PubMed Health⌕ Search

Biomedical subjects

Hans Gregersen

Publications and source records attributed to Hans Gregersen.

At least 55 records · Page 3Linked to original sources

Electrical stimulation to induce propulsive contractions in the porcine descending colon.

Electrical stimulation of the colon can improve transit in slow-transit constipation, or enable controlled emptying in colostomy patients. Preliminary studies showed that sequential stimulation of consecutive colon segments induced serial contractions resulting in colonic propulsion. This study was performed to optimize the stimulation parameters. The electrodes were inserted under the serosa of the descending colon of pigs. Charge-balanced rectangular pulses at 10 Hz were delivered in consecutive sessions. Electrically evoked contractions (ECs) were monitored using impedance planimetry and manometry. The luminal pressure and cross-sectional area (CSA), the latency and velocity of CSA decrease, and the wall tension were compared for ECs induced using 3 ms pulses of 9, 12, 15, and 30 mA. When using 15 mA, ECs induced by 0.03, 0.3, and 3 ms long pulses were compared. A current increase from 9 to 30 mA induced a significant increase in the pressure generated by contraction. The increase in pulse duration from 0.03 to 3 ms resulted in shorter latency, faster contraction, higher pressure, and higher wall tension. It is concluded that, at a frequency of 10 Hz, the best combination of current and pulse duration to elicit propulsive contractions in the descending colon of pigs is 15 mA and 3 ms.

Animals↗

Remodeling of strain energy function of common bile duct post obstruction.

Biliary duct obstruction is an important clinical condition that affects millions of people worldwide. We have previously shown that the common bile duct (CBD) undergoes significant growth and remodelling post obstruction. The mechanical stress-strain relation is expected to change due to growth and remodeling in response to obstruction and hence pressure-overload. The objective of the present study was to characterize the material properties of the CBD of the sham group and at 3 hours, 12 hours, 2 days, 8 days and 32 days (n=5 in each group) after obstruction. The Fung's exponential strain energy function was used to relate stress to strain of the normal and remodeled ducts. The Marquardt-Levenberg and genetic algorithm methods were used for the determination of material constants for the exponential strain energy function. The elastic constants obtained by the two methods did not differ (p>0.254). We obtained stable and convergent material constants at every time point. The material constant that dictates the nonlinear rate of change in the circumferential stress with respect to strain increased significantly after obstruction acutely in the first 12 hrs., decreased at 2 days and finally increased montonically during the remaining 30 days. The acute initial increase in stiffness was simply due to the elastic response. The chronic remodeling process results in an initial circumferential softening followed by stiffening of the CBD. This study has important clinical significance for patients with CBD obstruction and for endoscopists and surgeons who treat the condition.

Animals↗

A two-layered mechanical model of the rat esophagus. Experiment and theory.

BACKGROUND: The function of esophagus is to move food by peristaltic motion which is the result of the interaction of the tissue forces in the esophageal wall and the hydrodynamic forces in the food bolus. The structure of the esophagus is layered. In this paper, the esophagus is treated as a two-layered structure consisting of an inner collagen-rich submucosa layer and an outer muscle layer. We developed a model and experimental setup for determination of elastic moduli in the two layers in circumferential direction and related the measured elastic modulus of the intact esophagus to the elastic modulus computed from the elastic moduli of the two layers. METHODS: Inflation experiments were done at in vivo length and pressure-diameters relations were recorded for the rat esophagus. Furthermore, the zero-stress state was taken into consideration. RESULTS: The radius and the strain increased as function of pressure in the intact as well as in the individual layers of the esophagus. At pressures higher than 1.5 cmH2O the muscle layer had a larger radius and strain than the mucosa-submucosa layer. The strain for the intact esophagus and for the muscle layer was negative at low pressures indicating the presence of residual strains in the tissue. The stress-strain curve for the submucosa-mucosa layer was shifted to the left of the curves for the muscle layer and for the intact esophagus at strains higher than 0.3. The tangent modulus was highest in the submucosa-mucosa layer, indicating that the submucosa-mucosa has the highest stiffness. A good agreement was found between the measured elastic modulus of the intact esophagus and the elastic modulus computed from the elastic moduli of the two separated layers.

