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Effect of sympathetic nerve stimulation on cerebral and cephalic blood flow in dogs.

The effect of sympathetic stimulation (stellate ganglion) on dog cerebral and cephalic blood flows was studied via a cervical or a thoracic approach to the stellate ganglion under sodium pentobarbital or chloralose anesthesia. Two different stimulation voltages (3v and 5v) of monophasic pulses were applied for 1 minute. Venous outflow was measured at the confluence of the sagittal, straight and lateral sinuses with the lateral sinuses occluded and with them patent. When the lateral sinuses were occluded, stellate ganglion stimulation resulted in a marked decrease in common carotid blood flow to 38 plus or minus 2.5% (SE) of control and dilation of the ipsilateral pupil, but cerebral blood flow did not change. Similar effects were observed with each of the anatomic approaches, anesthetics, and voltages used and in dogs with low cerebral vascular tone induced by hypercapnia. When the lateral sinuses were kept patent, sympathetic nerve stimulation decreased the venous outflow to 89 plus or minus 2.9% of control and clamping both of the external jugular veins increased venous outflow to 120 plus or minus 2.7% of control. When the lateral sinuses were kept patent and the extracranial venous pressure was increased by clamping both of the external jugular veins, the decrease in venous outflow in response to sympathetic stimulation was even larger: venous outflow was only 65 plus or minus 4.9% of control. We conclude that stimulation of the stellate ganglion has no effect on the cerebral vasculature. Sympathetic stimulation significantly decreases venous blood flow measured at the confluence of the sinuses only when communications between the intracranial and extracranial venous vasculatures are present.

Animals↗

Comparative effects of stimulation of the trigeminal ganglion and the superior sagittal sinus on cerebral blood flow and evoked potentials in the cat.

The superior sagittal sinus (SSS) and the trigeminal ganglion (Vg) of anesthetized cats were stimulated electrically and field potentials in the upper cervical spinal cord and regional cerebral blood flow were recorded. Stimulation of the entire ganglion produced smaller field potential changes in two regions (medioventral area (MVA); dorsolateral area (DLA] of the upper spinal cord than did stimulation of the sagittal sinus (Vg/SSS response ratio = 17% for the MVA and 48% for the DLA). Stimulation of the trigeminal ganglion increased blood flow in only the frontal and parietal cortices (+93% and +33%), whereas stimulation of the sinus produced both larger changes in these areas (+137% and +139%) and also produced changes in regional cerebral blood flow in the thalamus (+122%).

Action Potentials↗

Transient increase of calcium in pre- and postsynaptic organelles of rat superior cervical ganglion after tetanizing stimulation.

The stimulation-dependent translocation and redistribution of intracellular calcium was studied in synapses of the rat superior cervical ganglion. For the cytochemical demonstration of calcium at the ultrastructural level the oxalate-pyroantimonate technique was used. Calcium-containing deposits were observed as electron-dense particles in synaptic vesicles and occasionally in presynaptic mitochondria. On the postsynaptic side, vesicles and vacuoles in dendrites contained increased amounts of reaction product. Following a short train of impulses (20 s, 20 c.p.s.), the ganglionic response to a single stimulus was increased. This potentiation effect which lasted about 1-5 min was accompanied by a change in the distribution of calcium at fine structural level. In ganglia fixed 1 and 5 min after the train, but not later, the number of calcium-containing synaptic vesicles and postsynaptic vacuoles increased significantly.

Animals↗

Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes.

