Increase In Sympathetic Outflow Research Articles

Angina with normal coronary arteries: diagnosis, pathophysiology and treatment.

Approximately 20% of patients undergoing diagnostic coronary arteriography for acute or chronic cardiac ischaemia have angiographically normal coronary arteries. The mechanism behind this phenomenon is likely to be the result of a combination of functional or anatomical abnormalities in the coronary microcirculation, a metabolic disorder which affects the handling of energy substrates by the heart, insulin resistance and a neurological component affecting pain perception. Indeed, it has been demonstrated that these patients often exhibit an increase in sympathetic outflow to the cardiovascular system, which might account for the reduction in coronary flow reserve, changes in metabolic utilization and development of insulin resistance that are seen in some of these patients. Therapeutically, beta-blockers appear to be most effective in controlling the symptoms associated with this condition, although those calcium antagonists which do not affect the neurohormonal system may be of some utility in patients with primary microvascular angina, in which microvascular spasm is operating or in whom excessive constriction of the distal component of the coronary circulation limits the vasodilatory reserve.

Acute and chronic cardiovascular responses to sleep disordered breathing.

Episodes of sleep disordered breathing are surprisingly common in asymptomatic, middle-aged individuals. The majority of these events are hypopneas, rather than apneas. Even though these events cause rather modest decreases in arterial oxygen saturation, they evoke substantial increases in arterial pressure. In this population, mild to moderate sleep disordered breathing is associated with elevated daytime blood pressure. The mechanisms responsible for the acute and chronic cardiovascular effects of sleep disordered breathing are incompletely understood. Chemoreflex mechanisms appear to be more important than intrathoracic pressure changes in causing the acute elevation in arterial pressure that occurs after obstructive sleep apnea. Arousal from sleep may contribute to this pressor response, either in an additive or synergistic manner. Relatively brief exposure to combined hypoxia and hypercapnia during wakefulness can produce an increase in sympathetic outflow to skeletal muscle that persists after return to room air breathing. This lingering post-asphyxic effect on sympathetic outflow may be the basis of chronically elevated sympathetic nervous system activity which accompanies sleep apnea syndrome and may contribute to sustained hypertension in these individuals.

Cardiac sympathetic afferent reflex in dogs with congestive heart failure.

It is well accepted that sympathetic tone is elevated in chronic heart failure (HF) and that the cardiac sympathetic afferent reflex is a sympathoexcitatory reflex. There have been no studies designed to examine the role of this reflex in control of sympathetic outflow in the HF state. In this study we tested the hypothesis that cardiac sympathetic afferent reflexes are enhanced in HF and are, therefore, capable of contributing to the increase in sympathetic outflow in this disease state. Ventricular pacing was carried out in 14 dogs until signs of HF were evident. Fourteen sham dogs served as controls. At the time of the acute experiment the dogs were anesthetized with alpha-chloralose. The hemodynamic [arterial pressure and heart rate (HR)] and renal sympathetic nerve activity (RSNA) responses to left ventricular epicardial application of two doses of bradykinin (BK) and capsaicin (Cap) were determined in the sinoaortic-denervated and vagotomized state. The MAP, RSNA, and HR responses to BK were greater in the HF group compared with the sham group. The RSNA response to BK (50 micrograms) in the HF group was significantly increased (34.0 +/- 5.9 vs. 11.5 +/- 4.2%, P < 0.05). The MAP, RSNA, and HR responses to Cap in the HF group were similar to the responses to BK. The RSNA response to Cap in the HF group was significantly increased (29.8 +/- 11.3 vs. 13.8 +/- 2.3% for 10 micrograms, P < 0.05 and 46.5 +/- 10.7 vs. 18.7 +/- 3.1% for 100 micrograms, P < 0.05). The cyclooxygenase blocker indomethacin (5 mg/kg i.v.) attenuated the reflex responses to BK in the HF group. These data suggest that the enhanced cardiac sympathetic afferent reflex to epicardial BK in HF appears to be mediated by altered levels of prostaglandin synthesis. Blockade of cardiac sympathetic afferents with topical lidocaine reduced baseline of RSNA significantly more in the HF state than in the normal state (-24.2 +/- 3.6 vs. -4.3 +/- 4.5%, P < 0.05). We conclude from these data that the cardiac sympathetic afferent reflex is sensitized in the HF state and speculate that this enhanced cardiac sympathetic afferent reflex may contribute to the sustained higher sympathetic tone in chronic HF.

