A comparison of function lumen imaging probe measurements of anal sphincter function in fecal incontinence.

BACKGROUND: The functional lumen imaging probe (FLIP) is a test of anal sphincter distensibility under evaluation by specialist centers. Two measurement protocols termed "stepwise" and "ramp" are used, risking a lack of standardization. This study aims to compare the performance of these protocols to establish if there are differences between them. METHODS: Patients with fecal incontinence were recruited and underwent measurement with both protocols at a tertiary pelvic floor referral unit. Differences in minimum diameter, FLIP bag pressure, and distensibility index (DI) at rest and during squeeze were calculated at various FLIP bag volumes. KEY RESULTS: Twenty patients (19 female, mean age 61 [range: 38-78]) were included. The resting minimum diameter at 30 and 40 mL bag volumes were less in the stepwise protocol (mean bias: -0.55 mm and -1.18 mm, p < 0.05) along with the DI at the same bag volumes (mean bias: -0.37 mm2/mmHg and -0.55 mm2/mmHg, p < 0.05). There was also a trend towards greater bag pressures at 30 mL (mean bias: +2.08 mmHg, p = 0.114) and 40 mL (mean bias: +2.81 mmHg, p = 0.129) volumes in the stepwise protocol. There were no differences between protocols in measurements of minimum diameter, maximum bag pressure, or DI during voluntary squeeze (p > 0.05). CONCLUSION AND INFERENCES: There are differences between the two commonly described FLIP measurement protocols at rest, although there are no differences in the assessment of squeeze function. Consensus agreement is required to agree the most appropriate FLIP measurement protocol in assessing anal sphincter function.

MRI-Based Quantification of Pan-Alimentary Function and Motility in Subjects with Diabetes and Gastrointestinal Symptoms.

Background: Diabetes-induced gastrointestinal (GI) symptoms are common but difficult to correctly diagnose and manage. We used multi-segmental magnetic resonance imaging (MRI) to evaluate structural and functional GI parameters in diabetic patients and to study the association with their symptomatic presentation. Methods: Eighty-six participants (46 with diabetes and GI symptoms, 40 healthy controls) underwent baseline and post-meal MRI scans at multiple timepoints. Questionnaires were collected at inclusion and following the scans. Data were collected from the stomach, small bowel, and colon. Associations between symptoms and collected data were explored. Utilizing machine learning, we determined which features differentiated the two groups the most. Key Results: The patient group reported more symptoms at inclusion and during MRI scans. They showed 34% higher stomach volume at baseline, 40% larger small bowel volume, 30% smaller colon volume, and less small bowel motility postprandially. They also showed positive associations between gastric volume and satiety scores, gastric emptying time and reflux scores, and small bowel motility and constipation scores. No differences in gastric emptying were observed. Small bowel volume and motility were used as inputs to a classification tool that separated patients and controls with 76% accuracy. Conclusions: In this work, we studied structural and functional differences between patients with diabetes and GI symptoms and healthy controls and observed differences in stomach, small bowel, and colon volumes, as well as an adynamic small bowel in patients with diabetes and GI symptoms. Associations between recorded parameters and perceived symptoms were also explored and discussed.

Pan-alimentary assessment of motility, luminal content, and structures: an MRI-based framework.