Animals↗

Morphologic and biomechanical changes of rat oesophagus in experimental diabetes.

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.

Animals↗

Tissue remodeling of rat pulmonary arteries in recovery from hypoxic hypertension.

The reversibility of tissue remodeling is of general interest to medicine. Pulmonary arterial tissue remodeling during hypertension induced by hypoxic breathing is well known, but little has been said about the recovery of the arterial wall when the blood pressure is lowered again. We hypothesize that tissue recovery is a function of the oxygen concentration, blood pressure, location on the vascular tree, and time. We measured the changes of blood pressure, vessel lumen, vessel wall thicknesses, and opening angle of each segment of the blood vessel at its zero-stress state after step changes of the oxygen concentration in the breathing gas. The zero-stress state of each vessel is emphasized because it is important to the analysis of stress and strain and in morphometry. Experimental results are presented as histories of tissue parameters after step changes of the oxygen level. Tissue characteristics are examined under the hypothesis that they are linearly related to changes in the local blood pressure. Under this linearity hypothesis, each aspect of the tissue change can be expressed as a convolution integral of the blood pressure history with a kernel called the indicial response function. It is shown the indicial response function for rising blood pressure is different from that for falling blood pressure. This difference represents a major nonlinearity of the tissue remodeling process of the blood vessels.

Animals↗

Mechanical properties of the porcine bile duct wall.

BACKGROUND AND AIM: The function of the common bile duct is to transport bile from the liver and the gall bladder to the duodenum. Since the bile duct is a distensible tube consisting mainly of connective tissue, it is important to obtain data on the passive mechanical wall properties. The aims of this study were to study morphometric and biomechanical wall properties during distension of the bile duct. METHODS: Ten normal porcine common bile ducts were examined in vitro. A computer-controlled volume ramp infusion system with concomitant pressure recordings was constructed. A video camera provided simultaneous measurement of outer dimensions of the common bile duct. Wall stresses and strains were computed. RESULTS: The common bile duct length increased by 25% from 24.4 +/- 1.8 mm at zero pressure to 30.5 +/- 2.0 mm at 5 kPa (p < 0.01). The diameter increased less than 10% in the same pressure range from 8.6 +/- 0.4 mm to 9.3 +/- 0.4 mm (p < 0.01). The stress-strain relations showed an exponential behavior with a good fit to the equation: sigma = alpha x (exp(betaepsilon) - 1). The circumferential stress-strain curve was shifted to the left when compared to the longitudinal stress-strain curve, i.e. the linear constants (alpha values) were different (p < 0.01) whereas the exponential constants (beta values) did not differ (p > 0.5). CONCLUSION: The porcine bile duct exhibited nonlinear anisotropic mechanical properties.

Animals↗

Measurement of coronary lumen area using an impedance catheter: finite element model and in vitro validation.

The measurement of coronary lumen cross-sectional area (CSA) is important for coronary physiology and cardiology. The general objective of this study is to develop an accurate and reproducible method to measure the lumen CSA of left anterior descending (LAD) artery using an impedance or conductance catheter. The conductance catheter technique is based on a cylindrical model of the chamber of interest. The first aim of this study was to validate the assumptions of the cylindrical model using a finite-element analysis (FEA) of the conductance catheter in the lumen of the vessel that takes into account the conductance of current through the vessel wall and surrounding tissue (parallel conductance, Gp). The FEA was used to determine the heterogeneity of potential and electrical fields and to optimize the design of the catheter relative to the diameter of the vessel. An optimum relationship between vessel and catheter diameter was obtained based on FEA. The second aim was to validate the in vitro CSA of LAD artery obtained from the conductance catheter method using A-mode ultrasound (US). The present study offers a novel approach to correct for the Gp that involves the injection of two solutions of NaCl (0.5% and 1.5%) with known conductivities directly into the lumen of the coronary artery in a porcine heart. In six hearts obtained from a slaughterhouse, we showed that the CSA and Gp can be determined analytically from two Ohm's law-type algebraic equations (cylindrical model) that account for the parallel conductance. The mean difference in diameter between the conductance catheter using the proposed two-injection method and U.S. was -0.02. The root mean square error for the impedance measurements was 2.8% of the mean US diameter. The future application of this technique to the in vivo condition is discussed.