Regional Sympathetic Nervous Activation after a Large Meal in Humans

1. To investigate the link between post-prandial thermogenesis and sympathetic nervous activation we have studied the effects of a single large meal on regional sympathetic nervous activity in healthy, lean subjects. 2. In nine male subjects, noradrenaline spillover was measured from the heart, kidney and liver using isotope dilution, both while fasting and after consumption of a high-energy liquid meal of composition 53% carbohydrate, 32% fat and 15% protein (energy value 2.64-3.51 MJ). Regional oxygen consumption, whole-body oxygen consumption and, in a subset of subjects, muscle sympathetic nerve firing (microneurography) were also measured. 3. Both whole-body oxygen consumption (P < 0.03) and total body spillover of noradrenaline (P < 0.01) rose after the meal, with peak increases of 24% and 56% respectively. Spillover of noradrenaline from the heart was unchanged, that from the hepatosplanchnic circulation increased marginally (0.377 nmol/min to 0.480 nmol/min, P = 0.09), while renal noradrenaline spillover more than doubled (0.440 nmol/min to 0.937 nmol/min, P < 0.05). Skeletal muscle sympathetic nerve activity (peroneal nerve) increased from 7.7 bursts/min at rest to peak at 17.9 bursts/min 60 min after the meal in the three subjects in whom stable recordings were obtained. 4. The meal increased oxygen consumption in the kidneys and liver significantly, from 11.5 +/- 1.6 ml/min to 14.5 +/- 1.1 ml/min and from 46 +/- 7 ml/min to 57 +/- 6 ml/min respectively (P < 0.05), but not in the heart. 5. Consumption of a large meal produces a substantial and relatively selective increase in sympathetic outflow to the kidneys and skeletal muscle. While resting regional oxygen consumptions and noradrenaline spillovers were related, the changes that occurred in each were unrelated, so that no direct relationship could be demonstrated between postprandial thermogenesis and sympathetic activity.

Attenuation of the reflex responses to muscle contraction by the coadministration of antagonists to substance P and somatostatin into the dorsal horn

The aim was to determine if the coadministration of antagonists to substance P and somatostatin into the L7 dorsal horn blunts the reflex cardiovascular responses to static contraction to a greater extent than each antagonist alone. The possibility that this attenuation is mediated by blunting the contraction evoked increases in sympathetic outflow was also tested. Using alpha chloralose anaesthetised cats (n = 8), static contraction and stretch of the triceps surae muscle were performed before and after microinjecting (1 microliter) 250 ng of the substance P antagonist, D-Pro2-D-Phe7-D-Trp9-substance P, and the somatostatin antagonist, cyclo(7-amino-heptanoyl-phenylalanyl-D-tryptophyl-lysyl-threonyl-[ benzyl]). The muscle was contracted by electrically stimulating the peripheral end of the cut L7 ventral root. Before injecting the antagonists, static muscle contraction increased mean arterial blood pressure by 40(SEM 6) mm Hg, heart rate by 13(2) beats.min-1, and renal sympathetic nerve activity (RSNA) by 41(7)%. These changes were blunted by the antagonists since the increases in blood pressure, heart rate, and RSNA were reduced to 21(3) mm Hg, 8(1) beats.min-1, and 23(5)%, respectively. In contrast, antagonist administration did not affect the pressor [33(5) v 31(5) mm Hg], heart rate [9(2) v 10(2) beats.min-1], or RSNA [23(4)% v 25(5)%] responses to muscle stretch. Microinjection of 2% lignocaine into the dorsal horn virtually abolished the reflex changes elicited by muscle stretch. The release of substance P and somatostatin in the spinal cord plays a role in mediating the cardiovascular changes caused by static contraction, but the release of other neurotransmitters/neuromodulators is also involved. The attenuation produced by these antagonists is mediated, at least in part, by reducing sympathetic outflow.

Cardiac autonomic control and muscle sympathetic nerve activity during dynamic exercise.

