A model of blood flow in the mesenteric arterial system

<p>Abstract</p> <p>Background</p> <p>There are some early clinical indicators of cardiac ischemia, most notably a change in a person's electrocardiogram. Less well understood, but potentially just as dangerous, is ischemia that develops in the gastrointestinal system. Such ischemia is difficult to diagnose without angiography (an invasive and time-consuming procedure) mainly due to the highly unspecific nature of the disease.</p> <p>Understanding how perfusion is affected during ischemic conditions can be a useful clinical tool which can help clinicians during the diagnosis process. As a first step towards this final goal, a computational model of the gastrointestinal system has been developed and used to simulate realistic blood flow during normal conditions.</p> <p>Methods</p> <p>An anatomically and biophysically based model of the major mesenteric arteries has been developed to be used to simulate normal blood flows. The computational mesh used for the simulations has been generated using data from the Visible Human project. The 3D Navier-Stokes equations that govern flow within this mesh have been simplified to an efficient 1D scheme. This scheme, together with a constitutive pressure-radius relationship, has been solved numerically for pressure, vessel radius and velocity for the entire mesenteric arterial network.</p> <p>Results</p> <p>The computational model developed shows close agreement with physiologically realistic geometries other researchers have recorded <it>in vivo</it>. Using this model as a framework, results were analyzed for the four distinct phases of the cardiac cycle – diastole, isovolumic contraction, ejection and isovolumic relaxation. Profiles showing the temporally varying pressure and velocity for a periodic input varying between 10.2 kPa (77 mmHg) and 14.6 kPa (110 mmHg) at the abdominal aorta are presented. An analytical solution has been developed to model blood flow in tapering vessels and when compared with the numerical solution, showed excellent agreement.</p> <p>Conclusion</p> <p>An anatomically and physiologically realistic computational model of the major mesenteric arteries has been developed for the gastrointestinal system. Using this model, blood flow has been simulated which show physiologically realistic flow profiles.</p

Effects of gastrointestinal tissue structure on computed dipole vectors

<p>Abstract</p> <p>Background</p> <p>Digestive diseases are difficult to assess without using invasive measurements. Non-invasive measurements of body surface electrical and magnetic activity resulting from underlying gastro-intestinal activity are not widely used, in large due to their difficulty in interpretation. Mathematical modelling of the underlying processes may help provide additional information. When modelling myoelectrical activity, it is common for the electrical field to be represented by equivalent dipole sources. The gastrointestinal system is comprised of alternating layers of smooth muscle (SM) cells and Interstitial Cells of Cajal (ICC). In addition the small intestine has regions of high curvature as the intestine bends back upon itself. To eventually use modelling diagnostically, we must improve our understanding of the effect that intestinal structure has on dipole vector behaviour.</p> <p>Methods</p> <p>Normal intestine electrical behaviour was simulated on simple geometries using a monodomain formulation. The myoelectrical fields were then represented by their dipole vectors and an examination on the effect of structure was undertaken. The 3D intestine model was compared to a more computationally efficient 1D representation to determine the differences on the resultant dipole vectors. In addition, the conductivity values and the thickness of the different muscle layers were varied in the 3D model and the effects on the dipole vectors were investigated.</p> <p>Results</p> <p>The dipole vector orientations were largely affected by the curvature and by a transmural gradient in the electrical wavefront caused by the different properties of the SM and ICC layers. This gradient caused the dipoles to be oriented at an angle to the principal direction of electrical propagation. This angle increased when the ratio of the longitudinal and circular muscle was increased or when the the conductivity along and across the layers was increased. The 1D model was able to represent the geometry of the small intestine and successfully captured the propagation of the slow wave down the length of the mesh, however, it was unable to represent transmural diffusion within each layer, meaning the equivalent dipole sources were missing a lateral component and a reduced magnitude when compared to the full 3D models.</p> <p>Conclusion</p> <p>The structure of the intestinal wall affected the potential gradient through the wall and the orientation and magnitude of the dipole vector. We have seen that the models with a symmetrical wall structure and extreme anisotropic conductivities had similar characteristics in their dipole magnitudes and orientations to the 1D model. If efficient 1D models are used instead of 3D models, then both the differences in magnitude and orientation need to be accounted for.</p

A physiologically based, multi-scale model of skeletal muscle structure and function

Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle’s response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modeling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle’s response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modeling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibers and their grouping. Together with a well-established model of motor-unit recruitment, the electro-physiological behavior of single muscle fibers within motor units is computed and linked to a continuummechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenization. The effect of homogenization has been investigated by varying the number of embedded skeletal muscle fibers and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the tibialis anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modeling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behavior ranging from motor-unit recruitment to force generation and fatigue

The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail

BACKGROUND: Gastrointestinal contractions are controlled by an underlying bioelectrical activity. High-resolution spatiotemporal electrical mapping has become an important advance for investigating gastrointestinal electrical behaviors in health and motility disorders. However, research progress has been constrained by the low efficiency of the data analysis tasks. This work introduces a new efficient software package: GEMS (Gastrointestinal Electrical Mapping Suite), for analyzing and visualizing high-resolution multi-electrode gastrointestinal mapping data in spatiotemporal detail. RESULTS: GEMS incorporates a number of new and previously validated automated analytical and visualization methods into a coherent framework coupled to an intuitive and user-friendly graphical user interface. GEMS is implemented using MATLAB®, which combines sophisticated mathematical operations and GUI compatibility. Recorded slow wave data can be filtered via a range of inbuilt techniques, efficiently analyzed via automated event-detection and cycle clustering algorithms, and high quality isochronal activation maps, velocity field maps, amplitude maps, frequency (time interval) maps and data animations can be rapidly generated. Normal and dysrhythmic activities can be analyzed, including initiation and conduction abnormalities. The software is distributed free to academics via a community user website and forum (http://sites.google.com/site/gimappingsuite). CONCLUSIONS: This software allows for the rapid analysis and generation of critical results from gastrointestinal high-resolution electrical mapping data, including quantitative analysis and graphical outputs for qualitative analysis. The software is designed to be used by non-experts in data and signal processing, and is intended to be used by clinical researchers as well as physiologists and bioengineers. The use and distribution of this software package will greatly accelerate efforts to improve the understanding of the causes and clinical consequences of gastrointestinal electrical disorders, through high-resolution electrical mapping

