH. The pattern of SSR waves in alcoholic patients seems to suggest a possible central origin of this type of hyperhidrosis.

Sympathetic skin response following thermal, electrical, acoustic, and inspiratory gasp stimulation in familial dysautonomia patients and healthy persons.

Abstract: To determine whether sympathetic skin response (SSR) testing evaluates afferent small or efferent sympathetic nerve fiber dysfunction, we studied SSR in patients with familial dysautonomia (FD) in whom both afferent small and efferent sympathetic fibers are largely reduced. We analyzed whether the response pattern to a combination of stimuli specific for large or small fiber activation allows differentiation between afferent and efferent small fiber dysfunction. In 52 volunteers and 13 FD patients, SSR was studied at palms and soles after warm, cold and heat as well as electrical, acoustic, and inspiratory gasp stimulation. In addition, thermal thresholds were assessed at four body sites using a Thermotest device (Somedic; Stockholm, Sweden). In volunteers, any stimulus induced reproducible SSRs. Only cold failed to evoke SSR in two volunteers. In all FD patients, electrical SSR was present, but amplitudes were reduced. Five patients had no acoustic SSR, four had no inspiratory SSR. Thermal SSR was absent in 10 patients with abnormal thermal perception and present in one patient with preserved thermal sensation. In two patients, thermal SSR was present only when skin areas with preserved temperature perception were stimulated. In patients with FD, preserved electrical SSR demonstrated the overall integrity of the SSR reflex but amplitude reduction suggested impaired sudomotor activation. SSR responses were dependent on the perception of the stimulus. In the presence of preserved electrical SSR, absent thermal SSR reflects afferent small fiber dysfunction. A combination of SSR stimulus types allows differentiation between afferent small or efferent sympathetic nerve fiber dysfunction.

Diagnosis of tachycardia syndromes associated with orthostatic symptoms.

Abstract: The postural tachycardia syndrome (POTS) is characterized by excessive tachycardia only in upright position without evidence of a cardiac or metabolic disease in combination with orthostatic symptoms like dizziness, lightheadedness or syncope but without relevant falls in blood pressure. The cause is unknown. A specific diagnostic marker has not been found so far. Eighteen patients with typical symptoms of POTS were examined. They underwent standard autonomic function tests with continuous measurement of heart rate (HR) and blood pressure. All fulfilled the inclusion criteria of pathologically increased HR activation during passive tiltor standing over 90 seconds. The upper limits of normal were based on data from 137 healthy volunteers between 18 and 85 years of age. Actively standing up induced more POTS-typical HR increases and lead to more consistent results than passive tilt. HR responses during Valsalva manoeuvre and deep breathing were normal in all except one patient each, indicating that assessment of HR during these tests does not contribute to the diagnosis of POTS. Frequency of symptoms reducing overall well-being and the degree of impairment of life quality by symptoms typical of POTS were measured with a self-assessment scale. The majority of patients reported a permanent reduction of overall wellbeing and a relevant impairment of life quality due to dizziness, tachycardia, and syncopes. This underlines the importance of considering POTS as a differential diagnosis of orthostatic syndromes and the necessity of treating it adequately.

Pyridostigmine blunts the increases in myocardial oxygen demand elicited by the stimulation of the central nervous system in anesthetized rats.

