Mechanical Interdependence Research Articles

The Stria Vascularis: Renewed Attention on a Key Player in Age-Related Hearing Loss.

Age-related hearing loss (HL), or presbycusis, is a complex and heterogeneous condition, affecting a significant portion of older adults and involving various interacting mechanisms. Metabolic presbycusis, a type of age-related HL, is characterized by the dysfunction of the stria vascularis, which is crucial for maintaining the endocochlear potential necessary for hearing. Although attention on metabolic presbycusis has waned in recent years, research continues to identify strial pathology as a key factor in age-related HL. This narrative review integrates past and recent research, bridging findings from animal models and human studies, to examine the contributions of the stria vascularis to age-related HL. It provides a brief overview of the structure and function of the stria vascularis and then examines mechanisms contributing to age-related strial dysfunction, including altered ion transport, changes in pigmentation, inflammatory responses, and vascular atrophy. Importantly, this review outlines the contribution of metabolic mechanisms to age-related HL, highlighting areas for future research. It emphasizes the complex interdependence of metabolic and sensorineural mechanisms in the pathology of age-related HL and highlights the importance of animal models in understanding the underlying mechanisms. The comprehensive and mechanistic investigation of all factors contributing to age-related HL, including cochlear metabolic dysfunction, remains crucial to identifying the underlying mechanisms and developing personalized, protective, and restorative treatments.

СТРАТЕГІЧНІ ПРІОРИТЕТИ УПРАВЛІННЯ ФОРМУВАННЯМ ІНВЕСТИЦІЙНОГО ПОТЕНЦІАЛУ РОЗВИТКУ ТЕРИТОРІАЛЬНИХ ГРОМАД НА ЗАСАДАХ АКТИВІЗАЦІЇ ПІДПРИЄМНИЦТВА

The assessment of the investment attractiveness of territorial communities allowed us to identify the main problems in attracting investments. The article highlights the problems of social, economic and investment potential, which involve the interdependence and interrelationship of many factors and mechanisms that are not purely material in nature, as they belong to culture, politics, institutions and society in general. The purpose of the study is to study the main strategic priorities of the formation of the investment potential of the socio-economic development of territorial communities in the conditions of martial law. In the research process, general scientific and special methods were used, in particular: system-structural analysis (when analyzing the directions of development of territorial communities and incredible villages); extrapolation (when substantiating the involvement of investment potential in the development of territorial communities for the future) and others. It has been proven that entrepreneurship plays an important role in the implementation of strategies for the formation of investment potential for socio-economic development of territorial communities. It is highlighted that the investment attractiveness of the territorial community should include: the existing economic potential, the network of settlements and the network of public services, as well as social and human capital, since this will allow to make the most of the opportunities that arise in the socio-economic environment, in particular, the direction that will lead to connected with the favorable economic situation in the country. An assessment of the institutional system for managing investment in the development of territorial communities of Ukraine was carried out, and in particular, the name of the territorial community, the purpose of the investment project, future benefits for the territorial community and the cost of the investment project were disclosed. It has been proven that the investment factors of the development of territorial communities allows business structures to have freedom in choosing strategic decisions, forming the effective implementation of the strategy in terms of investment and requires the use of appropriate management tools.

Decomposing the Mutual Information Rate of Heart Period and Respiration Variability Series to Assess Cardiorespiratory Interactions.

Heart rate variability results from the coupled activity of the cardiovascular and cardiorespiratory systems, which have their own internal regulation mechanisms but also interact with each other and with the autonomic nervous system to maintain homeostasis. In this work, the assessment of these physiological mechanisms is carried out decomposing the Mutual Information Rate (MIR), an information-theoretic measure of the interdependence between coupled processes, into terms of entropy rate or conditional mutual information related respectively to complexity and causality measures. These measures are computed using a non-parametric approach based on nearest-neighbors. The proposed framework is first tested on simulated autoregressive processes and then applied to experimental data consisting of heart period and respiratory time series measured in healthy subjects monitored at rest and during head-up tilt. Our results evidence that MIR decomposition is able to highlight the interdependence of short-term physiological mechanisms of cardiorespiratory interactions during postural stress.

