[Estimated stress verifies autonomic dysfunction].
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We prospectively evaluated autonomic function in 50 patients with clinical and manometric features of a neuropathic form of chronic intestinal pseudo-obstruction (CIP). In 26 patients, there were underlying disease processes that may have affected extrinsic neural control to viscera: diabetes mellitus (n = 16), previous gastric surgery (n = 5), and other neurologic disorders (n = 5). Our aim was to characterize autonomic function in these patients, and those 24 with CIP unassociated with a known underlying neurologic disorder (idiopathic group). We assessed vagal function and sympathetic cholinergic and adrenergic function by means of standardized autonomic tests and quantitated postprandial antral pressure activity. We also measured postprandial levels of pancreatic polypeptide and neurotensin as indicators of vagal function and of the delivery of nutrients to the distal small bowel. Among the idiopathic group (n = 24), two had evidence of a generalized sympathetic neuropathy and five abdominal vagal dysfunction (one had both). Among diabetic patients, three had sympathetic adrenergic failure, six had orthostasis with normal plasma noradrenaline, ten had signs of generalized sympathetic neuropathy and eight had abdominal vagal dysfunction. Vagal dysfunction was identified in all three patients who underwent vagotomy as part of their previous gastric surgery. In the other neurologic syndromes, vagal function was abnormal in three of the five patients. Thus, autonomic and, particularly, vagal dysfunction are confirmed in a majority of patients with CIP associated with known diabetes or neurologic disorders; however, a previously unrecognized autonomic (chiefly vagal) neuropathy of undetermined cause has been identified in five of the 24 'idiopathic' CIP patients.
1. The prevalence of cardiac autonomic alterations was evaluated in 23 obese subjects with body mass index 37.2 +/- 3.03 kg/m2 (mean +/- SD), compared with 78 controls with body mass index 22.5 +/- 2.6 kg/m2 (P less than 0.001). 2. Cardiac autonomic function was assessed by four standard tests (heart rate response to deep breathing and to the Valsalva manoeuvre, systolic blood pressure fall after standing and diastolic pressure rise during handgrip) and by the cross-correlation test, a new method of computerized analysis of respiratory sinus arrhythmia based on spectral analysis of electrocardiographic and respiratory signal. 3. Considering tests indicative of parasympathetic function, only the heart rate response to the deep breathing and the cross-correlation test were significantly lower in the obese than in the control group [deep breathing = 13.95 +/- 8.65 beats/min (mean +/- SD) vs 24.5 +/- 7.65, P less than 0.001; cross-correlation 4.28 +/- 0.74 units vs 5.14 +/- 0.63, P less than 0.001]. Deep breathing and/or cross-correlation were abnormal in 10 (43.5%) obese subjects (deep breathing: seven subjects, cross-correlation: eight subjects). No significant difference between groups was found for the response to the Valsalva manoeuvre: the Valsalva ratio was 1.69 +/- 0.45 in obese subjects and 1.88 +/- 0.33 in controls (P = NS). The Valsalva ratio was abnormal in three obese subjects. 4. No significant differences were found between groups for tests indicative of sympathetic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Autonomic vagal heart rate (HR) control, office BP and ambulatory BP were examined in 54 diabetic subjects, aged 63 +/- 6 years. Sixteen subjects were insulin-dependent. The HR response to deep breathing (the bradypnoea test) was used to evaluate the vagal HR control, and ambulatory BP was determined by the Spacelabs 5200 system (one determination every 15 minutes, for 24 hours). Twenty-seven subjects had normal office BP (SBP < or = 140 mmHg and DBP < or = 90 mmHg), seven had established hypertension (SBP > or = 160 mmHg and DBP > or = 95 mmHg) and 30 were borderline hypertensives. Over the total group, office systolic/diastolic BP (mean +/- SD) was 142 +/- 20/85 +/- 10 mmg. Systolic/diastolic ambulatory BP was 123 +/- 13/77 +/- 10 mmHg and ambulatory HR was 70 +/- 8 beats/min. Because of the small age range of our subjects, the HR score was not correlated with age (r = 0.19, NS). The HR score was not correlated with the levels of office and ambulatory pressures. In contrast, it was significantly correlated with the variability of ambulatory SBP, whether the variability was defined by the pressure standard deviation, or by the ratio SD/mean value (r = 0.40, P = 0.005 and r = 0.33, P < 0.017, respectively). We suggest that an impairment of the autonomic control in diabetics might induce an increase in variability of SBP. BP variability might play a role in the cardiovascular complications observed in diabetics.
