Improved experimental model for complete gastric vagotomy in the rat

Transection vagotomy, dividing both vagal trunks and the esophagus just below the diaphragmatic hiatus, is a simple and rapid procedure for vagal denervation of the rat stomach. This form of vagotomy is significantly (P less than 0.01) more effective than the traditional truncal vagotomy in depressing the basal acid output (10.9 mumol +/- 1.4 vs 17.4 mumol +/- 1.8, mean +/- SEM, N = 10). It is also more effective (P less than 0.01) than truncal vagotomy in preventing reserpine-stimulated gastric acid secretion (9.9 mumol +/- 0.9 vs 20 mumol +/- 1.5, mean +/- SEM, N = 10). Furthermore, this vagotomy is more powerful (P less than 0.01) than truncal vagotomy in combating insulin-stimulated gastric acid secretion (10.5 mumol +/- 1.1 and 21 mumol +/- 1.6, respectively vs 169 mumol +/- 3.8, mean +/- SEM, N = 10). It is, therefore, concluded that the vagal denervation of the rat stomach achieved by transection vagotomy is more complete than that afforded by truncal vagotomy.     

The vagus exerts trophic control of the stomach in the rat

Bilateral subdiaphragmatic truncal vagotomy results in great functional changes in the stomach although the changes in the gastric mucosal architecture are small. A trophic effect of the vagus on the stomach is revealed after unilateral vagal sectioning, taking advantage of the fact that, in the rat, each vagal trunk innervates only one side of the stomach, and that denervation of one side does not impair the functional capacity of the other. The denervated side of the stomach displayed atrophy that was reflected in reduced weight and height of the oxyntic mucosa and a reduced density of argyrophil cells. The lack of atrophy after bilateral vagotomy can be explained by counteracting forces, in that the subsequent rise in gastrin secretion (due to lack of acid feedback inhibition of gastrin release) probably masks antitrophic effects of the vagotomy per se. Interestingly, the number of somatostatin cells in the oxyntic mucosa was not reduced after unilateral vagotomy, nor was the weight of the antral mucosa or the density of enterochromaffin and gastrin cells in the antrum on the denervated side.     

The effects of varying the extent of the vagotomy on the myoelectrical and motor activity of the stomach

The effects of varying the extent of vagotomy on the myoelectrical and motor activity of the stomach have been successfully studied in 21 patients undergoing either truncal, selective, or highly selective vagotomy for the treatment of chronic duodenal ulceration. The mean percentage time that regular antral myoelectrical activity was recorded preoperatively was 95.8% +/- 1.0 and this was decreased following highly selective vagotomy (74.0% +/- 6.6), selective vagotomy (37.8% +/- 12.4), and truncal vagotomy (30.2% +/- 10.4). The mean amplitude of the pacesetter potential was less following truncal (0.86 mV +/- 0.05), selective (1.32 mV +/- 0.09), and highly selective vagotomy (1.67 +/- 0.09) than in preoperative studies (2.21 mV +/- 0.12). Following truncal and selective vagotomies the triphasic waveform of the pacesetter potential changed to a sinusoidal shape. No significant change in the mean preoperative frequency of the myoelectrical activity (3.03 cpm +/- 0.08) occurred after vagotomy. Thus the changes in the electrical activity of the stomach are related to the extent of the vagal denervation. Intravenous administration of insulin did not alter these patterns except after highly selective vagotomy when the amplitude of the electrical waves, the incidence of action potentials, and percentage motor activity were increased.     

Sample taking problems in measuring actual histamine levels of human gastroduodenal mucosa: specific and general relevance in clinical trials on peptic ulcer pathogenesis and selective proximal vagotomy.

