Muscle nerve sympathetic activity in migraine. Lack of abnormality

Microelectrode recordings of muscle nerve sympathetic activity (MSA) in the peroneal nerve were performed in eight patients with common migraine, when they were free of headache and during a spontaneously occurring attack of migraine. During the migraine headache all subjects remained on the same level of MSA as in the control situation and the responses to manoeuvres (slow deep breathing, the Valsalva manoeuvre, sustained hand grip, immersion of one hand into ice water) showed no qualitative or quantitative change. Assessment of vagal influence on the heart showed no change from control situation to attack of migraine. The study provides direct evidence against the existence of any abnormality of MSA during ongoing migraine headache and does not support the assumption that migraine is a generalized vasomotor disorder. No conclusions about possible dysfunction in other parts of the sympathetic nervous system can be drawn.     

Augmented sympathetic neural response to simulated obstructive apnoea in human heart failure

Sleep apnoea in heart failure increases mortality risk, possibly as a result of greater activation of the sympathetic nervous system. In healthy subjects, simulated central apnoeas (holding breath) and obstructive apnoeas (Mueller manoeuvres) increase muscle sympathetic activity equally, primarily through chemoreceptor stimulation. In heart failure, however, Mueller manoeuvres cause greater reductions in blood pressure than breath holds. We hypothesized that in heart failure, the summation of arterial baroreceptor unloading and chemoreceptor stimulation would increase sympathetic activity more during obstructive than central apnoeas. Healthy human subjects and heart failure patients (seven of each) performed 15-s breath holds and 15-s Mueller manoeuvres. Breath holds evoked a progressive increase in muscle sympathetic nerve activity in both groups, but had no effect on blood pressure. In healthy subjects, breath holds and Mueller manoeuvres caused equal peaks in sympathetic activity. In contrast, in heart failure patients, Mueller manoeuvres caused a progressive decrease in blood pressure (P < 0.05) and greater increases in sympathetic activity than breath holds (P < 0.01). In heart failure, simulated obstructive apnoea elicits greater increases in sympathetic activity than simulated central apnoea, due to its additional hypotensive effect. These present findings offer novel insight into the potential role of sleep apnoea in augmenting sympathetic activity and accelerating disease progression in heart failure.     

Sympathetic response to oral carbohydrate administration. Evidence from microelectrode nerve recordings.

Microneurography was used to measure sympathetic outflow in human muscle nerves (MSA) for up to 90 min after the ingestion of 100 g D-glucose, 75.8 g D-xylose, intravenous D-glucose (0.35 g/kg), and 300 ml water. 19 healthy subjects were examined using a microelectrode positioned in the right peroneal nerve. MSA increased from 21 +/- 0.9 bursts/min at rest to 36.9 +/- 4.3 bursts/min 30 min after ingestion of D-glucose and from 18.9 +/- 2.9 to 26.3 +/- 3.4 bursts/min 30 min after D-xylose. The increase in MSA was already significant by 15 min. MSA had not returned to the basal level after 90 min. Neither intravenous D-glucose nor water intake enhanced MSA. MSA increased in parallel with plasma norepinephrine, and a significant correlation (r = 0.55; P less than 0.001) was observed between the plasma insulin concentration and MSA after D-glucose ingestion. In three subjects the outflow of sympathetic nerve activity to the skin was examined after oral D-glucose and no change was observed, emphasizing the differentiated nature of the sympathetic nerve response to carbohydrate. Multiple factors such as insulin alone, hemodynamic adjustment to splanchnic vasodilation, and gastrointestinal distension are probably involved in the increased muscle nerve sympathetic outflow after carbohydrate ingestion.     