We compared sympathetic outflow to the heart and skeletal muscle (MSNA) during dynamic exercise to test whether their mechanisms of control were the same. The sympathetic component to the heart was evaluated by heart rate variability analysis of the power spectrum. MSNA was recorded from the median nerve during graded leg cycling lasting 16 min at loads of 20, 40, 60, and 75% of maximal oxygen uptake (VO2max) in the sitting position. The R-R interval and heart rate variability as well as low (Pl) and high (Ph) power frequency decreased with increasing exercise intensity while no significant change was observed in total power (Pt). The indicator of the cardiac sympathetic component, Pl/Ph, and the parasympathetic component, Ph/Pt, increased and decreased relative to exercise intensities, respectively. MSNA, represented as burst frequency (BF), was suppressed by 21.4% at 20% VO2max, and thereafter BF increased with the exercise intensity by 23.5% and by 79.4% at 60 and 75% VO2max, respectively, compared to the baseline level. There was a close positive and negative correlation between changes in BF and those in Pl/Ph (r = 0.593, p < 0.002) and Ph/Pt (r = -0.681, p < 0.0001), respectively. These results indicate acceleration of the sympathetic component of heart rate and increase in sympathetic outflow to the skeletal muscle during graded exercise. However, the exact control mechanisms of these sympathetic responses to graded exercise in two different organs remain unclear.

Increase of sympathetic discharge to skeletal muscle but not to skin during mild lower body negative pressure in humans.

1. Haemodynamic studies in humans have concluded that the cutaneous circulation is regulated by cardiopulmonary baroreceptors. In contrast, neurophysiological studies have indicated that skin sympathetic outflow, unlike muscle sympathetic outflow, is unaffected by perturbations in baroreceptor activity. 2. Thus, in an attempt to resolve this discrepancy, both muscle and skin sympathetic nerve activity was recorded during unloading of mainly cardiopulmonary afferents with non-hypotensive lower body negative pressure (LBNP) performed in both normothermic and hyperthermic conditions. The function of the sympathetic activity was studied by estimations of skin blood flow (laser Doppler velocimetry), of calf blood flow (plethysmography) and of sudomotor activity (electrodermal responses). 3. A level of LBNP that caused robust increases in sympathetic outflow and vascular resistance in the skeletal muscle of the lower leg had no effect on sympathetic activity and vascular resistance in the skin of the same region in the same subjects. Both at normothermia and during hyperthermia LBNP decreased electrodermal activity. Experiments performed during sham LBNP and with skin temperature kept constant suggest that the electrodermal response was due to a decrease in skin temperature produced by the LBNP. 4. In conclusion, these findings challenge the concept that the cutaneous circulation participates importantly in the peripheral circulatory adjustments to unloading of cardiopulmonary afferents during orthostatic stress in humans. During non-hypotensive LBNP, the skeletal muscle bed accounts for all of the reflex vasoconstriction in the calf.

Human sympathetic nerve activity to glabrous skin does not increase during simulated diving

In humans, cardiovascular adjustment to simulated diving causes a marked increase in sympathetic outflow to intramuscular vessels and muscle vasoconstriction. Skin vasoconstriction in the hand also occurs during diving in humans. Skin nerve sympathetic activity (SSA), containing vasoconstrictor signals to glabrous skin, unexpectedly was reduced during diving in a previous study of SSA recorded in the peroneal nerve. SSA was recorded by microneurography in the median nerve in 13 healthy volunteers during simulated diving. Skin blood flow in the hand and one finger was monitored. The typical SSA response, irrespective of duration of diving and water temperature, was an increase during the control period immediately prior to immersion of the face and a sudden reduction of SSA when the face was immersed. The increase in SSA preceding the dive was accompanied by vasoconstriction, which continued during the dive, but re-dilation regularly occurred before the end of the dive. Inhibition of SSA was not total. Mental arithmetic during diving evoked strong bursts of SSA, similar to those seen normally during mental stress. It is concluded that the true response of SSA to simulated diving is an inhibition of the immediately preceding outflow, in agreement with observations of cutaneous blood flow in animals. The skin vasoconstriction recorded during simulated diving is a consequence of an SSA increase before the procedure, suggested to be a stress response before the forthcoming manoeuvre. The SSA response during simulated diving is the opposite to that of sympathetic outflow to muscle, which emphasizes the diversity of sympathetic regulation of different organ systems.