Hybrid Governance in Online Drug Distribution

A growing share of illicit drug dealing occurs on online platforms. Technological innovations, such as encryption and anonymous payments, have enabled new and more complex ways of organizing transactions. This conceptual essay advances the study of online drug dealing by describing how governance mechanisms from markets, networks, and hierarchies are combined to reduce transactional uncertainty. Based on published research, I argue that cryptomarkets and social media drug distribution prioritize prices, trust, and rules differently, and that this can be understood as hybrid governance. In cryptomarkets, networked reputation scores are important, but their reliability is interdependent of administrators’ sanctioning capacity. Similarly, the open advertisement of prices and products relies on the ability to expose fraudulent vendors. On social media, buyers prioritize easy access and fast delivery and characteristics of market governance, while hierarchical rules are absent, and networked reputations play only a small role. Existing typologies of drug dealing organization do not capture these combinations of governance mechanisms. Hybrid governance and the interdependence of several governance mechanisms better capture the empirical reality of new and emerging modes in online drug distribution.

Modeling of a non-aqueous Li-O2 battery incorporating synergistic reaction mechanisms, microstructure, and species transport in the porous electrode

Li-O2 batteries are considered to be the next generation of new energy storage technology due to the extremely high theoretical energy density. The microstructure of the porous electrode takes an important role in the battery performance since the solid discharge product Li2O2 occupies the surface and void volume, increasing the transfer resistance. The product morphology and reaction mechanisms are affected by the electrode catalytic activity, electrolyte, and operating conditions. To systematically portray the microscopic processes in non-aqueous Li-O2 batteries, a model by coupling the above multiple factors is developed in this work. Unlike previous models where a single surface pathway or pore size distribution is considered alone, the present model focus on the interdependence of the reaction mechanisms and the electrode microstructure evolution, in which the reaction pathways are controlled by dynamic pore size. Moreover, the effective species transport relationship is modified, and the volume fraction and the corresponding active area of the products with different morphologies are calculated. The simulation results demonstrate the significant effects of microstructure on performance and explain the phenomenon of two discharge platforms, which comes from the tortuous variation of the electrode active area and are further influenced by current density and oxygen diffusion coefficient. This work is expected to guide the design of electrode structures and operating conditions for achieving improved performance.

Structural origins of cartilage shear mechanics.

Articular cartilage is a remarkable material able to sustain millions of loading cycles over decades of use outperforming any synthetic substitute. Crucially, how extracellular matrix constituents alter mechanical performance, particularly in shear, remains poorly understood. Here, we present experiments and theory in support of a rigidity percolation framework that quantitatively describes the structural origins of cartilage’s shear properties and how they arise from the mechanical interdependence of the collagen and aggrecan networks making up its extracellular matrix. This framework explains that near the cartilage surface, where the collagen network is sparse and close to the rigidity threshold, slight changes in either collagen or aggrecan concentrations, common in early stages of cartilage disease, create a marked weakening in modulus that can lead to tissue collapse. More broadly, this framework provides a map for understanding how changes in composition throughout the tissue alter its shear properties and ultimate in vivo function.

Right ventricular free wall contractility in subcostal views: A proof-of-concept study to assess right ventricular systolic function.

