IN VIVO SYNTHESIS OF STABLE RNA WITHIN THE RAT NODOSE GANGLIA FOLLOWING VAGOTOMY

Abstract— We have investigated the in vivo synthesis of stable RNA in the rat nodose ganglia following unilateral vagotomy. Incorporation of precursor into rRNA, and possibly tRNA, in the injured ganglion increases rapidly after vagotomy, reaching twice the normal value at 2 days post-crush. In contrast to this, incorporation within the uninjured colateral ganglion decreases to about 65% of normal values after 4 days. But, by 7 days, both ganglia appear to be returning to their normal levels. One phase of DNA synthesis is detected in the injured ganglion, at days 1 and 2. while two phases are found in the contralateral ganglion, at days 2 and 34.     

VAGOTOMY—Clinical Results,with a Note on Temporary Gastrostomy

Sixty replies to questionnaires sent to more than 100 patients who had had vagotomy for peptic ulcer showed that 93 per cent had satisfactory results. There were no deaths in this series. Three times as many unsatisfactory results occurred in a group of patients who had had gastrectomy. There were no proved recurrent or marginal ulcers in either group.Vagotomy plus a complementary procedure has proved, in the author''s experience, to be the operation of choice in chronic duodenal ulcer. At present gastrectomy plus vagotomy appears to be less desirable than vagotomy plus pyloroplasty or gastroenterostomy.     

PYLOROPLASTY FOR GASTRIC DRAINAGE WITH VAGOTOMY

Heineke-Mikulicz pyloroplasty for gastric drainage in connection with vagotomy was carried out in 50 cases.Postoperatively a nasogastric tube with suction was used for 72 hours. The diet then was increased very slowly from liquid to bland, over a period of several weeks. If symptoms suggestive of retention developed, the oral intake was sharply decreased and if no relief was noted the tube was reinserted for 24 to 48 hours.Of the 50 patients, 46 had no retention symptoms after operation. Of the four who had, one required gastroenterostomy but was later found to have carcinoma of the pancreas with ulceration into the duodenum. The remaining three responded to conservative measures.     

IN VIVO SYNTHESIS OF RAPIDLY-LABELLED RNA WITHIN THE RAT NODOSE GANGLIA FOLLOWING VAGOTOMY

Abstract— The synthesis of rapidly-labelled RNA was studied in the nodose ganglia following unilateral vagotomy. Early changes were detected in the electrophoretic patterns of RNA from both ganglia following a crush of the right vagus. The right ganglionic response is characterized by two phases, the first involving rapid processing of rRNA with associated changes in 'message-like' RNA (mlRNA). A second change, detected by 14 days, appears to involve an increase in the heterodispersity of mlRNA and decreased processing of rRNA. The left ganglion follows a very similar response to that of the right with the exception of the changes in rRNA. However, the left response lags behind that of the right by at least 1 day. We conclude that extensive changes in gene expression are occurring in both ganglia. The similarity of the responses of both ganglia suggests that axon regeneration (in the right) and collateral sprouting (in the left) may produce analogous changes in gene expression, but not in rRNA synthesis.     

Comparative concurrent results of vagotomy procedures,conventional gastric resection and hemigastrectomy with subtotal vagotomy

The question of the best surgical treatment of duodenal ulcer remains unanswered. In a series of 132 patients, results following gastric resection and hemigastrectomy with subtotal vagotomy were better than those following vagotomy procedures alone.     

Breathing pattern in anesthetized chickens: CO2 inhalation and vagotomy

The breathing patterns of 20 anesthetized chickens were studied during progressive suppression of intrapulmonary chemoreceptors (IPC) by various concentrations of CO2 and following bilateral vagotomy. The vagotomy breathing pattern, characterized by a marked accentuation of expiratory times with prolonged expiratory pauses, was markedly different from that induced by CO2 inhalation. Removal of neural input to the central respiratory centers from IPC does not appear to be solely responsible for the altered breathing pattern following vagotomy in birds.     

Effect of tidal volume and anesthetic agent on airway responsiveness to histamine

