The diagnostic value of the rate-corrected QT interval in long-term type-1 diabetes mellitus

OBJECTIVE: To assess the relationship between rate-corrected QT interval (QTc interval) and cardiac reflex tests in order to determine the value of QTc interval measurements in the diagnosis of diabetic cardiac autonomic neuropathy. INVESTIGATIONS: The QTc interval was measured in the resting ECG of 97 type 1 diabetics (58 women, 39 men; mean age 35 +/- 12 years; duration of diabetes 18 +/- 10 years; HbA1c 7.8 +/- 1.8%). Age-related results were compared with five cardiac function tests (heart rate variation at rest and on forced breathing; 30/15 ratio of heart rate; Valsalva manoeuvre; orthostasis). RESULTS: The QTc interval was not prolonged ( < or = 440 ms) in 68 patients (70%), while in 29 (30%) it was prolonged ( > 440 ms). No significant differences regarding QTc interval were found between patients with autonomic cardiac neuropathy ( > or = 2 abnormal function tests) and those without ( < 2 abnormal function tests) (QTc interval 436 +/- 25 vs 426 +/- 19 ms). QTc intervals correlated with the coefficients of variation for heart rate variation at rest and on forced breathing and the 30/15 ratio of heart rate (p = 0.001; p = 0.001; p = 0.03), but not with the results of the Valsalva manoeuvre and the orthostasis test. CONCLUSION: Prolongation of the QTc interval in longstanding type 1 diabetes does not provide a reliable indication of cardiac autonomic neuropathy and this measure cannot replace conventional reflex tests for its diagnosis.     

DC photoplethysmography in the evaluation of sympathetic vasomotor responses

The d.c. component of the photoplethsmographic signal was used to determine the response of the finger vasculature to three standard tests of vasomotor function: (1) an inspiratory gasp (IG), (2) immersion of the contralateral hand in ice water (IW), and (3) the Valsalva manoeuvre. The vasoconstrictor response to the first two of these stimuli could be measured in all of 25 normal subjects. The response to the Valsalva manoeuvre could not be detected consistently. Seven patients with known sympathetic autonomic dysfunction showed no response to either IG or IW. In 30 patients with diabetes mellitus of over 10 years duration, 46.7% had no response to IG, and 20% had no response to IW. Absent responses correlated with abnormal autonomic cardiovascular reflexes, with absent sympathetic skin responses and with the severity of peripheral somatic neuropathy. The d.c. photoplethysmographic determination of the vasoconstrictor response in the finger after a deep inspiratory gasp and after ice water immersion offers an additional measure of the function of small (2 mu-6 mu) peripheral nerve fibres. Because of variability in the amplitude of the responses in normals, only an absent response should be accepted as abnormal.     

Paclitaxel changes sympathetic control of blood pressure

Paclitaxel has become part of standard therapy in the treatment of ovarian and breast cancer. Concern has been raised about the effects of paclitaxel on cardiovascular function. Therefore, this study of the effects of paclitaxel on autonomic cardiovascular control was initiated. Eighteen women treated for ovarian or breast cancer were examined with autonomic cardiovascular function tests, once before the treatment and once after the second course of paclitaxel. Heart rate and blood pressure variability and changes in heart rate and blood pressure responses to the tests were measured. Baroreflex sensitivity was calculated from the Valsalva manoeuvre non-invasively. Paclitaxel did not change heart rate variability at rest compared with the pretreatment level. However, medium frequency variability of blood pressure was smaller after treatment with paclitaxel. Paclitaxel treatment did not impair the heart rate and blood pressure responses to the autonomic function tests. The results do imply that paclitaxel alters sympathetic control of blood pressure. Nevertheless, paclitaxel does not appear to precipitate autonomic cardiac neuropathy.     

