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Kuruppu S, Cheng LK, Avci R, Angeli-Gordon TR, Paskaranandavadivel N. Relationship Between Intestinal Slow-waves, Spike-bursts, and Motility, as Defined Through High-resolution Electrical and Video Mapping. J Neurogastroenterol Motil 2022; 28:664-677. [PMID: 36250373 PMCID: PMC9577564 DOI: 10.5056/jnm21183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 12/01/2022] [Accepted: 12/17/2022] [Indexed: 11/20/2022] Open
Abstract
Background/Aims High-resolution extracellular mapping has improved our understanding of bioelectric slow-wave and spike-burst activity in the small intestine. The spatiotemporal correlation of electrophysiology and motility patterns is of critical interest to intestinal function but remains incompletely defined. Methods Intestinal jejunum segments from in vivo pigs and rabbits were exteriorized, and simultaneous high-resolution extracellular recordings and video recordings were performed. Contractions were quantified with strain fields, and the frequencies and velocities of motility patterns were calculated. The amplitudes, frequencies, and velocities of slow-wave propagation patterns and spike-bursts were quantified and visualized. In addition, the duration, size and energy of spike-burst patches were quantified. Results Slow-wave associated spike-bursts activated periodically at 10.8 ± 4.0 cycles per minute (cpm) in pigs and 10.2 ± 3.2 cpm in rabbits, while independent spike-bursts activated at a frequency of 3.2 ± 1.8 cpm. Independent spike-bursts had higher amplitude and longer duration than slow-wave associated spike-bursts (1.4 ± 0.8 mV vs 0.1 ± 0.1 mV, P < 0.001; 1.8 ± 1.4 seconds vs 0.8 ± 0.3 seconds, P < 0.001 in pigs). Spike-bursts that activated as longitudinal or circumferential patches were associated with contractions in the respective directions. Spontaneous peristaltic contractions were elicited by independent spike-bursts and travelled slower than slow-wave velocity (3.7 ± 0.5 mm/sec vs 10.1 ± 4.7 mm/sec, P = 0.007). Cyclic peristaltic contractions were driven by slow-wave associated spike-bursts and were coupled to slow-wave velocity and frequency in rabbit (14.2 ± 2.3 mm/sec vs 11.5 ± 4.6 mm/sec, P = 0.162; 11.0 ± 0.6 cpm vs 10.8 ± 0.6 cpm, P = 0.970). Conclusions Motility patterns were dictated by patterns of spike-burst patches. When spike-bursts were coupled to slow-waves, periodic motility patterns were observed, while when spike-bursts were not coupled to slow-waves, spontaneous aperiodic motility patterns were captured.
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Affiliation(s)
- Sachira Kuruppu
- Auckland Bioengineering Institute, University of Auckland, New Zealand
| | - Leo K Cheng
- Auckland Bioengineering Institute, University of Auckland, New Zealand
- Riddet Institute, Center of Research Excellence, New Zealand
- Department of Surgery, Vanderbilt University, Nashville, USA
| | - Recep Avci
- Auckland Bioengineering Institute, University of Auckland, New Zealand
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Sukasem A, Calder S, Angeli-Gordon TR, Andrews CN, O’Grady G, Gharibans A, Du P. In vivo experimental validation of detection of gastric slow waves using a flexible multichannel electrogastrography sensor linear array. Biomed Eng Online 2022; 21:43. [PMID: 35761323 PMCID: PMC9238032 DOI: 10.1186/s12938-022-01010-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 06/14/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Cutaneous electrogastrography (EGG) is a non-invasive technique that detects gastric bioelectrical slow waves, which in part govern the motility of the stomach. Changes in gastric slow waves have been associated with a number of functional gastric disorders, but to date accurate detection from the body-surface has been limited due to the low signal-to-noise ratio. The main aim of this study was to develop a flexible active-electrode EGG array. Methods: Two Texas Instruments CMOS operational amplifiers: OPA2325 and TLC272BID, were benchtop tested and embedded in a flexible linear array of EGG electrodes, which contained four recording electrodes at 20-mm intervals. The cutaneous EGG arrays were validated in ten weaner pigs using simultaneous body-surface and serosal recordings, using the Cyton biosensing board and ActiveTwo acquisition systems. The serosal recordings were taken using a passive electrode array via surgical access to the stomach. Signals were filtered and compared in terms of frequency, amplitude, and phase-shift based on the classification of propagation direction from the serosal recordings. Results: The data were compared over 709 cycles of slow waves, with both active cutaneous EGG arrays demonstrating comparable performance. There was an agreement between frequencies of the cutaneous EGG and serosal recordings (3.01 ± 0.03 vs 3.03 ± 0.05 cycles per minute; p = 0.75). The cutaneous EGG also demonstrated a reduction in amplitude during abnormal propagation of gastric slow waves (310 ± 50 µV vs 277 ± 9 µV; p < 0.01), while no change in phase-shift was observed (1.28 ± 0.09 s vs 1.40 ± 0.10 s; p = 0.36). Conclusion: A sparse linear cutaneous EGG array was capable of reliably detecting abnormalities of gastric slow waves. For more accurate characterization of gastric slow waves, a two-dimensional body-surface array will be required.