Dose-response relationships for bronchoconstriction in response to aerosal histamine were assessed before and after vagotomy in 11 dogs anesthetized with barbiturates and in 9 dogs anesthetized with alpha-chloralose-urethan. The dose-response relationships following vagotomy were assessed during spontaneous ventilation and during muscular paralysis and mechanical ventilation with tidal volume (VT) similar to each animal's VT prior to vagotomy. After vagotomy the spontaneous VT of both groups increased but the VT of the alpha-chloralose-urethan group was significantly less than that of the barbiturate group. The histamine responsiveness of the animals anesthetized with barbiturates was significantly greater during mechanical ventilation when VT was reduced to prevagotomy levels compared with during spontaneous ventilation. In contrast, the histamine responsiveness of the alpha-chloralose-urethan group was not significantly changed by reducing VT to prevagotomy levels. In six other dogs anesthetized with pentobarbital sodium and studied after vagotomy, responsiveness to histamine aerosol during controlled ventilation with breaths of prevagotomy VT was greater than responsiveness during mechanical ventilation with large volume breaths given immediately afterward. Thus the magnitude of VT of dogs after vagotomy may influence airway responsiveness, and the influence of anesthetic agents on airway responsiveness after vagotomy may in part be due to their effects on VT. Furthermore, bronchodilation accompanying large volume ventilation persists after vagotomy, suggesting that it is not exclusively mediated by changes in parasympathetic activity.     

Alkaline phosphatase distribution in the inferior vagal ganglion of the cat following vagotomy

Summary The object of this study was to demonstrate sites of alkaline phosphatase activity within the cellular elements of the inferior vagal (nodosal) ganglion of the cat and chronologically observe and describe alterations in enzyme activity following vagotomy.In control tissues alkaline phosphatase activity was localized to the wall of perineuronal blood vessels and the satellite cell cytoplasm which envelops the neuronal perikarya. In the experimental tissues alkaline phosphatase activity was increased in the above locations during the first 20 days following vagotomy then gradually decline to approximate control levels by 60 days post-operatively.The functional significance of changes in alkaline phosphatase activity occurring within an altered metabolic environment induced by vagotomy is discussed.Part of a dissertation submitted in partial fulfillment of the requirements for the degree Doctor of PhilosophySupported by Public Health Service Fellowship 1-Fl-GM-33, 597-01 from the National Institutes of Health     

Morphofunctional stateof the cholinergic nervous apparatus of the normal duodenum and the duodenum after subdiaphragmatic vagotomy

Histochemical study of the intramural nervous apparatus of the duodenum was carried out under normal conditions and following bilateral subphrenic vagotomy. Morphometric and microspectrofluorimetric methods gave informations on the reduction of the number of the cholinergic nervous fibers and of the acetylcholinesterase activity in them after a brief increase of these indices during the first 24 hours after vagotomy, with their subsequent return to the initial values.     

Altered cardiovascular reflex responses during positive pressure breathing

Cardiovascular responses during hyperinflation produced by positive end-expiratory pressure (PEEP) are considered to be reflexly influenced by pulmonary mechanoreceptors. Numerous studies have indicated heart and vascular effects attributed to mechanical events and cardiopulmonary mechanoreflexes. Yet interactions of these modalities with the systemic baroreflexes are not clear. We examined aspects of these modulatory interactions by distinguishing changes in pulmonary, heart, and vascular responses during PEEP-hyperinflation before and after progressive elimination of chemo-, mechano-, and baroreflex influences in the closed-chest anesthetized rabbit. During respiratory alkalosis PEEP was imposed in increments of 2.5 cm H2O (range 0.0 to 7.5 cm H2O) before and during control of carotid intrasinus pressure and following aortic denervation and vagotomy. Heart rate responses during PEEP increased prior to aortic denervation, decreased following elimination of baroreflexes, and were abolished after vagotomy. The fall in mean arterial pressure (MAP) during PEEP was accentuated during elimination of the baroreflexes and ameliorated following vagotomy. Mean right atrial (MRAP), intrapleural (MIP), and right atrial transmural pressure increased during PEEP prior to vagotomy. Regression analyses of MAP versus MRAP and MAP versus MIP suggest that vagally receptors reflexly influence venous as well as systemic arterial vascular pressure. Conclusion indicate that when superimposed on mechanical events, cardiopulmonary mechanoreceptors and arterial baroreceptors effect conflicting facilitory reflex influences on heart and vascular responses during PEEP-hyperinflation.     

Vagotomy enhances experimental metastases of 4THMpc breast cancer cells and alters substance P level

We have previously demonstrated that inactivation of capsaicin-sensitive sensory neurons enhances lung and heart metastases of breast carcinoma. Because a significant part of sensory innervation of lung tissue is supplied by the vagus nerve, we here examined the effects of unilateral mid-cervical vagotomy in the metastases of 4THMpc breast carcinoma and tissue Substance P (SP) levels. Balb-c mice were injected orthotopically with 4THMpc cells 1 week after vagotomy. Animals were sacrificed 27-30 days after injection of 4THMpc cells and the extent of metastases was determined. Unilateral vagotomy, right or left significantly increased the lung, liver and kidney metastases without altering the growth rate of the primary tumor. Heart metastases were increased only following left vagotomy. The changes in SP levels were somewhat surprising such that vagotomy actually increased while sham-operation decreased SP levels in lung. The effect of sham-operation was reversed by unilateral vagotomy demonstrating that vagal activity decreases total SP levels in the lung. Increased SP levels might be due to decreased degradation of the peptide. Presence of the tumor markedly increased SP level in the lung, which was more prominent in vagotomized animals. These results provide evidence that vagal activity may protect against metastatic disease.     