Nonneural Mediation of Digital Vasodilation during Menopausal Hot Flushes

Menopausal hot flushes are accompanied by profuse sweating, decreased skin resistance, modest tachycardia and cutaneous vasodilation. With the exception of the last effect, these events are consistent with an abrupt increase in sympathetic outflow. Blood flow in the human finger is controlled through sympathetic vasoconstricting nerves, and increased sympathetic activation results in digital vasoconstriction. We therefore sought to determine if digital vasodilation during hot flushes was mediated through efferent sympathetic nerves. Bilateral finger temperature and blood flow were recorded after the digital nerves on one hand had been blocked with a local injection of lidocaine. The effectiveness of the nerve blocks was verified by a reflex vasoconstriction test. Hot flushes were objectively defined using skin conductance responses recorded from the sternum. Fifteen hot flushes occurred in 8 women. Significant elevations in finger temperature and blood flow occurred during the flushes, in nerve-blocked and intact fingers. These findings suggest that digital vasodilation during hot flushes is due to a circulating vasodilating substance.

Renal sympathetic responses to conflicting baroreceptor inputs: rapid ventricular pacing in dogs.

1. Ventricular tachycardia generates complex changes in baroreceptor input to the central nervous system: arterial baroreceptors are unloaded while cardiopulmonary receptors are stimulated. In humans with heart diseases, muscle sympathetic nerve activity increases during ventricular tachycardia. This suggests that arterial baroreceptor-mediated sympathoexcitation overrides cardiopulmonary receptor-mediated sympathoinhibition. However, the relative roles of each reflex are difficult to determine in humans. 2. We measured efferent renal sympathetic neural responses to simulated ventricular tachycardia, to determine what pathophysiological mechanisms are invoked when inputs from different baroreceptive areas change in opposite directions. In alpha-chloralose anaesthetized, mechanically ventilated dogs, we recorded the electrocardiogram, mean left atrial and arterial pressures and multifibre efferent renal sympathetic nerve activity (RSNA) during 1 min of right ventricular pacing at 214 beats min-1. Pacing was repeated after either sinoaortic or vagal cardiopulmonary denervation and again after both sinoaortic and cardiopulmonary denervation. 3. With all afferent baroreceptor pathways intact, right ventricular pacing elicited transient sympathoinhibition (delta RSNA, -19 +/- 10%, mean +/- S.E.M.). After sinoaortic denervation (cardiopulmonary receptors intact), right ventricular pacing elicited abrupt and sustained sympathoinhibition (delta RSNA, -53 +/- 8%, P < 0.05 vs. intact). After vagal cardiopulmonary denervation (sinoaortic receptors intact), right ventricular pacing elicited abrupt and sustained sympathoexcitation (delta RSNA, + 56 +/- 19%, P < 0.05 vs. intact). After both sinoaortic and vagal cardiopulmonary denervation, right ventricular pacing elicited a gradual increase in sympathetic outflow (delta RSNA, + 16 +/- 6%, P < 0.05 vs. intact). 4. We conclude that interactions between vagal cardiopulmonary and arterial baroreflexes determine renal sympathetic outflow during simulated ventricular tachycardia. In healthy anaesthetized dogs, the balance of the two opposing reflexes is weighted towards vagal cardiopulmonary-mediated sympathoinhibition.

A comparison between two forms of aerobic dance and treadmill running

Aerobic dance has been reported to result in a disproportionately higher heart rate than running at a similar percent of VO2max. It has been suggested that the extensive use of the arms overhead during aerobic dance results in an increase in sympathetic outflow thereby disproportionately increasing the heart rate. To compare the hemodynamic and sympathetic nervous system activity responses during aerobic dance and treadmill running, nine healthy females exercised at approximately 50% of their VO2max during each of the following three exercise trials: aerobic dance where the arms were used extensively overhead (ABOVE), aerobic dance where the arms were kept below the shoulders (BELOW), and treadmill running (TR). Mean heart rate values during the ABOVE, BELOW, and TR trials were 136 beats.min-1 for all three trials. Mean VO2 values during the ABOVE, BELOW, and TR trials were 1.48, 1.51, and 1.47 l.min-1, respectively, and were not significantly different. Mean cardiac output for the ABOVE, BELOW, and TR trials were 13.5, 14.0, and 13.0 1. min-1, respectively, and were not significantly different. Postexercise blood lactate and norepinephrine values were not significantly different among the three trials. These results suggest a similar relationship between heart rate and VO2 during low intensity aerobic dance and running and do not support the contention that the use of the arms overhead during aerobic dance exercise elicits a disproportionately greater increase in heart rate as compared with running. Additionally these results demonstrate similar cardiovascular and sympathetic nervous system responses between aerobic dance exercise and running.