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Kuruppu S, Cheng LK, Nielsen PMF, Gamage TPB, Avci R, Angeli TR, Paskaranandavadivel N. High-Resolution Spatiotemporal Quantification of Intestinal Motility with Free-Form Deformation. IEEE Trans Biomed Eng 2021; 69:2077-2086. [PMID: 34910629 DOI: 10.1109/tbme.2021.3135855] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
OBJECTIVE To develop a method to quantify strain fields from in vivo intestinal motility recordings that mitigate accumulation of tracking error. METHODS The deforming geometry of the intestine in video sequences was modeled by a biquadratic B-spline mesh. Green-Lagrange strain fields were computed to quantify the surface deformations from motility. A nonlinear optimization scheme was applied to mitigate the accumulation of tracking error associated with image registration. RESULTS The optimization scheme maintained the RMS strain error under 1% and reduced the rate of strain error by 97% during synthetic tests. The algorithm was applied to map 64 segmental, 12 longitudinal, and 23 propagating circular contractions in the jejunum. Coordinated activity of the two muscle layers could be identified and the strain fields were able to map and quantify the anisotropic contractions of the intestine. Frequency and velocity were also quantified, from which two types of propagating circular contractions were identified: (i) -0:360:04 strain contractions that originated spontaneously and propagated at 31 mm/s in two pigs, and (ii) cyclic propagating contractions of -0:170:02 strain occurred at 11:00:6 cpm and propagated at 164 mm/s in a rabbit. CONCLUSION The algorithm simultaneously mapped the circular, longitudinal activity of the intestine with high spatial resolution and quantified anisotropic contractions and relaxations. SIGNIFICANCE The proposed algorithm can now be used to define the interactions of muscle layers during motility patterns. It can be integrated with high-resolution bioelectrical recordings to investigate the regulatory mechanisms of motility.
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Liu JYH, Rudd JA, Du P. A pipeline for phase-based analysis of in vitro micro-electrode array recordings of gastrointestinal slow waves. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2021; 2021:261-264. [PMID: 34891286 DOI: 10.1109/embc46164.2021.9630494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Motility of the gastrointestinal tract (GI) is governed by an bioelectrical event termed slow waves. Accurately measuring the characteristics of GI slow waves is critical to understanding its role in clinical applications. High-resolution (HR) bioelectrical mapping involves placing a spatially dense array of electrodes directly over the surface of the GI wall to record the spatiotemporal changes in slow waves. A micro-electrode array (MEA) with spatial resolution of 200 μm in an 8x8 configuration was employed to record intestinal slow waves using isolated tissues from small animals including rodents, shrews and ferrets. A filtering, processing, and analytic pipeline was developed to extract useful metrics from the recordings. The pipeline relied on CWT and Hilbert Transform to identify the frequency and phase of the signals, from which the individual activation times of slow waves were identified and clustered using k-means. A structural similarity index was applied to group the major activation patterns. Overall, the pipeline identified 91 cycles of slow waves from 300 s of recordings in mice, with an average frequency of 20.68 ± 0.71 cpm, amplitude of 7.94 ± 2.15 µV, and velocity of 3.64 ± 1.75 mm s-1. Three major propagation patterns were identified during this period. The findings of this study will inform the development of a high throughput software platform for future in vitro pharmacological studies using the MEA.
