Spontaneous Sympathetic Activity Research Articles

Electrodermal lability and sensorimotor preparation: effects on reaction time, contingent negative variation, and heart rate

Electrodermal lability is a trait-like measure of spontaneous sympathetic resting activity. In the present study, we addressed whether interindividual differences in this lability have an impact on the reaction time (RT) and on two physiological indicators of a goal-oriented sensorimotor preparation in a long-running, forewarned RT task (S1-S2 paradigm). The two indicators were the brain’s contingent negative variation (CNV) and a heart rate deceleration (HRD). The interindividual differences were determined by counting spontaneous skin conductance fluctuations during a 5-min resting phase and dividing the subjects into two groups: individuals below (stable) and above (labile) the median of these fluctuations. In the task, labile individuals had a shorter RT compared with stable individuals and showed in the final phase of preparation in both physiological indicators the stronger response. Thus, lability-dependent effects in forewarned RT tasks cannot be explained by differences in stimulus-driven or passively controlled processes alone. Rather, goal-oriented, deliberately controlled processes that serve to adequately prepare for an imperative stimulus—the S2 in our paradigm—also must be considered to explain them. Labile individuals not only react faster than stable ones but also intentionally prepare themselves more appropriately for the imperative stimulus. A norepinephrine hypothesis focusing on the tonic activity of the locus coeruleus (LC) is proposed as an explanation for these and other lability-dependent effects. The frequency of spontaneous electrodermal fluctuations at rest may represent a peripheral, noninvasive, and easily measurable indicator of the baseline LC activity during wakefulness.

Skin temperature side differences – a diagnostic tool for CRPS?

Complex regional pain syndrome type I (CRPS I) is a chronic painful disease of one extremity that may develop as a disproportionate consequence of a trauma affecting the limbs without overt nerve injury. It is clinically characterized by sensory, motor and autonomic symptoms including vascular abnormalities. Previously, we have reported that pathophysiological alterations of the ongoing sympathetic activity play a crucial role in vasomotor disturbances (Brain 124 (2001) 587). As a companion article, the aim of this study was to evaluate the diagnostic value of skin temperature side differences in consideration of the spontaneous sympathetic vasoconstrictor activity. Twenty-five patients with CRPS I were studied. Fifteen patients with painful limbs of other origin and 20 healthy individuals served as controls. Controlled thermoregulation was performed to change cutaneous sympathetic vasoconstrictor activity by the use of a thermal suit: skin sympathetic vasoconstrictor neurones were activated by whole-body cooling and nerve activity was abolished by whole-body warming. Skin temperature at the affected and unaffected limbs (infra-red thermometry) was measured under resting conditions and continuously monitored during controlled modulation of sympathetic activity. The results showed only minor skin temperature asymmetries between both limbs under resting conditions in most CRPS patients. However, during controlled thermoregulation temperature differences between both sides increased dynamically and were most prominent at a high to medium level of vasoconstrictor activity. In both control groups, there were only minor side differences in temperature both in rest and during thermoregulatory changes of sympathetic activity. When comparing the diagnostic value of skin temperature asymmetries in CRPS I, sensitivity was only 32% under resting conditions, but increased up to 76% during controlled alteration of sympathetic activity. Specificity was 100% at rest and 93% at controlled thermoregulation. We concluded that the degree of unilateral vascular disturbances in CRPS I depends critically on spontaneous sympathetic activity. Taking this into consideration, skin temperature differences in the distal limbs are capable of reliably distinguishing CRPS I from other extremity pain syndromes with high sensitivity and specificity.

