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Sample records for cardiovascular system model

  1. Computer model of cardiovascular control system responses to exercise

    NASA Technical Reports Server (NTRS)

    Croston, R. C.; Rummel, J. A.; Kay, F. J.

    1973-01-01

    Approaches of systems analysis and mathematical modeling together with computer simulation techniques are applied to the cardiovascular system in order to simulate dynamic responses of the system to a range of exercise work loads. A block diagram of the circulatory model is presented, taking into account arterial segments, venous segments, arterio-venous circulation branches, and the heart. A cardiovascular control system model is also discussed together with model test results.

  2. Artificial neural networks to model and diagnose cardiovascular systems

    SciTech Connect

    Kangas, L.J.; Keller, P.E.; Allen, P.A.

    1995-12-31

    In this paper, a novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and. the actual variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  3. A novel approach to modeling and diagnosing the cardiovascular system

    SciTech Connect

    Keller, P.E.; Kangas, L.J.; Hashem, S.; Kouzes, R.T.; Allen, P.A.

    1995-07-01

    A novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  4. Haemodynamic modeling of the cardiovascular system using mock circulation loops to test cardiovascular devices.

    PubMed

    Timms, Daniel L; Gregory, Shaun D; Stevens, Michael C; Fraser, John F

    2011-01-01

    Comprehensive testing and evaluation of cardiovascular device function and performance is required prior to clinical implementation. Initial proof of concept investigations are conducted within in-vitro mock circulation loops, before proof of principle is demonstrated via in-vivo animal testing. To facilitate the rapid transition of cardiovascular devices through this development period, a testing apparatus was developed that closely models the natural human cardiovascular system haemodynamics. This mock circulation system accurately replicates cardiac function, coupled to systemic and pulmonary circulations. The physiological response produced by a number of clinical cardiovascular conditions can be actively controlled by variable parameters such as vascular resistance, arterial/venous compliance, ventricle contractility, heart rate, and heart /vascular volumes, while anatomical variations such as valve regurgitation and septal defects can be included. Auto-regulation of these parameters was attempted to reproduce the Frank-Starling mechanism, baroreceptor reflex, skeletal muscle pump, and postural changes. Steady state validation of loop performance was achieved by replicating the progression of a patient's clinical haemodynamics from heart failure, through VAD support, to heart transplantation. The system has been used to evaluate pulsatile and non-pulsatile ventricular assist devices, counter pulsation devices, non-invasive cardiac output monitors and cardiovascular stents. The interaction of these devices with the cardiovascular system was also investigated with regards to physiological control strategies and cannula placement. The system is a valuable tool for the accelerated progression of cardiovascular device development.

  5. A Computer Model of the Cardiovascular System for Effective Learning.

    ERIC Educational Resources Information Center

    Rothe, Carl F.

    1980-01-01

    Presents a model of the cardiovascular system which solves a set of interacting, possibly nonlinear, differential equations. Figures present a schematic diagram of the model and printouts that simulate normal conditions, exercise, hemorrhage, reduced contractility. The nine interacting equations used to describe the system are described in the…

  6. A Computer Model of the Cardiovascular System for Effective Learning.

    ERIC Educational Resources Information Center

    Rothe, Carl F.

    1979-01-01

    Described is a physiological model which solves a set of interacting, possibly nonlinear, differential equations through numerical integration on a digital computer. Sample printouts are supplied and explained for effects on the components of a cardiovascular system when exercise, hemorrhage, and cardiac failure occur. (CS)

  7. Multi-scale modeling of hemodynamics in the cardiovascular system

    NASA Astrophysics Data System (ADS)

    Liu, Hao; Liang, Fuyou; Wong, Jasmin; Fujiwara, Takashi; Ye, Wenjing; Tsubota, Ken-iti; Sugawara, Michiko

    2015-08-01

    The human cardiovascular system is a closed-loop and complex vascular network with multi-scaled heterogeneous hemodynamic phenomena. Here, we give a selective review of recent progress in macro-hemodynamic modeling, with a focus on geometrical multi-scale modeling of the vascular network, micro-hemodynamic modeling of microcirculation, as well as blood cellular, subcellular, endothelial biomechanics, and their interaction with arterial vessel mechanics. We describe in detail the methodology of hemodynamic modeling and its potential applications in cardiovascular research and clinical practice. In addition, we present major topics for future study: recent progress of patient-specific hemodynamic modeling in clinical applications, micro-hemodynamic modeling in capillaries and blood cells, and the importance and potential of the multi-scale hemodynamic modeling.

  8. Isolated heart models: cardiovascular system studies and technological advances.

    PubMed

    Olejnickova, Veronika; Novakova, Marie; Provaznik, Ivo

    2015-07-01

    Isolated heart model is a relevant tool for cardiovascular system studies. It represents a highly reproducible model for studying broad spectrum of biochemical, physiological, morphological, and pharmaceutical parameters, including analysis of intrinsic heart mechanics, metabolism, and coronary vascular response. Results obtained in this model are under no influence of other organ systems, plasma concentration of hormones or ions and influence of autonomic nervous system. The review describes various isolated heart models, the modes of heart perfusion, and advantages and limitations of various experimental setups. It reports the improvements of perfusion setup according to Langendorff introduced by the authors.

  9. A forward model-based validation of cardiovascular system identification

    NASA Technical Reports Server (NTRS)

    Mukkamala, R.; Cohen, R. J.

    2001-01-01

    We present a theoretical evaluation of a cardiovascular system identification method that we previously developed for the analysis of beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure, and instantaneous lung volume. The method provides a dynamical characterization of the important autonomic and mechanical mechanisms responsible for coupling the fluctuations (inverse modeling). To carry out the evaluation, we developed a computational model of the cardiovascular system capable of generating realistic beat-to-beat variability (forward modeling). We applied the method to data generated from the forward model and compared the resulting estimated dynamics with the actual dynamics of the forward model, which were either precisely known or easily determined. We found that the estimated dynamics corresponded to the actual dynamics and that this correspondence was robust to forward model uncertainty. We also demonstrated the sensitivity of the method in detecting small changes in parameters characterizing autonomic function in the forward model. These results provide confidence in the performance of the cardiovascular system identification method when applied to experimental data.

  10. Pharmacodynamic effects in the cardiovascular system: the modeller's view.

    PubMed

    Fink, Martin; Noble, Denis

    2010-03-01

    Cardiovascular disease, and the cardiovascular side effects of drugs, are essentially multifactorial problems involving interactions between many proteins, dependent on highly organized cell, tissue and organ structures. This is one reason why the side effects of drugs are often unanticipated. It is impossible to unravel such problems without using a systems approach, i.e. focussing on processes, not just molecular components. This inevitably involves modelling as the interactions require quantitative analysis. Modelling is a tool of analysis aimed at understanding, first, and predicting, eventually. We illustrate these principles using modelling of the heart. Models of the cardiac myocyte have benefited from several decades of interaction between experimentation and simulation. They are now sufficiently detailed to have been of use in the development of new drug compounds like ranolazine and ivabradine. With the help of cardiac modelling, we have also been able to unravel the mechanisms underlying the beneficial effect of sodium calcium exchange block for long QT syndrome (LQTS) 2 and LQTS3 patients. Detailed models of the interaction between ion channels and blocking agents provide the basis for modelling drug action from basic principles and predict changes in the inhomogeneous tissue of the heart. We demonstrate that mathematical models are beneficial for unravelling the complex interactions of pharmacodynamics in the heart. Embedding these detailed biophysical cellular scale models into anatomically correct models of the ventricle geometry will enable reconstructions of Torsades de Pointes arrhythmias and of fibrillation, providing a mechanism for linking detailed cellular scale experimental data to clinical applications.

  11. Patient-specific modeling of human cardiovascular system elements

    NASA Astrophysics Data System (ADS)

    Kossovich, Leonid Yu.; Kirillova, Irina V.; Golyadkina, Anastasiya A.; Polienko, Asel V.; Chelnokova, Natalia O.; Ivanov, Dmitriy V.; Murylev, Vladimir V.

    2016-03-01

    Object of study: The research is aimed at development of personalized medical treatment. Algorithm was developed for patient-specific surgical interventions of the cardiovascular system pathologies. Methods: Geometrical models of the biological objects and initial and boundary conditions were realized by medical diagnostic data of the specific patient. Mechanical and histomorphological parameters were obtained with the help mechanical experiments on universal testing machine. Computer modeling of the studied processes was conducted with the help of the finite element method. Results: Results of the numerical simulation allowed evaluating the physiological processes in the studied object in normal state, in presence of different pathologies and after different types of surgical procedures.

  12. Mathematical modelling of flow distribution in the human cardiovascular system

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1992-01-01

    The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite-element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes.

  13. Reintrepreting the cardiovascular system as a mechanical model

    NASA Astrophysics Data System (ADS)

    Lemos, Diogo; Machado, José; Minas, Graça; Soares, Filomena; Barros, Carla; Leão, Celina Pinto

    2013-10-01

    The simulation of the different physiological systems is very useful as a pedagogical tool, allowing a better understanding of the mechanisms and the functions of the processes. The observation of the physiological phenomena through mechanical simulators represents a great asset. Furthermore, the development of these simulators allows reinterpreting physiological systems, with the advantage of using the same transducers and sensors that are commonly used in diagnostic and therapeutic cardiovascular procedures for the monitoring of system' parameters. The cardiovascular system is one of the most important systems of the human body and has been the target of several biomedical studies. The present work describes a mechanical simulation of the cardiovascular system, in particularly, the systemic circulation, which can be described in terms of its hemodynamic variables. From the mechanical process and parameters, physiological system's behavior was reproduced, as accurately as possible.

  14. Mathematical modelling and electrical analog equivalent of the human cardiovascular system.

    PubMed

    Abdolrazaghi, Mona; Navidbakhsh, Mahdi; Hassani, Kamran

    2010-06-01

    The objective of this study is to develop a model of the cardiovascular system capable of simulating the normal operation of the systemic and pulmonary circulation, starts from aorta, and follows by upper and lower extremities vessels, finally ends with pulmonary veins. The model consists of a closed loop lumped elements with 43 compartments representing the cardiovascular system. The model parameters have been extracted from the literature. Using MATLAB software, the mathematical model has been simulated for the cardiovascular system. Each compartment includes a Resistor-Inductor-Capacitor (RLC) segment. The normal cardiovascular operation is characterised by the pressure-volume curves in different parts of the system. Model verification is performed by comparing the simulation results with the clinical observation reported in the literature. The described model is a useful tool in studying the physiology of cardiovascular system, and the related diseases. Also, it could be a great tool to investigate the effects of the pathologies of the cardiovascular system.

  15. Cardiovascular modeling and diagnostics

    SciTech Connect

    Kangas, L.J.; Keller, P.E.; Hashem, S.; Kouzes, R.T.

    1995-12-31

    In this paper, a novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  16. Mathematical modeling of human cardiovascular system for simulation of orthostatic response

    NASA Technical Reports Server (NTRS)

    Melchior, F. M.; Srinivasan, R. S.; Charles, J. B.

    1992-01-01

    This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

  17. Mathematical modeling of human cardiovascular system for simulation of orthostatic response.

    PubMed

    Melchior, F M; Srinivasan, R S; Charles, J B

    1992-06-01

    This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system. PMID:1621848

  18. Space physiology IV: mathematical modeling of the cardiovascular system in space exploration.

    PubMed

    Keith Sharp, M; Batzel, Jerry Joseph; Montani, Jean-Pierre

    2013-08-01

    Mathematical modeling represents an important tool for analyzing cardiovascular function during spaceflight. This review describes how modeling of the cardiovascular system can contribute to space life science research and illustrates this process via modeling efforts to study postflight orthostatic intolerance (POI), a key issue for spaceflight. Examining this application also provides a context for considering broader applications of modeling techniques to the challenges of bioastronautics. POI, which affects a large fraction of astronauts in stand tests upon return to Earth, presents as dizziness, fainting and other symptoms, which can diminish crew performance and cause safety hazards. POI on the Moon or Mars could be more critical. In the field of bioastronautics, POI has been the dominant application of cardiovascular modeling for more than a decade, and a number of mechanisms for POI have been investigated. Modeling approaches include computational models with a range of incorporated factors and hemodynamic sophistication, and also physical models tested in parabolic and orbital flight. Mathematical methods such as parameter sensitivity analysis can help identify key system mechanisms. In the case of POI, this could lead to more effective countermeasures. Validation is a persistent issue in modeling efforts, and key considerations and needs for experimental data to synergistically improve understanding of cardiovascular responses are outlined. Future directions in cardiovascular modeling include subject-specific assessment of system status, as well as research on integrated physiological responses, leading, for instance, to assessment of subject-specific susceptibility to POI or effects of cardiovascular alterations on muscular, vision and cognitive function.

  19. HeMoLab--Hemodynamics Modelling Laboratory: an application for modelling the human cardiovascular system.

    PubMed

    Larrabide, I; Blanco, P J; Urquiza, S A; Dari, E A; Vénere, M J; de Souza e Silva, N A; Feijóo, R A

    2012-10-01

    In this work we present HeMoLab (Hemodynamics Modeling Laboratory), a computational environment for modeling the Human Cardiovascular System. Its integrates novel computational tools, running from medical image processing to numerical simulation and visualization. As a simulation tool, it allows to accommodate complex physiological and/or pathophysiological (virtual) scenarios aimed to retrieve detailed information from the numerical computations. Such application makes possible to speed up research in the study and analysis of the cardiovascular system and, to provide a virtual laboratory for medical training and education, and specialized Human Resources development. In order to demonstrate the modeling and simulation capabilities of HeMoLab some cases of use are presented.

  20. Chronic stress impacts the cardiovascular system: animal models and clinical outcomes.

    PubMed

    Golbidi, Saeid; Frisbee, Jefferson C; Laher, Ismail

    2015-06-15

    Psychological stresses are associated with cardiovascular diseases to the extent that cardiovascular diseases are among the most important group of psychosomatic diseases. The longstanding association between stress and cardiovascular disease exists despite a large ambiguity about the underlying mechanisms. An array of possibilities have been proposed including overactivity of the autonomic nervous system and humoral changes, which then converge on endothelial dysfunction that initiates unwanted cardiovascular consequences. We review some of the features of the two most important stress-activated systems, i.e., the humoral and nervous systems, and focus on alterations in endothelial function that could ensue as a result of these changes. Cardiac and hematologic consequences of stress are also addressed briefly. It is likely that activation of the inflammatory cascade in association with oxidative imbalance represents key pathophysiological components of stress-induced cardiovascular changes. We also review some of the commonly used animal models of stress and discuss the cardiovascular outcomes reported in these models of stress. The unique ability of animals for adaptation under stressful conditions lessens the extrapolation of laboratory findings to conditions of human stress. An animal model of unpredictable chronic stress, which applies various stress modules in a random fashion, might be a useful solution to this predicament. The use of stress markers as indicators of stress intensity is also discussed in various models of animal stress and in clinical studies.

  1. A cardiovascular system model for lower-body negative pressure response

    NASA Technical Reports Server (NTRS)

    Mitchell, B. A., Jr.; Giese, R. P.

    1971-01-01

    Mathematical models used to study complex physiological control systems are discussed. Efforts were made to modify a model of the cardiovascular system for use in studying lower body negative pressure. A computer program was written which allows orderly, straightforward expansion to include exercise, metabolism (thermal stress), respiration, and other body functions.

  2. Study report on guidelines and test procedures for investigating stability of nonlinear cardiovascular control system models

    NASA Technical Reports Server (NTRS)

    Fitzjerrell, D. G.

    1974-01-01

    A general study of the stability of nonlinear as compared to linear control systems is presented. The analysis is general and, therefore, applies to other types of nonlinear biological control systems as well as the cardiovascular control system models. Both inherent and numerical stability are discussed for corresponding analytical and graphic methods and numerical methods.

  3. Mathematical modelling of the human cardiovascular system in the presence of stenosis

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1993-01-01

    This paper reports a theoretical study on the distribution of blood flow in the human cardiovascular system when one or more blood vessels are affected by stenosis. The analysis employs a mathematical model of the entire system based on the finite element method. The arterial-venous network is represented by a large number of interconnected segments in the model. Values for the model parameters are based upon the published data on the physiological and rheological properties of blood. Computational results show how blood flow through various parts of the cardiovascular system is affected by stenosis in different blood vessels. No significant changes in the flow parameters of the cardiovascular system were found to occur when the reduction in the lumen diameter of the stenosed vessels was less than 65%.

  4. Review of Zero-D and 1-D Models of Blood Flow in the Cardiovascular System

    PubMed Central

    2011-01-01

    Background Zero-dimensional (lumped parameter) and one dimensional models, based on simplified representations of the components of the cardiovascular system, can contribute strongly to our understanding of circulatory physiology. Zero-D models provide a concise way to evaluate the haemodynamic interactions among the cardiovascular organs, whilst one-D (distributed parameter) models add the facility to represent efficiently the effects of pulse wave transmission in the arterial network at greatly reduced computational expense compared to higher dimensional computational fluid dynamics studies. There is extensive literature on both types of models. Method and Results The purpose of this review article is to summarise published 0D and 1D models of the cardiovascular system, to explore their limitations and range of application, and to provide an indication of the physiological phenomena that can be included in these representations. The review on 0D models collects together in one place a description of the range of models that have been used to describe the various characteristics of cardiovascular response, together with the factors that influence it. Such models generally feature the major components of the system, such as the heart, the heart valves and the vasculature. The models are categorised in terms of the features of the system that they are able to represent, their complexity and range of application: representations of effects including pressure-dependent vessel properties, interaction between the heart chambers, neuro-regulation and auto-regulation are explored. The examination on 1D models covers various methods for the assembly, discretisation and solution of the governing equations, in conjunction with a report of the definition and treatment of boundary conditions. Increasingly, 0D and 1D models are used in multi-scale models, in which their primary role is to provide boundary conditions for sophisticate, and often patient-specific, 2D and 3D models

  5. Adaptive life simulator: A novel approach to modeling the cardiovascular system

    SciTech Connect

    Kangas, L.J.; Keller, P.E.; Hashem, S.

    1995-06-01

    In this paper, an adaptive life simulator (ALS) is introduced. The ALS models a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. These models are developed for use in applications that require simulations of cardiovascular systems, such as medical mannequins, and in medical diagnostic systems. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the actual variables of an individual can subsequently be used for diagnosis. This approach also exploits sensor fusion applied to biomedical sensors. Sensor fusion optimizes the utilization of the sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  6. Flow and pressure regulation in the cardiovascular system. [engineering systems model

    NASA Technical Reports Server (NTRS)

    Iberall, A.

    1974-01-01

    Principles and descriptive fragments which may contribute to a model of the regulating chains in the cardiovascular system are presented. Attention is given to the strain sensitivity of blood vessels, the law of the autonomy of the heart beat oscillator, the law of the encapsulation of body fluids, the law of the conservation of protein, the law of minimum 'arterial' pressure, the design of the 'mammalian' kidney, questions of homeokinetic organization, and the development of self-regulatory chains. Details concerning the development program for the heart muscle are considered along with the speed of response of the breathing rate and the significance of the pulmonary vascular pressure-flow characteristics.

  7. Modeling the cardiovascular system using a nonlinear additive autoregressive model with exogenous input

    NASA Astrophysics Data System (ADS)

    Riedl, M.; Suhrbier, A.; Malberg, H.; Penzel, T.; Bretthauer, G.; Kurths, J.; Wessel, N.

    2008-07-01

    The parameters of heart rate variability and blood pressure variability have proved to be useful analytical tools in cardiovascular physics and medicine. Model-based analysis of these variabilities additionally leads to new prognostic information about mechanisms behind regulations in the cardiovascular system. In this paper, we analyze the complex interaction between heart rate, systolic blood pressure, and respiration by nonparametric fitted nonlinear additive autoregressive models with external inputs. Therefore, we consider measurements of healthy persons and patients suffering from obstructive sleep apnea syndrome (OSAS), with and without hypertension. It is shown that the proposed nonlinear models are capable of describing short-term fluctuations in heart rate as well as systolic blood pressure significantly better than similar linear ones, which confirms the assumption of nonlinear controlled heart rate and blood pressure. Furthermore, the comparison of the nonlinear and linear approaches reveals that the heart rate and blood pressure variability in healthy subjects is caused by a higher level of noise as well as nonlinearity than in patients suffering from OSAS. The residue analysis points at a further source of heart rate and blood pressure variability in healthy subjects, in addition to heart rate, systolic blood pressure, and respiration. Comparison of the nonlinear models within and among the different groups of subjects suggests the ability to discriminate the cohorts that could lead to a stratification of hypertension risk in OSAS patients.

  8. Phase and frequency locking in the model of cardiovascular system baroreflectory regulation

    NASA Astrophysics Data System (ADS)

    Ishbulatov, Yurii M.; Karavaev, Anatoly S.; Kiselev, Anton R.; Ponomarenko, Vladimir I.; Prokhorov, Mikhail D.

    2016-04-01

    We proposed the model of cardiovascular system which describes the sinus rhythm, autonomic regulation of heart and arterial vessels, baroreflex, arterial pressure and respiration process. The model included a self-oscillating loop of regulation of mean arterial pressure. It was shown that suggested model more accurately simulated the spectral and statistical characteristics of heart rate variability signal in comparison with the model proposed earlier by Seidel and Herzel.

  9. Computational Models of the Cardiovascular System and Its Response to Microgravity

    NASA Technical Reports Server (NTRS)

    Kamm, Roger D.

    1999-01-01

    Computational models of the cardiovascular system are powerful adjuncts to ground-based and in-flight experiments. We will provide NSBRI with a model capable of simulating the short-term effects of gravity on cardiovascular function. The model from this project will: (1) provide a rational framework which quantitatively defines interactions among complex cardiovascular parameters and which supports the critical interpretation of experimental results and testing of hypotheses. (2) permit predictions of the impact of specific countermeasures in the context of various hypothetical cardiovascular abnormalities induced by microgravity. Major progress has been made during the first 18 months of the program: (1) We have developed an operational first-order computer model capable of simulating the cardiovascular response to orthostatic stress. The model consists of a lumped parameter hemodynamic model and a complete reflex control system. The latter includes cardiopulmonary and carotid sinus reflex limbs and interactions between the two. (2) We have modeled the physiologic stress of tilt table experiments and lower body negative pressure procedures (LBNP). We have verified our model's predictions by comparing them with experimental findings from the literature. (3) We have established collaborative efforts with leading investigators interested in experimental studies of orthostatic intolerance, cardiovascular control, and physiologic responses to space flight. (4) We have established a standardized method of transferring data to our laboratory from the ongoing NSBRI bedrest studies. We use this data to estimate input parameters to our model and compare our model predictions to actual data to further verify our model. (5) We are in the process of systematically simulating current hypotheses concerning the mechanism underlying orthostatic intolerance by matching our simulations to stand test data from astronauts pre- and post-flight. (6) We are in the process of developing a

  10. Object-oriented modeling and simulation of the closed loop cardiovascular system by using SIMSCAPE.

    PubMed

    de Canete, J Fernandez; del Saz-Orozco, P; Moreno-Boza, D; Duran-Venegas, E

    2013-05-01

    The modeling of physiological systems via mathematical equations reflects the calculation procedure more than the structure of the real system modeled, with the simulation environment SIMULINK™ being one of the best suited to this strategy. Nevertheless, object-oriented modeling is spreading in current simulation environments through the use of the individual components of the model and its interconnections to define the underlying dynamic equations. In this paper we describe the use of the SIMSCAPE™ simulation environment in the object-oriented modeling of the closed loop cardiovascular system. The described approach represents a valuable tool in the teaching of physiology for graduate medical students.

  11. Mixed quantitative/qualitative modeling and simulation of the cardiovascular system.

    PubMed

    Nebot, A; Cellier, F E; Vallverdú, M

    1998-02-01

    The cardiovascular system is composed of the hemodynamical system and the central nervous system (CNS) control. Whereas the structure and functioning of the hemodynamical system are well known and a number of quantitative models have already been developed that capture the behavior of the hemodynamical system fairly accurately, the CNS control is, at present, still not completely understood and no good deductive models exist that are able to describe the CNS control from physical and physiological principles. The use of qualitative methodologies may offer an interesting alternative to quantitative modeling approaches for inductively capturing the behavior of the CNS control. In this paper, a qualitative model of the CNS control of the cardiovascular system is developed by means of the fuzzy inductive reasoning (FIR) methodology. FIR is a fairly new modeling technique that is based on the general system problem solving (GSPS) methodology developed by G.J. Klir (Architecture of Systems Problem Solving, Plenum Press, New York, 1985). Previous investigations have demonstrated the applicability of this approach to modeling and simulating systems, the structure of which is partially or totally unknown. In this paper, five separate controller models for different control actuations are described that have been identified independently using the FIR methodology. Then the loop between the hemodynamical system, modeled by means of differential equations, and the CNS control, modeled in terms of five FIR models, is closed, in order to study the behavior of the cardiovascular system as a whole. The model described in this paper has been validated for a single patient only. PMID:9568385

  12. A dimensionally-heterogeneous closed-loop model for the cardiovascular system and its applications.

    PubMed

    Blanco, P J; Feijóo, R A

    2013-05-01

    In the present work a computational model of the entire cardiovascular system is developed using heterogeneous mathematical representations. This model integrates different levels of detail for the blood circulation. The arterial tree is described by a one dimensional model in order to simulate the wave propagation phenomena that take place at the larger arterial vessels. The inflow and outflow locations of this 1D model are coupled with lumped parameter descriptions of the remainder part of the circulatory system, closing the loop. The four cardiac valves are considered using a valve model which allows for stenoses and regurgitation phenomena. In addition, full 3D geometrical models of arterial districts are embedded in this closed-loop circuit to model the local blood flow in specific vessels. This kind of detailed closed-loop network for the cardiovascular system allows hemodynamics analyses of patient-specific arterial district, delivering naturally the appropriate boundary conditions for different cardiovascular scenarios. An example of application involving the effect of aortic insufficiency on the local hemodynamics of a cerebral aneurism is provided as a motivation to reproduce, through numerical simulation, the hemodynamic environment in patients suffering from infective endocarditis and mycotic aneurisms. The need for incorporating homeostatic control mechanisms is also discussed in view of the large sensitivity observed in the results, noting that this kind of integrative modeling allows such incorporation.

  13. Cardiovascular information systems.

    PubMed

    Marion, Joe

    2012-01-01

    The ARRA/HITECH Act has made electronic medical records a front burner issue, and many believe that EMRs will make departmental systems redundant. Some cardiologists beg to differ, arguing that cardiovascular information systems are deeply clinical and essential to the cardiovascular workflow. Here's a look at the evolution of CVIS, EMR, and their roles as the healthcare landscape is being transformed by meaningful use.

  14. A simplified computer model of cardiovascular system with an arm branch.

    PubMed

    Chen, Baoming; Song, Tianyi; Guo, Tao; Xiang, Haiyan; Liu, Yanyong; Qin, Yufei; Cao, Zhengtao; Yu, Mengsun

    2014-01-01

    Non-invasive pressure simulators that regenerate oscillometric waveforms promise an alternative to expensive clinical trials for validating oscillometric noninvasive blood pressure devices. However, existing simulators only provide oscillometric pressure in cuff and thus have a limited accuracy. It is promising to build a physical simulator that contains a synthetic arm with a built-in brachial artery and an affiliated hydraulic model of cardiovascular system. To guide the construction of this kind of simulator, this paper presents a computer model of cardiovascular system with a relatively simple structure, where the distribution of pressures and flows in aorta root and brachial artery can be simulated, and the produced waves are accordant with the physical data. This model can be used to provide the parameters and structure that will be needed to build the new simulator.

  15. Development of a mathematical model of the human cardiovascular system: An educational perspective

    NASA Astrophysics Data System (ADS)

    Johnson, Bruce Allen

    A mathematical model of the human cardiovascular system will be a useful educational tool in biological sciences and bioengineering classrooms. The goal of this project is to develop a mathematical model of the human cardiovascular system that responds appropriately to variations of significant physical variables. Model development is based on standard fluid statics and dynamics principles, pressure-volume characteristics of the cardiac cycle, and compliant behavior of blood vessels. Cardiac cycle phases provide the physical and logical model structure, and Boolean algebra links model sections. The model is implemented using VisSim, a highly intuitive and easily learned block diagram modeling software package. Comparisons of model predictions of key variables to published values suggest that the model reasonably approximates expected behavior of those variables. The model responds plausibly to variations of independent variables. Projected usefulness of the model as an educational tool is threefold: independent variables which determine heart function may be easily varied to observe cause and effect; the model is used in an interactive setting; and the relationship of governing equations to model behavior is readily viewable and intuitive. Future use of this model in classrooms may give a more reasonable indication of its value as an educational tool.* *This dissertation includes a CD that is multimedia (contains text and other applications that are not available in a printed format). The CD requires the following applications: CorelPhotoHouse, CorelWordPerfect, VisSinViewer (included on CD), Internet access.

  16. Fluctuations in a coupled-oscillator model of the cardiovascular system

    NASA Astrophysics Data System (ADS)

    González, Jorge A.; Suárez-Vargas, Jose J.; Stefanovska, Aneta; McClintock, Peter V. E.

    2007-06-01

    We present a model of the cardiovascular system (CVS) based on a system of coupled oscillators. Using this approach we can describe several complex physiological phenomena that can have a range of applications. For instance, heart rate variability (HRV), can have a new deterministic explanation. The intrinsic dynamics of the HRV is controlled by deterministic couplings between the physiological oscillators in our model and without the need to introduce external noise as is commonly done. This new result provides potential applications not only for physiological systems but also for the design of very precise electronic generators where the frequency stability is crucial. Another important phenomenon is that of oscillation death. We show that in our CVS model the mechanism leading to the quenching of the oscillations can be controlled, not only by the coupling parameter, but by a more general scheme. In fact, we propose that a change in the relative current state of the cardiovascular oscillators can lead to a cease of the oscillations without actually changing the strength of the coupling among them. We performed real experiments using electronic oscillators and show them to match the theoretical and numerical predictions. We discuss the relevance of the studied phenomena to real cardiovascular systems regimes, including the explanation of certain pathologies, and the possible applications in medical practice.

  17. An integrative model of the cardiovascular system coupling heart cellular mechanics with arterial network hemodynamics.

    PubMed

    Kim, Young-Tae; Lee, Jeong Sang; Youn, Chan-Hyun; Choi, Jae-Sung; Shim, Eun Bo

    2013-08-01

    The current study proposes a model of the cardiovascular system that couples heart cell mechanics with arterial hemodynamics to examine the physiological role of arterial blood pressure (BP) in left ventricular hypertrophy (LVH). We developed a comprehensive multiphysics and multiscale cardiovascular model of the cardiovascular system that simulates physiological events, from membrane excitation and the contraction of a cardiac cell to heart mechanics and arterial blood hemodynamics. Using this model, we delineated the relationship between arterial BP or pulse wave velocity and LVH. Computed results were compared with existing clinical and experimental observations. To investigate the relationship between arterial hemodynamics and LVH, we performed a parametric study based on arterial wall stiffness, which was obtained in the model. Peak cellular stress of the left ventricle and systolic blood pressure (SBP) in the brachial and central arteries also increased; however, further increases were limited for higher arterial stiffness values. Interestingly, when we doubled the value of arterial stiffness from the baseline value, the percentage increase of SBP in the central artery was about 6.7% whereas that of the brachial artery was about 3.4%. It is suggested that SBP in the central artery is more critical for predicting LVH as compared with other blood pressure measurements.

  18. Model of human cardiovascular system with a loop of autonomic regulation of the mean arterial pressure.

    PubMed

    Karavaev, Anatoly S; Ishbulatov, Yurii M; Ponomarenko, Vladimir I; Prokhorov, Mikhail D; Gridnev, Vladimir I; Bezruchko, Boris P; Kiselev, Anton R

    2016-03-01

    A model of human cardiovascular system is proposed which describes the main heart rhythm, the regulation of heart function and blood vessels by the autonomic nervous system, baroreflex, and the formation of arterial blood pressure. The model takes into account the impact of respiration on these processes. It is shown that taking into account nonlinearity and introducing the autonomous loop of mean arterial blood pressure in the form of self-oscillating time-delay system allow to obtain the model signals whose statistical and spectral characteristics are qualitatively and quantitatively similar to those for experimental signals. The proposed model demonstrates the phenomenon of synchronization of mean arterial pressure regulatory system by the signal of respiration with the basic period close to 10 seconds, which is observed in the physiological experiments. PMID:26847603

  19. [Animal models of cardiovascular disease].

    PubMed

    Chorro, Francisco J; Such-Belenguer, Luis; López-Merino, Vicente

    2009-01-01

    The use of animal models to study cardiovascular disease has made a substantial contribution to increasing our understanding of disease pathogenesis, has led to the development of diagnostic techniques, and has made it possible to verify the effectiveness of different preventative and therapeutic approaches, whether pharmacological or interventional. The main limitations stem from differences between human and experimentally induced pathology, in terms of both genetic regulatory mechanisms and factors that influence cardiovascular function. The experimental models and preparations used in cardiovascular research include those based on isolated cells or tissues or structures immersed in organ baths. The Langendorff system enables isolated perfused hearts to be studied directly under conditions of either no load or controlled loading. In small mammals, a number of models have been developed of cardiovascular conditions that result from spontaneous genetic mutations or, alternatively, that may be induced by specific genomic modification. One of the techniques employed is gene transfer, which can involve the controlled induction of mutations that result in the expression of abnormalities associated with the development of a broad range of different types of cardiovascular disease. Larger animals are used in experimental models in which it is important that physiological regulatory and homeostatic mechanisms are present.

  20. A Closed-Loop Lumped Parameter Computational Model for Human Cardiovascular System

    NASA Astrophysics Data System (ADS)

    Liang, Fuyou; Liu, Hao

    For purpose of a better understanding of the behavior of the global hemodynamic interactions, a closed-loop lumped parameter computational model was developed for the human cardiovascular system with a detailed compartmental description of the heart and the main vascular circulations. Construction of the model was implemented based on a phenomenological characterization of hemodynamics using an electrical analog method and solution of the governing differential equations of the model was carried out by use of a fourth-order Runge-Kutta method. Most of the hemodynamic parameters predicted by the present model were either consonant with the clinical measurements or within reasonable physiological ranges. Furthermore, the present model was applied to predict the clinical cardiac hemodynamic characteristics observed in patients with heart abnormalities. Reasonable agreements between predictions and measurements indicate that the present computational model can serve as a useful assistant tool for computer-aided diagnosis and surgical treatment, as well as posttreatment prediction.

  1. A mathematical model of the cardiovascular system under graded exercise levels.

    PubMed

    Wang, Lu; Zhang, Yi; Guo, Ying; Nguyen, Nghia; Zhang, Daoming; Celler, Branko G

    2012-01-01

    This paper presents a nonlinear cardiovascular model for the study of cardiovascular response during graded exercise. There are two major innovations embedded in this model. Firstly, by tuning only three parameters, all major cardiovascular variables were accurately reproduced. Secondly, a robust and efficient function, which was built up using Support Vector Machine Regression, was added to the model to estimate metabolic demand. Experimental results for ten untrained males indicated that the established model is accurate in the sense that its predicted output was in good agreement with the measured data.

  2. Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention.

    PubMed

    Zhang, Yanhang; Barocas, Victor H; Berceli, Scott A; Clancy, Colleen E; Eckmann, David M; Garbey, Marc; Kassab, Ghassan S; Lochner, Donna R; McCulloch, Andrew D; Tran-Son-Tay, Roger; Trayanova, Natalia A

    2016-09-01

    Cardiovascular diseases (CVDs) are the leading cause of death in the western world. With the current development of clinical diagnostics to more accurately measure the extent and specifics of CVDs, a laudable goal is a better understanding of the structure-function relation in the cardiovascular system. Much of this fundamental understanding comes from the development and study of models that integrate biology, medicine, imaging, and biomechanics. Information from these models provides guidance for developing diagnostics, and implementation of these diagnostics to the clinical setting, in turn, provides data for refining the models. In this review, we introduce multi-scale and multi-physical models for understanding disease development, progression, and designing clinical interventions. We begin with multi-scale models of cardiac electrophysiology and mechanics for diagnosis, clinical decision support, personalized and precision medicine in cardiology with examples in arrhythmia and heart failure. We then introduce computational models of vasculature mechanics and associated mechanical forces for understanding vascular disease progression, designing clinical interventions, and elucidating mechanisms that underlie diverse vascular conditions. We conclude with a discussion of barriers that must be overcome to provide enhanced insights, predictions, and decisions in pre-clinical and clinical applications.

  3. A multiformalism and multiresolution modelling environment: application to the cardiovascular system and its regulation

    PubMed Central

    Hernández, Alfredo I.; Le Rolle, Virginie; Defontaine, Antoine; Carrault, Guy

    2009-01-01

    The role of modelling and simulation on the systemic analysis of living systems is now clearly established. Emerging disciplines, such as Systems Biology, and world-wide research actions, such as the Physiome project or the Virtual Physiological Human, are based on an intensive use of modelling and simulation methodologies and tools. One of the key aspects in this context is to perform an efficient integration of various models representing different biological or physiological functions, at different resolutions, spanning through different scales. This paper presents a multi-formalism modelling and simulation environment (M2SL) that has been conceived to ease model integration. A given model is represented as a set of coupled and atomic model components that may be based on different mathematical formalisms with heterogeneous structural and dynamical properties. A co-simulation approach is used to solve these hybrid systems. The pioneering model of the overall regulation of the cardiovascular system, proposed by Guyton, Coleman & Granger in 1972 has been implemented under M2SL and a pulsatile ventricular model, based on a time-varying elastance has been integrated, in a multi-resolution approach. Simulations reproducing physiological conditions and using different coupling methods show the benefits of the proposed environment. PMID:19884187

  4. A multiformalism and multiresolution modelling environment: application to the cardiovascular system and its regulation.

    PubMed

    Hernández, Alfredo I; Le Rolle, Virginie; Defontaine, Antoine; Carrault, Guy

    2009-12-13

    The role of modelling and simulation in the systemic analysis of living systems is now clearly established. Emerging disciplines, such as systems biology, and worldwide research actions, such as the Physiome Project or the Virtual Physiological Human, are based on an intensive use of modelling and simulation methodologies and tools. One of the key aspects in this context is to perform an efficient integration of various models representing different biological or physiological functions, at different resolutions, spanning through different scales. This paper presents a multiformalism modelling and simulation environment (M2SL) that has been conceived to ease model integration. A given model is represented as a set of coupled and atomic model components that may be based on different mathematical formalisms with heterogeneous structural and dynamical properties. A co-simulation approach is used to solve these hybrid systems. The pioneering model of the overall regulation of the cardiovascular system proposed by Guyton and co-workers in 1972 has been implemented under M2SL and a pulsatile ventricular model based on a time-varying elastance has been integrated in a multi-resolution approach. Simulations reproducing physiological conditions and using different coupling methods show the benefits of the proposed environment.

  5. Modeling ventricular interaction: a multiscale approach from sarcomere mechanics to cardiovascular system hemodynamics.

    PubMed

    Lumens, Joost; Delhaas, Tammo; Kirn, Borut; Arts, Theo

    2008-01-01

    Direct ventricular interaction via the interventricular septum plays an important role in ventricular hemodynamics and mechanics. A large amount of experimental data demonstrates that left and right ventricular pump mechanics influence each other and that septal geometry and motion depend on transmural pressure. We present a lumped model of ventricular mechanics consisting of three wall segments that are coupled on the basis of balance laws stating mechanical equilibrium at the intersection of the three walls. The input consists of left and right ventricular volumes and an estimate of septal wall geometry. Wall segment geometry is expressed as area and curvature and is related to sarcomere extension. With constitutive equations of the sarcomere, myofiber stress is calculated. The force exerted by each wall segment on the intersection, as a result of wall tension, is derived from myofiber stress. Finally, septal geometry and ventricular pressures are solved by achieving balance of forces. We implemented this ventricular module in a lumped model of the closed-loop cardiovascular system (CircAdapt model) The resulting multiscale model enables dynamic simulation of myofiber mechanics, ventricular cavity mechanics, and cardiovascular system hemodynamics. The model was tested by performing simulations with synchronous and asynchronous mechanical activation of the wall segments. The simulated results of ventricular mechanics and hemodynamics were compared with experimental data obtained before and after acute induction of left bundle branch block (LBBB) in dogs. The changes in simulated ventricular mechanics and septal motion as a result of the introduction of mechanical asynchrony were very similar to those measured in the animal experiments. In conclusion, the module presented describes ventricular mechanics including direct ventricular interaction realistically and thereby extends the physiological application range of the CircAdapt model.

