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Evaluation of the control of glucagon secretion by the parasympathetic nervous system in man.

To evaluate the influence of the parasympathetic nervous system on human glucagon secretion, we have measured the plasma immunoreactive glucagon (IRG) levels after the administration of edrophonium, bethanechol chloride, and 2-deoxyglucose, and have compared the IRG responses to hypoglycemia in normal, atropinized, and vagotomized man. Edrophonium administered i.v. and bethanechol chloride administered s.c. did not affect IRG levels. Two-deoxy-glucose resulted in symptomatic neuroglucopenia with resultant vagal discharge, as evidenced by increased gastric acid secretion; but no changes in IRG concentrations were observed. The IRG response to insulin-induced hypoglycemia in normal subjects was not influenced by the administration of atropine. In seven subjects with a truncal vagotomy and no increased gastric acid secretion during insulin-induced hypoglycemia, the IRG increases were indistinguishable from those of control subjects in terms of timing, peak level obtained, or total glucagon response. We conclude that the cholinergic system is unlikely to play an important role in modulating glucagon secretion in man.

Adult

Asystole and its treatment: the possible role of the parasympathetic nervous system in cardiac arrest.

Parasympathetic tone may be high during ventricular asystole because of reflex vagal stimulation from a number of sources. Eight patients in cardiac arrest were treated with cardiopulmonary resuscitation. All eight patients had ventricular asystole as the initial rhythm or as the result of defibrillation. Six patients failed to respond to 5 cc to 20 cc of 1:10,000 epinephrine intravenously (IV). In all eight cases a regular rhythm (sinus in seven, idioventricular in one) appeared within 30 seconds of administration of the last dose of atropine (1 mg to 2 mg IV). Five patients (62.5%) lived 12 hours, three (37.5%) were discharged from the hospital. These results suggest that atropine may be of value in the treatment of ventricular asystole.

Adult

[Experimental studies on the parasympathetic nervous system of the trachea].

3 sheep of approximately 4 years of age were used in the experiments. In 2 sheep in the cervical part of trachea all the nervous branches reaching this organ were cut and the remaining sheep was control. The animals were alive for 21 days. The following material was sampled for investigations: medulla oblongata, cervical part of spinal cord, bilateral spinal ganglions from C1 to C8, bilateral nodus ganglion and zygomatic ganglion and left and right parts of the cervical vagus nerve. The material was fixed and cut into 15 micron sections and stained according to the modified method of Nissl. The experiments evoked vast regressive changes in the nervous cells of both central and peripheral nervous system which helped to determine the source of outlet of fibers innervating this organ. In this paper the sources of outlet for the parasympathetic nervous fibers were presented. It was found that parasympathetic nervous centers connected with trachea were located in 1/3 of the central part of nucleus parasympathicus, anterior to obex, so in this part of nucleus which is the main source of outlet for the esophageal dorsal trunk and the ventral vagus nerve.

Animals

The effect of parasympathetic nervous system on hydrodynamics of intraocular fluids and distribution of electrolytes and amino acids.

Tonographic determinations Po and C), cannulation of the anterior chamber and measurements of the secreted aqueous humor volume by the method of posterior-anterior chamber perfusion with inulin solution were carried out in normal eyes, in eyes after parasympathetic denervation and during the action of a cholinergic neurotransmitter under the conditions of postdenervation hyperexcitability. Parasympathetic denervation of the eyeball was obtained by excision of the ciliary ganglion. Additonally, pharmacological blockade of the adrenergic neurons was applied. In the aqueous humor from the posterior and anterior chamber osmolality, as well as concentrations of sodium potassium, calcium, magnesium and total alpha-amino nitrogen were determined. The cholinergic effect on the volume of secreted aqueous humor and on the channels of its outflow was described. This effect was enhanced by the postdenervation hyperexcitability state, indicating a stimulating parasympathetic influence on the passage of electrolytes and amino acids into the intraocular fluids.

Amino Acids

Fast detoxification of heroin addicts by acupuncture and electrical stimulation (AES) in combination with naloxone.