Synergism Between Sevoflurane and Intravenous Fentanyl on A delta and C Somatosympathetic Reflexes in Dogs

In this study, we defined the nature of the interactions between sevoflurane and fentanyl on spontaneous and reflex-evoked sympathetic activity, resting heart rate (HR), and mean arterial pressure (MAP). Spontaneous renal sympathetic nerve activity (RSNA) and A delta- and C-fiber-mediated somatosympathetic reflexes, evoked by electrical stimulation of radial nerves, and HR and MAP were recorded in anesthetized dogs. In one group, the effects of incremental doses of 2-64 micrograms/kg fentanyl i.v. were observed. It had a greater inhibitory effect on C than on A delta reflexes, which were abolished by mean cumulative doses of 64 micrograms/kg and approximately 128 micrograms/kg, respectively. Although 1.5% sevoflurane reduced C reflexes by 28% and A delta reflexes by only 12%, it reduced the total doses of fentanyl required for their abolition to 32 micrograms/kg and 64 micrograms/kg, respectively. Mean RSNA, HR, and MAP values were reduced by 46%, 54%, and 30%, respectively, by fentanyl alone and by 23%, 11%, and 17%, respectively, in response to 1.5% sevoflurane. The combination of fentanyl and sevoflurane caused reductions of 44%, 54%, and 41%, respectively, which indicates a less than additive effect. These results indicate that sevoflurane interacts synergistically with fentanyl to depress A delta and C somatosympathetic reflexes, whereas for RSNA, HR, and MAP, their effects were less than the additive. Although fentanyl caused a greater depression of C than of A delta reflexes to the point of abolition, the maximal depression of spontaneous sympathetic activity, heart rate, and arterial pressure occurred at smaller doses. The combined depressant effects of sevoflurane and fentanyl were synergistic on somatosympathetic reflexes but were less than additive on spontaneous sympathetic activity, heart rate, and arterial pressure.

The Effect of Sevoflurane on Spontaneous Sympathetic Activity, A delta and C Somatosympathetic Reflexes, and Associated Hemodynamic Changes in Dogs

This study examined the effect of sevoflurane on spontaneous renal sympathetic nerve activity (RSNA), A delta- and C-fiber-mediated somatosympathetic reflexes, and hemodynamic changes in anesthetized dogs. RSNA, and A delta and C reflexes evoked by electrical stimulation of the radial nerve were observed in multifiber recordings of efferent activity in renal sympathetic nerves. Sevoflurane was administered at 1%, 2%, 3%, and 4% end-tidal concentrations for periods of 20 min. The mean A delta reflexes decreased by 20%, 39%, and 54% (P < 0.05 to < 0.01), and the C reflexes decreased by 38%, 62%, and 74% (P < 0.05 to < 0.01) at concentrations of 2%, 3%, and 4%, respectively. The relatively greater effect on C reflexes was significant (P < 0.05) and comparable with the effect of mu-opioids. There was no change in mean RSNA, heart rate (HR), and cardiac output (CO) up to 3% sevoflurane, but these decreased by 36%, 24%, and 13% (P < 0.05), respectively, at 4% sevoflurane. Sevoflurane 1%-4% caused a virtually linear reduction in systemic vascular resistance (SVR) from 7% (P < 0.05) to 44% (P < 0.05), together with a reduction in mean arterial pressure (MAP) that was significant for concentrations greater than 2%. The results indicate that sevoflurane causes a greater depression of C compared with A delta reflexes, and that the reduction in MAP was entirely due to a decrease in SVR up to 3%, whereas at 4% sevoflurane, reductions in sympathetic activity, HR, and CO also contributed its depressor effect. The relatively greater depressant effect of sevoflurane on C compared with A delta nociceptive somatosympathetic reflexes is similar to mu-opioids. The hypotensive effect of sevoflurane was significant at 2% concentration, whereas heart rate, cardiac output and sympathetic activity were reduced only at concentrations greater than 3%.

