G.H. Wieneke

Reduction of Sympathetic Hyperactivity by Enalapril in Patients with Chronic Renal Failure

BACKGROUND Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.

Measurement of the Conductivity of Skull, Temporarily Removed During Epilepsy Surgery

The conductivity of the human skull plays an important role in source localization of brain activity, because it is low as compared to other tissues in the head. The value usually taken for the conductivity of skull is questionable. In a carefully chosen procedure, in which sterility, a stable temperature, and relative humidity were guaranteed, we measured the (lumped, homogeneous) conductivity of the skull in five patients undergoing epilepsy surgery, using an extended four-point method. Twenty-eight current configurations were used, in each of which the potential due to an applied current was measured. A finite difference model, incorporating the geometry of the skull and the electrode locations, derived from CT data, was used to mimic the measurements. The conductivity values found were ranging from 32 mS/m to 80 mS/m, which is much higher than the values reported in other studies. Causes for these higher conductivity values are discussed.

Transcranial pulsed doppler measurements of blood velocity in the middle cerebral artery: Reference values at rest and during hyperventilation in healthy volunteers in relation to age and sex

Transcranial pulsed Doppler analysis of blood velocity in the middle cerebral artery was performed in 120 healthy volunteers (age 20-70 y, 12 male and 12 female subjects per decade), meeting strict selection criteria. The intention was to create normative reference data, both at rest and during hyperventilation, for the assessment of abnormality in patients with cerebral vascular disorders. The measured blood velocity at rest decreased significantly with increasing age. Females up to 50 years of age had significantly higher blood velocity values than males. Blood velocity diminution was induced by means of voluntary hyperventilation, under capnographic control. An age related decline of blood velocity as present at rest was not found during hyperventilation, thus the relative value of hyperventilation induced changes diminished with increasing age. The pCO2 related change in the blood velocity index appeared not to be a constant value, as suggested by previous authors. The blood velocity index was largest in the change from resting condition to 4 kPa pCO2, and smallest in the change 3 kPa pCO2 to 2 kPa pCO2. When examining the blood velocity in the MCA, the age, sex and end-tidal pCO2 pressure have to be taken into account for a correct interpretation of the data obtained.

The need for correct realistic geometry in the inverse EEG problem

For accurate electroencephalogram-based localization of mesial temporal and frontal sources correct modeling of skull shape and thickness is required. In a simulation study in which results for matched sets of computed tomography and magnetic resonance (MR) images are compared, it is found that errors arising from skull models based on smooth and inflated segmented MR images of the cortex are of the order of 1 cm. These errors are comparable to those found when overestimating or underestimating skull conductivity by a factor of two.

The effect of relative humidity of inhaled air onacoustic parameters of voice in normal subjects

The hypothesis that relative humidity (RH) of air exerts an effect on voice has been widely accepted. The aim of this study has been to assess whether this can be demonstrated. Eight healthy subjects inhaled during ten minutes three different air conditions: dry, standard room, and humidified air. After inhalation, the subjects produced repeatedly a sustained /a/ of controlled pitch and loudness, which was analyzed for perturbation and noise-to-harmonic parameters. Perturbation measures increased after inhalation of dry air. No significant differences existed between standard and humidified air. No significant difference in the noise-to-harmonic ratio was found among the three conditions. We conclude that the human voice is very sensitive to decreases in RH of inhaled air, because even after a short provocation with dry air, a significant increase in perturbation measures was found.

Lack of bilateral coherence of mu rhythm.

An investigation has been carried out in 25 normal subjects on quantitative differences of mu rhythm and alpha rhythm parameters. The parameters were frequency, average power over 102 sec and bilateral coherence. It was found that: (1) in the majority of cases the frequencies of the mu rhythms were higher than those of the alpha rhythms; (2) in the majority of subjects the average power was smaller for the mu rhythms for the alpha rhythms; (3) in none of the subjects was bilateral coherence of mu rhythms observed while in the majority the alpha rhythms were obviously bilaterally coherent. It is proposed that the latter difference represents a fundamental difference in the origin of alpha and mu rhythms.