Effect of sub-diaphragmatic vagotomy on gastric mucosal mast cell population in pylorus ligated rats.

Gastric mucosal mast cell population was studied following sub-diaphragmatic vagotomy in albino rats, 6 and 12 h after pylorus ligation. Sub-diaphragmatic vagotomy significantly increased the gastric mucosal mast cell population in both 6 and 12 h groups, the increase being more in the latter. The results suggest that the vagal impulses act on the gastric mucosal mast cells causing their degranulation. Following vagotomy the contents stay bound within the mast cells. Increase in mast cell population with the longer experimental situation was possibly due to the continuation of normal turnover of the mast cells in the gastric mucosa. The present study, however, does not lead to a conclusion that the vagal influence on mast cell population is similar throughout the gastro-intestinal tract.     

Vagal nerve and the gastric mucosal defense

An essential role for an intact vagal nerve has been proven in the development of gastric mucosal cyto- and general protection. On the other hand, chemically-induced (ethanol, HCl, indomethacin) gastric mucosal damage is enhanced after acute surgical vagotomy. The aims of this paper were to study the possible mechanisms of the vagal nerve in the development of gastric mucosal defense. The following questions were addressed: 1) effect of surgical vagotomy on the development of ethanol- (ETOH), HCl-, and indomethacin (IND)-induced gastric mucosal damage; 2) changes in the gastric mucosal defense by scavengers, prostacyclin and other compounds (small doses of atropine and cimetidine: 3) changes in the gastric mucosal vascular permeability due to chemicals; 4) effect of indomethacin in the ETOH and HCl models with and without surgical vagotomy; 5) changes in the gastric mucosal content of prostacyclin and PGE₂ in the ETOH and HCl models after surgical vagotomy; and 6) changes in the role of SH-groups in gastric mucosal defense after surgical vagotomy. It was found that: 1) the gastric mucosal damage produced by chemicals (ETOH, HCl, and indomethacin) was enhanced after surgical vagotomy; 2) the cyto- and general gastric protective effects of β-carotene, prostacyclin, and small doses of atropine and cimetidine disappeared after surgical vagotomy; 3) the vascular permeability due to chemicals (ETOH, HCl, indomethacin) significantly increased after surgical vagotomy in association with an increase in both number and severity of gastric mucosal lesions; 4) IND alone (in animals with an intact vagus) did not produce gastric mucosal lesions (in 1-h experiments), but it aggravated ETOH-induced gastric mucosal damage (both its number and severity); 5) the gastric mucosal levels of prostacyclin and PGE₂ decreased after surgical vagotomy; 6) IND application (after surgical vagotomy) decreased further the tissue levels of prostacyclin and PGE₂ in association with an increase of gastric mucosal damage; and 7) the gastric mucosal protective effects of SH-groups were abolished by surgical vagotomy.     

Effect of vagotomy and atropine on plasma somatostatin response to a meal in conscious dogs

In 4 conscious dogs with gastric fistulas the somatostatin responses to a meal were measured and compared to the responses seen after i.v. infusion of atropine sulfate (20 and 50 micrograms.kg-1.h-1) or cimetidine (8 mg.kg-1.h-1). The experiments were repeated after truncal vagotomy. The somatostatin responses to bombesin (0.5 micrograms.kg-1.h-1) were also measured before and after vagotomy. Vagotomy decreased basal and postprandial somatostatin levels and reduced the somatostatin responses to feeding during the first 30-min period following the ingestion of the meal but not during subsequent periods. Bombesin-induced somatostatin release was increased after vagotomy. Atropine decreased the somatostatin responses to the meal before and after vagotomy. Cimetidine had no significant effect. These studies suggest that, in conscious dogs, somatostatin released into the circulation is partly under vagal control and that, as for gastrin release, vagal pathways for stimulation and inhibition are present. Our studies also suggest that cholinergic mechanisms are involved in the control of postprandial somatostatin release.     