Normal right ventricular (RV) function has been traditionally assessed from the apical window. However, in several patients the subcostal window is the only available acoustic. Given the intricate functional and mechanical inter-dependence between longitudinal tricuspid annular (TA) displacement and RV free wall contractility (RVFW), we studied the utility of RVFW inward motion using both M-mode and velocity with tissue Doppler imaging (TDI) from the subcostal transthoracic view. If a TAPSE value ≥ 2cm is used to identify normal RV function, an RVFW M-mode value>.8cm, TA TDI s' velocity>.06cm/s and TA TDI e' velocity value>.05cm/s identify normal RV systolic function. Furthermore, ROC curve analysis for the RVFW M-mode showed an area under the curve (AUC) of .753 (95% CI: .604-.868) with a cut-off value>.8, sensitivity 75% and specificity 73%; for TA TDI s' AUC at .822 (95% CI: .681-.919) with a cut-off value>.06, sensitivity 75% and specificity 77% and for TA TDI e' the AUC was .771 (95% CI: .624-.882) with a cut-off value>.05, sensitivity 90% and specificity 46%. Reproducibility of repeat RVFW M-mode, TDI s' and e' measurements was good with strong inter-rater agreement (Kappa>.8). The subcostal window appears useful for assessing RV systolic function. Additional studies are now required to prospectively use these measures in the routine evaluation of RV systolic function particularly in patients with suboptimal apical windows.

Tricuspid Annular Systolic Velocity to Left Ventricular Outflow Velocity Time Integral Ratio: Proof of Concept Utility Analysis.

BackgroundThe tricuspid annular plane systolic excursion (TAPSE) / pulmonary artery systolic pressure (PASP) ratio has been a useful marker of right ventricular (RV)-pulmonary artery coupling. However, given the intricate functional and mechanical interdependence of the right and left ventricles, we believe this ratio would be less useful when assessing reduced left ventricular (LV) systolic function. Instead, we proposed using the tricuspid annular tissue Doppler imaging systolic velocity to LV outflow tract velocity time integral ratio (TA TDI s’ / LVOT VTI r) for this purpose. MethodsFor this proof-of-concept study, a retrospective analysis was conducted on 60 patients with complete echocardiographic studies while in sinus rhythm. The population was divided as follows; Group 1 included 20 individuals with normal left ventricular ejection fraction (LVEF) as well as normal RV and PASP. Group 2 was composed of 20 patients known to have been evaluated or treated for pulmonary hypertension, while group 3 was comprised of 20 patients treated for heart failure (HF). ResultsTAPSE/PASP ratios were no different from any of the studied groups. However, the proposed TA TDI s' /LVOT VTI r was statistically different among all three groups (Group 1: 0.6 ± 0.1*; Group 2: 0.5 ± 0.1°; and Group 3: 0.8 ± 0.3#; p < 0.001).ConclusionsBased on these results, there is now a need for additional prospective studies to explore the overall utility of using this TA TDI s' / LVOT VTI r in day-to-day routine assessments not only for diagnostic purposes but also to determine how this ratio correlates with symptoms and changes with therapy.

Roles of constitutive and signal-dependent protein phosphatase 2A docking motifs in burst attenuation of the cyclic AMP response element-binding protein

The cAMP response element-binding protein (CREB) is an important regulator of cell growth, metabolism, and synaptic plasticity. CREB is activated through phosphorylation of an evolutionarily conserved Ser residue (S133) within its intrinsically disordered kinase-inducible domain (KID). Phosphorylation of S133 in response to cAMP, Ca2+, and other stimuli triggers an association of the KID with the KID-interacting (KIX) domain of the CREB-binding protein (CBP), a histone acetyl transferase (HAT) that promotes transcriptional activation. Here we addressed the mechanisms of CREB attenuation following bursts in CREB phosphorylation. We show that phosphorylation of S133 is reversed by protein phosphatase 2A (PP2A), which is recruited to CREB through its B56 regulatory subunits. We found that a B56-binding site located at the carboxyl-terminal boundary of the KID (BS2) mediates high-affinity B56 binding, while a second binding site (BS1) located near the amino terminus of the KID mediates low affinity binding enhanced by phosphorylation of adjacent casein kinase (CK) phosphosites. Mutations that diminished B56 binding to BS2 elevated both basal and stimulus-induced phosphorylation of S133, increased CBP interaction with CREB, and potentiated the expression of CREB-dependent reporter genes. Cells from mice harboring a homozygous CrebE153D mutation that disrupts BS2 exhibited increased S133 phosphorylation stoichiometry and elevated transcriptional bursts to cAMP. These findings provide insights into substrate targeting by PP2A holoenzymes and establish a new mechanism of CREB attenuation that has implications for understanding CREB signaling in cell growth, metabolism, synaptic plasticity, and other physiologic contexts.

