Mikael Elam

Increased Cardiac Adrenergic Drive Precedes Generalized Sympathetic Activation in Human Heart Failure

BACKGROUND Previous studies with radiotracer methods have indicated increases in cardiac norepinephrine (NE) and renal NE spillover in patients with severe congestive heart failure (CHF). However, data on the regional sympathetic profile in early stages of CHF are limited. In this study, sympathetic function in the heart, kidneys, and skeletal muscle was evaluated in patients with mild-to-moderate CHF and compared with that in patients with severe CHF and healthy subjects. METHODS AND RESULTS Total body and regional NE spillover from the heart and kidney was assessed with isotope dilution with steady state infusions of [3H]NE. Sympathetic nerve traffic to the skeletal muscle vascular bed (MSA) was recorded intraneurally. Cardiac NE spillover in patients with mild-to-moderate CHF (n = 21) was increased threefold versus that in healthy subjects (n = 12, P < .05), whereas total body and renal NE spillover and MSA did not differ from those in healthy subjects. In the severe CHF group (n = 12), cardiac NE spillover was increased fourfold (P < .05), and total body and renal NE spillover and MSA were high compared with both mild-to-moderate CHF subjects and healthy subjects (P < .05 for both). Fractional extraction of [3H]NE across the heart was reduced by approximately 40% in both CHF groups versus control subjects (P < .05). CONCLUSIONS These results indicate a selective increase in cardiac adrenergic drive (increased amounts of transmitter available at neuroeffector junctions) in patients with mild-to-moderate CHF. This increase appears to precede the augmented sympathetic outflow to the kidneys and skeletal muscle found in advanced CHF.

Two sites for modulation of human sympathetic activity by arterial baroreceptors

1 Peroneal muscle sympathetic nerve activity (MSA), finger blood pressure and cardiac intervals were recorded at rest in 60 healthy subjects, aged 18–71 years. Arterial baroreflex control of MSA was analysed by relating each spontaneous sympathetic burst to the diastolic blood pressure and the cardiac interval of the heart beat during which the burst was generated. The results were expressed as blood pressure/cardiac interval threshold for occurrence of bursts, and as baroreflex sensitivity (i.e. the relationship between diastolic pressure/cardiac interval and burst strength). 2 Significant blood pressure/cardiac interval thresholds were present in all subjects and old subjects had less variability of thresholds than young subjects. In contrast, significant baroreflex sensitivity for diastolic pressure and cardiac interval was present in only 55 and 73 % of the subjects, respectively. There was no age‐related difference in sensitivity. 3 In 40 subjects, two 5 min periods from the same recording were analysed. The number of sympathetic bursts and the threshold for occurrence of bursts were reproducible in all subjects. In contrast, significant baroreflex sensitivity in both periods was present in only 30 % (diastolic pressure) and 40 % (cardiac interval) of the subjects. 4 The results show that the baroreflex mechanisms regulating the occurrence and strength of sympathetic bursts are not identical. We suggest that the modulation occurs at two sites, one which determines whether or not a burst will occur, and another at which the strength of the discharge is determined.

Excess of high frequency electroencephalogram oscillations in boys with autism.

BACKGROUND An elevated excitation/inhibition ratio has been suggested as one mechanism underpinning autism. An imbalance between cortical excitation and inhibition may manifest itself in electroencephalogram (EEG) abnormalities in the high frequency range. The aim of this study was to investigate whether beta and gamma range EEG abnormalities are characteristic for young boys with autism (BWA). METHODS EEG was recorded during sustained visual attention in two independent samples of BWA from Moscow and Gothenburg, aged 3 to 8 years, and in age matched typically developing boys (TDB). High frequency EEG spectral power was analyzed. RESULTS In both samples, BWA demonstrated a pathological increase of gamma (24.4-44.0 Hz) activity at the electrode locations distant from the sources of myogenic artefacts. In both samples, the amount of gamma activity correlated positively with degree of developmental delay in BWA. CONCLUSIONS The excess of high frequency oscillations may reflect imbalance in the excitation-inhibition homeostasis in the cortex. Given the important role of high frequency EEG rhythms for perceptual and cognitive processes, early and probably genetically determined abnormalities in the neuronal mechanisms generating high frequency EEG rhythms may contribute to development of the disorder. Further studies are needed to investigate the specificity of the findings for autism.

Increased sympathetic nerve activity in renovascular hypertension.

