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Effect of beta-adrenoceptor blockade on cardiac activity in rats during postnatal ontogeny.

Electrical stimulation of the right stellate ganglion produces a positive chronotropic effect in 21-, 56-, and 100-day-old rats. The response of the heart rate to suprathreshold stimulation increased from the 21st to 100th day. By contrast, during beta-adrenoceptor blockade the heart rate response decreased. The data suggest that the role of beta-adrenoceptor in the regulation of cardiac chronotropic function increased with age.

Adrenergic beta-Antagonists↗

Post-tetanic potentiation in ganglia which are blocked with hexamethonium.

1 Post-tetanic potentiation (p.t.p.) of the compound action potential in the presence of hexamethonium was observed in the isolated stellate ganglion of the hamster using extracellular postganglionic recordings. 2 The magnitude of the p.t.p. was small (less than a 20% increase) in the control solution, but increased as the depth of blockade with hexamethonium was increased. 3 The magnitude of the p.t.p. was frequency-dependent between 1 and 40 Hz. 4 Atropine partially blocked the p.t.p. 5 McN-A-343, a muscarinic agonist, potentiated ganglionic transmission which had been partially blocked by hexamethonium. 6 Repetitive stimulation in the presence of hexamethonium potentiated the discharges induced by DMPP, a nicotonic agonist. The potentiation was blocked by atropine. 7 It was concluded that the p.t.p. in the presence of hexamethonium has the same characteristics as p.t.p. in the control solution. There appears to be both a muscarinic component and a presynaptic component of the p.t.p.

Action Potentials↗

'Neuropeptide tyrosine' (NPY) is co-stored with noradrenaline in vascular but not in parenchymal sympathetic nerves of brown adipose tissue.

By using immunohistochemistry it is shown that both the parenchymal and vascular sympathetic innervation in the interscapular depot of brown adipose tissue in the rat contain the catecholamine-synthesizing enzyme tyrosine-hydroxylase (TH). In contrast, 'neuropeptide tyrosine' (NPY) is selectively present in the vascular sympathetic nerves of the tissue--but not in nerves around brown fat cells. This is consistent with the presence of two populations of neurons (containing either TH alone or TH plus NPY) in the stellate ganglion, which is the probable origin of the sympathetic nerves in the interscapular brown adipose tissue. Furthermore, the perivascular NPY-positive nerves in the brown adipose tissue disappeared after 6-hydroxydopamine treatment, demonstrating their noradrenergic nature. Taken together, these findings suggest that sympathetic nerves to blood vessels and brown fat cells represent two separate subpopulations of autonomic neurons.

Adipose Tissue, Brown↗

Visualization of differential neurofilament phosphorylation in the pre- and postsynaptic axoplasm of the squid giant synapse: an electron spectroscopic study.

When inelastically scattered electrons with an energy loss specific for interaction with phosphorus atoms were used for visualization of sections of squid axons, bead-like domains of elongated proteins, presumably neurofilaments, exhibited distinct phosphorus signals. A marked asymmetry of these phosphorus signals was detectable between the pre- and the postsynaptic cytoskeleton of the giant synapse. Signals were very numerous and intense in the presynaptic terminal, while rare and weak in the postsynaptic axoplasm. The giant axon revealed a delayed appearance of phosphorus signals in its course from the cell bodies in the giant fibre lobe to its exit from the stellate ganglion. Numerous and intense phosphorylation signals were evident only in the peripheral giant axon. Asymmetry in the distribution of phosphorus signals between pre- and postsynaptic axoplasm paralleled differences in Ca(2+)-buffering mechanisms, as shown in a previous study. In the presynaptic terminal patterns of phosphorus signals correlated with precipitates which had formed after intra-axonal injection of calcium. Our observations suggest a role of phosphorylated neurofilaments in binding of calcium in the squid synapse.

Animals↗

Cluster headache and the sympathetic nerve.

