The effect of stellatectomy on gastric acid secretion in the dog

The stellate ganglion is the major contributor of adrenergic fibers to the vagus nerve and stellatectomy causes a degeneration of vagal adrenergic fibers. The purpose of this experiment was to evaluate the effect of stellatectomy on gastric acid secretion (GAS) and gastrin levels in the dog. GAS in response to pentagastrin stimulation was measured in six gastric fistula dogs before and after stellatectomy. Likewise, blood was collected for basal and meat meal-stimulated serum gastrin levels before and after stellatectomy. After bilateral stellatectomy acid secretion increased in response to submaximal doses of pentagastrin stimulation whereas maximal secretion was unchanged. Resting and meal-stimulated gastrin levels did not change. A Horner's syndrome developed in each dog. It is concluded that bilateral stellatectomy increases GAS in response to submaximal stimulation while not altering gastrin release. These results suggest that the vagal adrenergic innervation of the stomach has an inhibitory role in the control of GAS in the dog.     

Value of simplified,highly selective transgastric vagotomy in duodenal ulcer surgery

The technique of preservation of the antral vagal nerve supply of the stomach and division of the gastric branches of the nerves of Latarjet remains unchanged. By replacing the transection of the hiatal cardioesophageal vagus nerve branches (including the nerve branches accompanying the arteries entering the fundus of the stomach) with transgastric intramural transection and excision of all nerve fibers entering the fundus, highly superselective vagotomy is achieved. Completeness of this type of vagotomy is controlled intraoperatively by a gastric pH meter and by measuring the oxygen tension of the gastric mucosa. The decrease in oxygen tension of the gastric mucosa below and in the vicinity of the seromuscular incision was similar to that of the rest of the fundus. One year to 18 months after application of highly selective transgastric vagotomy in 74 patients with uncomplicated duodenal ulcers, there was no mortality and insignificant morbidity. The previous ulcer symptoms disappeared. No significant complications such as dumping syndrome or recurrence of ulcer were observed.     

Neurohumoral inhibitory mechanism initiated by antral distension.

This study examines the effect of graded antral distension with acid (0.1 M HCl) or alkali (0.1 M NaHCO3) on pentagastrin-stimulated acid secretion in two groups of dogs. Group A consisted of six dogs provided with innervated antral pouch. In these dogs, the vagal branches to the fundus, as well as the extragastric vagal divisions (hepatic and celiac), were preserved. All of these animals had a gastric fistula in the main stomach, and in two a denervated fundic pouch or Heidenhain pouch was constructed in addition. Group B consisted of four dogs with an innervated antral pouch and gastric fistula. In this latter group, however, parietal cell vagotomy as well as extragastric vagotomy (division of the hepatic and celiac branches) was performed so that the only vagal communication was between the antrum and the CNS. Antral distension with acid caused significant inhibition of pentagastrin-stimulated acid secretion from both the gastric fistula and the Heidenhain pouch in Group A dogs. Antral acidification without distension did not inhibit. Alkaline antral distension in this group caused much less inhibition of acid secretion, but did cause significant increase in circulating immunoreactive gastrin. In Group B dogs, antral distension with neither acid nor alkali caused inhibition of pentagastrin-stimulated acid secretion, indicating that intact vagal supply to the oxyntic mucosa and/or to the extragastric abdominal organs is necessary for the inhibitory mechanism to operate. The results of this study suggest that: a) antral acidification per se does not inhibit pentagastrin-stimulated acid secretion; and b) antral distension with acid, and to a lesser extent with alkali, is inhibitory only if vagal innervation to the fundus and other abdominal viscera is preserved. The observations are compatible with the hypothesis that antral distension activates a neurohumoral inhibitory mechanism releasing the inhibitor reflexly from sites other than the antrum or CNS.     