  6. Incorporating autoregulatory mechanisms of the cardiovascular system in three-dimensional finite element models of arterial blood flow.

    PubMed

    Kim, H J; Jansen, K E; Taylor, C A

    2010-07-01

    The cardiovascular system is a closed-loop system in which billions of vessels interact with each other, and it enables the control of the systemic arterial pressure and varying organ flow through autoregulatory mechanisms. In this study, we describe the development of mathematical models of autoregulatory mechanisms for systemic arterial pressure and coronary flow and discuss the connection of these models to a hybrid numerical/analytic closed-loop model of the cardiovascular system. The closed-loop model consists of two lumped parameter heart models representing the left and right sides of the heart, a three-dimensional finite element model of the aorta with coronary arteries, three-element Windkessel models and lumped parameter coronary vascular models that represent the systemic circulation, and a three-element Windkessel model to approximate the pulmonary circulation. Using the connection between the systemic arterial pressure and coronary flow regulation systems, and the hybrid closed-loop model, we studied how the heart, coronary vascular beds, and arterial system respond to physiologic changes during light exercise and showed that these models can realistically simulate temporal behaviors of the heart, coronary vascular beds, and arterial system during exercise of healthy subjects. These models can be used to study temporal changes occurring in the heart, coronary vascular beds, and arterial system during cardiovascular intervention or changes in physiological states.

  7. Optimization in Cardiovascular Modeling

    NASA Astrophysics Data System (ADS)

    Marsden, Alison L.

    2014-01-01

    Fluid mechanics plays a key role in the development, progression, and treatment of cardiovascular disease. Advances in imaging methods and patient-specific modeling now reveal increasingly detailed information about blood flow patterns in health and disease. Building on these tools, there is now an opportunity to couple blood flow simulation with optimization algorithms to improve the design of surgeries and devices, incorporating more information about the flow physics in the design process to augment current medical knowledge. In doing so, a major challenge is the need for efficient optimization tools that are appropriate for unsteady fluid mechanics problems, particularly for the optimization of complex patient-specific models in the presence of uncertainty. This article reviews the state of the art in optimization tools for virtual surgery, device design, and model parameter identification in cardiovascular flow and mechanobiology applications. In particular, it reviews trade-offs between traditional gradient-based methods and derivative-free approaches, as well as the need to incorporate uncertainties. Key future challenges are outlined, which extend to the incorporation of biological response and the customization of surgeries and devices for individual patients.

  8. Ghrelin and the cardiovascular system.

    PubMed

    Tokudome, Takeshi; Kishimoto, Ichiro; Miyazato, Mikiya; Kangawa, Kenj

    2014-01-01

    Ghrelin is a peptide that was originally isolated from the stomach. It exerts potent growth hormone (GH)-releasing and orexigenic activities. Several studies have highlighted the therapeutic benefits of ghrelin for the treatment of cardiovascular disease. In animal models of chronic heart failure, the administration of ghrelin improved cardiac function and remodeling; these findings were replicated in human patients with heart failure. Moreover, in an animal study, ghrelin administration effectively reduced pulmonary hypertension induced by chronic hypoxia. In addition, repeated administration of ghrelin to cachectic patients with chronic obstructive pulmonary disease had positive effects on overall body function, including muscle wasting, functional capacity and sympathetic activity. The administration of ghrelin early after myocardial infarction (MI) reduced fatal arrhythmia and related mortality. In ghrelin-deficient mice, both exogenous and endogenous ghrelin were protective against fatal arrhythmia and promoted remodeling after MI. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system remain unclear, there are indications that its beneficial effects are mediated through both direct physiological actions, including increased GH levels, improved energy balance and direct actions on cardiovascular cells, and regulation of autonomic nervous system activity. Therefore, ghrelin is a promising novel therapeutic agent for cardiovascular disease.

  9. A computational physiology approach to personalized treatment models: the beneficial effects of slow breathing on the human cardiovascular system.

    PubMed

    Fonoberova, Maria; Mezić, Igor; Buckman, Jennifer F; Fonoberov, Vladimir A; Mezić, Adriana; Vaschillo, Evgeny G; Mun, Eun-Young; Vaschillo, Bronya; Bates, Marsha E

    2014-10-01

    Heart rate variability biofeedback intervention involves slow breathing at a rate of ∼6 breaths/min (resonance breathing) to maximize respiratory and baroreflex effects on heart period oscillations. This intervention has wide-ranging clinical benefits and is gaining empirical support as an adjunct therapy for biobehavioral disorders, including asthma and depression. Yet, little is known about the system-level cardiovascular changes that occur during resonance breathing or the extent to which individuals differ in cardiovascular benefit. This study used a computational physiology approach to dynamically model the human cardiovascular system at rest and during resonance breathing. Noninvasive measurements of heart period, beat-to-beat systolic and diastolic blood pressure, and respiration period were obtained from 24 healthy young men and women. A model with respiration as input was parameterized to better understand how the cardiovascular processes that control variability in heart period and blood pressure change from rest to resonance breathing. The cost function used in model calibration corresponded to the difference between the experimental data and model outputs. A good match was observed between the data and model outputs (heart period, blood pressure, and corresponding power spectral densities). Significant improvements in several modeled cardiovascular functions (e.g., blood flow to internal organs, sensitivity of the sympathetic component of the baroreflex, ventricular elastance) were observed during resonance breathing. Individual differences in the magnitude and nature of these dynamic responses suggest that computational physiology may be clinically useful for tailoring heart rate variability biofeedback interventions for the needs of individual patients.

  10. Estrogen actions in the cardiovascular system.

    PubMed

    Mendelsohn, M E

    2009-01-01

    This brief review summarizes the current state of the field for estrogen receptor actions in the cardiovascular system and the cardiovascular effects of hormone replacement therapy (HRT). It is organized into three parts: a short Introduction and overview of the current view of how estrogen works on blood vessels; a summary of the current status of clinical information regarding HRT and cardiovascular effects; and an update on state-of-the-art mouse models of estrogen action using estrogen receptor knockout mice.

  11. On the integration of the baroreflex control mechanism in a heterogeneous model of the cardiovascular system.

    PubMed

    Blanco, P J; Trenhago, P R; Fernandes, L G; Feijóo, R A

    2012-04-01

    The aim of the present work is to describe the integration of a mathematical model for the baroreceptor reflex mechanism to provide regulatory action into a dimensionally heterogeneous (3D-1D-0D) closed-loop model of the cardiovascular system. Such heterogeneous model comprises a 1D description of the arterial tree, a 0D network for the venous, cardiac and pulmonary circulations and 3D patient-specific geometries for vascular districts of interest. Thus, the detailed topological description of the arterial network allows us to perform vasomotor control actions in a differentiated way, while gaining insight about the effects of the baroreflex regulation over hemodynamic quantities of interest throughout the entire network. Two examples of application are presented. Firstly, we simulate the hemorrhage in the abdominal aorta artery and analyze the action of the baroreflex over the system. Secondly, the self-regulated closed-loop model is applied to study the influence of the control action in the hemodynamic environment that determines the blood flow pattern in a cerebral aneurism in the presence of a regurgitating aortic valve. PMID:25365656

  12. Development of the Patient-specific Cardiovascular Modeling System Using Immersed Boundary Technique

    NASA Astrophysics Data System (ADS)

    Tay, Wee-Beng; Lin, Liang-Yu; Tseng, Wen-Yih; Tseng, Yu-Heng

    2010-05-01

    A computational fluid dynamics (CFD) based, patient-specific cardiovascular modeling system is under-developed. The system can identify possible diseased conditions and facilitate physicians' diagnosis at early stage through the hybrid CFD simulation and time-resolved magnetic resonance imaging (MRI). The CFD simulation is initially based on the three-dimensional heart model developed by McQueen and Peskin, which can simultaneously compute fluid motions and elastic boundary motions using the immersed boundary method. We extend and improve the three-dimensional heart model for the clinical application by including the patient-specific hemodynamic information. The flow features in the ventricles and their responses are investigated under different inflow and outflow conditions during diastole and systole phases based on the quasi-realistic heart model, which takes advantage of the observed flow scenarios. Our results indicate distinct differences between the two groups of participants, including the vortex formation process in the left ventricle (LV), as well as the flow rate distributions at different identified sources such as the aorta, vena cava and pulmonary veins/artery. We further identify some key parameters which may affect the vortex formation in the LV. Thus it is hypothesized that disease-related dysfunctions in intervals before complete heart failure can be observed in the dynamics of transmitral blood flow during early LV diastole.

  13. An Integrated Model of the Cardiovascular and Central Nervous Systems for Analysis of Microgravity Induced Fluid Redistribution

    NASA Technical Reports Server (NTRS)

    Price, R.; Gady, S.; Heinemann, K.; Nelson, E. S.; Mulugeta, L.; Ethier, C. R.; Samuels, B. C.; Feola, A.; Vera, J.; Myers, J. G.

    2015-01-01

    A recognized side effect of prolonged microgravity exposure is visual impairment and intracranial pressure (VIIP) syndrome. The medical understanding of this phenomenon is at present preliminary, although it is hypothesized that the headward shift of bodily fluids in microgravity may be a contributor. Computational models can be used to provide insight into the origins of VIIP. In order to further investigate this phenomenon, NASAs Digital Astronaut Project (DAP) is developing an integrated computational model of the human body which is divided into the eye, the cerebrovascular system, and the cardiovascular system. This presentation will focus on the development and testing of the computational model of an integrated model of the cardiovascular system (CVS) and central nervous system (CNS) that simulates the behavior of pressures, volumes, and flows within these two physiological systems.

  14. Multi-scale modeling of the human cardiovascular system with applications to aortic valvular and arterial stenoses.

    PubMed

    Liang, Fuyou; Takagi, Shu; Himeno, Ryutaro; Liu, Hao

    2009-07-01

    A computational model of the entire cardiovascular system is established based on multi-scale modeling, where the arterial tree is described by a one-dimensional model coupled with a lumped parameter description of the remainder. The resultant multi-scale model forms a closed loop, thus placing arterial wave propagation into a global hemodynamic environment. The model is applied to study the global hemodynamic influences of aortic valvular and arterial stenoses located in various regions. Obtained results show that the global hemodynamic influences of the stenoses depend strongly on their locations in the arterial system, particularly, the characteristics of hemodynamic changes induced by the aortic valvular and aortic stenoses are pronounced, which imply the possibility of noninvasively detecting the presence of the stenoses from peripheral pressure pulses. The variations in aortic pressure/flow pulses with the stenoses play testimony to the significance of modeling the entire cardiovascular system in the study of arterial diseases.

  15. Validation of subject-specific cardiovascular system models from porcine measurements.

    PubMed

    Revie, James A; Stevenson, David J; Chase, J Geoffrey; Hann, Christopher E; Lambermont, Bernard C; Ghuysen, Alexandre; Kolh, Philippe; Shaw, Geoffrey M; Heldmann, Stefan; Desaive, Thomas

    2013-02-01

    A previously validated mathematical model of the cardiovascular system (CVS) is made subject-specific using an iterative, proportional gain-based identification method. Prior works utilised a complete set of experimentally measured data that is not clinically typical or applicable. In this paper, parameters are identified using proportional gain-based control and a minimal, clinically available set of measurements. The new method makes use of several intermediary steps through identification of smaller compartmental models of CVS to reduce the number of parameters identified simultaneously and increase the convergence stability of the method. This new, clinically relevant, minimal measurement approach is validated using a porcine model of acute pulmonary embolism (APE). Trials were performed on five pigs, each inserted with three autologous blood clots of decreasing size over a period of four to five hours. All experiments were reviewed and approved by the Ethics Committee of the Medical Faculty at the University of Liege, Belgium. Continuous aortic and pulmonary artery pressures (P(ao), P(pa)) were measured along with left and right ventricle pressure and volume waveforms. Subject-specific CVS models were identified from global end diastolic volume (GEDV), stroke volume (SV), P(ao), and P(pa) measurements, with the mean volumes and maximum pressures of the left and right ventricles used to verify the accuracy of the fitted models. The inputs (GEDV, SV, P(ao), P(pa)) used in the identification process were matched by the CVS model to errors <0.5%. Prediction of the mean ventricular volumes and maximum ventricular pressures not used to fit the model compared experimental measurements to median absolute errors of 4.3% and 4.4%, which are equivalent to the measurement errors of currently used monitoring devices in the ICU (∼5-10%). These results validate the potential for implementing this approach in the intensive care unit.

  16. Long-term regulation in the cardiovascular system - Cornerstone in the development of a composite physiological model

    NASA Technical Reports Server (NTRS)

    White, R. J.

    1974-01-01

    The present work discusses a model of the cardiovascular system and related subsystems capable of long-term simulations of the type desired for in-space hypogravic human physiological performance prediction. The discussion centers around the model of Guyton and modifications of it. In order to draw attention to the fluid handling capabilities of the model, one of several transfusion simulations performed is presented, namely, the isotonic saline transfusion simulation.

  17. Modeling of short-term mechanism of arterial pressure control in the cardiovascular system: object-oriented and acausal approach.

    PubMed

    Kulhánek, Tomáš; Kofránek, Jiří; Mateják, Marek

    2014-11-01

    This letter introduces an alternative approach to modeling the cardiovascular system with a short-term control mechanism published in Computers in Biology and Medicine, Vol. 47 (2014), pp. 104-112. We recommend using abstract components on a distinct physical level, separating the model into hydraulic components, subsystems of the cardiovascular system and individual subsystems of the control mechanism and scenario. We recommend utilizing an acausal modeling feature of Modelica language, which allows model variables to be expressed declaratively. Furthermore, the Modelica tool identifies which are the dependent and independent variables upon compilation. An example of our approach is introduced on several elementary components representing the hydraulic resistance to fluid flow and the elastic response of the vessel, among others. The introduced model implementation can be more reusable and understandable for the general scientific community.

  18. Modeling of short-term mechanism of arterial pressure control in the cardiovascular system: object-oriented and acausal approach.

    PubMed

    Kulhánek, Tomáš; Kofránek, Jiří; Mateják, Marek

    2014-11-01

    This letter introduces an alternative approach to modeling the cardiovascular system with a short-term control mechanism published in Computers in Biology and Medicine, Vol. 47 (2014), pp. 104-112. We recommend using abstract components on a distinct physical level, separating the model into hydraulic components, subsystems of the cardiovascular system and individual subsystems of the control mechanism and scenario. We recommend utilizing an acausal modeling feature of Modelica language, which allows model variables to be expressed declaratively. Furthermore, the Modelica tool identifies which are the dependent and independent variables upon compilation. An example of our approach is introduced on several elementary components representing the hydraulic resistance to fluid flow and the elastic response of the vessel, among others. The introduced model implementation can be more reusable and understandable for the general scientific community. PMID:25240104

  19. Bayesian network modeling: A case study of an epidemiologic system analysis of cardiovascular risk.

    PubMed

    Fuster-Parra, P; Tauler, P; Bennasar-Veny, M; Ligęza, A; López-González, A A; Aguiló, A

    2016-04-01

    An extensive, in-depth study of cardiovascular risk factors (CVRF) seems to be of crucial importance in the research of cardiovascular disease (CVD) in order to prevent (or reduce) the chance of developing or dying from CVD. The main focus of data analysis is on the use of models able to discover and understand the relationships between different CVRF. In this paper a report on applying Bayesian network (BN) modeling to discover the relationships among thirteen relevant epidemiological features of heart age domain in order to analyze cardiovascular lost years (CVLY), cardiovascular risk score (CVRS), and metabolic syndrome (MetS) is presented. Furthermore, the induced BN was used to make inference taking into account three reasoning patterns: causal reasoning, evidential reasoning, and intercausal reasoning. Application of BN tools has led to discovery of several direct and indirect relationships between different CVRF. The BN analysis showed several interesting results, among them: CVLY was highly influenced by smoking being the group of men the one with highest risk in CVLY; MetS was highly influence by physical activity (PA) being again the group of men the one with highest risk in MetS, and smoking did not show any influence. BNs produce an intuitive, transparent, graphical representation of the relationships between different CVRF. The ability of BNs to predict new scenarios when hypothetical information is introduced makes BN modeling an Artificial Intelligence (AI) tool of special interest in epidemiological studies. As CVD is multifactorial the use of BNs seems to be an adequate modeling tool. PMID:26777431

  20. Arrestins in the cardiovascular system.

    PubMed

    Lymperopoulos, Anastasios; Bathgate, Ashley

    2013-01-01

    Of the four mammalian arrestins, only the β-arrestins (βarrs; Arrestin2 and -3) are expressed throughout the cardiovascular system, where they regulate, as either desensitizers/internalizers or signal transducers, several G-protein-coupled receptors (GPCRs) critical for cardiovascular homeostasis. The cardiovascular roles of βarrs have been delineated at an accelerated pace via a variety of techniques and tools, such as knockout mice, siRNA knockdown, artificial or naturally occurring polymorphic GPCRs, and availability of new βarr "biased" GPCR ligands. This chapter summarizes the current knowledge of cardiovascular arrestin physiology and pharmacology, addressing the individual cardiovascular receptors affected by βarrs in vivo, as well as the individual cell types, tissues, and organs of the cardiovascular system in which βarr effects are exerted; for example, cardiac myocyte or fibroblast, vascular smooth muscle, adrenal gland and platelet. In the broader scope of cardiovascular βarr pharmacology, a discussion of the βarr "bias" of certain cardiovascular GPCR ligands is also included.

  1. Towards patient-specific cardiovascular modeling system using the immersed boundary technique

    PubMed Central

    2011-01-01

    Background Previous research shows that the flow dynamics in the left ventricle (LV) reveal important information about cardiac health. This information can be used in early diagnosis of patients with potential heart problems. The current study introduces a patient-specific cardiovascular-modelling system (CMS) which simulates the flow dynamics in the LV to facilitate physicians in early diagnosis of patients before heart failure. Methods The proposed system will identify possible disease conditions and facilitates early diagnosis through hybrid computational fluid dynamics (CFD) simulation and time-resolved magnetic resonance imaging (4-D MRI). The simulation is based on the 3-D heart model, which can simultaneously compute fluid and elastic boundary motions using the immersed boundary method. At this preliminary stage, the 4-D MRI is used to provide an appropriate comparison. This allows flexible investigation of the flow features in the ventricles and their responses. Results The results simulate various flow rates and kinetic energy in the diastole and systole phases, demonstrating the feasibility of capturing some of the important characteristics of the heart during different phases. However, some discrepancies exist in the pulmonary vein and aorta flow rate between the numerical and experimental data. Further studies are essential to investigate and solve the remaining problems before using the data in clinical diagnostics. Conclusions The results show that by using a simple reservoir pressure boundary condition (RPBC), we are able to capture some essential variations found in the clinical data. Our approach establishes a first-step framework of a practical patient-specific CMS, which comprises a 3-D CFD model (without involving actual hemodynamic data yet) to simulate the heart and the 4-D PC-MRI system. At this stage, the 4-D PC-MRI system is used for verification purpose rather than input. This brings us closer to our goal of developing a practical patient

  2. Mathematical multi-scale model of the cardiovascular system including mitral valve dynamics. Application to ischemic mitral insufficiency

    PubMed Central

    2011-01-01

    Background Valve dysfunction is a common cardiovascular pathology. Despite significant clinical research, there is little formal study of how valve dysfunction affects overall circulatory dynamics. Validated models would offer the ability to better understand these dynamics and thus optimize diagnosis, as well as surgical and other interventions. Methods A cardiovascular and circulatory system (CVS) model has already been validated in silico, and in several animal model studies. It accounts for valve dynamics using Heaviside functions to simulate a physiologically accurate "open on pressure, close on flow" law. However, it does not consider real-time valve opening dynamics and therefore does not fully capture valve dysfunction, particularly where the dysfunction involves partial closure. This research describes an updated version of this previous closed-loop CVS model that includes the progressive opening of the mitral valve, and is defined over the full cardiac cycle. Results Simulations of the cardiovascular system with healthy mitral valve are performed, and, the global hemodynamic behaviour is studied compared with previously validated results. The error between resulting pressure-volume (PV) loops of already validated CVS model and the new CVS model that includes the progressive opening of the mitral valve is assessed and remains within typical measurement error and variability. Simulations of ischemic mitral insufficiency are also performed. Pressure-Volume loops, transmitral flow evolution and mitral valve aperture area evolution follow reported measurements in shape, amplitude and trends. Conclusions The resulting cardiovascular system model including mitral valve dynamics provides a foundation for clinical validation and the study of valvular dysfunction in vivo. The overall models and results could readily be generalised to other cardiac valves. PMID:21942971

  3. Role of Telomerase in the Cardiovascular System

    PubMed Central

    Zurek, Mark; Altschmied, Joachim; Kohlgrüber, Stefanie; Ale-Agha, Niloofar; Haendeler, Judith

    2016-01-01

    Aging is one major risk factor for the incidence of cardiovascular diseases and the development of atherosclerosis. One important enzyme known to be involved in aging processes is Telomerase Reverse Transcriptase (TERT). After the discovery of the enzyme in humans, TERT had initially only been attributed to germ line cells, stem cells and cancer cells. However, over the last few years it has become clear that TERT is also active in cells of the cardiovascular system including cardiac myocytes, endothelial cells, smooth muscle cells and fibroblasts. Interference with the activity of this enzyme greatly contributes to cardiovascular diseases. This review will summarize the findings on the role of TERT in cardiovascular cells. Moreover, recent findings concerning TERT in different mouse models with respect to cardiovascular diseases will be described. Finally, the extranuclear functions of TERT will be covered within this review. PMID:27322328

  4. Role of Telomerase in the Cardiovascular System.

    PubMed

    Zurek, Mark; Altschmied, Joachim; Kohlgrüber, Stefanie; Ale-Agha, Niloofar; Haendeler, Judith

    2016-06-17

    Aging is one major risk factor for the incidence of cardiovascular diseases and the development of atherosclerosis. One important enzyme known to be involved in aging processes is Telomerase Reverse Transcriptase (TERT). After the discovery of the enzyme in humans, TERT had initially only been attributed to germ line cells, stem cells and cancer cells. However, over the last few years it has become clear that TERT is also active in cells of the cardiovascular system including cardiac myocytes, endothelial cells, smooth muscle cells and fibroblasts. Interference with the activity of this enzyme greatly contributes to cardiovascular diseases. This review will summarize the findings on the role of TERT in cardiovascular cells. Moreover, recent findings concerning TERT in different mouse models with respect to cardiovascular diseases will be described. Finally, the extranuclear functions of TERT will be covered within this review.

  5. Lymphatic System in Cardiovascular Medicine.

    PubMed

    Aspelund, Aleksanteri; Robciuc, Marius R; Karaman, Sinem; Makinen, Taija; Alitalo, Kari

    2016-02-01

    The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease.

  6. Animal models of cardiovascular diseases.

    PubMed

    Zaragoza, Carlos; Gomez-Guerrero, Carmen; Martin-Ventura, Jose Luis; Blanco-Colio, Luis; Lavin, Begoña; Mallavia, Beñat; Tarin, Carlos; Mas, Sebastian; Ortiz, Alberto; Egido, Jesus

    2011-01-01

    Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases. PMID:21403831

  7. Biofluid Dynamics in Cardiovascular System

    NASA Astrophysics Data System (ADS)

    Chung, Hansol; Yoo, Su Jung; Kyung, Richard

    2011-11-01

    Biofluid dynamics is characterized by the study of fluids in biological systems. Common biofluid systems include blood flow in the cardiovascular system and airflow in the lungs. The mathematical modeling of blood flow through the complex geometry of a prosthetic heart valve is a difficult task. In such a problem the complex geometries of the valve must be modeled properly so that they can be studied numerically. The present analysis is performed on a disk-type prosthetic heart valve. The valve is assumed to be in the aortic position and observed the structure of the valve cage influence the flow field near an aortic valve. For the purpose of mathematical modeling, the laminar incompressible two-dimensional steady flow of a homogeneous Newtonian fluid with constant viscosity is assumed. The flow is considered during the greater part of systole when the valve is fully open. Convergent numerical solutions are obtained for Reynolds numbers of 30, 180, 900 and 4500. Stream function, horizontal velocity, vertical velocity and shear stress solutions are computed at every grid point.

  8. Cardiovascular Biology of the Incretin System

    PubMed Central

    Ussher, John R.; Drucker, Daniel J.

    2012-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. Two classes of medications that enhance incretin action, GLP-1R agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus (T2DM). We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure and postprandial lipoprotein secretion. Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. Incretin-based agents control body weight, improve glycemic control with a low risk of hypoglycemia, decrease blood pressure, inhibit the secretion of intestinal chylomicrons, and reduce inflammation in preclinical studies. Nevertheless, there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease. Hence, a more complete understanding of the cardiovascular risk:benefit ratio of incretin-based therapies will require completion of long term cardiovascular outcome studies currently underway in patients with T2DM. PMID:22323472

  9. PPARs and the Cardiovascular System

    PubMed Central

    Hamblin, Milton; Chang, Lin; Fan, Yanbo; Zhang, Jifeng

    2009-01-01

    Abstract Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone-receptor superfamily. Originally cloned in 1990, PPARs were found to be mediators of pharmacologic agents that induce hepatocyte peroxisome proliferation. PPARs also are expressed in cells of the cardiovascular system. PPARγ appears to be highly expressed during atherosclerotic lesion formation, suggesting that increased PPARγ expression may be a vascular compensatory response. Also, ligand-activated PPARγ decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells. PPARα, similar to PPARγ, also has pleiotropic effects in the cardiovascular system, including antiinflammatory and antiatherosclerotic properties. PPARα activation inhibits vascular smooth muscle proinflammatory responses, attenuating the development of atherosclerosis. However, PPARδ overexpression may lead to elevated macrophage inflammation and atherosclerosis. Conversely, PPARδ ligands are shown to attenuate the pathogenesis of atherosclerosis by improving endothelial cell proliferation and survival while decreasing endothelial cell inflammation and vascular smooth muscle cell proliferation. Furthermore, the administration of PPAR ligands in the form of TZDs and fibrates has been disappointing in terms of markedly reducing cardiovascular events in the clinical setting. Therefore, a better understanding of PPAR-dependent and -independent signaling will provide the foundation for future research on the role of PPARs in human cardiovascular biology. Antioxid. Redox Signal. 11, 1415–1452. PMID:19061437

  10. PPARs and the cardiovascular system.

    PubMed

    Hamblin, Milton; Chang, Lin; Fan, Yanbo; Zhang, Jifeng; Chen, Y Eugene

    2009-06-01

    Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone-receptor superfamily. Originally cloned in 1990, PPARs were found to be mediators of pharmacologic agents that induce hepatocyte peroxisome proliferation. PPARs also are expressed in cells of the cardiovascular system. PPAR gamma appears to be highly expressed during atherosclerotic lesion formation, suggesting that increased PPAR gamma expression may be a vascular compensatory response. Also, ligand-activated PPAR gamma decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells. PPAR alpha, similar to PPAR gamma, also has pleiotropic effects in the cardiovascular system, including antiinflammatory and antiatherosclerotic properties. PPAR alpha activation inhibits vascular smooth muscle proinflammatory responses, attenuating the development of atherosclerosis. However, PPAR delta overexpression may lead to elevated macrophage inflammation and atherosclerosis. Conversely, PPAR delta ligands are shown to attenuate the pathogenesis of atherosclerosis by improving endothelial cell proliferation and survival while decreasing endothelial cell inflammation and vascular smooth muscle cell proliferation. Furthermore, the administration of PPAR ligands in the form of TZDs and fibrates has been disappointing in terms of markedly reducing cardiovascular events in the clinical setting. Therefore, a better understanding of PPAR-dependent and -independent signaling will provide the foundation for future research on the role of PPARs in human cardiovascular biology.

  11. Closed-loop real-time simulation model of hemodynamics and oxygen transport in the cardiovascular system

    PubMed Central

    2013-01-01

    Background Computer technology enables realistic simulation of cardiovascular physiology. The increasing number of clinical surgical and medical treatment options imposes a need for better understanding of patient-specific pathology and outcome prediction. Methods A distributed lumped parameter real-time closed-loop model with 26 vascular segments, cardiac modelling with time-varying elastance functions and gradually opening and closing valves, the pericardium, intrathoracic pressure, the atrial and ventricular septum, various pathological states and including oxygen transport has been developed. Results Model output is pressure, volume, flow and oxygen saturation from every cardiac and vascular compartment. The model produces relevant clinical output and validation of quantitative data in normal physiology and qualitative directions in simulation of pathological states show good agreement with published data. Conclusion The results show that it is possible to build a clinically relevant real-time computer simulation model of the normal adult cardiovascular system. It is suggested that understanding qualitative interaction between physiological parameters in health and disease may be improved by using the model, although further model development and validation is needed for quantitative patient-specific outcome prediction. PMID:23842033

  12. Modeling the interaction between the intra-aortic balloon pump and the cardiovascular system: the effect of timing.

    PubMed

    Schampaert, Stéphanie; Rutten, Marcel C M; van T Veer, Marcel; van Nunen, Lokien X; Tonino, Pim A L; Pijls, Nico H J; van de Vosse, Frans N

    2013-01-01

    Because of the large number of interaction factors involved, the effects of the intra-aortic balloon pump (IABP) have not been investigated deeply. To enhance its clinical efficiency and to better define indications for use, advanced models are required to test the interaction between the IABP and the cardiovascular system. A patient with mild blood pressure depression and a lowered cardiac output is modeled in a lumped parameter computational model, developed with physiologically representative elements for relevant components of circulation and device. IABP support is applied, and the moments of balloon inflation and deflation are varied around their conventional timing modes. For validation purposes, timing is adapted within acceptable ranges in ten patients undergoing IABP therapy for typical clinical indications. In both model and patients, the IABP induces a diastolic blood pressure augmentation as well as a systolic reduction in afterload. The support capabilities of the IABP benefit the most when the balloon is deflated simultaneously with ventricular contraction, whereas inflation before onset of diastole unconditionally interferes with ejection. The physiologic response makes the model an excellent tool for testing the interaction between the IABP and the cardiovascular system, and how alterations of specific IABP parameters (i.e., timing) affect this coupling.

  13. Ghrelin and the cardiovascular system.

    PubMed

    Isgaard, Jörgen

    2013-01-01

    Although ghrelin was initially associated with regulation of appetite, the cardiovascular system has also been recognized as a potentially important target for its effects. Moreover, experimental and a limited number of clinical studies suggest a potential role for ghrelin in the treatment of congestive heart failure. So far, reported cardiovascular effects of growth hormone secretagogues and/or ghrelin include lowering of peripheral resistance, either direct at the vascular level and/or by modulating sympathetic nervous activity. Other observed effects indicate possible improvement of contractility and cardioprotective and anti-inflammatory effects both in vivo and in vitro. Taken together, these results offer an interesting perspective on the future where further studies aiming at evaluating a role of growth hormone secretagogues and ghrelin in the treatment of cardiovascular disease are warranted.

  14. Bioengineering and the cardiovascular system

    PubMed Central

    Nerem, Robert M

    2013-01-01

    The development of the modern era of bioengineering and the advances in our understanding of the cardiovascular system have been intertwined over the past one-half century. This is true of bioengineering as an area for research in universities. Bioengineering is ultimately the beginning of a new engineering discipline, as well as a new discipline in the medical device industry. PMID:24688999

  15. A computational model of cardiovascular physiology and heart sound generation.

    PubMed

    Watrous, Raymond L

    2009-01-01

    A computational model of the cardiovascular system is described which provides a framework for implementing and testing quantitative physiological models of heart sound generation. The lumped-parameter cardiovascular model can be solved for the hemodynamic variables on which the heart sound generation process is built. Parameters of the cardiovascular model can be adjusted to represent various normal and pathological conditions, and the acoustic consequences of those adjustments can be explored. The combined model of the physiology of cardiovascular circulation and heart sound generation has promise for application in teaching, training and algorithm development in computer-aided auscultation of the heart.

  16. PPAR-γ in the Cardiovascular System

    PubMed Central

    Duan, Sheng Zhong; Ivashchenko, Christine Y.; Usher, Michael G.; Mortensen, Richard M.

    2008-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ), an essential transcriptional mediator of adipogenesis, lipid metabolism, insulin sensitivity, and glucose homeostasis, is increasingly recognized as a key player in inflammatory cells and in cardiovascular diseases (CVD) such as hypertension, cardiac hypertrophy, congestive heart failure, and atherosclerosis. PPAR-γ agonists, the thiazolidinediones (TZDs), increase insulin sensitivity, lower blood glucose, decrease circulating free fatty acids and triglycerides, lower blood pressure, reduce inflammatory markers, and reduce atherosclerosis in insulin-resistant patients and animal models. Human genetic studies on PPAR-γ have revealed that functional changes in this nuclear receptor are associated with CVD. Recent controversial clinical studies raise the question of deleterious action of PPAR-γ agonists on the cardiovascular system. These complex interactions of metabolic responsive factors and cardiovascular disease promise to be important areas of focus for the future. PMID:18288291

  17. Computational fluid dynamics modelling in cardiovascular medicine.

    PubMed

    Morris, Paul D; Narracott, Andrew; von Tengg-Kobligk, Hendrik; Silva Soto, Daniel Alejandro; Hsiao, Sarah; Lungu, Angela; Evans, Paul; Bressloff, Neil W; Lawford, Patricia V; Hose, D Rodney; Gunn, Julian P

    2016-01-01

    This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges.

  18. Computational fluid dynamics modelling in cardiovascular medicine

    PubMed Central

    Morris, Paul D; Narracott, Andrew; von Tengg-Kobligk, Hendrik; Silva Soto, Daniel Alejandro; Hsiao, Sarah; Lungu, Angela; Evans, Paul; Bressloff, Neil W; Lawford, Patricia V; Hose, D Rodney; Gunn, Julian P

    2016-01-01

    This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards ‘digital patient’ or ‘virtual physiological human’ representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges. PMID:26512019

  19. Computational fluid dynamics modelling in cardiovascular medicine.

    PubMed

    Morris, Paul D; Narracott, Andrew; von Tengg-Kobligk, Hendrik; Silva Soto, Daniel Alejandro; Hsiao, Sarah; Lungu, Angela; Evans, Paul; Bressloff, Neil W; Lawford, Patricia V; Hose, D Rodney; Gunn, Julian P

    2016-01-01

    This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges. PMID:26512019

  20. Cardiovascular system simulation in biomedical engineering education.

    NASA Technical Reports Server (NTRS)

    Rideout, V. C.

    1972-01-01

    Use of complex cardiovascular system models, in conjunction with a large hybrid computer, in biomedical engineering courses. A cardiovascular blood pressure-flow model, driving a compartment model for the study of dye transport, was set up on the computer for use as a laboratory exercise by students who did not have the computer experience or skill to be able to easily set up such a simulation involving some 27 differential equations running at 'real time' rate. The students were given detailed instructions regarding the model, and were then able to study effects such as those due to septal and valve defects upon the pressure, flow, and dye dilution curves. The success of this experiment in the use of involved models in engineering courses was such that it seems that this type of laboratory exercise might be considered for use in physiology courses as an adjunct to animal experiments.

  1. [Pathophysiological and clinical correlations between endocrine and cardiovascular systems. An inter-systemic model of internal medicine].

    PubMed

    Andreoli, Mario

    2006-12-01

    This review focuses on the mechanisms by which thyroid hormones affect the regulation of the cardiovascular system and the thermogenic and hemodynamic variation induced by thyroid disfunction. It is also stressed the hormonal role of the cardiac myocytes realising natriuretic peptides, involved in plasma volume homeostasis and cardiovascular remodelling; its rapid measurement is a useful clinical tool, in the diagnostic and prognostic of left ventricular dysfunction, correlating with the degree of the clinical symptoms. The endothelial layer is a receptor-effector endocrine organ that produces substances that maintain vasomotor balance and vascular-tissue homeostasis. Cardiovascular risk factors causes oxidative stress that alter endothelial function and leads to endothelial dysfunction. On the basis of the present body of evidence there is no doubt that endothelial dysfunction contributes to the initiation, and progression, of atherosclerotic disease and that it could be considered an independent vascular risk factor for the micro- and macrovascular damages in the diabetes disease. In several extrathyroidal pathological condition, as well as in heart failure, the main alteration of the thyroid function is referred to as "low T3 syndrome". This syndrome is due to an adaptative reaction of the metabolic pathway of thyroxine, producing an increased amount of rT3, metabolically inactive, thus decreasing the detrimental metabolic effects of T3, in conditions of critically impaired hemodynamic and metabolic efficiency. Preliminary clinical trials, in heart failure, suggest the prognostic value of the level of circulating T3, as well as usefulness of T3, or of thyromimetic derivatives (DITPA), in chronic treatment of the heart ventricular dysfunction.

  2. An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.

    PubMed

    Bhattacharya-Ghosh, Benjamin; Bozkurt, Selim; Rutten, Marcel C M; van de Vosse, Frans N; Díaz-Zuccarini, Vanessa

    2014-10-01

    Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view. PMID:25147131

  3. An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.

    PubMed

    Bhattacharya-Ghosh, Benjamin; Bozkurt, Selim; Rutten, Marcel C M; van de Vosse, Frans N; Díaz-Zuccarini, Vanessa

    2014-10-01

    Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.

  4. KATP Channels in the Cardiovascular System.

    PubMed

    Foster, Monique N; Coetzee, William A

    2016-01-01

    KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease.

  5. Computational modeling as part of alternative testing strategies in the respiratory and cardiovascular systems: inhaled nanoparticle dose modeling based on representative aerosol measurements and corresponding toxicological analysis.

    PubMed

    Pilou, Marika; Mavrofrydi, Olga; Housiadas, Christos; Eleftheriadis, Kostas; Papazafiri, Panagiota

    2015-05-01

    The objectives of modeling in this work were (a) the integration of two existing numerical models in order to connect external exposure to nanoparticles (NPs) with internal dose through inhalation, and (b) to use computational fluid-particle dynamics (CFPD) to analyze the behavior of NPs in the respiratory and the cardiovascular system. Regarding the first objective, a lung transport and deposition model was combined with a lung clearance/retention model to estimate NPs dose in the different regions of the human respiratory tract and some adjacent tissues. On the other hand, CFPD was used to estimate particle transport and deposition of particles in a physiologically based bifurcation created by the third and fourth lung generations (respiratory system), as well as to predict the fate of super-paramagnetic particles suspended in a liquid under the influence of an external magnetic field (cardiovascular system). All the above studies showed that, with proper refinement, the developed computational models and methodologies may serve as an alternative testing strategy, replacing transport/deposition experiments that are expensive both in time and resources and contribute to risk assessment.

  6. A Priori Identifiability Analysis of Cardiovascular Models

    PubMed Central

    Kirk, Jonathan A.; Saccomani, Maria P.; Shroff, Sanjeev G.