The Effect of Sevoflurane on Spontaneous Sympathetic Activity, A delta and C Somatosympathetic Reflexes, and Associated Hemodynamic Changes in Dogs

The Effect of Sevoflurane on Spontaneous Sympathetic Activity, A delta and C Somatosympathetic Reflexes, and Associated Hemodynamic Changes in Dogs

Spinal cord segments mediating tonic sympathetic nerve discharge to the kidney in the anesthetized cat

According to anatomical data, preganglionic neurons projecting to the kidney via sympathetic ganglia occupy a wide range of adjacent segments in the thoracolumbar spinal cord, from Th7 to L2. Since, however, the majority of preganglionic neurons is silent at resting states, the active segments indeed transmitting sympathetic activity, at rest, may be different. In the present experiments, the spontaneous sympathetic activity was recorded before and after the sympathetic trunk and white rami (WR) Th8–L3 were cut in a sequential manner. The step-by-step changes in the power of renal nerve discharge were estimated and used for mapping tonic renal outflow to the spinal cord. We found that powerful activity comprising 70–95% of the power of control recordings remained after eliminating the input from Th1–Th12, indicating that thoracic spinal cord including segments that contain the largest number of cells projecting to renal postganglionic neurons contributes relatively weakly to tonic renal nerve activity. It appeared that resting sympathetic nerve discharge was predominantly maintained by the caudalmost division of the renal preganglionic neuron population since the largest decrease in nerve power occurred after severing WR Th13, L1, and L2. These findings suggest that the `active segmental map' of preganglionic neurons controlling a certain organ at rest does not necessarily match the distribution of the total population of neurons projecting to the same effector.

Effect of sevoflurane on spontaneous sympathetic activity and baroreflexes in rabbits

Sevoflurane causes a decrease in mean arterial pressure (MAP). We have studied in anaesthetized rabbits its interactive effects on MAP, the autonomic nervous system and baroreflexes. During sevoflurane administration changes in renal sympathetic nerve activity (RSNA) and heart rate (HR) were observed: (1) when the normal decrease in MAP occurred; (2) when this was prevented by angiotensin II; (3) during a similar decrease in MAP induced by infusion of sodium nitroprusside (SNP) without sevoflurane administration; and (4) during pressor and depressor responses to phenylephrine and SNP. There was a reduction in MAP from 80 to 40 mm Hg after 1-4% sevoflurane without changes in HR, while RSNA remained unchanged only up to concentrations of 3% and was depressed by 37% (P < 0.05) with 4% sevoflurane. When MAP was maintained constant with angiotensin II, both HR and RSNA decreased, by 12% and 69%, respectively, after 4% sevoflurane (P < 0.05). A decrease in MAP of 40 mm Hg during infusion of SNP increased HR and RSNA by 22% (P < 0.05) and 150% (P < 0.01), respectively. At 2% sevoflurane, baroreflex sensitivity (i.e. delta RSNA/delta MAP and delta HR/delta MAP) was depressed by 36% and 57%, respectively, for the pressor effects of pherylephrine, and by 89% and 81%, respectively, for the depressor effects of SNP. We conclude that the baroreflexes continued to compensate for the effects of sevoflurane on sympathetic and cardiomotor activity with concentrations up to 3% and 4%, respectively.

Carotid bifurcation pressure modulation of spontaneous activity in external and internal carotid nerves can occur in the superior cervical ganglion

Previous reports have suggested that a peripheral pressure-modulated reflex operates at the level of the superior cervical ganglion to alter evoked activity in the postganglionic nerves of the ganglion in both the cat and rabbit. In the present study we have examined if spontaneous activity of the external and internal carotid nerves of the rabbit superior cervical ganglion can be modulated during changes of the carotid bifurcation pressure (CBP), independent of central nervous system (CNS) integration. For external carotid nerve recordings increases in CBP resulted in a reduction in spontaneous activity while decreases in CBP were associated with an increase in spontaneous activity. For internal carotid nerve recordings similar effects were observed in the majority of recordings although a subset of recordings showed opposite effects or were not responsive to changes in pressure. To determine if vagus nerve afferents contribute to the observed pressure-modulated spontaneous activity effects, the influence of CBP on external carotid nerve recordings was examined before and after section of the vagus nerve rostral to the nodose ganglion. We found that even following section of the vagus nerve the external carotid nerve response to an increase in pressure remained intact. These results demonstrate that, after section of centrally-projecting afferent pathways from the carotid bifurcation to the CNS, changes in CBP can still modify spontaneous sympathetic activity of the rabbit superior cervical ganglion. The data reinforce previous findings related to evoked responses in the postganglionic nerves and also suggest that a pressure-modulated reflex, integrated at the level of the superior cervical ganglion, can influence ongoing sympathetic nervous outflow from the superior cervical ganglion in the rabbit.