Changes in histamine storage in the oxyntic mucosa of duodenal ulcer patients and their reversal by vagotomy and the histamine H2-antagonist cimetidine supported the hypothesis that histamine could be a causal factor in peptic ulcer pathogenesis. The specificity of these findings was impaired by problems in biopsy taking, however, and in the preparative steps before measuring the actual histamine contents in all parts of the gastric mucosa and in the duodenum. A prospective trial was carried out in 190 patients to identify these sources of bias and to overcome them by appropriate study designs. Usually a direct correlation was found between weight of biopsy and mucosal histamine content. This problem was solved by selecting a biopsy forceps producing smaller variations in sample size, by limiting the time of cold ischaemia to four to five minutes only and by taking three biopsy specimens for each single histamine value. The actual histamine content of mucosal biopsies remained constant for about four to five minutes only. The 'disappearance' rate was faster in control subjects than in duodenal ulcer patients. Hence by variation of the cold ischaemia time any artefacts of differences between mucosal histamine levels in controls and duodenal ulcer patients could be produced. Using the optimised sample taking procedure mucosal histamine contents of several gastric regions and the duodenal bulb were measured in 24 patients with duodenal ulcer, after selective proximal vagotomy without drainage and in control subjects without any stomach disease (randomised controlled trial). The histamine content was lower in all parts of the upper gastrointestinal tract in duodenal ulcer patients than in controls and was raised again in all regions after selective proximal vagotomy. As the most likely hypothesis it is suggested that vagal reflexes with afferent fibres coming from the oxyntic mucosa stimulate histamine release in duodenal ulcer patients by efferent peptidergic neurones to all parts of the stomach and the duodenum where the ulcer lesion is situated.     

Mechanisms governing the biphasic pattern of gastric emptying after truncal vagotomy and pyloroplasty.

The pattern of gastric emptying after truncal vagotomy and drainage is usually biphasic. An early rapid phase is followed by a characteristically abrupt transition to slow emptying. The mechanisms responsible for this pattern were studied in six dogs with truncal vagotomy and pyloroplasty, fitted with a proximal duodenal cannula. Gastric emptying was measured using gamma camera imaging of a radiolabelled 15% dextrose test meal. Sixty one hour studies were done using five designs. (1) With the cannula closed gastric emptying was initially rapid, followed by stasis (emptying at 15 min - 32% (5.3), 60 min - 34% (4.8); mean (SE)). (2) With the cannula open emptying was very rapid (15 min - 76% (4.2) p less than 0.001, 60 min - 88% (2.6) p less than 0.001 ANOVA). (3) Distal duodenal instillation of isotonic saline, at a rate equivalent to gastric emptying with the cannula closed, did not retard this rapid emptying (15 min - 78% (10.6), 60 min - 90% (5.4)). (4) With duodenal instillation of 15% dextrose, gastric emptying remained faster than in studies without diversion (15 min - 50% (7.0) NS, 60 min - 65% (6.8) p less than 0.01), but was slower than during diversion alone (p less than 0.05). (5) Finally, duodenal instillation of 15% dextrose before administration of the test meal produced slower initial emptying without subsequent stasis (15 min - 24% (4.5), 60 min - 47% (10.6)), although the amounts emptied were not significantly different from those with the cannula closed. These results indicate that after truncal vagotomy and pyloroplasty small bowel resistances play a significant role in controlling gastric emptying. Osmoreceptor responses persist after truncal vagotomy, but sympathetic inhibitory responses to small bowel distension are not involved in the regulatory process.     

Parietal cell structure and acid secretion in the vagally innervated stomach and the vagally denervated fundic pouch in cats.

In seven cats provided with gastric fistula (GF) of the main stomach and a denervated Heidenhain pouch (HP) the structure of the innervated and denervated mucosa was examined by light and electron microscopy. In four of these cats dose-response curves for acid output to pentagastrin were determined before and after vagal denervation of the fundic pouch. Vagal denervation reduced the acid response to pentagastrin by decreasing both the secretory capacity and the sensitivity of the oxyntic glands. Accordingly, in the same cat the parietal cells of the HP were less sensitive to pentagastrin than the cells of the innervated main stomach. Light and electron microscopic investigations revealed that the fundic mucosa was thinner, and the size and proportion of the parietal cells was smaller in the HP than in the GF. It is likely that the morphological changes in the pouch were caused by the vagal denervation rather than by the loss of mucosal contact with food. The secretory and morphological changes produced by the vagotomy are not necessarily related.     

Surgery or chemoneurolysis for complete vagal denervation of rat stomach?