The effect of vagotomy on the increase in food intake induced by the cholecystokinin antagonist, proglumide

Cholecystokinin, secreted when ingested food enters the duodenum, may act as a satiety factor. Injection of proglumide, a specific antagonist of cholecystokinin, induced an increase in food intake. The satiety effect of administered cholecystokinin is abolished by bilateral subdiaphragmatic vagotomy. If endogenous and exogenous cholecystokinin act via the same mechanism, then vagotomy should abolish the proglumide-induced increase in food intake. Proglumide was used to block the satiety effect of a food preload in sham-operated and vagotomized rats. Proglumide induced an increase in food intake in sham-operated rats confirming earlier results. No change in meal size was observed in vagotomized rats following proglumide injection. These results suggest that vagotomy abolishes the effect of endogenous cholecystokinin on food intake. However, evidence of dumping in vagotomized rats prevents the interpretation of the data as a direct vagal involvement in endogenous CCK-induced satiety.     

Ultrastructural alterations of the pancreatic D cell in the domestic fowl following vagotomy

Summary In an attempt to determine the neural control of pancreatic D cells, the pancreatic islets of the domestic fowl were examined electron microscopically from 1 to 28 days after abdominal vagotomy. Exocytotic release of many secretory granules from D cells occurred one day after vagotomy. Rough endoplasmic reticulum developed and formed an arrangement of concentric whorls in the cytoplasm of D cells after axotomy. The altered D cells were also characterized by the occurrence of many peculiar dense bodies in the apical cytoplasm at all time periods studied. These bodies varied in shape and size, containing several round vesicles. The D cells were extensively depleted of granules after the longer time periods following vagotomy. The present results provide new morphological evidence for the vagus-nerve control of D cells, which may regulate the activity of islet cells.     

Effects of abdominal vagotomy on serum LH concentrations in female rats

Vagotomy on the morning of pro-oestrus did not prevent the pro-oestrous LH surge and rats became oestrous on the following day. However, vagotomized rats then exhibited a period of acyclicity which lasted for 20.4 +/- 1.3 (s.e.m.) days. Food intake and body weight also declined after vagotomy. During the first week after vagotomy, afternoon LH surges generally did not occur, a pattern which was similar in animals pair fed with vagotomized rats. However, pair-fed rats showed oestrous cycles while vagotomized rats were acyclic. At 7 days after vagotomy, LH surges were induced by oestradiol benzoate and progesterone treatment of ovariectomized rats. Vagotomy suppressed the post-ovariectomy increase in serum LH at 7 and 21 days after surgery. These results, combined with those of other studies, suggest impairment of LH release in vagotomized rats.     

The effect of afterload on the cardiodepressor reflex response to coronary artery occlusion in dogs

The acute hemodynamic responses to anterior and posterior wall ischemia were examined at different afterloads in 30 open-chest anaesthetized dogs. Regional and global left ventricular responses to acute ischemia were also measured before and following bilateral cervical vagotomy in 18 dogs. As the preocclusion afterload (mean aortic pressure) was progressively raised with intravenous methoxamine, a significant decrease in stroke volume occurred following circumflex artery occlusion, whereas no change in stroke volume occurred following occlusion of the left anterior descending artery. Bilateral cervical vagotomy completely inhibited the decrease in stroke volume during circumflex occlusion at high afterload. Vagotomy had no effect on the hemodynamic response to acute anterior wall ischemia. Reversible cold vagal block in paced hearts at high afterload unmasked compensatory inotropy in the nonischemic anterior myocardial segment during circumflex occlusion. Restoring vagal tone by rewarming attenuated the fractional shortening of the nonischemic segment. The results indicate that a relationship exists between myocardial wall tension and reflex cardioinhibition during acute posterior wall but not anterior wall ischemia in dogs.     

NADPH-diaphorase activity in the nodose ganglion of normal and vagotomized guinea-pigs

The activity and distribution of reduced nico-tinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) in the nodose ganglion of normal and vagotomized guinea-pigs were examined by light and electron microscopy. Light microscopy confirmed a remarkable increase in the number of NADPH-diaphorase-reactive neurons in the nodose ganglion following unilateral cervical vagotomy. The increase was present at 5 days but became more prominent at 10 days and was sustained until at least 30 days after vagotomy when compared with the non-lesioned side. The NADPH-diaphorase reaction product was associated with the membrane of the rough endoplasmic reticulum, Golgi apparatus, mitochondria and nucleus of the nodose neurons. In animals killed 5 days post-operation, there was no noticeable degeneration in the nodose neurons. However, at 10 days, the mitochondria in some neurons appeared swollen and vacuolated with disrupted cristae. These changes were accentuated in some nodose neurons 20 and 30 days after vagotomy but there was no evidence of cell death. All the degenerating neurons exhibited NADPH-diaphorase activity. The increase in NADPH-diaphorase activity in the neuronal somata after vagotomy suggests that the enzyme is involved in either the retrograde degeneration or the recovery of the lesioned neurons. Received: 15 June 1995 / Accepted: 15 February 1996