    2013-01-01

    Model parameters, estimated from experimentally measured data, can provide insight into biological processes that are not experimentally measurable. Whether this optimized parameter set is a physiologically relevant complement to the experimentally measured data, however, depends on the optimized parameter set being unique, a model property known as a priori global identifiability. However, a priori identifiability analysis is not common practice in the biological world, due to the lack of easy-to-use tools. Here we present a program, Differential Algebra for Identifiability of Systems (DAISY), that facilitates identifiability analysis. We applied DAISY to several cardiovascular models: systemic arterial circulation (Windkessel, T-Tube) and cardiac muscle contraction (complex stiffness, crossbridge cycling-based). All models were globally identifiable except the T-Tube model. In this instance, DAISY was able to provide insight into making the model identifiable. We applied numerical parameter optimization techniques to estimate unknown parameters in a model DAISY found globally identifiable. While all the parameters could be accurately estimated, a sensitivity analysis was first necessary to identify the required experimental data. Global identifiability is a prerequisite for numerical parameter optimization, and in a variety of cardiovascular models, DAISY provided a reliable, fast, and simple platform to provide this identifiability analysis. PMID:26726299

  7. Cardiovascular Magnetic Resonance Imaging in Experimental Models

    PubMed Central

    Price, Anthony N.; Cheung, King K.; Cleary, Jon O; Campbell, Adrienne E; Riegler, Johannes; Lythgoe, Mark F

    2010-01-01

    Cardiovascular magnetic resonance (CMR) imaging is the modality of choice for clinical studies of the heart and vasculature, offering detailed images of both structure and function with high temporal resolution. Small animals are increasingly used for genetic and translational research, in conjunction with models of common pathologies such as myocardial infarction. In all cases, effective methods for characterising a wide range of functional and anatomical parameters are crucial for robust studies. CMR is the gold-standard for the non-invasive examination of these models, although physiological differences, such as rapid heart rate, make this a greater challenge than conventional clinical imaging. However, with the help of specialised magnetic resonance (MR) systems, novel gating strategies and optimised pulse sequences, high-quality images can be obtained in these animals despite their small size. In this review, we provide an overview of the principal CMR techniques for small animals for example cine, angiography and perfusion imaging, which can provide measures such as ejection fraction, vessel anatomy and local blood flow, respectively. In combination with MR contrast agents, regional dysfunction in the heart can also be identified and assessed. We also discuss optimal methods for analysing CMR data, particularly the use of semi-automated tools for parameter measurement to reduce analysis time. Finally, we describe current and emerging methods for imaging the developing heart, aiding characterisation of congenital cardiovascular defects. Advanced small animal CMR now offers an unparalleled range of cardiovascular assessments. Employing these methods should allow new insights into the structural, functional and molecular basis of the cardiovascular system. PMID:21331311

  8. Cardiovascular disease in systemic sclerosis

    PubMed Central

    Cannarile, Francesca; Valentini, Valentina; Mirabelli, Giulia; Alunno, Alessia; Terenzi, Riccardo; Luccioli, Filippo; Bartoloni, Elena

    2015-01-01

    Cardiovascular (CV) system involvement is a frequent complication of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It still remains unclear if a premature atherosclerosis (ATS) occurs even in systemic sclerosis (SSc). Although microvascular disease is a hallmark of SSc, in the last few years a number of studies highlighted a higher prevalence of macrovascular disease in SSc patients in comparison to healthy individuals and these data have been correlated with a poorer prognosis. The mechanisms promoting ATS in SSc are not fully understood, but it is believed to be secondary to multi-system organ inflammation, endothelial wall damage and vasculopathy. Both traditional risk factors and endothelial dysfunction have been proposed to participate to the onset and progression of ATS in such patients. In particular, endothelial cell injury induced by anti-endothelial antibodies, ischemia/reperfusion damage, immune-mediated cytotoxicity represent the main causes of vascular injury together with an impaired vascular repair mechanism that determine a defective vasculogenesis. Aim of this review is to analyse both causes and clinical manifestations of macrovascular involvement and ATS in SSc. PMID:25705640

  9. [OVERWEIGHT CAUSES A DECREASE STOCKS CARDIOVASCULAR SYSTEM].

    PubMed

    Dobrostan, O V; Plyska, O I; Lazoryshunets, V V; Filimonova, N B

    2015-01-01

    Examined 117 students of the National Pedagogical Dragomanov University to assess body mass index and indicators of the functional state of the cardiovascular system. Was established that regulatory mechanisms in students with overweight and underweight are in a state of tension and functionalities of the cardiovascular system are reduced under normal conditions of learning.

  10. [OVERWEIGHT CAUSES A DECREASE STOCKS CARDIOVASCULAR SYSTEM].

    PubMed

    Dobrostan, O V; Plyska, O I; Lazoryshunets, V V; Filimonova, N B

    2015-01-01

    Examined 117 students of the National Pedagogical Dragomanov University to assess body mass index and indicators of the functional state of the cardiovascular system. Was established that regulatory mechanisms in students with overweight and underweight are in a state of tension and functionalities of the cardiovascular system are reduced under normal conditions of learning. PMID:27491148

  11. Allergy and the cardiovascular system.

    PubMed

    Triggiani, M; Patella, V; Staiano, R I; Granata, F; Marone, G

    2008-09-01

    The most dangerous and life-threatening manifestation of allergic diseases is anaphylaxis, a condition in which the cardiovascular system is responsible for the majority of clinical symptoms and for potentially fatal outcome. The heart is both a source and a target of chemical mediators released during allergic reactions. Mast cells are abundant in the human heart, where they are located predominantly around the adventitia of large coronary arteries and in close contact with the small intramural vessels. Cardiac mast cells can be activated by a variety of stimuli including allergens, complement factors, general anesthetics and muscle relaxants. Mediators released from immunologically activated human heart mast cells strongly influence ventricular function, cardiac rhythm and coronary artery tone. Histamine, cysteinyl leukotrienes and platelet-activating factor (PAF) exert negative inotropic effects and induce myocardial depression that contribute significantly to the pathogenesis of anaphylactic shock. Moreover, cardiac mast cells release chymase and renin that activates the angiotensin system locally, which further induces arteriolar vasoconstriction. The number and density of cardiac mast cells is increased in patients with ischaemic heart disease and dilated cardiomyopathies. This observation may help explain why these conditions are major risk factors for fatal anaphylaxis. A better understanding of the mechanisms involved in cardiac mast cell activation may lead to an improvement in prevention and treatment of systemic anaphylaxis.

  12. Patient-specific Modeling of Cardiovascular Mechanics

    PubMed Central

    Taylor, C.A.; Figueroa, C.A.

    2015-01-01

    Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Patient-specific models are being used to guide cell culture and animal experiments and test hypotheses related to the role of biomechanical factors in vascular diseases. Furthermore, biomechanical models based on noninvasive medical imaging could provide invaluable data on the in vivo service environment where cardiovascular devices are employed and the effect of the devices on physiologic function. Finally, the patient-specific modeling has enabled an entirely new application of cardiovascular mechanics, namely predicting outcomes of alternate therapeutic interventions for individual patients. We will review methods to create anatomic and physiologic models, obtain properties, assign boundary conditions, and solve the equations governing blood flow and vessel wall dynamics. Applications of patient-specific models of cardiovascular mechanics will be presented followed by a discussion of the challenges and opportunities that lie ahead. PMID:19400706

  13. Magnetic resonance imaging and spectroscopy of the murine cardiovascular system.

    PubMed

    Akki, Ashwin; Gupta, Ashish; Weiss, Robert G

    2013-03-01

    Magnetic resonance imaging (MRI) has emerged as a powerful and reliable tool to noninvasively study the cardiovascular system in clinical practice. Because transgenic mouse models have assumed a critical role in cardiovascular research, technological advances in MRI have been extended to mice over the last decade. These have provided critical insights into cardiac and vascular morphology, function, and physiology/pathophysiology in many murine models of heart disease. Furthermore, magnetic resonance spectroscopy (MRS) has allowed the nondestructive study of myocardial metabolism in both isolated hearts and in intact mice. This article reviews the current techniques and important pathophysiological insights from the application of MRI/MRS technology to murine models of cardiovascular disease.

  14. Feedback control of mean aortic pressure in a dynamic model of the cardiovascular system.

    PubMed

    O'Leary, D S; Pantalos, G M; Sharp, M K

    1999-01-01

    Orbital measurements of the cardiac function of Space Shuttle crew members have shown an initial increase in cardiac stroke volume upon entry into weightlessness, followed by a gradual reduction in stroke volume to a level approximately 15% less than preflight values. In an effort to explain this response, it was hypothesized that gravity plays a role in cardiac filling. A mock circulatory system was designed to investigate this effect. Preliminary studies carried out with this system on the NASA KC-135 aircraft, which provides brief periods of weightlessness, showed a strong correlation between cardiac filling, stroke volume, and the presence or absence of gravity. The need for extended periods of high quality zero gravity was identified to verify this observation. To accomplish this, the aircraft version of the experiment was reduced in size and fully automated for eventual integration into a Get Away Special canister to conduct an orbital version of the experiment. This article describes the automated system, as well as the development and implementation of a control algorithm for the servoregulation of the mean aortic pressure in the orbital experiment. Three nonlinearities that influence the ability of the apparatus to regulate to a mean aortic pressure of 95 mm Hg were identified and minimized. In preparation for a Space Shuttle flight, the successful function of the servoregulatory scheme was demonstrated during ground tests and additional test flights aboard the KC-135. The control algorithm was successful in carrying out the experimental protocol, including regulation of mean aortic pressure. The algorithm could also be used for the automated operation of long-term tests of circulatory support systems, which may require a scheduled cycling of the pumping conditions on a daily basis. PMID:10593691

  15. Vitamin D and the cardiovascular system.

    PubMed

    Beveridge, L A; Witham, M D

    2013-08-01

    Vitamin D, a secosteroid hormone, affects multiple biological pathways via both genomic and nongenomic signalling. Several pathways have potential benefit to cardiovascular health, including effects on parathyroid hormone, the renin-angiotensin-aldosterone system, vascular endothelial growth factor and cytokine production, as well as direct effects on endothelial cell function and myocyte calcium influx. Observational data supports a link between low vitamin D metabolite levels and cardiovascular health. Cross-sectional data shows associations between low 25-hydroxyvitamin D levels and stroke, myocardial infarction, diabetes mellitus, hypertension, and heart failure. Longitudinal data also suggests a relationship with incident hypertension and new cardiovascular events. However, these associations are potentially confounded by reverse causality and by the effects that other cardiovascular risk factors have on vitamin D metabolite levels. Intervention studies to date suggest a modest antihypertensive effect of vitamin D, no effect on serum lipids, a small positive effect on insulin resistance and fasting glucose, and equivocal actions on arterial stiffness and endothelial function. Analysis of cardiovascular event data collected from osteoporosis trials does not currently show a clear signal for reduced cardiovascular events with vitamin D supplementation, but results may be confounded by the coadministration of calcium, and by the secondary nature of the analyses. Despite mechanistic and observational data that suggest a protective role for vitamin D in cardiovascular disease, intervention studies to date are less promising. Large trials using cardiovascular events as a primary outcome are needed before vitamin D can be recommended as a therapy for cardiovascular disease.

  16. Vitamin D and the cardiovascular system.

    PubMed

    Artaza, Jorge N; Mehrotra, Rajnish; Norris, Keith C

    2009-09-01

    Several epidemiologic and clinical studies have suggested that there is a strong association between hypovitaminosis D and cardiovascular disease (CVD). Hypovitaminosis D was reported as a risk factor for increased cardiovascular events among 1739 adult participants in the Framingham Offspring Study. Analysis of more than 13,000 adults in the Third National Health and Nutrition Examination Survey (NHANES III) showed that even though hypovitaminosis D is associated with an increased prevalence of CVD risk factors, its association with all-cause mortality is independent of these risk factors. Importantly, epidemiologic studies suggested that patients who had chronic kidney disease and were treated with activated vitamin D had a survival advantage when compared with those who did not receive treatment with these agents. Mechanistically, emerging data have linked vitamin D administration with improved cardiac function and reduced proteinuria, and hypovitaminosis D is associated with obesity, insulin resistance, and systemic inflammation. Preliminary studies suggested that activated vitamin D inhibits the proliferation of cardiomyoblasts by promoting cell-cycle arrest and enhances the formation of cardiomyotubes without inducing apoptosis. Activated vitamin D has also been shown to attenuate left ventricular dysfunction in animal models and humans. In summary, emerging studies suggest that hypovitaminosis D has emerged as an independent risk factor for all-cause and cardiovascular mortality, reinforcing its importance as a public health problem. There is a need to advance our understanding of the biologic pathways through which vitamin D affects cardiovascular health and to conduct prospective clinical interventions to define precisely the cardioprotective effects of nutritional vitamin D repletion.

  17. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    PubMed Central

    Rice, K. M.; Fannin, J. C.; Gillette, C.; Blough, E. R.

    2014-01-01

    Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging. PMID:25610649

  18. Evaluating the hemodynamical response of a cardiovascular system under support of a continuous flow left ventricular assist device via numerical modeling and simulations.

    PubMed

    Bozkurt, Selim; Safak, Koray K

    2013-01-01

    Dilated cardiomyopathy is the most common type of the heart failure which can be characterized by impaired ventricular contractility. Mechanical circulatory support devices were introduced into practice for the heart failure patients to bridge the time between the decision to transplant and the actual transplantation which is not sufficient due to the state of donor organ supply. In this study, the hemodynamic response of a cardiovascular system that includes a dilated cardiomyopathic heart under support of a newly developed continuous flow left ventricular assist device--Heart Turcica Axial--was evaluated employing computer simulations. For the evaluation, a numerical model which describes the pressure-flow rate relations of Heart Turcica Axial, a cardiovascular system model describing the healthy and pathological hemodynamics, and a baroreflex model regulating the heart rate were used. Heart Turcica Axial was operated between 8000 rpm and 11,000 rpm speeds with 1000 rpm increments for assessing the pump performance and response of the cardiovascular system. The results also give an insight about the range of the possible operating speeds of Heart Turcica Axial in a clinical application. Based on the findings, operating speed of Heart Turcica Axial should be between 10,000 rpm and 11,000 rpm.

  19. Notch signaling in the developing cardiovascular system.

    PubMed

    Niessen, Kyle; Karsan, Aly

    2007-07-01

    The Notch proteins encompass a family of transmembrane receptors that have been highly conserved through evolution as mediators of cell fate. Recent findings have demonstrated a critical role of Notch in the developing cardiovascular system. Notch signaling has been implicated in the endothelial-to-mesenchymal transition during development of the heart valves, in arterial-venous differentiation, and in remodeling of the primitive vascular plexus. Mutations of Notch pathway components in humans are associated with congenital defects of the cardiovascular system such as Alagille syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and bicuspid aortic valves. This article focuses on the role of the Notch pathway in the developing cardiovascular system and congenital human cardiovascular diseases.

  20. Cardiovascular Toxicities from Systemic Breast Cancer Therapy

    PubMed Central

    Guo, Shuang; Wong, Serena

    2014-01-01

    Cardiovascular toxicity is unfortunately a potential short- or long-term sequela of breast cancer therapy. Both conventional chemotherapeutic agents such as anthracyclines and newer targeted agents such as trastuzumab can cause varying degrees of cardiac dysfunction. Type I cardiac toxicity is dose-dependent and irreversible, whereas Type II is not dose-dependent and is generally reversible with cessation of the drug. In this review, we discuss what is currently known about the cardiovascular effects of systemic breast cancer treatments, with a focus on the putative mechanisms of toxicity, the role of biomarkers, and potential methods of preventing and minimizing cardiovascular complications. PMID:25538891

  1. Cardiovascular magnetic resonance in systemic hypertension

    PubMed Central

    2012-01-01

    Systemic hypertension is a highly prevalent potentially modifiable cardiovascular risk factor. Imaging plays an important role in the diagnosis of underlying causes for hypertension, in assessing cardiovascular complications of hypertension, and in understanding the pathophysiology of the disease process. Cardiovascular magnetic resonance (CMR) provides accurate and reproducible measures of ventricular volumes, mass, function and haemodynamics as well as uniquely allowing tissue characterization of diffuse and focal fibrosis. In addition, CMR is well suited for exclusion of common secondary causes for hypertension. We review the current and emerging clinical and research applications of CMR in hypertension. PMID:22559053

  2. Thyroid disease and the cardiovascular system.

    PubMed

    Danzi, Sara; Klein, Irwin

    2014-06-01

    Thyroid hormones, specifically triiodothyronine (T3), have significant effects on the heart and cardiovascular system. Hypothyroidism, hyperthyroidism, subclinical thyroid disease, and low T3 syndrome each cause cardiac and cardiovascular abnormalities through both genomic and nongenomic effects on cardiac myocytes and vascular smooth muscle cells. In compromised health, such as occurs in heart disease, alterations in thyroid hormone metabolism may further impair cardiac and cardiovascular function. Diagnosis and treatment of cardiac disease may benefit from including analysis of thyroid hormone status, including serum total T3 levels.

  3. Amyloid in the cardiovascular system: a review

    PubMed Central

    Kholová, I; Niessen, H W M

    2005-01-01

    The cardiovascular system is a common target of amyloidosis. This review presents the current clinical and diagnostic approach to amyloidosis, with the emphasis on cardiovascular involvement. It summarises recent nomenclature, classification, and pathogenesis of amyloidosis. In addition, non-invasive possibilities are discussed, together with endomyocardial biopsies in the diagnosis of cardiac amyloidosis. Finally, recent advances in treatment and prognostic implications are presented. PMID:15677530

  4. Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device

    PubMed Central

    Gohean, Jeffrey R.; George, Mitchell J.; Pate, Thomas D.; Kurusz, Mark; Longoria, Raul G.; Smalling, Richard W.

    2012-01-01

    The purpose of this investigation is to utilize a computational model to compare a synchronized valveless pulsatile left ventricular assist device to continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous, pulsatile, valveless, dual piston positive displacement pump. These results were compared to measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared to the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device. PMID:23438771

  5. Modeling of Cardiovascular Response to Weightlessness

    NASA Technical Reports Server (NTRS)

    Sharp, M. Keith

    1999-01-01

    pressure and, to a limited extent, in extravascular and pedcardial hydrostatic pressure were investigated. A complete hydraulic model of the cardiovascular system was built and flown aboard the NASA KC-135 and a computer model was developed and tested in simulated microgravity. Results obtained with these models have confirmed that a simple lack of hydrostatic pressure within an artificial ventricle causes a decrease in stroke volume. When combined with the acute increase in ventricular pressure associated with the elimination of hydrostatic pressure within the vasculature and the resultant cephalad fluid shift with the models in the upright position, however, stroke volume increased in the models. Imposition of a decreased pedcardial pressure in the computer model and in a simplified hydraulic model increased stroke volume. Physiologic regional fluid shifting was also demonstrated by the models. The unifying parameter characterizing of cardiac response was diastolic ventricular transmural pressure (DVDELTAP) The elimination of intraventricular hydrostatic pressure in O-G decreased DVDELTAP stroke volume, while the elimination of intravascular hydrostatic pressure increased DVDELTAP and stroke volume in the upright posture, but reduced DVDELTAP and stroke volume in the launch posture. The release of gravity on the chest wall and its associated influence on intrathoracic pressure, simulated by a drop in extraventricular pressure4, increased DVDELTAP ans stroke volume.

  6. A population model of integrative cardiovascular physiology.

    PubMed

    Pruett, William A; Husband, Leland D; Husband, Graham; Dakhlalla, Muhammad; Bellamy, Kyle; Coleman, Thomas G; Hester, Robert L

    2013-01-01

    We present a small integrative model of human cardiovascular physiology. The model is population-based; rather than using best fit parameter values, we used a variant of the Metropolis algorithm to produce distributions for the parameters most associated with model sensitivity. The population is built by sampling from these distributions to create the model coefficients. The resulting models were then subjected to a hemorrhage. The population was separated into those that lost less than 15 mmHg arterial pressure (compensators), and those that lost more (decompensators). The populations were parametrically analyzed to determine baseline conditions correlating with compensation and decompensation. Analysis included single variable correlation, graphical time series analysis, and support vector machine (SVM) classification. Most variables were seen to correlate with propensity for circulatory collapse, but not sufficiently to effect reasonable classification by any single variable. Time series analysis indicated a single significant measure, the stressed blood volume, as predicting collapse in situ, but measurement of this quantity is clinically impossible. SVM uncovered a collection of variables and parameters that, when taken together, provided useful rubrics for classification. Due to the probabilistic origins of the method, multiple classifications were attempted, resulting in an average of 3.5 variables necessary to construct classification. The most common variables used were systemic compliance, baseline baroreceptor signal strength and total peripheral resistance, providing predictive ability exceeding 90%. The methods presented are suitable for use in any deterministic mathematical model. PMID:24058546

  7. A Population Model of Integrative Cardiovascular Physiology

    PubMed Central

    Pruett, William A.; Husband, Leland D.; Husband, Graham; Dakhlalla, Muhammad; Bellamy, Kyle; Coleman, Thomas G.; Hester, Robert L.

    2013-01-01

    We present a small integrative model of human cardiovascular physiology. The model is population-based; rather than using best fit parameter values, we used a variant of the Metropolis algorithm to produce distributions for the parameters most associated with model sensitivity. The population is built by sampling from these distributions to create the model coefficients. The resulting models were then subjected to a hemorrhage. The population was separated into those that lost less than 15 mmHg arterial pressure (compensators), and those that lost more (decompensators). The populations were parametrically analyzed to determine baseline conditions correlating with compensation and decompensation. Analysis included single variable correlation, graphical time series analysis, and support vector machine (SVM) classification. Most variables were seen to correlate with propensity for circulatory collapse, but not sufficiently to effect reasonable classification by any single variable. Time series analysis indicated a single significant measure, the stressed blood volume, as predicting collapse in situ, but measurement of this quantity is clinically impossible. SVM uncovered a collection of variables and parameters that, when taken together, provided useful rubrics for classification. Due to the probabilistic origins of the method, multiple classifications were attempted, resulting in an average of 3.5 variables necessary to construct classification. The most common variables used were systemic compliance, baseline baroreceptor signal strength and total peripheral resistance, providing predictive ability exceeding 90%. The methods presented are suitable for use in any deterministic mathematical model. PMID:24058546

  8. A population model of integrative cardiovascular physiology.

    PubMed

    Pruett, William A; Husband, Leland D; Husband, Graham; Dakhlalla, Muhammad; Bellamy, Kyle; Coleman, Thomas G; Hester, Robert L

    2013-01-01

    We present a small integrative model of human cardiovascular physiology. The model is population-based; rather than using best fit parameter values, we used a variant of the Metropolis algorithm to produce distributions for the parameters most associated with model sensitivity. The population is built by sampling from these distributions to create the model coefficients. The resulting models were then subjected to a hemorrhage. The population was separated into those that lost less than 15 mmHg arterial pressure (compensators), and those that lost more (decompensators). The populations were parametrically analyzed to determine baseline conditions correlating with compensation and decompensation. Analysis included single variable correlation, graphical time series analysis, and support vector machine (SVM) classification. Most variables were seen to correlate with propensity for circulatory collapse, but not sufficiently to effect reasonable classification by any single variable. Time series analysis indicated a single significant measure, the stressed blood volume, as predicting collapse in situ, but measurement of this quantity is clinically impossible. SVM uncovered a collection of variables and parameters that, when taken together, provided useful rubrics for classification. Due to the probabilistic origins of the method, multiple classifications were attempted, resulting in an average of 3.5 variables necessary to construct classification. The most common variables used were systemic compliance, baseline baroreceptor signal strength and total peripheral resistance, providing predictive ability exceeding 90%. The methods presented are suitable for use in any deterministic mathematical model.

  9. Models of Cheyne-Stokes respiration with cardiovascular pathologies.

    PubMed

    Dong, Fang; Langford, William F

    2008-10-01

    Cheyne-Stokes respiration (CSR) is a periodic breathing pattern, characterized by short intervals of very little or no breathing (apnea), each followed by an interval of very heavy breathing (hyperpnea). This work presents a new compartmental model of the human cardio-respiratory system, simulating the factors that determine the concentrations of carbon dioxide in the compartments of the cardiovascular system and the lungs. The parameter set on which a Hopf bifurcation gives birth to stable CSR oscillations has been determined. The model predicts that the onset of CSR oscillations may result from an increase in any of: ventilation-perfusion ratio, feedback control gain, transport delay, left heart volume, lung congestion, or cardiovascular efficiency. The model is employed to investigate the relationship between CSR and serious cardiovascular pathologies, such as congestive heart failure and encephalitis, as well as the effects of acclimatization to higher altitudes. In all cases, the model is consistent with medical observations.

  10. Modelling of long-term and short-term mechanisms of arterial pressure control in the cardiovascular system: an object-oriented approach.

    PubMed

    Fernandez de Canete, J; Luque, J; Barbancho, J; Munoz, V

    2014-04-01

    A mathematical model that provides an overall description of both the short- and long-term mechanisms of arterial pressure regulation is presented. Short-term control is exerted through the baroreceptor reflex while renal elimination plays a role in long-term control. Both mechanisms operate in an integrated way over the compartmental model of the cardiovascular system. The whole system was modelled in MODELICA, which uses a hierarchical object-oriented modelling strategy, under the DYMOLA simulation environment. The performance of the controlled system was analysed by simulation in light of the existing hypothesis and validation tests previously performed with physiological data, demonstrating the effectiveness of both regulation mechanisms under physiological and pathological conditions.

  11. Modelling of long-term and short-term mechanisms of arterial pressure control in the cardiovascular system: an object-oriented approach.

    PubMed

    Fernandez de Canete, J; Luque, J; Barbancho, J; Munoz, V

    2014-04-01

    A mathematical model that provides an overall description of both the short- and long-term mechanisms of arterial pressure regulation is presented. Short-term control is exerted through the baroreceptor reflex while renal elimination plays a role in long-term control. Both mechanisms operate in an integrated way over the compartmental model of the cardiovascular system. The whole system was modelled in MODELICA, which uses a hierarchical object-oriented modelling strategy, under the DYMOLA simulation environment. The performance of the controlled system was analysed by simulation in light of the existing hypothesis and validation tests previously performed with physiological data, demonstrating the effectiveness of both regulation mechanisms under physiological and pathological conditions. PMID:24561348

  12. Hydrogen sulfide in the mammalian cardiovascular system.

    PubMed

    Liu, Yi-Hong; Lu, Ming; Hu, Li-Fang; Wong, Peter T-H; Webb, George D; Bian, Jin-Song

    2012-07-01

    For more than a century, hydrogen sulfide (H(2)S) has been regarded as a toxic gas. This review surveys the growing recognition of the role of H(2)S as an endogenous signaling molecule in mammals, with emphasis on its physiological and pathological pathways in the cardiovascular system. In biological fluids, H(2)S gas is a weak acid that exists as about 15% H(2)S, 85% HS(-), and a trace of S(2-). Here, we use "H(2)S" to refer to this mixture. H(2)S has been found to influence heart contractile functions and may serve as a cardioprotectant for treating ischemic heart diseases and heart failure. Alterations of the endogenous H(2)S level have been found in animal models with various pathological conditions such as myocardial ischemia, spontaneous hypertension, and hypoxic pulmonary hypertension. In the vascular system, H(2)S exerts biphasic regulation of a vascular tone with varying effects based on its concentration and in the presence of nitric oxide. Over the past decade, several H(2)S-releasing compounds (NaHS, Na(2)S, GYY4137, etc.) have been utilized to test the effect of exogenous H(2)S under different physiological and pathological situations in vivo and in vitro. H(2)S has been found to promote angiogenesis and to protect against atherosclerosis and hypertension, while excess H(2)S may promote inflammation in septic or hemorrhagic shock. H(2)S-releasing compounds and inhibitors of H(2)S synthesis hold promise in alleviating specific disease conditions. This comprehensive review covers in detail the effects of H(2)S on the cardiovascular system, especially in disease situations, and also the various underlying mechanisms.

  13. Role of TRP channels in the cardiovascular system.

    PubMed

    Yue, Zhichao; Xie, Jia; Yu, Albert S; Stock, Jonathan; Du, Jianyang; Yue, Lixia

    2015-02-01

    The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca(2+)-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca(2+) entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases.

  14. Role of TRP channels in the cardiovascular system

    PubMed Central

    Yue, Zhichao; Xie, Jia; Yu, Albert S.; Stock, Jonathan; Du, Jianyang

    2014-01-01

    The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca2+-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. PMID:25416190

  15. Characterization of Angiotensin-(1-7) effects on the cardiovascular system in an experimental model of type-1 diabetes.

    PubMed

    Yousif, Mariam H M; Dhaunsi, Gursev S; Makki, Batoul M; Qabazard, Bedour A; Akhtar, Saghir; Benter, Ibrahim F

    2012-09-01

    Although exogenous administration of Angiotensin-(1-7) [Ang-(1-7)] can prevent development of diabetes induced end-organ damage, little is known about the role of endogenous Ang-(1-7) in diabetes and requires further characterization. Here, we studied the effects of chronically inhibiting endogenous Ang-(1-7) formation with DX600, a selective angiotensin converting enzyme-2 (ACE2) inhibitor, on renal and cardiac NADPH oxidase (NOX) activity, vascular reactivity and cardiac function in a model of Type-1 diabetes. The contribution of endogenous Ang-(1-7) to the protective effects of Losartan and Captopril and that of prostaglandins to the cardiovascular effects of exogenous Ang-(1-7) were also examined. Cardiac and renal NOX activity, vascular reactivity to endothelin-1 (ET-1) and cardiac recovery from ischemia/reperfusion (I/R) injury were evaluated in streptozotocin-treated rats. Chronic treatment with DX600 exacerbated diabetes-induced increase in cardiac and renal NOX activity. Diabetes-induced abnormal vascular reactivity to ET-1 and cardiac dysfunction were improved by treatment with Ang-(1-7) and worsened by treatment with DX600 or A779, a Mas receptor antagonist. Ang-(1-7)-mediated improvement in cardiac recovery or vascular reactivity was attenuated by Indomethacin. Captopril and Losartan-induced improvement in cardiovascular function was attenuated when these drugs were co-administered with A779. Ang-(1-7)-mediated decrease in renal NOX activity was prevented by indomethacin. Losartan also decreased renal NOX activity that could be attenuated with A779 co-treatment. In conclusion, endogenous Ang-(1-7) inhibits diabetes-induced cardiac/renal NOX activity and end-organ damage, and mediates the actions of Captopril and Losartan. Further, prostaglandins are important intermediaries in the beneficial effects of Ang-(1-7) in diabetes. Combining either Losartan or Captopril with Ang-(1-7) had additional beneficial effects in preventing diabetes-induced cardiac

  16. Sex hormones in the cardiovascular system.

    PubMed

    dos Santos, Roger Lyrio; da Silva, Fabrício Bragança; Ribeiro, Rogério Faustino; Stefanon, Ivanita

    2014-05-01

    Gender-associated differences in the development of cardiovascular diseases have been described in humans and animals. These differences could explain the low incidence of cardiovascular disease in women in the reproductive period, such as stroke, hypertension, and atherosclerosis. The cardiovascular protection observed in females has been attributed to the beneficial effects of estrogen on endothelial function. Besides estrogen, sex hormones are able to modulate blood pressure by acting on important systems as cardiovascular, renal, and neural. They can have complementary or antagonistic actions. For example, testosterone can raise blood pressure by stimulating the renin-angiotensin-aldosterone system, whereas estrogen alone or combined with progesterone has been associated with decreased blood pressure. The effects of testosterone in the development of cardiovascular disease are contradictory. Although some researchers suggest a positive effect, others indicate negative actions of testosterone. Estrogens physiologically stimulate the release of endothelium-derived vasodilator factors and inhibit the renin-angiotensin system. Although the cardioprotective effects of estrogen are widely appreciated, little is known about the effects of progesterone, which is commonly used in hormone replacement therapy. Progesterone has both vasodilatory and vasoconstrictive effects in the vasculature, depending on the location of the vessel and the level of exposure. Nevertheless, the mechanisms through which sex hormones modulate blood pressure have not been fully elucidated. Therefore, the characterization of those could lead to a better understanding of hypertension in women and men and perhaps to improved forms of therapy.

  17. Ginsenoside Re: pharmacological effects on cardiovascular system.

    PubMed

    Peng, Lu; Sun, Shi; Xie, Lai-Hua; Wicks, Sheila M; Xie, Jing-Tian

    2012-08-01

    Ginsenosides are the bioactive constituents of ginseng, a key herb in traditional Chinese medicine. As a single component of ginseng, ginsenoside Re (G-Re) belongs to the panaxatriol group. Many reports demonstrated that G-Re possesses the multifaceted beneficial pharmacological effects on cardiovascular system. G-Re has negative effect on cardiac contractility and autorhythmicity. It causes alternations in cardiac electrophysiological properties, which may account for its antiarrhythmic effect. In addition, G-Re also exerts antiischemic effect and induces angiogenic regeneration. In this review, we first outline the chemistry and the pharmacological effects of G-Re on the cardiovascular system.

  18. A Mechanical System to Reproduce Cardiovascular Flows

    NASA Astrophysics Data System (ADS)

    Lindsey, Thomas; Valsecchi, Pietro

    2010-11-01

    Within the framework of the "Pumps&Pipes" collaboration between ExxonMobil Upstream Research Company and The DeBakey Heart and Vascular Center in Houston, a hydraulic control system was developed to accurately simulate general cardiovascular flows. The final goal of the development of the apparatus was the reproduction of the periodic flow of blood through the heart cavity with the capability of varying frequency and amplitude, as well as designing the systolic/diastolic volumetric profile over one period. The system consists of a computer-controlled linear actuator that drives hydraulic fluid in a closed loop to a secondary hydraulic cylinder. The test section of the apparatus is located inside a MRI machine, and the closed loop serves to physically separate all metal moving parts (control system and actuator cylinder) from the MRI-compatible pieces. The secondary cylinder is composed of nonmetallic elements and directly drives the test section circulatory flow loop. The circulatory loop consists of nonmetallic parts and several types of Newtonian and non-Newtonian fluids, which model the behavior of blood. This design allows for a periodic flow of blood-like fluid pushed through a modeled heart cavity capable of replicating any healthy heart condition as well as simulating anomalous conditions. The behavior of the flow inside the heart can thus be visualized by MRI techniques.

  19. User's instructions for the cardiovascular Walters model

    NASA Technical Reports Server (NTRS)

    Croston, R. C.

    1973-01-01

    The model is a combined, steady-state cardiovascular and thermal model. It was originally developed for interactive use, but was converted to batch mode simulation for the Sigma 3 computer. The model has the purpose to compute steady-state circulatory and thermal variables in response to exercise work loads and environmental factors. During a computer simulation run, several selected variables are printed at each time step. End conditions are also printed at the completion of the run.

  20. Testosterone Replacement Therapy and the Cardiovascular System.

    PubMed

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  1. Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.

    PubMed

    Lavie, Carl J; Arena, Ross; Swift, Damon L; Johannsen, Neil M; Sui, Xuemei; Lee, Duck-Chul; Earnest, Conrad P; Church, Timothy S; O'Keefe, James H; Milani, Richard V; Blair, Steven N

    2015-07-01

    Substantial evidence has established the value of high levels of physical activity, exercise training (ET), and overall cardiorespiratory fitness in the prevention and treatment of cardiovascular diseases. This article reviews some basics of exercise physiology and the acute and chronic responses of ET, as well as the effect of physical activity and cardiorespiratory fitness on cardiovascular diseases. This review also surveys data from epidemiological and ET studies in the primary and secondary prevention of cardiovascular diseases, particularly coronary heart disease and heart failure. These data strongly support the routine prescription of ET to all patients and referrals for patients with cardiovascular diseases, especially coronary heart disease and heart failure, to specific cardiac rehabilitation and ET programs.

  2. Magnetic resonance imaging and spectroscopy of the murine cardiovascular system

    PubMed Central

    Akki, Ashwin; Gupta, Ashish

    2013-01-01

    Magnetic resonance imaging (MRI) has emerged as a powerful and reliable tool to noninvasively study the cardiovascular system in clinical practice. Because transgenic mouse models have assumed a critical role in cardiovascular research, technological advances in MRI have been extended to mice over the last decade. These have provided critical insights into cardiac and vascular morphology, function, and physiology/pathophysiology in many murine models of heart disease. Furthermore, magnetic resonance spectroscopy (MRS) has allowed the nondestructive study of myocardial metabolism in both isolated hearts and in intact mice. This article reviews the current techniques and important pathophysiological insights from the application of MRI/MRS technology to murine models of cardiovascular disease. PMID:23292717

  3. Effect of zero magnetic field on cardiovascular system and microcirculation

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Yu. I.; At'kov, O. Yu.; Vasin, A. L.; Breus, T. K.; Sasonko, M. L.; Pishchalnikov, R. Yu.

    2016-02-01

    The effects of zero magnetic field conditions on cardiovascular system of healthy adults have been studied. In order to generate zero magnetic field, the facility for magnetic fields modeling "ARFA" has been used. Parameters of the capillary blood flow, blood pressure, and the electrocardiogram (ECG) monitoring were measured during the study. All subjects were tested twice: in zero magnetic field and, for comparison, in sham condition. The obtained results during 60 minutes of zero magnetic field exposure demonstrate a clear effect on cardiovascular system and microcirculation. The results of our experiments can be used in studies of long-term stay in hypo-magnetic conditions during interplanetary missions.

  4. Effect of zero magnetic field on cardiovascular system and microcirculation.

    PubMed

    Gurfinkel, Yu I; At'kov, O Yu; Vasin, A L; Breus, T K; Sasonko, M L; Pishchalnikov, R Yu

    2016-02-01

    The effects of zero magnetic field conditions on cardiovascular system of healthy adults have been studied. In order to generate zero magnetic field, the facility for magnetic fields modeling "ARFA" has been used. Parameters of the capillary blood flow, blood pressure, and the electrocardiogram (ECG) monitoring were measured during the study. All subjects were tested twice: in zero magnetic field and, for comparison, in sham condition. The obtained results during 60 minutes of zero magnetic field exposure demonstrate a clear effect on cardiovascular system and microcirculation. The results of our experiments can be used in studies of long-term stay in hypo-magnetic conditions during interplanetary missions. PMID:26948007

  5. Principal component analysis of HPLC retention data and molecular modeling structural parameters of cardiovascular system drugs in view of their pharmacological activity.

    PubMed

    Stasiak, Jolanta; Koba, Marcin; Bober, Leszek; Baczek, Tomasz

    2010-07-09

    Evaluation of relationships between molecular modeling structural parameters and high-performance liquid chromatography (HPLC) retention data of 11 cardiovascular system drugs by principal component analysis (PCA) in relation to their pharmacological activity was performed. The six retention data parameters were determined on three different HPLC columns (Nucleosil C18 AB with octadecylsilica stationary phase, IAM PC C10/C3 with chemically bounded phosphatidylcholine, and Nucleosil 100-5 OH with chemically bounded propanodiole), and using isocratically acetonitrile: Britton-Robinson buffer as the mobile phase. Additionally, molecular modeling studies were performed with the use of HyperChem software and MM+ molecular mechanics with the semi-empirical AM1 method deriving 20 structural descriptors. Factor analysis obtained with the use of various sets of parameters: structural parameters, HPLC retention data, and all 26 considered parameters, led to the extraction of two main factors. The first principal component (factor 1) accounted for 44-57% of the variance in the data. The second principal component (factor 2) explained 29-33% of data variance. Moreover, the total data variance explained by the first two factors was at the level of 73-90%. More importantly, the PCA analysis of the HPLC retention data and structural parameters allows the segregation of circulatory system drugs according to their pharmacological (cardiovascular) properties as shown by the distribution of the individual drugs on the plane determined by the two principal components (factors 1 and 2).

  6. Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems

    PubMed Central

    Choma, Michael A.; Suter, Melissa J.; Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.

    2011-01-01

    SUMMARY The physiology of the Drosophila melanogaster cardiovascular system remains poorly characterized compared with its vertebrate counterparts. Basic measures of physiological performance remain unknown. It also is unclear whether subtle physiological defects observed in the human cardiovascular system can be reproduced in D. melanogaster. Here we characterize the cardiovascular physiology of D. melanogaster in its pre-pupal stage by using high-speed dye angiography and optical coherence tomography. The heart has vigorous pulsatile contractions that drive intracardiac, aortic and extracellular-extravascular hemolymph flow. Several physiological measures, including weight-adjusted cardiac output, body-length-adjusted aortic velocities and intracardiac shear forces, are similar to those in the closed vertebrate cardiovascular systems, including that of humans. Extracellular-extravascular flow in the pre-pupal D. melanogaster circulation drives convection-limited fluid transport. To demonstrate homology in heart dysfunction, we showed that, at the pre-pupal stage, a troponin I mutant, held-up2 (hdp2), has impaired systolic and diastolic heart wall velocities. Impaired heart wall velocities occur in the context of a non-dilated phenotype with a mildly depressed fractional shortening. We additionally derive receiver operating characteristic curves showing that heart wall velocity is a potentially powerful discriminator of systolic heart dysfunction. Our results demonstrate physiological homology and support the use of D. melanogaster as an animal model of complex cardiovascular disease. PMID:21183476

  7. Clinical models of cardiovascular regulation after weightlessness

    NASA Technical Reports Server (NTRS)

    Robertson, D.; Jacob, G.; Ertl, A.; Shannon, J.; Mosqueda-Garcia, R.; Robertson, R. M.; Biaggioni, I.

