Five- to Eight-year Results of Truncal Vagotomy and Pyloroplasty for Duodenal Ulcer

From January 1963 to December 1965 inclusive 192 men with duodenal ulcer were treated by elective truncal vagotomy and pyloroplasty with one death. Ten subsequent deaths were due to causes unrelated to the ulcer or operation, and 17 patients became untraceable. The remaining 164 patients have been followed up for five to eight years. The late results have been compared with those obtained in a previous study of patients five to eight years after truncal vagotomy and gastroenterostomy, truncal vagotomy and antrectomy, and subtotal gastrectomy respectively for duodenal ulcer.Of the various postgastric operation syndromes early dumping, late dumping, bilious vomiting, and diarrhoea were all less frequent, but not significantly so, after vagotomy and pyloroplasty than after vagotomy and gastroenterostomy.Recurrent ulceration was commoner after vagotomy and pyloroplasty than after all the other operations, the incidence of proved and suspected recurrent ulcers being respectively 6·7 and 7·3% after vagotomy and pyloroplasty, but only 2·5 and 5·9% after vagotomy and gastroenterostomy, 0 and 5·2% after vagotomy and antrectomy, and 0·9 and 3·7% after subtotal gastrectomy. The differences between vagotomy and pyloroplasty and vagotomy and antrectomy or subtotal gastrectomy are statistically significant, but those between vagotomy and pyloroplasty and vagotomy and gastroenterostomy are not.Overall assessment (Visick grading) of the outcome gave poorer results after vagotomy and pyloroplasty than after any other operation, with 14% of category IV cases after vagotomy and pyloroplasty, 11% after vagotomy and gastroenterostomy, 8% after vagotomy and antrectomy, and 6% after subtotal gastrectomy—differences that are significant between vagotomy and pyloroplasty and vagotomy and antrectomy or subtotal gastrectomy but not between vagotomy and pyloroplasty and vagotomy and gastroenterostomy.In the light of these findings it is suggested that truncal vagotomy and pyloroplasty has not lived up to expectations and its place as the currently most popular procedure in the elective surgical treatment of duodenal ulcer should be reconsidered.     

Changes in intestinal endocrine cells in the mouse after unilateral cervical vagotomy

The effect of right or left unilateral cervical vagotomy on the intestinal endocrine cells was studied in 23 mice at 2 and 8 weeks after operation, respectively. The results were compared with that from 10 sham operated mice. Various types of endocrine cells in duodenum and proximal colon were detected by immunohistochemistry and quantified by computerized image analysis. In mouse duodenum, chromogranin-, CCK/gastrin-, GIP- and somatostatin-cells were significantly decreased at 2 weeks after right vagotomy, but returned to the control levels at 8 weeks. Serotonin-cells were reduced at both 2 and 8 weeks after right vagotomy. The amount of the duodenal endocrine cells did not change after left vagotomy with the exception of secretin-cells, which were diminished at 8 weeks after both right and left vagotomy. In the proximal colon, chromogranin-cells were also decreased at 2 weeks after right vagotomy. Serotonin-cells were reduced at 8 weeks after left vagotomy but not right vagotomy. There was no significant difference between the unilaterally vagotomized and the sham operated mice with regard to PYY- and glucagon-cells. It was concluded that vagotomy affected the intestinal endocrine cells in mouse. The influence was more pronounced in the small intestine than the proximal colon. The right vagus nerves seemed to exert more effect on the intestinal endocrine cells than the left ones.     

Comparison of different strategies for treatment of duodenal ulcer.

A simple model of a Markov chain was used to study the long term outcome of different strategies for the treatment of duodenal ulcer. Maintenance treatment with H2 receptor antagonists surpassed intermittent drug treatment and proximal gastric vagotomy with respect to the relapse free interval and severe postoperative morbidity. With maintenance treatment the rate of complications and the number of deaths related to ulcer were slightly higher than after proximal gastric vagotomy. Nevertheless, because the few deaths from proximal gastric vagotomy occur at the initiation of treatment the loss of life years during maintenance treatment exceeded that of proximal gastric vagotomy only after 20 years. Despite its rarity, severe postoperative morbidity after proximal gastric vagotomy far exceeded that after the few emergency operations which would become necessary in the course of maintenance treatment. The superiority of maintenance treatment over proximal gastric vagotomy remained insensitive to changes in the assumptions underlying the recurrence rate with both treatments and the postoperative morbidity of proximal gastric vagotomy.     

