Charles F. Code

DUODENAL-GASTRIC REFLUX AND SLOWED GASTRIC EMPTYING BY ELECTRICAL PACING OF THE CANINE DUODENAL PACESETTER POTENTIAL

In 6 (10 to 12 kg) mongrel female dogs, silver electrodes for recording electrical activity and for pacing of pacesetter potentials (PP) were implanted on the stomach and duodenum and a catheter for intraluminal instillations was inserted into the duodenum. Beginning 2 weeks after operation, electrical recordings were made intermittently from the fasted, conscious dogs with no pacing and during pacing of the PP in the proximal and in the distal duodenum. A suspension of BaSO4 injected into the unpaced duodenum and observed cinefluoroscopically was swept quickly from the duodenum into the jejunum; little or none passed orad into the proximal duodenum, and BaSO4 rarely entered the stomach. Only 1 to 3% of a duodenal infusate of 154 mM NaCl with [14C] polyethylene glycol (2 ml per min) appeared in the stomach after 15 min. The results during proximal duodenal pacing were the same as with no pacing. However, distal duodenal pacing, which reversed the direction of propagation of the duodenal PPs, caused duodenal-gastric reflux of BaSO4 in every dog and forced about 30% of the duodenal infusate into the stomach during fasting and during gastric emptying of 400 ml of 154 mM NaCl; at the same time, the rate of emptying of the gastric instillate was slowed about 25%.

A Study of Esophageal Pressures in Normal Persons and Patients with Cardiospasm

Summary A miniature electromagnetic transducer was utilized to record accurately esophageal pressures after swallowing. The changes in pressure in normal persons followed a definite pattern, which consisted of an initial wave of negative pressure and three subsequent waves of positive pressure. Analysis indicated that the final positive wave was produced by a true peristaltic wave passing the transducer. Patients who had cardiospasm showed considerable spontaneous motility as well as extremely variable responses in pressure as the result of deglutition. Though waves of positive pressure were noted occasionally in these patients after swallowing, a co-ordinated, distally traveling wave of the peristaltic type could not be identified.

Effect of Histamine and Its Methyl Derivatives on Cyclic AMP Metabolism in Gastric Mucosa and Its Blockade by an H2 Receptor Antagonist

In a cell-free system prepared from guinea pig gastric mucosa, histamine and Nalpha-methyl-histamine produced dose-dependent stimulation of cyclic AMP formation and 1,4-methylhistamine had a minimal stimulatory effect. N-methyl-N-(2-[5-methylimidazole-4-yl-methylthio]-ethyl) -thiourea (metiamide), a new H2 receptor inhibitor, selectively blocked the stimulation of adenylate cyclase by histamine and its active methyl derivative but had no substantial effect on the basal adenylate cyclase activity or adenylate cyclase stimulated by sodium fluoride. Metiamide inhibited the histamine stimulation of adenylate cyclase at 1/100 the concentration of the histamine. Histamine, its methyl derivatives, and metiamide did not influence the activity of cyclic AMP phosphodiesterase from gastric mucosa. Therefore, histamine stimulates gastric mucosal adenylate cyclase via interaction with the H2 receptor without influencing cyclic AMP breakdown, and N-methylation of histamine on the side chain preserves or even increases its stimulating ability. On the other hand, N-methylation in the ring nearly abolishes the ability of histamine to interact with the H2 receptor.