An additional variant of the persistent primitive trigeminal artery: accessory meningeal artery--antero-superior cerebellar artery anastomosis associated with moyamoya disease

Neuropathy is a frequent complication in diabetes mellitus. Since the involvement of the autonomic nervous system indicates a poor prognosis, early detection and subsequent management are important. Analysis of heart rate variability (HRV) provides a quantitative measure of sympathovagal modulation activities on the heart and has been proven to be useful for the early assessment of the diabetic autonomic neuropathy. We recently developed a simple method of measuring pulse wave velocity (PWV) to evaluate sympathetic nervous activity in the vascular system. In this paper, we examined 33 diabetic patients with and without peripheral neuropathy (15 and 18 respectively) using these methods. In time domain analysis, the mean heart rate, standard deviation and coefficient of variation of HRVs significantly differed between these two groups, whereas the indices of PWVs did not show a significant difference. In frequency domain analysis of HRV, both low and high frequency components were decreased, and the low frequency component in normalized unit did not increase after standing in patients with peripheral neuropathy. We previously reported that the mean PWV decreased after standing in patients with diabetic neuropathy. This disagreement suggests that beta sympathetic dysfunction precedes alpha sympathetic dysfunction in diabetic neuropathy.     

Preservation of the pattern of tyrosine phosphorylation in human neutrophil lysates

Diabetic cardiovascular autonomic neuropathy increases the risk of deterioration in renal function and is associated with increased mortality in patients with renal failure. Type 1 diabetic patients with long diabetes duration, matched for age (38 +/- 9 years) and diabetes duration (28 +/- 8 years) were studied regarding the association between cardiovascular autonomic nerve function and different degrees of diabetic nephropathy. Eighteen patients were normo- (< 30 mg/l), six micro- (30-300 mg/l), and 13 macroalbuminuric (> 300 mg/l) based on urinary albumin concentrations in three separate morning samples. They were compared with 33 control subjects with similar age. Autonomic nerve function was evaluated by measuring the response of heart rate to deep breathing and active standing. Beat-to-beat finger artery blood pressure (Finapres) was tested during active standing. During deep breathing both change in heart rate (17 +/- 11, 9 +/- 7 and 4 +/- 3 beats/min) and ratio between expiratory and inspiratory R-R intervals (1.32 +/- 0.24, 1.14 +/- 0.15 and 1.05 +/- 0.04) decreased from normo- over micro- to macroalbuminuria (p < 0.05 vs normoalbuminuric and control subjects [17 +/- 5 beats/min and 1.28 +/- 0.10, respectively]). Similar results were obtained during active standing with respect to change in systolic arterial blood pressure (3 +/- 8, 2 +/- 13 and -6 +/- 11 mmHg; p < 0.05 vs control subjects [8 +/- 11 mmHg]). However, the response of diastolic arterial blood pressure or mean heart rate to standing up did not differ between any of the groups. The ratio of maximum to minimum R-R interval during the dynamic response of heart rate to active standing decreased with the degree of nephropathy (1.27 +/- 0.17, 1.11 +/- 0.11 and 1.05 +/- 0.06) with significantly higher values in patients with normo- compared with patients with macroalbuminuria (p < 0.05). All patients groups had significantly lower values than control subjects (1.46 +/- 0.22, p < 0.05). The overshoot of the blood pressure after an initial fall during active standing decreased with the degree of diabetic nephropathy. In conclusion, type 1 diabetic patients with long duration of diabetes have signs of cardiovascular autonomic neuropathy, the severity of which is related to the degree of nephropathy.     

Autonomic cardiovascular neuropathy in Sj?gren's syndrome. A controlled study

OBJECTIVE: To test patients with primary Sj?gren's syndrome (SS) for evidence of autonomic neuropathy. METHODS: Thirty-two patients with primary SS and 22 age and sex matched healthy individuals were asked specific questions about symptoms suggestive of autonomic neuropathy, and were subjected to a battery of 5 cardiovascular tests: response of blood pressure to sustained hand grip, Valsalva maneuver, heart rate response to deep breathing, and heart rate and blood pressure response to standing up. The chi-squared test with Yates' correction and 95% confidence intervals were used for statistical analysis of the results. RESULTS: Sixteen patients (50%) had symptoms of autonomic neuropathy when specifically asked versus none of the controls (p < 0.0005). The frequency of abnormal responses to the tests was 68.8% in patients and 12.7% in controls (p < 0.0001). Severe autonomic cardiovascular neuropathy was found in 87.5% of the patients but in none of the healthy individuals (p < 0.0001). CONCLUSION: Our results suggest that autonomic neuropathy is a feature of a significant portion of the SS population, and such patients should have appropriate evaluation. Similarly, patients with unexplained autonomic neuropathy should be investigated for evidence of SS.     