Neuroendocrine peptide levels in the gastrointestinal tract of mice after unilateral cervical vagotomy

The effects of left and right unilateral cervical vagotomy on the content of several neuroendocrine peptides were studied in different parts of the murine gastrointestinal tract, known to receive vagal innervation. The neuroendocrine peptides investigated were secretin, gastric inhibitory peptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, substance P, VIP, neurotensin, neuropeptide Y (NPY), and galanin. The neuroendocrine peptide concentration was affected after both left and right vagotomy, and that the changes in the concentrations of the neuroendocrine peptide levels occurred in all the gastrointestinal segments investigated, namely antrum, small and large intestine. However, these changes varied, depending on which side was vagotomized and the interval after vagotomy. It is concluded that the vagus nerve had an important impact on the neuroendocrine system in the murine gut. It is suggested, furthermore that the contradictory results obtained earlier on the effect of vagotomy on the gastrointestinal peptides may depend on differences in the vagotomy methods used and on differences in observation time after vagotomy.     

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.     

Incidence of Dumping after Truncal and Selective Vagotomy with Pyloroplasty and Highly Selective Vagotomy without Drainage Procedure

The incidence of dumping after truncal or selective vagotomy with pyloroplasty and highly selective vagotomy without a drainage procedure was assessed both clinically and experimentally. At a gastric follow-up clinic dumping was found to be significantly less frequent in patients who had undergone highly selective vagotomy without a drainage procedure than in patients who had undergone truncal or selective vagotomy with pyloroplasty (P < 0·05 or < 0·001, respectively). Hypertonic glucose given by mouth provoked the onset of dumping in 20% of patients with duodenal ulcer before operation, in 73% after truncal vagotomy and pyloroplasty, in 80% after selective vagotomy and pyloroplasty, and in 47% after highly selective vagotomy. The test meal also produced significantly greater decreases in blood pressure and increases in pulse rate in patients who had undergone vagotomy with pyloroplasty than in patients who had undergone highly selective vagotomy.     

Effects of truncal,selective, and highly selective vagotomy on glucose tolerance and insulin secretion in patients with duodenal ulcer. Part I-Effect of vagotomy on response to oral glucose.

An oral glucose tolerance test was performed in patients who had undergone truncal vagotomy and pyloroplasty, bilateral selective vagotomy and pyloroplasty, or highly selective vagotomy without a drainage procedure at least six months earlier. The results were compared with those from patients with chronic duodenal ulcer before operation. In all three groups of patients after vagotomy more rapid rates of rise of blood glucose and higher peak concentrations were observed than in patients who were tested before operation. These differences were statistically significant only in patients who had undergone truncal or selective vagotomy with pyloroplasty and were probably due to more rapid rates of gastric emptying after these operations. Plasma insulin concentrations were lower after truncal vagotomy than after selective or highly selective vagotomy, the difference between truncal vagotomy and highly selective vagotomy being statistically significant. Truncal vagotomy resulted in a diminished insulin response to oral glucose, which could have been due to vagal denervation of the pancreas or, more probably, impaired release of small-bowel hormones which normally augment the pancreatic insulin response.     