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Humenick A, Chen BN, Lauder CIW, Wattchow DA, Zagorodnyuk VP, Dinning PG, Spencer NJ, Costa M, Brookes SJH. Characterization of projections of longitudinal muscle motor neurons in human colon. Neurogastroenterol Motil 2019; 31:e13685. [PMID: 31355986 DOI: 10.1111/nmo.13685] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 07/07/2019] [Accepted: 07/08/2019] [Indexed: 12/08/2022]
Abstract
BACKGROUND The enteric nervous system contains inhibitory and excitatory motor neurons which modulate smooth muscle contractility. Cell bodies of longitudinal muscle motor neurons have not been identified in human intestine. METHODS We used retrograde tracing ex vivo with DiI, with multiple labeling immunohistochemistry, to characterize motor neurons innervating tenial and inter-tenial longitudinal muscle of human colon. KEY RESULTS The most abundant immunohistochemical markers in the tertiary plexus were vesicular acetylcholine transporter, nitric oxide synthase (NOS), and vasoactive intestinal polypeptide (VIP). Of retrogradely traced motor neurons innervating inter-tenial longitudinal muscle, 95% were located within 6mm oral or anal to the DiI application site. Excitatory motor neuron cell bodies, immunoreactive for choline acetyltransferase (ChAT), were clustered aborally, whereas NOS-immunoreactive cell bodies were distributed either side of the DiI application site. Motor neurons had small cell bodies, averaging 438 + 18µm2 in cross-sectional area, similar for ChAT- and NOS-immunoreactive subtypes. Motor neurons innervating the tenia had slightly longer axial projections, with 95% located within 9mm. ChAT-immunoreactive excitatory motor neurons to tenia were clustered aborally, whereas NOS-immunoreactive inhibitory motor neurons had both ascending and descending projections. VIP immunoreactivity was rarely present without NOS immunoreactivity in motor neurons. CONCLUSIONS AND INFERENCES Tenial and inter-tenial motor neurons innervating the longitudinal muscle have short projections. Inhibitory motor neurons have less polarized projections than cholinergic excitatory motor neurons. Longitudinal and circular muscle layers are innervated by distinct local populations of excitatory and inhibitory motor neurons. A population of human enteric neurons that contribute significantly to colonic motility has been characterized.
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Affiliation(s)
- Adam Humenick
- Human Physiology, Medical Bioscience, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Bao Nan Chen
- Human Physiology, Medical Bioscience, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Chris I W Lauder
- Department of Surgery, Flinders Medical Centre, Adelaide, SA, Australia
| | - David A Wattchow
- Department of Surgery, Flinders Medical Centre, Adelaide, SA, Australia
| | - Vladimir P Zagorodnyuk
- Human Physiology, Medical Bioscience, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Phil G Dinning
- Department of Surgery, Flinders Medical Centre, Adelaide, SA, Australia
| | - Nick J Spencer
- Human Physiology, Medical Bioscience, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Marcello Costa
- Human Physiology, Medical Bioscience, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Simon J H Brookes
- Human Physiology, Medical Bioscience, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
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Huizinga JD. Recent advances in intestinal smooth muscle research: from muscle strips and single cells, via ICC networks to whole organ physiology and assessment of human gut motor dysfunction. J Smooth Muscle Res 2019; 55:68-80. [PMID: 31956167 PMCID: PMC6962316 DOI: 10.1540/jsmr.55.68] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Accepted: 11/01/2019] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal smooth muscle research has evolved from studies on muscle strips to spatiotemporal mapping of whole organ motor and electrical activities. Decades of research on single muscle cells and small sections of isolated musculature from animal models has given us the groundwork for interpretation of human in vivo studies. Human gut motility studies have dramatically improved by high-resolution manometry and high-resolution electrophysiology. The details that emerge from spatiotemporal mapping of high-resolution data are now of such quality that hypotheses can be generated as to the physiology (in healthy subjects) and pathophysiology (in patients) of gastrointestinal (dys) motility. Such interpretation demands understanding of the musculature as a super-network of excitable cells (neurons, smooth muscle cells, other accessory cells) and oscillatory cells (the pacemaker interstitial cells of Cajal), for which mathematical modeling becomes essential. The developing deeper understanding of gastrointestinal motility will bring us soon to a level of precision in diagnosis of dysfunction that is far beyond what is currently available.
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Affiliation(s)
- Jan D. Huizinga
- Department of Medicine-Gastroenterology, McMaster University,
Hamilton, Ontario, Canada
- Farncombe Family Digestive Health Research Institute,
Hamilton, Ontario, Canada
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Schreiber D, Marx L, Felix S, Clasohm J, Weyland M, Schäfer M, Klotz M, Lilischkis R, Erkel G, Schäfer KH. Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models. Front Physiol 2017; 8:566. [PMID: 28824460 PMCID: PMC5545603 DOI: 10.3389/fphys.2017.00566] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 07/20/2017] [Indexed: 01/01/2023] Open
Abstract
Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS) cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml), TNF-α (10 ng/ml), and IL-1β (5 ng/ml). Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD.