Gender differences and defensive coping behavior in patients with inflammatory bowel disorders

IntroductionInflammatory bowel disorders (IBD) are chronic diseases with severe course. In this regard, research aimed at identifying adaptive behavior styles potentially significant for individual resilience to disease-related stress is of particular importanceObjectivesThe study population included 45 patients with the inflammatory bowel disorders: 19 male, 26 female (mean age 36,0±4,8), whose clinical and experimental psychological characteristics were studied.MethodsThe following methods were used: ‘Life Style Index’ by R. Plutchik, Н. Kellerman, ‘Ways of Coping’ by R. Lazarus, S. Folkman.ResultsThe experimental psychological study revealed interdependence of psychological defense mechanisms and coping behaviors. Thus, in female patients, such psychological defense mechanisms as ‘denial r=-0,51’ and ‘compensation г=-0,43’ showed negative correlation with ‘planning problem-solving’ coping strategy and positive correlation with such coping strategies, as ‘escape - avoidance г=0,38’ and ‘confrontation г=0,32’ р&lt;0,05; in male patients, such psychological defense mechanisms as ‘regression г= -0,41;’ and ‘displacement г= -0,30’ demonstrated negative correlation with ‘planning problem-solving’ and ‘exercising self-control’, but positive correlation with such coping strategies, as ‘escape - avoidance г= 0,34’, ‘confrontation г= 0,40;’, р&lt;0,05. Maladaptive attitude towards disease correlated with avoidance reactions in both male and female patients, which is indicated by the central rank position in disease coping structure of ‘confrontation’ coping strategy М=69,3±0,1, along with insufficient utilization of ‘planning problem-solving’ coping strategy М=39.3± 0,1, р&lt; 0,001.ConclusionsThe identified manifestations of psychological maladaptation in both male and female inflammatory bowel disorder patients are moderately pronounced, but require psychotherapeutic correction

Interrelation of defense mechanisms and motivational orientations of corporate leaders at different stages of business development

This article is dedicated to examination of the degree of defense mechanisms and their interrelation with the motivational orientation of corporate leaders at different stages of business development. The subject of this research is the motivational orientations and defense mechanisms of corporate leaders at different stages of business development. The aim goal consists in studying the interdependence of defense mechanisms and motivational orientations of the leaders of companies founded less than 3 years ago (crisis state) and over 10 years (sustainable development). The article employs cross-sectional method based on the questionnaire &amp;ldquo;Life Style Index&amp;rdquo; (LSI) developed by R. Plutchik, H. Kellerman, and H. R. Conte; the method of diagnostics of socio-psychological attitudes of the individual in the motivational and consumer sphere developed by O. F. Potemkina. The analysis of the acquired results with determination of statistically significant interdependences of psychological indicators was carried out by means of the method of mathematical statistics. The novelty of this work consists in examination of the impact of motivational orientations of corporate leaders upon manifestation of their defense mechanisms during the crisis stages of business development in accordance with the theory of psychoanalysis. Such research is carried out for the first time. The practical importance of the results lies in the application of knowledge of psychoanalytic concepts for revealing the latent pathogenic factors in the company that affect personnel&amp;rsquo;s behavior. This would allow the corporate psychologists to choose effective recommendations for balancing such factors. The conclusion is made that the protective mechanisms of the business owner and corporate leadership are interrelated with their motivational orientations; the degree of defense mechanisms of leaders of newly established companies and long established companies differ. The author's special contribution to this research consists in interpretation of the results through the prism of psychoanalytic approach.