Gastrin release after truncal vagotomy in fistula dogs: Hypersensitivity to bombesin but not bethanechol

Integrated gastrin response was measured by the serial changes in serum immunoreactive gastrin after various stimuli in three dogs with gastric fistula and highly selective fundic vagotomy, who were then subjected to truncal vagotomy. Truncal vagotomy eliminated the gastrin as well as the gastric acid response to vagal excitation by 2-deoxy-glucose, but did not significantly change the responses to bethanechol (20 or 120 μg/kg/hr by IV infusion). Acid output was the same with bombesin or its nonapeptide in the dogs with fundic vagotomy as it was after subsequent truncal vagotomy, but gastrin release was very much increased by truncal vagotomy. For a 3-hour infusion of bombesin integrated gastrin release was 65 and 143 ng/ml/min and for its nonapeptide 43 and 109 ng/ml/min in the dogs with fundic and truncal vagotomy respectively. The marked hypersensitivity of the gastrin response after truncal vagotomy to bombesin but not to a cholinergic agonist suggests that the antral denervation led to a post-denervation hyper-response to the putative transmitter, bombesin, and that the vagal release of antral gastrin may thus represent a peptidergic neurohormonal mechanism. Also, a long half-life of effect suggests that bombesin binds avidly to its receptors.     

Evidence for intrinsic regulation of met-enkephalin-immunoreactivity in gastroenteropancreatic tissues of the rat

In a study whether gastrointestinal endogenous opioids can be modified by vagal denervation or by pharmacological application of an opiate, we examined met-enkephalin-immunoreactivity in gastrointestinal tissue in rats with and without truncal vagotomy and with and without subcutaneously implanted morphine pellets. The immunoreactivity of the tissue extracts gave dose-response lines in the radioimmunoassay for met-enkephalin which were near parallel to that for the standard. On Sephadex chromatography the met-enkephalin immunoreactivity eluted at a position similar to synthetic met-enkephalin. Tissue concentration of met-enkephalin immunoreactivity was not significantly different from the respective control after vagotomy and after morphine treatment. Total gastric met-enkephalin immunoreactive content increased significantly after vagotomy in line with gastric hypertrophy occurring after vagotomy without a drainage procedure. From these results it is concluded that met-enkephalin immunoreactivity in the rat gastrointestinal tract is regulated intrinsically, it is neither altered by vagal denervation nor by exogenous opiate administration.     

Vagotomy without Diarrhoea

The incidence of diarrhoea after three types of vagotomy was assessed “blind” at a gastric follow-up clinic one year after operation. Diarrhoea was recorded in 24% of patients after truncal vagotomy and pyloroplasty, in 18% after selective vagotomy and pyloroplasty, but in only 2% of patients after highly selective vagotomy without a drainage procedure. The incidence of diarrhoea was significantly less (P < 0·01) after highly selective vagotomy than after either of the other procedures.Hypertonic glucose solution given by mouth to 15 representative patients from each group and to 15 patients before operation provoked the onset of diarrhoea in 67% of the patients who had undergone truncal vagotomy and pyloroplasty, in 60% of those who had undergone selective vagotomy and pyloroplasty, in 13% of those who had undergone highly selective vagotomy without a drainage procedure, and in none of the preoperative patients. Again the difference between the “highly selective” group and the other two groups of vagotomized patients was statistically significant.It is suggested that postvagotomy diarrhoea is attributable both to unregulated gastric emptying after truncal or selective vagotomy with a drainage procedure and to the extragastric denervation produced by truncal vagotomy. “Postvagotomy” diarrhoea can be virtually eliminated by using highly selective vagotomy without a drainage procedure.     