Influence of gender on the sympathetic neural adjustments to alterations in systemic oxygen levels in humans

The purpose of this investigation was to determine whether gender influences the muscle sympathetic nerve activity (MSA) and systemic cardiovascular adjustments to alterations in systemic oxygen levels. To accomplish this, we performed direct (intraneural) measurements of muscle sympathetic nerve activity in 11 male and seven female young healthy adults during room air breathing, moderate isocapnic hypoxaemia and hyperoxaemia. During hypoxaemia, arterial oxygen saturation declined similarly in men and women. The magnitudes of the peak increases in MSA and stimulus–response `gain' were not different between groups. However, the women had a shorter latency of response (P<0·05). Women also demonstrated a greater increase in heart rate and a modest elevation in diastolic blood pressure, whereas the ventilatory responses were identical in the two groups. During normoxic recovery, MSA returned to baseline more quickly in women than in men (P<0·05). During hyperoxaemia, muscle sympathetic nerve activity decreased only in the men (P<0·05). Heart rate decreased slightly (P<0·05) in both men and women, whereas blood pressure and minute ventilation were unchanged from normoxic control levels. Our findings fail to support an effect of gender on the peak muscle sympathetic nerve activity response to moderate isocapnic hypoxaemia in healthy young adult humans, although women demonstrate a shorter latency for sympathoexcitation and recovery under these conditions. In response to hyperoxaemia, women fail to demonstrate the sympathoinhibition consistently observed in men, possibly because of the low resting levels of MSA characteristic of young adult women. Thus, gender appears to contribute to the interindividual variability in sympathetic and cardiovascular responses to alterations in systemic oxygen levels.     

Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy

OBJECTIVE: This study examines whether autonomic nerve autoantibodies (ANabs) are associated with development of autonomic neuropathy using a prospective study design. RESEARCH DESIGN AND METHODS: A group of type 1 diabetic patients were followed prospectively with regard to autonomic nerve function on four occasions. At the third examination, 41 patients were tested for ANabs (complement-fixing autoantibodies to the sympathetic ganglion, vagus nerve, and adrenal medulla), and the results were related to cardiac autonomic nerve function (heart rate variation during deep breathing [expiration/inspiration ratio] and heart-rate reaction to tilt [acceleration and brake index]) and to peripheral sympathetic nerve function (vasoconstriction after indirect cooling [vasoconstriction index]). RESULTS: ANabs were detected in 23 of 41 (56%) patients at the third examination. Compared with patients without ANabs (ANabs-), patients with ANabs (ANabs+) showed significantly higher frequencies of at least one abnormal cardiac autonomic nerve function test at the third examination (17 of 23 [74%] vs. 7 of 18 [39%]; P = 0.03) and fourth examination (15 of 21 [71%] vs. 4 of 16 [25%]; P < 0.01). In contrast, there was no similar difference at the first or second examination. The relative risk for ANabs(+) patients to develop cardiac autonomic neuropathy at follow-up was 7.5 (95% CI 1.72-32.80). The vasoconstriction index was more abnormal in ANabs+ than in ANabs- patients at the fourth examination (median 1.40 [interquartile range 1.58] vs. 0.35 [2.05]; P = 0.01). CONCLUSIONS: ANabs were associated with future development of cardiac and peripheral autonomic neuropathy in diabetic patients, implying an etiological relationship between nervous tissue autoimmunity and these diabetes complications.     

Impairment of sympathetic activation during static exercise in patients with muscle phosphorylase deficiency (McArdle''s disease).

Static exercise in normal humans causes reflex increases in muscle sympathetic nerve activity (MSNA) that are closely coupled to the contraction-induced decrease in muscle cell pH, an index of glycogen degradation and glycolytic flux. To determine if sympathetic activation is attenuated when muscle glycogenolysis is blocked due to myophosphorylase deficiency (McArdle's disease), an inborn enzymatic defect localized to skeletal muscle, we now have performed microelectrode recordings of MSNA in four patients with McArdle's disease during static handgrip contraction. A level of static handgrip that more than doubled MSNA in normal humans had no effect on MSNA and caused an attenuated rise in blood pressure in the patients with myophosphorylase deficiency. In contrast, two nonexercise sympathetic stimuli, Valsalva's maneuver and cold pressor stimulation, evoked comparably large increases in MSNA in patients and normals. The principal new conclusion is that defective glycogen degradation in human skeletal muscle is associated with a specific reflex impairment in sympathetic activation during static exercise.     