OBJECTIVE: To determine the effect of a sympathetic block at C7 on cluster headache. BACKGROUND: Eleven patients presenting to a pain control unit with cluster headache were included in the study after giving informed consent. METHODS: In all patients, a mixture of 5 mL of 0.5% bupivacaine hydrochloride and 1 cc of methylprednisolone acetate was injected onto the base of the C7 transverse process. RESULTS: The injection was applied during the acute phase of headache in 6 patients and all experienced immediate and complete relief. The other 5 patients received the injection between attacks. Of the 11 patients treated, 8 went into remission by aborting the cluster. In some patients, repeated injections were given before the cluster was aborted. Three patients did not respond to treatment. One patient with chronic paroxysmal hemicrania experienced pain relief of the acute attack after treatment, but the procedure did not abort the subsequent attacks. A surgical sympathectomy removing the stellate ganglion rendered him pain-free for 15 months after which he was lost to follow-up. CONCLUSION: Blocking the sympathetic nerve aborts an acute attack of cluster headache and may play a major role in aborting the cluster. Although only one patient with chronic paroxysmal hemicrania responded to surgical sympathectomy, this procedure may be considered as an alternative if there is poor response to oral medication or a sympathetic block.

Acute Disease↗

Segmental alpha-receptor-mediated vasoconstriction in the canine coronary circulation.

Recent studies from this laboratory have indicated that sympathetic alpha-receptor-mediated coronary vasoconstriction can compete with local metabolic vasodilation to reduce the oxygen supply to the myocardium. In vitro studies from other laboratories on isolated coronary vessel strips suggest that large epicardial vessels are the dominant site of adrenergic alpha-receptor activity. In this study we used anesthetized, open-chest dogs to test the hypothesis that alpha-receptor-mediated vasoconstriction occurs predominantly in epicardial vessels, which are partially removed from the metabolic milieu in the myocardium. Adrenergic beta-receptor blockade was achieved by propranolol (3 mg/kg, iv). The circumflex coronary artery was pump-perfused at constant pressure to minimize passive changes in large vessel resistance. Pressure was measured at the tip of the perfusion cannula sealed in the circumflex artery, and in an apical branch of the circumflex artery. Large vessel resistance was calculated as the pressure gradient along the vessel segment divided by the coronary flow. Intracoronary injections of nitroglycerin were used as an independent measure of the vasomotor responsiveness of the large vessel segment. Adrenergic alpha-receptor activation was produced by intracoronary bolus injections of norepinephrine and by electrical stimulation of the left stellate ganglion. Alpha-receptor stimulation caused an increase in total coronary vascular resistance; however, the relative increase in the resistance of the large vessel was only about 60% of that seen for the entire coronary bed. These data suggest that, contrary to the proposed hypothesis, adrenergic alpha-receptor-mediated vasoconstriction in the large coronary vessels is not proportionally greater than that observed in the total coronary vascular bed.

Animals↗

[A case of central retinal artery occlusion after anterior posterior fusion of the lumbar spine].

We report a case of central retinal artery occlusion after anterior-posterior fusion of the lumbar spine. The patient suddenly lost his vision of the right eye in the ICU just after the end of long procedure for anterior-posterior fusion of the lumbar spine. The patient was diagnosed as having central retinal artery occlusion, and treated successfully with treatments including immediate administration of urokinase and PGE1, stellate ganglion block, and hyperbaric oxygen therapy. The patient was discharged from the hospital on the 54th postoperative day with adequate vision to drive a car. Central retinal artery occlusion is a rare but very serious complication during and after supine surgery with prone position. It is very important for us to be aware of its possible occurrence. We have to diagnose and treat, as soon as possible, the vision loss after the spine surgery.

Adult↗

Reversal of serotonin vasodilatation in the dog external carotid bed by sympathetic denervation.

In view of the conflicting reports of both constrictor and dilator effects of serotonin on the external carotid vascular bed of dogs, the influence of intraarterial infusions of the amine on blood flow through this territory was assessed by electromagnetic flowmeter techniques. In anesthetized intact dogs, serotonin produced dose-related increases in flow. These vasodilator responses were markedly diminished after ipsilateral vagotomy and were followed by delayed vasoconstriction, which then became the predominant response. Pretreatment with atropine did not modify dilator responses, while resection of the ipsilateral stellate ganglion reversed them to pure constriction. In the internal carotid, serotonin elicited constriction, and this effect was unaffected by vagotomy. These results were interpreted in terms of the hypothesis relating serotonin reactivity to vascular tone. The amine would elicit dilatation through an effect on tonically constricted small vessels. Removal of this tone by section of the vagosympathetic trunk or stellectomy would unmask the constrictor effect of serotonin on large vessels. Such reversal of responses would not occur in the internal carotid, a territory normally devoid of important sympathetic tone.

Animals↗

Effect of visceral afferent activation on leg extension induced by sciatic afferent stimulation.