    1996-01-01

    After several days in microgravity, return to earth is attended by alterations in cardiovascular function. The mechanisms underlying these effects are inadequately understood. Three clinical disorders of autonomic function represent possible models of this abnormal cardiovascular function after spaceflight. They are pure autonomic failure, baroreflex failure, and orthostatic intolerance. In pure autonomic failure, virtually complete loss of sympathetic and parasympathetic function occurs along with profound and immediate orthostatic hypotension. In baroreflex failure, various degrees of debuffering of blood pressure occur. In acute and complete baroreflex failure, there is usually severe hypertension and tachycardia, while with less complete and more chronic baroreflex impairment, orthostatic abnormalities may be more apparent. In orthostatic intolerance, blood pressure fall is minor, but orthostatic symptoms are prominent and tachycardia frequently occurs. Only careful autonomic studies of human subjects in the microgravity environment will permit us to determine which of these models most closely reflects the pathophysiology brought on by a period of time in the microgravity environment.

  8. A model for educational simulation of infant cardiovascular physiology.

    PubMed

    Goodwin, Jane A; van Meurs, Willem L; Sá Couto, Carla D; Beneken, Jan E W; Graves, Shirley A

    2004-12-01

    Full-body patient simulators provide the technology and the environment necessary for excellent clinical education while eliminating risk to the patient. The extension of simulator-based training into management of basic and critical situations in complex patient populations is natural. We describe the derivation of an infant cardiovascular model through the redefinition of a complete set of parameters for an existing adult model. Specifically, we document a stepwise parameter estimation process, explicit simplifying assumptions, and sources for these parameters. The simulated vital signs are within the target hemodynamic variables, and the simulated systemic arterial pressure wave form and left ventricular pressure volume loop are realistic. The system reacts appropriately to blood loss, and incorporation of aortic stenosis is straightforward. This infant cardiovascular model can form the basis for screen-based educational simulations. The model is also an essential step in attaining a full-body, model-driven infant simulator.

  9. Mathematical biomarkers for the autonomic regulation of cardiovascular system.

    PubMed

    Campos, Luciana A; Pereira, Valter L; Muralikrishna, Amita; Albarwani, Sulayma; Brás, Susana; Gouveia, Sónia

    2013-10-07

    Heart rate and blood pressure are the most important vital signs in diagnosing disease. Both heart rate and blood pressure are characterized by a high degree of short term variability from moment to moment, medium term over the normal day and night as well as in the very long term over months to years. The study of new mathematical algorithms to evaluate the variability of these cardiovascular parameters has a high potential in the development of new methods for early detection of cardiovascular disease, to establish differential diagnosis with possible therapeutic consequences. The autonomic nervous system is a major player in the general adaptive reaction to stress and disease. The quantitative prediction of the autonomic interactions in multiple control loops pathways of cardiovascular system is directly applicable to clinical situations. Exploration of new multimodal analytical techniques for the variability of cardiovascular system may detect new approaches for deterministic parameter identification. A multimodal analysis of cardiovascular signals can be studied by evaluating their amplitudes, phases, time domain patterns, and sensitivity to imposed stimuli, i.e., drugs blocking the autonomic system. The causal effects, gains, and dynamic relationships may be studied through dynamical fuzzy logic models, such as the discrete-time model and discrete-event model. We expect an increase in accuracy of modeling and a better estimation of the heart rate and blood pressure time series, which could be of benefit for intelligent patient monitoring. We foresee that identifying quantitative mathematical biomarkers for autonomic nervous system will allow individual therapy adjustments to aim at the most favorable sympathetic-parasympathetic balance.

  10. Mathematical biomarkers for the autonomic regulation of cardiovascular system.

    PubMed

    Campos, Luciana A; Pereira, Valter L; Muralikrishna, Amita; Albarwani, Sulayma; Brás, Susana; Gouveia, Sónia

    2013-01-01

    Heart rate and blood pressure are the most important vital signs in diagnosing disease. Both heart rate and blood pressure are characterized by a high degree of short term variability from moment to moment, medium term over the normal day and night as well as in the very long term over months to years. The study of new mathematical algorithms to evaluate the variability of these cardiovascular parameters has a high potential in the development of new methods for early detection of cardiovascular disease, to establish differential diagnosis with possible therapeutic consequences. The autonomic nervous system is a major player in the general adaptive reaction to stress and disease. The quantitative prediction of the autonomic interactions in multiple control loops pathways of cardiovascular system is directly applicable to clinical situations. Exploration of new multimodal analytical techniques for the variability of cardiovascular system may detect new approaches for deterministic parameter identification. A multimodal analysis of cardiovascular signals can be studied by evaluating their amplitudes, phases, time domain patterns, and sensitivity to imposed stimuli, i.e., drugs blocking the autonomic system. The causal effects, gains, and dynamic relationships may be studied through dynamical fuzzy logic models, such as the discrete-time model and discrete-event model. We expect an increase in accuracy of modeling and a better estimation of the heart rate and blood pressure time series, which could be of benefit for intelligent patient monitoring. We foresee that identifying quantitative mathematical biomarkers for autonomic nervous system will allow individual therapy adjustments to aim at the most favorable sympathetic-parasympathetic balance. PMID:24109456

  11. Estrogen in Cardiovascular Disease during Systemic Lupus Erythematosus

    PubMed Central

    Gilbert, Emily L.; Ryan, Michael J.

    2015-01-01

    Purpose Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. Methods PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. Findings The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against

  12. Drug releasing systems in cardiovascular tissue engineering

    PubMed Central

    Spadaccio, Cristiano; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto; Toyoda, Yoshiya; Genovese, Jorge A

    2009-01-01

    Abstract Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date. PMID:19379142

  13. O-GlcNAc and the cardiovascular system.

    PubMed

    Dassanayaka, Sujith; Jones, Steven P

    2014-04-01

    The cardiovascular system is capable of robust changes in response to physiologic and pathologic stimuli through intricate signaling mechanisms. The area of metabolism has witnessed a veritable renaissance in the cardiovascular system. In particular, the post-translational β-O-linkage of N-acetylglucosamine (O-GlcNAc) to cellular proteins represents one such signaling pathway that has been implicated in the pathophysiology of cardiovascular disease. This highly dynamic protein modification may induce functional changes in proteins and regulate key cellular processes including translation, transcription, and cell death. In addition, its potential interplay with phosphorylation provides an additional layer of complexity to post-translational regulation. The hexosamine biosynthetic pathway generally requires glucose to form the nucleotide sugar, UDP-GlcNAc. Accordingly, O-GlcNAcylation may be altered in response to nutrient availability and cellular stress. Recent literature supports O-GlcNAcylation as an autoprotective response in models of acute stress (hypoxia, ischemia, oxidative stress). Models of sustained stress, such as pressure overload hypertrophy, and infarct-induced heart failure, may also require protein O-GlcNAcylation as a partial compensatory mechanism. Yet, in models of Type II diabetes, O-GlcNAcylation has been implicated in the subsequent development of vascular, and even cardiac, dysfunction. This review will address this apparent paradox and discuss the potential mechanisms of O-GlcNAc-mediated cardioprotection and cardiovascular dysfunction. This discussion will also address potential targets for pharmacologic interventions and the unique considerations related to such targets.

  14. Cardiovascular response to dynamic aerobic exercise: a mathematical model.

    PubMed

    Magosso, E; Ursino, M

    2002-11-01

    An original mathematical model of the cardiovascular response to dynamic exercise is presented. It includes the pulsating heart, the pulmonary and systemic circulation, a separate description of the vascular bed in active tissues, the local metabolic vasodilation in these tissues and the mechanical effects of muscular contractions on venous return. Moreover, the model provides a description of the ventilatory response to exercise and various neural regulatory mechanisms working on cardiovascular parameters. These mechanisms embrace the so-called central command, the arterial baroreflex and the lung inflation reflex. All parameters in the model have been given in accordance with physiological data from the literature. In this work, the model has been used to simulate the steady-state value of the main cardiorespiratory quantities at different levels of aerobic exercise and the temporal pattern in the transient phase from rest to moderate exercise. Results suggest that, with suitable parameter values the model is able accurately to simulate the cardiorespiratory response in the overall range of aerobic exercise. This response is characterised by a moderate hypertension (10-30%) and by a conspicuous increase in systemic conductance (80-130%), heart rate (64-150%) and cardiac output (100-200%). The transient pattern exhibits three distinct phases (lasting approximately 5s, 15s and 2 min), that reflect the temporal heterogeneity of the mechanisms involved. The model may be useful to improve understanding of exercise physiology and as an educational tool to analyse the complexity of cardiovascular and respiratory regulation.

  15. Cardiovascular response to dynamic aerobic exercise: a mathematical model.

    PubMed

    Magosso, E; Ursino, M

    2002-11-01

    An original mathematical model of the cardiovascular response to dynamic exercise is presented. It includes the pulsating heart, the pulmonary and systemic circulation, a separate description of the vascular bed in active tissues, the local metabolic vasodilation in these tissues and the mechanical effects of muscular contractions on venous return. Moreover, the model provides a description of the ventilatory response to exercise and various neural regulatory mechanisms working on cardiovascular parameters. These mechanisms embrace the so-called central command, the arterial baroreflex and the lung inflation reflex. All parameters in the model have been given in accordance with physiological data from the literature. In this work, the model has been used to simulate the steady-state value of the main cardiorespiratory quantities at different levels of aerobic exercise and the temporal pattern in the transient phase from rest to moderate exercise. Results suggest that, with suitable parameter values the model is able accurately to simulate the cardiorespiratory response in the overall range of aerobic exercise. This response is characterised by a moderate hypertension (10-30%) and by a conspicuous increase in systemic conductance (80-130%), heart rate (64-150%) and cardiac output (100-200%). The transient pattern exhibits three distinct phases (lasting approximately 5s, 15s and 2 min), that reflect the temporal heterogeneity of the mechanisms involved. The model may be useful to improve understanding of exercise physiology and as an educational tool to analyse the complexity of cardiovascular and respiratory regulation. PMID:12507317

  16. Cardiovascular imaging: what have we learned from animal models?

    PubMed Central

    Santos, Arnoldo; Fernández-Friera, Leticia; Villalba, María; López-Melgar, Beatriz; España, Samuel; Mateo, Jesús; Mota, Ruben A.; Jiménez-Borreguero, Jesús; Ruiz-Cabello, Jesús

    2015-01-01

    Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a non-destructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, (i) the technical development of different imaging tools, (ii) to test hypothesis generated from human studies and finally, (iii) to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function, and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models. PMID:26539113

  17. Effects of artificial gravity on the cardiovascular system: Computational approach

    NASA Astrophysics Data System (ADS)

    Diaz Artiles, Ana; Heldt, Thomas; Young, Laurence R.

    2016-09-01

    Artificial gravity has been suggested as a multisystem countermeasure against the negative effects of weightlessness. However, many questions regarding the appropriate configuration are still unanswered, including optimal g-level, angular velocity, gravity gradient, and exercise protocol. Mathematical models can provide unique insight into these questions, particularly when experimental data is very expensive or difficult to obtain. In this research effort, a cardiovascular lumped-parameter model is developed to simulate the short-term transient hemodynamic response to artificial gravity exposure combined with ergometer exercise, using a bicycle mounted on a short-radius centrifuge. The model is thoroughly described and preliminary simulations are conducted to show the model capabilities and potential applications. The model consists of 21 compartments (including systemic circulation, pulmonary circulation, and a cardiac model), and it also includes the rapid cardiovascular control systems (arterial baroreflex and cardiopulmonary reflex). In addition, the pressure gradient resulting from short-radius centrifugation is captured in the model using hydrostatic pressure sources located at each compartment. The model also includes the cardiovascular effects resulting from exercise such as the muscle pump effect. An initial set of artificial gravity simulations were implemented using the Massachusetts Institute of Technology (MIT) Compact-Radius Centrifuge (CRC) configuration. Three centripetal acceleration (artificial gravity) levels were chosen: 1 g, 1.2 g, and 1.4 g, referenced to the subject's feet. Each simulation lasted 15.5 minutes and included a baseline period, the spin-up process, the ergometer exercise period (5 minutes of ergometer exercise at 30 W with a simulated pedal cadence of 60 RPM), and the spin-down process. Results showed that the cardiovascular model is able to predict the cardiovascular dynamics during gravity changes, as well as the expected

  18. A Pulsatile Cardiovascular Computer Model for Teaching Heart-Blood Vessel Interaction.

    ERIC Educational Resources Information Center

    Campbell, Kenneth; And Others

    1982-01-01

    Describes a model which gives realistic predictions of pulsatile pressure, flow, and volume events in the cardiovascular system. Includes computer oriented laboratory exercises for veterinary and graduate students; equations of the dynamic and algebraic models; and a flow chart for the cardiovascular teaching program. (JN)

  19. User's instructions for the high speed version of the cardiovascular exercise model

    NASA Technical Reports Server (NTRS)

    Croston, R. C.

    1973-01-01

    A mathematical model and digital computer simulation of the human cardiovascular system and its controls were developed to simulate transient responses to bicycle ergometer exercise. The purpose of the model was to provide a method to analyze cardiovascular control hypotheses which cannot be easily tested in an animal or human or in a spaceflight environment.

  20. Exercise and the Cardiovascular System: Clinical Science and Cardiovascular Outcomes

    PubMed Central

    Lavie, Carl J.; Arena, Ross; Swift, Damon L.; Johannsen, Neil M.; Sui, Xuemei; Lee, Duck-chul; Earnest, Conrad P.; Church, Timothy S.; O’Keefe, James H.; Milani, Richard V.; Blair, Steven N.

    2015-01-01

    Substantial evidence has established the value of high levels of physical activity (PA), exercise training (ET), and overall cardiorespiratory fitness (CRF) in the prevention and treatment of cardiovascular diseases (CVD). This paper reviews some basics of exercise physiology and the acute and chronic responses of ET, as well as the impact of PA and CRF on CVD. This review also surveys data from epidemiologic and ET studies in the primary and secondary prevention of CVD, particularly coronary heart disease (CHD) and heart failure (HF). These data strongly support the routine prescription of ET to all patients and referrals for patients with CVD, especially CHD and HF, to specific cardiac rehabilitation and ET programs. PMID:26139859

  1. A wave dynamics criterion for optimization of mammalian cardiovascular system.

    PubMed

    Pahlevan, Niema M; Gharib, Morteza

    2014-05-01

    The cardiovascular system in mammals follows various optimization criteria covering the heart, the vascular network, and the coupling of the two. Through a simple dimensional analysis we arrived at a non-dimensional number (wave condition number) that can predict the optimum wave state in which the left ventricular (LV) pulsatile power (LV workload) is minimized in a mammalian cardiovascular system. This number is also universal among all mammals independent of animal size maintaining a value of around 0.1. By utilizing a unique in vitro model of human aorta, we tested our hypothesis against a wide range of aortic compliance (pulse wave velocity). We concluded that the optimum value of the wave condition number remains to be around 0.1 for a wide range of aorta compliance that we could simulate in our in-vitro system.

  2. Degradation Model of Bioabsorbable Cardiovascular Stents

    PubMed Central

    Luo, Qiyi; Liu, Xiangkun; Li, Zhonghua; Huang, Chubo; Zhang, Wen; Meng, Juan; Chang, Zhaohua; Hua, Zezhao

    2014-01-01

    This study established a numerical model to investigate the degradation mechanism and behavior of bioabsorbable cardiovascular stents. In order to generate the constitutive degradation material model, the degradation characteristics were characterized with user-defined field variables. The radial strength bench test and analysis were used to verify the material model. In order to validate the numerical degradation model, in vitro bench test and in vivo implantation studies were conducted under physiological and normal conditions. The results showed that six months of degradation had not influenced the thermodynamic properties and mechanical integrity of the stent while the molecular weight of the stents implanted in the in vivo and in vitro models had decreased to 61.8% and 68.5% respectively after six month's implantation. It was also found that the degradation rate, critical locations and changes in diameter of the stents in the numerical model were in good consistency in both in vivo and in vitro studies. It implies that the numerical degradation model could provide useful physical insights and prediction of the stent degradation behavior and evaluate, to some extent, the in-vivo performance of the stent. This model could eventually be used for design and optimization of bioabsorbable stent. PMID:25365310

  3. Imaging of cardiovascular complications in patients with systemic lupus erythematosus

    PubMed Central

    Lin, Kai; Lloyd-Jones, Donald M.; Li, Debiao; Liu, Ying; Yang, Jie; Markl, Michael; Carr, James C.

    2015-01-01

    In the long-term survivals of patients with systemic lupus erythematosus (SLE), cardiovascular disease (CVD) is a leading cause of death. Recently, multi-modality cardiovascular imaging methods have been adopted for the evaluation of cardiovascular risk, which has shown to be associated with both traditional cardiovascular risk factors and SLE-specific conditions. Quantitative imaging biomarkers, which can describe both morphological and functional abnormalities in the heart, are expected to provide new insights to stratify cardiovascular risks and to guide SLE management by assessing the individual responses to therapies either protecting the cardiovascular system or suppressing the autoimmune reactions. In this review, we will discuss cutting-edge cardiovascular imaging techniques and discuss potential clinical applications and limitations of those techniques for the evaluation of major SLE related heart disorders. PMID:26038342

  4. Imaging of cardiovascular complications in patients with systemic lupus erythematosus.

    PubMed

    Lin, K; Lloyd-Jones, D M; Li, D; Liu, Y; Yang, J; Markl, M; Carr, J C

    2015-10-01

    In the long-term survival of patients with systemic lupus erythematosus (SLE), cardiovascular disease (CVD) is a leading cause of death. Recently, multimodality cardiovascular imaging methods have been adopted for the evaluation of cardiovascular risk, which has shown to be associated with both traditional cardiovascular risk factors and SLE-specific conditions. Quantitative imaging biomarkers, which can describe both morphological and functional abnormalities in the heart, are expected to provide new insights to stratify cardiovascular risks and to guide SLE management by assessing individual responses to therapies either protecting the cardiovascular system or suppressing the autoimmune reactions. In this review, we will discuss cutting-edge cardiovascular imaging techniques and potential clinical applications and limitations of those techniques for the evaluation of major SLE-related heart disorders. PMID:26038342

  5. Space weather and cardiovascular system. New findings

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Yury; Breus, Tamara

    2014-05-01

    Researches of last two decades have shown that the cardiovascular system represents the most probable target for influence of helio - and geomagnetic activity. Both cardiovascular system and system of blood are connected very closely: one system cannot exist without another. For the same reason the effects perceived by one system, are easily transferred to another. Laboratory tests such as blood coagulation, platelet aggregation, and capillary blood velocity (CBV) performed in Scientific Clinical Center JSC "Russian Railways in patients suffering from coronary heart disease (CHD) revealed a high dependence with a level of geomagnetic activity. Results of these and other findings allow to assume that blood itself can be a sensor of geomagnetic fields variations because erythrocytes, platelets, and leucocytes bearing electric charge on membranes, and in a comparable magnetic field can change as own properties and properties of blood flow. It is interesting that not only geomagnetic disturbances, but also the periods of very quiet geomagnetic conditions affect a capillary blood velocity, slowing down it. It was shown during long-term experiment with isolation named 'MARS-500' in spatial facility of the Institute of Biomedical Problems in Moscow as imitation of an extended space mission to Mars. Using digital capillaroscope 'Russia', two crewmembers - medical doctors made records of microcirculation parameters at themselves and other four participants of 'Martian' team. Capillary records were performed before, during, and after period of isolation in medical module of MARS-500 facility. At the period of experiment nobody of crewmembers knew about real geomagnetic conditions. In days of active geomagnetic conditions average CBV has registered as 389 ± 167 μm/s, that statistically significant (p

  6. The human cardiovascular system during space flight

    NASA Astrophysics Data System (ADS)

    Grigoriev, A. I.; Kotovskaya, A. R.; Fomina, G. A.

    2011-05-01

    Purpose of the work is to analyze and to summarize the data of investigations into human hemodynamics performed over 20 years aboard orbital stations Salyut-7 and Mir with participation of 26 cosmonauts on space flights (SF) from 8 to 438 days in duration. The ultrasonic techniques and occlusive plethysmography demonstrated dynamics of changes in the cardiovascular system during SF of various durations. The parameters of general hemodynamics, the pumping function of the heart and arterial circulation in the brain remained stable in all the space flights; however, there were alterations in peripheral circulation associated with blood redistribution and hypovolemie in microgravity. The anti-gravity distribution of the vascular tone decayed gradually as unneeded. The most considerable changes were observed in leg vessels, equally in arteries (decrease in resistance) and veins (increase in maximum capacity). The lower body negative pressure test (LBNP) revealed deterioration of the gravity-dependent reactions that changed for the worse as SF duration extended. The cardiovascular deconditioning showed itself as loss of descent acceleration tolerance and orthostatic instability in the postflight period.

  7. [Remodeling of Cardiovascular System: Causes and Consequences].

    PubMed

    Lopatina, E V; Kipenko, A V; Penniyaynen, V A; Pasatetckaia, N A; Tsyrline, V A

    2016-01-01

    Literature and our data suggest the regulatory action of a number of biologically active substances (catecholamines, cardiac glycosides, β-blockers, angiotensin-converting-enzyme inhibitor) on the growth and proliferation of heart cells. By using of organotypic tissue culture has proved that the basis of this regulation is the ability of test substances, receptor- or transducer-mediated signaling to modulate the function of Na⁺, K⁺-ATPase. There is a delay in the development of vascular smooth muscle in the late postnatal period in rats with the blockade of the sympathetic nervous system in the prenatal period. The relationship between vascular remodeling and contractile activity is described. It seems that one of the causes of high blood pressure is a remodeling of the cardiovascular system, which precedes the development of hypertension. PMID:27530043

  8. [Remodeling of Cardiovascular System: Causes and Consequences].

    PubMed

    Lopatina, E V; Kipenko, A V; Penniyaynen, V A; Pasatetckaia, N A; Tsyrline, V A

    2016-01-01

    Literature and our data suggest the regulatory action of a number of biologically active substances (catecholamines, cardiac glycosides, β-blockers, angiotensin-converting-enzyme inhibitor) on the growth and proliferation of heart cells. By using of organotypic tissue culture has proved that the basis of this regulation is the ability of test substances, receptor- or transducer-mediated signaling to modulate the function of Na⁺, K⁺-ATPase. There is a delay in the development of vascular smooth muscle in the late postnatal period in rats with the blockade of the sympathetic nervous system in the prenatal period. The relationship between vascular remodeling and contractile activity is described. It seems that one of the causes of high blood pressure is a remodeling of the cardiovascular system, which precedes the development of hypertension.

  9. Systems Medicine as an Emerging Tool for Cardiovascular Genetics

    PubMed Central

    Haase, Tina; Börnigen, Daniela; Müller, Christian; Zeller, Tanja

    2016-01-01

    Cardiovascular disease (CVD) is a major contributor to morbidity and mortality worldwide. However, the pathogenesis of CVD is complex and remains elusive. Within the last years, systems medicine has emerged as a novel tool to study the complex genetic, molecular, and physiological interactions leading to diseases. In this review, we provide an overview about the current approaches for systems medicine in CVD. They include bioinformatical and experimental tools such as cell and animal models, omics technologies, network, and pathway analyses. Additionally, we discuss challenges and current literature examples where systems medicine has been successfully applied for the study of CVD. PMID:27626034

  10. Systems Medicine as an Emerging Tool for Cardiovascular Genetics

    PubMed Central

    Haase, Tina; Börnigen, Daniela; Müller, Christian; Zeller, Tanja

    2016-01-01

    Cardiovascular disease (CVD) is a major contributor to morbidity and mortality worldwide. However, the pathogenesis of CVD is complex and remains elusive. Within the last years, systems medicine has emerged as a novel tool to study the complex genetic, molecular, and physiological interactions leading to diseases. In this review, we provide an overview about the current approaches for systems medicine in CVD. They include bioinformatical and experimental tools such as cell and animal models, omics technologies, network, and pathway analyses. Additionally, we discuss challenges and current literature examples where systems medicine has been successfully applied for the study of CVD.

  11. Systems Medicine as an Emerging Tool for Cardiovascular Genetics.

    PubMed

    Haase, Tina; Börnigen, Daniela; Müller, Christian; Zeller, Tanja

    2016-01-01

    Cardiovascular disease (CVD) is a major contributor to morbidity and mortality worldwide. However, the pathogenesis of CVD is complex and remains elusive. Within the last years, systems medicine has emerged as a novel tool to study the complex genetic, molecular, and physiological interactions leading to diseases. In this review, we provide an overview about the current approaches for systems medicine in CVD. They include bioinformatical and experimental tools such as cell and animal models, omics technologies, network, and pathway analyses. Additionally, we discuss challenges and current literature examples where systems medicine has been successfully applied for the study of CVD. PMID:27626034

  12. Cardiovascular

    NASA Video Gallery

    Overview of Cardiovascular research which addresses risks of space flight, including adaptive changes to the cephalad fluid shift (such as reduced circulating blood volume), potential for heart rhy...

  13. Update: Systemic Diseases and the Cardiovascular System (II). The endocrine system and the heart: a review.

    PubMed

    Rhee, Soo S; Pearce, Elizabeth N

    2011-03-01

    Normal endocrine function is essential for cardiovascular health. Disorders of the endocrine system, consisting of hormone hyperfunction and hypofunction, have multiple effects on the cardiovascular system. In this review, we discuss the epidemiology, diagnosis, and management of disorders of the pituitary, thyroid, parathyroid, and adrenal glands, with respect to the impact of endocrine dysfunction on the cardiovascular system. We also review the cardiovascular benefits of restoring normal endocrine function.

  14. Sleep apnoea syndromes and the cardiovascular system.

    PubMed

    Pepperell, Justin C

    2011-06-01

    Management of SAS and cardiovascular disease risk should be closely linked. It is important to screen for cardiovascular disease risk in patients with SAS and vice versa. CSA/CSR may be improved by ventilation strategies in heart failure, but benefit remains to be proven. For OSA, although CPAP may reduce cardiovascular disease risk, its main benefit is symptom control. In the longer-term, CPAP should be used alongside standard cardiovascular risk reduction strategies including robust weight management programmes, with referral for bariatric surgery in appropriate cases. CPAP and NIV should be considered for acute admissions with decompensated cardiac failure. PMID:21902085

  15. Predictions of cardiovascular responses during STS reentry using mathematical models

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.; Srinivasan, R.

    1985-01-01

    The physiological adaptation to weightless exposure includes cardiovascular deconditioning arising in part from a loss of total circulating blood volume and resulting in a reduction of orthostatic tolerance. The crew of the Shuttle orbiter are less tolerant to acceleration forces in the head-to-foot direction during the reentry phase of the flight at a time they must function at a high level of performance. The factors that contribute to orthostatic intolerance during and following reentry and to predict the likelihood of impaired crew performance are evaluated. A computer simulation approach employing a mathematical model of the cardiovascular system is employed. It is shown that depending on the severity of blood volume loss, the reentry acceleration stress may be detrimental to physiologic function and may place the physiologic status of the crew near the borderline of some type of impairment. They are in agreement with conclusions from early ground-based experiments and from observations of early Shuttle flights.

  16. Regulation of sympathetic nervous system function after cardiovascular deconditioning

    NASA Technical Reports Server (NTRS)

    Hasser, E. M.; Moffitt, J. A.

    2001-01-01

    Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently

  17. Identification of cardiovascular dilution systems by contrast ultrasound.

    PubMed

    Mischi, Massimo; Jansen, Annemieke H M; Korsten, Hendrikus H M

    2007-03-01

    Indicator dilution techniques permit accurate measurements of important cardiovascular parameters, such as pulmonary blood volume (PBV) and ejection fraction (EF). However, their use is limited by the need for central catheterization. Contrast ultrasonography allows overcoming this problem. PBV and EF can be measured by a dilution system identification algorithm after detection of multiple dilution curves by an ultrasound scanner. In this paper, we present a system identification method that exploits the a priori knowledge on the dilution system and finds the optimum parameters for the parametric model representing the dilution system impulse response. No subsequent model interpolation is needed. Volume measurements show accurate in-vitro results and clinical feasibility, while 50 EF measurements in patients show a 0.88 correlation coefficient with echocardiographic biplane estimates. In conclusion, adding a priori knowledge to the system identification algorithm leads to increased accuracy and robustness of the method for PBV and EF measurements.

  18. Model-referenced cardiovascular circulatory simulator: construction and control.

    PubMed

    Gwak, Kwan-Woong

    2015-04-01

    Physiological feasibility is the most important requirement for cardiovascular circulatory simulators (CCSs). However, previous simulators have been validated by a comparison with specific human data sets, which are valid only for very limited conditions, and so it is difficult to validate the fidelity of a CCS for various body conditions. To overcome this critical limitation, we propose a model-referenced CCS that reproduces the behavior of an electrical-analog model of the cardiovascular circulatory system, for which physiological fidelity is well established over a wide range. In this study, the electrical-analog reference model was realized in the hardware simulator using fluidic element modeling and by the feedback control of a mock ventricle. The proposed simulator showed a good match with the reference model behavior, and its physiological validity was thereby verified. The proposed simulator is able to show responsiveness to various body conditions as well. To the best of the author's knowledge, this is the first report of an in vitro CCS verified to be consistent with reference model behavior. PMID:25345617

  19. Gravitational Force and the Cardiovascular System

    NASA Technical Reports Server (NTRS)

    Pendergast, D. R.; Olszowka, A. J.; Rokitka, M. A.; Farhi, L. E.

    1991-01-01

    Cardiovascular responses to changes in gravitational force are considered. Man is ideally suited to his 1-g environment. Although cardiovascular adjustments are required to accommodate to postural changes and exercise, these are fully accomplished for short periods (min). More challenging stresses are those of short-term microgravity (h) and long-term microgravity (days) and of gravitational forces greater than that of Earth. The latter can be simulated in the laboratory and quantitative studies can be conducted.

  20. The role of PPARδ signaling in the cardiovascular system.

    PubMed

    Ding, Yishu; Yang, Kevin D; Yang, Qinglin

    2014-01-01

    Peroxisome proliferator-activated receptors (PPARα, β/δ, and γ), members of the nuclear receptor transcription factor superfamily, play important roles in the regulation of metabolism, inflammation, and cell differentiation. All three PPAR subtypes are expressed in the cardiovascular system with various expression patterns. Among the three PPAR subtypes, PPARδ is the least studied but has arisen as a potential therapeutic target for cardiovascular and many other diseases. It is known that PPARδ is ubiquitously expressed and abundantly expressed in cardiomyocytes. Accumulated evidence illustrates the role of PPARδ in regulating cardiovascular function and determining pathological progression. In this chapter, we will discuss the current knowledge in the role of PPARδ in the cardiovascular system, the mechanistic insights, and the potential therapeutic utilization for treating cardiovascular disease.

  1. Human thermoregulation and the cardiovascular system.

    PubMed

    González-Alonso, José

    2012-03-01

    A key but little understood function of the cardiovascular system is to exchange heat between the internal body tissues, organs and the skin to maintain internal temperature within a narrow range in a variety of conditions that produce vast changes in external (exogenous) and/or internal (endogenous) thermal loads. Heat transfer via the flowing blood (i.e. vascular convective heat transfer) is the most important heat-exchange pathway inside the body. This pathway is particularly important when metabolic heat production increases many-fold during exercise. During exercise typical of many recreational and Olympic events, heat is transferred from the heat-producing contracting muscles to the skin surrounding the exercising limbs and to the normally less mobile body trunk and head via the circulating blood. Strikingly, a significant amount of heat produced by the contracting muscles is liberated from the skin of the exercising limbs. The local and central mechanisms regulating tissue temperature in the exercising limbs, body trunk and head are essential to avoid the deleterious consequences on human performance of either hyperthermia or hypothermia. This brief review focuses on recent literature addressing the following topics: (i) the dynamics of heat production in contracting skeletal muscle; (ii) the influence of exercise and environmental heat and cold stress on limb and systemic haemodynamics; and (iii) the impact of changes in muscle blood flow on heat exchange in human limbs. The paper highlights the need to investigate the responses and mechanisms of vascular convective heat exchange in exercising limbs to advance our understanding of local tissue temperature regulation during exercise and environmental stress. PMID:22227198

  2. Cardiovascular model for the simulation of exercise, lower body negative pressure, and tilt experiments

    NASA Technical Reports Server (NTRS)

    Croston, R. C.; Fitzjerrell, D. G.

    1974-01-01

    A mathematical model and digital computer simulation of the human cardiovascular system and its controls have been developed to simulate pulsatile dynamic responses to the cardiovascular experiments of the Skylab missions and to selected physiological stresses of manned space flight. Specific model simulations of the bicycle ergometry, lower body negative pressure, and tilt experiments have been developed and verified for 1-g response by comparison with available experimental data. The zero-g simulations of two Skylab experiments are discussed.

  3. The paleopathology of the cardiovascular system.

    PubMed Central

    Zimmerman, M R

    1993-01-01

    Paleopathology, the study of disease in ancient remains, adds the dimension of time to our study of health and disease. The oldest preserved heart is from a mummified rabbit of the Pleistocene epoch, over 20,000 years old. Cardiovascular disease has been identified in human mummies from Alaska and Egypt, covering a time span ranging from approximately 3,000 to 300 years ago. An experimental study suggests that the potential exists for identifying a wide range of cardiovascular pathologic conditions in mummified remains. The antiquity and ubiquity of arteriosclerotic heart disease is considered in terms of pathogenesis. Images PMID:8298320

  4. The role of histamine in the cardiovascular system.

    PubMed

    Cabanié, M; Godfraind, T

    1988-01-01

    This article reviews briefly the role of histamine through its H1 and H2 receptors on the cardiovascular system and its action on calcium and catecholamines. The analogy between the adrenergic and the histaminergic systems is well demonstrated and there is evidence that histamine participates in myocardial damage and arrythmias, but the question of its exact role in the early stages of cardiovascular diseases, such as myocardial ischaemia and atherosclerosis, requires further study.

  5. Endothelins and NADPH oxidases in the cardiovascular system.

    PubMed

    Dammanahalli, Karigowda J; Sun, Zhongjie

    2008-01-01

    1. The endothelin (ET) system and NADPH oxidase play important roles in the regulation of cardiovascular function, as well as in the pathogenesis of hypertension and other cardiovascular diseases. 2. Endothelins activate NADPH oxidases and thereby increase superoxide production, resulting in oxidative stress and cardiovascular dysfunction. Thus, NADPH oxidases may mediate the role of endothelins in some cardiovascular diseases. However, the role of reactive oxygen species (ROS) in mediating ET-induced vasoconstriction and cardiovascular disease remains under debate, as evidenced by conflicting reports from different research teams. Conversely, activation of NADPH oxidase can stimulate ET secretion via ROS generation, which further enhances the cardiovascular effects of NADPH oxidase. However, little is known about how ROS activate the endothelin system. It seems that the relationship between ET-1 and ROS may vary with cardiovascular disorders. 3. Endothelins activate NADPH oxidase via the ET receptor-proline-rich tyrosine kinase-2 (Pyk2)-Rac1 pathway. Rac1 is an important regulator of NADPH oxidase. There is ample evidence supporting direct stimulation by Rac1 of NADPH oxidase activity. In addition, Rac1-induced cardiomyocyte hypertrophy is mediated by the generation of ROS.

  6. Cardiovascular Events in Systemic Lupus Erythematosus

    PubMed Central

    Fernández-Nebro, Antonio; Rúa-Figueroa, Íñigo; López-Longo, Francisco J.; Galindo-Izquierdo, María; Calvo-Alén, Jaime; Olivé-Marqués, Alejandro; Ordóñez-Cañizares, Carmen; Martín-Martínez, María A.; Blanco, Ricardo; Melero-González, Rafael; Ibáñez-Rúan, Jesús; Bernal-Vidal, José Antonio; Tomero-Muriel, Eva; Uriarte-Isacelaya, Esther; Horcada-Rubio, Loreto; Freire-González, Mercedes; Narváez, Javier; Boteanu, Alina L.; Santos-Soler, Gregorio; Andreu, José L.; Pego-Reigosa, José M.

    2015-01-01

    Abstract This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2–66.1], and SLE duration of 212.0 months [120.8–289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02–1.04]), hypertension (1.71 [1.20–2.44]), smoking (1.48 [1.06–2.07]), diabetes (2.2 [1.32–3.74]), dyslipidemia (2.18 [1.54–3.09]), neurolupus (2.42 [1.56–3.75]), valvulopathy (2.44 [1.34–4.26]), serositis (1.54 [1.09–2.18]), antiphospholipid antibodies (1.57 [1.13–2.17]), low complement (1.81 [1.12–2.93]), and azathioprine (1.47 [1.04–2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows—for the first time—an association between diabetes and CV events in SLE patients. PMID:26200625

  7. Emerging role of neurotensin in regulation of the cardiovascular system.

    PubMed

    Osadchii, Oleg E

    2015-09-01

    There is increasing evidence in support of an important role played by neurotensin (NT), a tridecapeptide originally found in bovine hypothalamus, in regulation of cardiovascular system. Elevated systemic levels of NT may contribute to pathogenesis of acute circulatory disoders, and predict the risk for cardiovascular morbidity and mortality in population-based studies. Within cardiovascular system, NT-containing neural fibers are found in close contact with atrial and ventricular cardiac myocytes, cardiac conduction system, intracardiac ganglia, as well as coronary vessels in humans and various animal species. The density of NT-immunoreactive innervation is reduced in cardiac disease. NT produces a variety of cardiovascular actions including effects on heart rate, myocardial contractility, systemic blood pressure, coronary vascular tone, venous smooth muscle tone, and regional blood flow in gastrointestinal tract, cutaneous and adipose tissue. NT could trigger cardiovascular reflexes by stimulating primary visceral afferents synaptically connected with preganglionic sympathetic neurons at the spinal cord. Structural determinants of biological activity of NT reside primarily in the C-terminal portion of its molecule which is responsible for receptor activation. NT effects are mediated via activation of NT receptors, or produced indirectly via stimulation of release of various endogenous neuromodulators/neurotransmitters such as histamine, catecholamines and prostaglandins. Three subtypes of NT receptor (NTS1, NTS2 and NTS3) have been shown to be expressed in the myocardium. NTS1, a high-affinity NT binding site coupled to phospholipase C-inositoltrisphosphate transduction pathway, is thought to mediate NT-induced cardiovascular responses.

  8. Is the cardiovascular system a therapeutic target for cannabidiol?

    PubMed

    Stanley, Christopher P; Hind, William H; O'Sullivan, Saoirse E

    2013-02-01

    Cannabidiol (CBD) has beneficial effects in disorders as wide ranging as diabetes, Huntington's disease, cancer and colitis. Accumulating evidence now also suggests that CBD is beneficial in the cardiovascular system. CBD has direct actions on isolated arteries, causing both acute and time-dependent vasorelaxation. In vitro incubation with CBD enhances the vasorelaxant responses in animal models of impaired endothelium-dependent vasorelaxation. CBD protects against the vascular damage caused by a high glucose environment, inflammation or the induction of type 2 diabetes in animal models and reduces the vascular hyperpermeability associated with such environments. A common theme throughout these studies is the anti-inflammatory and anti-oxidant effect of CBD. In the heart, in vivo CBD treatment protects against ischaemia-reperfusion damage and against cardiomyopathy associated with diabetes. Similarly, in a different model of ischaemia-reperfusion, CBD has been shown to reduce infarct size and increase blood flow in animal models of stroke, sensitive to 5HT(1A) receptor antagonism. Although acute or chronic CBD treatment seems to have little effect on haemodynamics, CBD reduces the cardiovascular response to models of stress, applied either systemically or intracranially, inhibited by a 5HT(1A) receptor antagonist. In blood, CBD influences the survival and death of white blood cells, white blood cell migration and platelet aggregation. Taken together, these preclinical data appear to support a positive role for CBD treatment in the heart, and in peripheral and cerebral vasculature. However, further work is required to strengthen this hypothesis, establish mechanisms of action and whether similar responses to CBD would be observed in humans.