BACKGROUND Increased sympathetic nerve activity may contribute to the progression of renovascular hypertension. Because previous results have been inconclusive, we investigated whether renovascular hypertensives show increased total and regional sympathetic nerve activity. METHODS AND RESULTS Sixty-five patients underwent renal angiography and measurements of plasma renin activity and angiotensin II in conjunction with estimation of sympathetic nerve activity by means of radiotracer dilution and intraneural recordings of muscle sympathetic nerve activity (MSNA). Age-matched healthy subjects (n=15) were examined for comparison. Total body norepinephrine (NE) spillover, an index of overall sympathetic nerve activity, was increased by 100% and MSNA by 60% in the hypertensive patients compared with healthy subjects (P<0.01 for both). A subgroup of 24 patients with well-defined renovascular hypertension (cured or improved hypertension after renal angioplasty) showed similar increases in total body NE spillover compared with the group at large. Patients with arterial plasma renin activity and angiotensin II levels above median had higher values for total body NE spillover than patients below median (P<0.01). CONCLUSIONS This study unequivocally demonstrates elevated sympathetic nerve activity in patients with renovascular hypertension. The adrenergic overactivity may contribute to the blood pressure elevation and perhaps also to the high cardiovascular mortality in renovascular hypertension.

Sympathetic nerve activity after acupuncture in humans

&NA; The aim of the present study was to determine if acupuncture stimulation inhibits sympathetic nerve activity in humans. Multiunit efferent postganglionic sympathetic activity was recorded with a tungsten microelectrode inserted in a muscle fascicle of the peroneal nerve. Mean arterial pressure, heart rate and skin blood flow were also monitored. Pain thresholds were measured by electrical tooth pain stimulation. After a 30 min rest, acupuncture needles were inserted bilaterally into the Li 11 and the Li 4 acupuncture points, and manipulated until ‘chi’ cramp‐like sensation was reported. Electrical stimulation (2 Hz, 0.6–0.8 ms duration, maximal tolerated stimulation without discomfort) was delivered for 30 min and the physiological recordings were continued for 90 min after the end of acupuncture. In a placebo control experiment, the same procedure was followed, except that acupuncture needles were inserted subcutaneously and no manipulation or stimulation was given. The stimulator delivered pulses to an unconnected channel, hence, the same audiovisual stimuli were experienced as with acupuncture, and care was taken to ask the same questions about sensations in the placebo and the acupuncture groups. Electroacupuncture produced an increase in pain threshold which was paralleled by a transient increase in muscle sympathetic nerve activity. During acupuncture, there was a small increase in heart rate and mean arterial pressure, but there was no post‐acupuncture hypotension. The placebo control procedure did not change pain threshold or sympathetic nerve traffic. The findings suggest that electroacupuncture produces moderate hypoalgesia in humans paralleled by a significant increase in muscle sympathetic nerve activity.

Sympathetic Muscle Nerve Activity, Peripheral Blood Flows, and Baroreceptor Reflexes in Humans during Propofol Anesthesia and Surgery

BackgroundWith percutaneous recordings of muscle nerve sympathetic activity (MSA), it is possible to study interactions between the autonomic nervous system and anesthetics. This study describes the effects of propofol infusion both before and during microlaryngoscopy. MethodsNine patients participated. MSA was recorded, muscle and skin blood flows were measured. Sodium nitro-prusside-induced decreases in blood pressure were used to quantitate baroreceptor reflex sensitivity. ResultsDuring steady state propofol anesthesia (0.1 mg · kg−1. min−1), “total MSA‘’ (MSA burst area per minute) was 37% (P < 0.05) of awake control value; leg blood flow recorded by strain-gauge plethysmography was 227% (difference not significant); and skin blood flow recorded by laser Doppler flowmetry and finger pulse plethysmography was 300% (P < 0.05) and 376% (P < 0.05) of respective awake control values. During microlaryngoscopy, when mean arterial blood pressure was controlled as close as possible to mean arterial blood pressure in the awake state by individually adjusted propofol infusion rates (average 0.33 mg · kg−1. min−1) MSA was restored to 93% of the activity before anesthesia, and leg blood flow increased further. Both cardiac and muscle sympathetic baroreflex sensitivities were depressed by propofol. During surgery the cardiac baroreflex sensitivity decreased further, whereas the muscle sympathetic baroreflex sensitivity was unchanged. ConclusionsPropofol is a potent inhibitor of sympathetic neuronal activity and decreases the sensitivity of the baroreflex. When used to control the pressor response during surgery, the vasodilatating effect of propofol overrides the neural vasoconstriction induced by surgery, and a further inhibition of the cardiac baroreflex is observed.