Effect of gastric mucosal denervation on gastric carcinogenesis]

Numerous nerve fibers containing various neuropeptides are found in gastric mucosa. They play an important role not only in regulation of gastric secretion, motility and microcirculation but also in regeneration and differentiation of gastric mucosa. These nerve fibers are reduced in chronic atrophic gastritis which is considered a lesion closely related to carcinogenesis. We investigated the effect of gastric gastric mucosal denervation (vagotomy) on gastric carcinogenesis by using two experimental rat models in which chronic atrophic gastritis is induced by duodenogastric reflux. At first, following administration of MNNG, vagotomy with duodenogastric reflux enhanced gastric carcinogenesis compared to reflux only. At second, in the model of gastric remnant in which no carcinogenic agent was given, both B-I and B-II gastrectomy with vagotomy showed an increase of carcinoma and/or adenoma at the anastomotic site compared to those without vagotomy. Moreover, in vagotomized groups, there were an increase of labeling index of PCNA positive cells in gastric mucosa and a marked reduction of intramucosal neutral mucin in PAS-Alcian blue staining. These results indicate that the lack of gastric mucosal innervation not only induces the decrease of gastric mucosal cell function and cytoprotection but also enhances the increase of immature cell regeneration.     

Pyloro-oxyntic neurohumoral inhibitory reflex of acid secretion

Antral distension has previously been shown to activate a neurohumoral mechanism that inhibits acid secretion from the main stomach and from a denervated fundic pouch. Neither the antrum nor the central nervous system (CNS) appears to be the source of the inhibitory substance since, when only vagal communication between the antrum and the CNS is maintained, with vagal denervation of all other abdominal organs, antral distension no longer causes inhibition of acid secretion. The present study was designed to investigate whether intact vagal innervation to the oxyntic cell mucosa was a necessary pathway for this inhibitory mechanism. In four dogs with innervated antral pouch (AP) and gastric fistula (GF), the effect of antral distension with 0.1 M HCl at 40-cm pressure on a plateau of GF acid secretion in response to pentagastrin (4.0 μg kg^?1 hr^?1) was studied before and after proximal gastric vagotomy (PGV). The completeness of vagal denervation of the proximal stomach was shown by failure of acid response to insulin hypoglycemia after PGV. Prior to PGV, antral distension caused a significant inhibition of GF acid response to pentagastrin, with a maximal inhibition of 55% of the plateau of acid secretion. After PGV, antral distension was without inhibitory effect. These results indicate that the inhibitory action of antral distension is mediated by a pyloro-oxyntic reflex. Further, since antral distension inhibits a denervated pouch, the study suggests that this pyloro-oxyntic reflex might release a humoral inhibitor from the oxyntic mucosa.     

Role of gastrin in vagally-stimulated pancreatic secretion.

In an attempt to clarify the contribution of antral gastrin to the vaginal stimulation of pancreatic secretion, we have measured the effect of total excision of the antral mucosa on pancreatic secretion induced by electrical vagal stimulation in eight anesthetized dogs. Stimulation was done before excision of the mucosa, and after excision, with and without a gastrin background. Mucosal excision reduced pancreatic volume response to 25% and pancreatic protein response to 32% of the respective responses obtained before excision; gastrin release in response to vagal stimulation was completely abolished. With a gastrin background (0.5 microgram/kg-hr of synthetic human gastrin-17-I), which resulted in serum gastrin concentrations higher than those obtained by vagal stimulation before excision of antral mucosa, the pancreatic volume and protein response showed only partial restoration. These studies provide evidence that vagal pancreatic secretion is only partially gastrin-dependent, and that other antral factors, probably vagally modulated intramural cholinergic pathways, are involved.     

Proximal gastric vagotomy interferes with a fundic inhibitory mechanism: A hypothesis for the high recurrence rate of peptic ulceration

The mucosa of the proximal stomach contains a powerful inhibitor of acid secretion and gastrin release. The release of this inhibitor is dependent on intact vagal innervation of the proximal stomach. Thus, proximal gastric vagotomy interferes with the release of the inhibitor. After proximal gastric vagotomy for peptic ulcer, recurrence rates increase over time. In addition, there is some recovery of acid secretion. Although nerve regeneration or sprouting has been suggested as the possible explanation for these events, we propose that interference with the inhibitory mechanism of the proximal stomach may be another possible explanation for the increasing ulcer recurrence rates after proximal gastric vagotomy. At present, this is only a hypothesis and is suggested only by indirect evidence. Direct testing of the hypothesis will require complete purification of the inhibitor and the development of a specific radioimmunoassay.     