A Study of the Motility Patterns and the Basic Rhythm in the Duodenum and Upper Part of the Jejunum of Human Beings

Summary 1. Balloon-photokymographic recordings of duodenal and upper jejunal motility have been made in 21 normal persons, 5 patients who had duodenal ulcer and 5 who had chronic ulcerative colitis. 2. The waves seen in the records were classified in two types designated I and III. Measurements of the dimensions of these waves and their frequency of occurrence were made and the percentage of the observation time during which activity was present was also determined in each record. 3. In all of the records, periods of activity alternated with periods of quiescence. When the normal persons and the patients fasted overnight, motility was present 60 to 70 per cent of the time. This percentage was reduced in normal persons to 34 by a fast of 24 to 36 hours. During the active periods, type I waves occurred almost continuously and type III waves were seen about half of the time. 4. Bursts of type I waves in rhythmic sequence occupied about 2 per cent of the tracings from normal persons and from patients who had duodenal ulcer. In the patients who had ulcerative colitis the incidence exceeded 6 per cent. In all of the persons studied, the mean rate of the type I waves when in rhythmic sequence was 11 per minute and the variations around this mean were less than 1 per minute. This rate of rhythmic type I waves has been presented as representing the basic rhythm of the small intestine.

Localization of the duodenal pacemaker and its role in the organization of duodenal myoelectric activity

In two series of conscious healthy dogs, a study of duodenal electric activity was made to locate the pacemaker or site of the greatest intrinsic frequency of the pacesetter potential. In three dogs, an annular myotomy of the duodenum about 1 cm proximal (orad) to the biliary ampulla caused a reduction in the frequency of the pacesetter potential distal (caudad) to the conduction block and demonstrated that the pacemaker was not in the region of the ampulla, as had been suggested previously. Annular myotomy of the duodenum at increasing intervals distal to the pylorus in a second series of eight dogs showed that the pacemaker was present in the proximal 5 to 6 mm of duodenum. The greater frequency of the pacemaker was found to maintain constant distal conduction of the pacesetter potential. Distal conduction of the pacesetter potential was shown on occasion to be associated with the distal propagation of action potentials along the duodenum.

The pressure profile of the gastroduodenal junctional zone in dogs

EDITORIAL SYNOPSIS A narrow zone of raised pressure has been found at the gastroduodenal junction in fasting dogs, indicating that the diameter of the lumen is less than 1-7 mm. most of the time. Instillation of acid into the duodenum increased the pressure in the junctional zone and stimulated duodenal motility while antral motility decreased. Instillation of olive oil into the duodenum also increased the pressure at the junction but only after a lapse of 15 minutes whereas antral motility was inhibited immediately.

Chronic Histamine Action.

Histamine placed in the body in watery solution rapidly produces acute effects of relatively short duration (Dale and Laidlaw 1 ). During the past 2 years studies have been undertaken to develop a procedure by which injected histamine would act over prolonged periods and produce chronic effects. The ultimate aim of the investigation was the study of chronic histamine poisoning. Experimental Procedure. Histamine was administered by subcutaneous or intramuscular injection. All doses mentioned are in terms of histamine base. Two tests were employed to determine the efficacy of the methods used to slow the rate of absorption of histamine from the sites of injection. The first was a comparison in normal guinea pigs of the effects of large doses of histamine in saline solution with the effects of the same dose of histamine in other substances. While this method was satisfactory for the preliminary experiments it was inadequate for the quantitative determination of the extent and degree of prolonged histamine action. The second test was the measurement of the amount and quality of the secretion from gastric pouches of dogs made according to the method of Heidenhain. This test provided a quantitative basis for studying the extended action of histamine. The pouches were prepared under ether or nembutal anaesthesia using the usual surgical technic and sufficient time for recovery was allowed before tests were commenced. Histamine was first ground with glycol stearate and then suspended in mineral oil. In guinea pigs, injection of this material was quickly followed by typical symptoms and fatalities. Similar results were obtained when histamine particles were covered with paraffin and suspended in oil. Definite protection was obtained with a mixture of finely powdered histamine, pure beeswax or beeswax containing resin and mineral oil.