Psychophysical observations on patients with neuropathic pain relieved by a sympathetic block

Patients with sympathetically maintained pain (SMP) were tested with noxious heat pulses, innocuous mechanical stimuli, and transcutaneous electrical nerve stimulation before and during local anesthetic sympathetic blocks that relieved their pain. The perceived intensity of the pain evoked by these stimuli was measured by the patients' responses on a visual analog scale and compared to the responses obtained when the same stimuli were applied to contralateral normal skin. In 5 of 7 patients tested, graded noxious heat stimuli (43-51 degrees C) applied to painful skin resulted in heat-pain intensity ratings that were essentially identical to the responses obtained when the same stimuli were applied to the normal side. Of the remaining two patients, one was clearly hypoalgesic for heat-pain and the other was probably hyperalgesic. The normal and subnormal heat-evoked responses obtained from abnormal skin were unchanged during completely successful sympathetic blocks. Trains of noxious heat pulses (52 degrees C) evoked summation of the second pain sensation in each of the 4 patients tested. This summation effect was normal and unaffected by a sympathetic block. Four of the patients had allodynia evoked by mechanical stimulation. In each of the 3 allodynia cases tested, transcutaneous nerve stimulation at an intensity that was at threshold for detection evoked burning pain and a coexistent sensation of tingle, indicating that both sensations were due to the activation of A beta axons. Patients without touch-evoked pain reported that electrical stimuli at threshold for detection produced only the sensation of tingle. The pains evoked by touch and by threshold-strength nerve stimulation were eliminated during sympathetic block. In patients with allodynia, trains of gentle mechanical stimuli and trains of threshold-strength electrical nerve stimuli produced summation of the intensity of the burning pain sensation when the stimuli were presented at 0.3 Hz. These results add to a growing body of evidence indicating that the touch-evoked pain of some patients is due to abnormal central activity evoked by input from A beta low-threshold mechanoreceptors. The coexistence of A beta-evoked pain with normal heat-evoked pain and normal heat-pain summation suggests that the central abnormality cannot be a simple hypersensitivity of wide-dynamic-range neurons. The effect of sympathetic blockade on A beta-evoked pain and its summation suggests that the crucial sympathetic interaction may take place centrally. The results show that there is considerable heterogeneity of sensory abnormalities among patients with SMP.(ABSTRACT TRUNCATED AT 400 WORDS)     

Autonomic Nervous System-Controlled Cardiac Pacing: A Comparison Between Intracardiac Impedance Signal and Muscle Sympathetic Nerve Activity

BINGGELI, C., et al. : Autonomic Nervous System‐Controlled Cardiac Pacing: A Comparison Between Intracardiac Impedance Signal and and Muscle Sympathetic Nerve Activity. A recently introduced rate responsive cardiac pacing system is based on information derived from the intracardiac impedance signal containing information on the inotropic state of the ventricle. This study compared the inotropic state index (ISI) with muscle sympathetic activity (MSA), both being modulated by the autonomic nervous system. Nine patients (66 ± 3 years, mean ± SEM ) with Inos2DR pacemakers were included. Each patient was studied at rest and during cold pressor test (CPT). Microneurography of the peroneal nerve was performed to measure MSA continuously, which was digitally stored along with continuous surface ECG and blood pressure. The intracardiac impedance signal was transmitted by the pacemaker and stored simultaneously. Linear correlation between ISI and MSA was calculated for the period of the CPT. During CPT, mean systolic blood pressure increased from 122 ± 4 to 149 ± 6 mmHg (P < 0.0001), diastolic blood pressure increased from 74 ± 8 to 86 ± 4 mmHg (P = 0.02 ), and intrinsic heart rate increased from 69 ± 7 to 75 ± 7 beats/mill (P = 0.019 ). ISI increased by 21 ± 7% (P = 0.018 ), MSA by 26 ± 6% (P = 0.004 ). ISI and MSA were positively correlated during the CPT in eight of nine patients (R2 = 0.86–0.99, P < 0.0001 ). Negative correlation was found in one patient (R2 = 0.94 ). This study demonstrates parallel increases of the ISI and MSA during CPT. ISI and MSA showed a close linear relationship during provoked changes of sympathetic activity. These results provide further evidence that the sympathetic nervous system is responsible for the observed ISI changes.     