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Affiliation(s)
- Dominik Schreiber
- Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, Germany.,Department of Biotechnology, Technical University of KaiserslauternKaiserslautern, Germany
| | - Lisa Marx
- Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, Germany
| | - Silke Felix
- Department of Biotechnology, Technical University of KaiserslauternKaiserslautern, Germany
| | - Jasmin Clasohm
- Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, Germany
| | - Maximilian Weyland
- Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, Germany
| | - Maximilian Schäfer
- Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, Germany
| | - Markus Klotz
- Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, Germany
| | - Rainer Lilischkis
- Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, Germany
| | - Gerhard Erkel
- Department of Biotechnology, Technical University of KaiserslauternKaiserslautern, Germany
| | - Karl-Herbert Schäfer
- Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, Germany.,Pediatric Surgery, University Hospital MannheimMannheim, Germany
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Parsons SP, Huizinga JD. The phase response and state space of slow wave contractions in the small intestine. Exp Physiol 2017; 102:1118-1132. [DOI: 10.1113/ep086373] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 06/29/2017] [Indexed: 12/28/2022]
Affiliation(s)
- Sean P. Parsons
- Farncombe Family Digestive Health Research Institute; McMaster University; Hamilton Ontario Canada
| | - Jan D. Huizinga
- Farncombe Family Digestive Health Research Institute; McMaster University; Hamilton Ontario Canada
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Kendig DM, Hurst NR, Grider JR. Spatiotemporal Mapping of Motility in Ex Vivo Preparations of the Intestines. J Vis Exp 2016:e53263. [PMID: 26863156 PMCID: PMC4781693 DOI: 10.3791/53263] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Multiple approaches have been used to record and evaluate gastrointestinal motility including: recording changes in muscle tension, intraluminal pressure, and membrane potential. All of these approaches depend on measurement of activity at one or multiple locations along the gut simultaneously which are then interpreted to provide a sense of overall motility patterns. Recently, the development of video recording and spatiotemporal mapping (STmap) techniques have made it possible to observe and analyze complex patterns in ex vivo whole segments of colon and intestine. Once recorded and digitized, video records can be converted to STmaps in which the luminal diameter is converted to grayscale or color [called diameter maps (Dmaps)]. STmaps can provide data on motility direction (i.e., stationary, peristaltic, antiperistaltic), velocity, duration, frequency and strength of contractile motility patterns. Advantages of this approach include: analysis of interaction or simultaneous development of different motility patterns in different regions of the same segment, visualization of motility pattern changes over time, and analysis of how activity in one region influences activity in another region. Video recordings can be replayed with different timescales and analysis parameters so that separate STmaps and motility patterns can be analyzed in more detail. This protocol specifically details the effects of intraluminal fluid distension and intraluminal stimuli that affect motility generation. The use of luminal receptor agonists and antagonists provides mechanistic information on how specific patterns are initiated and how one pattern can be converted into another pattern. The technique is limited by the ability to only measure motility that causes changes in luminal diameter, without providing data on intraluminal pressure changes or muscle tension, and by the generation of artifacts based upon experimental setup; although, analysis methods can account for these issues. When compared to previous techniques the video recording and STmap approach provides a more comprehensive understanding of gastrointestinal motility.
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Affiliation(s)
- Derek M Kendig
- Department of Physiology and Biophysics, Virginia Commonwealth University; Department of Biology, Loyola University Maryland;
| | - Norm R Hurst
- Department of Physiology and Biophysics, Virginia Commonwealth University
| | - John R Grider
- Department of Physiology and Biophysics, Virginia Commonwealth University
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Abstract
BACKGROUND Ethanol ingestion causes a variety of gastrointestinal disturbances including motility alterations. Slow wave propagation coordinates gastrointestinal motility, and abnormal slow wave activity is thought to contribute to motility disorders. To date, however, little is known about the effect of acute ethanol on motility disturbances associated with slow wave activity. AIM To investigate the effect of ethanol on small intestine slow wave activity. METHODS Segments (3-5 cm long) were isolated from the rat duodenum, jejunum, and ileum and mounted in an organ bath superfused with a normal Tyrode solution or with 1, 3, or 5% ethanol containing Tyrode. The electrical activities were recorded using an array of 121 extracellular electrodes, and motility recordings were performed using a digital video camera. RESULTS The frequency and amplitude of slow wave activity were not altered at 1, 3, or 5% ethanol concentrations, but a significant drop in velocity was found at 3 and 5% ethanol. Furthermore, inexcitable areas appeared in a dose-dependent manner. Slow wave was sometimes also seen to propagate in a circular fashion, thereby describing a reentrant loop. Finally, in all duodenal, jejunal, and ileal segments, ethanol inhibited contractions and became fully quiescent at 3-5%. CONCLUSIONS These studies for the first time demonstrate that ethanol significantly inhibits slow wave and spike activity in a dose-dependent manner and could also initiate reentrant activities. Intestinal contractions were also inhibited in a dose-dependent manner. In conclusion, ethanol inhibits both slow wave activity and motor activity to cause ethanol-induced intestinal disturbances.