Do patients with primary fibromyalgia have an altered muscle sympathetic nerve activity

&NA; This study was performed to test the existing notion that an increased muscle sympathetic nerve discharge is part of the underlying mechanism for the chronic pain syndrome of primary fibromyalgia. Muscle sympathetic nerve activity was recorded in the peroneal nerve in eight patients with primary fibromyalgia and eight age‐matched controls. No difference in baseline sympathetic activity was observed between patients and controls. Furthermore, patients did not show exaggerated sympathetic nerve responses to static handgrip or jaw muscle contractions, postcontraction ischemia or mental stress. Thus the results do not indicate muscle sympathetic nerve overactivity in primary fibromyalgic patients.

Effect of energy-restricted diet on sympathetic muscle nerve activity in obese women.

Twenty obese women aged 45–65 years with borderline hypertension were allocated randomly to either a group with an energy-restricted diet or to a control group. Body weight, blood pressure, urinary sodium, and urinary excretion of norepinephrine and plasma volume were recorded. Resting muscle sympathetic nerve activity was measured in the peroneal nerve by tungsten microelectrodes and expressed as bursts per minute. These measurements were repeated after 3 days of semistarvation and after a body weight reduction of 7% while each patients weight was in a steady state. After 3 days of semistarvation, only body weight was reduced, whereas after the long-term energy intake restriction, there were reductions of body weight (79.9±3.4 versus 74.1±3.4 kg;p <0.001), diastolic blood pressure (93±3 versus 86±4 mm Hg; p=0.01), and muscle sympathetic nerve activity (49±2 versus 42±3 bursts/min; p<0.05). Other variables were unchanged. There were no changes in body weight, blood pressure, or muscle sympathetic nerve activity in the control group. We conclude that body weight decrease in obesity results in a reduction of blood pressure that is at least partially caused by a reduction of sympathetic vasoconstrictor activity.

Microwave-Based Stroke Diagnosis Making Global Prehospital Thrombolytic Treatment Possible

Here, we present two different brain diagnostic devices based on microwave technology and the associated two first proof-of-principle measurements that show that the systems can differentiate hemorrhagic from ischemic stroke in acute stroke patients, as well as differentiate hemorrhagic patients from healthy volunteers. The system was based on microwave scattering measurements with an antenna system worn on the head. Measurement data were analyzed with a machine-learning algorithm that is based on training using data from patients with a known condition. Computer tomography images were used as reference. The detection methodology was evaluated with the leave-one-out validation method combined with a Monte Carlo-based bootstrap step. The clinical motivation for this project is that ischemic stroke patients may receive acute thrombolytic treatment at hospitals, dramatically reducing or abolishing symptoms. A microwave system is suitable for prehospital use, and therefore has the potential to allow significantly earlier diagnosis and treatment than today.

Firing Properties of Single Muscle Vasoconstrictor Neurons in the Sympathoexcitation Associated With Congestive Heart Failure

BACKGROUND Congestive heart failure (CHF) in humans is associated with a marked sympathoexcitation, including an augmented muscle sympathetic nerve activity (MSNA) in intraneural multiunit recordings. In the present study, single-unit recording was used to evaluate whether the firing properties of individual muscle vasoconstrictor neurons can reveal underlying mechanisms for this increase in MSNA. METHODS AND RESULTS Eight patients with CHF (NYHA class II to IV; left ventricular ejection fraction, 29+/-5%, mean+/-SEM) were studied. In standard multiunit recordings, MSNA burst incidence (bursts/100 heartbeats) ranged from 65% to 100% (88+/-5%). Using selective tungsten microelectrodes, we made recordings from 16 single muscle vasoconstrictor axons. Mean unit firing probability (ie, the percentage of cardiac intervals in which a single axon fired) was 54.5+/-5.2% (range, 21 to 89%), and mean firing frequency was 0.98+/-0.22 Hz (0.14 to 3.86 Hz), both of which were higher than seen previously in healthy subjects (P<0.001). Although single neurons occasionally generated multiple spikes per sympathetic burst, such multiple firing was rare and was not different from that seen in healthy subjects. CONCLUSIONS An increased firing frequency of individual vasoconstrictor neurons is one mechanism for the increased number of multiunit MSNA bursts at rest in CHF. The neurons discharge in more diastoles than in healthy subjects (ie, firing probability is increased), but the likelihood of discharging >1 impulse per sympathetic burst is not increased. Despite the intense multiunit activity at rest, the firing characteristics of individual vasoconstrictor axons indicate a remaining capacity for transient increases of MSNA in CHF.