BACKGROUND: Gastrointestinal symptoms originating from different segments overlap and complicate diagnosis and treatment. In this study, we aimed to develop and test a pan-alimentary framework for the evaluation of gastrointestinal (GI) motility and different static endpoints based on magnetic resonance imaging (MRI) without contrast agents or bowel preparation. METHODS: Twenty healthy volunteers (55.6 ± 10.9 years, BMI 30.8 ± 9.2 kg/m2) underwent baseline and post-meal MRI scans at multiple time points. From the scans, the following were obtained: Gastric segmental volumes and motility, emptying half time (T50), small bowel volume and motility, colonic segmental volumes, and fecal water content. Questionnaires to assess GI symptoms were collected between and after MRI scans. KEY RESULTS: We observed an increase in stomach and small bowel volume immediately after meal intake from baseline values (p<.001 for the stomach and p=.05 for the small bowel). The volume increase of the stomach primarily involved the fundus (p<.001) in the earliest phase of digestion with a T50 of 92.1 ± 35.3 min. The intake of the meal immediately elicited a motility increase in the small bowel (p<.001). No differences in colonic fecal water content between baseline and 105 min were observed. CONCLUSION & INFERENCES: We developed a framework for a pan-alimentary assessment of GI endpoints and observed how different dynamic and static physiological endpoints responded to meal intake. All endpoints aligned with the current literature for individual gut segments, showing that a comprehensive model may unravel complex and incoherent gastrointestinal symptoms in patients.

Electrocardiography Assessment of Sympatico-Vagal Balance during Resting and Pain Using the Texas Instruments ADS1299.

Sympatico-vagal balance is essential for regulating cardiac electrophysiology and plays an important role in arrhythmogenic conditions. Various noninvasive methods, including electrocardiography (ECG), have been used for clinical assessment of the sympatico-vagal balance. This study aimed to use a custom-designed wearable device to record ECG and ECG-based cardiac function biomarkers to assess sympatico-vagal balance during tonic pain in healthy controls. Nineteen healthy volunteers were included for the ECG measurements using the custom-designed amplifier based on the Texas Instruments ADS1299. The ECG-based biomarkers of the sympatico-vagal balance, (including heart rate variability, deceleration capacity of the heart rate, and periodic repolarization dynamic), were calculated and compared between resting and pain conditions (tonic pain). The custom-designed device provided technically satisfactory ECG recordings. During exposure to tonic pain, the periodic repolarization dynamics increased significantly (p = 0.02), indicating enhancement of sympathetic nervous activity. This study showed that custom-designed wearable devices can potentially be useful in healthcare as a new telemetry technology. The ECG-based novel biomarkers, including periodic repolarization dynamic and deceleration capacity of heart rate, can be used to identify the cold pressor-induced activation of sympathetic and parasympathetic systems, making it useful for future studies on pain-evoked biomarkers.

A novel MRI-based three-dimensional model of stomach volume, surface area, and geometry in response to gastric filling and emptying.

BACKGROUND: Gastric motility and accommodation have a critical role in maintaining normal gastrointestinal homeostasis. Different modalities can be adopted to quantify those processes, that is, scintigraphy to measure emptying time and intragastric Barostat for accommodation assessment. However, magnetic resonance imaging (MRI) can assess the same parameters noninvasively without ionizing radiation. Our study aimed to develop a detailed three-dimensional (3D) MRI model of the stomach to describe gastric volumes, surface areas, wall tension distribution, and interobserver agreement. METHODS: Twelve healthy volunteers underwent an MRI protocol of six axial T2-weighted acquisitions. Each dataset was used to construct a 3D model of the stomach: First, the volumes of the whole stomach, gastric liquid, and air were segmented. After landmark placing, a raw 3D model was generated from segmentation data. Subsequently, irregularities were removed, and the model was divided into compartments. Finally, surface area and 3D geometry parameters (inverse curvatures) were extracted. The inverse curvatures were used as a proxy for wall tension distribution without measuring the intragastric pressure. KEY RESULTS: The model was able to describe changes in volume and surface geometry for each compartment with a distinct pattern in response to filling and emptying. The surface tension was distributed nonhomogeneously between compartments and showed dynamical changes at various time points. CONCLUSION & INFERENCES: The presented model offers a detailed tool for evaluating gastric volumes, surface geometry, and wall tension in response to filling and emptying and will provide insights into gastric emptying and accommodation in diseases such as diabetic gastroparesis.

Current and future perspectives on the utility of provocative tests of anal sphincter function: A state-of-the-art summary.

