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1
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Durcan C, Hossain M, Chagnon G, Perić D, Girard E. Characterization of the layer, direction and time-dependent mechanical behaviour of the human oesophagus and the effects of formalin preservation. J R Soc Interface 2024; 21:20230592. [PMID: 38593841 PMCID: PMC11003784 DOI: 10.1098/rsif.2023.0592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 03/05/2024] [Indexed: 04/11/2024] Open
Abstract
The mechanical characterization of the oesophagus is essential for applications such as medical device design, surgical simulations and tissue engineering, as well as for investigating the organ's pathophysiology. However, the material response of the oesophagus has not been established ex vivo in regard to the more complex aspects of its mechanical behaviour using fresh, human tissue: as of yet, in the literature, only the hyperelastic response of the intact wall has been studied. Therefore, in this study, the layer-dependent, anisotropic, visco-hyperelastic behaviour of the human oesophagus was investigated through various mechanical tests. For this, cyclic tests, with increasing stretch levels, were conducted on the layers of the human oesophagus in the longitudinal and circumferential directions and at two different strain rates. Additionally, stress-relaxation tests on the oesophageal layers were carried out in both directions. Overall, the results show discrete properties in each layer and direction, highlighting the importance of treating the oesophagus as a multi-layered composite material with direction-dependent behaviour. Previously, the authors conducted layer-dependent cyclic experimentation on formalin-embalmed human oesophagi. A comparison between the fresh and embalmed tissue response was carried out and revealed surprising similarities in terms of anisotropy, strain-rate dependency, stress-softening and hysteresis, with the main difference between the two preservation states being the magnitude of these properties. As formalin fixation is known to notably affect the formation of cross-links between the collagen of biological materials, the differences may reveal the influence of cross-links on the mechanical behaviour of soft tissues.
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Affiliation(s)
- Ciara Durcan
- Zienkiewicz Institute for Modelling, Data and Artificial Intelligence, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, UK
- CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Grenoble Alpes University, Grenoble 38000, France
| | - Mokarram Hossain
- Zienkiewicz Institute for Modelling, Data and Artificial Intelligence, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, UK
| | - Grégory Chagnon
- CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Grenoble Alpes University, Grenoble 38000, France
| | - Djordje Perić
- Zienkiewicz Institute for Modelling, Data and Artificial Intelligence, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, UK
| | - Edouard Girard
- CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Grenoble Alpes University, Grenoble 38000, France
- Laboratoire d’Anatomie des Alpes Françaises, Grenoble Alpes University, Grenoble, France
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Durcan C, Hossain M, Chagnon G, Perić D, Girard E. Mechanical experimentation of the gastrointestinal tract: a systematic review. Biomech Model Mechanobiol 2024; 23:23-59. [PMID: 37935880 PMCID: PMC10901955 DOI: 10.1007/s10237-023-01773-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 09/10/2023] [Indexed: 11/09/2023]
Abstract
The gastrointestinal (GI) organs of the human body are responsible for transporting and extracting nutrients from food and drink, as well as excreting solid waste. Biomechanical experimentation of the GI organs provides insight into the mechanisms involved in their normal physiological functions, as well as understanding of how diseases can cause disruption to these. Additionally, experimental findings form the basis of all finite element (FE) modelling of these organs, which have a wide array of applications within medicine and engineering. This systematic review summarises the experimental studies that are currently in the literature (n = 247) and outlines the areas in which experimentation is lacking, highlighting what is still required in order to more fully understand the mechanical behaviour of the GI organs. These include (i) more human data, allowing for more accurate modelling for applications within medicine, (ii) an increase in time-dependent studies, and (iii) more sophisticated in vivo testing methods which allow for both the layer- and direction-dependent characterisation of the GI organs. The findings of this review can also be used to identify experimental data for the readers' own constitutive or FE modelling as the experimental studies have been grouped in terms of organ (oesophagus, stomach, small intestine, large intestine or rectum), test condition (ex vivo or in vivo), number of directions studied (isotropic or anisotropic), species family (human, porcine, feline etc.), tissue condition (intact wall or layer-dependent) and the type of test performed (biaxial tension, inflation-extension, distension (pressure-diameter), etc.). Furthermore, the studies that investigated the time-dependent (viscoelastic) behaviour of the tissues have been presented.
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Affiliation(s)
- Ciara Durcan
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Mokarram Hossain
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK.
| | - Grégory Chagnon
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Djordje Perić
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK
| | - Edouard Girard
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
- Laboratoire d'Anatomie des Alpes Françaises, Université Grenoble Alpes, Grenoble, France
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3
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Rosalia L, Hallou A, Cochrane L, Savin T. A magnetically actuated, optically sensed tensile testing method for mechanical characterization of soft biological tissues. SCIENCE ADVANCES 2023; 9:eade2522. [PMID: 36630495 PMCID: PMC9833656 DOI: 10.1126/sciadv.ade2522] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 12/10/2022] [Indexed: 06/17/2023]
Abstract
Mechanical properties of soft biological tissues play a critical role in physiology and disease, affecting cell behavior and fate decisions and contributing to tissue development, maintenance, and repair. Limitations of existing tools prevent a comprehensive characterization of soft tissue biomechanics, hindering our understanding of these fundamental processes. Here, we develop an instrument for high-fidelity uniaxial tensile testing of soft biological tissues in controlled environmental conditions, which is based on the closed-loop interaction between an electromagnetic actuator and an optical strain sensor. We first validate the instrument using synthetic elastomers characterized via conventional methods; then, we leverage the proposed device to investigate the mechanical properties of murine esophageal tissue and, individually, of each of its constitutive layers, namely, the epithelial, connective, and muscle tissues. The enhanced reliability of this instrument makes it an ideal platform for future wide-ranging studies of the mechanics of soft biological tissues.
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Affiliation(s)
- Luca Rosalia
- Health Sciences and Technology Program, Harvard-MIT, Cambridge, MA, USA
- Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA
| | - Adrien Hallou
- Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK
- Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK
- Wellcome/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK
| | | | - Thierry Savin
- Department of Engineering, University of Cambridge, Cambridge, UK
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Durcan C, Hossain M, Chagnon G, Perić D, Bsiesy L, Karam G, Girard E. Experimental investigations of the human oesophagus: anisotropic properties of the embalmed muscular layer under large deformation. Biomech Model Mechanobiol 2022; 21:1169-1186. [PMID: 35477829 PMCID: PMC9045687 DOI: 10.1007/s10237-022-01583-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 03/31/2022] [Indexed: 11/24/2022]
Abstract
The oesophagus is a primarily mechanical organ whose material characterisation would aid in the investigation of its pathophysiology, help in the field of tissue engineering, and improve surgical simulations and the design of medical devices. However, the layer-dependent, anisotropic properties of the organ have not been investigated using human tissue, particularly in regard to its viscoelastic and stress-softening behaviour. Restrictions caused by the COVID-19 pandemic meant that fresh human tissue was not available for dissection. Therefore, in this study, the layer-specific material properties of the human oesophagus were investigated through ex vivo experimentation of the embalmed muscularis propria layer. For this, a series of uniaxial tension cyclic tests with increasing stretch levels were conducted at two different strain rates. The muscular layers from three different cadaveric specimens were tested in both the longitudinal and circumferential directions. The results displayed highly nonlinear and anisotropic behaviour, with both time- and history-dependent stress-softening. The longitudinal direction was found to be stiffer than the circumferential direction at both strain rates. Strain rate-dependent behaviour was apparent, with an increase in strain rate resulting in an increase in stiffness in both directions. Histological analysis was carried out via various staining methods; the results of which were discussed with regard to the experimentally observed stress-stretch response. Finally, the behaviour of the muscularis propria was simulated using a matrix-fibre model able to capture the various mechanical phenomena exhibited, the fibre orientation of which was driven by the histological findings of the study.