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Du P, Paskaranandavadivel N, Angeli TR, Cheng LK, O'Grady G. The virtual intestine: in silico modeling of small intestinal electrophysiology and motility and the applications. WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE 2015; 8:69-85. [PMID: 26562482 DOI: 10.1002/wsbm.1324] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 10/01/2015] [Accepted: 10/02/2015] [Indexed: 02/06/2023]
Abstract
The intestine comprises a long hollow muscular tube organized in anatomically and functionally discrete compartments, which digest and absorb nutrients and water from ingested food. The intestine also plays key roles in the elimination of waste and protection from infection. Critical to all of these functions is the intricate, highly coordinated motion of the intestinal tract, known as motility, which is coregulated by hormonal, neural, electrophysiological and other factors. The Virtual Intestine encapsulates a series of mathematical models of intestinal function in health and disease, with a current focus on motility, and particularly electrophysiology. The Virtual Intestine is being cohesively established across multiple physiological scales, from sub/cellular functions to whole organ levels, facilitating quantitative evaluations that present an integrative in silico framework. The models are also now finding broad physiological applications, including in evaluating hypotheses of slow wave pacemaker mechanisms, smooth muscle electrophysiology, structure-function relationships, and electromechanical coupling. Clinical applications are also beginning to follow, including in the pathophysiology of motility disorders, diagnosing intestinal ischemia, and visualizing colonic dysfunction. These advances illustrate the emerging potential of the Virtual Intestine to effectively address multiscale research challenges in interdisciplinary gastrointestinal sciences.
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Affiliation(s)
- Peng Du
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | | | - Timothy R Angeli
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Leo K Cheng
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Gregory O'Grady
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
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Fullard LA, Lammers WJ, Ferrua MJ. Advective mixing due to longitudinal and segmental contractions in the ileum of the rabbit. J FOOD ENG 2015. [DOI: 10.1016/j.jfoodeng.2015.03.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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A review of mixing and propulsion of chyme in the small intestine: fresh insights from new methods. J Comp Physiol B 2015; 185:369-87. [PMID: 25648621 DOI: 10.1007/s00360-015-0889-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 01/05/2015] [Accepted: 01/17/2015] [Indexed: 01/18/2023]
Abstract
The small intestine is a convoluted flexible tube of inconstant form and capacity through which chyme is propelled and mixed by varying patterns of contraction. These inconstancies have prevented quantitative comparisons of the manner in which contractile activity engenders mixing of contained chyme. Recent quantitative work based on spatiotemporal mapping of intestinal contractions, macro- and micro-rheology, particle image velocimetry and real-time modelling has provided new insights into this process. Evidence indicates that the speeds and patterns of the various types of small intestinal contraction are insufficient to secure optimal mixing and enzymatic digestion over a minimal length of intestine. Hence particulate substrates and soluble nutrients become dispersed along the length of the lumen. Mixing within the lumen is not turbulent but results from localised folding and kneading of the contents by contractions but is augmented by the inconstant spatial disposition of the contractions and their component contractile processes. The latter include inconstancies in the sites of commencement and the directions of propagation of contraction in component groups of smooth muscle cells and in the coordination of the radial and circular components of smooth muscle contraction. Evidence suggests there is ongoing augmentation of mixing at the periphery of the lumen, during both the post-prandial and inter-meal periods, to promote flow around and between adjacent villi. This results largely from folding of the relatively inelastic mucosa during repeated radial and longitudinal muscular contraction, causing chyme to be displaced by periodic crowding and separation of the tips of the relatively rigid villi. Further, micro-rheological studies indicate that such peripheral mixing may extend to the apices of enterocytes owing to discontinuities in the mobile mucus layer that covers the ileal mucosa.