BACKGROUND: The maintenance of fecal continence depends upon coordinated interactions between the pelvic floor, anorectum, and anal sphincter complex orchestrated by central and peripheral neural activities. The current techniques to objectively measure anorectal function rely on fixed diameter catheters placed inside the anal canal with a rectal balloon to obtain measurements of anal resting and squeeze function, and rectal compliance. Until recently it had not been possible to measure the distensibility of the anal canal, or in other words its ability to resist opening against an increasing pressure, which has been proposed as the main determinant of a biological sphincter's function. Anal acoustic reflectometry (AAR) and the functional lumen imaging probe (FLIP) are two novel, provocative techniques that dynamically assess the anal sphincter complex under volume-controlled distension. In doing so, both provide information on the viscoelastic properties of the anal canal and offer new insights into its function. PURPOSE: This review details the current and potential future applications of AAR and FLIP and highlights the unanswered questions relevant to these new technologies.

Indentation of a pressurized silicon stomach model - A non-invasive study of gastric wall stiffness and pressurized gastric content stiffness.

BACKGROUND AND AIMS: Evaluation of gastric wall stiffness and intragastric pressure is essential for detailed assessments of gastric accommodation. However, non-invasive assessments are needed for large scale clinical studies and none of the existing methods takes abdominal wall effect into the calculation. This study aimed to assess gastric wall stiffness and gastric content stiffness as a proxy for intragastric pressure using novel mechanical modeling and non-invasive indentation tests on a silicon stomach model. METHODS: A silicon stomach model (scaling 1:1 with the human stomach) was indented using a pressure algometer at intragastric pressures from 0 to 0.8 kPa. Wall thicknesses and luminal cross-sectional areas along the stomach were measured with ultrasound images. The gastric wall stiffness was compared between measurements from tensile tests on strips cut from the silicon stomach and estimations from a shell indentation model. The pressurized gastric content stiffness was predicted from a bonded two-layer axisymmetric half-space indentation model. RESULTS: The gastric wall stiffness estimated from the shell indentation model showed no difference to measurements from the mechanical tests on the cutting strips (p = 0.14). The predicted gastric content stiffness was strongly associated with the intragastric pressure (r > 0.83, p < 0.001). CONCLUSIONS: The mechanical model developed in this study can simultaneously predict the gastric wall stiffness and the pressurized gastric content stiffness. In future studies, the method can be applied to reveal intragastric pressure conditions non-invasively via the pressurized gastric content stiffness during gastric accommodation and emptying such as with magnetic resonance imaging.

Central neuronal transmission in response to tonic cold pain is modulated in people with type 1 diabetes and severe polyneuropathy.

AIMS: This study aimed to investigate cortical source activity and identify source generators in people with type 1 diabetes during rest and tonic cold pain. METHODS: Forty-eight participants with type 1 diabetes and neuropathy, and 21 healthy controls were investigated with electroencephalography (EEG) during 5-minutes resting and 2-minutes tonic cold pain (immersing the hand into water at 2 °C). EEG power was assessed in eight frequency bands, and EEG source generators were analyzed using standardized low-resolution electromagnetic tomography (sLORETA). RESULTS: Compared to resting EEG, cold pain EEG power differed in all bands in the diabetes group (all p < 0.001) and six bands in the controls (all p < 0.05). Source generator activity in the diabetes group was increased in delta, beta2, beta3, and gamma bands and decreased in alpha1 (all p < 0.006) with changes mainly seen in the frontal and limbic lobe. Compared to controls, people with diabetes had decreased source generator activity during cold pain in the beta2 and beta3 bands (all p < 0.05), mainly in the frontal lobe. CONCLUSIONS: Participants with type 1 diabetes had altered EEG power and source generator activity predominantly in the frontal and limbic lobe during tonic cold pain. The results may indicate modulated central transmission and neuronal impairment.