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Affiliation(s)
- Ciara Durcan
- Zienkiewicz Centre for Computational Engineering, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK.,Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Mokarram Hossain
- Zienkiewicz Centre for Computational Engineering, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK.
| | - Grégory Chagnon
- Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Djordje Perić
- Zienkiewicz Centre for Computational Engineering, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK
| | - Lara Bsiesy
- Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Georges Karam
- Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Edouard Girard
- Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France.,Laboratoire d'Anatomie des Alpes Françaises, Univ. Grenoble Alpes, Grenoble, France
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5
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Acharya S, Halder S, Kou W, Kahrilas PJ, Pandolfino JE, Patankar NA. A fully resolved multiphysics model of gastric peristalsis and bolus emptying in the upper gastrointestinal tract. Comput Biol Med 2022; 143:104948. [PMID: 35091365 PMCID: PMC9014465 DOI: 10.1016/j.compbiomed.2021.104948] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 10/09/2021] [Accepted: 10/13/2021] [Indexed: 11/22/2022]
Abstract
Over the past few decades, in silico modeling of organ systems has significantly furthered our understanding of their physiology and biomechanical function. In spite of the relative importance of the digestive system in normal functioning of the human body, there is a scarcity of high-fidelity models for the upper gastrointestinal tract including the esophagus and the stomach. In this work, we present a detailed numerical model of the upper gastrointestinal tract that not only accounts for the fiber architecture of the muscle walls, but also the multiphasic components they help transport during normal digestive function. Construction details for 3D models of representative stomach geometry are presented along with a simple strategy for assigning circular and longitudinal muscle fiber orientations for each layer. We developed a fully resolved model of the stomach to simulate gastric peristalsis by systematically activating muscle fibers embedded in the stomach. Following this, for the first time, we simulate gravity-driven bolus emptying into the stomach due to density differences between ingested contents and fluid contents of the stomach. Finally, we present a case of retrograde flow of fluid from the stomach into the esophagus, resembling the phenomenon of acid reflux. This detailed computational model of the upper gastrointestinal tract provides a foundation for future models to investigate the biomechanics of acid reflux and probe various strategies for gastric bypass surgeries to address the growing problem of obesity.
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Affiliation(s)
- Shashank Acharya
- Department of Mechanical Engineering, Northwestern University, Evanston, IL, 60208, USA
| | - Sourav Halder
- Theoretical and Applied Mechanics Program, Northwestern University, Evanston, IL, 60208, USA
| | - Wenjun Kou
- Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - John E Pandolfino
- Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Neelesh A Patankar
- Department of Mechanical Engineering, Northwestern University, Evanston, IL, 60208, USA; Theoretical and Applied Mechanics Program, Northwestern University, Evanston, IL, 60208, USA.
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6
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Jadcherla SR, Hasenstab KA, Gulati IK, Helmick R, Ipek H, Yildiz V, Wei L. Impact of Feeding Strategies With Acid Suppression on Esophageal Reflexes in Human Neonates With Gastroesophageal Reflux Disease: A Single-Blinded Randomized Clinical Trial. Clin Transl Gastroenterol 2020; 11:e00249. [PMID: 33259163 PMCID: PMC7643906 DOI: 10.14309/ctg.0000000000000249] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Aims were to test hypothesis that esophageal provocation-induced reflexes are superior with acid suppression plus feeding modifications vs acid suppression alone among infants treated for gastroesophageal reflux disease (GERD). METHODS Infants (N = 49, 41.3 ± 2.6 of postmenstrual age) with acid reflux index >3% underwent longitudinal motility testing (weeks 0 and 5) with graded midesophageal provocation to test randomly allocated therapies (4 weeks' proton pump inhibitor [PPI] ± feeding modifications) on sensory-motor aerodigestive reflexes. Feeding modification included restricted fluid volume <140 mL/kg per day, fed over 30 minutes in right lateral position and supine postprandial position. Primary motility outcome was frequency-occurrence of peristaltic reflex. Secondary outcomes included upper esophageal sphincter contractile reflex, lower esophageal sphincter (LES) relaxation reflex, respiratory change, and symptom characteristics. RESULTS Treatment groups did not differ for primary outcome (odds ratio = 0.8, 95% confidence interval 0.4-1.6, P = 0.99) or secondary outcomes (all P > 0.05). For both treatment groups at follow-up, distal esophageal contraction and LES tone decreased, and LES relaxation reflex occurrence is less frequent (all P < 0.05). In a subgroup analysis, comparing infants with PPI washout (N = 40) vs with continued (N = 9) PPI therapy, no differences were noted for aerodigestive reflex response frequency-occurrence (all P > 0.05). DISCUSSION In infants with GERD, feeding modification with acid suppression is not superior to acid suppression alone in modifying aerodigestive reflexes (frequency, sensation, or magnitude). Contiguous areas targeted by GER, i.e., LES and distal esophageal functions, worsened at follow-up for both groups despite PPI therapy. Maturation is likely the key factor for GERD resolution in infants, justifying the use of placebo in clinical trials for objectively determined GERD.
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Affiliation(s)
- Sudarshan R. Jadcherla
- Innovative Infant Feeding Disorders Research Program, Nationwide Children's Hospital, Columbus, Ohio, USA
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
- Division of Neonatology, Nationwide Children's Hospital Columbus, Ohio, USA
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Kathryn A. Hasenstab
- Innovative Infant Feeding Disorders Research Program, Nationwide Children's Hospital, Columbus, Ohio, USA
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Ish K. Gulati
- Innovative Infant Feeding Disorders Research Program, Nationwide Children's Hospital, Columbus, Ohio, USA
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
- Division of Neonatology, Nationwide Children's Hospital Columbus, Ohio, USA
| | - Roseanna Helmick
- Innovative Infant Feeding Disorders Research Program, Nationwide Children's Hospital, Columbus, Ohio, USA
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Haluk Ipek
- Innovative Infant Feeding Disorders Research Program, Nationwide Children's Hospital, Columbus, Ohio, USA
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Vedat Yildiz
- Biostatistics Resource at Nationwide Children's Hospital (BRANCH), Columbus, Ohio, USA
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Lai Wei
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio, USA
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Cock C, Leibbrandt RE, Dinning PG, Costa MC, Wiklendt L, Omari TI. Changes in specific esophageal neuromechanical wall states are associated with conscious awareness of a solid swallowed bolus in healthy subjects. Am J Physiol Gastrointest Liver Physiol 2020; 318:G946-G954. [PMID: 32281396 DOI: 10.1152/ajpgi.00235.2019] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Esophageal neuromechanical wall states are the physical manifestations of circular muscle inhibition and contraction resulting from neural inputs and leading to bolus propulsion. A novel method infers esophageal neuromechanical wall states through simultaneous determination of pressure and diameter in vivo using impedance manometry. We hypothesized that changes in esophageal neuromechanical wall states relate to conscious awareness of esophageal bolus passage ("bolus perception"). Seven healthy participants were selected for perception of solid bolus passage and were compared with seven healthy participants with no conscious awareness of solid bolus passage. Participants were studied using impedance manometry (MMS Solar, Unisensor, 20 Hz). Subjects swallowed ten 5-ml liquid and ten 2-cm square saline-soaked bread boluses and rated bolus perception using a visual analog scale. Esophageal neuromechanical wall states were calculated and analyzed. Proportions of time spent in states with and without luminal distension were compared using a two-proportions Z-test. Bolus perception was associated with neuromechanical wall states corresponding to luminal distension more frequently than matching states without distension in the proximal esophagus (P < 0.001) and transition zone (P < 0.001), whereas there were no differences for the distal esophagus. In healthy volunteers, perceived swallows relate to changes in esophageal neuromechanical wall states in the proximal esophagus. We postulate that these changes relate to bolus retention and summation of active and passive wall tension activating intramural tension receptors.NEW & NOTEWORTHY This study explores esophageal neuromechanical wall states derived from changes in pressure and impedance-derived distension in relation to conscious awareness of esophageal solid bolus transit in healthy volunteers. There are increases in neuromechanical wall states indicative of esophageal distension in healthy volunteers with conscious awareness of bolus transit as compared with unaware individuals. Bolus-based esophageal distension is postulated as a mechanism for esophageal symptoms such as dysphagia.
