Contribution of sensitivity, volume and tone to visceral perception in the upper gastrointestinal tract in man: emphasis on testing

Abstract  Upper gastrointestinal (GI) symptoms occur frequently in the general population, making them among the most common indications responsible for patients consulting the healthcare system. Consequently, understanding and characterization of the upper GI symptoms is important for the diagnosis and assessment of organ dysfunction. In practice, assessment of clinical symptoms is difficult and it is still to a large extent unclear how sensitivity, volume and tone contribute to visceral perception in the upper GI tract. The goal of advanced research in upper GI symptoms is to obtain a better understanding of the mechanisms involved in transduction, transmission, and perception under normal and pathophysiological conditions. An important step towards this goal is understanding the information provided by and the inherent limitations of the currently available measuring techniques. This article focuses on the sensory testing of the oesophagus, and methods and concepts used to assess the relation between gastric volumes or tone and upper GI symptoms. It also summarizes the contributions of these techniques towards identifying the components responsible for the generation of upper GI symptoms.     

Three-dimensional biomechanical properties of the human rectum evaluated with magnetic resonance imaging

A method to evaluate the three-dimensional (3-D) geometry of the human gastrointestinal wall may be valuable for understanding tissue biomechanics, mechano-sensation and function. In this paper we present a magnetic resonance imaging (MRI) based method to determine rectal geometry and validation of data obtained in three volunteers. A specially designed rectal bag was filled in a stepwise manner while MRI and bag pressure were recorded. 3-D models of curvatures, radii of curvature, tension and stress were generated and the circumferential and longitudinal strains were calculated. The computed bag volumes corresponded to the infused volumes. A pronounced bag elongation and decrease in wall thickness was observed during the bag filling. The spatial distributions of the biomechanical parameters were distinctly different between individuals and non-homogeneous throughout the rectal wall due to its complex geometry. The average tension and stress increased as a function of infused volume and circumferential strain. The present study provides a method for characterizing the complex in vivo 3-D geometry of the human rectum. The non-homogenous spatial curvature distribution suggests that simple estimates of tension based on pressure and volume do not reflect the true 3-D biomechanical properties of the rectum.     

A multimodal laser Doppler and endosonographic distension device for studying mechanosensation and mucosal blood flow in the oesophagus

We describe the development of a multimodal device combining bag distension, manometry, high frequency intraluminal ultrasound, laser Doppler flowmetry and symptom registration. Bench tests showed that the different modalities did not influence each other. During bag distension we obtained high quality images of the oesophageal wall for computing biomechanical parameters, and laser Doppler signals showing variation in mucosal perfusion. We conclude that the principle of measurement is sound and that the device can provide a basis for further studies.     

Strain measurement during antral contractions by ultrasound strain rate imaging: influence of erythromycin

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.     

An endoscopic method for thermal and chemical stimulation of the human oesophagus

Abstract  Previous methods for visceral thermal stimulation have lacked control of the temperature rate and visual inspection of the organ. The aims of this study was to develop a method for linear control of heat stimulation in the human oesophagus combined with endoscopy, to assess the reproducibility of this method and to investigate sensitivity to thermal stimulation of the distal oesophagus before and after acid perfusion. A probe with a 2.8 mm endoscope inside was constructed permitting heat and chemical stimulation. Three different temperature ramps were applied in the distal oesophagus in 12 healthy subjects by recirculation of heated water in a bag. Endoscopy of the oesophageal mucosa was performed prior to experimental stimulation. The temperature, the time of stimulation and the area under the temperature curve (AUC) were measured at the pain detection threshold. Thermal stimulation was repeated after perfusion of the oesophagus with acid. The method was tested on two subsequent days to assess reproducibility. All subjects had a normal endoscopic examination. Day-to-day reproducibility was good for the three temperature ramps (intra-class correlations >0.6). The subjects tolerated less heat stimulation, a decrease in AUC ( P  =   0.0003), a decrease in time to pain detection threshold ( P  =   0.005) and decreased temperature at pain detection threshold ( P  =   0.0001) after acid perfusion. The slow ramp was the most sensitive, showing a decrease in AUC of 29%. The present method was easily implemented and showed good reproducibility. It can potentially be used in basic experiments, drug and clinical studies as it provides a controllable thermal stimulus.     

Modelling the elastin, collagen and smooth muscle contribution to the duodenal mechanical behaviour in patients with systemic sclerosis

Abstract  Systemic sclerosis (SS) is a connective tissue disease that involves the gastrointestinal tract. Previous experiments have shown abnormal intestinal motility, dilatation, wall stiffening and impaired smooth muscle function. Consequently, understanding the association between intestinal wall mechanics, structure and function is important. The aim was to establish a model for differentiating the biomechanical remodelling of elastin, collagen and smooth muscle in the duodenum in SS patients. A duodenal distension protocol was used in six patients and five healthy controls. A theoretical model for evaluating the mechanical contributions of elastin, collagen and smooth muscle tone was established. The tension–strain curves computed from pressure and cross-sectional area data were analysed. The elastic modulus of elastin, the relationship between the collagen recruitment, collagen density and the active tension were calculated. The model fitted the clinical data well. The material constant for elastin in the patients was 30% lower than in the control group ( P  =   0.005). More collagen was recruited in patients than in healthy volunteers. Eighty percent of the collagen fibres were recruited at stretch ratio 0.85–2.26 (1.61 averaged) in patients and at the stretch ratio 2.55–3.73 (2.97 averaged) in healthy controls. The maximum active muscle tension and the corresponding strain were lowest in the patients ( P  =   0.01). The model can be used to determine the contribution of tissue components to the mechanical behaviour of duodenum. The stiffer wall in patient was due to the small stretch ratio for the maximum collagen recruitment but the muscle activity was also impaired.     

Geometric and mechanosensory properties of the sigmoid colon evaluated with magnetic resonance imaging

The aim of this study was to use magnetic resonance imaging (MRI) to evaluate the three-dimensional geometry and mechanosensory properties of the sigmoid colon. The sigmoid colon was stepwise distended by a water-filled bag in eight subjects. Simultaneous MRI, bag pressure recording and sensory assessment were performed before and after smooth muscle relaxation with butylscopolamine. The surface distributions of principal curvature radii, wall thickness, tension, stress and circumferential strain were calculated. The geometry of the distended sigmoid colon was complex and the spatial distributions of the biomechanical parameters were non-homogeneous. The circumferential length, strain, pressure and wall stress increased as a function of bag volume (all P < 0.001). In response to butylscopolamine, the pressure and wall stress were reduced (P < 0.05) and the stress-strain curves were shifted to the right. The sensory response was a linear function of the biomechanical parameters (all P < 0.001) and decreased in response to butylscopolamine as a function of volume (P = 0.02). The stimulus-response data indicate that the mechanosensitive afferents are affected by smooth muscle tone. The present study provides a method for characterizing the complex geometry and mechanical properties of the sigmoid colon, including the role of smooth muscle tone. This may be valuable in understanding of the biomechanical and mechanosensory functions in colonic diseases.     

Sensation and distribution of stress and deformation in the human oesophagus

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.     

A new method for evaluation of intestinal muscle contraction properties: studies in normal subjects and in patients with systemic sclerosis

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.