Electrophysiological tests of autonomic function in patients with idiopathic autonomic failure syndromes

Three electrophysiological tests of autonomic function were performed in patients with autonomic nervous system dysfunction to define test sensitivities and specificities. The skin sympathetic response, Valsalva ratio, and heart rate variation with deep breathing were studied in 10 patients with multiple system atrophy (MSA) and in 7 patients with pure (also called progressive or primary) autonomic failure (PAF); control subjects were 17 normal individuals of similar age. Thirteen patients had abnormal skin sympathetic responses, and 16 had abnormal Valsalva ratios. Fourteen patients had an abnormal variation of the heart rate with deep breathing. Taking the three tests together, binary logistic regression for distinguishing between patients and normal subjects correctly classified 91% of the 33 individuals for whom there were complete data with sensitivity of 88% and specificity of 94%. However, only 69% of the patients could be correctly classified by a logistic regression for discriminating between MSA and PAF. Electromyography (EMG) studies showed that 7 of 8 patients with MSA but only 2 of 7 patients with PAF (both multiparous women) had denervation of the rectal sphincter muscle. The EMG study is, therefore, valuable in men, but has a high false positive rate in women, probably because of pudendal nerve injury from parturition.     

Cardiovascular and sweating dysfunction in patients with Holmes-Adie syndrome

A cross-sectional study is reported in which 53 patients with Holmes-Adie syndrome have been subjected to a battery of tests of autonomic nervous function referable to the cardiovascular system, to two objective tests of sweating function, and to subjective assessment of sweating by application of quinizarin powder followed by body heating. The majority of patients were consecutive referrals; none was selected because of clinical indications of autonomic dysfunction. Eighty three per cent of these patients had at least one, 57% at least two, and 40% at least three objective test abnormalities, as defined by values lying outside 95 percentiles of healthy subjects who were matched for age and subjected to the same tests. In the context of multiple testing, the probability of finding outside values was such that a minimum of 3 was required to define abnormality. On this basis 40% of patients were found to have significant evidence of autonomic dysfunction. The most frequent abnormalities were impaired digital vasoconstriction to cold (23%), a reduced heart rate response to the Valsalva manoeuvre (17%), and excessive variability in sweating between test sites (in one of the tests, 43%) which is consistent with patchy loss. Abnormal quinizarin test appearances were seen in 10 patients and in a further five patients the appearances were thought to be suggestive of abnormality. Though assessment of the results of this test are subjective, the observations are consistent with the findings obtained from the objective tests which were applied. Cardiovascular and sweating abnormality did not concur significantly and only the former was found to increase progressively with known duration of the pupillotonia. It is concluded that Holmes-Adie syndrome is commonly accompanied by progressive mild but widespread autonomic involvement but rarely is this symptomatic. If symptoms suggestive of autonomic neuropathy are found in a patient with tonic pupils, a careful search for some other generalised disorder is recommended.     