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Affiliation(s)
- Charles Cock
- Department of Gastroenterology and Hepatology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Richard E Leibbrandt
- Department of Gastroenterology and Hepatology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.,Department of Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Phil G Dinning
- Department of Gastroenterology and Hepatology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.,Department of Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Marcello C Costa
- Department of Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Lukasz Wiklendt
- Department of Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Taher I Omari
- Department of Gastroenterology and Hepatology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.,Department of Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
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8
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9
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Jadcherla SR, Hanandeh N, Hasenstab KA, Nawaz S. Differentiation of esophageal pH-impedance characteristics classified by the mucosal integrity marker in human neonates. Pediatr Res 2019; 85:355-360. [PMID: 30467343 PMCID: PMC6377827 DOI: 10.1038/s41390-018-0237-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 10/22/2018] [Accepted: 10/24/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND In adults, distal baseline impedance (BI) is a determinant of esophageal mucosal integrity with values <900 Ω indicating inflammation. Relationships between acid gastroesophageal reflux (GER) and BI in neonates are unclear. METHODS NICU infants (N = 198, 30.4 ± 0.3 weeks gestation) were evaluated at 43 ± 0.4 weeks postmenstrual age using 24-h pH-impedance. Ten randomly selected 1-min windows during rest from the distal impedance channel (Z6) were averaged. Chi-square, t-tests, and ANOVA were used to compare pH-impedance and symptom characteristics by BI severity (BI < 900 Ω, BI 900-2000 Ω, BI > 2000 Ω). Regression analysis was used to identify potential contributing factors of BI. RESULTS In BI < 900 Ω: (1) pH-impedance characteristics were increased (acid reflux event frequency, duration, and severity, all P < 0.05 vs. BI > 2000 Ω), and (2) positive symptom correlations were noted with bolus (73%) and acid events (55%). Significant predictors of BI included chronological age, acid reflux index, and BPD diagnosis (all P < 0.05). CONCLUSIONS Low BI is associated with prolonged acid exposure, delayed clearance, and greater aerodigestive symptom prevalence, likely associated with inflammation and or increased mucosal permeability. BI > 2000 Ω likely involves little or no inflammation because acid exposure is minimal. Combination of SAP, pH-impedance metrics, and BI along with the clarification of dysmotility mechanisms provides the rationale for personalized anti-reflux therapies as needed.
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Affiliation(s)
- Sudarshan R. Jadcherla
- Innovative Neonatal and Infant Feeding Disorders Research Program, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH,Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH,Division of Neonatology, Pediatric Gastroenterology and Nutrition, Nationwide Children’s Hospital, Columbus, OH
| | - Nour Hanandeh
- Innovative Neonatal and Infant Feeding Disorders Research Program, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH
| | - Kathryn A Hasenstab
- Innovative Neonatal and Infant Feeding Disorders Research Program, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH
| | - Saira Nawaz
- Innovative Neonatal and Infant Feeding Disorders Research Program, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH
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10
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Gregersen H, Lo KM. What Is the Future of Impedance Planimetry in Gastroenterology? J Neurogastroenterol Motil 2018; 24:166-181. [PMID: 29605974 PMCID: PMC5885717 DOI: 10.5056/jnm18013] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 02/09/2018] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal (GI) tract is efficient in transporting ingested material to the site of delivery in healthy subjects. A fine balance exists between peristaltic forces, the mixing and delivery of the contents, and sensory signaling. This fine balance is easily disturbed by diseases. It is mandatory to understand the pathophysiology to enhance our understanding of GI disorders. The inaccessibility and complex nervous innervation, geometry and mechanical function of the GI tract make mechanosensory evaluation difficult. Impedance planimetry is a distension technology that assesses luminal geometry, mechanical properties including muscle dynamics, and processing of nociceptive signals from the GI tract. Since standardized models do not exist for GI muscle function in vivo, models, concepts, and terminology must be borrowed from other medical fields such as cardiac mechanophysiology. The review highlights the impedance planimetric technology, muscle dynamics assessment, and 3 applied technologies of impedance planimetry. These technologies are the multimodal probes that assesses sensory function, the functional luminal imaging probe that dynamically measures the geometry of the lumen it distends, and Fecobionics that is a simulated feces providing high-resolution measurements during defecation. The advanced muscle analysis and 3 applied technologies can enhance the quality of future interdisciplinary research for gaining more knowledge about mechanical function, sensory-motor disorders, and symptoms. This is a step in the direction of individualized treatment for GI disorders based on diagnostic subtyping. There seems to be no better alternatives to impedance planimetry, but only the functional luminal imaging probe is currently commercially available. Wider use depends on commercialization of the multimodal probe and Fecobionics.
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Affiliation(s)
- Hans Gregersen
- GIOME, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.,California Medical Innovations Institute, San Diego, California, USA
| | - Kar Man Lo
- GIOME Doublecove, Wu Kai Sha, New Territories, Hong Kong
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11
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Abstract
Dramatic progress has been made over the past decade in the sophistication and availability of equipment to test esophageal motility and sensation. High-resolution esophageal manometry and impedance have moved from the research clinic into clinical practice. Some of the testing is costly and time consuming, and requires extensive experience to perform the testing and properly interpret the results. These sensory studies are valuable in the interpretation of clinical problems, and provide important research information. Clinicians should evaluate the research studies to advance their understanding of the pathophysiology of the esophagus.
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Affiliation(s)
- Salman Nusrat
- Section of Digestive Disease and Nutrition, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Philip B Miner
- Division of Gastroenterology, Department of Medicine, Oklahoma Foundation for Digestive Research, Oklahoma University School of Medicine, 525 Northwest 9th Street, Suite 325, Oklahoma City, OK 73102, USA.
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12
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Almansa C, Achem SR. The Role of Acid Reflux in Non‐Cardiac Chest Pain. PRACTICAL MANUAL OF GASTROESOPHAGEAL REFLUX DISEASE 2013:132-153. [DOI: 10.1002/9781118444788.ch9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Lazarescu A, Karamanolis G, Aprile L, De Oliveira RB, Dantas R, Sifrim D. Perception of dysphagia: lack of correlation with objective measurements of esophageal function. Neurogastroenterol Motil 2010; 22:1292-7, e336-7. [PMID: 20718946 DOI: 10.1111/j.1365-2982.2010.01578.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND The mechanism underlying increased perception of food bolus passage in the absence of esophageal mechanical obstruction has not been completely elucidated. A correlation between the intensity of the symptom and the severity of esophageal dysfunction, either motility (manometry) or bolus transit (impedance) has not been clearly demonstrated. The aim of this study was to analyze the correlation between objective esophageal function assessment (with manometry and impedance) and perception of bolus passage in healthy volunteers (HV) with normal and pharmacologically-induced esophageal hypocontractility, and in patients with gastro-esophageal reflux disease (GERD) with and without ineffective esophageal motility (IEM). METHODS Combined manometry-impedance was performed in 10 HV, 19 GERD patients without IEM and nine patients with IEM. Additionally, nine HV were studied after 50 mg sildenafil, which induced esophageal peristaltic failure. Perception of each 5 mL viscous swallow was evaluated using a 5-point scale. Manometry identified hypocontractility (contractions lower than 30 mmHg) and impedance identified incomplete bolus clearance. KEY RESULTS In HV and in GERD patients with and without IEM, there was no association between either manometry or impedance and perception on per swallow analysis (OR: 0.842 and OR: 2.017, respectively), as well as on per subject analysis (P = 0.44 and P = 0.16, respectively). Lack of correlation was also found in HV with esophageal hypocontractility induced by sildenafil. CONCLUSIONS & INFERENCES There is no agreement between objective measurements of esophageal function and subjective perception of bolus passage. These results suggest that increased bolus passage perception in patients without mechanical obstruction might be due to esophageal hypersensitivity.