The nitric oxide response in plant-associated endosymbiotic bacteria

Nitric oxide (NO) is a gaseous signalling molecule which becomes very toxic due to its ability to react with multiple cellular targets in biological systems. Bacterial cells protect against NO through the expression of enzymes that detoxify this molecule by oxidizing it to nitrate or reducing it to nitrous oxide or ammonia. These enzymes are haemoglobins, c-type nitric oxide reductase, flavorubredoxins and the cytochrome c respiratory nitrite reductase. Expression of the genes encoding these enzymes is controlled by NO-sensitive regulatory proteins. The production of NO in rhizobia–legume symbiosis has been demonstrated recently. In functioning nodules, NO acts as a potent inhibitor of nitrogenase enzymes. These observations have led to the question of how rhizobia overcome the toxicity of NO. Several studies on the NO response have been undertaken in two non-dentrifying rhizobial species, Sinorhizobium meliloti and Rhizobium etli, and in a denitrifying species, Bradyrhizobium japonicum. In the present mini-review, current knowledge of the NO response in those legume-associated endosymbiotic bacteria is summarized

An integrated biochemical system for nitrate assimilation and nitric oxide detoxification in Bradyrhizobium japonicum

Rhizobia are recognized to establish N(2)-fixing symbiotic interactions with legume plants. Bradyrhizobium japonicum, the symbiont of soybeans, can denitrify and grow under free-living conditions with nitrate (NO(3)(−)) or nitrite (NO(2)(−)) as sole nitrogen source. Unlike related bacteria that assimilate NO(3)(−), genes encoding the assimilatory NO(3)(−) reductase (nasC) and NO(2)(−) reductase (nirA) in B. japonicum are located at distinct chromosomal loci. The nasC gene is located with genes encoding an ABC-type NO(3)(−) transporter, a major facilitator family NO(3)(−)/NO(2)(−) transporter (NarK), flavoprotein (Flp) and single-domain haemoglobin (termed Bjgb). However, nirA clusters with genes for a NO(3)(−)/NO(2)(−)-responsive regulator (NasS-NasT). In the present study, we demonstrate NasC and NirA are both key for NO(3)(−) assimilation and that growth with NO(3)(−), but not NO(2)(−) requires flp, implying Flp may function as electron donor to NasC. In addition, bjgb and flp encode a nitric oxide (NO) detoxification system that functions to mitigate cytotoxic NO formed as a by-product of NO(3)(−) assimilation. Additional experiments reveal NasT is required for NO(3)(−)-responsive expression of the narK-bjgb-flp-nasC transcriptional unit and the nirA gene and that NasS is also involved in the regulatory control of this novel bipartite assimilatory NO(3)(−)/NO(2)(−) reductase pathway

Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers

The effect of luminal content and rate of occlusion on the interpretation of colonic manometry

This is the accepted version of the following article: [Arkwright, J. W., Dickson, A., Maunder, S. A., Blenman, N. G., Lim, J., O’Grady, G., Archer, R., Costa, M., Spencer, N. J., Brookes, S., Pullan, A. and Dinning, P. G. (2013), The effect of luminal content and rate of occlusion on the interpretation of colonic manometry. Neurogastroenterology & Motility, 25: e52–e59.], which has been published in final form at [http://dx.doi.org/10.1111/nmo.12051]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery.Background Manometry is commonly used for diagnosis of esophageal and anorectal motility disorders. In the colon, manometry is a useful tool, but clinical application remains uncertain. This uncertainty is partly based on the belief that manometry cannot reliably detect non-occluding colonic contractions and, therefore, cannot identify reliable markers of dysmotility. This study tests the ability of manometry to record pressure signals in response to non-lumen-occluding changes in diameter, at different rates of wall movement and with content of different viscosities. Methods A numerical model was built to investigate pressure changes caused by localized, non-lumen-occluding reductions in diameter, similar to those caused by contraction of the gut wall. A mechanical model, consisting of a sealed pressure vessel which could produce localized reductions in luminal diameter, was used to validate the model using luminal segments formed from; (i) natural latex; and (ii) sections of rabbit proximal colon. Fluids with viscosities ranging from 1 to 6800 mPa s-1 and luminal contraction rates over the range 5-20 mmHg s-1 were studied. Key Results Manometry recorded non-occluding reductions in diameter, provided that they occurred with sufficiently viscous content. The measured signal was linearly dependent on the rate of reduction in luminal diameter and also increased with increasing viscosity of content (R2 = 0.62 and 0.96 for 880 and 1760 mPa s-1, respectively). Conclusions & Inferences Manometry reliably registers non-occluding contractions in the presence of viscous content, and is therefore a viable tool for measuring colonic motility. Interpretation of colonic manometric data, and definitions based on manometric results, must consider the viscosity of luminal content.Australian National Health & Medical Research Counci