Dissection of carotid sinus hypersensitivity: the timing of vagal and vasodepressor effects and the effect of body position

We assessed the timing of vagal and sympathetic factors that mediate hypotension during CSM (carotid sinus massage) in patients with carotid sinus hypersensitivity. We hypothesized that a fall in cardiac output would precede vasodepression, and that vasodepression would be exaggerated by head-up tilt. We performed pulse contour analyses on blood pressure recordings during CSM in syncope patients during supine rest and head-up tilt. In a subset we simultaneously recorded muscle sympathetic nerve activity supine. During supine rest, systolic blood pressure decreased from 150±7 to 107±7 mmHg (P<0.001) and heart rate from 64±2 to 39±3 beats/min (P<0.01). Cardiac output decreased with heart rate to nadir (66±6% of baseline), 3.1±0.4?s after onset of bradycardia. In contrast, total peripheral resistance reached nadir (77±3% of baseline) after 11±1?s. During head-up-tilt, systolic blood pressure fell from 149±10 to 90±11 mmHg and heart rate decreased from 73±4 to 60±7 beats/min. Compared with supine rest, cardiac output nadir was lower (60±8 compared with 83±4%, P<0.05), whereas total peripheral resistance nadir was similar (81±6 compared with 80±3%). The time to nadir from the onset of bradycardia did not differ from supine rest. At the onset of bradycardia there was an immediate withdrawal of muscle-sympathetic nerve activity while total peripheral resistance decay occurred much later (6-8?s). The haemodynamic changes following CSM have a distinct temporal pattern that is characterized by an initial fall in cardiac output (driven by heart rate), followed by a later fall in total peripheral resistance, even though sympathetic withdrawal is immediate. This pattern is independent of body position.     

The acute effects of amputation on peripheral trigeminal afferents in Gallus gallus var domesticus

In 10 adult Brown Leghorn hens electrical recordings were made from sensory afferent fibres in dissected nerve filaments of the trigeminal nerve innervating the lower beak. The lower beak was subjected to partial amputation using a heated blade and recordings were taken before, during and after amputation. Amputation produced a massive injury discharge which lasted from 2 to 48 sec (mean 15 sec). There were still active units present in the filament with receptive fields proximal to the site of cautery and for 90 min after amputation no abnormal activity was recorded in these units and no abnormal spontaneously active units were observed. From 90 to 270 min post-amputation single units were dissected and of the 93 rapidly adapting mechanoreceptors, 78 slowly adapting mechanoreceptors, 23 mechanothermal (polymodal) nociceptors, 7 cold and 3 warm thermoreceptors none showed any abnormal pattern of response to cutaneous stimulation. This absence of change in the peripheral neural input following amputation could provide a mechanism to explain the absence of observed pain immediately following partial beak amputation.     

Forearm vasoconstrictor response in uncomplicated type 1 diabetes mellitus

BACKGROUND: According to the 'haemodynamic hypothesis', increased tissue perfusion predisposes to microangiopathy in diabetic patients. We hypothesized that the typical haemodynamic changes underlying the increased tissue perfusion can be explained by a decreased sympathetic nerve activity caused by chronic hyperglycaemia. In this study we investigated sympathetic activity in patients with uncomplicated type 1 diabetes mellitus (DM). MATERIALS AND METHODS: In 15 DM patients (DM duration 6.3 +/- 3.8 year; HbA1c 7.9 +/- 1.3%) and 16 age- and sex-matched healthy volunteers (Control), sympathetic nervous system activity was measured at rest (baseline) and during sympathoneural stimulation (lower body negative pressure (LBNP)) by means of interstitial and plasma noradrenaline (NA) sampling and power spectral analysis. Muscle sympathetic nerve activity (MSNA) was measured before (baseline) and during a cold pressure test. Forearm blood flow was measured during forearm vascular alpha- and beta-adrenergic receptor blockade. RESULTS: At baseline, forearm vascular resistance (FVR), plasma NA concentrations, MSNA and heart rate variability were similar in both groups. LBNP-induced vasoconstriction was significantly attenuated in the DM group compared with the Control group (DeltaFVR: 12 +/- 4 vs. 19 +/- 3 arbitrary units, P < 0.05). The responses of plasma NA and heart rate variability did not differ. CONCLUSIONS: Baseline FVR and sympathetic nerve activity are normal in patients with uncomplicated type 1 diabetes. However, the forearm vasoconstrictor response to sympathetic stimulation is attenuated, which cannot be attributed to an impaired sympathetic responsiveness.     