In cats under light chloralose and sodium pentobarbital anesthesia the effects of electrical stimulation of various visceral afferent nerves on leg extension induced by sciatic afferent stimulation were studied. Stimulation of the central end of the cervical vagus and stellate ganglion produced inhibition of induced leg extension while stimulation of the distal end of the thoracic vagus, coeliac ganglion, and splanchnic nerves produced facilitation. Decortication slightly reduced the inhibitory effect and greatly reduced the facilitatory effect. Additional decerebration greatly reduced the inhibitory effect and almost abolished the facilitatory effect. Spinal transection at C1 completely abolished the inhibitory and facilitatory effects on induced leg extension. These results suggest that visceral afferents facilitate sciatic induced leg extension principally through the cortex while they inhibit extension through the midbrain and hypothalamus.

Afferent Pathways↗

Distribution and origin of the peripheral innervation of rat cervical esophagus.

Several neurotransmitters, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), galanin, enkephalin, calcitonin-gene related peptide (GGRP), substance P, as well as nitric oxide synthase (NOS), and the noradrenergic marker tyrosine-hydroxylase (TH) were localized by immunocytochemistry in the cervical esophagus of rat. Nerve fibers containing the neuropeptides, NOS, and TH were distributed in the myenteric plexus, around muscle bundles and small blood vessels. Injection of the retrograde tracer True Blue (TB) into the cervical esophagus resulted in the appearance of labeled nerve cell bodies in the superior cervical, the stellate, the nodose, the sphenopalatine, the dorsal root ganglia at levels C2-C7, and in local ganglia close to the thyroid. Most of the TB-labeled nerve cell bodies in the superior cervical ganglia contained NPY. In the stellate ganglion, a few labeled nerve cell bodies contained VIP whereas an additional few cell bodies stored VIP. In local ganglia, the majority of labeled cell bodies contained VIP. In the nodose ganglion and cervical dorsal root ganglia, the majority of the labeled nerve cell bodies stored CGRP. The results indicate that the cervical esophagus has a dense innervation with multiple neurotransmitters emanating from several ganglia. As judged by the pattern of nerve fiber distribution, they may regulate esophageal peristalsis and blood flow, some of them possibly in a cooperative manner.

Amino Acid Oxidoreductases↗

Effects of berberine on delayed afterdepolarizations in ventricular muscles in vitro and in vivo.

The effects of berberine on delayed afterdepolarizations in ventricular muscles in vitro and in vivo were investigated to help explain the mechanisms for its antiarrhythmic action. Berberine 3 mumol reduced the amplitude of delayed afterdepolarizations induced by ouabain or posthypoxic reoxygenation and abolished subsequent triggered activity in isolated guinea pig right ventricular papillary muscles. At 30 mumol, it decreased the incidence of delayed afterdepolarizations, associated with a further decrease in the amplitude of delayed afterdepolarizations. In rabbit left ventricular (LV) muscles in vivo, berberine 1 mg/kg intravenously (i.v.) decreased the amplitude of delayed afterdepolarizations evoked by ouabain and calcium gluconate from 9.6 +/- 1.9 to 6.8 +/- 0.8 mV and left stellate ganglion stimulation from 9.4 +/- 2.1 to 6.2 +/- 0.7 mV and blocked ventricular arrhythmias. After a 4-mg/kg i.v. bolus, the drug inhibited and even completely abolished development of delayed afterdepolarizations, yet still reduced maximal velocity of depolarization in isolated and in vivo ventricular muscles. Therefore, one of the important mechanisms for antiarrhythmic action of berberine may be suppression of delayed afterdepolarizations, which may be attributable in part to a decrease in Na+ influx.

Animals↗

Expression of neurofilament proteins during development of the nervous system in the squid Loligo pealei.