1. The effects of tonabersat (SB-220453) were evaluated on trigeminal nerve ganglion stimulation-induced sensory-autonomic neurovascular reflexes in the anaesthetized cat. Comparisons were made to intravenous administration of carabersat (SB-204269), and to valproate, gabapentin and lamotrigine following intraduodenal administration. 2. There were no effects on resting blood pressure, heart rate, carotid blood flow or carotid vascular resistance for any compound evaluated. 3. Trigeminal nerve ganglion stimulation increased carotid blood flow by 65% and reduced vascular resistance by 41% with minimal effect on blood pressure (< 10%) and no effect on heart rate. Intravenous infusion of tonabersat or carabersat (both 3.4 micromol h(-1)) produced time related reductions in stimulation-induced responses with a maximal inhibition (relative to control) of 30 +/- 7% (n=4), at 240 min for tonabersat and 33+/-4% (n=3) at 180 min for carabersat. Tonabersat (11.5 micromol h(-1)) produced a similar inhibitory effect (32 +/- 9%, n=4) after 120 min of infusion. 4. Following intraduodenal administration of tonabersat, the maximal inhibition of nerve stimulation-induced responses was 55 +/- 4% at 120 min (n=4) for tonabersat 10 mg kg(-1), and 24+/-2% after 180 min for 1 mg kg(-1) (n=4). 5. Intraduodenal administration of sodium valproate (10 or 100 mg kg(-1) n=4/group) had no effect on neurovascular reflexes. Maximal inhibition of nerve ganglion-stimulated reductions in carotid vascular resistance were observed at 150 min for lamotrigine (50 mg kg(-1), 52+/-12%, n=4) and gabapentin (100 mg kg(-1), 17+/-13%, n=3). Lamotrigine 10 mg kg(-1) produced 22+/-11% (n=3) inhibition after 180 min. 6. These data demonstrate blockade of trigeminal parasympathetic reflexes with tonabersat, carabersat and other anticonvulsants. These agents may therefore have therapeutic benefit in conditions where this type of reflex is evident.

Anesthesia↗

Effects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens.

We have studied spiral ganglion cell (SGC) survival and soma size in neonatally pharmacologically deafened kittens. They were implanted with a four-electrode array in the left cochlea at 100 to 180 or more days of age. Eight animals were chronically stimulated approximately 1000 hours over approximately 60 days with charge-balanced, biphasic current pulses; three were unstimulated controls. Using three-dimensional computer-aided reconstruction of the cochlea, the SGC position and cross-sectional area were stored. SGC position was mapped to the organ of Corti by perpendicular projections, starting from the basal end. The basal region of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1 mm of the length of the organ of Corti) and soma size for stimulated cochleae were compared statistically with implanted but unstimulated cochleae. There was no evidence of an effect of electrical stimulation on SGC survival under this protocol and with this duration. On the other hand, the cell size on the stimulated side was significantly larger than the control side in the middle segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after prolonged auditory deprivation; however, these changes may be partially moderated after chronic intracochlear electrical stimulation.

Animals↗

[Effect of unilateral extirpation of the superior cervical sympathetic ganglion and electric stimulation of the posterior hypothalamus on the rate of reflex conditioning in the dog].

The influence of the sympathetic nervous system and the posterior hypothalamus on the rate of conditioning and the magnitude of conditioned reflexes was studied on dogs by motor defensive method. Extirpation of the superior cervical sympathetic ganglion reduced the conditioned reflex magnitude, delayed the elaboration of positive reflexes facilitating the formation of the inhibitory process. Stimulation of the posterior hypothalamus with electrical current of medium strength (50 mcA) promoted the enhancement of positive conditioned reflexes, and while not substantially affecting the rate of their formation, facilitated elaboration of internal inhibition.

Animals↗

Synaptic responses evoked by lower urinary tract stimulation in superior cervical ganglion cells in the rat.

PURPOSE: Stimulation of afferent neurons from the urinary tract can evoke powerful cardiovascular reflexes in animals and in humans. Here we tested whether and to what extent postganglionic sympathetic neurons projecting to the head and neck are involved in these reflexes. MATERIALS AND METHODS: In adult anesthetized female Wistar rats, reflex changes in synaptic activity elicited from the lower urinary tract were recorded in neurons of the superior cervical ganglion using intracellular recording techniques. RESULTS: Gentle movements of the urethral cannula and/or slow injections of 0.3 to 0.6 ml. saline into the bladder modified synaptic activity in 75% of neurons tested: 11/15 neurons tested showed reflexes to urethral stimulation (8 excitatory, 3 inhibitory) and 8/12 neurons responded to bladder distension (5 excitatory, 3 inhibitory). Five neurons showed a reciprocal response pattern to the two stimuli. Suprathreshold and subthreshold inputs to a given cell mostly showed the same type of response. There was no evidence that urinary tract stimulation recruited preganglionic inputs that did not have ongoing activity prior to the stimulus. CONCLUSIONS: Reflexes from the lower urinary tract clearly reached sympathetic neurons located in remote segments. The response incidence in the population studied suggests that most sympathetic neurons involved in cardiovascular regulation participate in these reflexes. The different reflex patterns probably occur in neurons with different functional targets in the head and neck.