Dissociation between the effect of nitrous oxide on spontaneous and reflexly evoked sympathetic activity in dogs

We have examined the effect of nitrous oxide on spontaneous sympathetic activity and A delta- and C-fibre mediated somatosympathetic reflexes in renal nerves, evoked by supramaximal electrical stimulation of radial nerves in anaesthetized, paralysed dogs undergoing mechanical ventilation. In six preparations, nitrous oxide was administered at end-tidal concentrations of 10%, 30%, 50% and 70%, each for 20 min. Spontaneous renal sympathetic activity increased significantly to 147.8% and 151.2% of control values with 50% and 70% nitrous oxide, respectively (P < 0.05), but there were no significant changes in A delta and C reflexes. We conclude that the large increase in spontaneous sympathetic activity was dissociated from somatosympathetic reflexes which remained unchanged at these concentrations of nitrous oxide.

Clonidine Has Comparable Effects on Spontaneous Sympathetic Activity and Afferent Aδ– and C-Fiber-mediated Somatosympathetic Reflexes in Dogs

Clonidine, an alpha 2-adrenergic agonist, has been studied as an adjunct or alternative to spinal opioids in the management of moderate to severe pain. This study examined the relative effects of clonidine on efferent spontaneous sympathetic activity and afferent A delta and C fiber-mediated somatosympathetic responses. Spontaneous and evoked sympathetic activity in renal sympathetic nerves, mediated by A delta and C fibers by means of supramaximal electrical stimulation of the radial and tibial nerves, were observed in anesthetized dogs. Incremental doses of clonidine were administered intrathecally or intravenously in each of five preparations followed by intravenous naloxone 2 mg and yohimbine 5 mg. Both spontaneous sympathetic outflow and afferent A delta- and C fiber-mediated somatosympathetic responses evoked by tibial nerve stimulation were depressed in a similar dose dependent manner by clonidine administered intrathecally or intravenously in a dose ratio of approximately 1:4. Intrathecal clonidine inhibited and eliminated both local spontaneous sympathetic outflow and tibial nerve evoked sympathetic responses but had no significant depressant effect on the radial nerve evoked sympathetic reflexes. When administered intravenously clonidine had a similar depressant effect on both radial and tibial nerve elicited reflexes and spontaneous sympathetic activity. Clonidine, administered intrathecally or intravenously, has a similar depressant effect on both spontaneous sympathetic outflow and afferent A delta- and C fiber-mediated somatosympathetic reflexes. When administered intrathecally it has little effect on reflexes evoked via the descending pathway by radial nerve stimulation.

Specific enhancement by fentanyl of the effects of intrathecal bupivacaine on nociceptive afferent but not on sympathetic efferent pathways in dogs.

Bupivacaine alone, or in combination with opioids, has been shown to provide adequate pain relief without motor paralysis. This study examined the effects of bupivacaine administered intrathecally on sympathetic efferent and A delta- and C-fiber-mediated afferent pathways in dogs and the interactions with intrathecal fentanyl. Spontaneous activity in renal sympathetic nerves was observed, as were reflex somatosympathetic responses mediated by A delta and C fibers evoked by supramaximal electrical stimulation of the tibial and radial nerve. Bupivacaine was administered intrathecally in doses of 0.5, 1, 2, and 3.5 mg, each in 0.5 ml, and 7 mg in 1 ml with or without pretreatment with 5.4 mg intrathecal fentanyl (ED25 for depression of C tibial reflexes) in each of five preparations. Bupivacaine caused a dose-dependent inhibition of both A delta- and C-fiber-mediated somatosympathetic responses evoked by tibial nerve stimulation. The depression of radial and tibial nerve reflexes and spontaneous renal sympathetic activity was similar. Pretreatment with fentanyl (5.4 micrograms, intrathecally) depressed tibial C-fiber reflexes by only 23.8% without any significant effect on either tibial A delta or radial A delta and C fiber responses. Fentanyl markedly enhanced the effect of subsequent doses of bupivacaine on tibial A delta and C reflexes without any additional effect on either spontaneous sympathetic activity or radial responses. Intrathecal bupivacaine has no selectivity for the afferent and efferent pathways, and intrathecal fentanyl acts synergistically to enhance the effect of bupivacaine on the afferent pathway without a measurable effect on sympathetic outflow.