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Schreiber D, Jost V, Bischof M, Seebach K, Lammers WJEP, Douglas R, Schäfer KH. Motility patterns of ex vivo intestine segments depend on perfusion mode. World J Gastroenterol 2014; 20:18216-18227. [PMID: 25561789 PMCID: PMC4277959 DOI: 10.3748/wjg.v20.i48.18216] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Revised: 06/08/2014] [Accepted: 07/11/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate and characterize motility patterns from small intestinal gut segments depending on different perfusion media and pressures.
METHODS: Experiments were carried out in a custom designed perfusion chamber system to validate and standardise the perfusion technique used. The perfusion chamber was built with a transparent front wall allowing for optical motility recordings and a custom made fastener to hold the intestinal segments. Experiments with different perfusion and storage media combined with different luminal pressures were carried out to evaluate the effects on rat small intestine motility. Software tools which enable the visualization and characterization of intestinal motility in response to different stimuli were used to evaluate the videotaped experiments. The data collected was presented in so called heatmaps thus providing a concise overview of form and strength of contractility patterns. Furthermore, the effect of different storage media on tissue quality was evaluated. Haematoxylin-Eosin stainings were used to compare tissue quality depending on storage and perfusion mode.
RESULTS: Intestinal motility is characterized by different repetitive motility patterns, depending on the actual situation of the gut. Different motility patterns could be recorded and characterized depending on the perfusion pressure and media used. We were able to describe at least three different repetitive patterns of intestinal motility in vitro. Patterns with an oral, anal and oro-anal propagation direction could be recorded. Each type of pattern finalized its movement with or without a subsequent distension of the wavefront. Motility patterns could clearly be distinguished in heatmap diagrams. Furthermore undirected motility could be observed. The quantity of the different patterns varies and is highly dependent on the perfusion medium used. Tissue preservation varies depending on the perfusion medium utilized, therefore media with a simple composition as Tyrode solution can only be recommended for short time experiments. The more complex media, MEM-HEPES medium and especially AQIX® RS-I tissue preservation reagent preserved the tissue much better during perfusion.
CONCLUSION: Perfusion media have to be carefully chosen considering type and duration of the experiments. If excellent tissue quality is required, complex media are favorable. Perfusion pressure is also of great importance due to the fact that a minimum amount of luminal pressure seems to be necessary to trigger intestinal contractions.
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The mesenterially perfused rat small intestine: A versatile approach for pharmacological testings. Ann Anat 2014; 196:158-66. [DOI: 10.1016/j.aanat.2014.02.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Revised: 02/27/2014] [Accepted: 02/28/2014] [Indexed: 12/22/2022]
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The Principles and Practice of Gastrointestinal High-Resolution Electrical Mapping. LECTURE NOTES IN COMPUTATIONAL VISION AND BIOMECHANICS 2013. [DOI: 10.1007/978-94-007-6561-0_4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abstract
Extracellular electrical recordings underpin an important literature of basic and clinical motility science. In the November 2011 edition of Neurogastroenterology and Motility, Sanders and colleagues reported that contraction artifacts could be recorded from in vitro murine gastric tissues using extracellular electrodes, and that true extracellular bioelectrical activity could not be detected when the contractions were suppressed. The authors interpret their findings to mean that previous extracellular studies have generally assayed contraction artifacts, rather than bioelectrical activity, and suggest that movement suppression is an obligatory control for extracellular experiments. If their interpretation is correct, these claims would be significant, requiring a reinterpretation of many studies, and posing major challenges for future in vivo and especially clinical work. However, a demonstration that motion artifacts can be recorded from murine in vitro tissue does not necessarily mean that other extracellular studies also represented artifacts. This viewpoint evaluates a recently published by Sanders and colleagues in light of the competing literature, and finds a considerable volume of evidence to support the veracity of GI extracellular electrical recordings. It is reasoned from biophysical principles, technical considerations, and experimental studies that motion artifacts cannot explain GI extracellular electrical recordings in general, and that bioelectrical fact and artifact can be readily and reliably distinguished in most contexts. Calls for obligatory motion suppression for extracellular studies are therefore not supported. However, the artifacts recorded by Sanders and colleagues nevertheless serve as a reminder that educated caution is needed when recording, filtering and interpreting extracellular data.