Effect of antrectomy on the nervous phase of gastric secretion in the dog

A method is described for complete isolation of the stomach in the dog with vagal innervation intact. This involves esophagostomy, double mucosal closure of the pylorus and a Maydl gastric fistula combined with gastrojejunostomy. The latter is occluded during periods of study. In this preparation the responses to sham feeding and to insulin-induced hypoglycemia were reduced approximately 10-fold, reiterating the significant synergistic effect of gastrin on vagal stimulation of the parietal cell mass. However, significant acid secretion could still be induced in this preparation by both sham feeding and insulin-induced hypoglycemia.     

The effect of electrical vagal stimulation on canine pancreatic exocrine function.

The effect of electrical vagal stimulation on canine pancreatic exocrine function was studied in conscious dogs by stimulating intact thoracic vagus nerves, the distal ends of cut vagus nerves in animals with intact gastric denervation, and the distal ends of cut vagus nerves in dogs whose stomachs had been previously selectively denervated. The effectiveness of the stimulus was confirmed by monitoring gastric hydrogen ion output. The results indicate that stimulation of intact nerves produced minimal alteration in pancreatic output and bicarbonate and protein secretion while significantly increasing gastric fistula hydrogen ion output. Stimulation of the distal ends (efferent fibers) of cut vagus nerves in dogs with intact gastric innervation significantly increased the volume and protein output of the pancreas and the acid output of the stomach. Stimulation of the distal ends of cut right and both vagus nerves in dogs whose stomach had been denervated previously, again, significantly increased the volume and protein output of the pancreas without stimulation of stomach hydrogen ion output. The data presented in this study suggest that the canine pancreas is innervated directly by vagal fibers, which when stimulated produce an increase in protein (enzyme) output and volume of secretion. Maintenance of the pancreatic response following denervation of the stomach suggests that the response is primarily the result of direct vagal innervation and is not produced by gastrin released from the antrum.     

Neural control of blood flow in gastric mucosa.

The innervation of the small vessels in the fundic mucosa of the rat and the effects of vagotomy on this innervation were studied ultrastructurally. The capillaries and arterioles, but not the venules, were found to receive direct innervation. Vagotomy causes degeneration of the nerve endings that innervate these vessels, confirming their vagal origin. This finding, and the fact that some morphologic changes in the capillaries were observed after vagotomy, provides morphologic evidence for the neural control of blood flow in the rodent gastric mucosa.     

Vagal control of gastrin release in the dog: pathways for stimulation and inhibition

The vagus has a dual effect on gastrin: it both stimulates and inhibits its release. To determine the gastric vagal pathways for these opposing effects, plasma gastrin and acid responses to meal (intragastric titration of 15% liver extract, pH 5.5) and to insulin (0.5 U regular insulin intravenously) were studied in seven dogs in three consecutive stages: a control stage, after antral vagotomy (AV), and after subsequent proximal gastric vagotomy (PGV). AV abolished the plasma gastrin response to insulin but had no effect on either basal or meal-stimulated gastrin release. Subsequent PGV caused significant elevation in basal plasma gastrin concentration, no further change in the gastrin response to insulin, but a significant increase in meal-stimulated gastrin release. AV decreased acid response to insulin nonsignificantly and had no effect on meal-stimulated acid secretion. Subsequent PGV reduced by 90% the acid response to insulin, had negligible effect on the gastric fistula acid response to meal, but increased Heidenhain pouch response sixfold. These studies show that vagal stimulation of gastrin release is mediated along direct antral vagal pathways, while vagal inhibition requires intact vagal fibers to the proximal stomach. The mechanism by which the fundic vagal pathways exert an inhibitory influence on the G cell in the antrum is yet to be elucidated.     

Interdigestive gastric motility patterns: the role of vagal and nonvagal extrinsic innervation