The squid nervous system includes various brain ganglia, optic lobes (the visual center), and the stellate ganglia, the system of giant motor fibers responsible for rapid jet-propelled escape behavior. The large caliber of giant fibers is due, in part, to the accumulation of squid-specific neurofilaments (NFs) made up of a heavily phosphorylated NF 220 protein together with NF 70 and NF 60 subunits. Using antibodies prepared against known peptide sequences in these proteins, together with a mammalian-derived antibody that specifically recognizes phosphorylated squid NF 220, we studied the localization of NFs in adult tissues and during neural development. Immunoblot and immunohistochemical analyses showed that NFs were present in adult neural tissues, primarily in selected fibers, with giant axons showing the most robust expression. After the first neurons differentiated at stage 22, immunoblots showed NF 60- and NF 70-immunoreactive proteins at all stages. The NF 220 subunit, however, was not detected in immunoblots at any developmental stage. Phosphorylated NF 220 immunoreactivity, although absent in immunoblots, was first seen in selected fibers of the stellate ganglia at stage 25, increasing thereafter in all giant fibers until hatching (stage 30). The stellate ganglion is the first neural tissue to acquire a mature neurofilament complement (i.e., phosphorylated NF 220), shortly before the onset of jet-propelled escape behavior. The temporal pattern of expression of the NFs during development resembled that seen in vertebrates; i.e., the smaller NFs appeared before the larger subunit in most neural tissues. In the squid, the expression pattern seems to depend upon the post-transcriptional regulation of a single gene rather than upon transcriptional regulation of three independent genes as in vertebrates.

Animals↗

Chronic post thoracotomy pain.

Chronic post-thoracotomy pain (CPP) is a vexing clinical problem whose management has received scant attention. In order to identify the risk factors associated with CPP and determine the optimal treatment, the records of 238 consecutive patients who underwent thoracotomy were reviewed. CPP was defined as discomfort requiring the regular administration of analgesics that continued more than three months following surgery. CPP was present in 25 (11%) patients: 10/20 (50%) chest wall resections, 5/25 (20%) pleurectomies, 10/193 (5%) pulmonary resections. Among the 23 patients who required preoperative narcotics, 12 (52%) developed CPP. Improved pain control and decreased narcotic use was achieved via the administration of nonsteroidal anti-inflammatory medication and tricyclic anti-depressants. In addition, 10/25 patients required 11 pain procedures: trigger-point injection, intercostal blocks, injections of epidural steroids, stellate ganglion block. Recurrent pain occurred in 20 patients following initial control. All were found to have tumor regrowth. We conclude that CPP occurs more commonly following chest-wall resection and pleurectomy, and that preoperative narcotic use is a predictor of CPP. Worsening pain following initial relief should prompt a vigorous search for recurrent cancer.

Adult↗

Long-lasting adverse effects of prenatal hypoxia on developing autonomic nervous system and cardiovascular parameters in rats.

To determine whether prenatal hypoxia increases the risk of developing cardiovascular disorders as an adult and, if so, the identity of the cell mechanisms involved in such dysfunction, we evaluated the sympathoadrenal system and central areas related to cardiovascular events during development and the cardiovascular parameters in adults. Pregnant rats were exposed to hypoxia (10% oxygen) from embryonic day (E) 5 to E20 and the offspring studied at 1, 3, 9 and 12 weeks of age for neurochemistry and at 12 weeks of age for cardiovascular analysis. In the 1-, 3- and 9-week-old offspring, the levels and utilization of catecholamines were reduced in sympathetic ganglia, in target organs, in adrenals and in the rostral part of the A2 cell group in the nucleus tractus solitarius, but were increased in the locus coeruleus. In the 12-week-old adult offspring, the lowered autonomic nervous activity was restricted to cardiac-related structures, i.e. the stellate ganglion, heart and adrenals. In adult rats, prenatal hypoxia did not affect the cardiac parameters under resting conditions but increased blood pressure and the variability of blood pressure and heart rate under stress conditions. The altered metabolic activity of the sympathoadrenal system and related central areas during development and at adulthood for most structures might be part of the potential mechanisms contributing to cardiovascular disorders in adults.

Adrenal Glands↗

Temporary sympathectomy in the treatment of chronic refractory angina.

The aim of this study was to investigate the safety and efficacy of the two most commonly practiced temporary sympathectomy techniques in the treatment of chronic refractory angina. Fifty-nine consecutive refractory angina patients commencing outpatient temporary sympathectomy from November 1, 2000 to November 1, 2002, were prospectively audited for duration of pain relief and procedural complications over a two-year period. A total of 227 stellate ganglion blockades (SGB) and 100 paravertebral blockades (PVB) were performed on 59 chronic refractory angina (CRA) patients naïve to sympathectomy. The mean period of pain relief obtained following SGB was 3.48 weeks (SD 3.38) and the mean relief following PVB was 2.80 weeks (SD 2.00). Mild, fully reversible complications occurred in 3% of SGB and 3% of PVB procedures, with one patient requiring overnight hospitalization. This study demonstrates that temporary sympathectomy may provide a safe and effective outpatient procedure in refractory angina patients when applied as part of holistic care.