Abstract: The purpose of the present work was to verify the effect of pyridostigmine bromide, a reversible cholinesterase inhibitor, on the increases in cardiac work and myocardial oxygen demand produced by central sympathetic stimulation in pentobarbitalanesthetized Wistar rats. The pharmacological stimulation of the central nervous system with L-glutamate (1 mg/kg, intracerebroventricular) elicited marked increases in arterial pressure, dP/dtmax, rate-pressure product, and triple product, reproducing the cardiovascular alterations observed during physical effort and stressful situations. The oral administration of pyridostigmine bromide (5, 10 and 20 mg/kg) 2 hours before central stimulation blunted the increases in mean arterial pressure, dP/dtmax, and triple product elicited by glutamate (29, 28 and 57% for 5 mg/kg; 26, 23 and 46% for 10 mg/kg and 19, 17 and 37% for 20 mg/kg, respectively) when compared to the control group (41, 49 and 106%, respectively; p<0.05). Our results also showed that the activity of plasmatic cholinesterase was effectively inhibited by pyridostigmine bromide. In conclusion, the increases in endogenous acetylcholine induced by cholinesterase inhibition blunted the cetrally-evoked increases in myocardial oxygen demand in anesthetized rats. This effect could represent a cardioprotective action in a situation of ischemic heart disease.

A case of sinus arrest and vagal overactivity during REM sleep.

Abstract: A young man presented with tachycardia and faintness after an episode of influenza. He underwent 24-h heart rate recordings, each of which documented episodes of sinus arrest lasting up to 7.2 seconds. All episodes occurred in the second half of the night and were always accompanied by severe bradycardia. Cardiac function tests failed to disclose anything abnormal. Two polysomnographic recordings demonstrated that the sinus arrests occurred during REM sleep. Power spectral analysis of heart rate variability showed that during the second half of the night there was an abnormal prevalence of vagal activity, particularly during REM sleep stages, presumably responsible for the bradycardia and fall in blood pressure. We speculate that the episodes of sinus arrest are linked to a central mechanism that triggers the autonomic imbalance during REM sleep.

Abnormal suppression of arginine-vasopressin by clonidine in multiple system atrophy.

Abstract: In normal man, the centrally activeα2-adrenoceptor agonist clonidine reduces arginine-vasopressin (AVP) secretion, probably by presynaptic inhibition of noradrenergic neuron terminals in the supraoptic nucleus. A lesion of noradrenergic pathways in animals abolishes this response to clonidine. At postmortem in multiple system atrophy (MSA) there is marked loss of hypothalamic noradrenergic innervation. We hypothesized that the AVP response to clonidine in MSA may be abnormal and therefore studied the AVP response to clonidine (2μg/kg iv) in 10 subjects with MSA and compared them to six healthy age-matched control subjects. Basal levels of AVP were similar in controls and MSA. Following clonidine there was a significantly greater fall in controls than MSA (−47±4% vs −25±6%; p<0.05). There was a similar fall in mean arterial pressure (MAP) and plasma catecholamines in both groups, with no change in plasma osmolarity, excluding these as a contributary factor. In conclusion, there is an abnormal AVP response to clonidine in MSA, which probably represents loss of functional noradrenergic innervation of the supraoptic nucleus.

Non-invasive assessment of autonomic nervous system integrity in able-bodied and spinal cord-injured individuals.

Abstract: The purpose of this study is to identify features of the Valsalva maneuver (VM) that differentiate between able-bodied (AB,n=14) and spinal cord-injured individuals with high (T,n=11) and low (P,n=10) lesions. The systolic blood pressure (BP) recovery during the VM was used as a measure of sympathetic and vagal activity, whereas from the BP rise in phase IV of the VM baroreflex sensitivity was derived. After a similar initial BP decrease in all groups, BP recovered faster VM. After release of the VM, the BP overshoot was very similar in AB and P, suggesting that the BP overshoot reflects sympathetic activity onto the heart. The baroreflex sensitivity was smaller in P, but not in T, compared to AB. However, 36% of the observations of T had such a low correlation between BP and RR interval that a slope could not be determined, which caused loss of observations, but suggested a low baroreflex sensitivity as well.

Amplitude loss of electrically and magnetically evoked sympathetic skin responses in early stages of type 1 (insulin-dependent) diabetes mellitus without signs of dysautonomia.

