A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics

Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase; and ryanodine, a diterpenoid that modulates Ca2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca2+ dynamics. Cytosolic Ca2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental observations qualitatively, as well as quantitatively within a range of physiological parametric values. The model also illustrated how increased intercellular coupling led to smooth muscle coordination and the genesis of vascular tone

Analytical and numerical analyses of the micromechanics of soft fibrous connective tissues

State of the art research and treatment of biological tissues require accurate and efficient methods for describing their mechanical properties. Indeed, micromechanics motivated approaches provide a systematic method for elevating relevant data from the microscopic level to the macroscopic one. In this work the mechanical responses of hyperelastic tissues with one and two families of collagen fibers are analyzed by application of a new variational estimate accounting for their histology and the behaviors of their constituents. The resulting, close form expressions, are used to determine the overall response of the wall of a healthy human coronary artery. To demonstrate the accuracy of the proposed method these predictions are compared with corresponding 3-D finite element simulations of a periodic unit cell of the tissue with two families of fibers. Throughout, the analytical predictions for the highly nonlinear and anisotropic tissue are in agreement with the numerical simulations

Thermodynamically consistent orthotropic activation model capturing ventricular systolic wall thickening in cardiac electromechanics

The complex phenomena underlying mechanical contraction of cardiac cells and their influence in the dynamics of ventricular contraction are extremely important in understanding the overall function of the heart. In this paper we generalize previous contributions on the active strain formulation and propose a new model for the excitation-contraction coupling process. We derive an evolution equation for the active fiber contraction based on configurational forces, which is thermodynamically consistent. Geometrically, we link microscopic and macroscopic deformations giving rise to an orthotropic contraction mechanism that is able to represent physiologically correct thickening of the ventricular wall. A series of numerical tests highlights the importance of considering orthotropic mechanical activation in the heart and illustrates the main features of the proposed model

A transmurally heterogeneous orthotropic activation model for ventricular contraction and its numerical validation

Models for cardiac mechanics require an activation mechanism properly representing the stress-strain relations in the contracting myocardium. In this paper, we propose a new activation model that accounts for the transmural heterogeneities observed in myocardial strain measurements. In order to take the anisotropy of the active mechanics into account, our model is based on an active strain formulation. Thanks to multiplicative decomposition of the deformation gradient tensor, in this formulation, the active strains orthogonal to the fibers can be naturally described. We compare the results of our novel formulation against different anisotropic models of the active contraction of the cardiac muscle, as well as against experimental data available in the literature. We show that with the currently available models, the strain distributions are not in agreement with the reported experimental measurements. Conversely, we show that our new transmurally heterogeneous orthotropic activation model improves the accuracy of shear strains related to in-plane rotations and torsion

Toimintakäytäntöjen kehittäminen vapaaehtoistyöntekijöiden näkökulmasta

Toiminnallisen opinnäytetyön tarkoituksena oli kartoittaa keskustelun avulla Mikkelin kriisikeskuksessa vapaaehtoistyössä toimivien tukihenkilöiden näkemyksiä heitä itseään koskevista toimintakäytännöistä. Tukihenkilöiden ottamisella mukaan toimintakäytäntöjen suunnitteluun ja tukihenkilöiden kokoontumisilla tavoiteltiin toimintakäytäntöihin sitoutumisen ja yhteisöllisyyden tunteen vahvistumista. Mikkelin kriisikeskuksessa vapaaehtoiseen tukihenkilötyöhön osallistuu aktiivisesti lähes 30 koulutettua tukihenkilöä. He hoitavat Mikkelissä tehtävästä valtakunnallisesta kriisipuhelinpäivystyksestä lähes 70 %. Opinnäytetyön taustalla oli kriisityöntekijöiden huolehtiminen tukihenkilöiden hyvinvoinnista ja toive tukihenkilöiden osallistumisaktiivisuuden vahvistumisesta työnohjauksiin ja muihin yhteisiin kokoontu-misiin. Opinnäytetyö koostui kolmesta eri tilaisuudesta, joihin oli kutsuttu kaikki Mikkelin kriisikeskuksen vapaaehtoistyötä tekevät tukihenkilöt. Ensimmäisen tilaisuuden päätarkoituksena oli tukihenkilöiden yhdessäolo ja virkistäytyminen. Tilaisuus sisälsi myös koulutus- ja työnohjausosuuden. Kahdessa seuraavassa tilaisuudessa keskityttiin tukihenkilöiden kanssa keskustelemaan ryhmässä toimintakäytäntöjä koskevista mielipiteistä ja uusista ehdotuksista. Opinnäytetyöntekijä toimi tilaisuuksissa kaksoisroolissa ollen sekä tukihenkilö että tilaisuuden vetäjä. Kaikkiaan keskusteluun otti osaa seitsemän tukihenkilöä. Opinnäytetyön tuotoksena syntyi yhteenvetona kirjallista materiaalia, joka saatettiin tiedoksi kriisikeskuksen työntekijälle ja kaikille tukihenkilöille. Keskusteluryhmiin osallistumattomilla tukihenkilöillä oli mahdollisuus kommentoida keskustelua. Kirjallista yhteenvetoa hyödynnetään Mikkelin kriisikeskuksessa vapaaehtoiseen tukihenkilötoimintaan liittyvien käytäntöjen kehittämisessä. Opinnäytetyön aikana alkanutta tukihenkilöistä koostuvaa toimintaryhmätyöskentelyä tullaan myös jatkamaan tulevaisuudessa.This functional-based thesis aimed at surveying by conversation the point of views of volunteer support persons in Mikkelin kriisikeskus ( Mikkeli's crisis centre) of functional practices that concern themselves. The aim was to strengthen the engagement to the practices and the sense of community by taking the support persons into the planning of functional practices. There are almost 30 educated support persons in Mikkelin kriisikeskus that participate actively in volunteer work. They take care of nearly 70 % of the national crisis phone emergency duty that is done in Mikkeli. The background of the thesis was crisis workers´ consern about the support persons´ welfare and a hope of strengthening the support persons participation activity in supervision of work and other common conven-tions. The thesis consisted of three different occasions where were invited every support person who works voluntarily in Mikkelin kriisikeskus. The main purpose of the first occasion was the support persons´ association and refreshment. The occasion also included a training and a supervision of work part. In the next two occasions the aim was to discuss as a group with support persons´ the opinions of the functional practices and new suggestions. The author of the thesis acted in occasions in a double role, both as a support person and as the leader of the occasion. Overall there were seven support persons who took part in the conversation. As a result of the thesis came up written material in a summary that was informed to the employee of the crisis centre and to all of the support persons. Support persons that did not take part in the discussion groups had chance to comment the conversation. The written summary is utilized in Mikkelin kriisikeskus to develop practices associated with the action of volunteer support persons. The functional group working that consisted of support personnel and started during the thesis process is going to be continued in the future