Biomechanical Properties of Strictures in Crohn's Disease: Can Dynamic Contrast-Enhanced Ultrasonography and Magnetic Resonance Enterography Predict Stiffness?

Strictures and abdominal pain often complicate Crohn's disease (CD). The primary aim was to explore whether parameters obtained by preoperative contrast-enhanced (CE) ultrasonography (US) and dynamic CE MR Enterography (DCE-MRE) of strictures associates with biomechanical properties. CD patients undergoing elective small intestinal surgery were preoperatively examined with DCE-MRE and CEUS. The excised intestine was distended utilizing a pressure bag. Luminal and outer bowel wall cross-sectional areas were measured with US. The circumferential stricture stiffness (Young's modulus E) was computed. Stiffness was associated with the initial slope of enhancement on DCE-MRE (ρ = 0.63, p = 0.007), reflecting active disease, but lacked association with CEUS parameters. For structural imaging parameters, inflammation and stricture stiffness were associated with prestenotic dilatation on US (τb = 0.43, p = 0.02) but not with MRE (τb = 0.01, p = 1.0). Strictures identified by US were stiffer, 16.8 (14.0-20.1) kPa, than those graded as no or uncertain strictures, 12.6 (10.5-15.1) kPa, p = 0.02. MRE global score (activity) was associated with E (ρ = 0.55, p = 0.018). Elastography did not correlate with circumferential stiffness. We conclude that increasing activity defined by the initial slope of enhancement on DCE-MRE and MRE global score were associated with stricture stiffness. Prestenotic dilatation on US could be a potential biomarker of CD small intestinal stricture stiffness.

Gastrocolic Reflex Is Delayed and Diminished in Adults with Type 1 Diabetes.

BACKGROUND: Constipation is a prevalent gastrointestinal complication in diabetes. The pathophysiology may include neural dysfunction and impaired gastrocolic reflex; however, investigation of the latter has been limited in diabetes. Using the wireless motility capsule, we investigated whether the gastrocolic reflex was impaired in adults with type 1 diabetes compared to healthy. METHODS: One hundred and four adults with type 1 diabetes underwent investigation with the wireless motility capsule and recorded sleep cycle, eating habits, and bowel movements in a diary. Colonic motility index, contraction amplitudes, time-to-peak, peak motility, and colonic transit time were investigated directly in response to a meal. Diagnosis of peripheral (nerve conduction) and autonomic (orthostatic hypotension) polyneuropathy was verified. RESULTS: In comparison with health, people with diabetes had at the time of ingestion decreased motility index and contraction amplitudes (p < 0.001), prolonged time-to-peak (p = 0.01), and borderline decreased peak motility (p = 0.06), which taken together indicate impaired coordination of the gastrocolic reflex. These features were most prominent in those with concomitant peripheral or autonomic neuropathy. Additionally, they were associated with prolonged colonic transit time (p > 0.01). CONCLUSIONS: In type 1 diabetes, the gastrocolic reflex was delayed and diminished and further associated with the presence of neuropathy and constipation. These results suggest that impaired reflex is part of the underlying pathogenesis in the development of constipation.

Contractility patterns and gastrointestinal movements monitored by a combined magnetic tracking and motility testing unit.

BACKGROUND: Ingestible wireless capsules, including the 3D-transit magnetic capsule and the wireless motility capsule (WMC), describe gastrointestinal (GI) motility from changes in position or pressure. This study aimed to combine information on contractile events in terms of position (assessed with the 3D-transit) and change in pressure (assessed with the WMC) throughout the entire GI tract. METHODS: The 3D-transit capsule and WMC were combined into a single-wireless unit system. Three-dimensional space-time coordinates, pressure, and pH data from a pilot case were analyzed as the combined unit passed the GI tract. Two single and three continuous contraction patterns were defined according to pressure changes and quantified through the GI tract. KEY RESULTS: The combined unit was well tolerated and provided information on contractions throughout the gut. Single contraction patterns with no significant progressive movement of the unit were most prevalent in the stomach and the rectosigmoid colon. During the continuous contraction patterns, the unit moved in an antegrade or retrograde direction. Longer distance and higher velocity were seen during antegrade than during retrograde movements. The motility indices (as measured with WMC) in combined ascending, transverse and descending colon showed a positive linear association (r = 0.7) to the capsule movements (as measured with 3D-transit). CONCLUSIONS & INFERENCES: The combined system provides synchronous information about movements and gut contractions. These measurements can be used to extract more information from existing recordings and may enhance our understanding of GI motility in health and disease.

