In vitro culture of rabbit esophageal epithelial cells.

An in vitro model using esophageal epithelial explant cultures has been developed. Esophageal mucosa from New Zealand white rabbits was cut into 1.5-mm2 sections and fixed to a plastic petri dish using chick plasma. Appropriate outgrowth medium was added, and the explants were incubated in a humidified CO2 incubator at 37 degrees C. Cell outgrowth was measured directly, and lipid content was determined qualitatively. Esophageal epithelial cells grow as confluent sheets of multilayered cuboidal cells. Three growth phases were identified. Increased oxygen tensions inhibited growth. Optimum growth occurred at pH 7.4. Growth was significantly inhibited at pH 6.4, and no growth occurred at pH 5.8. Cells may be released by trypsin and five subcultures obtained. These results demonstrate that monolayer cultures of normal esophageal epithelium may be routinely established and maintained in cell culture for extended periods from small samples of tissue and that factors affecting growth may be quantitatively determined.

Responses of feline esophagus to cervical vagal stimulation.

We used an in vivo feline model to study striated and smooth-muscle esophageal responses to cervical vagal stimulation (VS). Circular esophageal contractions were measured by intraluminal pressure sensors and longitudinal contractions by a force transducer. Responses to VS were recorded before and after giving succinylcholine, atropine, or both. Circular contractions characteristic of striated and smooth muscle were recorded from the mid- and distal esophagus, respectively. With increases in VS frequency, the striated muscle showed rapid, repetitive twitches progressing to tetany. These fast contractions had a square-wave configuration at VS greater than or equal to 10 Hz and were abolished by succinylcholine. In contrast, the slow-twitch circular responses of smooth muscle showed no repetitive twitches and had a bell-shaped configuration. Two types of circular smooth-muscle contractions were observed: 1) A wave "on contractions" occurred 0.5-1.0 s after VS onset, regardless of stimulus length, and 2) infrequent B wave "off contractions" occurred only after stimulus cessation. The longitudinal esophageal contractions had a compound wave form with both striated and smooth-muscle components. Atropine abolished the slow component of the longitudinal contraction, the circular A wave, and peristalsis in the distal esophagus. We conclude that cholinergic motor neurons are an important pathway for eliciting peristalsis in feline esophageal smooth muscle.

Improved infusion system for intraluminal esophageal manometry.

An improved catheter infusion system is needed for esophageal intraluminal manometry. Using conventional syringe-pump infusion systems undesirably rapid infusion rates of 6 ml per min or more are often needed to achieve accurate recording of esophageal peristaltic pressure. These rapid base line infusion rates are necessitated by the high compliance of syringe-pump systems which causes substantial reduction in the infusion rate during dynamic pressure transients. In this study we tested a hydraulic-capillary infusion system designed to have low compliance. This minimally compliant system yields accurate recording of esophageal peristaltic pressure at infusion rates of 0.6 ml per min or less. We believe that the hydraulic-capillary infusion system is a useful tool for performing both clinical and investigative studies of esophageal motor function.

Quantitation of pharyngeal motor function in normal human subjects.

A need exists for accurate pressure recording of pharyngeal motor events. Results of this study indicate that accurate quantitation of pharyngeal motor activity is not possible using a water-filled catheter system, even when high infusion rates are used. An intraluminal strain gauge system, however, achieves high-fidelity recording. Quantitation of pharyngeal peristalsis using the intraluminal strain gauge system reveals peristaltic pressure amplitudes higher than those hitherto recorded. In normal subjects, peristaltic amplitude averages about 200 mmHg in the hypopharynx, complexes in one subject being as high as 600 mmHg. A zone of relatively low pressure exists in the oropharynx. Mean pharyngeal wave duration decreases progressively in an aboral direction, from 1.0 to 0.3 s, and peristaltic wave speeds range between 9 and 25 cm/s. Accurate quantitation of pharyngeal peristaltic variables provides the necessary basis for characterization and assessment of pharyngeal motor disorders.

Radial distribution of esophageal peristaltic pressure in normal subjects and patients with esophageal diverticulum.