This study compared the completeness of vagal denervation of the rat stomach by transection vagotomy to that by chemoneurolysis (30% ethyl alcohol) alone or supplemented by truncal vagotomy. The H⁺ output over 6 hr with vagotomy by chemoneurolysis (10.5±0.7 mol, mean±sem,N=10) or truncal vagotomy and chemoneurolysis (10.9 ±1.1 mol, mean±sem,N=10) was similar to that with transection vagotomy, but significantly (P<0.01) lower than that with truncal vagotomy by chemoneurolysis (17.9 ±1.1 mol,N=10). The latter output was similar to that of truncal vagotomy performed surgically (18.2±1.3 mol,N=10). Reserpine (0.1 mg/kg intraperitoneal) stimulated gastric acid secretion relative to control values (207±3.1 mol vs 67±3.2 mol,N=10),P<0.001) and transection vagotomy, vagotomy by chemoneurolysis, or truncal vagotomy and chemoneurolysis were more effective (P<0.01) than truncal vagotomy performed surgically or by chemoneurolysis in preventing this stimulation. Insulin stimulated the H⁺ output (184±2.9 mol vs 62±3.1 mol,N=10,P<0.001) and transection vagotomy, vagotomy by chemoneurolysis, or truncal vagotomy and chemoneurolysis were more effective (P<0.01) than truncal vagotomy done surgically or by chemoneurolysis in preventing this action. These results were reproducible in experiments done after three months. This investigation shows that transection vagotomy, vagotomy by chemoneurolysis, and truncal vagotomy plus chemoneurolysis are equally effective in achieving vagal denervation of the rat stomach and are superior in this respect to truncal vagotomy done surgically or by chemoneurolysis.     

Bile acid and lysolecithin concentrations in the stomach in patients with duodenal ulcer before operation and after treatment by highly selective vagotomy, partial gastrectomy, or truncal vagotomy and drainage

Duodenogastric reflux of bile acids and lysolecithin in the course of a standard test meal was measured in normal people and in patients with duodenal ulcer before operation and more than one year after highly selective vagotomy, Polya partial gastrectomy, truncal vagotomy and pyloroplasty, and truncal vagotomy and gastrojejunostomy. Before operation, duodenal ulcer patients had significantly higher fasting, post-prandial, and peak bile acid concentrations in the stomach than had normal subjects. After Polya partial gastrectomy, fasting, post-prandial, and peak concentrations of bile acids and lysolecithin were significantly higher than in preoperative duodenal ulcer patients. After highly selective vagotomy, in contrast, bile acid concentrations in the stomach were significantly lower than in preoperative duodenal ulcer patients and post-prandial and peak lysolecithin concentrations were less than half (NS) those recorded in preoperative duodenal ulcer patients. After highly selective vagotomy, bile acid concentrations were also significantly lower than bile acid concentrations after Polya partial gastrectomy, truncal vagotomy and pyloroplasty, and truncal vagotomy and gastrojejunostomy; and post-prandial and peak lysolecithin concentrations were significantly lower than after Polya partial gastrectomy and truncal vagotomy and gastrojejunostomy. Thus, when used in the treatment of patients with duodenal ulcer, highly selective vagotomy keeps `bile' out of the stomach, probably through its effect on gastric smooth muscle, combined with the preservation of an intact antropyloroduodenal segment. In contrast, Polya partial gastrectomy, truncal vagotomy and gastrojejunostomy, and truncal vagotomy and pyloroplasty all lead to a significant increase in reflux of bile acids and lysolecithin into the stomach. The clinical importance of these findings is that both gastritis and, in the long term, gastric carcinoma may prove to be less common after highly selective vagotomy than after partial gastrectomy or vagotomy with a drainage procedure.     

Lithium fluxes across the gastric mucosa after truncal vagotomy and drainage--an objective assessment of mucosal injury.

Gastric mucosal permeability to lithium has been measured in 20 patients with an untreated duodenal ulcer, eight patients who were asymptomatic for more than one year after truncal vagotomy and drainage, 14 patients with an endoscopically proven recurrent ulcer, and 21 patients with an unsatisfactory result from truncal vagotomy and drainage for other reasons. Lithium fluxes were lowest in the asymptomatic postoperative patients (0.149 +/- 0.028 mmol Li+/15 min), but were not significantly different to the measured fluxes in patients with a duodenal ulcer before treatment (0.160 +/- 0.020 mmol Li+/15 min) or a recurrent ulcer after truncal vagotomy and drainage (0.169 +/- 0.022 mmol Li+/15 min) (SEM). By comparison the mean lithium flux in patients who were dissatisfied with the results of their previous surgery for reasons other than a recurrent ulcer (0.234 +/- 0.019 mmol Li+/15 min) was significantly higher than that observed in patients with a duodenal ulcer (p less than 0.05), patients with a recurrent ulcer (p less than 0.05) or patients who were asymptomatic after definitive ulcer surgery (p less than 0.02). Furthermore, when the lithium fluxes observed in 11 patients whose major postoperative complaint was bile vomiting (0.243 +/- 0.027 mmol Li+/15 min) were compared with results from the remaining 52 patients included in the study (0.173 +/- 0.012 mmol Li+/15 min) fluxes were significantly higher in the 'bile vomiters' (p less than 0.05).     