Animals↗

Autonomic influences on regional cardiac [14C]2-deoxyglucose uptake in paced dog heart.

Sixteen dogs were anesthetized with pentobarbital sodium and placed on positive pressure ventilation. Twelve animals were cardiac paced and four animals were non-paced controls. In four of the paced animals, the left cut peripheral end of the cervical vagus was stimulated electrically. In another four animals, the decentralized left stellate ganglion was stimulated efferently. The four remaining paced animals were controls. The animals were injected i.v. with a single bolus of [14C]2-deoxyglucose, 100 microCi/kg. After 45 minutes of periodic stimulation, the hearts were removed, sectioned and prepared for autoradiography. Cardiac pacing significantly (p less than 0.02) decreased systolic blood pressure, and significantly increased (p less than 0.05) glucose utilization by all regions of the heart, with the exception of the left ventricular endocardium and the left ventricular papillary muscles. Vagal efferent stimulation elicited significant (p less than 0.05) decreases in glucose utilization in both the right atrium and right ventricle. Conversely, efferent stellate ganglion stimulation had no effect on the glucose utilization of any regions of the myocardium studied. This study demonstrates that both cardiac pacing and cardiac vagal efferent neuronal stimulation can produce distinct changes in regional myocardial glucose utilization.

Animals↗

Frequency-dependent activation of glucose utilization in the superior cervical ganglion by electrical stimulation of cervical sympathetic trunk.

Electrical stimulation of the distal stump of the transected cervical sympathetic trunk produces a frequency-dependent activation of glucose utilization, measured by the deoxy[14C]glucose method, in the superior cervical ganglion of the urethane-anesthetized rat. The frequency dependence falls between 0-15 Hz; at 20 Hz the activation of glucose utilization is no greater than at 15 Hz. Deafferentation of the superior cervical ganglion is transection of the cervical sympathetic trunk does not diminish the rate of glucose utilization in the ganglion in the urethane-anesthetized rat. These results indicate that the rate of energy metabolism in an innervated neural structure is, at least in part, regulated by the impulse frequency of the electrical input to the structure, and this regulation may be an essential component of the mechanism of the coupling of metabolic activity to functional activity in the nervous system.

Animals↗

WAL 2014--a muscarinic agonist with preferential neuron-stimulating properties.

The ability of WAL 2014 to elicit muscarinic responses was investigated in various in vitro and in vivo models. In CHO cells transfected with human m1- or m3- receptor genes, WAL 2014 was clearly more effective in stimulating the M1-mediated PI response. In isolated tissue preparations, WAL 2014 exhibited full agonist properties in the rabbit vas deferens (putative M1 receptor) and behaved like a partial agonist at M2 receptors in the atrium and M3 receptors in the ileum of guinea-pigs. In the pithed rat, in which the increase in blood pressure is mediated through a stimulation of M1 receptors in sympathetic ganglia, WAL 2014 produced a full dose response curve, whereas the reference compounds RS 86 and arecoline exhibited a bell-shaped behaviour. This is in accord with the view that WAL 2014 selectively activates M1 receptors in sympathetic ganglia, whereas conventional agonists in the same dose range stimulate both ganglionic M1 and vascular M3 receptors. The preferential neuron-stimulating properties were confirmed by EEG recording in the rabbit, in which muscarinic activation occurred at doses similar to those for ganglionic stimulation in the pithed rat. On the other hand, higher doses of WAL 2014 were needed to elicit muscarinic effects in peripheral effector organs, i.e. bradycardia, urinary bladder contraction and increase in airway resistance. It is concluded that WAL 2014 due to its preferential neuronal activity is a promising candidate for a cholinergic substitution therapy in Alzheimer's disease.

Animals↗

The effect of hemicholinium-3 on choline and acetylcholine levels in a sympathetic ganglion.