Muscle chemoreflexes and exercise in humans.

This review focuses on the role afferent nerves from the contracting muscles play in linking muscle metabolism to the cardiovascular adjustments during exercise by means of a 'muscle chemoreflex'. In the 1930s Alam and Smirk provided the first clear evidence that human (and animal) skeletal muscles are innervated by chemosensitive afferents that can evoke increases in arterial blood pressure. They proposed that the purpose of the increase in pressure was to improve blood flow to the active muscles. Subsequent studies have identified the slowly conducting group IV afferents as the major class of fibres participating in the sensory arm of this reflex. Most of these fibres travel via the dorsal roots to the ipsilateral spinal cord where they synapse in the substantia gelatinosa and release substance P or other peptide transmitters. The second order (or higher) neurons cross to the contralateral side of the spinal cord and travel rostrally to stimulate brainstem cardiovascular centres and increase arterial pressure. Current evidence favours the concept that substances associated with muscle acidosis provide the stimulus to the afferents. In humans, chemosensitive afferent activation causes a marked increase in vasoconstrictor efferent muscle sympathetic nerve activity. It is unclear if the muscle chemoreflex improves blood flow to 'underperfused' active muscles by augmenting arterial pressure, or if the increase in sympathetic outflow restrains metabolic vasodilatation to regulate arterial blood pressure during activities like running or cycling.

Vasopressin increases blood glucose in pygmy goats ( Capra hircus) by an α-adrenergic mechanism

1. 1. Twelve adult pygmy goats were used to investigate the mechanism of vasopressin (VP) induced hyperglycaemia. 2. 2. VP (0.4μg/kg or 0.75μg/kg body weight) injected i.p. produced a long lasting hyperglycaemia. 3. 3. This hyperglycaemia was partly reversed by α-adrenergic antagonists with an affinity to α 1- and α 2-adrenergic receptors (phentolamine) or to α 2-adrenergic receptors (yohimbine). An α 1adrenergic agonist (xylometazoline) produced a short-term hyperglycaemia. 4. 4. The ganglion blocking agent hexamethonium also reversed VP's hyperglycaemic effect. 5. 5. It is concluded that VP's hyperglycaemic effect in pygmy goats is due to an increase in sympathetic outflow and not to a direct action on the liver.

Stimulation of serotonin2 receptors in the ventrolateral medulla of the cat results in nonuniform increases in sympathetic outflow.

Topical application of the serotonin2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane or DOI, in a dose of 30 micrograms/side to the intermediate area of the ventrolateral surface of the medulla produced a significant increase in mean arterial pressure with no significant change in heart rate both in intact animals (n = 8) and in cervically vagotomized animals (n = 3). The pressor response of DOI was blocked by pretreatment of the intermediate area with ketanserin, a serotonin2 antagonist (n = 7). Pretreatment with intravenous phentolamine did not block the pressor response of DOI (n = 3). However, this pressor response could be counteracted by intravenous propranolol (n = 5) or by bilateral stellate ganglionectomy (n = 3). These data suggest that sympathoexcitation by centrally applied DOI selectively increased cardiac inotropy but not chronotropy. Further studies indicate that DOI increased contractile force without increasing heart rate and that the positive inotropic effect of DOI could be counteracted by bilateral stellate ganglionectomy. Bilateral microinjections of DOI into the subretrofacial nucleus in a dose of 100 ng (n = 3) and a dose of 300 ng (n = 3) increased mean arterial blood pressure by 23 +/- 2 and 44 +/- 6 mm Hg, respectively, without producing any changes in heart rate. These data suggest that DOI has a central site of action in the ventrolateral medulla, presumably at the subretrofacial nucleus, which leads to selective sympathoexcitation of the cardiac ventricles.

