Historical perspectives on gastric motility and gastroparesis

Introduction

Remarkable progress has been made in the study of gastrointestinal (GI) motility, particularly gastric motility, in the last century. This progress in GI motility has proceeded from contributions of a wide range of disciplines with advances in smooth-muscle physiology, electrophysiology, neurohormonal regulation of the GI tract, anatomic/mechanical factors, flow dynamics, as well as basic molecular and cellular biology. Increasingly sophisticated instrumentation, biomedical engineering, and pharmaceutical research have also added to this rich harvest over the past 50 years. A central theme to the progress is the greater understanding of the enteric nervous system, where more than 10 ⁶ neurons intercommunicate and integrate messages from the gut and brain to organize and coordinate control of GI motility.

The measurement and quantitation of gut motility has been a constant goal during this era, particularly the study of peristaltic contractions. The measurement of intraluminal pressures started with the use of balloons inflated in the stomach and intestine. In the 1950s, open-tipped catheters began to be used to study the esophagus. Subsequent improvements included the continuous-perfusion catheters with the low-compliance Arndorfer pump, and the development of the Dent sleeve which have facilitated the study of sphincters. At the turn of the century (1900s), gastric flow could be imaged by means of contrast radiograph. By the 1980s, scintigraphy enabled flow studies throughout the GI tract to be performed routinely in clinical practice. Scientific investigation of gut wall movement began with the use of miniature force transducers sewn to the luminal wall. Electromyography has also been used to enhance our understanding of wall movement. Magnetic resonance imaging (MRI) can be used to correlate gut wall motion with intraluminal pressures and other physiologic parameters.

Basic research has focused on neurohormonal regulation and myogenic components of GI motility. In the 1930s, gut motor activity was believed to occur as a result of opposition between excitatory parasympathetic (cholinergic) and inhibitory sympathetic (adrenergic) nerves. Electrical field stimulation of gut muscle preparations led to the discovery of nonadrenergic non-cholinergic (NANC) nerves as the predominant intrinsic inhibitory nerves of the GI tract. The identity of the NANC neurotransmitters, including vasoactive intestinal polypeptide (VIP) and nitric oxide then evolved. Electrical slow waves were appreciated to govern the rhythmicity of contractions, and slow waves of the stomach and small bowel began to be studied extensively by muscle electrophysiologists in the 1950s and 1960s.

W.B. Cannon and F.T. Murphy in 1906-7 reported that gastric emptying and intestinal motility may be inhibited by both central and peripheral mechanisms. In 1943, Wolf and Wolff suggested that certain emotional states can alter gastric motility, secretion and blood flow. Ongoing research defined the influence of GI peptides and hormones on the migrating motor complex (MMC). In a review 10 years after the demonstration of the migrating complex, Wingate noted that neural and hormonal factors are involved in regulation, but ‘specific details remain blurred’ – an observation which is slowly being unraveled.

This chapter is focused on more than a century of historical perspective to help us understand where we are today in the study of gastric motility.

Observation of flow through the gastrointestinal tract

Aside from Beaumont’s famous opportunity in the 1830s in his patient with a gastric fistula , no one had any way to examine directly the flow of the gut until more than 50 years later. Beaumont could only make a crude evaluation of gastric flow because his patient’s fistula extended into the fundus, and so Beaumont’s experiments on flow depended on the measurements of residual volumes collected by aspiration. However, he was more interested in gastric juice and digestion than gastric emptying.

The great impetus to the study of flow came with the development of the x-ray tube at the end of the 19th century. Roentgen’s development of the concepts and methods for x-ray soon found application in the study of gastrointestinal flow. The pioneers Bowditch and Cannon examined the stomach and intestine by contrast radiography before the turn of the century . Cannon and others were mainly interested in gastric motility and adopted contrast radiography as a new means to visualize peristalsis and flow from the stomach. Physicians soon recognized the ability of contrast radiography to demonstrate morphologic lesions in the stomach. Hurst led this advance in the clinical use of radiography . The use of contrast films to observe flow extended to the other organs, including the colon. The biggest problem in the study of flow in the stomach and intestine was the need for rapid changes of film, a need that was resolved only when rapid film-chargers and cineradiography were developed.

By 1933, radiographic techniques had revealed so much that an authoritative textbook could be written on the digestive tract from the point of view of the radiologist . It contained extensive descriptions of flows in all the organs as well as descriptions of peristaltic wall movements and morphologic abnormalities. The descriptions still appear quite modern to the contemporary reader.