Motility Patterns in the Terminal Ileum: Studies on Two Patients with Ulcerative Colitis and Ileac Stomas

Summary 1.The motor activity of the lower segments of the ileum of two patients with ulcerative colitis and ileac stomas has been studied repeatedly over a period of 1 year. Motility was followed by means of two small balloons placed in the ileum in tandem fashion through the abdominal stoma and connected to two glass-spoon manometers, the excursions of which were recorded photokymographically. 2.A wave which we have not recognized before in motility recordings of the small bowel was encountered. It has been designated type IV because of its close resemblance to type IV waves in the colon. It is apparently often caused by the simultaneous contraction of a number of adjacent segments of the lower ileum. The contraction is propulsive in action. When these contractions are in rhythmic sequence, the terminal ileum assumes the function of a rhythmically acting pump, which clears the lower small bowel of its contents by expelling them distally. 3.During the 28 1/2 and 19 hours of recordings obtained from the 2 patients after an overnight fast, motor activity was present in the terminal ileum about 90 per cent of the time. Type I waves were present most of the time, type III waves about one-third to one-half of the time, while type IV waves were uncommon. Basic rhythm (type I waves in rhythmic sequence) occupied 1.2 per cent of the fasting records of one patient and 8.3 per cent of the fasting records of the other patient. 4.When a hearty breakfast was ingested, the pattern changed. Nonrhythmic type I activity declined, type I waves in rhythmic sequence (basic rhythm) disappeared, while type IV activity greatly increased. These changes were almost identical to those seen following administration of neostigmine. 5.Administration of cholinergic blocking agents usually reduced all types of motor activity in the terminal ileum. 6.Following the administration of morphine, the pattern was changed, although the total activity—that is, the percentage of time during which activity was present—was unaltered. The propulsive type IV waves were reduced or eliminated. The incidence of rhythmic type I waves was greatly increased. The duration of type III waves (tone waves of base-line pressure changes) may have been prolonged. 7.The rate of occurrence of type I waves in the terminal ileum, that is, its basic rhythm, was exceedingly constant in all of the tests. In the records made during fasting the rate was 8.6 ± 0.1 per minute in one patient and 8.1 ± 0.1 per minute in the other. This is significantly slower than the rate of the basic rhythm in the upper small bowel reported by others. The finding indicates that there is a gradient in the rate of the basic rhythm from upper to lower small bowel in human beings.

Identification of the Gastroesophageal Mucosal Junction by Transmucosal Potential in Healthy Subjects and Patients with Hiatal Hernia

Summary The purpose of this investigation was to determine whether the contrasting transmucosal potentials of the stomach and the esophagus can be used to identify the gastroesophageal mucosal junction. To relate changes in the potential difference (PD) to other characteristics of the junctional zone, pressure and pH determinations were made simultaneously with those of PD. Observations were made during fasting on 18 healthy persons, 5 dogs, and 12 patients with hiatal hernia. A zone of elevated pressure was found at the junctional region in the healthy persons and the dogs. The PD changed within the region of elevated pressure. The greatest change was at the physiologic hiatus (site of respiratory reversal) or just distal to it. The pH in the healthy persons and the dogs usually changed within the zone of elevated pressure, and, as with PD, the greatest change usually occurred just distal to the point of respiratory reversal. In some tests, an acid pH extended into the esophagus. When the gastroesophageal junction was visualized in an anesthetized dog with the exploring electrode previously fixed at the site of maximal change in PD, the electrode was found within 5 mm of the mucosal junction. Pressure characteristics indicative of hiatal hernia were detected in the 12 patients known to have hiatal hernia. In these patients, the site of greatest change in PD was shifted to the proximal region of the zone, indicating displacement of the mucosal junction into the chest. An acid pH in the esophagus was common in the patients with hiatal hernia.

Measurement of gastrointestinal transmural electric potential difference in man

Measurement, in man, of the electric potential difference between venous blood and the mucosal surface of the gastrointestinal tract gave identical values to the potential difference between mucosa and serosa. Various parts of the peritoneum were equipotential with venous blood. By contrast, skin-enteric potential difference varied with time and among different subjects because of a potential difference between skin and blood that is unpredictably reduced by skin injury. The results with electrolyte bridges of KCl in agar or of flowing KCl were identical.