Pregangliaaonic stimulation of the cat's superior cervical ganglion in the presence of hemicholinium-3 (HC-3) produced the expected depletion of acetylcholine (ACh) stores, but failed to cause a corresponding reduction in the choline content. These results suggest that either HC-3 possesses an intracellular site of action or that in lower doses it selectively inhibits a specialized choline transport system in cholinergic nerves. At a dose of 2 mg/kg, HC-3 probably blocked ACh synthesis completely in ganglia stimulated at 20 Hz. Under these conditions, there was a rapid depletion of ACh to about 50% of control levels during the first 5 min of stimulation and thereafter the rate of decline in ACh levels proceeded at a much slower pace. Since the 2 mg/kg dose of HC-3 did not raise plasma choline concentrations, it may be assumed that non-specialized choline transport systems in other tissues were not significantly inhibited by this dose of HC-3. However, when the dose of HC-3 was increased to 4 mg/kg, plasma choline levels increased by 58%.

Acetylcholine↗

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was obtained by stimulation of the celiac ganglion with LPS.

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was developed by stimulation of the celiac ganglion with lipopolysaccharide (LPS) in pregnant rabbits. The renal and hepatic blood flow were measured after stimulation of the celiac ganglion with 10 microL (group 1), 100 microL (group II) and 300 microL (group III) of LPS (10 mg/mL conc.) and with 100 microL of normal saline (group IV). The bifurcation of the abdominal aorta was also stimulated with 300 microL of LPS (group V). A control experiment was also done in this study (group VI). Histopathological studies of kidney and liver tissue were also performed in this protocol. A significant reduction in renal and hepatic blood flow was observed in pregnant rabbits with the times and dosage dependent on stimulation of the celiac ganglion by LPS. Stimulation of the bifurcation of the abdominal aorta with LPS could not produce any changes in renal and hepatic blood flow. Preeclampsia-like histologic changes of kidney and liver tissue were also observed. These results suggest that exogenous stimulation of the celiac ganglion causes decreased renal and hepatic blood flow, resulting in preeclampsia-like histologic changes of kidney and liver in pregnant rabbits.

Animals↗

[Correlation of hemodynamic changes and mesenteric microcirculation in response to electric stimulation of the celiac ganglion in rats].

Acute experiments on anesthetized rats were made to study the time course of cardiac output (Cardiogreen dilution method) and systemic arterial pressure during electrical stimulation of the celiac ganglion. In other series of experiments a study was made of the time course of microcirculatory changes in the mesentery under the same conditions and with the use of intravital microscopy. An appreciable increase in the minute volume (23.44 +/- 4.91) was revealed 6 s after the onset of the stimulation. The increase in arterial pressure amounted to 7.06 +/- 2.45%. The increase of arterial pressure in the second series of experiments was 18.8 +/- 2.2%, and vasoconstriction 4.1 +/- 1.6% (the initial diameter of the vessels being 264.59 +/- 4.50 micrometers). Celiac ganglion stimulation led to a progressive deceleration of the blood flow and stoppage of the blood flow, with the diameter of the microvessels remaining unchanged. Regression analysis of the data obtained allows the conclusion that microcirculatory changes seen in the mesentery and initial hypertensive response are consequent on the increased cardiac output, on the one hand, and on the constriction of the mesenterial vessels, on the other.

Animals↗

Selective stimulation of jugular ganglion afferent neurons in guinea pig airways by hypertonic saline.

We evaluated the ability of hyperosmolar stimuli to activate afferent nerves in the guinea pig trachea and main bronchi and investigated the neural pathways involved. By using electrophysiological techniques, studies in vitro examined the effect of hyperosmolar solutions of sodium chloride (hypertonic saline) on guinea pig airway afferent nerve endings arising from either vagal nodose or jugular ganglia. The data reveal a differential sensitivity of airway afferent neurons to activation with hypertonic saline. Afferent fibers (both A delta and C fibers) with cell bodies located in jugular ganglia were much more sensitive to stimulation with hypertonic saline, compared with afferent neurons with cell bodies located in nodose ganglia. Additional studies in vivo demonstrated that inhalation of aerosols of hypertonic saline induced plasma extravasation in guinea pig trachea that was mediated via tachykinin NK1 receptors. Identification of a differential sensitivity of guinea pig airway afferent nerves to hypertonic saline leads to the speculation that airway responses to hyperosmolar stimuli may result from activation of afferent neurons originating predominantly from the jugular ganglion.

Administration, Inhalation↗