Increased excitability and spontaneous activity of rat sensory neurons following in vitro stimulation of sympathetic fiber sprouts in the isolated dorsal root ganglion

Many chronic pain conditions including complex regional pain syndrome are exacerbated by sympathetic activity. In animal models, sympathetic fibers sprout into the dorsal root ganglia (DRG) after peripheral nerve injury, forming abnormal connections with sensory neurons. However, functional studies of sympathetic-sensory connections have been limited largely to in vivo studies. This study describes a new method for studying sympathetic-sensory connections in an isolated whole DRG preparation in the rat spinal nerve ligation (SNL) model. Three days after ligation of the ventral ramus of the spinal nerve (SNL), sympathetic fibers sprouting into the DRG were observed to originate largely in the intact dorsal ramus of the spinal nerve, which at the lumbar level is a small branch of the spinal nerve separating from the ventral ramus near the intervertebral foramen. In whole DRG isolated 3 days after SNL, microelectrode recordings of sensory neurons showed that repeated stimulation of the dorsal ramus enhanced spontaneous activity in large and medium diameter neurons and reduced rheobase in large neurons. These effects, which were slow and long lasting, were attributed to stimulation of the sympathetic sprouts because: stimulation had no effect in uninjured DRG; and effects could be reduced or eliminated by a “cocktail” of antagonists of norepinephrine and ATP receptors, by pretreatment with the sympathetic release blocker bretylium, or by pre-cutting the grey ramus through which sympathetic fibers coursed to the ligated DRG. The latter treatment, a relatively minimal form of sympathectomy, was also highly effective in reducing mechanical pain ipsilateral to the SNL.     

Electromyographic tools to assess hemidiaphragm paralysis

Non‐invasive measurements of the phrenic nerve conduction time (CT) and diaphragmatic electromyographic response to voluntary inspiratory efforts may help to document an abnormal diaphragmatic function in the presence of hemidiaphragm elevation on chest radiographs. Twenty‐one patients were addressed for the diagnosis of abnormal placement and motion of the right (13) or left (8) cupola on chest radiographs. CT was measured by recording the diaphragmatic M‐wave evoked by electrical transcutaneous phrenic nerve stimulation. The integrated diaphragmatic surface electromyogram (Edi) was recorded during sniff and Müller manoeuvres. Four patients were followed up during the next 8–16 months. Among the twenty‐one patients, five (24%) had a lengthened or absent CT. A right‐to‐left peak Edi asymmetry was measured in fourteen (67%), including those having abnormal CT. Agreement between side‐related radiographic abnormalities and Edi asymmetry was high in the cases of an elevation of the right cupola (12/13, 92%) but poor when the left cupola was suspected (1/8, 13%). Long‐term follow‐up of Edi asymmetry showed a partial or total recovery. Thus, the combination of measurements of phrenic nerve CT and Edi recordings during voluntary inspiratory efforts confirmed 67% of the radiographic suspicion of diaphragmatic dysfunction.     

The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans

The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemoreceptors to sympatho-excitation by adenosine. Muscle sympathetic nerve activity was recorded during adenosine infusion (140 microg.kg(-1).min(-1) for 5 min) in five patients lacking carotid chemoreceptors after bilateral carotid body tumour resection (one male and four female, mean age 51 +/- 11 years) and in six healthy controls (two male and four female, mean age 50 +/- 7 years). Sympathetic responses to sodium nitroprusside injections were assessed to measure baroreceptor-mediated sympathetic activation. In response to adenosine, controls showed no change in blood pressure, an increase in heart rate (+48.2 +/- 13.2%; P<0.003) and an increase in sympathetic nerve activity (+195 +/- 103%; P<0.022). In contrast, patients showed a decrease in blood pressure (-14.6 +/- 4.9/-17.6 +/- 6.0%; P<0.05), an increase in heart rate (+25.3 +/- 8.4%; P<0.032) and no significant change in sympathetic activity. Adenosine-induced hypotension in individual patients elicited less sympathetic activation than equihypotensive sodium nitroprusside injections. In humans lacking carotid chemoreceptors, adenosine infusion elicits hypotension due to the absence of significant sympatho-excitation. Chemoreceptor activation is essential for counterbalancing the direct vasodilation by adenosine. In addition, blunting of the baroreflex sympathetic response to adenosine-induced hypotension may indicate a direct sympatho-inhibitory effect of adenosine.     