Analysis of Variance↗

Quantitative analysis of collagen fiber angle in the submucosa of small intestine.

It is of interest to know how distension changes the angle and content of collagen in the submucosa of small intestine. We describe the application of a two-dimensional quantitative analysis technology to determine the angles between collagen fibers in the submucosa using digital image processing. A polarization microscope was used to obtain a series of animal intestinal slice images. The images were studied by analyzing the relationship between the pixel values of each of the polarized angles to obtain the collagen fiber angle. The statistical distribution of the angle as function of the degree of distension can be analyzed.

Animals↗

Two-layered quasi-3D finite element model of the oesophagus.

Analysis of oesophageal mechanoreceptor-dependent responses requires knowledge about the distribution of stresses and strains in the layers of the organ. A two-layered and a one-layered quasi-3D finite element model of the rat oesophagus were used for simulation. An exponential pseudo-strain energy density function was used as the constitutive equation in each model. Stress and strain distributions at the distension pressures 0.25 and 1.0 kPa were studied. The stress and strain distributions depended on the wall geometry. In the one-layered model, the stress ranged from -0.24 to 0.38 kPa at a pressure of 0.25 kPa and from -0.67 to 2.57 kPa at a pressure of 1.0 kPa. The stress in the two-layered model at the pressure of 0.25 and 1.0 kPa varied from -0.52 to 0.64 kPa and from -1.38 to 3.84 kPa. In the two-layered model, the stress was discontinuous at the interface between the muscle layer and the mucosa-submucosa layer. The maximum stress jump was 1.67 kPa at the pressure of 1.0 kPa. The present study provides a numerical simulation tool for characterising the mechanical behaviour of a multi-layered, complex geometry organ.

Animals↗

Cold and heat pain assessment of the human oesophagus after experimental sensitisation with acid.

The aim of the present study was to investigate the effect of thermal stimulation of the oesophagus before and after sensitisation with acid. In 17 healthy subjects a stimulation bag was used to re-circulate water at 5 and 60 degrees C for up to 90 s in the lower part of the oesophagus. The area under the temperature curve was used to assess the caloric load. The thermal stimuli were repeated after perfusion of the oesophagus with acid. The evoked pain intensity and referred pain areas (at the pain threshold) were assessed. At baseline the subjects were able to tolerate less caloric load (42%) for the heat compared to the cold stimuli (P = 0.007). The heat stimuli resulted in an increased referred pain area as compared with the cold stimuli (P = 0.03). Following acid perfusion there was a selective sensitisation to the heat pain stimuli as only 36% of the initial caloric load was tolerated (P = 0.012) whereas the sensation to the cold stimuli was unchanged. After acid perfusion, the referred pain area to the heat pain stimulation increased 49% (P = 0.04) but was not changed to cold stimulation (P = 0.82). After sensitisation the words used to describe the sensations to heat pain stimuli shifted from a warmth quality towards a more burning quality in most subjects. This multi-modal sensory testing study showed that acid sensitises the oesophagus to heat but not to cold pain. This may account for the modality-specific symptoms and hypersensitivity reported in patients suffering from, e.g. gastro-oesophageal reflux disease.

Acids↗

Differences between male and female responses to painful thermal and mechanical stimulation of the human esophagus.