Detoxification can be accomplished more rapidly by first "flushing" the opiates from the receptor sites. Naloxone, a short acting antagonist displaces opiates from the receptor sites and such displacement precipitates an abstinence syndrome. Recently, a method of using acupuncture and electrical stimulation (AES) in combination with naloxone for fast detoxification was reported. This technique was applied to 50 cases of heroin addicts. Forty-one were detoxified. There were nine failures. Of the 41 cases, 18 patients were sent to rehabilitation centres and did not experience abstinence symptoms. Six were sent out of Hong Kong where heroin is not available, and two others did not go to a rehabilitation centre but still abstained. The other 15 were presumed to be on the drug. It is advocated that AES increases endorphin and relieves abstinence syndrome, but also at the same time inhibits the autonomic nervous system, mainly the parasympathetic nervous system. The technique does not stop the craving, therefore after detoxification, the patients should be sent for psycho-social rehabilitation, or alternatively be put on long acting antagonist.

Acupuncture Therapy

The effect of the parasympathetic autonomic nervous system on auditory fatigue.

Volunteers with normal hearing were tested for vegetative balance with the aid of vegetative reflexes and with the aid of the atropine test. The effect of white noise stimulated on hearing thresholds was then investigated together with their recovery. The vegetative system was affected experimentally by intravenous administration of atropine, and the beginning and recession of hearing fatigue was observed. Atropine caused a small change only. In a similarly arranged experiment, 1% pilocarpin administered subcutaneously in a dose of 1.4 minus 1.6 ml, resulted in increased hearing fatigue and retarded recovery at higher frequencies. The effect of pilocarpin is explained by the fact that it supports the inhibitory processes checked by the parasympathetic nervous system on the periphery.

Acetylcholine

Fisher's syndrome: a pharmacological study of the pupils.

A pharmacological study was performed in the involved pupils to demonstrate the site of lesion in a patient with Fisher's syndrome who showed marked ptosis, complete external ophthalmoplegia, pupillary involvement with anisocoria, facial paresis, ataxia, areflexia, and albuminocytological dissociation in the cerebrospinal fluid. The instillation of 2.5% methacholine produced mild constriction of one pupil. This response was not detectable in the recovery stage. The instillation of 1.25% l-epinephrine produced marked bilateral dilation of the pupils, in both the early and recovery stages. Instillation of 5% tyramine produced pupillary dilation as in the normal pupil. The response to 5% cocaine, tested only in the recovery stage, was weak in one pupil. These results imply that the pupillary involvement was due to peripheral involvement of the sympathetic and parasympathetic nervous systems. The lesion in the sympathetic nervous system was preganglionic, but in the parasympathetic nervous system the precise localization could not be determined.

Aged

Role of the nervous system in experimentally induced arrhythmias.

The purpose of our studies was to examine the role of the nervous system in arrhythmias produced by digitalis overdose and coronary artery occlusion in the cat. This was done by observing the effect of these arrhythmogenic procedures on cardiac efferent neural activity and then determining whether any observed alteration in neural activity contributed to the cardiac rhythm disturbances evoked by digitalis and coronary artery occlusion. Our data indicate that both procedures used to evoke arrhythmias activate each division of the autonomic nervous system. Activation of the sympathetic nervous system resulted in a deleterious effect on cardiac rhythm whereas activation of the parasympathetic nervous system, in general, resulted in a beneficial effect on cardiac rhythm. With coronary occlusion, the role exerted by the nervous system depended on the anatomic location of the involved myocardium. Studies directed at elucidating the mechanisms whereby the nervous system caused cardiac rhythm disturbances indicated that there may be an important difference between the antiarrhythmic efficacy of beta-adrenergic blockade and bilateral stellate ganglionectomy. The latter procedure proved to be a more effective way of removing deleterious sympathetic neural effects on the heart. In conclusion, our findings suggest that the development of new drugs for treating arrhythmias resulting from digitalis and coronary occlusion should be aimed at finding drugs that act to either depress central sympathetic outflow or enhance parasympathetic effects on the ventricle.

Animals

Signals for glucagon secretion.

The normal physiological role of glucagon is in controlling hepatic glucose output. Glucagon subserves the role of homeostasis by maintaining plasma glucose and of a stress hormone by producing hyperglycaemia. While control of glucagon release by circulating metabolites and also other hormones is clearly important, it seems likely that the nervous system exerts an over-riding influence. The parasympathetic nervous system maintains homeostasis and the sympathetic acts in stress. Glucagon levels are found to be high in cirrhosis and also after acute hepatic failure. It is likely that these changes in glucagon concentration are secondary to metabolic abnormalities. While some glucagon is cleared by the liver, a similar clearance is seen by many other tissues and it is not likely that the elevation of glucagon seen in liver failure is due solely to a gross deficiency of glucagon clearance. No liver abnormality is seen in the glucagonoma syndrome, where glucagon concentration are chronically high, or in patients who have had a total pancreatectomy, where plasma glucagon is undetectably low. It thus seems unlikely that liver mass is importantly controlled by glucagon.