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Affiliation(s)
- Gregory O’Grady
- Dept of Surgery, The University of Auckland, Auckland New Zealand,Auckland Bioengineering Institute, The University of Auckland, New Zealand
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Dinning PG, Arkwright JW, Costa M, Wiklendt L, Hennig G, Brookes SJH, Spencer NJ. Temporal relationships between wall motion, intraluminal pressure, and flow in the isolated rabbit small intestine. Am J Physiol Gastrointest Liver Physiol 2011; 300:G577-85. [PMID: 21193528 DOI: 10.1152/ajpgi.00532.2010] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Intraluminal manometry is a tool commonly used to record motility in the human digestive tract. The recorded signal results from a combination of factors, including the hydrodynamic pressure transmitted through the intestinal contents due to contraction of the gut wall and the force of the gut wall acting on the sensors in regions of a luminal occlusion. However, the actual relationships between small bowel wall contraction, the measured intraluminal pressure, and the resultant flow have not been directly addressed. Video recording and high-resolution fiber-optic manometry were used to create spatiotemporal video maps of diameter and intraluminal pressure from isolated segments of rabbit small intestine. In the unstimulated gut, longitudinal muscle contractions were the only detectable motor pattern; circular muscle contractions were elicited by distension or erythromycin (1 μM). Longitudinal muscle contractions were not lumen-occlusive, although they caused measurable low-amplitude changes in pressure. Localized nonpropagating circular muscle contractions caused small localized, nonpropagating peaks of intraluminal pressure. Propagating contractions of circular muscle evoked larger, propagating pressure changes that were associated with outflow. Propagating circular muscle contractions often caused dilation of aboral receiving segments, corresponding to "common cavities"; these were propulsive, despite their low intraluminal pressure. The highest-amplitude pressure events were caused by lumen-occlusive circular muscle contractions that squeezed directly against the catheter. These data allow us to define the complex relationships between wall motion, intraluminal pressure, and flow. A strong correlation between circular and longitudinal muscle contraction and intraluminal pressure was demonstrated. Common-cavity pressure events, caused by propulsion of content by circular muscle contractions into a receptive segment, were often of low amplitude but were highly propulsive. Studies of wall motion in isolated preparations, combined with manometry, can assist in interpretation of pressure recordings in vivo.
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Affiliation(s)
- P G Dinning
- St. George Clinical School, University of New South Wales, Australia.
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Gutzeit A, Patak MA, von Weymarn C, Graf N, Doert A, Willemse E, Binkert CA, Froehlich JM. Feasibility of small bowel flow rate measurement with MRI. J Magn Reson Imaging 2010; 32:345-51. [DOI: 10.1002/jmri.22254] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Huizinga JD, Zarate N, Farrugia G. Physiology, injury, and recovery of interstitial cells of Cajal: basic and clinical science. Gastroenterology 2009; 137:1548-56. [PMID: 19778538 PMCID: PMC2943431 DOI: 10.1053/j.gastro.2009.09.023] [Citation(s) in RCA: 125] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
In the last 15 years, our understanding of the cellular basis of gastrointestinal function has been altered irreversibly by the discovery that normal gastrointestinal motility requires interstitial cells of Cajal (ICC). Research in this relatively short time period has modified our original concept that the core unit that controls motility is made up of nerves and smooth muscle, to one that now includes ICC. This concept has now expanded to beyond the gastrointestinal tract, suggesting that it may be a fundamental property of the regulation of smooth muscle function that requires rhythmic contraction. ICC are distributed throughout the gastrointestinal tract, have important functions in the control of gastrointestinal motility and are often abnormal in diseased states. Recently, significant steps forward have been made in our understanding of the physiology of ICC as well as mechanisms of injury and recovery. These advances will be the focus of this review.
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Affiliation(s)
- Jan D. Huizinga
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton Canada
| | - Natalia Zarate
- Centre for Academic Surgery, Barts and The London School of Medicine and Dentistry, London UK
| | - Gianrico Farrugia
- Enteric Neuroscience Program, Mayo Clinic College of Medicine, Rochester USA
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Lammers WJEP, Cheng LK. Simulation and analysis of spatio-temporal maps of gastrointestinal motility. Biomed Eng Online 2008; 7:2. [PMID: 18194575 PMCID: PMC2254420 DOI: 10.1186/1475-925x-7-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2007] [Accepted: 01/14/2008] [Indexed: 12/04/2022] Open
Abstract
Background Spatio-temporal (ST) maps provide a method for visualizing a temporally evolving and spatially varying field, which can also be used in the analysis of gastrointestinal motility. However, it is not always clear what the underlying contractions are that are represented in ST maps and whether some types of contractions are poorly represented or possibly not at all. Methods To analyze the translation from stationary or propagating rhythmic contractions of the intestine to ST maps, a simulation program was used to represent different patterns of intestinal contraction and to construct their corresponding ST maps. A number of different types of contractions were simulated and their ST maps analyzed. Results Circular strong contractions were well represented in ST maps as well as their frequency and velocity. Longitudinal contractions were not detected at all. Combinations of circular and longitudinal contractions were, to a limited extent detectable at a point in space and time. The method also enabled the construction of specific ST-patterns to mimic real-life ST maps and the analysis of the corresponding contraction patterns. Conclusion Spatio-temporal simulations provide a method to understand, teach and analyze ST maps. This approach could be useful to determine characteristics of contractions under a variety of circumstances.