Cardiovascular effects of central injection of acetylcholine in anaesthetized dogs: a role for vasopressin release

1. The effect of an intracisternal injection of 20 micrograms kg-1 of acetylcholine was studied on systolic and diastolic blood pressures, heart rate, and plasma levels of noradrenaline, adrenaline, vasopressin, plasma renin activity and atrial natriuretic factor in chloralose-anaesthetized dogs, 8 of which were normal and 7 with diabetes insipidus (deprived of vasopressin secretion by surgical lesion of the hypothalamoneurohypophysial system). 2. Acetylcholine significantly increased systolic and diastolic blood pressures in both groups of animals. However, the rise in blood pressure was significantly shorter lived in the dogs with diabetes insipidus. 3. Acetylcholine significantly increased plasma levels of noradrenaline but not adrenaline in control animals and in dogs with diabetes insipidus. Noradrenaline and adrenaline responses after acetylcholine were not different in the two groups of animals. 4. Acetylcholine induced a significant increase in vasopressin plasma levels only in control animals while in dogs with diabetes insipidus vasopressin remained at nearly undetectable levels. 5. Acetylcholine significantly increased atrial natriuretic factor plasma levels only in control dogs. 6. Although plasma renin activity increased in both groups of animals after the i.c. injection of acetylcholine, this change was not significant in any group. 7. These results suggest that, in the anaesthetized dog, the central injection of acetylcholine induces a rise in blood pressure through both an increase in sympathetic outflow and a release of vasopressin.

Effect of stress on the control of renin release in spontaneously hypertensive rats.

Recent reports suggest that centrally induced increases in sympathetic outflow to the kidney have the potential to enhance the sensitivity of pressure-dependent renin release. In the present study, the possibility was investigated that spontaneously hypertensive rats (SHR), which are thought to have increased tonic sympathetic outflow to the kidney, exhibit enhanced renin release in response to reduced renal perfusion pressure. The increase in plasma renin activity in response to a graded suprarenal aortic constriction was determined in conscious young (6-9 weeks of age) and adult (14-16 weeks of age) SHR and age-matched Wistar-Kyoto (WKY) control rats. Under conditions of relatively little stress, the renin response to reduced renal perfusion pressure was not enhanced in young or adult SHR when compared with age-matched WKY rats. That is, this regulatory mechanism was not "reset" in the hypertensive animals. When challenged with an acute stress (air to the face) both age groups of SHR exhibited a significantly enhanced response. Neither age group of WKY rats was affected by the acute air stress. These data suggest that, under unstressed conditions, pressure-dependent renin release probably does not contribute to the elevation of arterial pressure in the SHR. However, under stressful conditions, the contribution of this system may be significant. Intermittent increases in sympathetic outflow to the kidney that can occur in the SHR in response to daily stresses have the potential to render it more sensitive to spontaneous reductions in perfusion pressure. Occasional exaggerated release of renin could then contribute to the hypertensive process.

Sustained increases in sympathetic outflow during prolonged lower body negative pressure in humans

The purpose of this study was to determine whether prolonged unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP) causes constant increases in sympathetic outflow to skeletal muscles. Eight healthy subjects underwent a 20-min control period followed by 20 min of 15-mmHg LBNP. This pressure was selected because it did not cause any significant change in mean arterial blood pressure (sphygmomanometry) or heart rate, suggesting that the cardiopulmonary baroreceptors were selectively unloaded and the activity of the arterial baroreceptors was unchanged. Muscle sympathetic nerve activity in the peroneal nerve (MSNA, microneurography) increased from an average of 21.8 +/- 1.7 bursts/min over the last 5 min of control to 29.0 +/- 2.9 bursts/min during the 1st min of LBNP (P less than 0.05 LBNP vs. control). The increase in MSNA observed during the 1st min was sustained throughout LBNP. Forelimb blood flow (plethysmography) decreased abruptly at the onset of the LBNP from a control value of 4.3 +/- 0.5 ml.min-1.100 ml-1 to 2.5 +/- 0.2 at the 1st min; the flow then increased and remained significantly above this value, but below the control value, throughout LBNP. Similar blood flow findings were obtained in additional studies, when the hand circulation was excluded during the flow measurements. Forearm skin blood flow (laser Doppler) also decreased abruptly at the onset of LBNP and was followed by partial recovery, but these changes were too small to account for all the increases in limb blood flow over the course of LBNP.(ABSTRACT TRUNCATED AT 250 WORDS)

Disturbances in ocular sympathetic function and facial blood flow in unilateral migraine headache.