Adverse effects of vagotomy on ethanol-induced gastric injury in the rat

Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects. Fasted rats (6–8/group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroscopically for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent. Thus, aberrations in glutathione metabolism do not explain the absence of adaptive cytoprotection following vagotomy or the exacerbation of alcohol-induced damage under conditions of vagal denervation.This work was supported by research grant DK 25838 from the National Institutes of Health.     

Vagotomy by chemoneurolysis: an experimental study in the rat

In the pylorus ligated rat vagotomy has been attempted by chemoneurolysis with alcohol. Surgical truncal vagotomy reduced the intragastric acid produced in a five-hour period from 310 +/- 17.6 (SD) mumol to 5.4 +/- 2.4 mumol with a marked reduction in the ulcer score. Injection of 30% alcohol in the region of the vagal trunks at the level of the lower oesophagus produced a marked reduction in gastric acid secretion (7.6 +/- 3.7 mumol). Injection of solutions of alcohol in concentrations over 10% along the lesser curvature reduced gastric acid output to less than 10 mumol with a corresponding reduction in the ulcer score. Four months after the injection of 30% alcohol along the lesser curvature the acid output was 23.0 +/- 5.7 mumol and no gastric ulceration occurred.     

Role of mucosal prostaglandins in vagally-mediated adaptive cytoprotection in the rat.

This study was designed to investigate whether vagal innervation and mucosal prostaglandins (PGs) participate in gastric adaptive cytoprotection. Rats were divided into three groups; sham operation (control), truncal vagotomy or splanchnicotomy. In the first experiment, 100% ethanol (EtOH) was orally administered 15 min after pretreatment with 20% EtOH to all 3 groups. One hour later, the gastric mucosa was examined macroscopically. In a second experiment, the mucosal PG contents 15 min after administration of either 20% EtOH or saline were measured by high performance liquid chromatography. In truncal vagotomized rats, the adaptive cytoprotection caused by exposure to 20% EtOH in control and splanchnicotomized rats was not observed and an increase in hemorrhagic lesion severity was seen. In the control and splanchnicotomized rats, PGE2 contents were elevated following 20% EtHO treatment, as compared to those in the saline-treated rats. However, PGE2 contents in vagotomized rats were not altered by EtOH exposure, and were significantly lower than in the control and splanchnicotomized groups, whereas PGF2 alpha and PGD2 contents were significantly higher after EtOH administration as compared to those in saline-treated rats. These results suggest that vagal innervation is essential for adaptive cytoprotection and that the vagotomy-induced decrease in PGE2 and increases in PGF2 alpha and PGD2 following 20% EtOH administration, may be caused by a disturbance in adaptive cytoprotection.     

Gastric acid and pancreatic polypeptide responses to modified sham feeding. Effects of truncal and parietal cell vagotomy.

The effects of truncal vagotomy and parietal cell vagotomy on gastric acid secretion and plasma gastrin and pancreatic polypeptide release were studied in 28 duodenal ulcer patients under basal conditions and after modified sham feeding and infusion of pentagastrin (2 micrograms/kg/h). Before vagotomy gastric acid output in response to modified sham feeding was significantly higher than basal acid secretion in all subjects tested and reached about 45% of the pentagastrin maximum. No difference in the increase in acid response, or in the pancreatic polypeptide response to modified sham feeding was found between patients with high and low basal secretion. Plasma gastrin concentration was unaltered by modified sham feeding before and after truncal vagotomy or parietal cell vagotomy, although after vagotomy it tended to reach higher values than before this procedure. After truncal vagotomy, basal pancreatic polypeptide concentration was decreased and modified sham feeding-induced pancreatic polypeptide increment was completely eliminated. Four weeks after parietal cell vagotomy, the modified sham feeding-induced increment in plasma pancreatic polypeptide was significantly decreased and observed only in seven of 12 patients. Four to five years after parietal cell vagotomy all subjects responded to modified sham feeding with pancreatic polypeptide increment similar to that before vagotomy and in three of 12 patients acid response to modified sham feeding was seen. This study indicates that truncal vagotomy eliminates gastric acid and plasma pancreatic polypeptide responses to vagal excitation while parietal cell vagotomy abolishes gastric acid response and reduces temporarily the pancreatic polypeptide response to modified sham feeding (possibly because of transient impairment of the vagal innervation of the pancreas). (2) A high ratio of basal to maximal acid output in non-operated duodenal ulcer patients is not associated with a low acid response to modified sham feeding, nor with a high pancreatic polypeptide concentration, and (3) Restitution of the pancreatic polypeptide response to modified sham feeding five years after parietal cell vagotomy does not indication ineffective denervation of the parietal cells.     