18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific 18F-dopa uptake into striatal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects (mean putamen Ki 0.005 min-1 MSA vs 0.013 min-1 controls; mean caudate Ki 0.007 min-1 MSA vs 0.013 min-1 controls). Reduction of putamen, but not caudate, 18F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen 18F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate 18F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific striatal S-11C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of striatal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostriatal nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present.
Cardiovascular autonomic nerve function and its relation to the clinical variables of untreated recent onset and levodopa-treated advanced disease parkinsonian patients were studied. Heart rate variations were diminished in both groups when compared with age-matched controls. An orthostatic blood pressure drop was found in both disease groups. The drop was stronger and related to the levodopa dose in the advanced disease group. In conclusion, 1) in Parkinson's disease a parasympathetic damage occurs which worsens during the course of the disease, 2) the orthostatic fall in blood pressure, indicating a sympathetic dysfunction, is partly due to the disease itself and partly due to levodopa treatment.
It has been suggested that achalasia is associated with extraoesophageal sympathetic and parasympathetic dysfunction. In a prospective study we applied conventional ultrasonography and duplex sonography to investigate basal and postprandial peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI) of superior mesenteric artery and PSV of portal vein in nine patients with achalasia and 10 healthy controls (study I). In addition, in eight of these patients autonomic nervous function was investigated by pupillary function tests as well as cardiovascular reflex tests and compared with eight age- and sex-matched controls (study II). The results indicated that postprandial increase of PSV in the superior mesenteric artery was significantly lower, and postprandial decrease of PI and RI significantly higher in achalasia compared to healthy controls. In contrast, postprandial increase of PSV in the portal vein was not significantly different between both groups. Autonomic function tests revealed significant lower maximal pupillary contraction and redilatation velocities, significantly lower heart rate variation during orthostasis, deep respiration test and Valsalva manoeuvre in achalasia compared to controls. It is concluded that achalasia is associated with extraoesophageal autonomic nervous dysfunction that involves cardiovascular and pupillary function as well as regulation of mesenteric arterial blood flow.
Isolated alterations in the autonomic nervous system (ANS) have been described in obstructive sleep-apnea syndrome (OSAS), but the exact nature and degree of ANS involvement in OSAS is as yet uncharted. In the present study we evaluated some autonomic nervous functions in 13 OSAS patients using cardiopressor and pupillometric tests. Almost all showed only slight alterations of ANS function, generally in the form of a hypofunction of both sympathetic and parasympathetic branches. Pupillometry was more sensitive than cardiovascular indexes in detecting neurovegetative involvement which correlated with some respiratory indices. The data suggest that autonomic involvement in OSAS is ascribable to metabolic changes (hypoxia, hypercapnia) rather than to primary "neurogenic" alterations.
The following tests of autonomic function were performed on seven patients with the Guillain-Barré syndrome and compared with controls: (1) measurement of heart rate and blood pressure in the supine and erect positions, (2) measurement of baroreflex sensitivity, (3) Valsalva's manoeuvre, (4) sweat test. In two patients the heart rates were fixed and greater than 100/min and in three there was postural hypotension. The baroflex sensitivity of four patients was abnormal and heart rate response to Valsalva's manoeuvre was impaired in two of the three patients who were able to perform the manoeuvre. Areas of anhidrosis were found in all seven patients. These abnormalities probably reflect pathological alterations of the sympathetic and parasympathetic components of the autonomic nervous system of patients with Guillain-Barré syndrome. The severity of autonomic involvement is not related to the degree of sensory and motor disturbance which is consistent with the patchy distribution of lesions throughout the peripheral and autonomic nervous systems.
Tests of autonomic function have been performed on 7 patients with the Landry-Guillain-Barre syndrome and 5 control subjects. These included a sweat test, and measurement of both postural hypotension and baroreflex sensitivity. Sweating was definitely abnormal in 5 patients. Postural hypotension was present in 4 patients. The baroreflex sensitivity was significantly reduced (p less than 0.01) in the patients when compared with the control group. The results demonstrate that both the sympathetic and parasympathetic nervous systems may be affected in the Landry-Guillain-Barre syndrome.