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY NEWCASTLE UPON TYNE MEETING April 2–3, 1993: RELATIVE EFFECTS OF CLONIDINE ON Aδ AND C REFLEXES AND SPONTANEOUS SYMPATHETIC ACTIVITY

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY NEWCASTLE UPON TYNE MEETING April 2–3, 1993: RELATIVE EFFECTS OF CLONIDINE ON Aδ AND C REFLEXES AND SPONTANEOUS SYMPATHETIC ACTIVITY

Non-linearity of skin resistance response to intraneural electrical stimulation of sudomotor nerves.

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.

Spontaneous rhythmic activity of single nerve fibers of the cervical sympathetic nerve trunk of the rabbit

In experiments on rabbits anesthetized with urethane, we recorded spontaneous sympathetic activity of single nerve fibers. The activity was recorded from fine filaments dissected from the cervical sympathetic nerve trunk (CSNT). Conduction velocities in CSNT fibers and action-potential amplitude of single B-fibers were measured during recording of whole nerve trunk. Spectral analysis of the activity recorded was carried out. It was shown that unmyelinated CSNT fibers are under stronger baroreceptor control than myelinated fibers. Also, a periodic component of 2–3 Hz, noted by a number of authors after denervation of baroreceptors, was detected in intact animals along with a rhythm at the pulse rate. This component was found equally often in the activity of B- and C-fibers. Cross-correlation analysis of the simultaneously recorded activities of 24 pairs of CSNT single fibers was carried out. A correlation due to synchronization of the activities of pairs of fibers with a physiological rhythm (respiration, pulse) was found in five pairs. The correlation in one pair suggests the presence of a common excitatory synaptic input into two distinct preganglionic neurons.

Respiratory modulation of sympathetic activity in neonatal swine

Spontaneous efferent sympathetic activity (cervical sympathetic and splanchnic nerves) was recorded simultaneously with efferent phrenic discharge, with aortic pressure, and with the electrocardiogram in less than 1- to 51-day-old neonatal swine anesthetized with Saffan (alfaxalone). Power spectral analyses of sympathetic discharge revealed a frequency range of 4-36 Hz, with peaks distributed in four regions of the spectrum (4-6 Hz, 8-15 Hz, 16-22 Hz, and 28-36 Hz). Inspiratory modulation was readily apparent since sympathetic power spectral energy was greatest during the time of phrenic activity. Alterations in pulmonary afferent inputs (e.g., lung inflation tests and/or vagotomy) altered both phrenic and sympathetic activity. Use of the respiratory-cardiac modulation ratio indicated that respiratory modulation of sympathetic activity was greater than cardiac modulation. Complex afferent inputs, i.e., fictive Valsalva maneuver, indicated an immaturity of integration within the cardiovascular regulatory system. The adult patterns of blood pressure changes and heart rate responses were delayed until approximately 1 mo of age. Calculations of Valsalva ratios (ratio of maximal R-R interval to minimal R-R interval) indicated delayed onset of heart rate responses, reflecting the maturation of cardiovascular reflexes during the neonatal period.

Neuroeffector characteristics of sweat glands in the human hand activated by regular neural stimuli.