Bowel stiffness associated with histopathologic scoring of stenosis in patients with Crohn's disease.

BACKGROUND AND AIMS: Intestinal stenosis is a common complication of Crohn's Disease (CD). Stenosis is associated with alteration of bowel mechanical properties. This study aims to quantitate the mechanical properties of the intestinal stenosis and to explore associations between histology and mechanical remodeling at stenotic intestinal sites in CD patients. METHODS: Intestinal segments from stenotic sites were studied in vitro from 19 CD patients. A luminal catheter with a bag was used to stepwise pressurize the intestinal segments from 0-100 cmH2O with 10 cmH2O increments. B-mode ultrasound images were obtained at the narrowest part of the stenosis at each pressure level and morphometric parameters were obtained from ultrasound images. The mechanical behavior of the stenotic tissue were characterized by using an isotropic three dimensional strain energy function in Demiray model form, the mechanical constants were obtained by fitting the model to the recorded intraluminal pressure and the inner radius of the stenotic segment of the small bowel. Grading scores were used for histological analysis of inflammation, fibrosis, muscular hypertrophy and adipocyte proliferation in the intestinal layers. The collagen area fraction in intestinal layers was also calculated. Associations between histological and the mechanical constants (stiffness) were analyzed. RESULTS: Chronic inflammation was mainly located in mucosa whereas fibrosis was found in submucosa. The mechanical remodeling was performed with changed mechanical constants ranged between 0.35-13.68kPa. The mechanical properties changes were associated mainly with chronic inflammation, fibrosis and combination of inflammation and fibrosis (R>0.69, P<0.001). Furthermore, the mechanical properties correlated with the collagen fraction in submucosa and muscular layers (R>0.53, P<0.05). CONCLUSIONS: We quantitated the intestinal stenosis stiffness. Associations were found between bowel mechanical remodeling and histological changes at the stenotic site in CD patients. STATEMENT OF SIGNIFICANCE: Although intestinal ultrasonography, CT and MRI can be used to diagnose Crohn's Disease (CD)-associated bowel strictures, these techniques may not have sufficient accuracy and resolution to differentiate predominantly inflammatory strictures from predominantly fibrotic strictures. The present study aims to quantitate the mechanical remodeling of intestinal stenosis and to explore the associations between histological parameters and mechanical properties at the intestinal stenotic sites in CD patients. For the first time, we quantitatively demonstrated that the mechanical properties of the intestinal wall in CD stenosis are associated with the chronic inflammation, fibrosis and collagen fraction in the intestinal layers. The results of this study may facilitate design and development of artificial biomaterials for gastrointestinal organs. The potential clinical implication of this study is that the histological characteristics in patients with CD can be predicted clinically by means of inflammation and fibrosis assessment in conjunction with tissue stiffness measurement.

The antroduodenal transition time is prolonged in adults with type 1 diabetes.