Prevalence of central autonomic neuropathy in elderly dialysis patients

BACKGROUND: Autonomic neuropathy is frequently present in dialysis patients. In addition, deterioration of autonomic function occurs with ageing. This study examines the true prevalence of autonomic neuropathy in elderly dialysis patients and questions whether the combination of age and uraemia further increases the chance of dysautonomia being present. METHODS: We compared the results of five different tests (30:15 ratio; Valsalva ratio; heart rate response to deep breathing and the blood pressure responses to sustained hand grip and standing) of parasympathetic and combined parasympathetic and sympathetic dysfunction in older haemodialysis patients (mean age 70.2 years), younger haemodialysis patients (mean age 48.1 years) and two groups of subjects with normal renal function (mean age 73.0 years and 42.5 years respectively). RESULTS: Parasympathetic dysfunction was most prevalent in older patients on dialysis (65.9% (95% confidence intervals 51.4-80.4%), compared with 33.3% (95% confidence intervals 19.0-47.5% in younger dialysis patients), and 11.8 and 0% in the old and young control groups respectively). Combined parasympathetic and sympathetic dysfunction was seen in 41.5% (95% confidence intervals 26.5-56.5%) and 11.9% (95% confidence intervals 2.1-56.5%) of the old and young dialysis patients respectively but not in any of the control subjects. No interaction was seen between age and subject type. CONCLUSIONS: We conclude that although older dialysis patients have severe impairment of cardiovascular autonomic innervation, the prevalence of dysfunction is not higher than would be expected in an ageing population with uraemia.     

Comparison of the effect of EMLA and semicircular subcutaneous anaesthesia in the prevention of tourniquet pain during plexus block anaesthesia of the arm

The present study examined resting heart rate variability (HRV; an index of parasympathetic tone) and heart rate response to the Valsalva maneuver (Valsalva ratio; an index of overall autonomic responsiveness) in 12 repeat users of 3.4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), and a matched comparison group of presumed nonusers. HRV and Valsalva ratio were smaller in users than in controls. Three out of 12 MDMA users but no controls had Valsalva ratios below 1.50, the cut-off for autonomic dysfunction. In several users, there was a total absence of post-Valsalva release bradycardia. All MDMA users were polydrug users. Parasympathetic cardiovascular tone appears impaired in repeat MDMA users, although the ubiquitous problems in such epidemiologic designs (including lack of testing before the first use of the drug and confounding with use of other drugs) preclude definitive causal interpretations.     

Cervical intraepithelial neoplasia in adolescents: study of cytological findings between 1987 and 1995 in S?o Paulo State-Brazil

Cardiovascular complications are the most common causes of morbidity and mortality in diabetic patients. Coronary atherosclerosis is enhanced in diabetics, whereas myocardial infarction represents 20% of deaths of diabetic subjects. Furthermore, re-infarction and heart failure are more common in the diabetics. Diabetic cardiomyopathy is characterized by an early diastolic dysfunction and a later systolic one, with intracellular retention of calcium and sodium and loss of potassium. In addition, diabetes mellitus accelerates the development of left ventricular hypertrophy in hypertensive patients and increases cardiovascular mortality and morbidity. Treating the cardiovascular problems in diabetics must be undertaken with caution. Special consideration must be given with respect to the ionic and metabolic changes associated with diabetes. For example, although ACE inhibitors and calcium channel blockers are suitable agents, potassium channel openers cause myocardial preconditioning and decrease the infarct size in animal models, but they inhibit the insulin release after glucose administration in healthy subjects. Furthermore, potassium channel blockers abolish myocardial preconditioning and increase infarct size in animal models, but they protect the heart from the fatal arrhythmias induced by ischemia and reperfusion which may be important in diabetes. For example, diabetic peripheral neuropathy usually presents with silent ischemia and infarction. Mechanistically, parasympathetic cardiac nerve dysfunction, expressed as increased resting heart rate and decreased respiratory variation in heart rate, is more frequent than the sympathetic cardiac nerve dysfunction expressed as a decrease in the heart rate rise during standing.     

Diagnosing community health by factorial analysis]

The electrophysiologic evaluation of patients with erectile dysfunction presents an important diagnostic challenge. The bulbocavernosus reflex (BCR) latency has been commonly used to evaluate these disorders. However, it is a measure of somatic penile innervation, whereas erection is primarily dependent on autonomic function. We evaluated 195 men with erectile dysfunction over a 3 year period. Each had electrophysiologic studies, nerve conduction studies and a BCR. BCR studies were abnormal in only 7%, of which most had diabetes or pelvic trauma. The BCR was the sole electrophysiologic abnormality in only 2%. Autonomic testing (AT) was additionally performed in 19 diabetic and 23 non-diabetic patients. This included sympathetic skin responses and measurement of the Valsalva ratio and heart rate variability with 6/min breathing. In the diabetic group, AT was positive in 63%, and most often was the sole abnormality. The bulbocavernosus reflex is relatively insensitive in the diagnosis of erectile dysfunction. Brief autonomic testing may provide valuable additional data, particularly in diabetics.     