  9. Is the cardiovascular system a therapeutic target for cannabidiol?

    PubMed Central

    Stanley, Christopher P; Hind, William H; O'Sullivan, Saoirse E

    2013-01-01

    Cannabidiol (CBD) has beneficial effects in disorders as wide ranging as diabetes, Huntington's disease, cancer and colitis. Accumulating evidence now also suggests that CBD is beneficial in the cardiovascular system. CBD has direct actions on isolated arteries, causing both acute and time-dependent vasorelaxation. In vitro incubation with CBD enhances the vasorelaxant responses in animal models of impaired endothelium-dependent vasorelaxation. CBD protects against the vascular damage caused by a high glucose environment, inflammation or the induction of type 2 diabetes in animal models and reduces the vascular hyperpermeability associated with such environments. A common theme throughout these studies is the anti-inflammatory and anti-oxidant effect of CBD. In the heart, in vivo CBD treatment protects against ischaemia-reperfusion damage and against cardiomyopathy associated with diabetes. Similarly, in a different model of ischaemia-reperfusion, CBD has been shown to reduce infarct size and increase blood flow in animal models of stroke, sensitive to 5HT1A receptor antagonism. Although acute or chronic CBD treatment seems to have little effect on haemodynamics, CBD reduces the cardiovascular response to models of stress, applied either systemically or intracranially, inhibited by a 5HT1A receptor antagonist. In blood, CBD influences the survival and death of white blood cells, white blood cell migration and platelet aggregation. Taken together, these preclinical data appear to support a positive role for CBD treatment in the heart, and in peripheral and cerebral vasculature. However, further work is required to strengthen this hypothesis, establish mechanisms of action and whether similar responses to CBD would be observed in humans. PMID:22670794

  10. Radiological features of uncommon aneurysms of the cardiovascular system

    PubMed Central

    Kalisz, Kevin; Rajiah, Prabhakar

    2016-01-01

    Although aortic aneurysms are the most common type encountered clinically, they do not span the entire spectrum of possible aneurysms of the cardiovascular system. As cross sectional imaging techniques with cardiac computed tomography and cardiac magnetic resonance imaging continue to improve and becomes more commonplace, once rare cardiovascular aneurysms are being encountered at higher rates. In this review, a series of uncommon, yet clinically important, cardiovascular aneurysms will be presented with review of epidemiology, clinical presentation and complications, imaging features and relevant differential diagnoses, and aneurysm management. PMID:27247710

  11. Physiological system integrations with emphasis on the respiratory-cardiovascular system

    NASA Technical Reports Server (NTRS)

    Gallagher, R. R.

    1975-01-01

    The integration of two types of physiological system simulations is presented. The long term model is a circulatory system model which simulates long term blood flow variations and compartmental fluid shifts. The short term models simulate transient phenomena of the respiratory, thermoregulatory, and pulsatile cardiovascular systems as they respond to stimuli such as LBNP, exercise, and environmental gaseous variations. An overview of the interfacing approach is described. Descriptions of the variable interface for long term to short term and between the three short term models are given.

  12. Zebrafish models of cardiovascular diseases and their applications in herbal medicine research.

    PubMed

    Seto, Sai-Wang; Kiat, Hosen; Lee, Simon M Y; Bensoussan, Alan; Sun, Yu-Ting; Hoi, Maggie P M; Chang, Dennis

    2015-12-01

    The zebrafish (Danio rerio) has recently become a powerful animal model for cardiovascular research and drug discovery due to its ease of maintenance, genetic manipulability and ability for high-throughput screening. Recent advances in imaging techniques and generation of transgenic zebrafish have greatly facilitated in vivo analysis of cellular events of cardiovascular development and pathogenesis. More importantly, recent studies have demonstrated the functional similarity of drug metabolism systems between zebrafish and humans, highlighting the clinical relevance of employing zebrafish in identifying lead compounds in Chinese herbal medicine with potential beneficial cardiovascular effects. This paper seeks to summarise the scope of zebrafish models employed in cardiovascular studies and the application of these research models in Chinese herbal medicine to date.

  13. Evaluation of the electromechanical properties of the cardiovascular system

    NASA Technical Reports Server (NTRS)

    Bergman, S. A., Jr.; Hoffler, G. W.; Johnson, R. L.

    1974-01-01

    Cardiovascular electromechanical measurements were collected on returning Skylab crewmembers at rest and during both lower body negative pressure and exercise stress testing. These data were compared with averaged responses from multiple preflight tests. Systolic time intervals and first heart sound amplitude changes were measured. Clinical cardiovascular examinations and clinical phonocardiograms were evaluated. All changes noted returned to normal within 30 days postflight so that the processes appear to be transient and self limited. The cardiovascular system seems to adapt quite readily to zero-g, and more importantly it is capable of readaptation to one-g after long duration space flight. Repeated exposures to zero-g also appear to have no detrimental effects on the cardiovascular system.

  14. The role of epoxyeicosatrienoic acids in the cardiovascular system

    PubMed Central

    Yang, L; Mäki-Petäjä, K; Cheriyan, J; McEniery, C; Wilkinson, I B

    2015-01-01

    There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of cardiovascular risk factors. This review discusses the current knowledge on the role of EETs in endothelium-dependent control of vascular tone in the healthy and in subjects with cardiovascular risk factors, and considers the pharmacological potential of targeting this pathway. PMID:25655310

  15. The role of epoxyeicosatrienoic acids in the cardiovascular system.

    PubMed

    Yang, L; Mäki-Petäjä, K; Cheriyan, J; McEniery, C; Wilkinson, I B

    2015-07-01

    There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of cardiovascular risk factors. This review discusses the current knowledge on the role of EETs in endothelium-dependent control of vascular tone in the healthy and in subjects with cardiovascular risk factors, and considers the pharmacological potential of targeting this pathway.

  16. [Changes in the cardiovascular system in selected endocrinopathies in children].

    PubMed

    Semeran, Kornel; Bossowski, Artur

    2011-01-01

    Hormones have influence on many tissues and organs including the cardiovascular system. This article analyzes fluctuations that happen in a child's cardiovascular system in selected endocrinopathies. We are pointing out the higher risk, in the course of diabetes, of development of arterial hypertension and atherosclerosis including participating mechanisms in their pathogenesis - disorders of the lipid metabolism, hiperinsulinaemia, insulin resistance or/and autonomic neuropathy. We are describing how the increased and reduced action of thyroid hormones on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangement. In the article, we are signaling also that the cardiovascular consequences of cortisol excess are elevation of blood pressure, obesity, hyperinsulinemia and/or dyslipidemia. This review analyzes the relationship of cortisol excess to these cardiovascular risk factors and to putative mechanisms for hypertension. In reference to clinical studies we are describing how the deficiency of the growth hormone is connected with a development of risk factors of cardiovascular diseases. In conclusion we underlined that early diagnosis and proper treatment of illnesses of the endocrine system can protect our pediatric patients from serious cardiac complications in later years. PMID:21489356

  17. RhoA/Rho-Kinase in the Cardiovascular System.

    PubMed

    Shimokawa, Hiroaki; Sunamura, Shinichiro; Satoh, Kimio

    2016-01-22

    Twenty years ago, Rho-kinase was identified as an important downstream effector of the small GTP-binding protein, RhoA. Thereafter, a series of studies demonstrated the important roles of Rho-kinase in the cardiovascular system. The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases. Furthermore, the important role of Rho-kinase has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. Cyclophilin A is secreted by vascular smooth muscle cells and inflammatory cells and activated platelets in a Rho-kinase-dependent manner, playing important roles in a wide range of cardiovascular diseases. Thus, the RhoA/Rho-kinase pathway plays crucial roles under both physiological and pathological conditions and is an important therapeutic target in cardiovascular medicine. Recently, functional differences between ROCK1 and ROCK2 have been reported in vitro. ROCK1 is specifically cleaved by caspase-3, whereas granzyme B cleaves ROCK2. However, limited information is available on the functional differences and interactions between ROCK1 and ROCK2 in the cardiovascular system in vivo. Herein, we will review the recent advances about the importance of RhoA/Rho-kinase in the cardiovascular system.

  18. Cardiovascular and nervous system changes during meditation

    PubMed Central

    Steinhubl, Steven R.; Wineinger, Nathan E.; Patel, Sheila; Boeldt, Debra L.; Mackellar, Geoffrey; Porter, Valencia; Redmond, Jacob T.; Muse, Evan D.; Nicholson, Laura; Chopra, Deepak; Topol, Eric J.

    2015-01-01

    Background: A number of benefits have been described for the long-term practice of meditation, yet little is known regarding the immediate neurological and cardiovascular responses to meditation. Wireless sensor technology allows, for the first time, multi-parameter and quantitative monitoring of an individual's responses during meditation. The present study examined inter-individual variations to meditation through continuous monitoring of EEG, blood pressure, heart rate and its variability (HRV) in novice and experienced meditators. Methods: Participants were 20 experienced and 20 novice meditators involved in a week-long wellness retreat. Monitoring took place during meditation sessions on the first and last full days of the retreat. All participants wore a patch that continuously streamed ECG data, while half of them also wore a wireless EEG headset plus a non-invasive continuous blood pressure monitor. Results: Meditation produced variable but characteristic EEG changes, significantly different from baseline, even among novice meditators on the first day. In addition, although participants were predominately normotensive, the mean arterial blood pressure fell a small (2–3 mmHg) but significant (p < 0.0001) amount during meditation. The effect of meditation on HRV was less clear and influenced by calculation technique and respiration. No clear relationship between EEG changes, HRV alterations, or mean blood pressure during meditation was found. Conclusion: This is the first study to investigate neurological and cardiovascular responses during meditation in both novice and experienced meditators using novel, wearable, wireless devices. Meditation produced varied inter-individual physiologic responses. These results support the need for further investigation of the short- and long-term cardiovascular effects of mental calm and individualized ways to achieve it. PMID:25852526

  19. Radiation Toxicity to the Cardiovascular System.

    PubMed

    Marmagkiolis, Konstantinos; Finch, William; Tsitlakidou, Despina; Josephs, Tyler; Iliescu, Cezar; Best, John F; Yang, Eric H

    2016-03-01

    Radiation therapy is an important component of cancer treatment, and today, it is applied to approximately 50% of malignancies, including valvular, myocardial, pericardial, coronary or peripheral vascular disease, and arrhythmias. An increased clinical suspicion and knowledge of those mechanisms is important to initiate appropriate screening for the optimal diagnosis and treatment. As the number of cancer survivors has been steadily increasing over the last decades, cardio-oncology, an evolving subspecialty of cardiology, will soon play a pivotal role in raising awareness of the increased cardiovascular risk and formulate strategies to optimally manage patients in this unique population.

  20. Gravitational force and the cardiovascular system

    NASA Technical Reports Server (NTRS)

    Pendergast, D. R.; Olszowka, A. J.; Rokitka, M. A.; Farhi, L. E.

    1991-01-01

    Ground-based simulation studies have been conducted to clarify the problems of the cardiovascular adaptation to alterations in gravitational force. Simulated microgravity experiments resulted in increases in cardiac stretch, urine flow, and sodium excretion, which were accompanied by lower plasma renin, aldosterone, and ADH. There appears to be a decrease in plasma volume as well as in sympathetic tone after 2-3 days of 0 Gz. Complete adjustment to 0 Gz is found within 8 h without a decrease in plasma volume, when subjects are allowed to dehydrate mildly.

  1. Computational modeling of cardiovascular response to orthostatic stress

    NASA Technical Reports Server (NTRS)

    Heldt, Thomas; Shim, Eun B.; Kamm, Roger D.; Mark, Roger G.

    2002-01-01

    The objective of this study is to develop a model of the cardiovascular system capable of simulating the short-term (< or = 5 min) transient and steady-state hemodynamic responses to head-up tilt and lower body negative pressure. The model consists of a closed-loop lumped-parameter representation of the circulation connected to set-point models of the arterial and cardiopulmonary baroreflexes. Model parameters are largely based on literature values. Model verification was performed by comparing the simulation output under baseline conditions and at different levels of orthostatic stress to sets of population-averaged hemodynamic data reported in the literature. On the basis of experimental evidence, we adjusted some model parameters to simulate experimental data. Orthostatic stress simulations are not statistically different from experimental data (two-sided test of significance with Bonferroni adjustment for multiple comparisons). Transient response characteristics of heart rate to tilt also compare well with reported data. A case study is presented on how the model is intended to be used in the future to investigate the effects of post-spaceflight orthostatic intolerance.

  2. Computational modeling of cardiovascular response to orthostatic stress.

    PubMed

    Heldt, Thomas; Shim, Eun B; Kamm, Roger D; Mark, Roger G

    2002-03-01

    The objective of this study is to develop a model of the cardiovascular system capable of simulating the short-term (< or = 5 min) transient and steady-state hemodynamic responses to head-up tilt and lower body negative pressure. The model consists of a closed-loop lumped-parameter representation of the circulation connected to set-point models of the arterial and cardiopulmonary baroreflexes. Model parameters are largely based on literature values. Model verification was performed by comparing the simulation output under baseline conditions and at different levels of orthostatic stress to sets of population-averaged hemodynamic data reported in the literature. On the basis of experimental evidence, we adjusted some model parameters to simulate experimental data. Orthostatic stress simulations are not statistically different from experimental data (two-sided test of significance with Bonferroni adjustment for multiple comparisons). Transient response characteristics of heart rate to tilt also compare well with reported data. A case study is presented on how the model is intended to be used in the future to investigate the effects of post-spaceflight orthostatic intolerance. PMID:11842064

  3. Cross-talk between the kidney and the cardiovascular system.

    PubMed

    Amann, Kerstin; Wanner, Christoph; Ritz, Eberhard

    2006-08-01

    In recent years, increasing evidence has been provided that even minor renal dysfunction is a powerful cardiovascular risk factor that induces typical cardiovascular alterations and thus predisposes to coronary heart disease as well as to noncoronary cardiovascular problems. This first had been noted in patients with diabetes but now has been confirmed amply in patients without diabetes as well. Numerous heterogeneous abnormalities have been described in patients with early renal dysfunction (e.g., microalbuminuria, reduced estimated GFR). One final common pathway seems to be endothelial cell dysfunction. The link between albuminuria and generalized endothelial cell dysfunction (as indicated by diminished flow-mediated vasodilation, markers of endothelial cell dysfunction, sloughed off endothelial cells, and high transcapillary albumin escape rate) is unclear. In patients with early renal dysfunction, a long list of classical and nonclassical cardiovascular risk factors have been identified: Elevated asymmetric dimethyl-l-arginine concentrations, markers of microinflammation, oxidative stress, features of metabolic syndrome, abnormal adipokine concentrations, dyslipidemia, inappropriate activation of the renin-angiotensin system, and sympathetic overactivity. The mechanisms that link dysfunction of the kidney and the cardiovascular system are being sought. The most interesting unifying concept, however, is deranged fetal programming linking nephron underdosing to the increased cardiovascular risk.

  4. Adipokines and the cardiovascular system: mechanisms mediating health and disease.

    PubMed

    Northcott, Josette M; Yeganeh, Azadeh; Taylor, Carla G; Zahradka, Peter; Wigle, Jeffrey T

    2012-08-01

    This review focuses on the role of adipokines in the maintenance of a healthy cardiovascular system, and the mechanisms by which these factors mediate the development of cardiovascular disease in obesity. Adipocytes are the major cell type comprising the adipose tissue. These cells secrete numerous factors, termed adipokines, into the blood, including adiponectin, leptin, resistin, chemerin, omentin, vaspin, and visfatin. Adipose tissue is a highly vascularised endocrine organ, and different adipose depots have distinct adipokine secretion profiles, which are altered with obesity. The ability of many adipokines to stimulate angiogenesis is crucial for adipose tissue expansion; however, excessive blood vessel growth is deleterious. As well, some adipokines induce inflammation, which promotes cardiovascular disease progression. We discuss how these 7 aforementioned adipokines act upon the various cardiovascular cell types (endothelial progenitor cells, endothelial cells, vascular smooth muscle cells, pericytes, cardiomyocytes, and cardiac fibroblasts), the direct effects of these actions, and their overall impact on the cardiovascular system. These were chosen, as these adipokines are secreted predominantly from adipocytes and have known effects on cardiovascular cells.

  5. Effects of apelin on the cardiovascular system.

    PubMed

    Folino, Anna; Montarolo, Pier Giorgio; Samaja, Michele; Rastaldo, Raffaella

    2015-07-01

    Apelin is an endogenous peptide acting on the APJ receptor. It consists of several isoforms characterized by different numbers of amino acids. The number of amino acids in the active isoforms range from 36 to 12. Apelin-13 and, to a lesser extent, apelin-36 are considered the most active isoforms with the greatest activity on the cardiovascular homeostasis. The effects normally exerted by the basal level of endogenous apelin can be enhanced not only by its up-regulation, but may also by its exogenous administration. The present review considers the effects of apelin on various aspects of the cardiovascular function, such as cardiac development, vasomotor tone, angiogenesis, myocardial inotropy in healthy and failing hearts as well as the prevention of ischemia-reperfusion injury, cardiac fibrosis and remodeling. Also the biphasic changes in apelin level during the evolution of heart failure are considered. Although the positive inotropic effect exerted by apelin in normal and failing hearts would suggest the use of this peptide in the treatment of heart failure, the limited duration and extent of its effect do not support this possibility, unless a long-lasting (6 h) infusion is performed to overcome the limit of its short life. However, although the data on the characteristics of the inotropic activity do not provide a strong support for the treatment of active heart failure, apelin may be used in the prevention of heart failure because of its activity in limiting the consequences of myocardial ischemia such as infarct size and cardiac remodeling.

  6. 76 FR 47143 - Approval for Manufacturing Authority, Foreign-Trade Zone 153; Abbott Cardiovascular Systems, Inc...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-04

    ... Cardiovascular Systems, Inc., (Cardiovascular Devices), Riverside County, CA Pursuant to its Authority Under the... 153, has requested manufacturing authority on behalf of Abbott Cardiovascular Systems, Inc., within... procedures at sites within FTZ 153, on behalf of Abbott Cardiovascular Systems, Inc., as described in...

  7. Central neural control of the cardiovascular system: current perspectives.

    PubMed

    Dampney, Roger A L

    2016-09-01

    This brief review, which is based on a lecture presented at the American Physiological Society Teaching Refresher Course on the Brain and Systems Control as part of the Experimental Biology meeting in 2015, aims to summarize current concepts of the principal mechanisms in the brain that regulate the autonomic outflow to the cardiovascular system. Such cardiovascular regulatory mechanisms do not operate in isolation but are closely coordinated with respiratory and other regulatory mechanisms to maintain homeostasis. The brain regulates the cardiovascular system by two general means: 1) feedforward regulation, often referred to as "central command," and 2) feedback or reflex regulation. In most situations (e.g., during exercise, defensive behavior, sleep, etc.), both of these general mechanisms contribute to overall cardiovascular homeostasis. The review first describes the mechanisms and central circuitry subserving the baroreceptor, chemoreceptor, and other reflexes that work together to regulate an appropriate level of blood pressure and blood oxygenation and then considers the brain mechanisms that defend the body against more complex environmental challenges, using dehydration and cold and heat stress as examples. The last section of the review considers the central mechanisms regulating cardiovascular function associated with different behaviors, with a specific focus on defensive behavior and exercise. PMID:27445275

  8. The effects of sighing on the cardiovascular system

    PubMed Central

    Vaschillo, Evgeny G.; Vaschillo, Bronya; Buckman, Jennifer F.; Nguyen-Louie, Tam; Heiss, Sydney; Pandina, Robert J.; Bates, Marsha E.

    2015-01-01

    Elicitation of high-amplitude oscillations in the cardiovascular system may serve to dampen psychophysiological reactivity to emotional and cognitive loading. Prior work has used paced breathing to impose clinically valuable high-amplitude ~0.1Hz oscillations. In this study, we investigated whether rhythmical sighing could likewise produce high-amplitude cardiovascular oscillations in the very low frequency range (0.003–0.05Hz). ECG, respiration, skin conductance, and beat-to-beat blood pressure were collected in 24 healthy participants during baseline, 0.1Hz paced breathing, and 0.02Hz paced sighing (1 sigh every 50 seconds, with normal breathing interspersed). Results showed that each sigh elicited a strong, well-defined reaction in the cardiovascular system. This reaction did not habituate when participants repeatedly sighed for 8.5 minutes. The result was a high-amplitude 0.02Hz oscillation in multiple cardiovascular parameters. Thus, paced sighing is a reliable method for imposing very low frequency oscillations in the cardiovascular system, which has research and clinical implications that warrant further study. PMID:25720947

  9. The effects of sighing on the cardiovascular system.

    PubMed

    Vaschillo, Evgeny G; Vaschillo, Bronya; Buckman, Jennifer F; Nguyen-Louie, Tam; Heiss, Sydney; Pandina, Robert J; Bates, Marsha E

    2015-03-01

    Elicitation of high-amplitude oscillations in the cardiovascular system may serve to dampen psychophysiological reactivity to emotional and cognitive loading. Prior work has used paced breathing to impose clinically valuable high-amplitude ∼ 0.1 Hz oscillations. In this study, we investigated whether rhythmical sighing could likewise produce high-amplitude cardiovascular oscillations in the very low frequency range (0.003-0.05 Hz). ECG, respiration, skin conductance, and beat-to-beat blood pressure were collected in 24 healthy participants during baseline, 0.1 Hz paced breathing, and 0.02 Hz paced sighing (1 sigh every 50s, with normal breathing interspersed). Results showed that each sigh elicited a strong, well-defined reaction in the cardiovascular system. This reaction did not habituate when participants repeatedly sighed for 8.5 min. The result was a high-amplitude 0.02 Hz oscillation in multiple cardiovascular parameters. Thus, paced sighing is a reliable method for imposing very low frequency oscillations in the cardiovascular system, which has research and clinical implications that warrant further study.

  10. Central neural control of the cardiovascular system: current perspectives.

    PubMed

    Dampney, Roger A L

    2016-09-01

    This brief review, which is based on a lecture presented at the American Physiological Society Teaching Refresher Course on the Brain and Systems Control as part of the Experimental Biology meeting in 2015, aims to summarize current concepts of the principal mechanisms in the brain that regulate the autonomic outflow to the cardiovascular system. Such cardiovascular regulatory mechanisms do not operate in isolation but are closely coordinated with respiratory and other regulatory mechanisms to maintain homeostasis. The brain regulates the cardiovascular system by two general means: 1) feedforward regulation, often referred to as "central command," and 2) feedback or reflex regulation. In most situations (e.g., during exercise, defensive behavior, sleep, etc.), both of these general mechanisms contribute to overall cardiovascular homeostasis. The review first describes the mechanisms and central circuitry subserving the baroreceptor, chemoreceptor, and other reflexes that work together to regulate an appropriate level of blood pressure and blood oxygenation and then considers the brain mechanisms that defend the body against more complex environmental challenges, using dehydration and cold and heat stress as examples. The last section of the review considers the central mechanisms regulating cardiovascular function associated with different behaviors, with a specific focus on defensive behavior and exercise.

  11. Central Neural Control of the Cardiovascular System: Current Perspectives

    ERIC Educational Resources Information Center

    Dampney, Roger A. L.

    2016-01-01

    This brief review, which is based on a lecture presented at the American Physiological Society Teaching Refresher Course on the Brain and Systems Control as part of the Experimental Biology meeting in 2015, aims to summarize current concepts of the principal mechanisms in the brain that regulate the autonomic outflow to the cardiovascular system.…

  12. Toxic effects of marijuana on the cardiovascular system.

    PubMed

    Pratap, Balaji; Korniyenko, Aleksandr

    2012-06-01

    We present a case of marijuana-induced ST segment elevation mimicking Brugada syndrome in a young man. Cannabis can have a multitude of effects on the different organ systems of the body; we take a closer look at its effects on the cardiovascular system, including acute coronary syndrome, arrhythmias and congestive heart failure. PMID:22194141

  13. O-GlcNAc signaling in the cardiovascular system.

    PubMed

    Ngoh, Gladys A; Facundo, Heberty T; Zafir, Ayesha; Jones, Steven P

    2010-07-23

    Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of posttranslational modifications. One such modification orchestrates input from numerous metabolic cues to modify proteins and alter their localization and/or function. Known as the beta-O-linkage of N-acetylglucosamine (ie, O-GlcNAc) to cellular proteins, this unique monosaccharide is involved in a diverse array of physiological and pathological functions. This review introduces readers to the general concepts related to O-GlcNAc, the regulation of this modification, and its role in primary pathophysiology. Much of the existing literature regarding the role of O-GlcNAcylation in disease addresses the protracted elevations in O-GlcNAcylation observed during diabetes. In this review, we focus on the emerging evidence of its involvement in the cardiovascular system. In particular, we highlight evidence of protein O-GlcNAcylation as an autoprotective alarm or stress response. We discuss recent literature supporting the idea that promoting O-GlcNAcylation improves cell survival during acute stress (eg, hypoxia, ischemia, oxidative stress), whereas limiting O-GlcNAcylation exacerbates cell damage in similar models. In addition to addressing the potential mechanisms of O-GlcNAc-mediated cardioprotection, we discuss technical issues related to studying protein O-GlcNAcylation in biological systems. The reader should gain an understanding of what protein O-GlcNAcylation is and that its roles in the acute and chronic disease settings appear distinct.

  14. Technological innovations in the development of cardiovascular clinical information systems.

    PubMed

    Hsieh, Nan-Chen; Chang, Chung-Yi; Lee, Kuo-Chen; Chen, Jeen-Chen; Chan, Chien-Hui

    2012-04-01

    Recent studies have shown that computerized clinical case management and decision support systems can be used to assist surgeons in the diagnosis of disease, optimize surgical operation, aid in drug therapy and decrease the cost of medical treatment. Therefore, medical informatics has become an extensive field of research and many of these approaches have demonstrated potential value for improving medical quality. The aim of this study was to develop a web-based cardiovascular clinical information system (CIS) based on innovative techniques, such as electronic medical records, electronic registries and automatic feature surveillance schemes, to provide effective tools and support for clinical care, decision-making, biomedical research and training activities. The CIS developed for this study contained monitoring, surveillance and model construction functions. The monitoring layer function provided a visual user interface. At the surveillance and model construction layers, we explored the application of model construction and intelligent prognosis to aid in making preoperative and postoperative predictions. With the use of the CIS, surgeons can provide reasonable conclusions and explanations in uncertain environments.

  15. Clinical Application of Stem Cells in the Cardiovascular System

    NASA Astrophysics Data System (ADS)

    Stamm, Christof; Klose, Kristin; Choi, Yeong-Hoon

    Regenerative medicine encompasses "tissue engineering" - the in vitro fabrication of tissues and/or organs using scaffold material and viable cells - and "cell therapy" - the transplantation or manipulation of cells in diseased tissue in vivo. In the cardiovascular system, tissue engineering strategies are being pursued for the development of viable replacement blood vessels, heart valves, patch material, cardiac pacemakers and contractile myocardium. Anecdotal clinical applications of such vessels, valves and patches have been described, but information on systematic studies of the performance of such implants is not available, yet. Cell therapy for cardiovascular regeneration, however, has been performed in large series of patients, and numerous clinical studies have produced sometimes conflicting results. The purpose of this chapter is to summarize the clinical experience with cell therapy for diseases of the cardiovascular system, and to analyse possible factors that may influence its outcome.

  16. Hydroxybenzoic acid isomers and the cardiovascular system

    PubMed Central

    2014-01-01

    Today we are beginning to understand how phytochemicals can influence metabolism, cellular signaling and gene expression. The hydroxybenzoic acids are related to salicylic acid and salicin, the first compounds isolated that have a pharmacological activity. In this review we examine how a number of hydroxyphenolics have the potential to ameliorate cardiovascular problems related to aging such as hypertension, atherosclerosis and dyslipidemia. The compounds focused upon include 2,3-dihydroxybenzoic acid (Pyrocatechuic acid), 2,5-dihydroxybenzoic acid (Gentisic acid), 3,4-dihydroxybenzoic acid (Protocatechuic acid), 3,5-dihydroxybenzoic acid (α-Resorcylic acid) and 3-monohydroxybenzoic acid. The latter two compounds activate the hydroxycarboxylic acid receptors with a consequence there is a reduction in adipocyte lipolysis with potential improvements of blood lipid profiles. Several of the other compounds can activate the Nrf2 signaling pathway that increases the expression of antioxidant enzymes, thereby decreasing oxidative stress and associated problems such as endothelial dysfunction that leads to hypertension as well as decreasing generalized inflammation that can lead to problems such as atherosclerosis. It has been known for many years that increased consumption of fruits and vegetables promotes health. We are beginning to understand how specific phytochemicals are responsible for such therapeutic effects. Hippocrates’ dictum of ‘Let food be your medicine and medicine your food’ can now be experimentally tested and the results of such experiments will enhance the ability of nutritionists to devise specific health-promoting diets. PMID:24943896

  17. Hydroxybenzoic acid isomers and the cardiovascular system.

    PubMed

    Juurlink, Bernhard H J; Azouz, Haya J; Aldalati, Alaa M Z; AlTinawi, Basmah M H; Ganguly, Paul

    2014-01-01

    Today we are beginning to understand how phytochemicals can influence metabolism, cellular signaling and gene expression. The hydroxybenzoic acids are related to salicylic acid and salicin, the first compounds isolated that have a pharmacological activity. In this review we examine how a number of hydroxyphenolics have the potential to ameliorate cardiovascular problems related to aging such as hypertension, atherosclerosis and dyslipidemia. The compounds focused upon include 2,3-dihydroxybenzoic acid (Pyrocatechuic acid), 2,5-dihydroxybenzoic acid (Gentisic acid), 3,4-dihydroxybenzoic acid (Protocatechuic acid), 3,5-dihydroxybenzoic acid (α-Resorcylic acid) and 3-monohydroxybenzoic acid. The latter two compounds activate the hydroxycarboxylic acid receptors with a consequence there is a reduction in adipocyte lipolysis with potential improvements of blood lipid profiles. Several of the other compounds can activate the Nrf2 signaling pathway that increases the expression of antioxidant enzymes, thereby decreasing oxidative stress and associated problems such as endothelial dysfunction that leads to hypertension as well as decreasing generalized inflammation that can lead to problems such as atherosclerosis. It has been known for many years that increased consumption of fruits and vegetables promotes health. We are beginning to understand how specific phytochemicals are responsible for such therapeutic effects. Hippocrates' dictum of 'Let food be your medicine and medicine your food' can now be experimentally tested and the results of such experiments will enhance the ability of nutritionists to devise specific health-promoting diets. PMID:24943896

  18. [Mathematical modeling for conditionality of cardiovascular disease by housing conditions].

    PubMed

    Meshkov, N A

    2014-01-01

    There was studied the influence of living conditions (housing area per capita, availability of housing water supply, sewerage and central heating) on the morbidity of the cardiovascular diseases in child and adult population. With the method of regression analysis the morbidity rate was established to significantly decrease with the increase in the area of housing, constructed models are statistically significant, respectively, p = 0.01 and p = 0.02. There was revealed the relationship of the morbidity rate of cardiovascular diseases in children and adults with the supply with housing central heating (p = 0.02 and p = 0.009). PMID:25950060

  19. Alcohol and the cardiovascular system: research challenges and opportunities.

    PubMed

    Lucas, Diane L; Brown, Ricardo A; Wassef, Momtaz; Giles, Thomas D

    2005-06-21

    Excessive alcohol consumption has long been associated with cardiovascular disorders, including cardiomyopathy, hypertension, coronary artery disease, and stroke. However, recent evidence suggests that moderate alcohol intake can actually provide a measure of cardioprotection, particularly against coronary heart disease and ischemia-reperfusion injury. To explore the various dimensions of these opposing actions of alcohol, the National Institute on Alcohol Abuse and Alcoholism and the National Heart, Lung, and Blood Institute sponsored a state-of-the-art workshop on "Alcohol and the Cardiovascular System: Research Challenges and Opportunities" in Bethesda, Maryland, in May 2003. Speakers discussed the following topics: the epidemiology of alcohol and cardiovascular disease, clinical manifestations of alcohol, genetics of alcohol and cardiovascular disease, mechanisms underlying the molecular and cellular effects of alcohol, the application of new and emerging technology, and translation from discovery to therapeutic modalities of treatment. The panel concluded that future studies are needed to: 1) determine the role of genes and the environment in assessing mechanisms underlying the benefits of alcohol use and cardiovascular disease risk; 2) define the biological mechanisms underlying alcohol-induced peripheral vascular damage; 3) clarify the role of genetic variation in alcohol-metabolizing enzymes, genetic susceptibility, and pharmacogenomics in determining cardiovascular disease risk and effective treatment; 4) determine common mechanisms underlying alcohol-induced cardiovascular disease, such as oxidative stress and inflammation; 5) assess the role of insulin resistance, blood clotting, protein kinase C isoforms, and signal transduction mechanisms mediating alcohol's beneficial effects; and 6) explore the potential of stem cells in myocardial regeneration and repair in hearts damaged by alcohol.

  20. Alcohol and the cardiovascular system: research challenges and opportunities.

    PubMed

    Lucas, Diane L; Brown, Ricardo A; Wassef, Momtaz; Giles, Thomas D

    2005-06-21

    Excessive alcohol consumption has long been associated with cardiovascular disorders, including cardiomyopathy, hypertension, coronary artery disease, and stroke. However, recent evidence suggests that moderate alcohol intake can actually provide a measure of cardioprotection, particularly against coronary heart disease and ischemia-reperfusion injury. To explore the various dimensions of these opposing actions of alcohol, the National Institute on Alcohol Abuse and Alcoholism and the National Heart, Lung, and Blood Institute sponsored a state-of-the-art workshop on "Alcohol and the Cardiovascular System: Research Challenges and Opportunities" in Bethesda, Maryland, in May 2003. Speakers discussed the following topics: the epidemiology of alcohol and cardiovascular disease, clinical manifestations of alcohol, genetics of alcohol and cardiovascular disease, mechanisms underlying the molecular and cellular effects of alcohol, the application of new and emerging technology, and translation from discovery to therapeutic modalities of treatment. The panel concluded that future studies are needed to: 1) determine the role of genes and the environment in assessing mechanisms underlying the benefits of alcohol use and cardiovascular disease risk; 2) define the biological mechanisms underlying alcohol-induced peripheral vascular damage; 3) clarify the role of genetic variation in alcohol-metabolizing enzymes, genetic susceptibility, and pharmacogenomics in determining cardiovascular disease risk and effective treatment; 4) determine common mechanisms underlying alcohol-induced cardiovascular disease, such as oxidative stress and inflammation; 5) assess the role of insulin resistance, blood clotting, protein kinase C isoforms, and signal transduction mechanisms mediating alcohol's beneficial effects; and 6) explore the potential of stem cells in myocardial regeneration and repair in hearts damaged by alcohol. PMID:15963387

  1. Molecular mechanisms of autophagy in the cardiovascular system.

    PubMed

    Gatica, Damián; Chiong, Mario; Lavandero, Sergio; Klionsky, Daniel J

    2015-01-30

    Autophagy is a catabolic recycling pathway triggered by various intra- or extracellular stimuli that is conserved from yeast to mammals. During autophagy, diverse cytosolic constituents are enveloped by double-membrane vesicles, autophagosomes, which later fuse with lysosomes or the vacuole to degrade their cargo. Dysregulation in autophagy is associated with a diverse range of pathologies including cardiovascular disease, the leading cause of death in the world. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been characterized widely in cardiomyocytes, cardiac fibroblasts, endothelial cells, and vascular smooth muscle cells. In all cases, a window of optimal autophagic activity seems to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. Here, we review the molecular mechanisms that govern autophagosome formation and analyze the link between autophagy and cardiovascular disease.

  2. The emerging role of the endocannabinoid system in cardiovascular disease

    PubMed Central

    2009-01-01

    Endocannabinoids are endogenous bioactive lipid mediators present both in the brain and various peripheral tissues, which exert their biological effects via interaction with specific G-protein-coupled cannabinoid receptors, the CB1 and CB2. Pathological overactivation of the endocannabinoid system (ECS) in various forms of shock and heart failure may contribute to the underlying pathology and cardiodepressive state by the activation of the cardiovascular CB1 receptors. Furthermore, tonic activation of CB1 receptors by endocannabinoids has also been implicated in the development of various cardiovascular risk factors in obesity/metabolic syndrome and diabetes, such as plasma lipid alterations, abdominal obesity, hepatic steatosis, inflammation, and insulin and leptin resistance. In contrast, activation of CB2 receptors in immune cells exerts various immunomodulatory effects, and the CB2 receptors in endothelial and inflammatory cells appear to limit the endothelial inflammatory response, chemotaxis, and inflammatory cell adhesion and activation in atherosclerosis and reperfusion injury. Here, we will overview the cardiovascular actions of endocannabinoids and the growing body of evidence implicating the dysregulation of the ECS in a variety of cardiovascular diseases. We will also discuss the therapeutic potential of the modulation of the ECS by selective agonists/antagonists in various cardiovascular disorders associated with inflammation and tissue injury, ranging from myocardial infarction and heart failure to atherosclerosis and cardiometabolic disorders. PMID:19357846

  3. Prediction models for early risk detection of cardiovascular event.

    PubMed

    Purwanto; Eswaran, Chikkannan; Logeswaran, Rajasvaran; Abdul Rahman, Abdul Rashid

    2012-04-01

    Cardiovascular disease (CVD) is the major cause of death globally. More people die of CVDs each year than from any other disease. Over 80% of CVD deaths occur in low and middle income countries and occur almost equally in male and female. In this paper, different computational models based on Bayesian Networks, Multilayer Perceptron,Radial Basis Function and Logistic Regression methods are presented to predict early risk detection of the cardiovascular event. A total of 929 (626 male and 303 female) heart attack data are used to construct the models.The models are tested using combined as well as separate male and female data. Among the models used, it is found that the Multilayer Perceptron model yields the best accuracy result.

  4. Nitric oxide, a protective molecule in the cardiovascular system.

    PubMed

    Lei, Jing; Vodovotz, Yoram; Tzeng, Edith; Billiar, Timothy R

    2013-11-30

    Nitric oxide (NO) is an intra- and inter-signaling molecule that regulates vessel dilatation, neuronal transmission, cardiac contraction, immunomodulation, and stem cell differentiation and proliferation. NO plays an important protective role in the cardiovascular system. NO inhibits smooth muscle cells proliferation and migration; enhances proliferation and migration of endothelial cell and inhibits apoptosis; suppresses platelet aggregation; and prevents platelet, leukocyte and monocyte adhesion to endothelium. NO exerts an inhibitory effect on the development of intimal hyperplasia in mechanically or immunologically injured vessel. New therapeutic approaches aimed at enhancing NO bioavailability or assisting delivery of NO locally may help patients with cardiovascular disease.

  5. Electronic circuit detects left ventricular ejection events in cardiovascular system

    NASA Technical Reports Server (NTRS)

    Gebben, V. D.; Webb, J. A., Jr.

    1972-01-01

    Electronic circuit processes arterial blood pressure waveform to produce discrete signals that coincide with beginning and end of left ventricular ejection. Output signals provide timing signals for computers that monitor cardiovascular systems. Circuit operates reliably for heart rates between 50 and 200 beats per minute.

  6. Decadal Cycles in the Human Cardiovascular System

    PubMed Central

    Halberg, Franz; Cornelissen, Germaine; Sothern, Robert B.; Hillman, Dewayne; Watanabe, Yoshihiko; Haus, Erhard; Schwartzkopff, Othild; Best, William R.