1. Intraneural electrical stimuli (0.3-1.2 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in twenty-eight normal subjects. The effects on sweat glands within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (WVPP). Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. 2. At stimulation frequencies of 0.1 Hz each stimulus evoked a transient skin resistance reduction, the amplitude of which varied initially but reached a steady state of less than 10 k omega after, on average, nine responses. If preceded by stimulation-free intervals of 5 min or more, up to fifteen stimuli were required before the first response occurred. With higher frequencies individual responses started to merge, skin resistance levels decreased successively and levelled off around 10 Hz. The total change of resistance (0-10 Hz) was 101 +/- 46 (n = 9) k omega and the higher the pre-stimulus level, the larger the reduction (r = 0.68, P less than 0.05). 3. Stimulus-response latencies to the onset of a skin resistance reduction (single stimuli or trains of six impulses/20 Hz given at 0.1 Hz) shortened initially but reached steady-state values after on average nine to twelve impulses. Average conduction velocity between stimulating electrode and skin resistance recording site was 0.78 m/s and average time for electrical neuroeffector transfer in sweat glands was estimated to be 348 ms. 4. In addition to direct stimulation-induced resistance responses there were also small spontaneous reductions of resistance. They were seen in all subjects and at all frequencies but were more common in some subjects and occurred predominantly at the beginning of stimulation or at changes of frequency. They occurred independently at two skin sites in the same subject and disappeared during stimulation-free periods and after atropine. 5. With train stimulation (six impulses/20 Hz) at 0.1 Hz, each train evoked transient increases of WVPP of 1 mmHg or less in some subjects (latency around 1.6 s). After averaging weak increases were seen also after single stimuli in two subjects. Increases of stimulation current or frequency led to slowly developing sustained increases of WVPP concomitant with decreases in skin resistance. 6. Responses in skin resistance and WVPP to train stimulation at 0.1 Hz were suppressed in a dose-dependent way by I.V. injections of atropine.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemosensitivity of sympathoexcitatory neurones in the rostroventrolateral medulla of the cat

The hypothesis that sympathoexcitatory neurones within the rostroventrolateral medulla (RVLM) may be chemosensitive was tested in chloralose-anaesthetized cats by artificial perfusion of the RVLM via the left vertebral artery. The baroreceptors and peripheral chemoreceptors were denervated by bilaterally dissecting the carotid sinus and vagus nerves. Either white ramus T3 (WR-T3) or the renal nerve was recorded to monitor sympathetic activity. Perfusion with saline or Ringer solution bubbled with CO2 (10%-100%) produced a rapid and pronounced increase in sympathetic activity and blood pressure. Solutions adjusted to the same pH (pH 5.2 for 100% CO2) with HCl resulted in a much weaker excitation. A linear relationship between PCO2 and sympathetic activity was demonstrated. During prolonged perfusion (90 s) sympathetic activity returned to the control level after initial excitation and fell below control levels when perfusion ceased. The sympathetic activity response to CO2-bubbled solutions was unaffected by blockade of synaptic input by microinjection of CoCl2 into the RVLM, whereas spontaneous sympathetic activity and the supraspinal somato-sympathetic reflex from intercostal nerve T4 to WR-T3 were markedly reduced. It is therefore concluded that sympathoexcitatory bulbospinal neurones in the RVLM are directly chemosensitive to changes in arterial PCO2 and pH.

Chemoreceptor stimulation on sympathetic activity: dependence on respiratory phase

Experiments were performed on chloralose-anesthetized, vagotomized, paralyzed, and artificially ventilated cats breathing 100% O2. Peripheral chemoreceptors were stimulated by rapid injections of CO2-saturated NaHCO3 in different phases of the respiratory cycle. Responses of cardiac and renal sympathetic nerves were computed by digital integration. Spontaneous sympathetic activity was consistently modulated by respiration, the modulation being greater for cardiac than for renal nerves. Cardiac nerve responses to peripheral chemoreceptor stimulation depended on the respiratory phase for at least one experimental condition in four of seven animals: the responses were largest during late inspiration and smallest (or absent) during postinspiration and early expiration. Renal nerve responses depended on respiratory phase in only two of eight animals. An average end-tidal CO2 concentration increase from 4.6 +/- 0.8% (SD) to 6.7 +/- 0.9% enhanced the respiratory modulation of spontaneous activity but reduced the responses to peripheral chemoreceptor stimulation. The results indicate that the respiratory modulation of chemoreceptor-induced sympathetic responses was less prominent than the modulation of spontaneous activity. It is hypothesized that the phase dependence of the responses is caused by the spontaneously occurring expiratory diminution of sympathetic activity rather than by an inherent gating of the chemoreceptor reflex.

