Neurally mediated propagating discrete clustered contractions superimposed on myogenic ripples in ex vivo segments of human ileum

Abstract

Kuizenga MH, Sia TC, Dodds KN, Wiklendt L, Arkwright JW, Thomas A, Brookes SJ, Spencer NJ, Wattchow DA, Dinning PG, Costa M. Neurally mediated propagating discrete clustered contractions superimposed on myogenic ripples in ex vivo segments of human ileum. Am J Physiol Gastrointest Liver Physiol 308: G1-G11, 2015. First published November 13, 2014; doi:10.1152/ajpgi.00230.2014.-Narrow muscle strips have been extensively used to study intestinal contractility. Larger specimens from laboratory animals have provided detailed understanding of mechanisms that underlie patterned intestinal motility. Despite progress in animal tissue, investigations of motor patterns in large, intact specimens of human gut ex vivo have been sparse. In this study, we tested whether neurally dependent motor patterns could be detected in isolated specimens of intact human ileum. Specimens (n ϭ 14; 7-30 cm long) of terminal ileum were obtained with prior informed consent from patients undergoing colonic surgery for removal of carcinomas. Preparations were set up in an organ bath with an array of force transducers, a fiberoptic manometry catheter, and a video camera. Spontaneous and distension-evoked motor activity was recorded, and the effects of lidocaine, which inhibits neural activity, were studied. Myogenic contractions (ripples) occurred in all preparations (6.17 Ϯ 0.36/min). They were of low amplitude and formed complex patterns by colliding and propagating in both directions along the specimen at anterograde velocities of 4.1 Ϯ 0.3 mm/s and retrogradely at 4.9 Ϯ 0.6 mm/s. In five specimens, larger amplitude clusters of contractions were seen (discrete clustered contractions), which propagated aborally at 1.05 Ϯ 0.13 mm/s and orally at 1.07 Ϯ 0.09 mm/s. These consisted of two to eight phasic contractions that aligned with ripples. These motor patterns were abolished by addition of lidocaine (0.3 mM). The ripples continued unchanged in the presence of this neural blocking agent. These results demonstrate that both myogenic and neurogenic motor patterns can be studied in isolated specimens of human small intestine. small intestine; motor patterns; enteric nervous system; myogenic; neurogenic PROPULSION AND MIXING OF INTESTINAL CONTENTS along the digestive tract are essential for normal digestion. The motor patterns underlying these functions are due to the coordinated contractions and relaxations of the smooth muscle layers of the intestine. The internal circular smooth muscle layer and the external longitudinal smooth muscle layer are controlled by two main mechanisms. Myogenic activity is driven by the nonneural pacemaker cells, the interstitial cells of Cajal. Neurogenic control is mediated by circuits in the enteric nervous system. These two types of activity combine to generate the motor patterns that mix and propel luminal content (14,29). Most of our understanding of these mechanisms has been derived from animal studies. Although the basic functions of the gastrointestinal tract are similar between human and animals, there are si...

Spatiotemporal Mapping of Motility in <em>Ex Vivo</em> Preparations of the Intestines

“…While these patterns were identified by earlier experimental methods, the current approach allows a more refined definition of localized contractile movements such as ripples and novel antiperistaltic contractions 9,24,25,30,31,42 . The construction of STmaps and analysis of changes in motility pattern have been applied to key questions in the gastrointestinal motility of intestine and colon.…”

“…Video recording and spatiotemporal mapping of intestinal and colonic segments have been applied to a variety of species including zebrafish 26 , mouse 25,[27][28][29][30] , rat 7,9,[30][31][32][33] , guinea pig 5,6,8,[13][14][15][16][17][18][19]24,30,32,34,35 , brushtail possum 12,36 , rabbit 2,30,37,38 , chicken 39 , pig 40,41 and human 42 . The most widely studied species is the guinea pig.…”

“…The isolated, vascularly perfused loop preparation for video recording and spatiotemporal mapping has also been applied to smaller species such as rat 33 . A recent study by Kuizenga et al is the first use of STmaps of video recorded motility patterns in ex vivo segments of human intestine 42 ; although, STmapping approaches have been applied to the analysis of manometric (pressure) recordings in humans in vivo 3,44 . The recorded motility patterns in human tissue are similar to those already recorded in animal models using similar techniques and validate the extension of this approach to human tissues.…”

“…The construction of STmaps and analysis of changes in motility pattern have been applied to key questions in the gastrointestinal motility of intestine and colon. These include: differentiation of neurogenic and myogenic contractions and defining the role of interstitial cells of Cajal 6,9,11,12,16,24,26,27,[29][30][31]33,[37][38][39][40]42 , understanding the complex interactions between the circular and longitudinal muscle layers 2,7,8,11,12,32,39,40 , examining the effects of intraluminal nutrients 10,18,19 , microbial strains 34 , and viscosities 12,36 on various motility patterns, and understanding the role of various endogenous neurohormonal agents and exogenous pharmacological agents 2,[4][5][6][7]9,10,[13][14][15][16][17]28,35,40 in the generation and modification of motility...…”

“…The future of this technique involves coupling it with other measurements including pressure, electrophysiology and tension/contractility. Recent studies have often incorporated one or more of these measurements in conjunction with video recording and spatiotemporal mapping to provide additional correlative details 2,42 . Moreover, the system can be used to measure motility in other tubular and non-tubular organs.…”