BACKGROUND: The gastroparetic syndrome encompasses antral hypomotility, gastric dysrhythmia, impaired antroduodenal coordination, pyloric dysfunction, and abnormal duodenal motility; the last three collectively referred to as pylorospasms. We hypothesized that antroduodenal motility is diminished and transition time is prolonged in adults with type 1 diabetes (T1D) and polyneuropathy. METHODS: This cross-sectional study included 124 participants, of which 21 were healthy, 53 had T1D and 50 had T1D with distal symmetrical polyneuropathy (T1D + DSPN). We used the wireless motility capsule to assess antroduodenal transition time, gastric emptying time, gastric and small bowel motility indices (MI), and numbers of alkalic/acidic exposures. RESULTS: In comparison with controls, patients with T1D had prolonged antroduodenal transition time (1.85±1.5 vs. 6.6±4.8 minutes; p=0.02), which was even more pronounced in patients with T1D+DSPN (1.85±1.5 vs. 17.8±28.5 minutes; p<0.008. T1D+DSPN tended to have diminished gastric MI (11.9±2.4 vs. 12.7±1.0, p=0.07) and small bowel MI (13.1±1.4 vs. 13.6±0.6, p=0.05) and experienced more antral/pyloric alkalic episodes (1.2±1.3 vs. 2.0±2.1, p=0.02) compared with controls. CONCLUSION: The current method may assess a proxy for severity of pylorospasms in patients with diabetes and other diseases associated with upper gastrointestinal motility disorders, which ultimately may optimize future management.

Long-term anorectal function in rectal cancer patients treated with chemoradiotherapy and endorectal brachytherapy.

AIM: The aim was to study anorectal function in long-term survivors after combined, curatively intended, chemoradiotherapy and endorectal brachytherapy for low rectal cancer. METHODS: This was a case-control design. We compared anorectal function by anal manometry, anal functional lumen imaging probe (EndoFLIP) and rectal bag distension in rectal cancer patients (RCPs) and healthy, normal subjects (NSs). Symptoms were assessed by the low anterior resection syndrome (LARS) and Wexner faecal incontinence scores. RESULTS: Thirteen RCPs (12 men, median age 68 years, range 52-92) after 60 Gy radiotherapy, 5 Gy endorectal brachytherapy and oral tegafur-uracil with complete clinical response (median time since treatment 2.8 years, range 2.2-5.6) were compared to 15 NSs (14 men, median age 64 years, range 47-75). RCPs had lower than normal anal resting pressure, 38.6 mmHg (range 8.8-67.7) versus 58.8 mmHg (25.7-105.2) (P < 0.003), and squeeze pressure, 117 mmHg (55.2-203) versus 188 mmHg (103-248) (P < 0.01). Squeeze-induced pressure increase recorded by EndoFLIP was also lower in RCPs (q > 7.56, P < 0.001) as was the anal canal resistance to increasing distension (q = 3.13, P < 0.05). No differences in median rectal volume at first sensation (72 [22-158] vs. 82 [36-190] ml, P = 0.4) or at urge to defaecate (107 [42-227] vs. 132 [59-334] ml, P = 0.2) were found. However, maximum tolerable rectal volume was lower in RCPs (145 [59-319] vs. 222 [106-447] ml, P < 0.02). The median (range) low anterior resection syndrome score was 27 (0-39) for RCPs and 7 (0-23) for NSs (P < 0.001), while the Wexner score was 0 (0-5) versus 0 (0-4) (P = 0.56). CONCLUSION: Radiotherapy combined with endorectal brachytherapy for rectal cancer causes long-term anorectal symptoms, impaired anal sphincter function and reduced rectal capacity.

Modeling and measurement of the mechano-physiological function of the gastrointestinal organs.

OBJECTIVE: Gastroenterological research has traditionally been based on experimental approaches rather than mathematical modeling. However, the various patterns of the gastrointestinal (GI) tract functions are generated by the integrated functions of multiple tissues and cell types. Hence, a thorough study of the gut requires an understanding of the interactions between cells, tissues and GI organs in both healthy and diseased conditions. APPROACH: A unique way of coping with the resulting explosion in complexity is mathematical modeling. Novel modeling analysis together with the development of medical imaging techniques and advanced medical devices can be integrated into different protocols, to aid understanding of the physiology of GI diseases and clinical decision-making in GI cases. MAIN RESULTS: This review summarizes the current advanced mechano-physiological modeling analyses of the human GI organs, including imaging modeling analysis of mass transit processing and mechano-physiological modeling during organ distension. SIGNIFICANCE: The proposed models have the potential to shed some light on the functional understanding of the physiology and pathophysiology of both healthy and diseased guts.