Abstract: The sympathetic skin responses following both electrical nerve (eSSRs) and magnetic (mSSRs) brain stimulations have been investigated in 19 insulin-dependent diabetic patients with no evidence of a peripheral neuropathy or dysautonomia and compared to those obtained in 10 age-matched healthy subjects. SSR was recorded from the right hand and foot, controlateral to the stimulated side. The main findings were amplitude loss and disappearance of the eSSR in 12/19 (63.2%) and 11/19 (57.9%) patients, occurring more frequently than the mSSR; 7/19 (36.8%) and 5/19 (26.3%) were recorded from the hand and foot, respectively. The SSR to electrical stimulation was significantly reduced in the upper and lower extremities (p<0.0001) compared to control results, whereas latencies were normal to both stimulation modalities. Only in two cases the responses were absent from the foot, one following electrical stimulation and the other after magnetic stimulation. No correlation was found between the SSR and metabolic indexes of diabetes mellitus or conduction velocity studies. On the basis of these data an early impairment of afferent pathways may be postulated.

The cutaneous vasoconstrictor response to venous stasis is normal in subjects with primary Raynaud's disease

Abstract: In control subjects and in subjects with primary Raynaud's disease, sudden sound or a mild cool stimulus evokes the pattern of alerting response that includes cutaneous vasoconstriction but vasodilatation in forearm muscle. In control subjects, response habituates on repetition of these stimuli both within experimental sessions and over successive days. However, in subjects with primary Raynaud's disease, the cutaneous vasoconstriction and the muscle vasodilatation persist. We have now tested whether a similar disparity exists for the cutaneous vasoconstriction evoked by venous stasis, a response considered to be a veno-arteriolar reflex mediated by sympathetic fibers, but not requiring transmission through the spinal cord. In 10 subjects with primary Raynaud's disease and in 10 matched controls, a sphygmomanometer cuff on the left arm was inflated to 40 mm Hg for 2 minutes, five times on each of three experimental sessions on days 1, 3, and 5. Cutaneous red cell flux (RCF) was recorded from the pulp and dorsum of the left index finger by using a laser Doppler meter; digital vascular conductance (DCVC) was computed as RCF divided by arterial pressure. The first venous stasis, in session 1, evoked a decrease in pulp and dorsum DCVC in the control and primary Raynaud's subjects. There were no differences between the groups in the magnitudes or durations of these responses. Within session 1, the magnitude of the decrease in DCVC diminished on repetition of venous stasis in the dorsum in controls and in the pulp in primary Raynaud's subjects. We propose these effects reflected the similar reductions in baseline DCVC over time; there was no change in the duration of the responses. Repetition of venous stasis had similar effects in both groups of subjects within sessions 2 and 3. Further, judging from the mean of the responses evoked in each Session the decreases evoked in pulp and dorsum DCVC by venous stasis were fully consistent in magnitude and duration over the three sessions in both groups. These results indicate that the direct constrictor influence of sympathetic fibers upon cutaneous blood vessels is similar in magnitude and similarly reproducible in controls and subjects with primary Raynaud's disease. This reinforces our view that the lack of habituation of the cutaneous vasoconstrictor component of the alerting response in subjects with primary Raynaud's disease reflects impairment of the central neural process of habituation, rather than a peripheral phenomenon, and that this lack of habituation predisposes these subjects to vasospasm.

Patients' choice of portable folding chairs to reduce symptoms of orthostatic hypotension

Abstract: Patients with neurogenic orthostatic hypotension may use portable folding chairs to prevent or reduce symptoms of low blood pressure. However, a concomitant movement disorder may limit the use of these chairs in daily living. In this prospective study, 13 patients with orthostatic hypotension, balance disturbance associated with motor disability, or both examined three commercially available portable folding chairs. A questionnaire was used to document the characteristics in chair design that were relevant for satisfactory use to these patients. Armrests, seat width, and an adjustable sitting height were found to be important features of a portable folding chair. One chair was selected by 11 of 13 patients to fit most needs.

Autonomic control of heart rate variability in vasovagal syncope: a study of the nighttime period in 24-hour recordings.