This study was designed to determine the radial profile of peristaltic pressure waves in the esophageal body of normal subjects and patients with isophageal diverticulum. We used a manometric assembly featuring four radial side hole recording orifices oriented at equidistant 90 degree angles. Each recording catheter was infused with water at a rate (6.1 ml per min) which provided high fidelity pressure recording. In normal subjects, the radially recorded peristaltic pressure complexes were similar in peak amplitude and wave form. The range of pressure differences between the four radial recordings averaged 9.0 +/- 4 SD mm Hg A range is less than or greater to 25 mm Hg occurring in 99% of observations. These variations in pressure amplitude showed no consistant spacial orientation. In 5 of the 6 patients with esophageal diverticulum, the range of radial peristaltic pressure differences exceeded 25 mm Hg in the region of the diverticulum, the lowest pressure occurring at the recording orifice facing the diverticulum mouth. In occasional peristaltic sequences abnormal wave forms featuring abrupt onsets or offsets were observed. These bizarre wave forms were probably caused by oralaboral diverticulum movement relative to the recording sensor during peristalsis. Two patients had abnormally high peristaltic pressure amplitudes, greater than 250 mm Hg. This latter finding introduces the possibility that hypertensive peristaltic contractions may contribute to diverticulum production in some patients.

Effect of increased intraabdominal pressure on lower esophageal sphincter pressure.

This study evaluates the effect of intraabdominal pressure increases on lower esophageal sphincter (LES) pressure in normal subjects and in patients with reflux esophagitis. Intraabdominal and intragastric pressure were increased by abdominal compression, the Valsalva maneuver, and leg raising. In normal subjects changes in pressure recorded from the LES equaled the changes in gastric pressure induced by abdominal compression and Valsalva. Consquently the LES-gastric pressure gradient remained unchanged. During leg raising, pressure recorded from the LES increased more than gastric pressure, thereby increasing the LES-gastric pressure gradient. Although statistically significant, the LES pressure increases associated with leg raising were modest, unrelated to initial sphincter pressure, and unaffected by atropine. When individuals demonstrating a "common cavity" phenomenon were exculed, LES pressure changes during abdominal compression were similar in patients with esophagitis and in normal volunteers. Consequently, response of the LES to abdominal compression generally does not separate patients with esophagitis from normal subjects. We believe that the LES responses to increased intra-abdominal pressure observed in this study are better accounted for by mechanical factors than by a physiologic adaptive response of intrinsic LES tone.

Relationship between serum gastrin concentration and lower-esophageal sphincter pressure.

Serum gastrin concentration [G] has been proposed as the major factor regulating resting lower-esophageal sphincter pressure (LESP). Available supporting evidence in man, however, is largely circumstantial. The present study directly compares measurements of LESP with concurrent levels of circulating serum gastrin in fasting human subjects. A direct correlation was not shown between [G] and resting LESP; rather, a trend existed toward an inverse relationship. The study results indicate that the concentration of serum immunoreactive gastrin is not a major determinant of lower-esophageal sphincter tone in humans.

A rapid pull-through technique for measuring lower esophageal sphincter pressure.

Because disadvantages are inherent in the conventional station pull-through technique (SPT) currently used for recording lower esophageal sphincter pressure (LESP), a more suitable recording method is needed. In study, we evaluated a rapid pull-through technique (RPT) for recording LESP and compared the results with those obtained by SPT. The RPT features rapid withdrawal of recording sensors across the LES during a 10- to 20-sec interval of suspended respiration. This method avoids recording "artifact" caused by respiratory LES motion and provides precise end points for scoring and measurement. In 12 normal subjects, LESP measured by RPT (24.3 plus or minus 0.5 mm Hg) was comparable, but significantly greater, than LESP measured by SPT (21.1 plus or minus 9.1 mm Hg). Analysis of LESP scores for the two recording methods revealed that both intraobserver and interobserver error were substantially less for RPT than SPT (P less than or equal to 0.01). Further correlation of LESP between studies was greater for the RPT than the SPT recording method. We conclude that RPT represents a convenient method for recording LESP which is easier to perform and yields more reproducible values than LESP recording by SPT.