Post-exposure environment modulates long-term developmental ethanol effects on behavior, neuroanatomy, and cortical oscillations

Developmental exposure to ethanol has a wide range of anatomical, cellular, physiological and behavioral impacts that can last throughout life. In humans, this cluster of effects is termed fetal alcohol spectrum disorder and is highly prevalent in western cultures. The ultimate expression of the effects of developmental ethanol exposure however can be influenced by post-exposure experience. Here we examined the effects of developmental binge exposure to ethanol (postnatal day 7) in C57BL/6By mice on a specific cohort of inter-related long-term outcomes including contextual memory, hippocampal parvalbumin-expressing neuron density, frontal cortex oscillations related to sleep-wake cycling including delta oscillation amplitude and sleep spindle density, and home-cage behavioral activity. When assessed in adults that were raised in standard housing, all of these factors were altered by early ethanol exposure compared to saline controls except home-cage activity. However, exposure to an enriched environment and exercise from weaning to postnatal day 90 reversed most of these ethanol-induced impairments including memory, CA1 but not dentate gyrus PV+ cell density, delta oscillations and sleep spindles, and enhanced home-cage behavioral activity in Saline- but not EtOH-treated mice. The results are discussed in terms of the inter-dependence of diverse developmental ethanol outcomes and potential mechanisms of post-exposure experiences to regulate those outcomes.

Discriminant analysis in establishing the relationship of pathogenetic mechanisms of gestational complications in urogenital infection in pregnant women.

Discriminant analysis in establishing the relationship of pathogenetic mechanisms of gestational complications in urogenital infection in pregnant women.

Corporate governance and privatization in selected countries in transition

Research on improvements effectiveness of corporate governance mechanisms is a very complex research topic in the field of corporate governance, as well as strategic management. Different theoretical models and empirical results indicate the interdependence of corporate governance mechanisms and procedures within strategic decision-making. However, tradition and research to date indicate that a range of different approaches to corporate governance are evolving around the world. In practice, it is known that there is no single and always optimal choice of corporate governance model, as it depends on legal regulations, institutional frameworks and traditions of the country. However, all of them have in common that there is a high priority that works to increase the interest of shareholders in company, that the shareholders' funds can be used efficiently and wisely. Practice has shown that the regulatory and legal framework of most countries in transition did not have enough time to develop and adapt to the needs of privatization, which significantly affected its course and results. With progress in implementing reform processes, transition countries have constantly innovated privatization models. At the same time, each of them has developed a relatively specific model of property transformation, in accordance with the characteristics of the economy and the political situation. The importance of the privatization process in transition countries is reflected in increasing the efficiency of the economy, building the foundations for the introduction of a market economy and increasing government revenues. The main goal of the research, in this paper, is to analyze the results of the privatization process so far, emphasizing the advantages and disadvantages of this process, ie pointing out the positive experiences and key limitations with which countries in transition were faced during the implementation of the privatization process, which influenced the profiling of their business environment.

Full-Length Transcript-Based Proteogenomics of Rice Improves Its Genome and Proteome Annotation.

Rice (Oryza sativa) molecular breeding has gained considerable attention in recent years, but inaccurate genome annotation hampers its progress and functional studies of the rice genome. In this study, we applied single-molecule long-read RNA sequencing (lrRNA_seq)-based proteogenomics to reveal the complexity of the rice transcriptome and its coding abilities. Surprisingly, approximately 60% of loci identified by lrRNA_seq are associated with natural antisense transcripts (NATs). The high-density genomic arrangement of NAT genes suggests their potential roles in the multifaceted control of gene expression. In addition, a large number of fusion and intergenic transcripts have been observed. Furthermore, 906,456 transcript isoforms were identified, and 72.9% of the genes can generate splicing isoforms. A total of 706,075 posttranscriptional events were subsequently categorized into 10 subtypes, demonstrating the interdependence of posttranscriptional mechanisms that contribute to transcriptome diversity. Parallel short-read RNA sequencing indicated that lrRNA_seq has a superior capacity for the identification of longer transcripts. In addition, over 190,000 unique peptides belonging to 9,706 proteoforms/protein groups were identified, expanding the diversity of the rice proteome. Our findings indicate that the genome organization, transcriptome diversity, and coding potential of the rice transcriptome are far more complex than previously anticipated.