Abstract: Patients experiencing vasovagal syncope have been claimed to show reduced vagal tone over 24-hour electrocardiography recordings. Assessment of sympathovagal balance in the absence of external stimuli,ie, nighttime electrocardiography monitoring, might help to clarify if increased sympathetic activity is present in these patients. Heart rate variability was examined at nighttime in 40 patients with recurrent episodes of vasovagal syncope within the last 2 years (22 men; mean age, 37 years) and 20 comparable healthy volunteers. Time domain parameters (pNN50 [proportion of successive RR intervals difference > 50 ms in %] and rMSSD [root-mean-square successive difference of RR intervals in ms]), indexes of vagal tone, and frequency domain parameters, expressing the overall heart rate variability, vagal (high frequency [HF]) and sympathetic (low frequency [LF]) activity, and autonomic balance (LF/HF ratio) were compared between groups by Mann-Whitney test. Significant (p<0.05) reduction of heart rate variability and vagal tone (pNN50 and rMSSD) were found for patients with vasovagal syncope, together with increased sympathetic activity (increased LF/HF ratio). These findings could open new insights in the pathogenesis of vasovagal syncope because of the shift of the autonomic balance toward sympathetic activation near the syncopal episode.

Contribution of nitric oxide to exercise-induced hypotension in human sympathetic denervation.

Abstract: The cardiovascular, catecholamine, and nitrate/nitrite (NOx) responses to bicycle exercise were measured in 14 normal subjects (controls) and two groups with sympathetic denervation; 14 with peripheral autonomic failure (pure autonomic failure [PAF]); and 13 with central autonomic failure (multiple system atrophy [MSA]). With exercise, blood pressure increased in control subjects by 40±7/24±5 mm Hg (p<0.001) and fell in PAF by 24±8/24±5 mm Hg (p<0.02 and p<0.007) and MSA by 31±7/11±3 mm Hg (p<0.005 and p<0.04). With exercise, the increase in heart rate was greater in control subjects (60±3 to 111±4/min; p<0.0001) than in PAF (69±3 to 86±4/min; p<0.0001) and MSA (70±4 to 90±4; p<0.001). Resting plasma noradrenaline levels were similar in controls (291±51 pg ml−1) and MSA (257±49 pg ml−1), but lower in PAF (82±14 pg ml−1). With exercise, plasma noradrenaline increased in controls but was unchanged in PAF and MSA. Resting NOx was similar in controls (50±5 nmol/L; range, 23.3–87.6 nmol/L) and PAF patients (59±8 nmol/l; range, 19.3–116.4 nmol/L), but was higher in MSA patients (87±14 nmol/L; p<0.025, range 15.4–157.2 nmol/L). With exercise, NOx was unchanged in control subjects and increased by 10% and 17% in PAF and MSA, respectively; these changes were not statistically significant. This study suggests that circulating changes in NOx levels do not exert a major role in exercise-induced hypotension in subjects with sympathetic denervation.

Forearm and calf blood flow in response to cortical arousal in normal male and female subjects.

Abstract: The aim of this study was to investigate cardiovascular changes, particularly in forearm and calf blood flows, in response to acute emotional stress in men and women. The study was approved by the Ethics Committee of the Queen's Medical Centre, Nottingham University.

Intrinsic vasomotor innervation of blood vessels in human ventrolateral medulla.

Abstract: Medullae were obtained at autopsy from seven patients with no neurologic disease, and sections were processed for tyrosine hydroxylase (TH), nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), or both. Both TH- and NADPH-d reactive neurons had close anatomical relationship with penetrating blood vessels in the ventrolateral medulla (VLM). Three patterns were identified: 1) processes arising from a neighboring neuron reaching the blood vessel; 2) direct appositions of cell bodies to blood vessels; and 3) fibers coursing parallel to the blood vessels. This intrinsic innervation may provide a mechanism of coupling among local metabolism, sympathetic activity, and blood flow in the VLM.