Interactions of Apomorphine and a Novel Neuroleptic Dibenzodioxazocine Derivative, as Evidenced by Changes of Somato-autonomic Reflexes and Spontaneous Sympathetic Activity in Cats

The apomorphine-antagonistic effects of EGYT-2509, a novel neuroleptic compound, has been studied by two different methods suitable for investigating the dopaminergic modulation of sympathetic output. (1) In cats lightly anaesthetized with urethane (600 mg kg-1 i.p.), blood pressure (BP) reflexes evoked by electrical stimulation of the sciatic nerve were inhibited by apomorphine (0.2 mg kg-1 i.v.) at low frequencies of stimuli (2-8 Hz), while the BP reflexes were facilitated by apomorphine at higher frequencies of stimulation; the evoked contractions of the nictitating membrane were depressed in the entire range of frequencies applied. EGYT-2509 (1.5 mg kg-1 i.v.) antagonized both the inhibition and facilitation of pressor reflexes induced by apomorphine. EGYT-2509, given alone, in doses exceeding 1.5 mg kg-1 either did not influence or inhibited the responses of nictitating membrane and of BP; the inhibition could be antagonized by haloperidol. The apomorphine-induced sustained hypotension was inhibited by EGYT-2509 (18.5 mg kg-1): after EGYT-2509, higher doses of apomorphine (0.7 vs 0.2 mg kg-1) were required for the effect. Sustained hypotension could be elicited by EGYT-2509, too; after apomorphine, smaller doses of EGYT-2509 (8.5 vs 18.5 mg kg-1) were enough to decrease BP. (2) In cats anaesthetized with chloralose and urethane (50 and 400 mg kg-1 i.p., respectively), apomorphine (0.2 mg kg-1) inhibited the spontaneous activity of the postganglionic renal sympathetic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathetic alterations after midline medullary raphe lesions.

The present study was designed to determine the functional importance of the midline medullary raphe nuclei in the autonomic regulation of the cardiovascular system in the anesthetized cat. Baroreceptor and somatosympathetic reflexes as well as the effects of electrical stimulation of vagal afferents and pressor and depressor sites in the hypothalamus and spinal trigeminal tract were determined before and after midline medullary lesions that extended from 2 to 7 mm rostral to the obex. Midline medullary lesions failed to affect baroreceptor reflexes as judged by the lack of effect on the sympathoinhibition associated with the pressor response to phenylephrine and the degree of slow-wave locking of sympathetic activity to the cardiac cycle. However, the lesion did significantly increase spontaneous sympathetic activity recorded from the inferior cardiac nerve. Blood pressure and heart rate were not altered by midline lesions. In addition, the computer-summed sympathoexcitatory response to electrical stimulation of somatic afferents in the sciatic nerve and the sympathoinhibitory response to stimulation of vagal afferent fibers were not affected by midline lesions. In contrast, the decrease in blood pressure and inhibition of sympathetic nerve activity elicited by electrical stimulation of the spinal trigeminal tract were completely abolished by the lesion. Depressor responses evoked from the anteroventral third ventricle region of the hypothalamus but not pressor responses elicited from the posterior hypothalamus were eliminated following midline medullary lesions. Finally, the sympathoinhibitory actions of the serotonin antagonist methysergide were blocked by medullary raphe lesions. These data indicate that neural elements in the medial medullary area function to provide a tonic inhibition of sympathetic nerve activity that is of nonbaroreceptor origin. Depressor responses evoked from the anterior hypothalamus and the spinal trigeminal tract also are mediated through this area of the medulla. Finally, the data support our contention that medullary serotonergic neurons have a sympathoexcitatory function.