Characterization of 5-HT7-receptor-mediated gastric relaxation in conscious dogs

We aimed to evaluate the gastric relaxant capacity of the 5-HT(1/7)-receptor agonist 5-carboxamidotryptamine (5-CT) in conscious dogs and to clarify the mechanism of action by use of selective antagonists, vagotomy, and in vitro experiments. A barostat enabled us to monitor the intragastric volume in response to different treatments (intravenously administered) before and after supradiaphragmatic vagotomy [results presented as the maximum volume change after treatment (mean; n = 5-11)]. In vitro experiments were performed with isolated muscle strips cut from four different stomach regions of the vagotomized dogs [results were fitted to the operational model of agonism to determine the efficacy parameter tau (n = 5)]. 5-CT (0.5-10 microg/kg) caused a dose-dependent gastric relaxation (29-267 ml) that was completely blocked by the selective 5-HT(7)-receptor antagonist SB-269970 (50 microg/kg). After vagotomy, the relaxation to 10 microg/kg 5-CT was significantly less pronounced (73 vs. 267 ml; P < 0.05) but still blocked by SB-269970, whereas the response to the nitric oxide donor nitroprusside was similar to that before vagotomy (178 vs. 218 ml). In vitro, 5-CT concentration dependently inhibited the PGF(2alpha)-contracted muscle strips before and after vagotomy. Although before and after vagotomy the response in every region was mediated by 5-HT(7) receptors (apparent affinity dissociation constant: SB-269970, 8.2-8.6 vs. 8.3-8.6, respectively), the response after vagotomy was less efficacious (log tau: 1.9 to 0.5 vs. 1.4 to -0.1). The results indicate that the 5-CT-induced proximal stomach relaxation in conscious dogs before and after vagotomy is mediated via 5-HT(7) receptors. The decreased efficacy of 5-CT in vitro after vagotomy is probably related to vagotomy-induced changes in receptor density or coupling efficiency and provides a possible explanation for the decreased in vivo response to 5-CT after vagotomy.     

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.     

Vagotomy effect on the content and synthesis of acetylcholine in autonomic ganglia in dog stomach

The effect of total, selective and highly selective vagotomy was studied on the content and synthesis of acetylcholine in the tissues of the gastric fundus and pyloric part of the stomach in mongrel dogs of either sex aged 3 to 6 years. Total vagotomy produced after 3 weeks a non-significant rise in the amount and a highly significant increase of the synthesis of ACh in the fundus, and a significant increase in the amount and synthesis of ACh in the pyloric part. Six weeks after the procedure the Ch content of the fundus and pyloric part decreased statistically significantly, while the synthesis rate was not different from the initial one. Three weeks after selective vagotomy the ACh content of the fundus and pyloric part was significantly increased. The rate of ACh synthesis was normal. Six weeks after vagotomy the content of ACh and its synthesis in the fundus were similar to those before vagotomy. In the same time the ACh synthesis rate was significantly decreased in the pyloric part, while the ACh content there was similar to the control value. Highly selective vagotomy with denervation of the fundus and corpus of the stomach but with maintenance of the innervation of the pyloric part caused after 3 weeks a rise of the ACh content of the fundus tissues. The ACh synthesis rate was not different from the normal one. In the pyloric part the ACh content was significantly decreased and the synthesis of ACh was somewhat inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)     

The behaviour of acetylcholinesterase activity in neurons of the bulbous part of the reticular formation in albino rats after bilateral vagotomy.

The influence of a bilateral vagotomy on the acetylcholinesterase activity (AChE) in the neurons of the bulbous part of the reticular formation of albino rats was investigated. An increase in the reaction to acetylcholinesterase (AChE) was ascertained in the large as well as the small neurons 8 h after the transection of the vagus nerves, which indicates their decreased activity. It may be assumed that a bilateral vagotomy causes a decrease in the activity of cholinergic mechanisms within the periphery of the reticular formation neurons.     

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 unilateral cervical vagotomy on antral endocrine cells in mouse.

The present study was carried out to investigate the effect of unilateral cervical vagotomy on the antral endocrine cells in mouse. Fifty-four mice were randomly divided into three groups, 18 in each, for left or right cervical vagotomy, or sham operation as controls. The animals were sacrificed 2, 4, and 8 weeks after the operation, respectively. Chromogranin-, gastrin/CCK-, serotonin-, and somatostatin-cells were detected by immunohistochemistry and quantitated by computerised image analysis. The results showed that the number of chromogranin-cells was decreased in both left and right vagotomized mice after 4 weeks and remained at the same level after 8 weeks. The numbers of gastrin-, serotonin- and somatostatin-cells did not change after right vagotomy. However, the numbers of gastrin- and somatostatin-cells were decreased after left vagotomy, whereas no change was found in serotonin-cells. Endocrine cells with vacuolated cytoplasm and pyknotic nuclei were also observed during the course of time. The alteration in the antral endocrine cells observed in this study seemed to be dynamic and depended on the observation time after the operation as well as the denervated branches of the vagus nerve. This may explain, at least partially the contradictory results obtained earlier by different investigators.     