It is uncertain to what degree sensation and pain relating to the gut are influenced by sex. The aim of the study was to explore sex differences to experimental multimodal stimulation of the esophagus in 22 age-matched males and females. A probe was positioned in the lower part of the esophagus. Mechanical stimuli were applied as distensions with a bag using an impedance planimetric method. The distensions were done before and after relaxation of the smooth muscle. Thermal stimulation was done with recirculating water at 1 and 60 degrees C in the bag. The sensory intensities were assessed during the stimulations, and the referred pain area was drawn at maximum pain intensities. An increased sensation to mechanical stimuli was found in the males for volume, pressure, and tension (P = 0.003, P = 0.02, P = 0.005), whereas cross-sectional area and strain showed no sex difference (P = 0.06, P = 0.9). Sex differences were not found for the cold and warmth stimulations (P = 0.6, P = 0.1). The mean size of the referred pain areas to the different stimuli was 23.6 cm2 in males and 48.7 cm2 in females (P = 0.002). As strain is believed to be the major determinant for the sensory response to mechanical stimulation of the gut, we conclude that no robust sex differences were observed in the assessments of the multimodal stimulations. However, the larger referred pain area in females reflects sex differences in central pain processing, which may explain the female preponderance in functional disorders relating to the gut.

Adult↗

Physiological growth is associated with esophageal morphometric and biomechanical changes in rats.

Esophageal geometry and biomechanical changes were studied during physiological growth in rats aged 1-32 weeks. Histological examination was done after the biomechanical study. The esophageal dimensions increased many-fold from 1-32 weeks, e.g. the weight per unit length increased six-fold and the wall cross-sectional area increased eight-fold. The inner and outer circumferential length of the mucosa and muscle, and the thickness and area of the layers increased as function of age. The opening angle was approximately 140 degrees at age 1 and 2 weeks and gradually decreased to approximately 80 degrees after 16 weeks. The circumferential and longitudinal stress-strain curves were exponential. The circumferential stress-strain curves shifted from left to the right up to 4 weeks of age (P < 0.001) where after no further change was observed, i.e. the esophagus became more compliant during the first 4 weeks of life. The longitudinal stress-strain curves shifted from left to the right up to 16 weeks of age (P < 0.001), i.e. the esophagus became more compliant longitudinally during the first 16 weeks of life. Bi-axial stress-strain analysis with determination of mechanical tissue constants showed that the esophagus was stiffer in the longitudinal direction than in the circumferential direction. In conclusion, a pronounced morphometric and biomechanical remodelling was observed in the rat esophagus during physiological growth. The observed changes likely reflect the development of the physiological function of the esophagus since for other tissues the function dictates the form of the tissue, and growth and remodelling depend on the mechanical loading.

Animals↗

Shear modulus of elasticity of the esophagus.

Experimental and diagnostic procedures like distension of a balloon catheter, bougie, and esophagogastroduodenoscopy can induce shear deformation in the esophageal wall. However, the shear modulus of the esophagus is yet unknown. The aim of this study was to determine the esophageal shear modulus and its dependence on the circumferential and longitudinal stresses and strains in the rat. The constitutive equation including the shear deformation based on a pseudo-strain-energy function was generated. Results were obtained using a new triaxial instrument to perform simultaneous torsion, inflation, and longitudinal stretching tests. The shear modulus varied with the inflation pressure and the longitudinal stretch ratio. The shear modulus at the longitudinal stretch ratio of 1.5 and between inflation pressures of 0 and 2.0 kPa ranged from 5.43 to 185.01 kPa. The mechanical constant of the esophagus showed that the esophageal wall was anisotropic with different stiffness in the circumferential, longitudinal, and the shear directions. The stiffness in the longitudinal direction was higher than in the circumferential direction (P < 0.001). This test can be extended for further mechanical remodeling experiments and for other tubular organs such as the small intestine or blood vessels.

Animals↗

Indicial response functions of growth and remodeling of common bile duct postobstruction.