Adrenalectomy

Role of autonomic nervous system controlling surface tension in fetal rabbit lungs.

After the maternal abdomen was opened under methoxyflurane anesthesia, fetal rabbits of 27.5 days gestation were given injections through the intact uterine wall of saline, pilocarpine, isoxsuprine, muscarine, phenylephrine, atropine, phenoxybenzamine, or propranolo, alone or in appropriate combinations. Fetal rabbits were delivered by hysterotomy and killed without breathing 2.5 h later. Static pressure-volume curves with air showed improved retention on deflation in fetal rabbits that had injections of pilocarpine, or isoxsuprine, but not of muscarine or phenylephrine. The effect of pilocarpine on the pressure-volume curve was blocked by atropine, phenoxybenzamine, and propranolol, and the effect of isoxsuprine was blocked by propranolol but not phenoxybenzamine. The data suggest that pilocarpine produces secretion of surfactant into lung air spaces by exciting the sympathetic nervous system, a known function of pilocarpine, rather than the parasympathetic nervous system. This may result in stimulation of the same beta-adrenergic receptors affected by isoxsuprine which is also thought to stimulate surfactant secretion.

Animals

[Vitamin B1 and autonomic drugs: a reprint].

The problem of the relationship between the thiamine and autonomic system drugs was studied about 30 years ago. To the vitamin was attributed an excitatory effect upon the peripheric section of parasympathetic nervous system and a synergic action with acetylcholine. Both an acetylcholine-like substance and thiamine are liberated at the nerve terminals after a stimulation. A similar synergic action of thiamine with adrenaline was also demonstrated. The study of the relationship between these drugs and the vitamin B1 is also now interesting. We want to stimulate a new series of experiments on this subject with the reprint of this review.

Acetylcholine

The influence of pilocarpine and atropine on pentobarbital-induced nystagmus in the New Zealand white rabbit.

Nystagmus, induced by intravenous pentobarbital in rabbits, increased in frequency and amplitude as a result of intravenous pilocarpine administration. In seven of nine animals anesthetized with pentobarbital but not showing eye movements, pilocarpine injection elicited nystagmus. In all rabbits, nystagmus was terminated by subsequent intravenous administration of atropine, indicating that the parasympathetic nervous system contributes to nystagmus observed in barbiturate treated animals. The results reported here are of value in their implication for an understanding of the physiologic mechanisms which underlie eye movement disorders commonly observed in barbituarate intoxicated individuals.

Anesthesia

In vitro behavior of human intestinal mucosa. The influence of acetyl choline on ion transport.

The possibility that the autonomic nervous system may influence the function of intestinal mucosa was investigated by assessing the effect of acetyl choline on ion transport in human intestine. Isolated pieces of stripped ileal mucosa were mounted in Perspex flux-chambers and bathed in isotonic glucose Ringer's solution. Acetyl choline caused a rise in mean potential difference (8.8-12.3 mV, P less than 0.002) and short circuit current (287.7-417.2 muA-cm-2, P less than 0.01) (n = 12), observable at a concentration of 0.01 mM and maximal at 0.1 mM. This effect was enhanced by neostigmine and blocked by atropine. Isotopic flux determinations revealed a change from a small mean net Cl absorption (58) to a net Cl secretion (-4.3mueq-cm-2-h-1P less than 0.001) due predominantly to an increase in the serosal to mucosal unidirectional flux of Cl (10.63-14.35 mueq-cm-2-h-1P less than 0.05) and a smaller reduction in the mucosal to serosal flux (11.22 to 10.02 mueq-cm-2-h-1P less than 0.05). Unidirectional and net Na transport was unaffected. A similar electrical and ion transport response was observed in a single study of two pieces of jejunal mucosa. In the absence of glucose net chloride secretion was produced and again an insignificant effect on net sodium transport was noted. Acetyl choline did not provoke a sustained effect on mucosal cyclic adenine nucleotide levels although a short-lived cyclic adenine nucleotide response was seen in some tissues 20-30 s after drug addition. These studies demonstrate that acetyl choline does influence human intestinal ion transport by stimulating chloride secretion and suggest a possible mechanism by which the parasympathetic nervous system could be concerned in the control of ion transport.

Acetylcholine