An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility

Abstract

Excitatory and inhibitory enteric neural input to intestinal muscle acting on ongoing myogenic activity determines the rich repertoire of motor patterns involved in digestive function. The enteric neural activity cannot yet be established during movement of intact intestine in vivo or in vitro. We propose the hypothesis that is possible to deduce indirectly, but reliably, the state of activation of the enteric neural input to the muscle from measurements of the mechanical state of the intestinal muscle. The fundamental biomechanical model on which our hypothesis is based is the “three-element model” proposed by Hill. Our strategy is based on simultaneous video recording of changes in diameters and intraluminal pressure with a fiber-optic manometry in isolated segments of rabbit colon. We created a composite spatiotemporal map (DPMap) from diameter (DMap) and pressure changes (PMaps). In this composite map rhythmic myogenic motor patterns can readily be distinguished from the distension induced neural peristaltic contractions. Plotting the diameter changes against corresponding pressure changes at each location of the segment, generates “orbits” that represent the state of the muscle according to its ability to contract or relax actively or undergoing passive changes. With a software developed in MatLab, we identified twelve possible discrete mechanical states and plotted them showing where the intestine actively contracted and relaxed isometrically, auxotonically or isotonically, as well as where passive changes occurred or was quiescent. Clustering all discrete active contractions and relaxations states generated for the first time a spatio-temporal map of where enteric excitatory and inhibitory neural input to the muscle occurs during physiological movements. Recording internal diameter by an impedance probe proved equivalent to measuring external diameter, making possible to further develop similar strategy in vivo and humans.

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

“…These were then resampled down to four frames per second in QuickTime (Apple, Cupertino, CA). The video images were used to create spatiotemporal diameter maps (DMaps) (11).…”

“…Analysis of the fiberoptic data was performed using software (that we called "PlotHRM") developed by one of the authors (L. Wiklendt). PlotHRM was written in Matlab (MathWorks, Natick, MA) and Java (Sun Microsystems, Santa Clara, CA) (11,19).…”

Neurogenic and myogenic motor activity in the colon of the guinea pig, mouse, rabbit, and rat

“…These were resampled down to four frames per second in Quicktime (Apple). Each video was then converted into spatiotemporal maps of changes in diameter (Dmaps) using custom-written software in Matlab (MathWorks, Natick, MA) (9). Based upon earlier work from our laboratory (16), the diameter at each point along the length of the colon was calculated for each frame and converted into grayscale pixels.…”

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

“…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...…”

“…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.…”