Our study was designed to determine separately the roles of vagal and nonvagal extrinsic innervation in the initiation and coordination of patterns of gastric contractile activity and in the organization of the gastric slow wave. Four dogs first underwent transection of all extrinsic and intrinsic neural continuity to the stomach, except for careful preservation of vagal innervation to the stomach (stage 1). Manometry catheters and serosal electrodes were placed in the antrum, and electrodes were fixed to the small intestine. After recovery, motility was recorded during fasting and after feeding. A cyclic motor pattern occurred in the stomach with a period that was not different from that of the migrating motor complex in the small intestine (113 +/- 11 minutes vs 112 +/- 11 minutes; p greater than 0.05). Gastric and intestinal motility remained coordinated in time. Feeding inhibited this cyclic motor pattern in stomach and intestine. Antral tachygastria (slow wave frequency greater than 8 cycles/min) was infrequent (less than 1% of time). Each animal was restudied after completing extrinsic gastric denervation by a transthoracic vagotomy (stage 2). Vagotomy did not alter the presence, appearance, or period of cyclic gastric activity, nor did it disrupt temporal coordination with the duodenal migrating motor complex or increase the prevalence of tachygastria. In conclusion, neither vagal nor nonvagal extrinsic innervation to the stomach was required for initiation or coordination of the characteristic cyclic gastric motility pattern during fasting; although vagal innervation may modulate gastric myoelectric activity, its precise role is not evident in this study.     

Gastrin release in vagally stimulated gastric acid secretion in dogs

Dogs prepared with gastric fistulas and Heidenhain pouches had vagal stimulation in a continuous fashion by 2-DG (25 mg/kg/hr) before and after antrectomy. An 86 per cent fall in gastric fistula acid output was seen after antrum removal.Heidenhain pouch acid output fell by 36 per cent after antrectomy and the mean acid output was not significantly greater than basal levels.Increased doses of 2-DG (50 mg/kg/hr and 100 mg/kg/hr) post antrectomy failed to restore gastric fistula output to preantrectomy levels.Small doses of pentagastrin coupled with 2-DG (25 mg/kg/hr) did significantly increase acid secretion more than did the individual effects of pentagastrin and 2-DG combined, demonstrating true synergism. 2-DG and barely suprathreshold pentagastrin were as effective as quadrupling the 2-DG dose alone. The loss of antral gastrin, however, after antrectomy was not compensated for by the supplementary pentagastrin.Vagal-antral gastrin, although small in magnitude, is believed to be an important contributor to the vagal mechanism of acid secretion by virtue of its potentiating synergism with parasympathetic innervation of the oxyntic glands.     

Inhibition of afferent vagus nerves decreases gastric stress lesions.

Capsaicin (Sigma Chemical Co.) is a unique chemical agent that causes degeneration of afferent nerve fibers. Previous conclusions about Capsaicin effects on the gastric mucosal response to stress have not precisely defined which afferent nerves were affected. Therefore, the aim of the first portion of this study was to define the origin of afferent vagus nerves to the anterior gastric wall after injections of fluorogold (which is an axonal tracer) into the stomach. The second part of this study was to compare the stress effects on the gastric mucosa in rats with impaired afferent nerve function after Capsaicin treatment.     

Measurement of regional gastric mucosal blood flow by hydrogen gas clearance

Gastric mucosal blood flow as measured by the hydrogen gas clearance method was compared with total gastric blood flow as determined by venous outflow in an isolated segment of canine stomach. During rest and histamine stimulation, hydrogen gas clearance correlated lineally with total gastric blood flow (p < 0.001). Correlation analysis revealed a slope of 1.21 and a correlation coefficient of 0.97. The slope of 1.21 indicates that the ratio of mucosal to total gastric blood flow was approximately 82 percent. This fractional distribution of blood flow is in agreement with that previously reported by microsphere technique. In the intact stomach of anesthetized rats and dogs, antral mucosal blood flow was significantly higher than that of the corpus. This finding may, in part, contribute to the observation that acute stress erosion occurs predominantly in the corpus of the stomach. Histamine stimulation selectively increased the mucosal blood flow of the corpus, whereas antral mucosal blood flow remained unchanged. As a result, there was no significant difference in mucosal blood flow between the antrum and the corpus during histamine stimulation.     

The relative effects of lesser curvature vagotomy and esophageal vagotomy on the acid secretory effect of proximal gastric vagotomy

Proximal gastric vagotomy is an operation consisting of division of all vagal fibers to the acid-secreting portion of the stomach. These fibers are usually divided along the lesser curvature of the stomach; however, because of a high rate of duodenal ulcer recurrence in some series, it has become apparent that it is important to divide the vagal fibers to the stomach leaving the main vagal trunks along the distal 5 cm of esophagus in order to achieve both adequate control of acid secretion and also a lower duodenal ulcer recurrence rate. The data presented in this study of ten mongrel dogs suggest that, in the dog, division of the vagal fibers along the lesser curvature is more important in reducing acid secretion than is esophageal vagotomy; but the data also emphasize the contribution of the vagal fibers along the distal esophagus since a marked reduction in 2 DG-stimulated acid secretion can only be achieved by dividing the vagal fibers around the distal esophagus as well as those along the lesser curvature.     