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Affiliation(s)
- A Lazarescu
- Centre for Gastroenterological Research, KU Leuven, Leuven, Belgium
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14
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Li WG, Luo XY, Hill NA, Ogden RW, Smythe A, Majeed A, Bird N. A Mechanical Model for CCK-Induced Acalculous Gallbladder Pain. Ann Biomed Eng 2010; 39:786-800. [PMID: 21108005 DOI: 10.1007/s10439-010-0205-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2010] [Accepted: 11/08/2010] [Indexed: 11/25/2022]
Affiliation(s)
- W G Li
- School of Mathematics and Statistics, University of Glasgow, Glasgow, UK
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15
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Nasr I, Attaluri A, Hashmi S, Gregersen H, Rao SSC. Investigation of esophageal sensation and biomechanical properties in functional chest pain. Neurogastroenterol Motil 2010; 22:520-6, e116. [PMID: 20067548 PMCID: PMC2949059 DOI: 10.1111/j.1365-2982.2009.01451.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND There is limited and conflicting data regarding the role of esophageal hypersensitivity in the pathogenesis of functional chest pain (FCP). We examined esophageal sensori-motor properties, mechanics, and symptoms in subjects with FCP. METHODS Esophageal balloon distension test was performed using impedance planimetry in 189 (m/f = 57/132) consecutive subjects with non-cardiac, non-reflux chest pain, and 36 (m/f = 16/20) healthy controls. The biomechanical and sensory properties of subjects with and without esophageal hypersensitivity were compared with controls. The frequency, intensity, and duration of chest pain were assessed. KEY RESULTS One hundred and forty-three (75%) subjects had esophageal hypersensitivity and 46 (25%) had normal sensitivity. Typical chest pain was reproduced in 105/143 (74%) subjects. Subjects with hypersensitivity demonstrated larger cross-sectional area (P < 0.001), decreased esophageal wall strain (P < 0.001) and distensibility (P < 0.001), and lower thresholds for perception (P < 0.01), discomfort (P < 0.01), and pain (P < 0.01) compared to those without hypersensitivity or healthy controls. Chest pain scores (mean +/- SD) for frequency, intensity and duration were 2.5 +/- 0.3, 2.2 +/- 0.2, and 2.2 +/- 0.2, respectively, and were similar between the two patient groups. CONCLUSIONS & INFERENCES Seventy-five per cent of subjects with FCP demonstrate esophageal hypersensitivity. Visceral hyperalgesia and sensori-motor dysfunction of the esophagus play a key role in the pathogenesis of chest pain.
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Affiliation(s)
- I Nasr
- Department of Internal Medicine, University of Iowa Carver College of medicine, Iowa City, IA, USA
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16
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Hoff DAL, Gregersen H, Odegaard S, Liao D, Hatlebakk JG. Mechanosensation and mucosal blood perfusion in the esophagus of healthy volunteers studied with a multimodal device incorporating laser Doppler flowmetry and endosonography. Dig Dis Sci 2010; 55:312-20. [PMID: 19241164 DOI: 10.1007/s10620-009-0731-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2008] [Accepted: 01/16/2009] [Indexed: 01/29/2023]
Abstract
Both mechanical and ischemic mechanisms can cause gastrointestinal pain. We investigated whether discomfort and pain caused by bag distension in the esophagus of healthy subjects correlated best with mechanical forces (stress), deformation (strain), or mucosal perfusion. Twenty-nine subjects underwent ramp bag distension using a novel catheter design incorporating high-frequency intraluminal ultrasound, laser Doppler flowmetry, and manometry. Perfusion, pressure, and geometric data were analyzed at visual analog scale (VAS) levels 1-7 in 19 subjects. The circumferential stress increased exponentially as a function of volume, whereas strain showed a linear increase. The perfusion showed a modest decline, on average 15% from baseline to VAS = 7. A significant association was found between the sensory response and stress and strain (P < 0.05). No significant association was found between the sensory response and perfusion. In conclusion, the discomfort and pain response to bag distension in the esophagus is likely to be caused by mechanical rather than ischemic mechanisms.
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17
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Ahmed AB, Gilja OH, Hausken T, Gregersen H, Matre K. Strain measurement during antral contractions by ultrasound strain rate imaging: influence of erythromycin. Neurogastroenterol Motil 2009; 21:170-9. [PMID: 18086208 DOI: 10.1111/j.1365-2982.2007.01043.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Strain rate imaging (SRI) is a non-invasive ultrasound (US) modality that enables the study of mechanical deformation (strain) with high spatial and temporal resolution. A total of 244 contractions in seven healthy volunteers were studied by SRI on two separate days to characterize radial strain of antral contractions in the fasting and fed states and to assess the influence of intravenous erythromycin. Gastric accommodation and emptying were assessed by 2D ultrasonography. The perception of hunger was registered by the participants. The strain increased from early to late phase II and phase III activity by (median) 18%, 58% and 82%, respectively, P < 0.05. Erythromycin infusion in phase I induced contractions with median strain of 35%, but did not increase postprandial strain. Both fasting and postprandially, lumen-occlusive contractions with erythromycin were more frequent than in naturally occurring contractions, 69%vs 48%, P = 0.036 and 40%vs 5%, P < 0.001 respectively. All subjects had rumbling in their abdomens when intraluminal air was detected sonographically (85% of all phase III contractions) and that rumbling was perceived by the participant as maximal awareness of hunger. SRI enabled detailed strain measurement of individual antral contractions. Erythromycin initiated fasting antral contractions and increased the number of lumen-occlusive contractions.
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Affiliation(s)
- A B Ahmed
- Institute of Medicine, University of Bergen, Bergen, Norway.
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18
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Brock C, Arendt-Nielsen L, Wilder-Smith O, Drewes AM. Sensory testing of the human gastrointestinal tract. World J Gastroenterol 2009; 15:151-9. [PMID: 19132764 PMCID: PMC2653306 DOI: 10.3748/wjg.15.151] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm (single, train, tetanic) influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation (cold or warm) activates selectively mucosal receptors, and chemical substances such as acid and capsaicin (either alone or in combination) are used to evoke pain and sensitization. The possibility of multimodal (e.g. mechanical, electrical, thermal and chemical) stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to clinicians about the underlying symptoms and treatment of these patients.
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19
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Hoff DAL, Gregersen H, Hatlebakk JG. Mucosal blood flow measurements using laser Doppler perfusion monitoring. World J Gastroenterol 2009; 15:198-203. [PMID: 19132770 PMCID: PMC2653312 DOI: 10.3748/wjg.15.198] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Perfusion of individual tissues is a basic physiological process that is necessary to sustain oxygenation and nutrition at a cellular level. Ischemia, or the insufficiency of perfusion, is a common mechanism for tissue death or degeneration, and at a lower threshold, a mechanism for the generation of sensory signalling including pain. It is of considerable interest to study perfusion of peripheral abdominal tissues in a variety of circumstances. Microvascular disease of the abdominal organs has been implicated in the pathogenesis of a variety of disorders, including peptic ulcer disease, inflammatory bowel disease and chest pain. The basic principle of laser Doppler perfusion monitoring (LDPM) is to analyze changes in the spectrum of light reflected from tissues as a response to a beam of monochromatic laser light emitted. It reflects the total local microcirculatory blood perfusion, including perfusion in capillaries, arterioles, venules and shunts. During the last 20-25 years, numerous studies have been performed in different parts of the gastrointestinal (GI) tract using LDPM. In recent years we have developed a multi-modal catheter device which includes a laser Doppler probe, with the intent primarily to investigate patients suffering from functional chest pain of presumed oesophageal origin. Preliminary studies show the feasibility of incorporating LDPM into such catheters for performing physiological studies in the GI tract. LDPM has emerged as a research and clinical tool in preference to other methods; but, it is important to be aware of its limitations and account for them when reporting results.