Biliary duct obstruction is an important clinical condition that stems from cholelithiasis, the neoplasm in the wall or, most commonly, gallbladder stones. The objective of this study is to understand the structural and mechanical remodeling of the common bile duct (CBD) postobstruction. Porcine CBD was ligated near the duodenum that increased the duct's pressure from 6.4 to 18.3 cmH(2)O in the first 12 h and to 30.7 cmH(2)O after 32 days. The remodeling process was studied after 3 h, 12 h, 2 days, 8 days, and 32 days (n = 5 in each group) after obstruction. One additional animal in each group was sham operated. At each scheduled time, the time course of change of morphometry (diameter, length, wall thickness, etc.) and mechanical properties (stress, strain, etc.) was documented. It was found that the diameter increased by about threefold and the wall thickness of the CBD doubled in the 32-day group compared with the sham group (P < 0.001). The stress and strain increased initially with increase in pressure but recovered to near the control values by day 32 due to the structural and mechanical adaptations. Hence, the net effect of the structural and mechanical remodeling is to restore the stress and strain to their homeostatic values. Furthermore, the strain recovers more rapidly and more completely than stress. Finally, the remodeling data were expressed mathematically in terms of indicial response functions (IRF), i.e., change of a particular feature of a CBD in response to a unit step change of the pressure. The IRF approach provides a quantitative description of the remodeling process in the CBD.

Algorithms↗

In vitro evaluation of ultrasound Doppler strain rate imaging: modification for measurement in a slowly moving tissue phantom.

Doppler strain rate imaging (SRI) was evaluated in vitro using a silicone strip phantom mimicking slowly moving tissue. A test apparatus was developed that enabled controlled strain experiments with variable strain and strain rate to be performed. SRI strain was measured at eight different calculated strains (range 5.7 to 63.4 %) at three different pump speeds with tissue velocity 0.1, 0.5 and 1.0 mm/s. The effect of varying tissue velocity and strain sample size on the measured SRI strain was elaborated. SRI strains agreed well with calculated values for strain when SRI strain was measured as the average over the whole strip cross-section and the strain sample size was 1.9 mm (mean difference = 2.78%, limits of agreement +/- 9.97% for tissue velocity 1.0 mm/s, n = 8). The variance was substantial if single central samples were used, especially for strain sample size of 0.8 mm (mean difference = -7.47%, limits of agreement +/- 20.90 for tissue velocity 0.5 mm/s, n = 24). Increasing the strain sample size to 1.9 mm removed some of the underestimation (giving mean difference of -4.46%, n = 24). We found low intra- and interobserver variation. This study indicates that, for the SRI method to give accurate estimates of strain, strain sample size should be in the region of 2 mm. Averaging over several ultrasound (US) beams increased the accuracy further.

Elasticity↗

Pain and biomechanical responses to distention of the duodenum in patients with systemic sclerosis.

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.

Adult↗

Gut pain and hyperalgesia induced by capsaicin: a human experimental model.

Human experimental visceral pain models using chemical stimulation are needed for the study of visceral hyperexcitability. Our aim was to stimulate the human gut with chemical activators (capsaicin, glycerol) and measure quantitatively the induced hyperexcitability to painful mechanical gut distension. Ten otherwise healthy subjects with an ileostoma participated. Increasing volumes of capsaicin 50 microg/ml (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, and 3 ml), glycerol (2.5, 5, and 10 ml) or saline (2.5, 5, and 10 ml) intermingled with sham stimuli were randomly applied to the ileum via the stomal opening at three occasions separated by a week. After each application, pain intensity, qualities, and referred pain area were assessed together with the pain threshold to distension of the proximal gut. 'Boring' and 'hot' pain were evoked in all subjects by low doses (median 0.5 ml) of capsaicin. The median pain onset, peak pain, and pain duration were 55, 85, and 420 s, respectively. Referred somatic pain developed around the stomal opening with a correlation between the pain area and pain intensity. After application of capsaicin, significant hyperalgesia was found to distension of the gut (a 28% reduction pressure in pain threshold). No significant manifestations were found after application of glycerol and saline. Application of capsaicin to the human ileum induces pain and mechanical hyperalgesia. Specific activation of nociceptors in the gut mucosa provides new possibilities to study clinical relevant visceral pain mechanisms.

Adult↗