Interdependence of balance mechanisms during bipedal locomotion.

Our main interest is to identify how humans maintain upright while walking. Balance during standing and walking is different, primarily due to a gait cycle which the nervous system must contend with a variety of body configurations and frequent perturbations (i.e., heel-strike). We have identified three mechanisms that healthy young adults use to respond to a visually perceived fall to the side. The lateral ankle mechanism and the foot placement mechanism are used to shift the center of pressure in the direction of the perceived fall, and the center of mass away from the perceived fall. The push-off mechanism, a systematic change in ankle plantarflexion angle in the trailing leg, results in fine adjustments to medial-lateral balance near the end of double stance. The focus here is to understand how the three basic balance mechanisms are coordinated to produce an overall balance response. The results indicate that lateral ankle and foot placement mechanisms are inversely related. Larger lateral ankle responses lead to smaller foot placement changes. Correlations involving the push-off mechanism, while significant, were weak. However, the consistency of the correlations across stimulus conditions suggest the push-off mechanism has the role of small adjustments to medial-lateral movement near the end of the balance response. This verifies that a fundamental feature of human bipedal gait is a highly flexible balance system that recruits and coordinates multiple mechanisms to maintain upright balance during walking to accommodate extreme changes in body configuration and frequent perturbations.

Time varying causal network reconstruction of a mouse cell cycle

BackgroundBiochemical networks are often described through static or time-averaged measurements of the component macromolecules. Temporal variation in these components plays an important role in both describing the dynamical nature of the network as well as providing insights into causal mechanisms. Few methods exist, specifically for systems with many variables, for analyzing time series data to identify distinct temporal regimes and the corresponding time-varying causal networks and mechanisms.ResultsIn this study, we use well-constructed temporal transcriptional measurements in a mammalian cell during a cell cycle, to identify dynamical networks and mechanisms describing the cell cycle. The methods we have used and developed in part deal with Granger causality, Vector Autoregression, Estimation Stability with Cross Validation and a nonparametric change point detection algorithm that enable estimating temporally evolving directed networks that provide a comprehensive picture of the crosstalk among different molecular components. We applied our approach to RNA-seq time-course data spanning nearly two cell cycles from Mouse Embryonic Fibroblast (MEF) primary cells. The change-point detection algorithm is able to extract precise information on the duration and timing of cell cycle phases. Using Least Absolute Shrinkage and Selection Operator (LASSO) and Estimation Stability with Cross Validation (ES-CV), we were able to, without any prior biological knowledge, extract information on the phase-specific causal interaction of cell cycle genes, as well as temporal interdependencies of biological mechanisms through a complete cell cycle.ConclusionsThe temporal dependence of cellular components we provide in our model goes beyond what is known in the literature. Furthermore, our inference of dynamic interplay of multiple intracellular mechanisms and their temporal dependence on one another can be used to predict time-varying cellular responses, and provide insight on the design of precise experiments for modulating the regulation of the cell cycle.

ВОЗМОЖНОСТИ ИСПОЛЬЗОВАНИЯ ВЗАИМОСВЯЗИ СЕГМЕНТОВ ФИНАНСОВОГО РЫНКА В КАЧЕСТВЕ ИНДИКАТОРА УРОВНЯ РАЗВИТИЯ РЫНОЧНЫХ ОТНОШЕНИЙ

The article, based on the scientific approach, attempts to justify the interconnection and interdependence of pricing mechanisms in various financial market segments. The fact that the market relations are developed in economy it suggests to consider the degree of this interconnection as an indicator of the market relations development contributing to the economic growth.

Microscale to mesoscale analysis of parenchymal tethering: the effect of heterogeneous alveolar pressures on the pulmonary mechanics of compliant airways.