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20
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Tytgat GN. Hyoscine butylbromide - a review on its parenteral use in acute abdominal spasm and as an aid in abdominal diagnostic and therapeutic procedures. Curr Med Res Opin 2008; 24:3159-73. [PMID: 18851775 DOI: 10.1185/03007990802472700] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Being a quaternary ammonium compound derived from scopolamine, the alkaloid hyoscine butylbromide (HBB) exerts anticholinergic effects without side effects related to the central nervous system because it does not pass the blood-brain barrier. Clinical experience with this antispasmodic dates back to the 1950s and led to its registration for treating abdominal cramps/spasm and for diagnostic imaging purposes. OBJECTIVES AND SCOPE: This review focuses on the therapeutic efficacy and safety of the parenteral administration of HBB for treating biliary and renal colic and acute spasm in the genito-urinary tract. In addition, its value for diagnostic or therapeutic procedures in the abdomen, as well as for labour and palliative care, is reviewed. With the generic and trade name of the drug combined with various search terms related to the relevant clinical applications, a thorough literature search was performed in the Medline and EMBASE databases in April 2008. FINDINGS In most clinical studies, recommended doses of 20-40 mg HBB were injected, mainly intravenously. Fast pain reduction was achieved by HBB in renal colic; about 90% of the patients showed good to moderate analgesic responses after 30 min and the onset of action was noticeable within 10 min. Similarly, a pain reduction of 42-78% was observed in patients with biliary colic within 30 min after a single intravenous injection of 20 mg. In contrast, no analgesic efficacy of a single injection of 20 mg was found after surgical or shock-wave procedures in the urogenital area. Administration of HBB prior to, or during, radiological imaging distended the gastrointestinal (GI) tract in double-contrast barium and computed tomographic colonography studies and reduced motion artefacts in magnetic resonance imaging. This improved diagnostic image quality and organ visualisation. Pre-medication led to shorter and easier endoscopy in some, but not all, studies. Because of cervical relaxation, HBB shortened total labour duration with 17-67%. It also relieved pain and reduced GI secretions in terminal cancer patients with inoperable bowel obstruction. With regard to its safety profile, parenteral administration of HBB is associated with mild and self-limiting adverse events, typical for anticholinergic drugs. CONCLUSIONS These clinical results of rapid action and beneficial efficacy combined with good tolerability support the use of HBB in a range of indications related to acute abdominal spasm, in labour and palliative care and for supporting diagnostic and therapeutic abdominal procedures, where spasm may be a problem.
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21
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Gregersen H, Liao D, Pedersen J, Drewes AM. A new method for evaluation of intestinal muscle contraction properties: studies in normal subjects and in patients with systemic sclerosis. Neurogastroenterol Motil 2007; 19:11-9. [PMID: 17187584 DOI: 10.1111/j.1365-2982.2006.00837.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Systemic sclerosis is a connective tissue disease that involves the gastrointestinal (GI) tract. Seventy-five per cent of systemic sclerosis patients experience symptoms arising from oesophagus. The intestine has less frequently been subject for studies than the oesophagus. When the small intestine becomes involved, nausea, vomiting, bloating, diarrhoea and malabsorption may occur. Previous studies have shown decreased and abnormal intestinal motility, dilatation and a stiffer wall. The aim was to study muscle mechanics in systemic sclerosis patients using novel analysis of intestinal muscle contraction force-velocity and power. A volume-controlled duodenal ramp-distension protocol was used in nine patients and eight healthy controls. The wall stretch ratio, tension, shortening velocity and muscle power were computed from pressure and cross-sectional area data recorded by an impedance planimetry system. The tension-stretch ratio relation obtained in patients was shifted to the left, indicating a stiffer wall. The in vivo tension-shortening velocity relationship was quantified using Hill's equation. The maximum preload tension (tension at zero velocity) was lower in the patients than in the healthy controls (P < 0.001). The muscle power was lowest in the patients. An association was found between the duration of the disease and the maximum stretch ratio (P < 0.05). The study represents the first data with application of in vivo muscle force-velocity relations in patients with gastrointestinal diseases. Systemic sclerosis patients had increased stiffness and impaired muscle dynamics of the duodenum. Decreased muscle function and increased wall stiffness may explain the GI symptoms reported in this patient group.
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Affiliation(s)
- H Gregersen
- Center of Excellence in Visceral Biomechanics and Pain, Aalborg Hospital, Aalborg, Denmark
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22
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McMahon BP, Frøkjaer JB, Kunwald P, Liao D, Funch-Jensen P, Drewes AM, Gregersen H. The functional lumen imaging probe (FLIP) for evaluation of the esophagogastric junction. Am J Physiol Gastrointest Liver Physiol 2007; 292:G377-84. [PMID: 16950760 DOI: 10.1152/ajpgi.00311.2006] [Citation(s) in RCA: 109] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
There is a need for new methods to study the dynamics of the esophagogastric junction (EGJ). The aims were to verify the efficacy and usefulness of a "functional lumen imaging probe" (FLIP) for the evaluation of the EGJ. Eight healthy volunteers (6 men), median age 26 (21-35) yr, and two achalasia patients underwent the FLIP procedure. The EGJ was located by manometry. The FLIP measured eight cross-sectional areas (CSAs) 4 mm apart together with the pressure inside a saline-filled cylindrical bag. The data showed the geometric profile of the EGJ reconstructed in a video animation of its dynamic activity. A plot of curve-fitted data for the smallest CSA vs. pressure after balloon distension indicated that the pressure increased from 18 cmH2O at a CSA of 38 mm2 to a pressure of 37 cmH2O at a CSA of 230 mm2 for the healthy controls. In one achalasia patient (unsuccessfully treated with dilations), the CSA never rose above the minimal measurable value despite the pressure increasing to 50 cmH2O. In another achalasia patient (successfully treated with dilations), the pressure only reached 15 cmH2O despite opening to a CSA of 250 mm2. In conclusion, FLIP represents the first dynamic technique to profile the function and anatomy of the EGJ. The method can be used practically to evaluate difficult cases of EGJ dysfunction and may provide a role in evaluating patients before and after therapies for diseases affecting the EGJ such as achalasia and gastroesophageal reflux disease.
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Affiliation(s)
- Barry P McMahon
- Centre for Visceral Biomechanics and Pain, Aalborg Hospital, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
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23
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Frøkjaer JB, Andersen SD, Drewes AM, Gregersen H. Ultrasound-determined geometric and biomechanical properties of the human duodenum. Dig Dis Sci 2006; 51:1662-9. [PMID: 16927153 DOI: 10.1007/s10620-005-9015-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2005] [Accepted: 08/17/2005] [Indexed: 12/15/2022]
Abstract
Methods based on cross-sectional ultrasound imaging may be valuable for assessment of biomechanical parameters in the duodenum in health and disease. In 12 healthy volunteers a specially designed duodenal bag containing a high-frequency ultrasound probe was inflated until the perception of moderate pain. The ultrasound images and bag pressures were recorded before and after administration of butylscopolamine. The duodenum approached a circular shape as the load was increased (P = 0.01). The tension-strain relations were exponential and the curve fitting constant alpha (stiffness) was 1.72+/-0.81 before and 1.13+/-0.22 after administration of butylscopolamine (P=0.5). In three subjects construction of stress-strain diagrams was possible. The wall thickness decreased after administration of butylscopolamine (P < 0.001). The wall thickness was nonhomogeneously distributed along the duodenal circumference, being thickest at high curvatures. In the future this may be useful for assessing the geometry, stiffness, remodeling, and mechanosensory properties in the duodenum and small intestine in health and disease.
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Affiliation(s)
- Jens Brøndum Frøkjaer
- Center for Visceral Biomechanics and Pain, The Research Administration, Aalborg Hospital, DK-9100, Aalborg, Denmark
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24
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Larsen E, Reddy H, Drewes AM, Arendt-Nielsen L, Gregersen H. Ultrasonographic study of mechanosensory properties in human esophagus during mechanical distension. World J Gastroenterol 2006; 12:4517-23. [PMID: 16874864 PMCID: PMC4125639 DOI: 10.3748/wjg.v12.i28.4517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus.
METHODS: Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale (VAS). The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAS levels. Distensions were done before and during administration of the anti-cholinergic drug butylscopolamine.
RESULTS: The stimulus-response (volume-VAS) curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains.
CONCLUSION: The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mechanosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors.