Graded vagotomy and gastric secretion

In 3 dogs with gastric fistulae, partial denervation of the acid secreting area of the stomach halved the insulin-stimulated acid secretion. Completion of a “highly selective” (proximal gastric) vagotomy resulted in a further fall of the peak acid output after insulin to 4% of control values, and there was no further change when selective and truncal vagotomy were performed. The pentagastrin dose-response curve was shifted to the right after partial denervation and remained so shifted after subsequent operations. At low doses there was a considerable decrease in acid output, and the maximal acid output was unchanged but achieved only with a higher dose of pentagastrin. These results suggest that the gastric secretory response after vagotomy is not an all-or-none phenomenon and that the fall in peak acid output after insulin is related to the extent of the acid-secreting mucosa denervated. Tailored vagotomy operations might lower the acid secretion sufficiently to heal an ulcer without interfering with other aspects of gastrointestinal function.     

Mucosal lesions due to gastric distension in the rat

The pathogenesis of acute gastric mucosal lesions produced by distension of the rat stomach was studied. One hour of distension with 0.1 N HCl, but not saline, produced lesions in the glandular stomach in all rats. Histologic studies revealed marked thinning of the mucosa plus thrombus formation in the ulcerated area. Gastric distension with 8 ml HCl (per 100 g body weight) produced severe lesions, 4 ml minimal lesions and 2 ml no lesions. Intragastric pressure in the 8-ml group remained above 110 mm H₂O for the first 10 min. Distension with 8 ml acid/100 g body weight for just 10 min resulted in significant lesion formation. Acid distension did not cause generalized disruption of the gastric mucosal barrier to H⁺ back-diffusion. It appears that an intragastric pressure of over 110 mm H₂O for 10 min damages the mucosa by pressure (with thinning) and ischemia (with thrombosis), resulting in decreased resistance to acid peptic digestion and consequent acute lesion formation.Dr. Gati was a Visiting Scientist under the National Academy of Sciences Scientific Exchange Program.     

Decreased apoptosis and increased ornithine decarboxylase activity in the intestinal mucosa of rats with bilateral ventromedial hypothalamus lesions

Background It has not been clearly demonstrated whether the ventromedial hypothalamus regulates intestinal cell growth. Ornithine decarboxylase is a key enzyme in polyamine synthesis, which plays an important role in intestinal mucosal growth. The aim of this study was to investigate whether bilateral ventromedial hypothalamus lesions affect mucosal cell growth. This was done by evaluating ornithine decarboxylase activity and apoptosis in rat small intestines.Methods Bilateral ventromedial hypothalamus lesions were produced by thermocoagulation, done with rats under halothane anesthesia 7 days before the experiments. Rats with lesions were pair-fed with sham-operated rats. Total (truncal) vagotomy was performed before the development of ventromedial hypothalamus lesions. Ornithine decarboxylase activity and apoptosis were evaluated in the jejunal mucosa.Results Ornithine decarboxylase activity in the jejunal mucosa increased significantly 1 week after the development of the bilateral ventromedial lesions, and was attenuated by truncal vagotomy. Apoptosis in the jejunal mucosa was suppressed in rats with ventromedial hypothalamus lesions. In contrast to the effect on ornithine decarboxylase activity, the truncal vagotomies had no effect on apoptosis in rats with lesions. Apoptosis increased in the sham-operated rats after 24-h and 48-h fasting. Apoptosis in the jejunal mucosa of rats with ventromedial hypothalamus lesions did not increase after 24-h fasting. After 48-h fasting, jejunal apoptosis increased in rats with lesions, but not markedly.Conclusions The ventromedial hypothalamus may regulate cell growth in the intestinal mucosa partly through the vagal nerve; however, the vagal nerve was not related to intestinal apoptosis controlled by the ventromedial hypothalamus.     