Thermographic observations on rats with experimental neuropathic pain.

Infrared thermographic images were obtained from the plantar hind paws of rats with an experimental nerve injury that produces signs of neuropathic pain. Thermograms confirmed that the experimental neuropathy produces signs resembling those of patients with neuropathic pain. The hind paws on the nerve-damaged side were abnormally hot, abnormally cold, or apparently normal 8-16 days post injury, a variability that is seen clinically in neuropathic pain patients. Abnormally cold hind paws became warm as soon as the injured sciatic nerve was transected, indicating that the underlying vasoconstriction was mediated by neural impulse activity. Xylazine (Rompun), a sympatho-inhibitory alpha 2-adrenoceptor agonist that normally increases cutaneous temperature, caused the hind paw on the control side to warm, as anticipated, while causing paradoxical cooling of abnormally hot hind paws, and even of 'normal temperature' paws on the nerve-injured side. These findings shed light on possible mechanisms underlying abnormal deviations of skin temperature as a symptom of nerve injury. The findings also attest to the usefulness of the experimental animal model of neuropathic pain and of the thermographic method.     

Differential control of heart rate and sympathetic nerve activity during dynamic exercise. Insight from intraneural recordings in humans.

We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in the leg during arm exercise in conscious humans to test the concept that central command and muscle afferent reflexes produce mass sympathetic discharge at the onset of exercise. Nonischemic rhythmic handgrip and mild arm cycling produced graded increases in heart rate and arterial pressure but did not increase MSNA, whereas ischemic handgrip and moderate arm cycling dramatically increased MSNA. There was a slow onset and offset of the MSNA responses, which suggested metaboreceptor mediation. When forearm ischemia was continued after ischemic handgrip, MSNA remained elevated (muscle chemoreflex stimulation) but heart rate returned to control (elimination of central command). The major new conclusions are that: the onset of dynamic exercise does not produce mass, uniform sympathetic discharge in humans, and muscle chemoreflexes and central command appear to produce differential effects on sympathetic and parasympathetic responses.     

Raynaud's phenomenon: blood supply to fingers during indirect cooling,evaluated by laser Doppler flowmetry

Summary. The effect of indirect cooling on finger-tip blood flow patterns were recorded in 31 patients suffering from Raynaud's phenomenon. Fifteen were suffering from generalized scleroderma with acrosclerosis (GS), and 16 from primary Raynaud's phenomenon (PR), and were compared to 13 healthy controls without cold sensitivity. Finger blood flow (FBF) was monitored by a laser Doppler flowmeter. Resting blood flow values were significantly lower in patients compared to controls. After two min of body cooling no difference could be observed in relative flow decrease between patients and controls or between PR and GS, but after 10 min of body cooling, relative flow decrease tended to be more pronounced in GS than in PR. Only in GS was the zero flow situation observed. During the resting condition, skin vessel vasomotion was observed as rhythmical variations in the blood flow of 5–10 cycles per minute. These seemed to be preserved in patients and in chronically sympathectomized patients, and could not be abolished by nerve blockade of the finger. The influence from sympathetic vasomotor fibres on FBF could be observed during cooling as irregular coarse flow fluctuations. This was observed in both patients and controls but not in the chronically sympathectomized patients and disappeared after nerve blockade of the finger. Finger temperature was measured simultaneously during body cooling, but significant changes were observed only in normals and PR. The conclusions were that (1) during body cooling, flow decrease in GS tends to be more pronounced than in PR, and only in GS could the zero flow situation be elicited; (2) influence on finger blood vessels from the sympathetic nervous system could be observed in both patients and control persons; (3) GS and PR patients seem to have preserved local vasomotion in cutaneous microvessels; (4) finger-tip temperature in sclerotic skin is an imprecise blood flow indicator.     