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Affiliation(s)
- Ejnar Larsen
- Department of Radiology, Aalborg Hospital, Aalborg DK-9100, Denmark
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25
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Dimcevski G, Schipper KP, Tage-Jensen U, Funch-Jensen P, Krarup AL, Toft E, Thorsgaard N, Arendt-Nielsen L, Drewes AM. Hypoalgesia to experimental visceral and somatic stimulation in painful chronic pancreatitis. Eur J Gastroenterol Hepatol 2006; 18:755-64. [PMID: 16772833 DOI: 10.1097/01.meg.0000223903.70492.c5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVES To gain more information of the pain mechanisms in chronic pancreatitis we applied standardized experimental pain stimulation of the duodenum, oesophagus and the skin in 12 healthy controls and 13 patients with chronic pancreatitis and typical pain attacks. METHODS Using endoscopy a guide wire was positioned into the horizontal part of the duodenum, and a probe with a distal balloon was introduced over the guide wire. Mechanical stimuli were given as tonic (38 ml/min) or phasic (increasing volume steps of 5 ml delivered for 60 s) distensions of the balloon. After stimulation of the duodenum, the distal oesophagus was stimulated with the same protocol. Finally, the skin was stimulated with 'single and repeated burst' electrical stimuli reflecting activation of peripheral and central pain mechanisms. RESULTS The stimuli reliably evoked both painful and non-painful local and referred sensations. The patients had hyposensitivity to both tonic and phasic mechanical stimuli of the duodenum and the oesophagus (P=0.001). Hypoalgesia was also observed to single and repeated electrical skin stimuli in the patients, most evident for repeated stimuli (P=0.001). The evoked referred pain did not differ between the groups, but the patients used on average more words from the McGill Pain Questionnaire to describe the pain evoked in the duodenum (P=0.02). CONCLUSIONS Generalized hypoalgesia to experimental visceral and somatic stimulations was found in chronic pancreatitis. The findings suggest that the activation and modulation of central mechanisms is fundamental in pancreatic pain, and future studies should address the effect of analgesics with central effects in the treatment of these patients.
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Affiliation(s)
- Georg Dimcevski
- Centre for Visceral Biomechanics and Pain, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
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26
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Liao D, Frøkjaer JB, Yang J, Zhao J, Drewes AM, Gilja OH, Gregersen H. Three-dimensional surface model analysis in the gastrointestinal tract. World J Gastroenterol 2006; 12:2870-5. [PMID: 16718811 PMCID: PMC4087803 DOI: 10.3748/wjg.v12.i18.2870] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The biomechanical changes during functional loading and unloading of the human gastrointestinal (GI) tract are not fully understood. GI function is usually studied by introducing probes in the GI lumen. Computer modeling offers a promising alternative approach in this regard, with the additional ability to predict regional stresses and strains in inaccessible locations. The tension and stress distributions in the GI tract are related to distensibility (tension-strain relationship) and smooth muscle tone. More knowledge on the tension and stress on the GI tract are needed to improve diagnosis of patients with gastrointestinal disorders. A modeling framework that can be used to integrate the physiological, anatomical and medical knowledge of the GI system has recently been developed. The 3-D anatomical model was constructed from digital images using ultrasonography, computer tomography (CT) or magnetic resonance imaging (MRI). Different mathematical algorithms were developed for surface analysis based on thin-walled structure and the finite element method was applied for the mucosa-folded three layered esophageal model analysis. The tools may be useful for studying the geometry and biomechanical properties of these organs in health and disease. These studies will serve to test the structure-function hypothesis of geometrically complex organs.
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Affiliation(s)
- Donghua Liao
- Center of Excellence in Visceral Biomechanics and Pain, Aalborg Hospital, Aalborg, Denmark
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27
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Abstract
Despite its role in disease there is still no definitive method to assess oesophago-gastric junction competence (OGJ). Traditionally the OGJ has been assessed using manometry with lower oesophageal sphincter pressure as the indicator. More recently this has been shown not to be a very reliable marker of sphincter function and competence against reflux. Disorders such as gastro-oesophageal reflux disease and to a lesser extend achalasia still effects a significant number of patients. This review looks at using a new technique known as impedance planimetry to profile the geometry and pressure in the OGJ during distension of a bag. The data gathered can be reconstructed into a dynamic representation of OGJ action. This has been shown to provide a useful representation of the OGJ and to show changes to the competence of the OGJ in terms of compliance and distensibility as a result of endoluminal therapy.
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Affiliation(s)
- Barry P McMahon
- Department of Medical Physics and Clinical Engineering, Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland.
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28
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Drewes AM, Arendt-Nielsen L, Funch-Jensen P, Gregersen H. Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain. World J Gastroenterol 2006; 12:2806-17. [PMID: 16718803 PMCID: PMC4087795 DOI: 10.3748/wjg.v12.i18.2806] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.
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Affiliation(s)
- Asbjørn Mohr Drewes
- Center for Visceral Biomechanics and Pain, Department of Medical Gastroenterology, Aalborg University Hospital, DK-9000 Aalborg, Denmark.
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29
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Gregersen H, Hausken T, Yang J, Ødegaard S, Gilja OH. Mechanosensory properties in the human gastric antrum evaluated using B-mode ultrasonography during volume-controlled antral distension. Am J Physiol Gastrointest Liver Physiol 2006; 290:G876-82. [PMID: 16293656 DOI: 10.1152/ajpgi.00131.2005] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The aims of this study were to evaluate gastric antral mechanical behavior and distension-induced sensorimotor responses in the human gastric antrum using transabdominal ultrasound scanning. Ten healthy volunteers underwent volume-controlled ramp inflation of a bag located in the antrum with volumes up to 125 ml. The active and passive circumferential tensions and stresses were calculated from measurements of pressure, diameter, and wall thickness before and during the administration of the anticholinergic drug butylscopolamine. The bag distensions elicited contractions in the antrum and sensory responses below the pain threshold. Butylscopolamine abolished the contractions and significantly reduced the sensory response. The length-tension diagram known from in vitro studies of smooth muscle strips could be reproduced as tension-volume diagrams in the human gastric antrum. The number of induced contractions and the contraction pressure amplitude (afterload) showed a parabolic behavior as function of the distension volume (preload), with maximum approximately at 70 ml. At the sensation threshold, the luminal circumference showed the lowest variation coefficient (13-25%), whereas the variation coefficient was more than 100% for the pressure, tensions, and stresses. We conclude that the muscle length-tension diagram and typical preload-afterload curves ad modem the Frank-Starling cardiac law can be obtained in the human gastric antrum. The sensory responses were most closely associated with the luminal circumference, indicating that the sensation during antral distension depends on deformation rather than on tension.
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Affiliation(s)
- H Gregersen
- Center for Visceral Biomechanics and Pain, Aalborg Hospital, Hobrovej 42A, DK-9100 Aalborg, Denmark.
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Abstract
Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation (e.g., electrical, mechanical, thermal and chemical stimulation) of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.
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Affiliation(s)
- Asbjorn Mohr Drewes
- Center for Visceral Biomechanics and Pain, Department of Medical Gastroenterology, Aalborg University Hospital, Denmark.
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Ahmed AB, Gilja OH, Gregersen H, Ødegaard S, Matre K. In vitro strain measurement in the porcine antrum using ultrasound doppler strain rate imaging. ULTRASOUND IN MEDICINE & BIOLOGY 2006; 32:513-22. [PMID: 16616598 DOI: 10.1016/j.ultrasmedbio.2005.12.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2005] [Revised: 12/19/2005] [Accepted: 12/29/2005] [Indexed: 05/08/2023]
Abstract
Strain rate imaging (SRI) enables study of deformation in soft tissues. The aim of this study was to evaluate the accuracy of SRI in measuring strain in the porcine antral wall in vitro. An experimental set-up enabled controlled distension of a porcine stomach in a saline reservoir. Radial strain obtained by SRI was compared with radial strain calculated from B-mode ultrasonography. Circumferential strain obtained by SRI was compared with circumferential strain calculated from sonomicrometry. The agreement between radial strain values measured by SRI and B-mode, along and across several ultrasound (US) beams, using US frequency 6.7 MHz and strain length (SL) = 1.9 mm was = -1.0 +/- 12.1% and 0.5 +/- 13.4%, respectively (mean difference +/- 2SD%) and it was better than with SL 1.2 mm. Compared with sonomicrometry, SRI-determined circumferential strain using 6.7 MHz and SL = 1.9 mm was less accurate, whether averaging along or across several US beams (-9.2 +/- 46.7% and 13.8 +/- 51.2%, respectively). In conclusion, SRI gave accurate measurement of radial strain of the antral wall, but seemed to be less accurate for measurement of circumferential strain for this in vitro set-up.