The relationship between thermographic asymmetry in various parts of the face and indices of ocular sympathetic outflow was examined in 80 patients with unilateral migrainous headache. Both during and between episodes of headache, the pupil on the symptomatic side dilated more slowly and less extensively in darkness than the opposite pupil, indicating that ocular sympathetic outflow was compromised in some patients. In such cases the upper forehead and orbital region were warmer on the symptomatic side during migraine. In contrast to these signs of a reduction in cervical sympathetic outflow, eyelid separation was greater on the symptomatic side in patients with headache on the side that was usually affected. During the headache-free interval no consistent thermographic asymmetry was detected and eyelid separation was similar on both sides. These findings suggest that extracranial vascular changes and ocular sympathetic dysfunction during migraine are secondary to activation of trigeminal-vascular reflexes or to antidromic release of vasoactive substances from trigeminal nerve terminals. A secondary deficit in the sympathetic pathway to the symptomatic pupil could also prevent the expression of an increase in sympathetic outflow during headache.

Relation between sympathetic outflow and vascular resistance in the calf during perturbations in central venous pressure. Evidence for cardiopulmonary afferent regulation of calf vascular resistance in humans.

Vascular studies in humans have advanced the concept that, during orthostatic stress, cardiopulmonary afferents reflexly regulate vascular resistance in the forearm but exert surprisingly little if any effects on vascular resistance in the calf. In contrast, neurophysiological studies have indicated that unloading of cardiopulmonary afferents during lower body negative pressure evokes comparable increases in sympathetic outflow to the muscles of both the forearm and the calf. The aim of this study, therefore, was to determine if alterations in central venous pressure over the physiological range trigger reflex changes in muscle sympathetic outflow that not only are statistically significant but also are large enough to alter vascular resistance in the calf. To accomplish this aim, we measured calf blood flow with plethysmography and simultaneously performed microelectrode recordings of sympathetic outflow to calf muscles in conscious humans during maneuvers designed to alter the loading conditions of the cardiopulmonary afferents. We found that calf vascular resistance increased by 33 +/- 7% (mean +/- SEM, p less than 0.05) during decreases in central venous pressure produced by nonhypotensive lower body negative pressure (LBNP) and decreased by 26 +/- 5% (p less than 0.05) during increases in central venous pressure produced by nonhypertensive infusion of normal saline. These changes in calf resistance were at least as large as the changes in forearm resistance evoked by these maneuvers and were accompanied by parallel changes in peroneal muscle sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrous Oxide Augments Sympathetic Outflow

Direct evidence for postganglionic sympathetic nerve activation to blood vessels supplying skeletal muscle was sought by recording from the peroneal nerve of 13 volunteers with a 5-mu tipped tungsten needle. Eight subjects breathed through an anesthesia face mask connected to a semiclosed anesthesia circuit for two consecutive 10-min periods while 25% and 40% nitrous oxide (N2O) was administered sequentially. Five subjects served as controls and breathed equivalent concentrations of nitrogen. Blood pressure and central venous pressure were recorded from radial artery and jugular vein catheters. Forearm blood flow was measured by venous occlusion plethysmography. Peroneal nerve recordings were amplified 100,000-fold and integrated for analysis of burst frequency. N2O did not significantly alter respiratory rate, end-tidal CO2 (mass spectrometry), and diastolic or central venous pressures but did produce small but significant increases in heart rate and systolic pressure compared to time-control (P less than 0.05). In contrast, N2O was associated with progressive, large increases in muscle sympathetic nerve activity (peak % delta = 69 +/- 22 burst/min [X +/- SEM]) and forearm vascular resistance (30 +/- 4%) and a nonsignificant increase in plasma norepinephrine levels. Thus, brief exposure to 25% and 40% N2O produces striking increases in sympathetic outflow to skeletal muscle in humans.