    2013-01-01

    Seven of the eight authors of this report each performed physiologic self-surveillance, some around the clock for decades. We here document the presence of long cycles (decadals, including circaundecennians) in the time structure of systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR). Because of the non-stationary nature in time and space of these and other physiologic and environmental periodic components that, like the wind, can appear and disappear in a given or other geographic location at one or another time, they have been called “Aeolian”. The nonlinear estimation of the uncertainties of the periods (τs) of two or more variables being compared has been used to determine whether these components are congruent or not, depending on whether their CIs (95% confidence intervals) overlap or not. Among others, congruence has been found for components with τs clustering around 10 years in us and around us. There is a selective assortment among individuals, variables and cycle characteristics (mean and circadian amplitude and acrophase). Apart from basic interest, like other nonphotic solar signatures such as transyears with periods slightly longer than one year or about 33-year Brückner-Egeson-Lockyer (BEL) cycles, about 10-year and longer cycles present in 7 of 7 self-monitoring individuals are of interest in the diagnosis of Vascular Variability Anomalies (VVAs), including MESOR-hypertension, and others. Some of the other VVAs, such as a circadian overswing, i.e., CHAT (Circadian Hyper-Aplitude-Tension), or an excessive pulse pressure, based on repeated 7-day around-the-clock records, can represent a risk of severe cardiovascular events, greater than that of a high BP. The differential diagnosis of physiologic cycles, infradians (components with a τ longer than 28 hours) as well as circadians awaits the collection of reference values for the infradian parameters of the cycles described herein. Just as in stroke-prone spontaneously

  7. User's instructions for the GE cardiovascular model to simulate LBNP and tilt experiments, with graphic capabilities

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The present form of this cardiovascular model simulates both 1-g and zero-g LBNP (lower body negative pressure) experiments and tilt experiments. In addition, the model simulates LBNP experiments at any body angle. The model is currently accessible on the Univac 1110 Time-Shared System in an interactive operational mode. Model output may be in tabular form and/or graphic form. The graphic capabilities are programmed for the Tektronix 4010 graphics terminal and the Univac 1110.

  8. Parasympathetic Stimuli on Bronchial and Cardiovascular Systems in Humans

    PubMed Central

    Zannin, Emanuela; Pellegrino, Riccardo; Di Toro, Alessandro; Antonelli, Andrea; Dellacà, Raffaele L.; Bernardi, Luciano

    2015-01-01

    Background It is not known whether parasympathetic outflow simultaneously acts on bronchial tone and cardiovascular system waxing and waning both systems in parallel, or, alternatively, whether the regulation is more dependent on local factors and therefore independent on each system. The aim of this study was to evaluate the simultaneous effect of different kinds of stimulations, all associated with parasympathetic activation, on bronchomotor tone and cardiovascular autonomic regulation. Methods Respiratory system resistance (Rrs, forced oscillation technique) and cardio-vascular activity (heart rate, oxygen saturation, tissue oxygenation index, blood pressure) were assessed in 13 volunteers at baseline and during a series of parasympathetic stimuli: O2 inhalation, stimulation of the carotid sinus baroreceptors by neck suction, slow breathing, and inhalation of methacholine. Results Pure cholinergic stimuli, like O2 inhalation and baroreceptors stimulation, caused an increase in Rrs and a reduction in heart rate and blood pressure. Slow breathing led to bradycardia and hypotension, without significant changes in Rrs. However slow breathing was associated with deep inhalations, and Rrs evaluated at the baseline lung volumes was significantly increased, suggesting that the large tidal volumes reversed the airways narrowing effect of parasympathetic activation. Finally inhaled methacholine caused marked airway narrowing, while the cardiovascular variables were unaffected, presumably because of the sympathetic activity triggered in response to hypoxemia. Conclusions All parasympathetic stimuli affected bronchial tone and moderately affected also the cardiovascular system. However the response differed depending on the nature of the stimulus. Slow breathing was associated with large tidal volumes that reversed the airways narrowing effect of parasympathetic activation. PMID:26046774

  9. A Multiscale Model of Cardiovascular System Including an Immersed Whole Heart in the Cases of Normal and Ventricular Septal Defect (VSD).

    PubMed

    Lee, Wanho; Jung, Eunok

    2015-07-01

    A mathematical and computational model combining the heart and circulatory system has been developed to understand the hemodynamics of circulation under normal conditions and ventricular septal defect (VSD). The immersed boundary method has been introduced to describe the interaction between the moving two-dimensional heart and intracardiac blood flow. The whole-heart model is governed by the Navier-Stokes system; this system is combined with a multi-compartment model of circulation using pressure-flow relations and the linearity of the discretized Navier-Stokes system. We investigate the velocity field, flowmeters, and pressure-volume loop in both normal and VSD cases. Simulation results show qualitatively good agreements with others found in the literature. This model, combining the heart and circulation, is useful for understanding the complex, hemodynamic mechanisms involved in normal circulation and cardiac diseases.

  10. A Multiscale Model of Cardiovascular System Including an Immersed Whole Heart in the Cases of Normal and Ventricular Septal Defect (VSD).

    PubMed

    Lee, Wanho; Jung, Eunok

    2015-07-01

    A mathematical and computational model combining the heart and circulatory system has been developed to understand the hemodynamics of circulation under normal conditions and ventricular septal defect (VSD). The immersed boundary method has been introduced to describe the interaction between the moving two-dimensional heart and intracardiac blood flow. The whole-heart model is governed by the Navier-Stokes system; this system is combined with a multi-compartment model of circulation using pressure-flow relations and the linearity of the discretized Navier-Stokes system. We investigate the velocity field, flowmeters, and pressure-volume loop in both normal and VSD cases. Simulation results show qualitatively good agreements with others found in the literature. This model, combining the heart and circulation, is useful for understanding the complex, hemodynamic mechanisms involved in normal circulation and cardiac diseases. PMID:26223734

  11. Endocannabinoids and the Cardiovascular System in Health and Disease.

    PubMed

    O'Sullivan, Saoirse Elizabeth

    2015-01-01

    The endocannabinoid system is widely distributed throughout the cardiovascular system. Endocannabinoids play a minimal role in the regulation of cardiovascular function in normal conditions, but are altered in most cardiovascular disorders. In shock, endocannabinoids released within blood mediate the associated hypotension through CB(1) activation. In hypertension, there is evidence for changes in the expression of CB(1), and CB(1) antagonism reduces blood pressure in obese hypertensive and diabetic patients. The endocannabinoid system is also upregulated in cardiac pathologies. This is likely to be cardioprotective, via CB(2) and CB(1) (lesser extent). In the vasculature, endocannabinoids cause vasorelaxation through activation of multiple target sites, inhibition of calcium channels, activation of potassium channels, NO production and the release of vasoactive substances. Changes in the expression or function of any of these pathways alter the vascular effect of endocannabinoids. Endocannabinoids have positive (CB(2)) and negative effects (CB(1)) on the progression of atherosclerosis. However, any negative effects of CB(1) may not be consequential, as chronic CB(1) antagonism in large scale human trials was not associated with significant reductions in atheroma. In neurovascular disorders such as stroke, endocannabinoids are upregulated and protective, involving activation of CB(1), CB(2), TRPV1 and PPARα. Although most of this evidence is from preclinical studies, it seems likely that cannabinoid-based therapies could be beneficial in a range of cardiovascular disorders.

  12. Cell death and survival signalling in the cardiovascular system.

    PubMed

    Tucka, Joanna; Bennett, Martin; Littlewood, Trevor

    2012-01-01

    The loss of cells is an important factor in many diseases, including those of the cardiovascular system. Whereas apoptosis is an essential process in development and tissue homeostasis, its occurrence is often associated with various pathologies. Apoptosis of neurons that fail to make appropriate connections is essential for the selection of correct neural signalling in the developing embryo, but its appearance in adults is often associated with neurodegenerative disease. Similarly, in the cardiovascular system, remodeling of the mammalian outflow tract during the transition from a single to dual series circulation with four chambers is accompanied by a precise pattern of cell death, but apoptosis of cardiomyocytes contributes to ischemia-reperfusion injury in the heart. In many cases, it is unclear whether apoptosis represents a causative association or merely a consequence of the disease itself. There are many excellent reviews on cell death in the cardiovascular system (1-5); in this review we outline the critical signalling pathways that promote the survival of cardiovascular cells, and their relevance to both physiological cell death and disease.

  13. Stress, depression and cardiovascular dysregulation: a review of neurobiological mechanisms and the integration of research from preclinical disease models.

    PubMed

    Grippo, Angela J; Johnson, Alan Kim

    2009-01-01

    Bidirectional associations between mood disorders and cardiovascular diseases are extensively documented. However, the precise physiological and biochemical mechanisms that underlie such relationships are not well understood. This review focuses on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders. The discussion places an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and the activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction involving the dopamine, norepinephrine and serotonin systems, and (e) behavioral changes including fatigue and physical inactivity. The review also discusses experimental investigations using preclinical disease models to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, (c) a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with an extensive human research literature, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance understanding the association between depression and cardiovascular disease. This will ultimately promote the development of better treatments and interventions for individuals with co-morbid psychological and somatic pathologies.

  14. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

    EPA Science Inventory

    This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

  15. Short-term cardiovascular oscillations in man: measuring and modelling the physiologies

    PubMed Central

    Cohen, Michael A; Taylor, J Andrew

    2002-01-01

    Research into cardiovascular variabilities intersects both human physiology and quantitative modelling. This is because respiratory and Mayer wave (or 10 s) cardiovascular oscillations represent the integrated control of a system through both autonomic branches by systemic haemodynamic changes within a fluid-filled, physical system. However, our current precise measurement of short-term cardiovascular fluctuations does not necessarily mean we have an adequate understanding of them. Empirical observation suggests that both respiratory and Mayer wave fluctuations derive from mutable autonomic and haemodynamic inputs. Evidence strongly suggests that respiratory sinus arrhythmia both contributes to and buffers respiratory arterial pressure fluctuations. Moreover, even though virtual abolition of all R-R interval variability by cholinergic blockade suggests that parasympathetic stimulation is essential for expression of these variabilities, respiratory sinus arrhythmia does not always reflect a purely vagal phenomenon. The arterial baroreflex has been cited as the mechanism for both respiratory and Mayer wave frequency fluctuations. However, data suggest that both cardiac vagal and vascular sympathetic fluctuations at these frequencies are independent of baroreflex mechanisms and, in fact, contribute to pressure fluctuations. Results from cardiovascular modelling can suggest possible sources for these rhythms. For example, modelling originally suggested low frequency cardiovascular rhythms derived from intrinsic delays in baroreceptor control, and experimental evidence subsequently corroborated this possibility. However, the complex stochastic relations between and variabilities in these rhythms indicate no single mechanism is responsible. If future study of cardiovascular variabilities is to move beyond qualitative suggestions of determinants to quantitative elucidation of critical physical mechanisms, both experimental design and model construction will have to be

  16. Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system.

    PubMed

    Khan, Amir S; Sane, David C; Wannenburg, Thomas; Sonntag, William E

    2002-04-01

    There is a large body of evidence that biological aging is related to a series of long-term catabolic processes resulting in decreased function and structural integrity of several physiological systems, among which is the cardiovascular system. These changes in the aging phenotype are correlated with a decline in the amplitude of pulsatile growth hormone secretion and the resulting decrease in plasma levels of its anabolic mediator, insulin like growth factor-1 (IGF-1). The relationship between growth hormone and biological aging is supported by studies demonstrating that growth hormone administration to old animals and humans raises plasma IGF-1 and results in increases in skeletal muscle and lean body mass, a decrease in adiposity, increased immune function, improvements in learning and memory, and increases in cardiovascular function. Since growth hormone and IGF-1 exert potent effects on the heart and vasculature, the relationship between age-related changes in cardiovascular function and the decline in growth hormone levels with age have become of interest. Among the age-related changes in the cardiovascular system are decreases in myocyte number, accumulation of fibrosis and collagen, decreases in stress-induced cardiac function through deterioration of the myocardial conduction system and beta-adrenergic receptor function, decreases in exercise capacity, vessel rarefaction, decreased arterial compliance and endothelial dysfunction leading to alterations in blood flow. Growth hormone has been found to exert potent effects on cardiovascular function in young animals and reverses many of the deficits in cardiovascular function in aged animals and humans. Nevertheless, it has been difficult to separate the effects of growth hormone deficiency from age-related diseases and associated pathologies. The development of novel animal models and additional research are required in order to elucidate the specific effects of growth hormone deficiency and assess its

  17. Differential Role of Leptin and Adiponectin in Cardiovascular System

    PubMed Central

    Ghantous, C. M.; Azrak, Z.; Hanache, S.; Abou-Kheir, W.; Zeidan, A.

    2015-01-01

    Leptin and adiponectin are differentially expressed adipokines in obesity and cardiovascular diseases. Leptin levels are directly associated with adipose tissue mass, while adiponectin levels are downregulated in obesity. Although significantly produced by adipocytes, leptin is also produced by vascular smooth muscle cells and cardiomyocytes. Plasma leptin concentrations are elevated in cases of cardiovascular diseases, such as hypertension, congestive heart failure, and myocardial infarction. As for the event of left ventricular hypertrophy, researchers have been stirring controversy about the role of leptin in this form of cardiac remodeling. In this review, we discuss how leptin has been shown to play an antihypertrophic role in the development of left ventricular hypertrophy through in vitro experiments, population-based cross-sectional studies, and longitudinal cohort studies. Conversely, we also examine how leptin may actually promote left ventricular hypertrophy using in vitro analysis and human-based univariate and multiple linear stepwise regression analysis. On the other hand, as opposed to leptin's generally detrimental effects on the cardiovascular system, adiponectin is a cardioprotective hormone that reduces left ventricular and vascular hypertrophy, oxidative stress, and inflammation. In this review, we also highlight adiponectin signaling and its protective actions on the cardiovascular system. PMID:26064110

  18. Cardiovascular parameters in rat model of chronic renal failure induced by subtotal nephrectomy.

    PubMed

    Svíglerová, J; Kuncová, J; Nalos, L; Tonar, Z; Rajdl, D; Stengl, M

    2010-01-01

    Chronic renal failure (CRF) is associated with high incidence of cardiovascular complications. To clarify pathogenesis of CRF numerous animal models have been developed. The aim of our work was to describe methodology of subtotal surgical renal ablation in rat and to characterize some biochemical and cardiovascular parameters of this animal model. Male rats underwent 5/6 surgical nephrectomy or sham operations in two steps. The following parameters were measured on day 10 and in week 10 after the surgery: plasma concentrations of creatinine and urea, blood pressure, resting heart rate, chronotropic response to atropine and metipranol, heart ventricles weight, contraction parameters and action potential duration in the left ventricle. Increased serum concentrations of creatinine and urea, decreased creatinine clearance, polyuria and alteration of the remnant kidney tissue were found in CRF rats. Changes in cardiovascular parameters identified after subtotal nephrectomy resembled alterations of cardiovascular system in uremic patients and included hypertension, elevated resting heart rate, diminished parasympathetic cardiac tone, hypertrophy of the left ventricle associated with weakened force of contraction, prolonged contraction and relaxation and shortening of action potential duration. These data suggest that the present model can be a useful tool in the study of CRF and its cardiovascular complications.

  19. The role of urocortins in the cardiovascular system.

    PubMed

    Walczewska, J; Dzieza-Grudnik, A; Siga, O; Grodzicki, T

    2014-12-01

    Urocortins (Ucn) 1, 2 and 3 are a group of endogenous peptide hormones belonging to the corticotropin-releasing hormone (CRH) family of peptides. The presence of urocortins has been detected in the central nervous system as well as in peripheral tissues. They play an important role in a stress response (with respect to its duration, intensity and restoration of homeostasis). They also act as regulatory factors of the cardiovascular, gastrointestinal, reproductive and immune systems. Urocortins act by binding to G-protein-coupled receptors (GPCR). The "central" effects of urocortins are mediated mainly by activation of CRH receptor 1 (CRH-R1), and the "peripheral" effects by activation of CRH-R2. Ucn2 and Ucn3 are selective CRH-R2 agonists and have much higher binding affinity to this receptor than CRH and Ucn1. Recent studies have shown that urocortins exert various biological effects in the cardiovascular system, such as vasodilation, positive inotropic and lusitropic effects, as well as cardioprotection against ischemia-reperfusion injury. They also suppress the renin-angiotensin system and may have an impact on the sympathetic nervous system. Urocortins and CRH-R2 may be a potential therapeutic target in coronary heart disease, congestive heart failure and hypertension. This review summarizes the data published to date on the role of urocortins in the cardiovascular system.

  20. Predictive modeling of cardiovascular complications in incident hemodialysis patients.

    PubMed

    Ion Titapiccolo, J; Ferrario, M; Barbieri, C; Marcelli, D; Mari, F; Gatti, E; Cerutti, S; Smyth, P; Signorini, M G

    2012-01-01

    The administration of hemodialysis (HD) treatment leads to the continuous collection of a vast quantity of medical data. Many variables related to the patient health status, to the treatment, and to dialyzer settings can be recorded and stored at each treatment session. In this study a dataset of 42 variables and 1526 patients extracted from the Fresenius Medical Care database EuCliD was used to develop and apply a random forest predictive model for the prediction of cardiovascular events in the first year of HD treatment. A ridge-lasso logistic regression algorithm was then applied to the subset of variables mostly involved in the prediction model to get insights in the mechanisms underlying the incidence of cardiovascular complications in this high risk population of patients.

  1. Non-genomic effect of glucocorticoids on cardiovascular system.

    PubMed

    Lee, Sung Ryul; Kim, Hyoung Kyu; Youm, Jae Boum; Dizon, Louise Anne; Song, In Sung; Jeong, Seung Hun; Seo, Dae Yun; Ko, Kyoung Soo; Rhee, Byoung Doo; Kim, Nari; Han, Jin

    2012-12-01

    Glucocorticoids (GCs) are essential steroid hormones for homeostasis, development, metabolism, and cognition and possess anti-inflammatory and immunosuppressive actions. Since glucocorticoid receptor II (GR) is nearly ubiquitous, chronic activation or depletion of GCs leads to dysfunction of diverse organs, including the heart and blood vessels, resulting predominantly from changes in gene expression. Most studies, therefore, have focused on the genomic effects of GC to understand its related pathophysiological manifestations. The nongenomic effects of GCs clearly differ from well-known genomic effects, with the former responding within several minutes without the need for protein synthesis. There is increasing evidence that the nongenomic actions of GCs influence various physiological functions. To develop a GC-mediated therapeutic target for the treatment of cardiovascular disease, understanding the genomic and nongenomic effects of GC on the cardiovascular system is needed. This article reviews our current understanding of the underlying mechanisms of GCs on cardiovascular diseases and stress, as well as how nongenomic GC signaling contributes to these conditions. We suggest that manipulation of GC action based on both GC and GR metabolism, mitochondrial impact, and the action of serum- and glucocorticoid-dependent kinase 1 may provide new information with which to treat cardiovascular diseases.

  2. Glucagon-like peptide 1 and the cardiovascular system.

    PubMed

    Fava, Stephen

    2014-01-01

    Glucagon-like peptide 1 (GLP1) is a major incretin hormone. This means that it is secreted by the gut in response to food and helps in reducing post-prandial glucose exertion. It achieves this through a number of mechanisms, including stimulating insulin release by pancreatic β-cells in a glucose-dependent manner; inhibition of glucagon release by pancreatic α-cells (also in a glucose-dependent manner); induction of central appetite suppression and by delaying gastric empting thereby inducing satiety and also reducing the rate of absorption of nutrients. However, GLP1 receptors have been described in a number of extra-pancreatic tissues, including the endothelium and the myocardium. This suggests that the physiological effects of GLP1 extend beyond post-prandial glucose control and raises the possibility that GLP1 might have cardiovascular effects. This is of importance in our understanding of incretin hormone physiology and especially because of the possible implications that it might have with regard to cardiovascular effects of incretin-based therapies, namely DPP-IV inhibitors (gliptins) and GLP1 analogues. This review analyzes the animal and human data on the effects of GLP1 on the cardiovascular system in health and in disease and the currently available data on cardiovascular effects of incretin-based therapies. It is the author's view that the physiological role of GLP1 is not only to minimize postprandial hypoglycaemia, but also protect against it.

  3. Xenobiotic pulmonary exposure and systemic cardiovascular response via neurological links.

    PubMed

    Stapleton, Phoebe A; Abukabda, Alaeddin B; Hardy, Steven L; Nurkiewicz, Timothy R

    2015-11-15

    The cardiovascular response to xenobiotic particle exposure has been increasingly studied over the last two decades, producing an extraordinary scope and depth of research findings. With the flourishing of nanotechnology, the term "xenobiotic particles" has expanded to encompass not only air pollution particulate matter (PM) but also anthropogenic particles, such as engineered nanomaterials (ENMs). Historically, the majority of research in these fields has focused on pulmonary exposure and the adverse physiological effects associated with a host inflammatory response or direct particle-tissue interactions. Because these hypotheses can neither account entirely for the deleterious cardiovascular effects of xenobiotic particle exposure nor their time course, the case for substantial neurological involvement is apparent. Indeed, considerable evidence suggests that not only is neural involvement a significant contributor but also a reality that needs to be investigated more thoroughly when assessing xenobiotic particle toxicities. Therefore, the scope of this review is several-fold. First, we provide a brief overview of the major anatomical components of the central and peripheral nervous systems, giving consideration to the potential biologic targets affected by inhaled particles. Second, the autonomic arcs and mechanisms that may be involved are reviewed. Third, the cardiovascular outcomes following neurological responses are discussed. Lastly, unique problems, future risks, and hurdles associated with xenobiotic particle exposure are discussed. A better understanding of these neural issues may facilitate research that in conjunction with existing research, will ultimately prevent the untoward cardiovascular outcomes associated with PM exposures and/or identify safe ENMs for the advancement of human health. PMID:26386111

  4. Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights

    NASA Technical Reports Server (NTRS)

    White, Ronald J.; Leonard, Joel I.; Srinivasan, R. Srini; Charles, John B.

    1991-01-01

    The purpose of NASA's Extended Duration Orbiter program is a gradual extension of the capabilities of the Space Shuttle Orbiter beyond its current 7-10 day limit on mission duration, as warranted by deepening understanding of the long-term physiological effects of weightlessness. Attention is being given to the cardiovascular problem of orthostatic tolerance loss due to its adverse effects on crew performance and health during reentry and initial readaptation to earth gravity. An account is given of the results of the application of proven mathematical models of circulatory and cardiovascular systems under microgravity conditions.

  5. Role of substance P in the cardiovascular system.

    PubMed

    Mistrova, Eliska; Kruzliak, Peter; Chottova Dvorakova, Magdalena

    2016-08-01

    This article provides an overview of the structure and function of substance P signalling system and its involvement in the cardiovascular regulation. Substance P is an undecapeptide originating from TAC1 gen and belonging to the tachykinin family. The biological actions of substance P are mainly mediated through neurokinin receptor 1 since substance P is the ligand with the highest affinity to neurokinin receptor 1. Substance P is widely distributed within the central and peripheral nervous systems as well as in the cardiovascular system. Substance P is involved in the regulation of heart frequency, blood pressure and in the stretching of vessels. Substance P plays an important role in ischemia and reperfusion and cardiovascular response to stress. Additionally, it has been also implicated in angiogenesis, pain transmission and inflammation. The substance P/neurokinin receptor 1 receptor system is involved in the molecular bases of many human pathological processes. Antagonists of neurokinin receptor 1 receptor could provide clinical solutions for a variety of diseases. Neurokinin receptor 1 antagonists are already used in the prevention of chemotherapy induced nausea and vomiting.

  6. A biokinetic model for nickel released from cardiovascular devices.

    PubMed

    Saylor, David M; Adidharma, Lingga; Fisher, Jeffrey W; Brown, Ronald P

    2016-10-01

    Many alloys used in cardiovascular device applications contain high levels of nickel, which if released in sufficient quantities, can lead to adverse health effects. While nickel release from these devices is typically characterized through the use of in-vitro immersion tests, it is unclear if the rate at which nickel is released from a device during in-vitro testing is representative of the release rate following implantation in the body. To address this uncertainty, we have developed a novel biokinetic model that combines a traditional toxicokinetic compartment model with a physics-based model to estimate nickel release from an implanted device. This model links the rate of in-vitro nickel release from a cardiovascular device to serum nickel concentrations, an easily measured endpoint, to estimate the rate and extent of in-vivo nickel release from an implanted device. The model was initially parameterized using data in the literature on in-vitro nickel release from a nickel-containing alloy (nitinol) and baseline serum nickel levels in humans. The results of this first step were then used to validate specific components of the model. The remaining unknown quantities were fit using serum values reported in patients following implantation with nitinol atrial occluder devices. The model is not only consistent with levels of nickel in serum and urine of patients following treatment with the atrial occluders, but also the optimized parameters in the model were all physiologically plausible. The congruity of the model with available data suggests that it can provide a framework to interpret nickel biomonitoring data and use data from in-vitro nickel immersion tests to estimate in-vivo nickel release from implanted cardiovascular devices.

  7. A biokinetic model for nickel released from cardiovascular devices.

    PubMed

    Saylor, David M; Adidharma, Lingga; Fisher, Jeffrey W; Brown, Ronald P

    2016-10-01

    Many alloys used in cardiovascular device applications contain high levels of nickel, which if released in sufficient quantities, can lead to adverse health effects. While nickel release from these devices is typically characterized through the use of in-vitro immersion tests, it is unclear if the rate at which nickel is released from a device during in-vitro testing is representative of the release rate following implantation in the body. To address this uncertainty, we have developed a novel biokinetic model that combines a traditional toxicokinetic compartment model with a physics-based model to estimate nickel release from an implanted device. This model links the rate of in-vitro nickel release from a cardiovascular device to serum nickel concentrations, an easily measured endpoint, to estimate the rate and extent of in-vivo nickel release from an implanted device. The model was initially parameterized using data in the literature on in-vitro nickel release from a nickel-containing alloy (nitinol) and baseline serum nickel levels in humans. The results of this first step were then used to validate specific components of the model. The remaining unknown quantities were fit using serum values reported in patients following implantation with nitinol atrial occluder devices. The model is not only consistent with levels of nickel in serum and urine of patients following treatment with the atrial occluders, but also the optimized parameters in the model were all physiologically plausible. The congruity of the model with available data suggests that it can provide a framework to interpret nickel biomonitoring data and use data from in-vitro nickel immersion tests to estimate in-vivo nickel release from implanted cardiovascular devices. PMID:27208438

  8. Heart Rate, Life Expectancy and the Cardiovascular System: Therapeutic Considerations.

    PubMed

    Boudoulas, Konstantinos Dean; Borer, Jeffrey S; Boudoulas, Harisios

    2015-01-01

    It has long been known that life span is inversely related to resting heart rate in most organisms. This association between heart rate and survival has been attributed to the metabolic rate, which is greater in smaller animals and is directly associated with heart rate. Studies have shown that heart rate is related to survival in apparently healthy individuals and in patients with different underlying cardiovascular diseases. A decrease in heart rate due to therapeutic interventions may result in an increase in survival. However, there are many factors regulating heart rate, and it is quite plausible that these may independently affect life expectancy. Nonetheless, a fast heart rate itself affects the cardiovascular system in multiple ways (it increases ventricular work, myocardial oxygen consumption, endothelial stress, aortic/arterial stiffness, decreases myocardial oxygen supply, other) which, in turn, may affect survival. In this brief review, the effects of heart rate on the heart, arterial system and survival will be discussed.

  9. Endothelial Interfaces - Master Gatekeepers of the Cardiovascular System

    NASA Astrophysics Data System (ADS)

    Junghans, Sylvia Ann; Pocivavsek, Luka; Zebda, Noureddine; Birukov, Konstantin; Waltman, Mary Jo; Majewski, Jaroslaw

    2014-03-01

    Endothelial cells, master gatekeepers of the cardiovascular system, line its inner boundary from the heart to distant capillaries constantly exposed to blood flow. Inter-endothelial signaling and the monolayer's adhesion to the underlying collagen rich basal lamina are key in physiology and disease. Using neutron scattering, we report the first-ever interfacial structure of endothelial monolayers under dynamic flow conditions mimicking the cardiovascular system. Endothelial adhesion strength (defined as the separation distance l between the basal cell membrane and solid boundary) is explained using developed interfacial potentials and intra-membrane segregation of specific adhesion proteins. Our method provides a powerful tool for the biophysical study of cellular layer adhesion strength in living tissues.

  10. [Helical (spiral or swirling) blood flow in cardiovascular system].

    PubMed

    Kirsanov, R I; Kulikov, V P

    2013-01-01

    In article covers theoretical preconditions for the hypothesis about helical (spiral or swirling) blood flow in cardiovascular system followed by its experimental corroboration. The role of the modern blood flow visualization methods--such as Color Doppler ultrasound and magnetic-resonance angiography--in registration and investigation of the regularities of the given phenomenon is described. The data describing the known parameters of helical blood flow--such as direction of the rotation and its quantitative parameters in large arteries--are given. The main hypotheses for flow screw mechanisms are considered from the point of view of cardiovascular system structural organization. Biological role of helical blood flow is discussed, in respect of which there are diametrically opposed points of view, which consider it as a physiological phenomenon on one side, and as a patogenetic factor of atherosclerosis development on the other.

  11. Patient-specific system for prognosis of surgical treatment outcomes of human cardiovascular system

    NASA Astrophysics Data System (ADS)

    Golyadkina, Anastasiya A.; Kalinin, Aleksey A.; Kirillova, Irina V.; Kossovich, Elena L.; Kossovich, Leonid Y.; Menishova, Liyana R.; Polienko, Asel V.

    2015-03-01

    Object of study: Improvement of life quality of patients with high stroke risk ia the main goal for development of system for patient-specific modeling of cardiovascular system. This work is dedicated at increase of safety outcomes for surgical treatment of brain blood supply alterations. The objects of study are common carotid artery, internal and external carotid arteries and bulb. Methods: We estimated mechanical properties of carotid arteries tissues and patching materials utilized at angioplasty. We studied angioarchitecture features of arteries. We developed and clinically adapted computer biomechanical models, which are characterized by geometrical, physical and mechanical similarity with carotid artery in norm and with pathology (atherosclerosis, pathological tortuosity, and their combination). Results: Collaboration of practicing cardiovascular surgeons and specialists in the area of Mathematics and Mechanics allowed to successfully conduct finite-element modeling of surgical treatment taking into account various features of operation techniques and patching materials for a specific patient. Numerical experiment allowed to reveal factors leading to brain blood supply decrease and atherosclerosis development. Modeling of carotid artery reconstruction surgery for a specific patient on the basis of the constructed biomechanical model demonstrated the possibility of its application in clinical practice at approximation of numerical experiment to the real conditions.

  12. Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS)

    PubMed Central

    Donner, Daniel G.; Elliott, Grace E.; Beck, Belinda R.; Bulmer, Andrew C.; Du Toit, Eugene F.

    2015-01-01

    Introduction Current models of obesity utilise normogonadic animals and neglect the strong relationships between obesity-associated metabolic syndrome (MetS) and male testosterone deficiency (TD). The joint presentation of these conditions has complex implications for the cardiovascular system that are not well understood. We have characterised and investigated three models in male rats: one of diet-induced obesity with the MetS; a second using orchiectomised rats mimicking TD; and a third combining MetS with TD which we propose is representative of males with testosterone deficiency and the metabolic syndrome (TDMetS). Methods Male Wistar rats (n = 24) were randomly assigned to two groups and provided ad libitum access to normal rat chow (CTRL) or a high fat/high sugar/low protein “obesogenic” diet (OGD) for 28 weeks (n = 12/group). These groups were further sub-divided into sham-operated or orchiectomised (ORX) animals to mimic hypogonadism, with and without diet-induced obesity (n = 6/group). Serum lipids, glucose, insulin and sex hormone concentrations were determined. Body composition, cardiovascular structure and function; and myocardial tolerance to ischemia-reperfusion were assessed. Results OGD-fed animals had 72% greater fat mass; 2.4-fold greater serum cholesterol; 2.3-fold greater serum triglycerides and 3-fold greater fasting glucose (indicative of diabetes mellitus) compared to CTRLs (all p<0.05). The ORX animals had reduced serum testosterone and left ventricle mass (p<0.05). In addition to the combined differences observed in each of the isolated models, the OGD, ORX and OGD+ORX models each had greater CK-MB levels following in vivo cardiac ischemia-reperfusion insult compared to CTRLs (p<0.05). Conclusion Our findings provide evidence to support that the MetS and TD independently impair myocardial tolerance to ischemia-reperfusion. The combined OGD+ORX phenotype described in this study is a novel animal model with associated cardiovascular risk

  13. How valuable is physical examination of the cardiovascular system?

    PubMed

    Elder, Andrew; Japp, Alan; Verghese, Abraham

    2016-01-01

    Physical examination of the cardiovascular system is central to contemporary teaching and practice in clinical medicine. Evidence about its value focuses on its diagnostic accuracy and varies widely in methodological quality and statistical power. This makes collation, analysis, and understanding of results difficult and limits their application to daily clinical practice. Specific factors affecting interpretation and clinical application include poor standardisation of observers' technique and training, the study of single signs rather than multiple signs or signs in combination with symptoms, and the tendency to compare physical examination directly with technological aids to diagnosis rather than explore diagnostic strategies that combine both. Other potential aspects of the value of physical examination, such as cost effectiveness or patients' perceptions, are poorly studied. This review summarises the evidence for the clinical value of physical examination of the cardiovascular system. The best was judged to relate to the detection and evaluation of valvular heart disease, the diagnosis and treatment of heart failure, the jugular venous pulse in the assessment of central venous pressure, and the detection of atrial fibrillation, peripheral arterial disease, impaired perfusion, and aortic and carotid disease. Although technological aids to diagnosis are likely to become even more widely available at the point of care, the evidence suggests that further research into the value of physical examination of the cardiovascular system is needed, particularly in low resource settings and as a potential means of limiting inappropriate overuse of technological aids to diagnosis.

  14. Redox modification of cell signaling in the cardiovascular system.

    PubMed

    Shao, Dan; Oka, Shin-ichi; Brady, Christopher D; Haendeler, Judith; Eaton, Philip; Sadoshima, Junichi

    2012-03-01

    Oxidative stress is presumed to be involved in the pathogenesis of many diseases, including cardiovascular disease. However, oxidants are also generated in healthy cells, and increasing evidence suggests that they can act as signaling molecules. The intracellular reduction-oxidation (redox) status is tightly regulated by oxidant and antioxidant systems. Imbalance between them causes oxidative or reductive stress which triggers cellular damage or aberrant signaling, leading to dysregulation. In this review, we will briefly summarize the aspects of ROS generation and neutralization mechanisms in the cardiovascular system. ROS can regulate cell signaling through oxidation and reduction of specific amino acids within proteins. Structural changes during post-translational modification allow modification of protein activity which can result in altered cellular function. We will focus on the molecular basis of redox protein modification and how this regulatory mechanism affects signal transduction in the cardiovascular system. Finally, we will discuss some techniques applied to monitoring redox status and identifying redox-sensitive proteins in the heart. This article is part of a Special Section entitled "Post-translational Modification."

  15. Salt, aldosterone, and insulin resistance: impact on the cardiovascular system.

    PubMed

    Lastra, Guido; Dhuper, Sonal; Johnson, Megan S; Sowers, James R

    2010-10-01

    Hypertension and type 2 diabetes mellitus (T2DM) are powerful risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), both of which are leading causes of morbidity and mortality worldwide. Research into the pathophysiology of CVD and CKD risk factors has identified salt sensitivity and insulin resistance as key elements underlying the relationship between hypertension and T2DM. Excess dietary salt and caloric intake, as commonly found in westernized diets, is linked not only to increased blood pressure, but also to defective insulin sensitivity and impaired glucose homeostasis. In this setting, activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS), as well as increased signaling through the mineralocorticoid receptor (MR), result in increased production of reactive oxygen species and oxidative stress, which in turn contribute to insulin resistance and impaired vascular function. In addition, insulin resistance is not limited to classic insulin-sensitive tissues such as skeletal muscle, but it also affects the cardiovascular system, where it participates in the development of CVD and CKD. Current clinical knowledge points towards an impact of salt restriction, RAAS blockade, and MR antagonism on cardiovascular and renal protection, but also on improved insulin sensitivity and glucose homeostasis.

  16. [The effect of neurotensin on the cardiovascular system].

    PubMed

    Osadchiĭ, O E; Pokrovskiĭ, V M

    1998-01-01

    Neurotensin is a peptide involved in regulation of cardiovascular system. Neurotensin immunoreactivity is found in myocardium, conduction system of the heart, intracardiac ganglion cells, coronary vessels. High content of this peptide is also determined in structures of sympathoadrenal system. This creates the possibility of hormonal neurotensin action on the heart following sympathetic activation. Neurotensin accelerates heart rate, increases myocardial contractility, affects central haemodynamics, regional blood flow and coronary circulation. Neurotensin modulates autonomic influences on the heart and plays role in mechanisms of cardiac arrhythmogenesis, especially in dynamics of vagally induced cardiac rhythm disorders. Cardiovascular effects of this peptide may be associated with direct influence on the heart and vessels, stimulating action on release of histamine and catecholamines and activation of capsaicin-sensitive afferent neurons which contain calcitonin-gene related peptide and substance P. Cardiovascular action of neurotensin is species dependent and it is followed by pronounced tachyphylaxis. Cellular mechanism of neurotensin action is associated with stimulation of phosphoinositide turnover, elevation of intracellular calcium and cyclic nucleotides level.

  17. How valuable is physical examination of the cardiovascular system?

    PubMed

    Elder, Andrew; Japp, Alan; Verghese, Abraham

    2016-01-01

    Physical examination of the cardiovascular system is central to contemporary teaching and practice in clinical medicine. Evidence about its value focuses on its diagnostic accuracy and varies widely in methodological quality and statistical power. This makes collation, analysis, and understanding of results difficult and limits their application to daily clinical practice. Specific factors affecting interpretation and clinical application include poor standardisation of observers' technique and training, the study of single signs rather than multiple signs or signs in combination with symptoms, and the tendency to compare physical examination directly with technological aids to diagnosis rather than explore diagnostic strategies that combine both. Other potential aspects of the value of physical examination, such as cost effectiveness or patients' perceptions, are poorly studied. This review summarises the evidence for the clinical value of physical examination of the cardiovascular system. The best was judged to relate to the detection and evaluation of valvular heart disease, the diagnosis and treatment of heart failure, the jugular venous pulse in the assessment of central venous pressure, and the detection of atrial fibrillation, peripheral arterial disease, impaired perfusion, and aortic and carotid disease. Although technological aids to diagnosis are likely to become even more widely available at the point of care, the evidence suggests that further research into the value of physical examination of the cardiovascular system is needed, particularly in low resource settings and as a potential means of limiting inappropriate overuse of technological aids to diagnosis. PMID:27598000

  18. Perspectives of induced pluripotent stem cells for cardiovascular system regeneration.

    PubMed

    Csöbönyeiová, Mária; Polák, Štefan; Danišovič, L'uboš

    2015-05-01

    Induced pluripotent stem cells (iPSCs) hold great promise for basic research and regenerative medicine. They offer the same advantages as embryonic stem cells (ESCs) and moreover new perspectives for personalized medicine. iPSCs can be generated from adult somatic tissues by over-expression of a few defined transcription factors, including Oct4, Sox2, Klf4, and c-myc. For regenerative medicine in particular, the technology provides great hope for patients with incurable diseases or potentially fatal disorders such as heart failure. The endogenous regenerative potentials of adult hearts are extremely limited and insufficient to compensate for myocardial loss occurring after myocardial infarction. Recent discoveries have demonstrated that iPSCs have the potential to significantly advance future cardiovascular regenerative therapies. Moreover, iPSCs can be generated from somatic cells of patients with genetic basis for their disease. This human iPSC derivates offer tremendous potential for new disease models. This paper reviews current applications of iPSCs in cardiovascular regenerative medicine and discusses progress in modeling cardiovascular diseases using iPSCs-derived cardiac cells.