Mechanophysiological analysis of anorectal function using simulated feces in human subjects.

INTRODUCTION: Defecation is a complex process that is difficult to study and analyze. OBJECTIVES: Here, we present new analytical tools to calculate frictional force and tension during expulsion of the Fecobionics simulated stool in human subjects. METHODS: The 12-cm-long Fecobionics device contained pressure sensors, motion processor units for measurement of orientation and bending, and impedance rings for measurement of cross-sectional areas. Eight normal subjects defecated Fecobionics. The bending angle of the device, frictional force between the device and the surrounding tissue, and the stretch tensions were calculated. RESULTS: The bending angle and pressures changed during expulsion with the maximum pressure recorded at the rear. The averaged circumferential tension, longitudinal tension and friction force in each subject were associated with the front-rear pressure difference (r > 0.7, p < 0.005). The peak circumferential tension, longitudinal tension, and friction force immediately before expulsion of the rear were significantly higher compared to when the front entered the anal canal (F = 164.7, p < 0.005; F = 152.1, p < 0.005; F = 71.4, p < 0.005; respectively.). CONCLUSION: This study shows that Fecobionics obtained reliable data under physiological conditions. Mechanical features such as frictional force and stretch tensions were assessable during Fecobionics expulsion.

Simulations of Myenteric Neuron Dynamics in Response to Mechanical Stretch.

BACKGROUND: Intestinal sensitivity to mechanical stimuli has been studied intensively in visceral pain studies. The ability to sense different stimuli in the gut and translate these to physiological outcomes relies on the mechanosensory and transductive capacity of intrinsic intestinal nerves. However, the nature of the mechanosensitive channels and principal mechanical stimulus for mechanosensitive receptors are unknown. To be able to characterize intestinal mechanoelectrical transduction, that is, the molecular basis of mechanosensation, comprehensive mathematical models to predict responses of the sensory neurons to controlled mechanical stimuli are needed. This study aims to develop a biophysically based mathematical model of the myenteric neuron with the parameters constrained by learning from existing experimental data. Findings. The conductance-based single-compartment model was selected. The parameters in the model were optimized by using a combination of hand tuning and automated estimation. Using the optimized parameters, the model successfully predicted the electrophysiological features of the myenteric neurons with and without mechanical stimulation. CONCLUSIONS: The model provides a method to predict features and levels of detail of the underlying physiological system in generating myenteric neuron responses. The model could be used as building blocks in future large-scale network simulations of intrinsic primary afferent neurons and their network.

Sacral Nerve Modulation Has No Effect on the Postprandial Response in Irritable Bowel Syndrome.

PURPOSE: Irritable bowel syndrome is a common gastrointestinal disorder with a global prevalence of approximately 11%. Onset or worsening of symptoms following digestion is one of the characteristics of the condition. The present study aimed at evaluating the postprandial sensory and motor response before and after treatment with sacral nerve modulation. PATIENTS AND METHODS: Twenty-one irritable bowel syndrome patients, 12 diarrhea-predominant and 9 mixed, were eligible for a 6-week sacral nerve modulation test period. Patients were investigated with multimodal impedance planimetry including a standardized meal at baseline and at the end of 2 weeks of suprasensory stimulation embedded in the 6-week sacral nerve modulation period. RESULTS: There was no statistical significant difference in the sensory response to heat or cold before and after sacral nerve modulation, p>0.05. At baseline, wall tension increased after the meal (mean 124.79 [range 82.5 to 237.3] mmHg.mm before the meal, mean 207.76 [range, 143.5 to 429] mmHg.mm after the meal), p=0.048 indicating a postprandial response. During sacral nerve modulation, the postprandial increase in wall tension did not reach statistical significance (mean 86.79 [range 28.8 to 204.5] mmHg.mm before the meal, mean 159.71 [range 71.3 to 270.8] mmHg.mm after the meal), p=0.277. However, there was no statistically significant difference between the postprandial wall tension at baseline and during sacral nerve modulation, p=0.489. Likewise, we found no difference between pressure or stretch ratio at baseline and during sacral nerve modulation, p>0.05. CONCLUSION: Sacral nerve modulation does not exert its positive treatments effects in diarrhea-predominant and mixed irritable bowel syndrome through a modulation of the postprandial response.