Abnormal autonomic stress responses in obstructive sleep apnoea are reversed by nasal continuous positive airway pressure

Obstructive sleep apnoea (OSA) is associated with abnormalities in autonomic stress tests, which are tests of cardiovascular response in the autonomic nervous system (ANS). The level of abnormality has been related to the level of overnight arterial oxygen saturation (Sa,O2). We have studied ANS function pre- and post-treatment with nasal continuous positive airway pressure (nCPAP) in six males with moderately severe or severe OSA (apnoea/hypopnoea index (AHI) median 51 (range 14-74 events.h-1 of sleep). Tests consisted of heart rate responses to Valsalva manoeuvre, deep breathing, and change of posture from lying to standing. In addition, systolic blood pressure (SBP) response to standing and diastolic blood pressure (DBP) response to handgrip were studied. Each abnormal test (compared to published normal values) scored +1.0 and each marginal test result (90-95% confidence interval for normals) scored +0.5. A total score was calculated for the five tests performed in the evening and morning (maximum score 10 per patient). Patients had been receiving treatment for more than 1 year (median 471 (389-624) days) and objective compliance was monitored by a clock counter in the nCPAP machines. Five of six patients had regularly used nCPAP (mean 7.8 h.night-1) and all showed a normalization in ANS test score: pre-nCPAP 2 (1-4.5), post-nCPAP 0.2 (0-0.5) (p < 0.05, Wilcoxon signed rank test). One poorly compliant subject (No. 6; nCPAP 3 h.night-1) had a deterioration in ANS test score: 1 pre-nCPAP to 1.5 post-nCPAP. The improvement in ANS test score in the five compliant patients was positively correlated with an improvement in mean Sa,O2 during sleep posttreatment. We conclude that successful treatment of obstructive sleep apnoea leads to normalization of impaired autonomic stress responses.     

Heart rate variability in depressed patients and differential effects of paroxetine and amitriptyline on cardiovascular autonomic functions

Twenty-four unmedicated patients with episodes of major depression (DSM-III-R) and an age- and sex-matched group of 24 normal subjects underwent a heart rate analysis. The battery of cardiovascular reflex tests included the coefficient of variation while resting (CVr) and during deep breathing (CVdr), a spectral analysis of heart rate variability, the Valsalva test, and the posture index. The depressed patients showed no significant abnormalities in any of the tests as compared to the healthy subjects. The 24 patients were randomly allocated for treatment with either amitriptyline or paroxetine. During treatment with 20 mg paroxetine per day, patients showed no changes in cardiovascular autonomic function tests after 14 days. However, treatment with 150 mg amitriptyline per day decreased all heart rate parameters significantly due to anticholinergic side effects, except heart rate, which increased significantly. As autonomic side effects are a potential hazard of antidepressant therapy, the data suggest that paroxetine is an appropriate antidepressant for cases with pre-existing cardiovascular autonomic neuropathy.     

The importance of vitamin B 6 for development of the infant. Human medical and animal experiment studies

Thirteen healthy subjects were tested for parasympathetic reactivity during head-up tilt and reversal of the tilt. Head-up tilt (70 degrees) resulted in significant increase in baseline heart rate and diastolic blood pressure. Head-up tilt also led to increased parasympathetic reactivity as measured by Valsalva manoeuvre and hand grip test. Heart rate response to deep breathing test did not change. The reversal of the tilt led to returning of heart responses to original values. Responses indicate towards enhanced parasympathetic reactivity during head-up tilt position.     