  19. Perspectives of induced pluripotent stem cells for cardiovascular system regeneration

    PubMed Central

    Csöbönyeiová, Mária; Polák, Štefan

    2015-01-01

    Induced pluripotent stem cells (iPSCs) hold great promise for basic research and regenerative medicine. They offer the same advantages as embryonic stem cells (ESCs) and moreover new perspectives for personalized medicine. iPSCs can be generated from adult somatic tissues by over-expression of a few defined transcription factors, including Oct4, Sox2, Klf4, and c-myc. For regenerative medicine in particular, the technology provides great hope for patients with incurable diseases or potentially fatal disorders such as heart failure. The endogenous regenerative potentials of adult hearts are extremely limited and insufficient to compensate for myocardial loss occurring after myocardial infarction. Recent discoveries have demonstrated that iPSCs have the potential to significantly advance future cardiovascular regenerative therapies. Moreover, iPSCs can be generated from somatic cells of patients with genetic basis for their disease. This human iPSC derivates offer tremendous potential for new disease models. This paper reviews current applications of iPSCs in cardiovascular regenerative medicine and discusses progress in modeling cardiovascular diseases using iPSCs-derived cardiac cells. PMID:25595188

  20. The human cardiovascular system in the absence of gravity

    NASA Technical Reports Server (NTRS)

    Bungo, M. W.; Charles, J. B.

    1985-01-01

    The data collected from a Space Shuttle crew to investigate cardiovascular changes due to microgravity are presented. The experimental procedures which involved preflight, immediate postflight, and one week following postflight echocardiograms of 13 individuals are described. The immediate postflight results reveal a 20 percent decrease in stroke volume, a 16 percent decrease in left ventricular diastolic volume index (LVDVI), no change in systolic volume, blood pressure, or cardiac index, and a 24 percent increase in heart rate. One week later a 17 percent stroke volume increase, a 29 percent increase in cardiac index, and normal blood pressure, and LVDVI were observed. It is concluded that upon reexposure to gravity a readaptation process for the cardiovascular system occurs.

  1. IRAG and novel PKG targeting in the cardiovascular system.

    PubMed

    Schlossmann, Jens; Desch, Matthias

    2011-09-01

    Signaling by nitric oxide (NO) determines several cardiovascular functions including blood pressure regulation, cardiac and smooth muscle hypertrophy, and platelet function. NO stimulates the synthesis of cGMP by soluble guanylyl cyclases and thereby activates cGMP-dependent protein kinases (PKGs), mediating most of the cGMP functions. Hence, an elucidation of the PKG signaling cascade is essential for the understanding of the (patho)physiological aspects of NO. Several PKG signaling pathways were identified, meanwhile regulating the intracellular calcium concentration, mediating calcium desensitization or cytoskeletal rearrangement. During the last decade it emerged that the inositol trisphosphate receptor-associated cGMP-kinase substrate (IRAG), an endoplasmic reticulum-anchored 125-kDa membrane protein, is a main signal transducer of PKG activity in the cardiovascular system. IRAG interacts specifically in a trimeric complex with the PKG1β isoform and the inositol 1,4,5-trisphosphate receptor I and, upon phosphorylation, reduces the intracellular calcium release from the intracellular stores. IRAG motifs for phosphorylation and for targeting to PKG1β and 1,4,5-trisphosphate receptor I were identified by several approaches. The (patho)physiological functions for the regulation of smooth muscle contractility and the inhibition of platelet activation were perceived. In this review, the IRAG recognition, targeting, and function are summarized compared with PKG and several PKG substrates in the cardiovascular system.

  2. Rational macromodeling of 1D blood flow in the human cardiovascular system.

    PubMed

    Ferranti, Francesco; Tamburrelli, Vincenzopio; Antonini, Giulio

    2015-03-01

    In this paper, we present a novel rational macromodeling approach for the description of 1D blood flow in the human cardiovascular system, which is suitable for time-domain simulations. Using the analogy of the blood flow propagation problem with transmission lines and considering the hypothesis of linearized Navier-Stokes equations, a frequency-domain rational macromodel for each arterial segment has been built. The poles and the residues of each arterial segment macromodel have been calculated by means of the Vector Fitting technique. Finally, the rational macromodel of the whole cardiovascular system is obtained by properly combining the macromodels of the single arterial segments using an interconnect matrix. The rational form of the proposed cardiovascular model leads to a state-space or electrical circuit model suitable for time-domain analysis. The stability and passivity properties of the global cardiovascular model are discussed to guarantee stable time-domain simulations. The proposed macromodeling approach has been validated by pertinent numerical results. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Racial Differences in Ideal Cardiovascular Health Metrics Among Mississippi Adults, 2009 Mississippi Behavioral Risk Factor Surveillance System

    PubMed Central

    Gamble, Abigail; Mendy, Vincent

    2013-01-01

    Introduction Cardiovascular disease is a leading cause of death and health disparities in Mississippi. Identifying populations with poor cardiovascular health may help direct interventions toward those populations disproportionately affected, which may ultimately increase cardiovascular health and decrease prominent disparities. Our objective was to assess racial differences in the prevalence of cardiovascular health metrics among Mississippi adults. Methods We used data from the 2009 Mississippi Behavioral Risk Factor Surveillance System to determine age-standardized prevalence estimates and 95% confidence intervals of cardiovascular health metrics among 2,003 black and 5,125 white adults. Logistic regression models were used to evaluate the relationship between race and cardiovascular health metrics. The mean cardiovascular metrics score and percentage of the population with ideal and poor cardiovascular health were calculated by subgroup. Results Approximately 1.3% of blacks and 2.6% of whites exhibited ideal levels of all 7 cardiovascular health metrics. The prevalence of 4 of the 7 cardiovascular health metrics was significantly lower among the total population of blacks than among whites, including a normal body mass index (20.8% vs 32.3%, P < .001), no history of diabetes (85.1% vs 91.3%, P < .001), no history of hypertension (53.9% vs 67.9%, P < .001), and physical activity (52.8% vs 62.2%, P < .001). The logistic regression models revealed significant race-by-sex interactions; differences between blacks and whites for normal body mass index, no history of diabetes mellitus, and no current smoking were found among women but not among men. Conclusion Cardiovascular health is poor among Mississippi adults overall, and racial differences exist. PMID:24262026

  4. Chronic kidney disease: effects on the cardiovascular system.

    PubMed

    Schiffrin, Ernesto L; Lipman, Mark L; Mann, Johannes F E

    2007-07-01

    Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.

  5. Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights

    NASA Astrophysics Data System (ADS)

    White, Ronald J.; Leonard, Joel I.; Srinivasan, R. Srini; Charles, John B.

    The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions.

  6. Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights.

    PubMed

    White, R J; Leonard, J I; Srinivasan, R S; Charles, J B

    1991-01-01

    The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions. PMID:11537147

  7. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    PubMed Central

    Bayzigitov, Daniel R.; Medvedev, Sergey P.; Dementyeva, Elena V.; Bayramova, Sevda A.; Pokushalov, Evgeny A.; Karaskov, Alexander M.; Zakian, Suren M.

    2016-01-01

    Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes. PMID:27110425

  8. The Equine Neonatal Cardiovascular System in Health and Disease.

    PubMed

    Marr, Celia M

    2015-12-01

    The neonatal foal is in a transitional state from prenatal to postnatal circulation. Healthy newborn foals often have cardiac murmurs and dysrhythmias, which are usually transient and of little clinical significance. The neonatal foal is prone to infection and cardiac trauma. Echocardiography is the main tool used for valuation of the cardiovascular system. With prompt identification and appropriate action, dysrhythmias and other sequel to cardiac trauma can be corrected. With infection, the management and prognosis are driven by concurrent sepsis. Congenital disease represents an interesting diagnostic challenge for the neonatologist, but surgical correction is not appropriate for most equids.

  9. Sex and the cardiovascular system: the intriguing tale of how women and men regulate cardiovascular function differently.

    PubMed

    Huxley, Virginia H

    2007-03-01

    The ability to recognize and appreciate from a reproductive standpoint that males and females possess different attributes has been long standing. Only more recently have we begun to look more deeply into both the similarities and differences between men and women, as well as between boys and girls, with respect to the structure and function of other organ systems. This article focuses on the cardiovascular system, with examples of sex differences in the control of coronary function, blood pressure, and volume. Recognizing the differences between the sexes with respect to cardiovascular function facilitates understanding of the mechanisms whereby homeostasis can be achieved using different contributions or components of the living system. Furthermore, recognition of the differences as well as the similarities permits the design of appropriate diagnostic instruments, recognition of sex-specific pathophysiology, and implementation of appropriate treatment of cardiovascular disease in men and women.

  10. Sex and the cardiovascular system: the intriguing tale of how women and men regulate cardiovascular function differently.

    PubMed

    Huxley, Virginia H

    2007-03-01

    The ability to recognize and appreciate from a reproductive standpoint that males and females possess different attributes has been long standing. Only more recently have we begun to look more deeply into both the similarities and differences between men and women, as well as between boys and girls, with respect to the structure and function of other organ systems. This article focuses on the cardiovascular system, with examples of sex differences in the control of coronary function, blood pressure, and volume. Recognizing the differences between the sexes with respect to cardiovascular function facilitates understanding of the mechanisms whereby homeostasis can be achieved using different contributions or components of the living system. Furthermore, recognition of the differences as well as the similarities permits the design of appropriate diagnostic instruments, recognition of sex-specific pathophysiology, and implementation of appropriate treatment of cardiovascular disease in men and women. PMID:17327577

  11. Variation Analysis of Sphygmogram to Assess Cardiovascular System under Meditation.

    PubMed

    Liu, Chuan-Yi; Wei, Ching-Chuan; Lo, Pei-Chen

    2009-03-01

    In this article, we studied how meditation affects the characteristics of the cardiovascular system, mainly based on blood pressure waveforms (BPW). Four parameters derived from BPW include the rising slope (h(1)/t(1)), normalized height of T wave (h(3)/h(1)), normalized height of V(3) valley (h(4)/h(1)) and normalized height of D wave (h(5)/h(1)), where t(1) and h(i), i = 1, ... ,5 are quantitative features of the BPW waveform pattern. A larger value of h(1)/t(1) reflects better heart ejection ability and aorta compliance. A larger value of h(3)/h(1) may infer an arterial system with good elasticity. The decrease (increase) of h(4)/h(1) parameter indicates the decrease (increase) of peripheral resistance of vessels. A larger value of h(5)/h(1) indicates better artery elasticity and aortic valve function. In comparison with the control group, Zen-meditation practitioners have more after-meditation h(1)/t(1), h(3)/h(1) and h(5)/h(1) increase, with more h(4)/h(1) decrease, with statistical significance (P < 0.05). The observation allows us to infer that Zen meditation may effectively improve relevant characteristics of the cardiovascular system.

  12. Endocannabinoid system in cardiovascular disorders - new pharmacotherapeutic opportunities.

    PubMed

    Cunha, Pedro; Romão, Ana M; Mascarenhas-Melo, Filipa; Teixeira, Helena M; Reis, Flávio

    2011-07-01

    The long history of Cannabis sativa had its development stimulated and oriented for medicine after the discovery and chemical characterization of its main active ingredient, the 9-tetrahydrocannabinol (9-THC). Consequently, a binding site for 9-THC was identified in rat brains and the first cannabinoid receptor (CB1) was cloned, followed by the CB2 and by the discover of two endogenous agonists: anandamide and 2-arachidonoyl glycerol. Cannabinoid receptors, endocannabinoids and the enzymes that catalyze its synthesis and degradation constitute the endocannabinoid system (ECS), which plays an important role in the cardiovascular system. In vivo experiments with rats have demonstrated the action of anandamide and 2-AG on the development of atherosclerotic plaque, as well as an effect on heart rate, blood pressure, vasoactivity and energy metabolism (action in dyslipidemia and obesity). Recent studies with an antagonist of CB1 receptors showed that the modulation of ECS can play an important role in reducing cardiovascular risk in obese and dyslipidemic patients. Similarly, studies in rats have demonstrated the action of CB2 receptors in adhesion, migration, proliferation and function of immune cells involved in the atherosclerotic plaque formation process. The evidence so far gathered shows that the modulation of ECS (as agonism or antagonism of its receptors) is an enormous potential field for research and intervention in multiple areas of human pathophysiology. The development of selective drugs for the CB1 and CB2 receptors may open a door to new therapeutic regimens.This review article aims to address the key findings and evidences on the modulation of ECS, in order to prospect future forms of therapeutic intervention at the cardiovascular level. A recent, emerging, controversial and of undoubted scientific interest subject, which states as a potential therapeutic target to reach in the 21(st) century. PMID:21966155

  13. Consequences of Circadian and Sleep Disturbances for the Cardiovascular System.

    PubMed

    Alibhai, Faisal J; Tsimakouridze, Elena V; Reitz, Cristine J; Pyle, W Glen; Martino, Tami A

    2015-07-01

    Circadian rhythms play a crucial role in our cardiovascular system. Importantly, there has been a recent flurry of clinical and experimental studies revealing the profound adverse consequences of disturbing these rhythms on the cardiovascular system. For example, circadian disturbance worsens outcome after myocardial infarction with implications for patients in acute care settings. Moreover, disturbing rhythms exacerbates cardiac remodelling in heart disease models. Also, circadian dyssynchrony is a causal factor in the pathogenesis of heart disease. These discoveries have profound implications for the cardiovascular health of shift workers, individuals with circadian and sleep disorders, or anyone subjected to the 24/7 demands of society. Moreover, these studies give rise to 2 new frontiers for translational research: (1) circadian rhythms and the cardiac sarcomere, which sheds new light on our understanding of myofilament structure, signalling, and electrophysiology; and (2) knowledge translation, which includes biomarker discovery (chronobiomarkers), timing of therapies (chronotherapy), and other new promising approaches to improve the management and treatment of cardiovascular disease. Reconsidering circadian rhythms in the clinical setting benefits repair mechanisms, and offers new promise for patients.

  14. A systematic review of image segmentation methodology, used in the additive manufacture of patient-specific 3D printed models of the cardiovascular system

    PubMed Central

    Byrne, N; Velasco Forte, M; Tandon, A; Valverde, I

    2016-01-01

    Background Shortcomings in existing methods of image segmentation preclude the widespread adoption of patient-specific 3D printing as a routine decision-making tool in the care of those with congenital heart disease. We sought to determine the range of cardiovascular segmentation methods and how long each of these methods takes. Methods A systematic review of literature was undertaken. Medical imaging modality, segmentation methods, segmentation time, segmentation descriptive quality (SDQ) and segmentation software were recorded. Results Totally 136 studies met the inclusion criteria (1 clinical trial; 80 journal articles; 55 conference, technical and case reports). The most frequently used image segmentation methods were brightness thresholding, region growing and manual editing, as supported by the most popular piece of proprietary software: Mimics (Materialise NV, Leuven, Belgium, 1992–2015). The use of bespoke software developed by individual authors was not uncommon. SDQ indicated that reporting of image segmentation methods was generally poor with only one in three accounts providing sufficient detail for their procedure to be reproduced. Conclusions and implication of key findings Predominantly anecdotal and case reporting precluded rigorous assessment of risk of bias and strength of evidence. This review finds a reliance on manual and semi-automated segmentation methods which demand a high level of expertise and a significant time commitment on the part of the operator. In light of the findings, we have made recommendations regarding reporting of 3D printing studies. We anticipate that these findings will encourage the development of advanced image segmentation methods. PMID:27170842

  15. An allometric analysis of the giraffe cardiovascular system.

    PubMed

    Mitchell, G; Skinner, J D

    2009-12-01

    There has been co-evolution of a long neck and high blood pressure in giraffes. How the cardiovascular system (CVS) has adapted to produce a high blood pressure, and how it compares with other similar sized mammals largely is unknown. We have measured body mass and heart structure in 56 giraffes of both genders ranging in body mass from 18 kg to 1500 kg, and developed allometric equations that relate changes in heart dimensions to growth and to cardiovascular function. Predictions made from these equations match measurements made in giraffes. We have found that heart mass increases as body mass increases but it has a relative mass of 0.51+/-0.7% of body mass which is the same as that in other mammals. The left ventricular and interventricular walls are hypertrophied and their thicknesses are linearly related to neck length. Systemic blood pressure increases as body mass and neck length increase and is twice that of mammals of the same body mass. Cardiac output is the same as, but peripheral resistance double that predicted for similar sized mammals. We have concluded that increasing hydrostatic pressure of the column of blood during neck elongation results in cardiac hypertrophy and concurrent hypertrophy of arteriole walls raising peripheral resistance, with an increase in blood pressure following.

  16. Aldosterone: effects on the kidney and cardiovascular system.

    PubMed

    Briet, Marie; Schiffrin, Ernesto L

    2010-05-01

    Aldosterone, a steroid hormone with mineralocorticoid activity, is mainly recognized for its action on sodium reabsorption in the distal nephron of the kidney, which is mediated by the epithelial sodium channel (ENaC). Beyond this well-known action, however, aldosterone exerts other effects on the kidney, blood vessels and the heart, which can have pathophysiological consequences, particularly in the presence of a high salt intake. Aldosterone is implicated in renal inflammatory and fibrotic processes, as well as in podocyte injury and mesangial cell proliferation. In the cardiovascular system, aldosterone has specific hypertrophic and fibrotic effects and can alter endothelial function. Several lines of evidence support the existence of crosstalk between aldosterone and angiotensin II in vascular smooth muscle cells. The deleterious effects of aldosterone on the cardiovascular system require concomitant pathophysiological conditions such as a high salt diet, increased oxidative stress, or inflammation. Large interventional trials have confirmed the benefits of adding mineralocorticoid-receptor antagonists to standard therapy, in particular to angiotensin-converting-enzyme inhibitor and angiotensin II receptor blocker therapy, in patients with heart failure. Small interventional studies in patients with chronic kidney disease have shown promising results, with a significant reduction of proteinuria associated with aldosterone antagonism, but large interventional trials that test the efficacy and safety of mineralocorticoid-receptor antagonists in chronic kidney disease are needed.

  17. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future. PMID:26201059

  18. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future.

  19. [Behavior of the cardiovascular system in outer space].

    PubMed

    Iglesias Leal, R

    1987-01-01

    One of the important factors in outer space is the absence of gravity (OG). During longterm missions, this factor is responsible for the larger number of anatomical and physiological changes that astronauts experience. The cardiovascular system undergoes these changes with severe intensity, which is part of an adaptation process to the new environmental conditions. The modifications observed in both the anatomy of the cardiovascular system and its hemodynamics occur in two phases. The first phase begins when the astronauts enter into Earth orbit or in interplanetary trajectory and extends until the second or fourth day of the mission. It is characterized by an important shifting of fluids from the lower extremities to the cephalic regions which produces an increase of the venous return and the preload, the heart rate is increased, the blood volume in the thorax is also increased, the cardiac chambers become dilated, and by reflex action, the antidiuretic hormone diminishes, diuresis increases and leads to a virtual state of dehydration. Clinically, the first stage is manifested by headache, dizziness, space disorientation, nausea, anorexia, projectile vomiting, sweating and pallor. This constalation of data is known as "The Space Adaptation Syndrome". The second phase begins at the end of the first phase and finishes toward the fortieth or fiftieth day of the mission.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Guidance Receptors in the Nervous and Cardiovascular Systems.

    PubMed

    Rubina, K A; Tkachuk, V A

    2015-10-01

    Blood vessels and nervous fibers grow in parallel, for they express similar receptors for chemokine substances. Recently, much attention is being given to studying guidance receptors and their ligands besides the growth factors, cytokines, and chemokines necessary to form structures in the nervous and vascular systems. Such guidance molecules determine trajectory for growing axons and vessels. Guidance molecules include Ephrins and their receptors, Neuropilins and Plexins as receptors for Semaphorins, Robos as receptors for Slit-proteins, and UNC5B receptors binding Netrins. Apart from these receptors and their ligands, urokinase and its receptor (uPAR) and T-cadherin are also classified as guidance molecules. The urokinase system mediates local proteolysis at the leading edge of cells, thereby providing directed migration. T-cadherin is a repellent molecule that regulates the direction of growing axons and blood vessels. Guidance receptors also play an important role in the diseases of the nervous and cardiovascular systems.

  1. Four-Dimensional Processing And Display System For Cardiovascular Data

    NASA Astrophysics Data System (ADS)

    Wixson, Steven E.

    1983-07-01

    This is a design paper describing a 4 dimensional processing and display system for cardiovascular research. A 4 dimensional image in this paper refers to a time (or other) series of 3 dimensional images. The system consists of components to develop, test and run programs and to manipulate and store multidimensional digital images. A 4 dimensional display is used to study raw and processed data. The display uses binocular stereo to generate a 3 dimensional image and bulk memory to store multiple stereo pairs for the fourth dimension. Voice input and output will be used to communicate with the system. A binocular infrared eye tracker will be used as a multidimensional cursor to interact with the data. Software development areas are summarized. The current state of the project is presented at the end of the paper. An up to date summary of progress will be presented at the conference.

  2. Preservation Of Native Aortic Valve Flow And Full Hemodynamic Support With The TORVAD™ Using A Computational Model Of The Cardiovascular System

    PubMed Central

    Gohean, Jeffrey R.; George, Mitchell J.; Chang, Kay-Won; Larson, Erik R.; Pate, Thomas D.; Kurusz, Mark; Longoria, Raul G.; Smalling, Richard W.

    2014-01-01

    This paper describes the stroke volume selection and operational design for the TORVAD™, a synchronous, positive-displacement ventricular assist device (VAD). A lumped parameter model was used to simulate hemodynamics with the TORVAD™ compared to those under continuous flow VAD support. Results from the simulation demonstrated that a TORVAD™ with a 30 mL stroke volume ejecting with an early diastolic counterpulse provides comparable systemic support to the HeartMate II® (HMII) (cardiac output 5.7 L/min up from 3.1 L/min in simulated heart failure). By taking advantage of synchronous pulsatility, the TORVAD™ delivers full hemodynamic support with nearly half the VAD flow rate (2.7 L/min compared to 5.3 L/min for the HMII) by allowing the left ventricle to eject during systole, thus preserving native aortic valve flow (3.0 L/min compared to 0.4 L/min for the HMII, down from 3.1 L/min at baseline). The TORVAD™ also preserves pulse pressure (26.7 mmHg compared to 12.8 mmHg for the HMII, down from 29.1 mmHg at baseline). Preservation of aortic valve flow with synchronous pulsatile support could reduce the high incidence of aortic insufficiency and valve cusp fusion reported in patients supported with continuous flow VADs. PMID:25485562

  3. Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities.

    PubMed

    Ryan, Caitriona; Kirby, Brian

    2015-01-01

    There is evidence that patients with moderate to severe psoriasis have an increased risk of conditions such as cardiovascular disease, obesity, diabetes mellitus, and metabolic syndrome. The precise mechanisms underlying the observed increase in cardiovascular disease in psoriasis remain to be defined but inflammatory pathways mutual to both conditions are probably involved. Suppression of systemic inflammation in psoriasis could help reduce cardiovascular inflammation but robust evidence is still lacking evidence is lacking. This article summarizes the current literature on cardiovascular and metabolic comorbidities in psoriasis, identifies research gaps, and suggests management strategies to reduce cardiovascular risk in patients with moderate to severe psoriasis.

  4. Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

    PubMed Central

    Ng, Chun-Yi; Jaarin, Kamsiah

    2015-01-01

    Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920

  5. Role of the endothelin system in sexual dimorphism in cardiovascular and renal diseases.

    PubMed

    Gohar, Eman Y; Giachini, Fernanda R; Pollock, David M; Tostes, Rita C

    2016-08-15

    Epidemiological studies of blood pressure in men and women and in experimental animal models point to substantial sex differences in the occurrence of arterial hypertension as well as in the various manifestations of arterial hypertension, including myocardial infarction, stroke, retinopathy, chronic kidney failure, as well as hypertension-associated diseases (e.g. diabetes mellitus). Increasing evidence demonstrates that the endothelin (ET) system is a major player in the genesis of sex differences in cardiovascular and renal physiology and diseases. Sex differences in the ET system have been described in the vasculature, heart and kidney of humans and experimental animals. In the current review, we briefly describe the role of the ET system in the cardiovascular and renal systems. We also update information on sex differences at different levels of the ET system including synthesis, circulating and tissue levels, receptors, signaling pathways, ET actions, and responses to antagonists in different organs that contribute to blood pressure regulation. Knowledge of the mechanisms underlying sex differences in arterial hypertension can impact therapeutic strategies. Sex-targeted and/or sex-tailored approaches may improve treatment of cardiovascular and renal diseases.

  6. TRPV4 channels: physiological and pathological role in cardiovascular system.

    PubMed

    Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

    2015-11-01

    TRPV4 channels are non-selective cation channels permeable to Ca(2+), Na(+), and Mg(2+) ions. Recently, TRPV4 channels have received considerable attention as these channels are widely expressed in the cardiovascular system including endothelial cells, cardiac fibroblasts, vascular smooth muscles, and peri-vascular nerves. Therefore, these channels possibly play a pivotal role in the maintenance of cardiovascular homeostasis. TRPV4 channels critically regulate flow-induced arteriogenesis, TGF-β1-induced differentiation of cardiac fibroblasts into myofibroblasts, and heart failure-induced pulmonary edema. These channels also mediate hypoxia-induced increase in proliferation and migration of pulmonary artery smooth muscle cells and progression of pulmonary hypertension. These channels also maintain flow-induced vasodilation and preserve vascular function by directly activating Ca(2+)-dependent KCa channels. Furthermore, these may also induce vasodilation and maintain blood pressure indirectly by evoking the release of NO, CGRP, and substance P. The present review discusses the evidences and the potential mechanisms implicated in diverse responses including arteriogenesis, cardiac remodeling, congestive heart failure-induced pulmonary edema, pulmonary hypertension, flow-induced dilation, regulation of blood pressure, and hypoxic preconditioning.

  7. Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System.

    PubMed

    Forrester, Steven J; Kawai, Tatsuo; O'Brien, Shannon; Thomas, Walter; Harris, Raymond C; Eguchi, Satoru

    2016-01-01

    Epidermal growth factor receptor (EGFR) activation impacts the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases including hypertension, cardiac hypertrophy, renal fibrosis, and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is called transactivation and is well described, yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight recent advancements in defining the signaling cascades and downstream consequences of EGFR transactivation in the cardiovascular renal system. We also focus on studies that link EGFR transactivation to animal models of the disease, and we discuss potential therapeutic applications.

  8. Role of silver nanoparticles (AgNPs) on the cardiovascular system.

    PubMed

    Gonzalez, Carmen; Rosas-Hernandez, Hector; Ramirez-Lee, Manuel Alejandro; Salazar-García, Samuel; Ali, Syed F

    2016-03-01

    With the advent of nanotechnology, the use and applications of silver nanoparticles (AgNPs) have increased, both in consumer products as well as in medical devices. However, little is known about the effects of these nanoparticles on human health, more specific in the cardiovascular system, since this system represents an important route of action in terms of distribution, bioaccumulation and bioavailability of the different circulating substances in the bloodstream. A collection of studies have addressed the effects and applications of different kinds of AgNPs (shaped, sized, coated and functionalized) in several components of the cardiovascular system, such as endothelial cells, isolated vessels and organs as well as integrative animal models, trying to identify the underlying mechanisms involved in their actions, to understand their implication in the field of biomedicine. The purpose of the present review is to summarize the most relevant studies to date of AgNPs effects in the cardiovascular system and provide a broader picture of the potential toxic effects and exposure risks, which in turn will allow pointing out the directions of further research as well as new applications of these versatile nanomaterials.

  9. Role of silver nanoparticles (AgNPs) on the cardiovascular system.

    PubMed

    Gonzalez, Carmen; Rosas-Hernandez, Hector; Ramirez-Lee, Manuel Alejandro; Salazar-García, Samuel; Ali, Syed F

    2016-03-01

    With the advent of nanotechnology, the use and applications of silver nanoparticles (AgNPs) have increased, both in consumer products as well as in medical devices. However, little is known about the effects of these nanoparticles on human health, more specific in the cardiovascular system, since this system represents an important route of action in terms of distribution, bioaccumulation and bioavailability of the different circulating substances in the bloodstream. A collection of studies have addressed the effects and applications of different kinds of AgNPs (shaped, sized, coated and functionalized) in several components of the cardiovascular system, such as endothelial cells, isolated vessels and organs as well as integrative animal models, trying to identify the underlying mechanisms involved in their actions, to understand their implication in the field of biomedicine. The purpose of the present review is to summarize the most relevant studies to date of AgNPs effects in the cardiovascular system and provide a broader picture of the potential toxic effects and exposure risks, which in turn will allow pointing out the directions of further research as well as new applications of these versatile nanomaterials. PMID:25543135

  10. A Large-Scale, Energetic Model of Cardiovascular Homeostasis Predicts Dynamics of Arterial Pressure in Humans

    PubMed Central

    Roytvarf, Alexander; Shusterman, Vladimir

    2008-01-01

    The energetic balance of forces in the cardiovascular system is vital to the stability of blood flow to all physiological systems in mammals. Yet, a large-scale, theoretical model, summarizing the energetic balance of major forces in a single, mathematically closed system has not been described. Although a number of computer simulations have been successfully performed with the use of analog models, the analysis of energetic balance of forces in such models is obscured by a big number of interacting elements. Hence, the goal of our study was to develop a theoretical model that represents large-scale, energetic balance in the cardiovascular system, including the energies of arterial pressure wave, blood flow, and the smooth muscle tone of arterial walls. Because the emphasis of our study was on tracking beat-to-beat changes in the balance of forces, we used a simplified representation of the blood pressure wave as a trapezoidal pressure-pulse with a strong-discontinuity leading front. This allowed significant reduction in the number of required parameters. Our approach has been validated using theoretical analysis, and its accuracy has been confirmed experimentally. The model predicted the dynamics of arterial pressure in human subjects undergoing physiological tests and provided insights into the relationships between arterial pressure and pressure wave velocity. PMID:18269976

  11. Pathophysiological effects of RhoA and Rho-associated kinase on cardiovascular system.

    PubMed

    Cai, Anping; Li, Liwen; Zhou, Yingling

    2016-01-01

    In past decades, growing evidence from basic and clinical researches reveal that small guanosine triphosphate binding protein ras homolog gene family, member A (RhoA) and its main effector Rho-associated kinase (ROCK) play central and complex roles in cardiovascular systems, and increasing RhoA and ROCK activity is associated with a broad range of cardiovascular diseases such as congestive heart failure, atherosclerosis, and hypertension. Favorable outcomes have been observed with ROCK inhibitors treatment. In this review, we briefly summarize the pathophysiological roles of RhoA/ROCK signaling pathway on cardiovascular system, displaying the potential benefits in the cardiovascular system with controlling RhoA/ROCK signaling pathway.

  12. [Effect of hormone replacement therapy on the cardiovascular system].

    PubMed

    Payer, J

    2001-02-15

    Hormonal replacement therapy becomes frequently used in peri- and postmenopausal women. It causally affects the climacteric syndrome, positively stimulates psychics, improves quality of the skin, decreases dryness of mucous membranes and frequency of recurrent inflammations of eyes and vagina. The positive influence on the bone metabolism and therefore on the incidence of osteoporosis highly dominates among its long-term effects. Long lasting hormonal replacement reduces also the incidence of Alzheimer disease, colorectal carcinoma and it has particularly favourable effect on the cardiovascular system. Estrogens positive affect the lipid spectrum, however, more than 50% of their beneficial influence comes from their direct vasodilatory effect. Estrogene replacement becomes in many countries indicated for the primary prevention of the ischemic heart disease. The question of its application for the secondary prevention remains still open.

  13. Use of implantable telemetry systems for study of cardiovascular phenomena.

    NASA Technical Reports Server (NTRS)

    Sandler, H.; Fryer, T. B.; Westbrook, R. M.; Stone, H. L.

    1972-01-01

    Preliminary observations of cardiovascular function have been made in four chimpanzees using multichannel implantable units. Measurements of right- and left-sided pressures were periodically made in these animals over a four-month period, including continuous observations for selected 24-hour periods. Pressures recorded with animals in an awake, unanesthetized, unrestrained state were much lower than pressures reported for restrained animals in similar situations. Diurnal variations of pressure tended to occur, but were not as clear-cut as those reported to occur for humans. The ability to implant a transmitter chronically and receive useful multichannel information in the chimpanzee encourages the future use of such implant devices as part of the control system for an artificial heart or directly for use in man.

  14. [Impact of aortic stiffness on central hemodynamics and cardiovascular system].

    PubMed

    Bulas, J; Potočárová, M; Filková, M; Simková, A; Murín, J

    2013-06-01

    Arterial stiffness increases as a result of degenerative processes accelerated by aging and many risk factors, namely arterial hypertension. Basic clinical examination reveals increased pulse pressure as its hemodynamic manifestation. The most serious consequence of increased vascular stiffness, which cannot be revealed by clinical examination, is a change of central hemodynamics leading to increased load of left ventricle, left ventricular hypertrophy, diastolic dysfunction and to overall increase of cardiovascular risk. This review aimed to point at some patophysiological mechanisms taking part in the development of vascular stiffness, vascular remodeling and hemodynamic consequences of these changes. This work also gives an overview of noninvasive examination methods and their characteristics enabling to evaluate the local, regional and systemic arterial stiffness and central pulse wave analysis and their meaning for central hemodynamics and heart workload. PMID:23808736

  15. Impact of atrial fibrillation on the cardiovascular system through a lumped-parameter approach.

    PubMed

    Scarsoglio, Stefania; Guala, Andrea; Camporeale, Carlo; Ridolfi, Luca

    2014-11-01

    Atrial fibrillation (AF) is the most common arrhythmia affecting millions of people in the Western countries and, due to the widespread impact on the population and its medical relevance, is largely investigated in both clinical and bioengineering sciences. However, some important feedback mechanisms are still not clearly established. The present study aims at understanding the global response of the cardiovascular system during paroxysmal AF through a lumped-parameter approach, which is here performed paying particular attention to the stochastic modeling of the irregular heartbeats and the reduced contractility of the heart. AF can be here analyzed by means of a wide number of hemodynamic parameters and avoiding the presence of other pathologies, which usually accompany AF. Reduced cardiac output with correlated drop of ejection fraction and decreased amount of energy converted to work by the heart during blood pumping, as well as higher left atrial volumes and pressures are some of the most representative results aligned with the existing clinical literature and here emerging during acute AF. The present modeling, providing new insights on cardiovascular variables which are difficult to measure and rarely reported in literature, turns out to be an efficient and powerful tool for a deeper comprehension and prediction of the arrythmia impact on the whole cardiovascular system.

  16. Current Scientific Evidence for a Polarized Cardiovascular Endurance Training Model.

    PubMed

    Hydren, Jay R; Cohen, Bruce S

    2015-12-01

    Recent publications have provided new scientific evidence for a modern aerobic or cardiovascular endurance exercise prescription that optimizes the periodization cycle and maximizes potential endurance performance gains in highly trained individuals. The traditional threshold, high volume, and high-intensity training models have displayed limited improvement in actual race pace in (highly) trained individuals while frequently resulting in overreaching or overtraining (physical injury and psychological burnout). A review of evidence for replacing these models with the proven polarized training model seems warranted. This review provides a short history of the training models, summarizes 5 key studies, and provides example training programs for both the pre- and in-season periods. A polarized training program is characterized by an undulating nonlinear periodization model with nearly all the training time spent at a "light" (≤13) and "very hard" (≥17) pace with very limited time at "hard" (14-16) or race pace (6-20 Rating of Perceived Exertion [RPE] scale). To accomplish this, the polarization training model has specific high-intensity workouts separated by one or more long slow distance workouts, with the exercise intensity remaining below ventilatory threshold (VT) 1 and/or blood lactate of less than 2 mM (A.K.A. below race pace). Effect sizes for increasing aerobic endurance performance for the polarized training model are consistently superior to that of the threshold training model. Performing a polarized training program may be best accomplished by: going easy on long slow distance workouts, avoiding "race pace" and getting after it during interval workouts. PMID:26595137

  17. Animal Models to Study Links between Cardiovascular Disease and Renal Failure and Their Relevance to Human Pathology

    PubMed Central

    Hewitson, Tim D.; Holt, Stephen G.; Smith, Edward R.

    2015-01-01

    The close association between cardiovascular pathology and renal dysfunction is well documented and significant. Patients with conventional risk factors for cardiovascular disease like diabetes and hypertension also suffer renal dysfunction. This is unsurprising if the kidney is simply regarded as a “modified blood vessel” and thus, traditional risk factors will affect both systems. Consistent with this, it is relatively easy to comprehend how patients with either sudden or gradual cardiac and or vascular compromise have changes in both renal hemodynamic and regulatory systems. However, patients with pure or primary renal dysfunction also have metabolic changes (e.g., oxidant stress, inflammation, nitric oxide, or endocrine changes) that affect the cardiovascular system. Thus, cardiovascular and renal systems are intimately, bidirectionally and inextricably linked. Whilst we understand several of these links, some of the mechanisms for these connections remain incompletely explained. Animal models of cardiovascular and renal disease allow us to explore such mechanisms, and more importantly, potential therapeutic strategies. In this article, we review various experimental models used, and examine critically how representative they are of the human condition. PMID:26441970

  18. Modeling and Simulation Approaches for Cardiovascular Function and Their Role in Safety Assessment

    PubMed Central

    Collins, TA; Bergenholm, L; Abdulla, T; Yates, JWT; Evans, N; Chappell, MJ; Mettetal, JT

    2015-01-01

    Systems pharmacology modeling and pharmacokinetic-pharmacodynamic (PK/PD) analysis of drug-induced effects on cardiovascular (CV) function plays a crucial role in understanding the safety risk of new drugs. The aim of this review is to outline the current modeling and simulation (M&S) approaches to describe and translate drug-induced CV effects, with an emphasis on how this impacts drug safety assessment. Current limitations are highlighted and recommendations are made for future effort in this vital area of drug research. PMID:26225237

  19. Modeling and Simulation Approaches for Cardiovascular Function and Their Role in Safety Assessment.

    PubMed

    Collins, T A; Bergenholm, L; Abdulla, T; Yates, Jwt; Evans, N; Chappell, M J; Mettetal, J T

    2015-03-01

    Systems pharmacology modeling and pharmacokinetic-pharmacodynamic (PK/PD) analysis of drug-induced effects on cardiovascular (CV) function plays a crucial role in understanding the safety risk of new drugs. The aim of this review is to outline the current modeling and simulation (M&S) approaches to describe and translate drug-induced CV effects, with an emphasis on how this impacts drug safety assessment. Current limitations are highlighted and recommendations are made for future effort in this vital area of drug research.

  20. Neural Control of the Cardiovascular System in Space

    NASA Technical Reports Server (NTRS)

    Levine, Benjamin D.; Pawelczyk, James A.; Zuckerman, Julie; Zhang, Rong; Fu, Qi; Iwasaki, Kenichi; Ray, Chet; Blomqvist, C. Gunnar; Lane, Lynda D.; Giller, Cole A.

    2003-01-01

    During the acute transition from lying supine to standing upright, a large volume of blood suddenly moves from the chest into the legs. To prevent fainting, the blood pressure control system senses this change immediately, and rapidly adjusts flow (by increasing heart rate) and resistance to flow (by constricting the blood vessels) to restore blood pressure and maintain brain blood flow. If this system is inadequate, the brain has a backup plan. Blood vessels in the brain can adjust their diameter to keep blood flow constant. If blood pressure drops, the brain blood vessels dilate; if blood pressure increases, the brain blood vessels constrict. This process, which is called autoregulation, allows the brain to maintain a steady stream of oxygen, even when blood pressure changes. We examined what changes in the blood pressure control system or cerebral autoregulation contribute to the blood pressure control problems seen after spaceflight. We asked: (1) does the adaptation to spaceflight cause an adaptation in the blood pressure control system that impairs the ability of the system to constrict blood vessels on return to Earth?; (2) if such a defect exists, could we pinpoint the neural pathways involved?; and (3) does cerebral autoregulation become abnormal during spaceflight, impairing the body s ability to maintain constant brain blood flow when standing upright on Earth? We stressed the blood pressure control system using lower body negative pressure, upright tilt, handgrip exercise, and cold stimulation of the hand. Standard cardiovascular parameters were measured along with sympathetic nerve activity (the nerve activity causing blood vessels to constrict) and brain blood flow. We confirmed that the primary cardiovascular effect of spaceflight was a postflight reduction in upright stroke volume (the amount of blood the heart pumps per beat). Heart rate increased appropriately for the reduction in stroke volume, thereby showing that changes in heart rate

  1. Comprehensive quality assurance phantom for cardiovascular imaging systems

    NASA Astrophysics Data System (ADS)

    Lin, Pei-Jan P.