Terfenadine (Seldane) was administered to 14 male subjects in a randomized, double-blinded, and crossed-over design to assess the efficacy of this peripherally active antihistamine as an anti-motion sickness drug. Terfenadine possesses practically no central side effects. A Staircase Profile Test was administered 4 h following placebo or a single oral dose of terfenadine (300 mg). The study revealed a statistically significant therapeutic effect from terfenadine (p less than 0.05). This led us to conclude that because the drug does not or only poorly crosses the blood-brain barrier, a selective peripheral antihistamine (H1) action may be sufficient in the control of motion sickness induced through cross-coupled accelerative semicircular canal stimulation using a rotating chair. This finding implies that other peripherally acting agents might be found that possess even greater anti-motion sickness efficacy. The present research raises additional questions regarding current theories on the etiology of motion sickness, its associated autonomic system dysfunction, and the validity of assumptions that effective pharmacological agents must act centrally.
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Increased sympathetic drive has been suggested to play a role in the pathogenesis of syndrome X (angina pectoris, positive exercise testing, and angiographically normal coronary arteries). Heart rate variability (HRV) studies have shown that patients with syndrome X have an imbalance in autonomic nervous system activity (sympathetic predominance). However, it is not known if transient ST-segment depression which occurs in syndrome X during daily activities is related to this autonomic nervous system dysfunction. This study investigates the relation between the response of the autonomic nervous system, as assessed by HRV analysis, and the occurrence of transient ST-segment depression during 24-hour ambulatory electrocardiographic monitoring in 23 patients (4 men and 19 women, mean age 55 +/- 6 years) with syndrome X. The frequency-domain variables of HRV low-frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.40 Hz) power were measured at 6-minute intervals during the 30 minutes preceding the onset of transient ST-segment depression. Fourteen patients (61%) had > or = 1 episode of ST-segment depression in the 24 hours, whereas the remaining 9 patients (39%) had no significant ST-segment change. HRV measures differed according to whether or not ST-segment depression was associated with increased heart rate. Episodes of ST-segment depression associated with increased heart rate were preceded by a reduction of high-frequency power and an increase in the low-frequency--high-frequency ratio, whereas episodes of ST-segment depression not associated with increased heart rate showed no significant HRV changes. Low-frequency power remained unchanged irrespective of heart rate. Thus, in patients with syndrome X, a sympathovagal imbalance (sympathetic predominance due to vagal tone withdrawal) precedes episodes of ST-segment depression that are associated with an increased heart rate.
The autonomic cardiovascular system was studied by means of autonomic tests and heart rate variability related to body movements during sleep, in 20 patients with relapsing-remitting multiple sclerosis in a stable phase and in 9 normal subjects. Responses to autonomic tests in multiple sclerosis and control subjects were similar. Heart rate variability, instead, showed a lower degree of adaptability in patients with multiple sclerosis than in controls during sleep, because of sympathetic system dysfunction. No significant correlation between magnetic resonance lesions and cardiovascular sleep indexes was found.
Cardiovascular autonomic function in normotensive awake patients with obstructive sleep apnoea syndrome was studied in 21 normotensive (mean age 48 +/- 14 years), drug-free men with obstructive sleep apnoea syndrome. Cardiovascular reflex tests with continuous blood pressure monitoring and biochemical indices were performed the morning after a standard polygraphic sleep recording. A group of 20 age-matched (mean age 49 +/- 19 years) normal subjects was used as controls. The obstructive sleep apnoea syndrome patients showed higher heart rate and noradrenaline plasma levels (p < 0.05) at rest and a higher blood pressure response to head-up tilt (p < 0.01), suggesting sympathetic overactivity. Respiratory arrhythmia, baroreflex sensitivity index and Valsalva ratio were significantly lower in the obstructive sleep apnoea syndrome group (p < 0.01) whereas the decrease in heart rate induced by the cold face test was significantly higher (p < 0.05) showing a blunting of reflexes dependent on baroreceptor or pulmonary afferents with normal or increased cardiac vagal efferent activity. These abnormalities in autonomic regulation may predispose obstructive sleep apnoea syndrome patients to cardiovascular complications like hypertension and cardiac arrhythmias.