Observations by contrast radiography are hard to quantify, cannot easily be repeated for verification, are usually performed with the subject fasting, and use a remarkably unphysiologic material. These problems of radiography to demonstrate motility were overcome with the development of scintigraphy in the 1980s . Scintigraphy made it feasible to do flow studies in routine clinical practice and made flow study more sensitive.

Before the advance of scintigraphy, Hunt had developed a beautifully simple and direct method to advance understanding of gastric emptying, especially of its regulation . He used test meals – liquid volumes of variable composition – passed through a nasogastric tube in various volumes and aspirated at variable times afterward to discover the residual volume. He used anaesthetized human subjects, studying the same subjects repeatedly because habituation eliminates the inhibition produced by anxiety. Thus, he was able to develop data for the rate of gastric emptying as it is regulated by meal composition .

Most discussions of flow in the gut have dealt with bulk flows, the mass translocations of fluid. Interest in microflows came about from theoretic considerations of intestinal absorption, in which the presence of an unstirred layer at the luminal surface of the intestine came to be recognized as a limitation to the rate of absorption. Little can be done to study microflows directly, because it requires the use of the principles of fluid mechanics, a discipline that is largely as foreign to gastrointestinal physiologists as gastrointestinal physiology is foreign to fluid-mechanists. The fluid mechanist, Mecagno, who had extensive experience on flow in rivers and seas, was curious about flow in a system that seemed unique to him. A fluid-mechanical approach to flow in the small intestine by Christensen and Macagno yielded a foundation for rigorous rheologic study of gastrointestinal microflow and a host of new methods and ideas in the 1970s , an area that remains to be explored more fully.

Observation of pressures in the gastrointestinal tract

The idea that one could study wall motions by the measurement of pressures in the gut lumen, by kymography (or manometry, as it came to be called later), arose quite early, even before the development of radiographic methods to study flow. It began largely with the use of balloons inflated in the stomach and intestine, a method used notably by Bayliss and Starling , Carlson , and Thomas , among others. Investigators could record pressure changes in such balloons easily enough, but they had much trouble interpreting the records. They slowly came to confront the problems of balloon recording, which seem so obvious to us today. The size of the balloon, degree to which it stretches the viscus wall, the compressibility of the recording fluid, and the compliance of the system all restrict the reliability of conclusions about the external forces that alter the pressure in such a closed recording system.

The idea of using open-tip catheters rather than balloons to record pressures was explored in the 1920s, but it was most aggressively developed in the 1950s mainly to examine the esophagus. The principal players in this development, which included Code and Ingelfinger , probably sought, at the outset, simply to measure pressures rather than to fully map peristaltic movements. At first, they used air-filled catheters, later changing to water-filled tubes. They adopted catheters with distal openings placed laterally rather than at the tip of the catheters and observed that, in the esophagus, they could measure the characteristics of peristalsis – velocity and force of contraction – with apparent reproducibility and accuracy. The method was soon improved by Dodds and Hogan , and others with the introduction of the continuous perfusion of the catheters with a low-compliance pump (the Arndorfer pump, developed by a colleague of Dodds) and other changes, and the technique soon passed into standard clinical use to describe esophageal motor functions. The technique subsequently has found use in the small intestine, but is used much less in the stomach and colon. Subsequent experimentation with methods led to developments of much more complex devices in which pressures are measured from miniature pressure transducers mounted on flexible catheters. These devices, combined with computer-aided analysis of pressure patterns, now provide objective long-term monitoring of motility in the stomach as well as more distally in the small intestine. A pressure transducer mounted on a radio signal generator, the “wireless motility capsule,” has also found use. Such devices hold the prospect for more careful characterization of gastrointestinal motor disorders.

Perfusion manometry for pressure measurement brought a new importance to the concept of sphincters. Physiologists had long debated the existence of sphincters because, aside from the external anal sphincter, the structures could not be directly observed and radiography was scarcely able to show them satisfactorily. Manometry, however, made it possible to define them, to describe their dimensions, the timing of their opening and closure, and the force with which they occluded the lumen. Thus, both the upper esophageal sphincter and the esophagogastric sphincter were not clearly described until the mid-1950s. The application of a small balloon, the “Dent sleeve,” named after its inventor – John Dent from Adelaide, Australia – greatly facilitated the study of sphincters in vivo, and it remains the major clinical and investigative technique to study sphincters, finding use especially in the esophagus, pylorus and the anal canal.