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Drewes AM, Frøkjaer JB, Larsen E, Reddy H, Arendt-Nielsen L, Gregersen H. Pain and mechanical properties of the rectum in patients with active ulcerative colitis. Inflamm Bowel Dis 2006; 12:294-303. [PMID: 16633051 DOI: 10.1097/01.mib.0000209365.09189.04] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The pain, urgency, and incontinence in ulcerative colitis may be related to changes in viscoelastic properties of the gut wall or to alterations of the sensory pathways. In the present study, we used an advanced rectal probe to study the mechanosensory and smooth muscle properties in patients with active disease. METHODS Nine patients with ulcerative colitis (mean age 39.5 years) with exacerbation limited to the rectum and sigmoid colon and 17 age-matched healthy subjects were included. The rectum was distended before and after pharmacological relaxation of the smooth muscle until moderate pain was reported, and the cross-sectional area, volume, pressure, tension, and strain were computed. To investigate central integration of a tonic stimulus, the bag was finally distended to the pain threshold; then, the cross-sectional area was held constant for 2 min. RESULTS The patients were hypersensitive to mechanical stimuli as assessed by the cross-sectional area (F = 21.7; P < 0.001). There were no differences in compliance or stiffness between the 2 groups, but the hypersensitivity was abolished after muscle relaxation. Together with the muscle analysis, this finding demonstrated that the smooth muscles were tonically contracted in the inflamed rectum, resulting in a decreased rectal circumference. The tonic distensions did not evoke central integration of the pain response, indicating that hyperalgesia is more likely related to peripheral factors. CONCLUSIONS Patients with active ulcerative colitis have hypersensitivity and increased tone of the smooth muscles, which may explain the symptoms. Drugs that affect smooth muscle contraction may be helpful in difficult cases.
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Affiliation(s)
- Asbjørn Mohr Drewes
- Center for Visceral Biomechanics and Pain, Department of Gastroenterology, Aalborg University, Denmark.
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Frøkjaer JB, Andersen SD, Lundbye-Christensen S, Funch-Jensen P, Drewes AM, Gregersen H. Sensation and distribution of stress and deformation in the human oesophagus. Neurogastroenterol Motil 2006; 18:104-14. [PMID: 16420288 DOI: 10.1111/j.1365-2982.2005.00734.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Evaluation of the distribution of stresses and strains in relation to distension-induced sensation in the human oesophagus is valuable for understanding oesophageal biomechanics and mechano-sensation. In 12 healthy volunteers a specially designed oesophageal bag containing an endoscopic ultrasound probe was inflated to the moderate pain level. Ultrasound images, bag pressure and perceived sensation were recorded before and after pharmacological relaxation of the smooth muscle with butylscopolamine. The oesophagus was assumed to be circular and thick-walled. Distension induced a tensile circumferential stretch, radial compression and longitudinal shortening. Both circumferential strain and stress were highest at the mucosal surface and decreased throughout the wall. The stiffness increased throughout the wall and was highest at the outer surface (P < 0.001). The decrease in stiffness in response to butylscopolamine was non-significant. The infused volume (P = 0.012) and circumferential stress (P < 0.001) were most closely associated with the distension-induced sensation (adjusted R2 = 0.88). The perceived sensation was highly individual but was unaffected by butylscopolamine (P > 0.08). The present study provides a method for computation of the stress-strain distribution throughout the wall and the mechano-sensory interaction in the human oesophagus. In the future, this may be useful for understanding of mechanoreceptor responses and generation of symptoms in visceral organs in health and in disease.
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Affiliation(s)
- J B Frøkjaer
- Center for Visceral Biomechanics and Pain, Department of Radiology, Aalborg Hospital, Aalborg, Denmark
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Abstract
Various underlying mechanisms have been described in patients with non-cardiac chest pain (NCCP). By far, gastroesophageal reflux disease (GERD) is the most common cause and thus requires initial attention when patients with NCCP are managed. Esophageal dysmotility can be demonstrated in 30% of the NCCP patients, but appears to play a very limited role in symptom generation. A significant number of patients with NCCP lack any evidence of GERD and have been consistently shown to have reduced perception thresholds for pain. Peripheral and/or central sensitization have been suggested to be responsible for visceral hypersensivity in NCCP patients. Further understanding of the underlying mechanisms for pain in patients with NCCP will likely improve our current therapeutic approach.
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Affiliation(s)
- Daniel Van Handel
- The Neuro-Enteric Clinical Research Group, Department of Medicine, Section of Gastroenterology, Southern Arizona VA Health Care System and University of Arizona Health Sciences Center, Tucson, AZ 85723-0001, USA
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Frøkjær JB, Andersen SD, Gale J, Arendt-Nielsen L, Gregersen H, Drewes AM. An experimental study of viscero-visceral hyperalgesia using an ultrasound-based multimodal sensory testing approach. Pain 2005; 119:191-200. [PMID: 16297555 DOI: 10.1016/j.pain.2005.09.031] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2005] [Revised: 08/15/2005] [Accepted: 09/29/2005] [Indexed: 12/13/2022]
Abstract
Widespread visceral hypersensitivity and the overlap of symptom complexes observed in functional gastrointestinal disorders may be related to central sensitization and neuroplastic changes. A multimodal and multi-segmental model was developed to evaluate viscero-visceral hyperalgesia induced by experimental esophageal sensitization in healthy volunteers. Twelve healthy subjects were studied using a double-blinded, placebo-controlled design. The sensitivity to mechanical and heat stimulations was assessed in the proximal esophagus, duodenum and rectum before and after perfusion of the distal esophagus with acid or saline. A special-designed probe was used allowing cross-sectional ultrasound imaging during mechanical and heat stimulation of the esophagus and duodenum. Another probe was used for mechanical stimulation of the rectum. The referred somatic pain areas to gut pain stimulations were also assessed. Following acid perfusion 11 of 12 volunteers showed increased sensitivity to one or more stimulation modalities. An overall increased sensitivity to mechanical stretch in the three gut segments was seen (P=0.0001). Posthoc analysis showed that this was mainly due to increased sensitivity in the rectum (P<0.001). No changes were seen to thermal stimulations (all P-values>0.4). The somatic referred pain area to duodenal stimulations increased (P=0.04), while it was unaffected to esophageal and rectal stimulations (P>0.3). The present method demonstrated a new approach to assess multimodal sensitivity to experimental sensitization of the esophagus and related viscero-visceral hyperalgesia. Central mechanisms can explain the remote hyperalgesia to mechanical visceral stimulation and the increase in referred pain areas. The present method may be used to explore pathophysiology and pharmacological interventions in patients with visceral hypersensitivity.