The use of neutral red as a peroperative test of vagal innervation.

The cervical vagi were stimulated electrically in four groups of dogs after the intravenous injection of 10 ml of 1% neutral red. One group had intact vagi, the second group had denervation of the distal parietal cell area of the stomach, the third group proximal parietal cell denervation, and the last group had had a complete transthoracic truncal vagotomy. The area of stomach secreting neutral red was significantly related to the insulin-stimulated acid secretion. This technique may provide the basis of a test of residual vagal innervation of parietal cells during vagotomy operations in man.     

Studies of the release of gastrin from the human duodenum induced by gastrin-releasing peptide

In the present study the influence of duodenal exclusion and vagotomy on basal release of gastrin from extra-antral stores has been investigated in addition to the consequences of these procedures on the gastrin response to gastrin-releasing peptide (GRP) infusion. Basal gastrin concentrations and the response to GRP were measured in seven patients after a Whipple operation, in seven patients after antrectomy combined with selective gastric vagotomy and B I reconstruction, in seven patients operated on with antrectomy, selective gastric vagotomy, and Roux-en-Y reconstruction, and finally in seven patients after antrectomy, truncal vagotomy, and Roux-en-Y reconstruction. Gastrin was measured by a highly specific radioimmunoassay. Very low concentrations were obtained after a Whipple operation, and no increase followed GRP infusion. The basal gastrin concentrations were slightly higher in antrectomized patients, irrespective of whether a selective gastric vagotomy had been added. However, in these patients a significant gastrin response followed GRP infusion. Duodenal exclusion seemed not to influence the response to GRP. On the other hand, extragastric vagotomy was followed by low gastrin concentrations in the basal state and only a marginal response to GRP administration. These results strongly suggest that GRP releases gastrin from the human duodenal mucosa and that duodenal exclusion does not alter the response of the duodenal gastrin cells to GRP stimulation. Vagal denervation of the duodenal mucosa seems to suppress the gastrin response to GRP, indicating an excitatory influence of the vagus nerve.     

Experimental study of the pathogenesis of acute acalculous cholecystitis: Role of autonomic denervation

This study was undertaken to elucidate the role of autonomic denervation in the pathogenesis of acute acalculous cholecystitis. In Experiment I, the gallbladder was denervated by performing either celiac neurotomy (sympathetic denervation) or truncal vagotomy (parasympathetic denervation), or both, in dogs. In Experiment II, 45-min ischemia and 90-min reperfusion of the gallbladder with or without autonomic denervation were performed by simultaneously occluding the middle hepatic artery and superior mesenteric vein. Celiac neurotomy, and truncal vagotomy, or both, did not cause cholecystitis. Sympathetic denervation, however, decreased the amount of mucin in the gallbladder mucosa and parasympathetic denervation caused reduction of the tissue blood flow, as well as the accumulation of lipid peroxide and xanthine oxidase in the gallbladder mucosa. These changes were most remarkable 1–2 weeks after denervation and were alleviated 4 weeks after denervation. Ischemia-reperfusion 2 weeks after denervation caused more severe cholecystitis than ischemia-reperfusion alone. The most severe inflammation developed in animals that received both celiac neurotomy and truncal vagotomy. These results suggest that autonomic denervation alone does not induce acute cholecystitis, but that it plays an important role in the progression of the inflammatory process in ischemia-reperfusion injury.     

Effect of vagotomy on the gastric secretory response to intraduodenal osmotic agents in man.

The effect of intraduodenal infusion of hypertonic saline and glucose on pentagastrin-stimulated gastric secretion was investigated in 35 normal subjects, 32 duodenal ulcer patients and 32 patients after truncal vagotomy and pyloroplasty. A significant gastric inhibitory response occurred after 0.51 M saline and 1-03 M glucose in the normal subjects and duodenal ulcer patients but after vagotomy there was no inhibition. This finding suggests that the inhibitory effect of these agents depends, at least in part, on a vagal reflex in man. The response to very high glucose concentrations persisted after vagotomy and it seems likely that a humoral mechanism may be involved in this situation.