Lester R. Dragstedt

Supra-Diaphragmatic Section of the Vagus Nerves in Treatment of Duodenal Ulcer.

Much of the experimental work on the pathogenesis of gastroduodenal ulcer that has appeared in recent years is in harmony with the concept that the cause of these ulcers is the corrosive action of the gastric juice. It has been adequately demonstrated that pure gastric juice can destroy and digest living tissues including the wall of the stomach itself, producing in this case a defect which appears to be identical with the lesion encountered in man. 1 Under normal conditions, the gastric wall is not digested away apparently because it is not exposed to pure gastric juice. Food, which in the normal individual is the stimulus for the formation of gastric juice, is also the chief factor which protects the tissues against its corrosive activity. Pancreatic juice, gastric and intestinal mucus, duodenal juice and bile (probably in the order named) constitute an additional mechanism which protects the duodenal and, to a certain extent, also the gastric and the jejunal mucosa. When excessive volumes of normal gastric juice are continuously secreted in experimental animals, this defensive neutralizing mechanism is overcome, and ulcer is produced. Wangensteen and his associates 2 have produced ulcers in many experimental animals by the implantation of pellets of histamine mixed with beeswax into the muscles or beneath the skin. The gradual liberation of histamine provoked a long continued secretion of gastric juice. Most ulcer patients display an excessive secretion of gastric juice in response to the stimulus of food, histamine, or alcohol. A considerable number secrete large amounts of gastric juice when there is no obvious stimulant, as at night when the stomach has been previously emptied of food by lavage. The cause of this abnormal secretion is unknown.

Vagotomy and drainage procedure for duodenal ulcer: The results of seventeen years' experience.

During the 10 years prior to January, 1968, 455 duodenal ulcer patients were operated upon at the University of Florida affiliated hospitals. The early results were reported in 1969. The present study is a followup of the same patients now 7 to 17 years after vagotomy and drainage. Twenty-four per cent were lost to followup. The ulcer recurrence rate was 5.8 per cent. All the recurrent ulcers that were not gastric in location (4.9%) occurred within 5 years after the original operative procedure with a mean of 2.6 years. The gastric ulcers (0.9%) occurred at a much later date with a mean of 6 years. It is concluded that vagotomy and gastric drainage is a satisfactory modality of therapy for duodenal ulcer. It can be accomplished with an acceptable morbidity and mortality and the long-term recurrence rate is low. If recurrences due to incomplete vagotomy do not occur within 5 years, they are unlikely to recur.

Significance of innervation in the function of the gastric antrum.

The antrum of the stomach in dogs was excluded by constructing a membrane of gastric mucosa separating the cavity of the antrum from that of the corpus. A fistula was made of the pylorus and intest...

Effect of vagotomy on gastric secretory response to histamine.

Conclusions 1. The gastric secretory response to a standard dose of histamine in dogs with a totally isolated stomach pouch is markedly reduced by bilateral vagotomy. 2. Atropine similarly reduces the gastric secretory response to histamine in these animals. 3. Gastric vagotomy in patients with peptic ulcer also markedly reduces the gastric secretory response to a standard dose of histamine.

Antrum Motility as a Stimulus for Gastric Secretion

Summary Observations have been recorded concerning the effects of various procedures such as removal of vagus innervation, transplantation of the antrum to the abdominal wall and into the colon, on the total output of gastric juice from a Pavlov pouch. It is concluded that the hormonal or antrum phase of gastric secretion is most important, the nervous phase of secretion is somewhat less, and the intestinal phase is least important in provoking the secretion of gastric juice from a Pavlov accessory stomach pouch. The antrum of the stomach, transplanted into the colon, causes a greater secretion of gastric juice than is produced when the antrum is in its normal location. This secretion may continue even though the original blood supply to the antrum is divided, and it is nourished by newly formed blood vessels from the colon. In the absence of other factors, the development of pressure within the isolated colon containing an antrum transplant as a result of peristalsis is a profound stimulation for antrum function. The significance of this finding as a possible explanation for the increase in gastric secretion accompanying pyloric stenosis in man is suggested.

Peptic ulcer: An abnormality in gastric secretion☆☆☆

Abstract I can perhaps best summarize this discussion by referring to Figures 18, 19, and 20. I am persuaded that duodenal ulcers are usually caused by a hypersecretion of gastric juice of nervous origin brought about in some way by the tensions, strains, and competitive efforts of modern life. These factors, increasing gradually over the years, produce an increase in the tonus of the vagus nerves which involves both motor and secretory fibers. The long-continued vagal stimulation of the gastric glands produces hyperplasia and hypertrophy with resultant increase in the parietal cell mass. The secretory hypertonus of the vagi causes a marked increase in the basal gastric secretion. This large secretion in the empty stomach without the buffering effect of food makes the gastric content very corrosive and, when it is hurried onward into the duodenum by the gastric hypermotility, produces the chronic progressive ulcer in the less resistant duodenal mucosa. Gastric ulcers on the other hand are usually caused by hypersecretion of gastric juice of humoral or gastrin origin caused by stasis of food in the stomach in contact with the gastric antrum. This stasis may be due to pyloric stenosis from an accompanying duodenal ulcer or to defective gastric tonus and motility. Patients with gastric ulcers and an accompanying duodenal ulcer display the nervous hypersecretion characteristic of the duodenal ulcer patient and also an excessive secretion of humoral origin due to prolonged contact of food with the antrum mucosa. Patients with gastric ulcers without organic obstruction at the pylorus usually display subnormal basal gastric secretion and a dilated poorly emptying stomach. Many patients secrete little or even no free hydrochloric acid in the basal secretions, indicating that the nervous phase of gastric secretion is markedly reduced. This is probably an indication of decreased tonus in the secretory fibers in the vagi and the stasis of food in the stomach suggests an accompanying decrease also in the tonus of the motor fibers. Stasis in gastric ulcer patients may not be revealed by the usual liquid barium meal of the roentgenologist but becomes evident when the patient eats a large meal of customary food. The gradually increasing acidity of the gastric content eight to twelve hours after eating testifies to the continuing secretion of gastric juice caused by gastrin and to the increase in the corrosive properties of the gastric content as the buffering effect of the food becomes exhausted.