Pressure overload changes mesenteric afferent nerve responses in a stress-dependent way in a fasting rat model.

It is well known that overload changes the mechanical properties of biological tissues and fasting changes the responsiveness of intestinal afferents. This study aimed to characterize the effect of overload on mechanosensitivity in mesenteric afferent nerves in normal and fasted Sprague-Dawley rats. Food was restricted for 7 days in the Fasting group. Jejunal whole afferent nerve firing was recorded during three distensions, i.e., ramp distension to 80 cmH2O luminal pressure (D1), sustained distension to 120 cmH2O for 2 min (D2), and again to 80 cmH2O (D3). Multiunit afferent recordings were separated into low-threshold (LT) and wide-dynamic-range (WDR) single-unit activity for D1 and D3. Intestinal deformation (strain), distension load (stress), and firing frequency of mesenteric afferent nerve bundles [spike rate increase ratio (SRIR)] were compared at 20 cmH2O and 40 cmH2O and maximum pressure levels among distensions and groups. SRIR and stress changes showed the same pattern in all distensions. The SRIR and stress were larger in the Fasting group compared to the Control group (P < 0.01). SRIR was lower in D3 compared to D1 in controls (P < 0.05) and fasting rats (P < 0.01). Total single units and LT were significantly lower in Fasting group than in Controls at D3. LT was significantly higher in D3 than in D1 in Controls. Furthermore, correlation was found between SRIR with stress (R = 0.653, P < 0.001). In conclusion, overload decreased afferent mechanosensitivity in a stress-dependent way and was most pronounced in fasting rats. Fasting shifts LT to WDR and high pressure shifts WDR to LT in response to mechanical stimulation.

Mechanical analysis of intestinal contractility in a neonatal maternal deprivation irritable bowel syndrome rat model.

The aims of the present study are to investigate biomechanical properties and provide mechanical analysis of contractility in ileum and colon in a neonatal maternal deprivation (NMD) irritable bowel syndrome (IBS) rat model. Mechanical testing was done on segments from ileum and colon in 25 IBS rats and 13 Control rats. Morphometric data were obtained from digitized images of the segments at no-load and zero-stress states. Pressure and diameter changes were measured during flow and ramp distensions under active and passive experimental conditions. Circumferential stresses (force per area) and strains (deformation) were computed with referenced to the zero-stress state. The contraction frequency was analyzed. Contraction thresholds and maximum contraction amplitude were calculated in terms of mechanical stress and strain. Compared with controls, the IBS rats had lower body weight (P < 0.01), smaller colonic opening angle (P < 0.05), higher colonic contraction frequency (P < 0.05 and P < 0.01) and lower contraction thresholds of pressure, stress and strain in both ileum and colon (P < 0.05 and P < 0.01). The maximum contraction pressure, stress and strain did not differ between IBS and Control groups (P > 0.05). In conclusion, the pressure, stress, and strain to evoke contractility in ileum and colon were lower whereas the frequency of induced colon contractions was higher in NMD IBS rats compared to normal rats. Furthermore, zero-stress state remodeling occur in colon in NMD IBS rats. Further studies on the association between intestinal biomechanical properties, hypersensitivity and afferent signaling in the IBS animal models are warranted.