Impaired rat sciatic nerve sodium-potassium adenosine triphosphatase in acute streptozocin diabetes and its correction by dietary myo-inositol supplementation.

Nerve conduction impairment in experimental diabetes has been empirically but not mechanistically linked to altered nerve myo-inositol metabolism. The phospholipid-dependent membrane-bound sodium-potassium ATPase provides a potential mechanism to relate defects in diabetic peripheral nerve myo-inositol-phospholipid metabolism, impulse conduction, and energy utilization. Therefore, the effect of streptozocin-induced diabetes mellitus and dietary myo-inositol supplementation on rat sciatic nerve sodium-potassium ATPase was studied. ATPase activity was measured enzymatically in sciatic nerve homogenates from 4-wk streptozocin diabetic rats and age-matched controls either fed a standard or 1% myo-inositol supplemented diet. The sodium-potassium ATPase components were assessed by ouabain inhibition or the omission of sodium and potassium ions. Diabetes reduced the composite ATPase activity recovered in crude homogenates of sciatic nerve. The 40% reduction in the sodium-potassium ATPase was selectively prevented by 1% myo-inositol supplementation (which preserved normal nerve conduction). Thus, in diabetic peripheral nerve, abnormal myo-inositol metabolism is associated with abnormal sodium-potassium ATPase activity. The mechanism of the effect of dietary myo-inositol to correct diabetic nerve conduction may be through changes in a sodium-potassium ATPase, possibly via changes in myo-inositol-containing phospholipids.     

Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans.

Euglycemic hyperinsulinemia evokes both sympathetic activation and vasodilation in skeletal muscle, but the mechanism remains unknown. To determine whether insulin per se or insulin-induced stimulation of carbohydrate metabolism is the main excitatory stimulus, we performed, in six healthy lean subjects, simultaneous microneurographic recordings of muscle sympathetic nerve activity, plethysmographic measurements of calf blood flow, and calorimetric determinations of carbohydrate oxidation rate. Measurements were made during 2 h of: (a) insulin/glucose infusion (hyperinsulinemic [6 pmol/kg per min] euglycemic clamp), (b) exogenous glucose infusion at a rate matched to that attained during protocol a, and (c) exogenous fructose infusion at the same rate as for glucose infusion in protocol b. For a comparable rise in carbohydrate oxidation, insulin/glucose infusion that resulted in twofold greater increases in plasma insulin concentrations than did glucose infusion alone, evoked twofold greater increases in both muscle sympathetic nerve activity and calf blood flow. Fructose infusion, which increased carbohydrate oxidation comparably, but had only a minor effect on insulinemia, did not stimulate either muscle sympathetic nerve activity or calf blood flow. These observations suggest that in humans hyperinsulinemia per se, rather than insulin-induced stimulation of carbohydrate metabolism, is the main mechanism that triggers both sympathetic activation and vasodilation in skeletal muscle.     

Local and central orthostatic sympathetic reflexes in Raynaud's phenomenon

Finger and hand blood flow was measured by 133xenon washout technique during orthostatic manoeuvres in patients with primary Raynaud's phenomenon (PR), Raynaud's phenomenon secondary to generalized scleroderma (GS) and in healthy, cold-tolerant controls. When supine, finger and hand washout rates in PR were significantly elevated over that of controls and GS. A significantly decreased response to a 40-cm lowering of the hand (local vasoconstrictor response) was observed in PR and was found to be normal in GS. During head-up tilting to 45 degrees (central sympathetic stimulation), all three groups showed parallel responses. We conclude that no increased responses on local or central orthostatic sympathetic reflexes were seen in patients with Raynaud's phenomena. A generally increased sympathetic activity as pathophysiological background for the vasospastic attacks is not likely. However, the increased finger 'blood flow' observed in patients with primary Raynaud's phenomenon in the resting condition, which we interpret as a 'hyperaemic' state, might have influenced the orthostatic sympathetic responses.