In the healthy lung, bronchi are tethered open by the surrounding parenchyma; for a uniform distribution of these peribronchial structures, the solution is well known. An open question remains regarding the effect of a distributed set of collapsed alveoli, as can occur in disease. Here, we address this question by developing and analyzing microscale finite-element models of systems of heterogeneously inflated alveoli to determine the range and extent of parenchymal tethering effects on a neighboring collapsible airway. This analysis demonstrates that micromechanical stresses extend over a range of ∼5 airway radii, and this behavior is dictated primarily by the fraction, not distribution, of collapsed alveoli in that region. A mesoscale analysis of the microscale data identifies an effective shear modulus, Geff, that accurately characterizes the parenchymal support as a function of the average transpulmonary pressure of the surrounding alveoli. We demonstrate the use of this formulation by analyzing a simple model of a single collapsible airway surrounded by heterogeneously inflated alveoli (a "pig-in-a-blanket" model), which quantitatively demonstrates the increased parenchymal compliance and reduction in airway caliber that occurs with decreased parenchymal support from hypoinflated obstructed alveoli. This study provides a building block from which models of an entire lung can be developed in a computationally tenable manner that would simulate heterogeneous pulmonary mechanical interdependence. Such multiscale models could provide fundamental insight toward the development of protective ventilation strategies to reduce the incidence or severity of ventilator-induced lung injury. NEW & NOTEWORTHY A destabilized lung leads to airway and alveolar collapse that can result in catastrophic pulmonary failure. This study elucidates the micromechanical effects of alveolar collapse and determines its range of influence on neighboring collapsible airways. A mesoscale analysis reveals a master relationship that can that can be used in a computationally efficient manner to quantitatively model alveolar mechanical heterogeneity that exists in acute respiratory distress syndrome (ARDS), which predisposes the lung to volutrauma and/or atelectrauma. This analysis may lead to computationally tenable simulations of heterogeneous organ-level mechanical interactions that can illuminate novel protective ventilation strategies to reduce ventilator-induced lung injury.

Investigating the Role of Interventricular Interdependence in Development of Right Heart Dysfunction During LVAD Support: A Patient-Specific Methods-Based Approach.

Predictive computation models offer the potential to uncover the mechanisms of treatments whose actions cannot be easily determined by experimental or imaging techniques. This is particularly relevant for investigating left ventricular mechanical assistance, a therapy for end-stage heart failure, which is increasingly used as more than just a bridge-to-transplant therapy. The high incidence of right ventricular failure following left ventricular assistance reflects an undesired consequence of treatment, which has been hypothesized to be related to the mechanical interdependence between the two ventricles. To investigate the implication of this interdependence specifically in the setting of left ventricular assistance device (LVAD) support, we introduce a patient-specific finite-element model of dilated chronic heart failure. The model geometry and material parameters were calibrated using patient-specific clinical data, producing a mechanical surrogate of the failing in vivo heart that models its dynamic strain and stress throughout the cardiac cycle. The model of the heart was coupled to lumped-parameter circulatory systems to simulate realistic ventricular loading conditions. Finally, the impact of ventricular assistance was investigated by incorporating a pump with pressure-flow characteristics of an LVAD (HeartMate II™ operating between 8 and 12 k RPM) in parallel to the left ventricle. This allowed us to investigate the mechanical impact of acute left ventricular assistance at multiple operating-speeds on right ventricular mechanics and septal wall motion. Our findings show that left ventricular assistance reduces myofiber stress in the left ventricle and, to a lesser extent, right ventricle free wall, while increasing leftward septal-shift with increased operating-speeds. These effects were achieved with secondary, potentially negative effects on the interventricular septum which showed that support from LVADs, introduces unnatural bending of the septum and with it, increased localized stress regions. Left ventricular assistance unloads the left ventricle significantly and shifts the right ventricular pressure-volume-loop toward larger volumes and higher pressures; a consequence of left-to-right ventricular interactions and a leftward septal shift. The methods and results described in the present study are a meaningful advancement of computational efforts to investigate heart-failure therapies in silico and illustrate the potential of computational models to aid understanding of complex mechanical and hemodynamic effects of new therapies.