Aged↗

[Directed sympathetic denervation of the heart--an actual therapeutic method or myth?].

Aimed sympathetic denervation of the heart, i. e. bilateral removal of the stellate ganglion Th 1-Th 3 was used in Czechoslovakia since 1981 in eight patients who were followed up for prolonged periods. The patients were operated on account of angina at rest which caused deterioration of the quality of their lives. In case of extensive affection of the coronary arteries surgical treatment was not feasible and pharmacological treatment did not bring relief. At the time of a five-year check up 7 patients survived. All patients reported relief and their efficiency during ergometry improved. Four of the patients worked for several years. The authors discuss whether the above treatment is still justified.

Adult↗

Sympathetic modulation of the relation between ventricular repolarization and cycle length.

Sympathetic influences on ventricular repolarization are not yet fully elucidated, despite their relevance to arrhythmogenesis. The sympathetic control of repolarization, measured from an endocardial monophasic action potential duration (APD) and from the QT interval, was investigated in 24 anesthetized cats. The effects of right and left stellectomy and of subsequent bilateral stellectomy or beta-blockade on the relation between APD (or QT) and cycle length (CL) at steady state, and on the kinetics of adaptation of APD to a sudden change in cycle length were studied separately. Steady-state APD/CL (or QT/CL) relations were obtained by atrial pacing at different cycle lengths. The kinetics of APD adaptation were evaluated for a sudden decrease of approximately 100 msec in pacing cycle length. The steady-state APD/CL (QT/CL) relation was fitted by the hyperbolic function APD = CL/[(a. CL) + b]. From this, two parameters were computed: 1) 1/a, that is, APD (QT) extrapolated at infinite cycle length (APDmax or QTmax) and 2) the cycle length at which 50% of the total change in APD (or QT) occurred (CL50 = b/a). Right stellectomy reduced APDmax and CL50, an effect reversed by subsequent left stellectomy or beta-blockade (propranolol, 0.5 mg/kg). Left stellectomy prolonged APDmax and CL50. Bilateral stellectomy, in both groups, caused a further increase in these variables. Results were similar for the QT/CL relation. The adaptation kinetics of APD to cycle length was described by the sum of two exponentials. The first time constant (tau fast, about three beats) was unchanged by any intervention; the second (tau slow) was shortened by right stellectomy and prolonged by left stellectomy. The further removal of the remaining stellate ganglion had the same effect in both groups, that is, an increase in tau slow. Thus, sympathetic innervation modulates both the steady-state dependence on cycle length and the kinetics of adaptation to sudden rate changes of ventricular repolarization. The effects of sympathetic influence are asymmetrical. Right stellectomy shortens APDmax and QTmax, reduces CL50, and accelerates APD adaptation to a new steady state. Because these effects are reversed by beta-blockade or left stellectomy, they are likely to be due to a reflexly enhanced sympathetic outflow to the ventricles through the left-sided nerves.

Action Potentials↗

Effects of sympathetic stimulation and applied catecholamines on mechanical and electrical responses to stimulation of the vagus nerve in guinea-pig isolated trachea.

Mechanical and electrical responses to stimulation of the vagus nerve were studied in the isolated, innervated trachea of the guinea-pig. In approximately half the preparations tested, the amplitudes of mechanical constrictor responses to stimulation of the vagus were reduced substantially during a period of sympathetic stimulation. Vagal responses were unaltered in the remainder. In single trachealis cells, stimulation of the vagus nerve or sympathetic stellate ganglion elicited depolarization and hyperpolarization, respectively. Vagally-mediated depolarization was decreased, unchanged or increased in amplitude after a period of sympathetic stimulation. Isoprenaline almost abolished mechanical responses induced by stimulation of the vagus, and this effect was blocked by propranolol. Noradrenaline attenuated markedly vagal mechanical responses also, and this effect was blocked by a combination of propranolol and phentolamine. Both noradrenaline and isoprenaline hyperpolarized single trachealis cells and greatly reduced the amplitude of vagally-mediated depolarization. Neither sympathetic stimulation nor applied catecholamines altered mechanical responses to applied acetylcholine, strongly suggesting that their effects on vagal responses are predominantly presynaptic.

Acetylcholine↗