Desheathing the nodose ganglion is not a reliable method of de-efferentation in the ferret

The present study reports the results of physiological and anatomical experiments in which the purpose was to determine whether desheathing the nodose ganglion is a reliable method of vagal de-efferentation in the ferret. In physiological studies, the effects of electrically stimulating the treated and untreated vagal nerves on cardiovascular and intestinal responses were examined and compared with previously obtained data after left supranodose vagotomy. The anatomical studies illustrated the effects of desheathing the left nodose ganglion on the transport of horseradish peroxidase (HRP) within a thoracic vagal communicating branch. These data were compared to data from control animals and animals that had undergone left supranodose vagotomy. The results demonstrated that severing the fascicles overlying the left nodose ganglion and allowing the nerve fibers to degenerate, caused no reduction in labeled efferent cell bodies in the left dorsal motor nucleus of the vagus as compared to controls. However, after left supranodose vagotomy there were no efferent cell bodies labeled in the left dorsal motor nucleus of the vagus. Following degeneration of the fascicles, electrical stimulation of the peripheral cut end of this nerve did not abolish the efferent responses in 7 out of 9 animals studied, whereas supranodose vagotomy abolished the responses in all animals. These findings demonstrate that desheathing the nodose ganglion and thereby removing the nerve bundles overlying the nodose ganglion is not a guaranteed method of destroying the efferent fibers in the vagus nerve of the ferret. Supranodose vagotomy, therefore, is a more reliable method of de-efferentation in this species.     

Evaluation of the functional state of the hepatocyte monooxygenase system in rats with damaged innervation of the liver

Cytochrome P-450 content measured spectrophotometrically 14 and 25 days after bilateral subdiaphragmal vagotomy in hepatocyte microsomes of inbred male rats was considerably reduced. The rate of aminopyrine demethylation and oxygen consumption decreased, while the duration of hexenal-induced sleep was prolonged. Monoxygenase responsible for p-hydroxylation of aniline proved relatively resistant to vagotomy.     

Vagal influence on compensatory ovarian growth is important only briefly after hemicastration

Hemicastration induces growth of the remnant ovary in the rat. As evidenced by the effects of total abdominal vagotomy, vagal innervation markedly influences this compensatory ovarian growth. In the present experiments, vagotomy inhibited compensatory ovarian growth when performed immediately after hemicastration, but not when delayed until 4.5 hr after hemicastration. Brief exposure of subdiaphragmal portion of the vagi nerves to 2% lidocaine shortly before hemicastration also inhibited compensatory growth. Fifteen minutes after hemicastration, markedly elevated tissue concentrations of cyclic adenosine monophosphate (cAMP) were recorded in the remnant ovaries. This accumulation of cAMP was inhibited by vagotomy that preceded hemicastration, as well as by lidocaine pretreatment of the vagi nerves, and partly by vagotomy that followed 10 min after hemicastration. At 5 hr after hemicastration, tissue cAMP concentrations in the remnant ovaries were not elevated and were not affected by vagotomy. The present results suggest that vagal influence on the compensatory ovarian growth is important only during a short period of time after hemicastration (apparently shorter than 4.5 hr), and that it, at least briefly after hemicastration, includes neural input to the ovary.     

交感神经对去迷走神经大鼠胃泌素释放的刺激作用

为了探讨迷走神经切除后血清胃泌素浓度增加的机制,本实验用放射免疫法系统观察了大鼠双侧膈下迷走神经切除后三个月血清胃泌素浓度的变化和交感神经在这种变化中的作用。结果发现,迷走神经切除后,血清胃泌素浓度增加6倍以上,而且这种增加不是继发于胃内pH和胃内压的改变;迷走神经和交感神经都切除的动物,血清胃泌素浓度也有增加,但明显低于单纯迷走神经切除组;迷走神经切除后两个月再切除交感神经可使已升高的胃泌素下降42％。实验说明,迷走神经切除后,交感神经可刺激胃泌素释放,这一作用是去迷走神经后血清胃泌素水平增加的原因之一。