Effect of vagal stimulation on the concentration of gastrin in serum and antral mucosa in dogs

The concentration of gastrin in serum and antral mucosa was studied in anesthetized dogs after electrical stimulation of the antral branch vagus nerve. Vagal stimulation caused immediate and sustained release of gastrin into the circulation. After stimulation for one hour, the gastrin concentration of antral mucosa increased significantly. This suggests that vagal release of gastrin triggers its rapid synthesis.     

Brain stem topography of vagus nerve to the greater curvature of the stomach

If preganglionic vagus nerve fibers enter the stomach via all of its neurovascular bundles, then proximal gastric vagotomy that divides only the bundles along the lesser curvature of the stomach neglects a potential source of innervation to the parietal cells. To determine whether or not these bundles contained preganglionic efferent vagal nerve fibers, horseradish peroxidase was applied to the central cut end of selected neurovascular bundles along the greater curvature of the stomach in rats and ferrets. Cells in the dorsal motor nucleus of the vagus (dmnX) of the rat were labeled after horseradish peroxidase applications to the right gastroepiploic, the splenic, and the short gastric bundles. The ferrets had horseradish peroxidase applied to the right gastroepiploic bundle and they also had cellular labeling of the dmnX. The labeling in cells of the dorsal motor nucleus of the vagus had a distinct topographic, rostrocaudal distribution in both species, and was maximal in the vicinity of the obex. Cells of the bilateral dmnX were labeled after horseradish peroxidase applications at all bundles. This study showed (1) that the bundles along the greater curvature of the stomach contained preganglionic efferent vagus nerve fibers, (2) that the cells of origin of these fibers were represented in the localized rostrocaudal position of the dmnX, and (3) that these fibers had their origins in the bilateral dmnX. Such nerve fibers may account for incomplete vagal denervation of the parietal cells after proximal gastric vagotomy.     

Effect of partial gastric devascularization on mucosal blood flow and acid secretion in cats.

Partial devascularization of the stomach was performed in cats anesthetized with pentobarbital. The devascularization included all blood vessels along the greater curvature and two of the main branches of the left gastric artery. Gastric mucosal blood flow and cardiac output were determined by means of the microsphere distribution technique. The acid (H+) output from the 30th to the 60th min of pentagastrin stimulation was used as the 'acid response value'. Blood flow and acid secretion were determined before and approximately 2 h after devascularization or sham operation. A marked decrease in acid secretion and mucosal blood flow of the corpus/fundus occurred after devascularization. A high degree of correlation was found between the decrease in acid secretion and the decrease in mucosal blood flow caused by the devascularization. The regression coefficient of acid secretion on mucosal blood flow did not change significantly after devascularization.     

下丘脑室旁核对胃的调控

下丘脑室旁核（hypothalamic paraventricular nucleus，PVN）位于下丘脑的上端第三脑室两侧，是下丘脑前区最显著的核团之一，在下丘脑对内脏活动的调节中占有重要地位。哺乳类的室旁核大多由大细胞神经元和小细胞神经元共同组成。大鼠室旁核的大细胞神经元可分为三部分，即：前大细胞核、内侧大细胞核及后大细胞核。室旁核小细胞神经元可分为五部分：室旁核室周核、室旁核前小细胞核、室旁核内侧小细胞核、室旁核背侧小细胞核及室旁核外侧小细胞部。PVN有广泛的投射，与脑干、边缘系统、脊髓及垂体等均有密切的联系，能合成或分泌30种左右的神经递质和调质，如促皮质激素释放激素（CRF），加压素（AVP），催产素（OXT），血管紧张素Ⅱ（ANGⅡ），神经肽Y（NPY），胆囊收缩素（CCK），神经降压素（NT），脑啡肽等，以及近年来发现的脑肠肽如Ghrelin和Apelin等。