Quantitative EEG changes due to cerebral vasoconstriction. Indomethacin versus hyperventilation-induced reduction in cerebral blood flow in normal subjects

Hyperventilation leads to an increase in slow EEG activity as well as to a decrease in alpha activity. These effects may be considered a result of reduction in cerebral blood flow due to vasoconstriction, but metabolic factors, such as alkalosis and the increased formation of cerebral lactate, may also have to be taken into account. As indomethacin decreases cerebral blood flow it is possible to study cerebral vasoconstriction, without concomitant metabolic alkalosis or cerebral lactate formation. Two parallel groups of 12 healthy male subjects (age 20-25) were studied with quantitative EEG (qEEG) and cerebral blood flow velocity as parameters. In the first group the effect of 100 mg indomethacin was studied. In the parallel group a standardized hyperventilation procedure was performed. In the indomethacin group the blood flow velocity decreased to 60% of the initial value; the qEEG showed a 0.5 Hz slowing of the alpha peak frequency (P less than 0.01) and a decrease in the power of the alpha band without any change in the delta or theta band. In the hyperventilation group the blood flow velocity decreased to 63% of the initial value and the qEEG showed a marked increase in delta and theta activity (P less than 0.01), but a non-significant change in alpha peak frequency. Indomethacin and hyperventilation caused similar degrees of vasoconstriction; however, the increase in qEEG slow wave activity, which was observed only in the hyperventilation group, is apparently related to metabolic rather than haemodynamic factors.

Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis

The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG), and respiration in 16 patients with sporadic ALS and in 12 age‐matched healthy volunteers, both at rest and during sympathoexcitatory stimulation. We measured MSNA by provoking venous pooling during short‐lasting lower body negative pressure (LBNP) and during the cold pressor test (CPT). To assess the vagal (baroreflex) control of heart rate (HR), we measured spontaneous baroreflex sensitivity (BRS). To assess the involvement of the ANS beyond the cardiovascular system, we measured the sympathetic skin response (SSR). The stand‐up test showed that none of the subjects had orthostatic intolerance. In comparison with the control group, the ALS patients had an increased HR and a decreased BRS at rest, and a reduced MSNA response to LBNP. The CPT response was normal and the total MSNA at rest did not differ significantly from that of controls. The latencies of the palmar and plantar SSR were prolonged, and in 3 ALS patients there was no plantar SSR. The results indicate that the sympathetic nervous system shows subtle abnormalities in ALS, predominantly sympathetic overactivity. They also point to the involvement of the preganglionic sympathetic column as the cause of the higher sympathetic activity and the absence of SSR. The higher sympathetic activity is postulated to be due to changes in modulation of the sympathetic system, whereas the absence of the SSR is probably caused by disruption of the reflex pathway.

Estimation of the number of motor units based on macro-EMG

The technique of the macro-EMG was used to estimate the number of motor units in the tibialis anterior muscles of healthy subjects in a wide range of ages, and of patients with myasthenia gravis and patients with amyotrophic lateral sclerosis or spinal muscular atrophy. The results obtained suggest a decrease in the number of motor units in the tibialis anterior muscle with increasing age in normal subjects. In myasthenic patients the motor unit count was within the normal range for their age group. Patients with motor neuron disorders on the average had a very low number of motor units.

Quantitative EEG changes due to hypobaric hypoxia in normal subjects.

A condition of hypobaric hypoxia was created in a low pressure chamber by reducing the atmospheric pressure to 46.5 kPa. Thirty-six subjects were exposed to hypobaric hypoxia during 19 min with a recovery period of 25 min. In 13 subjects the experiment was repeated after 1 week. Four EEG channels, HbSaO2, PeCO2, heart and respiration rate were continuously monitored. Quantitative EEG (qEEG) samples for the derivation P4-O2 were taken in normobaric normoxic (A), hypobaric normoxic (B) and hypobaric hypoxic (C) conditions and mutually compared. Subtraction spectra and standard qEEG parameters were studied, in an attempt to select those which are most reliable to detect hypoxia. Hypobaric normoxia caused no significant qEEG changes. Hypobaric hypoxia resulted in a significant increase in slow activity, a significant decrease in alpha activity and a non-significant decrease in beta activity. Two clusters of non-related standard qEEG parameters were found to be sensitive to hypoxia. The differences between the parameters within each cluster are too small to permit a definite choice of one of them. For the description of qEEG changes due to hypoxia at least one parameter from each cluster has to be taken into account.