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Affiliation(s)
- Jens Brøndum Frøkjær
- Center for Visceral Biomechanics and Pain, Aalborg Hospital, Denmark Department of Radiology, Aalborg Hospital, Denmark Pfizer Ltd, Sandwich, UK Department of Health Science and Technology, Center for Sensory-Motor Interaction, Aalborg University, Denmark
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Carmagnola S, Cantù P, Penagini R. Mechanoreceptors of the proximal stomach and perception of gastric distension. Am J Gastroenterol 2005; 100:1704-10. [PMID: 16086705 DOI: 10.1111/j.1572-0241.2005.41350.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To assess the role of tension receptors in gastric perception by pharmacologically modifying gastric contractile activity during isovolumetric distensions of the proximal stomach with the hypothesis that relaxation decreased perception and contraction increased it. METHODS Fourteen healthy subjects underwent two 30-min isovolumetric (75% of the threshold volume for discomfort) distensions using a barostat. During the second distension, either gastric relaxation was induced by intravenous (i.v.) glucagon 4.8 microg/kg bolus plus 9.6 microg/kg per h or contraction by i.v. erythromycin 3 mg/kg. Hunger and fullness were assessed with a 100-mm analog scale before and at 15 and 30 min during each distension. RESULTS Glucagon decreased baseline intrabag pressure (8.4 +/- 1.0 vs 10.7 +/- 1.3 mmHg; p < 0.05) and abolished the pressure waves (0 vs 16.7 +/- 2.3) when compared with placebo, whereas erythromycin increased baseline pressure (13.2 +/- 1.0 vs 11.9 +/- 0.9 mmHg; p < 0.05) and the rate of pressure waves (31.7 +/- 5.4 vs 20.5 +/- 3.1; p < 0.05). Fullness increased (p < 0.05) during distension, but it was unaffected by either of the drugs: Delta score (i.e., score during distension--baseline score) of 38 +/- 10 mm (glucagon) versus 22 +/- 10 (placebo) and 24 +/- 17 mm (erythromycin) versus 36 +/- 14 (placebo) at 15 min. Similar observation were made at 30 min. Hunger was influenced neither by distension nor by any of the two drugs consistently. CONCLUSIONS Our data do not support a prominent role of tension receptors of the proximal stomach on perception of fullness, suggesting that stretch, that is, volume, is the more relevant stimulus.
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Affiliation(s)
- Stefania Carmagnola
- Cattedra di Gastroenterologia, Dipartimento di Scienze Mediche, University of Milan-IRCCS, Ospedale Maggiore, Milan, Italy
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Drewes AM, Reddy H, Staahl C, Pedersen J, Funch-Jensen P, Arendt-Nielsen L, Gregersen H. Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid. World J Gastroenterol 2005; 11:4367-74. [PMID: 16038036 PMCID: PMC4434664 DOI: 10.3748/wjg.v11.i28.4367] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.
METHODS: Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine.
RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change.
CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs.
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Affiliation(s)
- Asbjørn-Mohr Drewes
- Center for Biomechanics and Pain, Department of Medical Gastroenterology, Aalborg Hospital, DK-9000 Aalborg, Denmark.
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Basavaraj S, Penumetcha KR, Cable HR, Umapathy N. Buscopan in oesophageal food bolus: is it really effective? Eur Arch Otorhinolaryngol 2004; 262:524-7. [PMID: 15592862 DOI: 10.1007/s00405-004-0852-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2003] [Accepted: 08/06/2004] [Indexed: 12/16/2022]
Abstract
Food bolus (FB) impaction of the oesophagus is one of the more common emergencies in otolaryngology. These patients are managed either conservatively or surgically. The guideline of the American Society of Gastrointestinal Endoscopy (ASGE) suggests that conservative management either with pharmacological agents or with an effervescent agent should be tried for 24 h usually prior to surgical intervention. Various pharmacological agents have been used to dislodge food bolus with varying success rates. We currently use buscopan as a pharmacological agent to dislodge obstruction. Our objective was to evaluate the efficacy of buscopan in the management of oesophageal food bolus. Dislodgement of food bolus and avoidance of oesophagoscopy were taken as a measure of the effectiveness of buscopan. There is no clear evidence in the literature for the time taken for spontaneous dislodgement or the proportion of cases needing oesophagoscopy. Reviewing the results in the last 5 years in our department, we found that food bolus obstruction was relieved in 68% of the patients who had buscopan and in 63% who did not have buscopan. There was no statistically significant difference in both groups (P = 0.37).
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Zeng YJ, Yang J, Zhao JB, Liao DH, Zhang EP, Gregersen H, Xu XH, Xu H, Xu CQ. Morphologic and biomechanical changes of rat oesophagus in experimental diabetes. World J Gastroenterol 2004; 10:2519-23. [PMID: 15300896 PMCID: PMC4572153 DOI: 10.3748/wjg.v10.i17.2519] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To study morphologic and biomechanical changes of oesophagus in diabetes rats.
METHODS: Diabetes was induced by a single injection of streptozotocin (STZ). The type of diabetes mellitus induced by parenteral STZ administration in rats was insulin-dependent (type I). The samples were excised and studied in vitro using a self-developed biomaterial test machine.
RESULTS: The body mass was decreased after 4 d with STZ treatment. The length of esophagus shortened after 4, 7, 14 d. The opening angle increased after 14 d. The shear, longitudinal and circumferential stiffness were obviously raised after 28 d of STZ treatment.
CONCLUSION: The changes of passive biomechanical properties reflect intra-structural alteration of tissue to a certain extent. This alteration will lead to some dysfunction of movement. For example, tension of esophageal wall will change due to some obstructive disease.
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Affiliation(s)
- Yan-Jun Zeng
- Forensic Medicine Department, Medical College, Shantou University, Shantou 515031, Guangdong Province, China.
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Abstract
Symptoms arising from the esophagus are produced generally in one of two ways: through stimulation of chemosensitive-nociceptors (eg, through excess esophageal exposure to refluxed gastric acid or the resulting inflammation arising in acid-damaged tissue) or through stimulation of mechanosensitive nociceptors (eg, through repeated deformation or distension of the esophageal wall resulting from peristaltic or lower esophageal sphincter dysfunction). These symptoms are usually attributed in most patients to such well recognized conditions as reflux esophagitis, achalasia,etc. that subsequently result in the delivery of specific and effective treatment.However, a subset of patients exists in which the etiology of "similar-sounding symptoms" remains obscure and their responses to standard specific treatments poor. Now recognized as among this group of patients are those with visceral hypersensitivity. Visceral hypersensitivity is not itself a disease but a definable aberrant sensory response (allodynia or hyper-algesia) to end-organ stimulation. Such an aberrant sensory response is neither specific for nor limited to the esophagus, and the etiopathogenesis for its development within this organ is unknown. Nonetheless, esophageal symptoms as a manifestation of visceral hypersensitivity are increasingly recognized and worthy of attention because they identify a disorder that responds to treatment aimed at the end organ's nociceptors or their neuroanatomic pathways within the CNS.
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Affiliation(s)
- Roy C Orlando
- Tulane University Medical School, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
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Pedersen J, Gao C, Egekvist H, Bjerring P, Arendt-Nielsen L, Gregersen H, Drewes AM. Pain and biomechanical responses to distention of the duodenum in patients with systemic sclerosis. Gastroenterology 2003; 124:1230-9. [PMID: 12730864 DOI: 10.1016/s0016-5085(03)00265-8] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Abnormalities of the small intestine have been indicated in systemic sclerosis. The aim was to use a new method to study the active-passive mechanical and sensory properties of the duodenum in these patients. METHODS A volume-controlled ramp-distention protocol was used in the duodenum in 9 patients and 8 healthy controls. The nonpainful/painful sensations, pressure, cross-sectional area, wall tension, and strain were evaluated. Using butylscopolamine for muscle relaxation, the active (contractile muscular component) and passive (other mechanical tissue components) were computed. RESULTS The contraction amplitude was smaller and the cross-sectional area higher in the patients (P < 0.05). Both the active and passive tension as function of strain was translated to the left in the patients, indicating a stiffer wall. The maximum active tension and the corresponding strain were 62% and 69% lower in the patients (P < 0.05). An association was found between the duration of the disease and the strain (P < 0.05). The perception score was higher as function of pressure, tension, and strain (P = 0.01, P = 0.03, and P < 0.01, respectively) in the patients than in the controls, with strain as the most sensitive variable to describe the sensory response. In 5 patients who complained of regular clinical symptoms, the referred pain area to distention was enlarged. CONCLUSIONS Systemic sclerosis resulted in increased stiffness and impaired muscle function of the duodenum. The pain evoked by a controlled strain of the gut was increased and can explain many of the symptoms reported in the clinic.
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Affiliation(s)
- Jan Pedersen
- Department of Medical Gastroenterology, Laboratory of Visceral Pain and Biomechanics, Aalborg University Hospital, Denmark
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