The etiology of gastric and duodenal ulcers.

Gastric and duodenal ulcers in the majority of cases are believed to be due to an increase in the corrosive properties of the gastric content and not to a local decrease in the resistance of the gastric wall. The increase in the corrosive properties of the gastric content is due to a hypersecretion of gastric juice. In duodenal ulcer patients this hypersecretion is predominantly of nervous origin and is due to the tensions and strain of modern life. It is abolished by a complete vagotomy. The hypersecretion of gastric juice in patients with gastric ulcer is of hormonal origin and is due to a hyperfunction of the gastric antrum in the presence of food in the stomach. This hypersecretion is abolished by excision of the antrum.

Blood Chemistry in Intestinal Obstruction.

The work of Tileston and Comfort, 1 Whipple and his associates, 2 Mac Callum, 3 Hastings, 4 Haden and Orr, 5 and others has demonstrated that obstruction in the upper intestinal tract produces characteristic changes in the blood chemistry. These may be summarized as follows: a decrease in the concentration of chlorides, a late increase in non-protein and urea nitrogen, and an increase in the carbon dioxide combining power of the blood plasma. As a result of a number of experiments reported by L. R. Dragstedt, 6 C. A. Dragstedt, 7 P. R. Cannon, 8 and their associates from 1916 to 1921, these authors concluded that the toxemia of intestinal obstruction was due to the absorption of chemical fractions produced by the proteolytic activity of the intestinal bacteria and that the factor permitting their absorption was circulatory damage to the intestinal mucosa as a result of distention. In the present experiments determinations were made of the non-protein nitrogen, urea nitrogen, and chloride concentration in the blood of dogs subjected to the various procedures described in the early reports. The following points are brought out.

Extensive Insulin Tolerance in Diabetic Dogs.

Soon after the introduction of insulin into clinical practice, it was observed that the amount of the new hormone required to control the glycosuria in patients with diabetes mellitus depended in part on the amount of available carbohydrate in the diet. Elaborate attempts were made to establish a quantitative relation between the insulin requirement of the patient and the amount of carbohydrate obtained as such in the food together with that which might arise through the conversion of protein and fat. Some success attended these efforts. It was soon found however that wide variations in the insulin requirement of certain patients occurred from time to time in spite of a constant diet and that enormous amounts of insulin were needed for certain patients. 1 The concept of insulin sensitivity and of insulin resistance thus arose. The precise nature of these states seems to be little understood and the present report is presented in the hope that it may contribute to the solution of this problem. In a recent monograph, Jensen 2 states that about one unit of insulin per kilogram of body weight is required per day to maintain normal carbohydrate metabolism in the depancreatized dog. In our experience this figure is too low. Most of these animals require from 2 to 3 units per kg if good control of the glycosuria is desired. In comparison with these figures the amounts of insulin required to establish a comparable control of glycosuria in dogs with certain types of partial pancreatectomy seem surprising. Nine male dogs, varying in weight from 8.2 to 13.4 kg, were operated upon and all of the pancreas removed save for a small portion in the region of the lesser duct.

Fatal Effect of Total Loss of Gastric Juice.

The present experiments were undertaken to determine the effect of the total loss of gastric juice from the body under conditions not complicated by obstruction such as are present after closure of the pylorus. Recourse was made to a method described by Lim, Ivy, and McCarthy 1 with this important modification that the vagus nerves to the isolated stomach were left intact. The stomach was cut across at the cardia and the pylorus. The cardiac end of the stomach was then inverted and closed and the open pyloric end brought to the surface as a fistula. An anastomosis was made between the lower end of the esophagus and the duodenum. Great care was taken in sectioning the cardia not to interfere with the vagus fibers to the stomach and as much of the blood supply to the isolated stomach was left as was technically possible. To date we have made 3 such preparations but the data to be presented here are from a single animal. At autopsy the vagus nerves to the isolated stomach in this animal were found intact. A daily record was kept of the water and food intake (food exclusively milk and muscle), the urinary output, and the quantity and composition of the gastric secretion collected from the isolated stomach. In addition blood was drawn at the end of each 24 hr. period and determinations made of the CO2 combining power of the blood plasma, the blood pH, and the NPN, urea N, and chloride concentration. The following points have been established: (1) The total loss of the gastric secretion from the body causes death in the dog with symptoms of weakness, anorexia, oliguria and profound depression. (2) Accompanying these symptoms and proportionate to their severity occurs a prompt fall in blood chloride, an increase in the CO2 combining power of the plasma, an increase in the pH, and a late increase in the NPN and urea N. (3) The symptoms may be relieved and the blood chemistry returned toward the normal by the intravenous injection of from 2,000 to 3,000 cc. of Ringers solution or 0.9% NaCl solution per 24 hrs. (4) The isolated stomach, with intact blood and vagal supply, will frequently secrete in 24 hrs. from 1000 to 1600 cc. of gastric juice with a chloride concentration of 0.5 to 0.55%.