Cardiac autonomic nerve function and insulin sensitivity in obese subjects

OBJECTIVE: To investigate whether obesity influences cardiac autonomic nerve function. DESIGN: Comparing two groups of subjects with different degrees of obesity to normal weight controls. SUBJECTS: 19 healthy controls (mean age 33 y, BMI 21.7 +/- 0.2 kg/m2) and 17 obese non-diabetic subjects (mean age 39 y, BMI 33.7 +/- 1.8 kg/m2). MEASUREMENTS: Insulin sensitivity was calculated by an oral glucose tolerance test. Autonomic nerve function was evaluated by analysing the variation of the heart frequency at rest (coefficient variation of R-R intervals, REST 1), during deep respiration, at a Valsalva maneuver (longest/shortest R-R interval during inspiration hold) and by the Ewing test (ratio between the 30th and 15th R-R interval after reaching up-right position). RESULTS: The obese showed a lower insulin sensitivity than healthy controls (3.09 vs 4.60 mg x l2/mmol x mU x min, P < 0.001). Their variation in heart frequency was reduced (REST 1: 1.95 vs 2.9, P < 0.01, Valsalva: 1.30 vs 1.52 and Ewing test: 1.03 vs 1.14, P < 0.05). However, patients with moderate (BMI 31.7 kg/m2) or severe obesity (39.0 kg/m2) with identical insulin sensitivity had no significant difference in autonomic nerve function. Except for the Ewing test all measured parameters for the evaluation of cardiac autonomic nerve function correlated with the degree of diminished insulin sensitivity (REST 1: r = 0.475, P < 0.001). CONCLUSION: Moderate obesity with significantly decreased insulin sensitivity is associated with impaired cardiac autonomic nerve function.     

DNA single strand breakage, DNA adducts, and sister chromatid exchange in lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven workers

During heart transplantation (HTX) all neural connections are severed. In humans, signs of autonomic reinnervation have been found. In this study non-invasive tests were used to compare signs of sympathetic and parasympathetic reinnervation. Non-invasive autonomic function tests and heart rate variability parameters (HRV; 24 h electrocardiographic registration) were used to investigate signs of reinnervation. 16 HTX patients (14 males) were compared with age-and sex-matched controls. Parasympathetic heart rate changes in HTX compared to controls were attenuated during the diving test, deep breathing, the Valsalva maneuver and standing up but not during carotid sinus massage. Sympathetic heart rate increases were lower during the cold pressor test and mental stress. The blood pressure responses were comparable to the control group, but not during active standing and tilting. This finding suggests an obligatory 'blood pressure' role for the innervated heart in these two tests. All HRV parameters were lower in HTX. One or more normal parasympathetic responses were found in 13 out of 16 patients versus 4 out of 16 with normal sympathetic responses (p < 0.05). Heart rate variations were less in case of a higher donor age, and higher in case of a longer time after HTX. Parasympathetic signs of reinnervation are more common than sympathetic signs of reinnervation. A higher donor age reduces signs of reinnervation. If the sympatho-vagal balance is a prognostic factor in HTX patients as it is in other cardiac diseases these findings are clinically relevant.     

Noninvasive assessment of cardiac diabetic neuropathy by carbon-11 hydroxyephedrine and positron emission tomography

OBJECTIVES: The purpose of this investigation was to evaluate the sympathetic nervous system of the heart by positron emission tomographic (PET) imaging in patients with diabetes mellitus with and without diabetic autonomic neuropathy. BACKGROUND: The clinical assessment of cardiac involvement in diabetic autonomic neuropathy has been limited to cardiovascular reflex testing. With the recent introduction of radiolabeled catecholamines such as carbon (C)-11 hydroxyephedrine, the sympathetic innervation of the heart can be specifically visualized with PET imaging. METHODS: Positron emission tomographic imaging was performed with C-11 hydroxyephedrine and rest myocardial blood flow imaging with nitrogen-13 ammonia. Three patient groups were studied, including healthy volunteers as control subjects, diabetic patients with normal autonomic function testing and diabetic patients with varying severity of autonomic neuropathy. Homogeneity of cardiac tracer retention as well as absolute tracer retention was determined by relating myocardial tracer retention to an arterial C-11 activity input function. RESULTS: Abnormal regional C-11 hydroxyephedrine retention was seen in seven of eight patients with autonomic neuropathy. Relative tracer retention was significantly reduced in apical, inferior and lateral segments. The extent of the abnormality correlated with the severity of conventional markers of autonomic dysfunction. Absolute myocardial tracer retention index measurements showed a 45 +/- 21% decrease in distal compared with proximal myocardial segments in autonomic neuropathy (0.069 +/- 0.037 min-1 vs. 0.13 +/- 0.052 min-1, p = 0.02). CONCLUSIONS: This study demonstrates a heterogeneous pattern of neuronal abnormalities in patients with diabetic cardiac neuropathy. The extent of this abnormality correlated with the severity of neuropathy assessed by conventional tests. Future studies in larger groups of patients are required to define the relative sensitivity of this imaging approach in detecting cardiac neuropathy and to determine the clinical significance of these scintigraphic findings in comparison with conventional markers of autonomic innervation.     