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Affiliation(s)
- Wim J E P Lammers
- Department of Physiology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
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Lentle RG, Janssen PWM, Asvarujanon P, Chambers P, Stafford KJ, Hemar Y. High definition mapping of circular and longitudinal motility in the terminal ileum of the brushtail possum Trichosurus vulpecula with watery and viscous perfusates. J Comp Physiol B 2007; 177:543-56. [PMID: 17342493 DOI: 10.1007/s00360-007-0153-8] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2006] [Revised: 02/08/2007] [Accepted: 02/12/2007] [Indexed: 12/15/2022]
Abstract
Longitudinal and radial movements during spontaneous contractions of isolated segments of terminal ileum of the brushtail possum, a species of arboreal folivore, were studied using high definition spatiotemporal maps. Segments obtained from specimens were continuously perfused with solutions of various apparent viscosities at 3 cm and 5 cm hydrostatic pressure. A series of sustained tetrodotoxin-sensitive peristaltic events occurred during perfusion. The leading edge of each peristaltic event progressed by a succession of rhythmic surges of circular contraction with concerted concurrent phasic longitudinal contractions. Three types of peristaltic event were observed, with differing durations of occlusion and patterns of cyclic, in phase, circular and longitudinal contractions. Each peristaltic event was preceded by a change of shade on the D map that indicated circumferential dilatation. Differences in the slopes of these phasic shade changes from those occurring during peristalsis indicate that this distension is passive and likely results from aboral displacement of fluid. Tetradotoxin insensitive longitudinal contraction waves of frequency 9.2 min(-1) occurred during and in the absence of peristalsis, originating at a variety of sites, and propagating either in an orad or aborad direction but predominantly in the latter. Perfusion with 1% guar gum, at 5 cm hydrostatic pressure caused the lumen to become distended and the generation of peristaltic events to cease pending reduction of the hydrostatic head to 3 cm but longitudinal contractile activity was preserved. Neither the frequencies nor the rates of progression of circular and longitudinal contractile events, nor the temporal coordination between these events, varied with the apparent viscosity of the perfusate or altered in a manner that could facilitate mixing.
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Affiliation(s)
- Roger G Lentle
- Institute of Food, Nutrition and Human Health, Massey University, Private Bag 11222, Palmerston North, New Zealand.
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Seerden TC, Lammers WJEP, De Winter BY, De Man JG, Pelckmans PA. Spatiotemporal electrical and motility mapping of distension-induced propagating oscillations in the murine small intestine. Am J Physiol Gastrointest Liver Physiol 2005; 289:G1043-G1051. [PMID: 16099869 DOI: 10.1152/ajpgi.00205.2005] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Since the development of knockout animals, the mouse has become an important model to study gastrointestinal motility. However, little information is available on the electrical and contractile activities induced by distension in the murine small intestine. Spatiotemporal electrical mapping and mechanical recordings were made from isolated intestinal segments from different regions of the murine small intestine during distension. The electrical activity was recorded with 16 extracellular electrodes while motility was assessed simultaneously by tracking the border movements with a digital camera. Distension induced propagating oscillatory contractions in isolated intestinal segments. These propagating contractions were dictated by the underlying propagating slow wave with superimposed spikes. The frequencies, velocities, and direction of the propagating oscillations strongly correlated with the frequencies (r = 0.86), velocities (r = 0.84), and direction (r = 1) of the electrical slow waves. N(omega)-nitro-L-arginine methyl ester decreased the maximal diameter of the segment and reduced the peak contraction amplitude of the propagating oscillatory contractions, whereas atropine and verapamil blocked the propagating oscillations. Tetrodotoxin had little effect on the maximal diameter and peak contraction amplitude. In conclusion, distension in the murine small intestine does not initiate peristaltic reflexes but induces a propagating oscillatory motor pattern that is determined by propagating slow waves with superimposed spikes. These spikes are cholinergic and calcium dependent.
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Affiliation(s)
- T C Seerden
- Division of Gastroenterology, University of Antwerp, Wilrijk, Belgium
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