Neurocardiogenic syncope in children with a normal heart

OBJECTIVES: The purpose of this study was to review the results of investigation and management of children with syncope and a structurally normal heart. BACKGROUND: Syncope is a common clinical problem and has many etiologies. Autonomic testing and, in particular, the tilt/orthostatic test have helped to positively diagnose neurocardiogenic syncope in a high proportion of such patients. METHODS: Patient case notes and autonomic test charts were reviewed in 162 children aged 1 to 20 years (mean age 12.8 years) with syncope. The autonomic test consisted of orthostatic maneuver, carotid sinus massage, diving reflex, Valsalva maneuver and dose response to intravenous boluses of isoproterenol and phenylephrine. Serum levels of epinephrine and norepinephrine were drawn during the orthostatic test. After confirmation of neurocardiogenic syncope, treatment was begun with fludrocortisone and salt, and beta-adrenergic blocking agents were used as a second line of therapy when indicated. RESULTS: The orthostatic test was positive for neurocardiogenic syncope in 100 patients (62%) and negative in 62 (38%). Patients in the former group were older, were more often female and had a diminished response to carotid sinus massage, a higher Valsalva ratio and a higher supine epinephrine level. Both groups showed an increase in epinephrine and norepinephrine levels at 5 min of standing. In the orthostatic positive group at the time of syncope, norepinephrine levels decreased, whereas epinephrine levels increased. Patients in this group were also more sensitive to the vasodilating effect of isoproterenol but not to its chronotropic effects. Eleven patients had cardioinhibitory syncope (asystole > or = 3 s). Of these, three had pacemaker implantation. Fludrocortisone and salt used in 84 patients in the orthostatic positive group produced resolution of symptoms in 55 patients (65%) and improvement in 14 (17%). Ten patients received beta-blockers, with resolution in four and improvement in four. CONCLUSIONS: Patients with orthostatic test-proved neurocardiogenic syncope show evidence of autonomic dysfunction. They also show beta-adrenergic hypersensitivity. Treatment initiated on the basis of the protocol was associated with amelioration of symptoms in the majority of patients.     

The haemodynamic and antithrombotic effects of intermittent pneumatic calf compression of femoral vein blood flow. A comparison between different pump types

Postural changes in plasma renin activity were studied in three groups of age and duration-matched male diabetics (potent, impotent and with postural hypotension) and in non-diabetic control subjects. Those diabetic subjects with postural hypotension due to automatic neuropathy had no increase in plasma renin activity to the erect posture whereas both the potent and impotent groups had similar plasma renin activity responses to the control subjects. There was a significant inverse correlation between the rise in plasma renin activity on standing and the postural drop in blood pressure (r = 0.476, P less than 0.01) but no correlation with other tests of autonomic reflex function such as the Valsalva manoeuvre and blood pressure response to sustained handgrip. The results suggested that the lesion responsible for the postural hypotension is in the efferent sympathetic pathway. However, neuropathy per se did not wholly explain the decreased postural plasma renin activity response. Diabetic nephropathy, with involvement of cells of juxtaglomerular apparatus, may also be implicated.