    1998-07-01

    With the advent of high heat loading capacity x-ray tubes, high frequency inverter type generators, and the use of spectral shaping filters, the automatic brightness/exposure control (ABC) circuit logic employed in the new generation of angiographic imaging equipment has been significantly reprogrammed. These new angiographic imaging systems are designed to take advantage of the power train capabilities to yield higher contrast images while maintaining, or lower, the patient exposure. Since the emphasis of the imaging system design has been significantly altered, the system performance parameters one is interested and the phantoms employed for the quality assurance must also change in order to properly evaluate the imaging capability of the cardiovascular imaging systems. A quality assurance (QA) phantom has been under development in this institution and was submitted to various interested organizations such as American Association of Physicists in Medicine (AAPM), Society for Cardiac Angiography & Interventions (SCA&I), and National Electrical Manufacturers Association (NEMA) for their review and input. At the same time, in an effort to establish a unified standard phantom design for the cardiac catheterization laboratories (CCL), SCA&I and NEMA have formed a joint work group in early 1997 to develop a suitable phantom. The initial QA phantom design has since been accepted to serve as the base phantom by the SCA&I- NEMA Joint Work Group (JWG) from which a comprehensive QA Phantom is being developed.

  2. National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module VI. Cardiovascular System.

    ERIC Educational Resources Information Center

    National Highway Traffic Safety Administration (DOT), Washington, DC.

    This instructor's lesson plan guide on the cardiovascular system is one of fifteen modules designed for use in the training of emergency medical technicians (paramedics). Seven units of study are presented: (1) the anatomy and physiology of the cardiovascular system; (2) patient assessment for the cardiac patient; (3) pathophysiology; (4) reading…

  3. Cell Systems to Investigate the Impact of Polyphenols on Cardiovascular Health

    PubMed Central

    Grootaert, Charlotte; Kamiloglu, Senem; Capanoglu, Esra; Van Camp, John

    2015-01-01

    Polyphenols are a diverse group of micronutrients from plant origin that may serve as antioxidants and that contribute to human health in general. More specifically, many research groups have investigated their protective effect against cardiovascular diseases in several animal studies and human trials. Yet, because of the excessive processing of the polyphenol structure by human cells and the residing intestinal microbial community, which results in a large variability between the test subjects, the exact mechanisms of their protective effects are still under investigation. To this end, simplified cell culture systems have been used to decrease the inter-individual variability in mechanistic studies. In this review, we will discuss the different cell culture models that have been used so far for polyphenol research in the context of cardiovascular diseases. We will also review the current trends in cell culture research, including co-culture methodologies. Finally, we will discuss the potential of these advanced models to screen for cardiovascular effects of the large pool of bioactive polyphenols present in foods and their metabolites. PMID:26569293

  4. [Simulation Analysis of the Pulse Signal on the Electricity Network of Cardiovascular System].

    PubMed

    Liu, Ying; Yin, Yanfei; Zhang, Defa; Wang, Menghong; Bi, Yongqiang

    2015-12-01

    Pulse waves contain abundant physiological and pathological information of human body. Research of the relationship between pulse wave and human cardiovascular physiological parameters can not only help clinical diagnosis and treatment of cardiovascular diseases, but also contribute to develop many new medical instruments. Based on the traditional double elastic cavity model, the human cardiovascular system was established by using the electric network model in this paper. The change of wall pressure and blood flow in artery was simulated. And the influence of the peripheral resistance and vessel compliance to the distribution of blood flow in artery was analyzed. The simulation results were compared with the clinical monitoring results to predict the physiological and pathological state of human body. The result showed that the simulation waveform of arterial wall pressure and blood flow was stabile after the second cardiac cycle. With the increasing of peripheral resistance, the systolic blood pressure of artery increased, the diastolic blood pressure had no significant change, and the pulse pressure of artery increased gradually. With the decreasing of vessel compliance, the vasoactivity became worse and the pulse pressure increased correspondingly. The simulation results were consistent with the clinical monitoring results. The increasing of peripheral resistance and decreasing of vascular compliance indicated that the incidence of hypertension and atherosclerosis was increased.

  5. Cell Systems to Investigate the Impact of Polyphenols on Cardiovascular Health.

    PubMed

    Grootaert, Charlotte; Kamiloglu, Senem; Capanoglu, Esra; Van Camp, John

    2015-11-01

    Polyphenols are a diverse group of micronutrients from plant origin that may serve as antioxidants and that contribute to human health in general. More specifically, many research groups have investigated their protective effect against cardiovascular diseases in several animal studies and human trials. Yet, because of the excessive processing of the polyphenol structure by human cells and the residing intestinal microbial community, which results in a large variability between the test subjects, the exact mechanisms of their protective effects are still under investigation. To this end, simplified cell culture systems have been used to decrease the inter-individual variability in mechanistic studies. In this review, we will discuss the different cell culture models that have been used so far for polyphenol research in the context of cardiovascular diseases. We will also review the current trends in cell culture research, including co-culture methodologies. Finally, we will discuss the potential of these advanced models to screen for cardiovascular effects of the large pool of bioactive polyphenols present in foods and their metabolites.

  6. Role for primary cilia as flow detectors in the cardiovascular system.

    PubMed

    Van der Heiden, Kim; Egorova, Anastasia D; Poelmann, Robert E; Wentzel, Jolanda J; Hierck, Beerend P

    2011-01-01

    The cardiovascular system is exposed to biochemical and biomechanical signals. Various sensors for these signals have been described and they contribute to cardiovascular development, maintenance of vessel integrity during adult life, and to pathogenesis. In the past 10years, primary cilia, membrane-covered, rod-like cellular protrusions, were discovered on multiple cell types of the cardiovascular system. Primary cilia are sensory organelles involved in several key (developmental) signaling pathways and in chemo- and mechanosensing on a myriad of cell types. In the embryonic and adult cardiovascular system, they have been demonstrated to function as shear stress sensors on endothelial cells and could act as strain sensors on smooth muscle cells and cardiomyocytes and as chemosensors on fibroblasts. This review will cover their occurrence and elaborate on established and possible functions of primary cilia in the cardiovascular system.

  7. Chemokines and Heart Disease: A Network Connecting Cardiovascular Biology to Immune and Autonomic Nervous Systems

    PubMed Central

    Dusi, Veronica; Ghidoni, Alice; Ravera, Alice; De Ferrari, Gaetano M.; Calvillo, Laura

    2016-01-01

    Among the chemokines discovered to date, nineteen are presently considered to be relevant in heart disease and are involved in all stages of cardiovascular response to injury. Chemokines are interesting as biomarkers to predict risk of cardiovascular events in apparently healthy people and as possible therapeutic targets. Moreover, they could have a role as mediators of crosstalk between immune and cardiovascular system, since they seem to act as a “working-network” in deep linkage with the autonomic nervous system. In this paper we will describe the single chemokines more involved in heart diseases; then we will present a comprehensive perspective of them as a complex network connecting the cardiovascular system to both the immune and the autonomic nervous systems. Finally, some recent evidences indicating chemokines as a possible new tool to predict cardiovascular risk will be described. PMID:27242392

  8. Theory and Developments in an Unobtrusive Cardiovascular System Representation: Ballistocardiography

    PubMed Central

    Pinheiro, Eduardo; Postolache, Octavian; Girão, Pedro

    2010-01-01

    Due to recent technological improvements, namely in the field of piezoelectric sensors, ballistocardiography – an almost forgotten physiological measurement – is now being object of a renewed scientific interest. Transcending the initial purposes of its development, ballistocardiography has revealed itself to be a useful informative signal about the cardiovascular system status, since it is a non-intrusive technique which is able to assess the body’s vibrations due to its cardiac, and respiratory physiological signatures. Apart from representing the outcome of the electrical stimulus to the myocardium – which may be obtained by electrocardiography – the ballistocardiograph has additional advantages, as it can be embedded in objects of common use, such as a bed or a chair. Moreover, it enables measurements without the presence of medical staff, factor which avoids the stress caused by medical examinations and reduces the patient’s involuntary psychophysiological responses. Given these attributes, and the crescent number of systems developed in recent years, it is therefore pertinent to revise all the information available on the ballistocardiogram’s physiological interpretation, its typical waveform information, its features and distortions, as well as the state of the art in device implementations. PMID:21673836

  9. Discovery of the cardiovascular system: from Galen to William Harvey.

    PubMed

    Aird, W C

    2011-07-01

    The goal of this review is to examine the events that led to discovery of blood circulation. The Ancient Greeks, including Hippocrates and Galen viewed the cardiovascular system as comprising two distinct networks of arteries and veins. Galen claimed that the liver produced blood that was then distributed to the body in a centrifugal manner, whereas air or pneuma was absorbed from the lung into the pulmonary veins and carried by arteries to the various tissues of the body. Arteries also contained blood, which passed from the venous side via invisible pores in the interventricular septum and peripheral anastomoses. This was an open-ended system in which blood and air simply dissipated at the ends of veins and arteries according to the needs of the local tissue. Blood was not seen to circulate but rather to slowly ebb and flow. This view would hold sway for 15 centuries until 1628 when William Harvey published his momentous 72-page book, On the Motion of the Heart and Blood in Animals. Harvey employed experiment and deductive logic to show that arteries and veins are functionally, if not structurally, connected in the lung and the peripheral tissues, and that blood circulates. The mechanical force of the heart replaced Galen's elusive attractive powers. Ultimately, Galenism would collapse under the weight of Harvey's evidence, and a new paradigm of blood circulation would prevail.

  10. A simple ballistocardiographic system for a medical cardiovascular physiology course.

    PubMed

    Eblen-Zajjur, Antonio

    2003-12-01

    Ballistocardiography is an old, noninvasive technique used to record the movements of the body synchronous with the heartbeat due to left ventricular pump activity. Despite the fact that this technique to measure cardiac output has been superseded by more advanced and precise techniques, it is useful for teaching cardiac cycle physiology in an undergraduate practical course because of its noninvasive application in humans, clear physiological and physiopathological analysis, and practical approach to considering cardiac output issues. In the present report, a simple, low cost, easy-to-build ballistocardiography system is implemented together with a theoretical and practical session that includes Newton's laws, cardiac output, cardiac pump activity, anatomy and physiology of the vessel circulation, vectorial composition, and signal transduction, which makes cardiovascular physiology easy to understand and focuses on the study of cardiac output otherwise seen only with the help of computer simulation or echocardiography. The proposed system is able to record body displacement or force as ballistocardiography traces and its changes caused by different physiological factors. The ballistocardiography session was included in our medical physiology course six years ago with very high acceptance and approval rates from the students.

  11. Effects of Tetrodotoxin on the Mammalian Cardiovascular System

    PubMed Central

    Zimmer, Thomas

    2010-01-01

    The human genome encodes nine functional voltage-gated Na+ channels. Three of them, namely Nav1.5, Nav1.8, and Nav1.9, are resistant to nanomolar concentrations of tetrodotoxin (TTX; IC50 ≥ 1 μM). The other isoforms, which are predominantly expressed in the skeletal muscle and nervous system, are highly sensitive to TTX (IC50 ~ 10 nM). During the last two decades, it has become evident that in addition to the major cardiac isoform Nav1.5, several of those TTX sensitive isoforms are expressed in the mammalian heart. Whereas immunohistochemical and electrophysiological methods demonstrated functional expression in various heart regions, the physiological importance of those isoforms for cardiac excitation in higher mammals is still debated. This review summarizes our knowledge on the systemic cardiovascular effects of TTX in animals and humans, with a special focus on cardiac excitation and performance at lower concentrations of this marine drug. Altogether, these data strongly suggest that TTX sensitive Na+ channels, detected more recently in various heart tissues, are not involved in excitation phenomena in the healthy adult heart of higher mammals. PMID:20411124

  12. The role of the apelinergic and vasopressinergic systems in the regulation of the cardiovascular system and the pathogenesis of cardiovascular disease.

    PubMed

    Czarzasta, Katarzyna; Cudnoch-Jedrzejewska, Agnieszka

    2014-01-01

    Research studies indicate a role of the apelinergic and vasopressinergic systems both in the regulation of the cardiovascular system and the pathogenesis of CVD, including in such settings as obesity and stress. Based on these data, it may be suggested that interactions between these systems underlie numerous physiological and pathophysiological processes, some of them related to the cardiovascular system. Better understanding of the role of these systems and their interactions, both physiological and related to the pathogenesis of CVD, will allow further advances in prevention and drug therapy.

  13. Community-Based ECG Monitoring System for Patients with Cardiovascular Diseases.

    PubMed

    Lin, Bor-Shyh; Wong, Alice M; Tseng, Kevin C

    2016-04-01

    This study aims to develop a community-based electrocardiogram (ECG) monitoring system for cardiac outpatients to wirelessly detect heart rate, provide personalized healthcare, and enhance interactive social contact because of the prevalence of deaths from cardiovascular disease and the growing problem of aging in the world. The system not only strengthens the performance of the ECG monitoring system but also emphasizes the ergonomic design of wearable devices and user interfaces. In addition, it enables medical professionals to diagnose cardiac symptoms remotely and electronically manage medical reports and suggestions. The experimental result shows high performance of the dry electrode, even in dynamic conditions. The comparison result with different ECG healthcare systems shows the essential factors that the system should possess and the capability of the proposed system. Finally, a user survey was conducted based on the unified theory of acceptance and users of technology (UTAUT) model.

  14. G-protein Coupled Receptor Signaling in Pluripotent Stem Cell-derived Cardiovascular Cells: Implications for Disease Modeling

    PubMed Central

    Dolatshad, Nazanin F.; Hellen, Nicola; Jabbour, Richard J.; Harding, Sian E.; Földes, Gabor

    2015-01-01

    Human pluripotent stem cell derivatives show promise as an in vitro platform to study a range of human cardiovascular diseases. A better understanding of the biology of stem cells and their cardiovascular derivatives will help to understand the strengths and limitations of this new model system. G-protein coupled receptors (GPCRs) are key regulators of stem cell maintenance and differentiation and have an important role in cardiovascular cell signaling. In this review, we will therefore describe the state of knowledge concerning the regulatory role of GPCRs in both the generation and function of pluripotent stem cell derived-cardiomyocytes, -endothelial, and -vascular smooth muscle cells. We will consider how far the in vitro disease models recapitulate authentic GPCR signaling and provide a useful basis for discovery of disease mechanisms or design of therapeutic strategies. PMID:26697426

  15. Vascular system: role of nitric oxide in cardiovascular diseases.

    PubMed

    Bian, Ka; Doursout, Marie-Françoise; Murad, Ferid

    2008-04-01

    In contrast with the short research history of the enzymatic synthesis of nitric oxide (NO), the introduction of nitrate-containing compounds for medicinal purposes marked its 150th anniversary in 1997. Glyceryl trinitrate (nitroglycerin) is the first compound of this category. On October 12, 1998, the Nobel Assembly awarded the Nobel Prize in Medicine or Physiology to scientists Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning NO as a signaling molecule in the cardiovascular system. NO-mediated signaling is a recognized component in various physiologic processes (eg, smooth muscle relaxation, inhibition of platelet and leukocyte aggregation, attenuation of vascular smooth muscle cell proliferation, neurotransmission, and immune defense), to name only a few. NO has also been implicated in the pathology of many inflammatory diseases, including arthritis, myocarditis, colitis, and nephritis and a large number of pathologic conditions such as amyotrophic lateral sclerosis, cancer, diabetes, and neurodegenerative diseases. Some of these processes (eg, smooth muscle relaxation, platelet aggregation, and neurotransmission) require only a brief production of NO at low nanomolar concentrations and are dependent on the recruitment of cyclic guanosine monophosphate (cGMP)-dependent signaling. Other processes are associated with direct interaction of NO or reactive nitrogen species derived from it with target proteins and requires a more sustained production of NO at higher concentrations but do not involve the cGMP pathway.

  16. Peroxisome proliferator-activated receptors in the cardiovascular system

    PubMed Central

    Bishop-Bailey, David

    2000-01-01

    Peroxisome proliferator-activated receptor (PPAR)s are a family of three nuclear hormone receptors, PPARα, -δ, and -γ, which are members of the steriod receptor superfamily. The first member of the family (PPARα) was originally discovered as the mediator by which a number of xenobiotic drugs cause peroxisome proliferation in the liver. Defined functions for all these receptors, until recently, mainly concerned their ability to regulate energy balance, with PPARα being involved in β-oxidation pathways, and PPARγ in the differentiation of adipocytes. Little is known about the functions of PPARδ, though it is the most ubiquitously expressed. Since their discovery, PPARs have been shown to be expressed in monocytes/macrophages, the heart, vascular smooth muscle cells, endothelial cells, and in atherosclerotic lesions. Furthermore, PPARs can be activated by a vast number of compounds including synthetic drugs, of the clofibrate, and anti-diabetic thiazoldinedione classes, polyunsaturated fatty acids, and a number of eicosanoids, including prostaglandins, lipoxygenase products, and oxidized low density lipoprotein. This review will aim to introduce the field of PPAR nuclear hormone receptors, and discuss the discovery and actions of PPARs in the cardiovascular system, as well as the source of potential ligands. PMID:10696077

  17. Nitric oxide transport and storage in the cardiovascular system.

    PubMed

    Muller, Bernard; Kleschyov, Andrei L; Alencar, Jacicarlos L; Vanin, Anatoly; Stoclet, Jean-Claude

    2002-05-01

    Despite short halflife in biological fluids, nitric oxide (NO) can produce remote or long lasting effect in the cardiovascular system. Long distance transport or local storage of NO might explain these effects. In blood, recent findings suggest that in addition to being a major consumption pathway, interaction of NO with hemoglobin may permit O(2)-governed transport of NO (as S-nitrosohemoglobin) to tissues in which NO may be released together with O(2), via transnitrosation of a transport protein. In blood vessels, two different putative NO stores have been characterized. The first is the photosensitive store, formed from endothelium-derived NO. The mechanism of NO release from this store in the body (in absence of light) and its physiological relevance are unknown. The second store is generated in conditions of high tissue NO levels, as a consequence of the inducible NO synthase activity or in various stress conditions. This NO store involves formation of protein-bound dinitrosyl iron complexes or S-nitrosated proteins, or both. Low molecular weight thiols can displace NO from these stores and probably transfer it to target membrane protein(s) such as K(+) channels, via transnitrosation reactions. These stores may be involved in defence mechanisms against inflammation or stress. Thus, NO transport and storage mechanisms may be implicated in a variety of NO effects. The mechanisms of their formation and of NO release and their physiologic and pathophysiologic relevance deserve further investigations.

  18. Gravity, the hydrostatic indifference concept and the cardiovascular system.

    PubMed

    Hinghofer-Szalkay, Helmut

    2011-02-01

    Gravity, like any acceleration, causes a hydrostatic pressure gradient in fluid-filled bodily compartments. At a force of 1G, this pressure gradient amounts to 10 kPa/m. Postural changes alter the distribution of hydrostatic pressure patterns according to the body's alignment to the acceleration field. At a certain location--referred to as hydrostatically indifferent--within any given fluid compartment, pressure remains constant during a given change of position relative to the acceleration force acting upon the body. At this specific location, there is probably little change in vessel volume, wall tension, and the balance of Starling forces after a positional manoeuvre. In terms of cardiac function, this is important because arterial and venous hydrostatic indifference locations determine postural cardiac preload and afterload changes. Baroreceptors pick up pressure signals that depend on their respective distance to hydrostatic indifference locations with any change of body position. Vascular shape, filling volume, and compliance, as well as temperature, nervous and endocrine factors, drugs, and time all influence hydrostatic indifference locations. This paper reviews the physiology of pressure gradients in the cardiovascular system that are operational in a gravitational/acceleration field, offers a broadened hydrostatic indifference concept, and discusses implications that are relevant in physiological and clinical terms.

  19. A method to construct a points system to predict cardiovascular disease considering repeated measures of risk factors

    PubMed Central

    Carbayo-Herencia, Julio Antonio; Vigo, Maria Isabel; Gil-Guillén, Vicente Francisco

    2016-01-01

    Current predictive models for cardiovascular disease based on points systems use the baseline situation of the risk factors as independent variables. These models do not take into account the variability of the risk factors over time. Predictive models for other types of disease also exist that do consider the temporal variability of a single biological marker in addition to the baseline variables. However, due to their complexity these other models are not used in daily clinical practice. Bearing in mind the clinical relevance of these issues and that cardiovascular diseases are the leading cause of death worldwide we show the properties and viability of a new methodological alternative for constructing cardiovascular risk scores to make predictions of cardiovascular disease with repeated measures of the risk factors and retaining the simplicity of the points systems so often used in clinical practice (construction, statistical validation by simulation and explanation of potential utilization). We have also applied the system clinically upon a set of simulated data solely to help readers understand the procedure constructed. PMID:26893963

  20. Metal ions affecting the pulmonary and cardiovascular systems.

    PubMed

    Corradi, Massimo; Mutti, Antonio

    2011-01-01

    Some metals, such as copper and manganese, are essential to life and play irreplaceable roles in, e.g., the functioning of important enzyme systems. Other metals are xenobiotics, i.e., they have no useful role in human physiology and, even worse, as in the case of lead, may be toxic even at trace levels of exposure. Even those metals that are essential, however, have the potential to turn harmful at very high levels of exposure, a reflection of a very basic tenet of toxicology--"the dose makes the poison." Toxic metal exposure may lead to serious risks to human health. As a result of the extensive use of toxic metals and their compounds in industry and consumer products, these agents have been widely disseminated in the environment. Because metals are not biodegradable, they can persist in the environment and produce a variety of adverse effects. Exposure to metals can lead to damage in a variety of organ systems and, in some cases, metals also have the potential to be carcinogenic. Even though the importance of metals as environmental health hazards is now widely appreciated, the specific mechanisms by which metals produce their adverse effects have yet to be fully elucidated. The unifying factor in determining toxicity and carcinogenicity for most metals is the generation of reactive oxygen and nitrogen species. Metal-mediated formation of free radicals causes various modifications to nucleic acids, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Whilst copper, chromium, and cobalt undergo redox-cycling reactions, for metals such as cadmium and nickel the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. This chapter attempts to show that the toxic effects of different metallic compounds may be manifested in the pulmonary and cardiovascular systems. The knowledge of health effects due to metal exposure is necessary for practising physicians, and should be assessed by inquiring

  1. Prediction of hemodynamic changes towards PEEP titrations at different volemic levels using a minimal cardiovascular model.

    PubMed

    Starfinger, C; Chase, J G; Hann, C E; Shaw, G M; Lambert, P; Smith, B W; Sloth, E; Larsson, A; Andreassen, S; Rees, S

    2008-08-01

    A cardiovascular system model and parameter identification method have previously been validated for porcine experiments of induced pulmonary embolism and positive end-expiratory pressure (PEEP) titrations, accurately tracking all the main hemodynamic trends. In this research, the model and parameter identification process are further validated by predicting the effect of intervention. An overall population-specific rule linking specific model parameters to increases in PEEP is formulated to predict the hemodynamic effects on arterial pressure, pulmonary artery pressure and stroke volume. Hemodynamic changes are predicted for an increase from 0 to 10 cm H(2)O with median absolute percentage errors less than 7% (systolic pressures) and 13% (stroke volume). For an increase from 10 to 20 cm H(2)O median absolute percentage errors are less than 11% (systolic pressures) and 17% (stroke volume). These results validate the general applicability of such a rule, which is not pig-specific, but holds over for all analyzed pigs. This rule enables physiological simulation and prediction of patient response. Overall, the prediction accuracy achieved represents a further clinical validation of these models, methods and overall approach to cardiovascular diagnosis and therapy guidance.

  2. Impact of gestational risk factors on maternal cardiovascular system

    PubMed Central

    Perales, María; Santos-Lozano, Alejandro; Luaces, María; Pareja-Galeano, Helios; Garatachea, Nuria; Barakat, Rubén; Lucia, Alejandro

    2016-01-01

    Background Scarce evidence is available on the potential cardiovascular abnormalities associated with some common gestational complications. We aimed to analyze the potential maternal cardiac alterations related to gestational complications, including body mass index (BMI) >25 kg/m2, gaining excessive weight, or developing antenatal depression. Methods The design of this study was a secondary analysis of a randomized controlled trial. Echocardiography was performed to assess cardiovascular indicators of maternal hemodynamic, cardiac remodeling and left ventricular (LV) function in 59 sedentary pregnant women at 20 and 34 weeks of gestation. Results Starting pregnancy with a BMI >25 kg/m2, gaining excessive weight, and developing antenatal depression had no cardiovascular impact on maternal health (P value >0.002). Depressed women were more likely to exceed weight gain recommendations than non-depressed women (P value <0.002). Conclusions The evaluated gestational complications seem not to induce cardiovascular alterations in hemodynamic, remodeling and LV function indicators. However, developing antenatal depression increases the risk of an excessive weight gain. This finding is potentially important because excessive weight gain during pregnancy associates with a higher risk of cardiovascular diseases (CVD) later in life. PMID:27500154

  3. Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome

    PubMed Central

    Yanes, Licy L.; Romero, Damian G.; Moulana, Mohaddetheh; Lima, Roberta; Davis, Deborah D.; Zhang, Huimin; Lockhart, Rachel; Reckelhoff, Jane F.

    2011-01-01

    Background Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease at the time of PCOS and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS has not been elucidated. Objectives To characterize the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Methods Female Sprague Dawley rats, aged 4–6 weeks, were implanted with DHT or placebo pellets lasting 90 days. Following 10–12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, oral glucose tolerance test), inflammation (plasma TNF-α), oxidative stress (mRNA expression of NADPH oxidase subunits, p22phox, p47phox, gp91phox, and NOX4, nitrate/nitrite excretion), and mRNA expression of components of the renin-angiotensin system (RAS) (angiotensinogen, angiotensin-I-converting enzyme (ACE), AT1 receptor) were determined. Results Plasma DHT was increased 3-fold in hyperandrogenemic female 1 rats, whereas plasma estradiol levels were not different compared to control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. Conclusions The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model in order to study the mechanisms responsible for hypertension. PMID:21536229

  4. Pulmonary Complications Resulting from Genetic Cardiovascular Disease in Two Rat Models

    EPA Science Inventory

    Underlying cardiovascular disease (CVD) has been considered a risk factor for exacerbation of air pollution health effects. Therefore, rodent models of CVD are increasingly used to examine mechanisms of variation in susceptibility. Pulmonary complications and altered iron homeost...

  5. Pulmonary Transcriptional Response to Ozone in Healthy and Cardiovascular Compromised Rat Models

    EPA Science Inventory

    The genetic cardiovascular disease (CVD) and associated metabolic impairments can influence the lung injury from inhaled pollutants. We hypothesized that comparative assessment of global pulmonary expression profile of healthy and CVD-prone rat models will provide mechanistic ins...

  6. Pulmonary oxidative stress, inflammation and dysregulated iron homeostatis in rat models of cardiovascular disease

    EPA Science Inventory

    Underlying cardiovascular disease (CVD) is considered a risk factor for the exacerbation of air pollution health effects. Therefore, rodent models of CVD are increasingly used to examine mechanisms ofvariation in susceptibility. Pulmonary oxidative stress, inflammation and altere...

  7. FoxO proteins: cunning concepts and considerations for the cardiovascular system.

    PubMed

    Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen; Hou, Jinling

    2009-02-01

    Dysfunction in the cardiovascular system can lead to the progression of a number of disease entities that can involve cancer, diabetes, cardiac ischaemia, neurodegeneration and immune system dysfunction. In order for new therapeutic avenues to overcome some of the limitations of present clinical treatments for these disorders, future investigations must focus upon novel cellular processes that control cellular development, proliferation, metabolism and inflammation. In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs) have increasingly become recognized as important and exciting targets for disorders of the cardiovascular system. In the present review, we describe the role of these transcription factors in the cardiovascular system during processes that involve angiogenesis, cardiovascular development, hypertension, cellular metabolism, oxidative stress, stem cell proliferation, immune system regulation and cancer. Current knowledge of FoxO protein function combined with future studies should continue to lay the foundation for the successful translation of these transcription factors into novel and robust clinical therapies.

  8. Direct and indirect effects of particulate matter on the cardiovascular system.

    PubMed

    Nelin, Timothy D; Joseph, Allan M; Gorr, Matthew W; Wold, Loren E

    2012-02-01

    Human exposure to particulate matter (PM) elicits a variety of responses on the cardiovascular system through both direct and indirect pathways. Indirect effects of PM on the cardiovascular system are mediated through the autonomic nervous system, which controls heart rate variability, and inflammatory responses, which augment acute cardiovascular events and atherosclerosis. Recent research demonstrates that PM also affects the cardiovascular system directly by entry into the systemic circulation. This process causes myocardial dysfunction through mechanisms of reactive oxygen species production, calcium ion interference, and vascular dysfunction. In this review, we will present key evidence in both the direct and indirect pathways, suggest clinical applications of the current literature, and recommend directions for future research.

  9. Effects of pirarubicin, an antitumor antibiotic, on the cardiovascular system.

    PubMed

    Hirano, S; Agata, N; Hara, Y; Iguchi, H; Shirai, M; Tone, H; Urakawa, N

    1991-01-01

    In the present study we examined the effects of pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39-3.13 mg/kg, i.v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5 x 10(-6)-1.5 x 10(-5) M, THP markedly relaxed a contraction induced by 10(-7) M norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02-0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5 x 10(-5)-1.5 x 10(-4) M), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10(-6)-5 x 10(-5) M), chlorpheniramine (3 x 10(-7)-3 x 10(-5) M), and tripelennamine (3 x 10(-7)-3 x 10(-5) M) but not by propranolol (10(-6) M), cimetidine (10(-5) M), diltiazem (10(-6) M), or ryanodine (10(-8) M). THP given i.v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine.

  10. Role of the autonomic nervous system and baroreflex in stress-evoked cardiovascular responses in rats.

    PubMed

    Dos Reis, Daniel Gustavo; Fortaleza, Eduardo Albino Trindade; Tavares, Rodrigo Fiacadori; Corrêa, Fernando Morgan Aguiar

    2014-07-01

    Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint.

  11. [State of the immune system in children with tonsillitis-induced lesions of the cardiovascular system].

    PubMed

    Smiian, O I; Mozhova, Iu A; Bynda, T P; Sichnenko, P I; Romaniuk, O K; Slyva, V V

    2013-03-01

    Purpose of work was study the state of the immune system in children with non-inflammatory tonzillogenic lesions of the cardiovascular system. The article describes the main features of the immune status of children 6-18 years with chronic tonsillitis with lesions of the cardiovascular system. We analyzed the content of serum lymphocytes, T-lymphocytes, T-helper cells, T-suppressor, null cells, B-cells, the concentration of immunoglobulin (Ig) A, G, M, immunoregulatory index. Found that children with chronic tonsillitis and tonzillogenic heart disease immune status changes were more significant in contrast to children with chronic tonsillitis without cardiac complications and manifested significant increase in T-suppressor cells, Ig M and decreased T-lymphocytes (P < 0.01).

  12. Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells

    PubMed Central

    Tanaka, Atsushi; Yuasa, Shinsuke; Node, Koichi; Fukuda, Keiichi

    2015-01-01

    The generation of induced pluripotent stem cells (iPSCs) has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use. PMID:26274955

  13. Associations Between Cardiovascular Health and Health-Related Quality of Life, Behavioral Risk Factor Surveillance System, 2013

    PubMed Central

    Fang, Jing; Zack, Matthew; Moore, Latetia; Loustalot, Fleetwood

    2016-01-01

    Introduction The American Heart Association established 7 cardiovascular health metrics as targets for promoting healthier lives. Cardiovascular health has been hypothesized to play a role in individuals’ perception of quality of life; however, previous studies have mostly assessed the effect of cardiovascular risk factors on quality of life. Methods Data were from the 2013 Behavioral Risk Factor Surveillance System, a state-based telephone survey of adults 18 years or older (N = 347,073). All measures of cardiovascular health and health-related quality of life were self-reported. The 7 ideal cardiovascular health metrics were normal blood pressure, cholesterol, body mass index, not having diabetes, not smoking, being physically active, and having adequate fruit or vegetable intake. Cardiovascular health was categorized into meeting 0–2, 3–5, or 6–7 ideal cardiovascular health metrics. Logistic regression models examined the association between cardiovascular health, general health status, and 3 measures of unhealthy days per month, adjusting for age, sex, race/ethnicity, education, and annual income. Results Meeting 3 to 5 or 6 to 7 ideal cardiovascular health metrics was associated with a 51% and 79% lower adjusted prevalence ratio (aPR) of fair/poor health, respectively (aPR = 0.49, 95% confidence interval [CI] [0.47–0.50], aPR = 0.21, 95% CI [0.19–0.23]); a 47% and 72% lower prevalence of ≥14 physically unhealthy days (aPR = 0.53, 95% CI [0.51–0.55], aPR = 0.28, 95% CI [0.26–0.20]); a 43% and 66% lower prevalence of ≥14 mentally unhealthy days (aPR = 0.57, 95% CI [0.55–0.60], aPR = 0.34, 95% CI [0.31–0.37]); and a 50% and 74% lower prevalence of ≥14 activity limitation days (aPR = 0.50, 95% CI [0.48–0.53], aPR = 0.26, 95% CI [0.23–0.29]) in the past 30 days. Conclusion Achieving a greater number of ideal cardiovascular health metrics may be associated with less impairment in health-related quality of life. PMID:27468158

  14. [Modern data regarding the cardiovascular system lesions in patients with bronchopulmonary diseases and tuberculosis].

    PubMed

    Gadzhieva, N A

    2010-01-01

    The article presents literature review on modern data regarding cardiovascular system lesions in patients with bronchopulmonary diseases and tuberculosis. To detect these changes is of great importance for an assessment of a functional condition of an organism as a whole.

  15. Applicability of implantable telemetry systems in cardiovascular research.

    NASA Technical Reports Server (NTRS)

    Krutz, R. W.; Rader, R. D.; Meehan, J. P.; Henry, J. P.

    1971-01-01

    This paper briefly describes the results of an experimental program undertaken to develop and apply implanted telemetry to cardiovascular research. Because of the role the kidney may play in essential hypertension, emphasis is placed on telemetry's applicability in the study of renal physiology. Consequently, the relationship between pressure, flow, and hydraulic impedance are stressed. Results of an exercise study are given.

  16. Physical exercise and epigenetic adaptations of the cardiovascular system.

    PubMed

    Zimmer, P; Bloch, W

    2015-05-01

    During the last decade, epigenetics became one of the fastest growing research fields in numerous clinical and basic science disciplines. Evidence suggests that chromatin modifications (e.g., histone modifications and DNA methylation) as well as the expression of micro-RNA molecules play a crucial role in the pathogenesis of several cardiovascular diseases. On the one hand, they are involved in the development of general risk factors like chronic inflammation, but on the other hand, epigenetic modifications are conducive to smooth muscle cell, cardiomyocyte, and endothelial progenitor cell proliferation/differentiation as well as to extracellular matrix processing and endothelial function (e.g., endothelial nitric oxide synthase regulation). Therefore, epigenetic medical drugs have gained increased attention and provided the first promising results in the context of cardiovascular malignancies. Beside other lifestyle factors, physical activity and sports essentially contribute to cardiovascular health and regeneration. In this review we focus on recent research proposing physical activity as a potent epigenetic regulator that has the potential to counteract pathophysiological alterations in almost all the aforementioned cardiovascular cells and tissues. As with epigenetic medical drugs, more knowledge about the molecular mechanisms and dose-response relationships of exercise is needed to optimize the outcome of preventive and rehabilitative exercise programs and recommendations.

  17. Development of the Digital Astronaut Project for the analysis of the mechanisms of physiologic adaptation to microgravity: Validation of the cardiovascular system module

    NASA Astrophysics Data System (ADS)

    Summers, Richard; Coleman, Thomas; Meck, Janice

    The physiologic adaptation of humans to the microgravity environment is complex and requires an integrative perspective to fully understand the mechanisms involved. A large computer model of human systems physiology provides the framework for the development of the Digital Astronaut to be used by NASA in the analysis of adaptive mechanisms. While project expansion is ongoing to include all relevant systems, we describe the validation results of the cardiovascular phase of model development. The cardiovascular aspects of the model were validated by benchmark comparisons to published literature findings of changes in left ventricular mass, right atrial pressure and plasma volumes. Computer simulations using the model predicted microgravity induced changes in the target endpoints within statistical validity of experimental findings. Therefore, the current cardiovascular portion of the Digital Astronaut Project computer model appears to accurately predict observed microgravity induced physiologic adaptations. The ongoing process of model development to include all spaceflight relevant systems will require similar validations.

  18. [Peculiarities of cardiovascular system pathology depending on psychological profile in patients of senior age groups].

    PubMed

    Prokhorenko, I O

    2013-01-01

    Interrelations between peculiarities of psychological profile of patients of senior age groups (according to Cattel), level of stress hormones in blood and background pathology of cardiovascular system were studied. Levels of catecholamine and corticosteroids in dynamics, rate of magnesium in erythrocytes and calcium in plaques of coronary arteries as well as fats, Holter ECG, daily profiles of blood pressure, vasomotor function of endothelium and microcirculation were analysed. It is established that stress hormones indirectly determine original form of stress reaction depending on patients' psychological profile. This contributes to the development of one or another form of cardiovascular system pathology. Excessive alcohol intake also promotes progression of cardiovascular system pathology. Depression, being a reflection of disbalance of stress hormones levels, can be used as a marker of unfavourable course of cardiovascular pathology.

  19. Endogenous Sulfur Dioxide: A New Member of Gasotransmitter Family in the Cardiovascular System

    PubMed Central

    Huang, Yaqian; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

    2016-01-01

    Sulfur dioxide (SO2) was previously regarded as a toxic gas in atmospheric pollutants. But it has been found to be endogenously generated from metabolism of sulfur-containing amino acids in mammals through transamination by aspartate aminotransferase (AAT). SO2 could be produced in cardiovascular tissues catalyzed by its synthase AAT. In recent years, studies revealed that SO2 had physiological effects on the cardiovascular system, including vasorelaxation and cardiac function regulation. In addition, the pathophysiological effects of SO2 were also determined. For example, SO2 ameliorated systemic hypertension and pulmonary hypertension, prevented the development of atherosclerosis, and protected against myocardial ischemia-reperfusion (I/R) injury and isoproterenol-induced myocardial injury. These findings suggested that endogenous SO2 was a novel gasotransmitter in the cardiovascular system and provided a new therapy target for cardiovascular diseases. PMID:26839635

  20. The effect of mirthful laughter on the human cardiovascular system.

    PubMed

    Miller, Michael; Fry, William F

    2009-11-01

    It has become increasingly recognized and more widely acknowledged during the past several decades, that a complex relationship exists between behavior associated with emotion and the human cardiovascular (CV) system. Early studies focused on the interplay between negative emotions and elevated CV risk, an effect that has in large part been attributed to increased adrenergic activity. Thus, a variety of adverse CV effects ranging from sudden cardiac death triggered by natural disasters such as earthquakes to transient myocardial stunning resulting from heightened sympathetic overload have been identified in response to acute emotional distress. In fact, the biologic interplay between emotion and CV health has been greatly enhanced through studies of the vascular endothelium. As the largest organ in humans, the inner blood vessel lining serves as a conduit for the transfer of blood cells, lipids and various nutrients across the lumen to neighboring tissues. Healthy endothelial cells secrete vasoactive chemicals, most notably endothelial-derived relaxing factor or nitric oxide (NO), that effects smooth muscle relaxation and vessel dilation via a cyclic guanosine monophosphate (cGMP) dependent protein kinase signaling pathway. In addition, endothelial derived NO may reduce vascular inflammation by attenuating or inhibiting leukocyte adhesion and subendothelial transmigration as well as decreasing platelet activation via cGMP mediated pathways. Taken together, studying the endothelium provides an exceptional opportunity to advance our understanding of the potentially important interrelationship between emotions and the vasculature. Premised on the identification of physiological and biochemical correlates, the former was demonstrated after intracoronary administration of acetylcholine yielded paradoxical endothelial vasoconstriction in response to mental stress exercises. More recently, the brachial artery reactivity test (BART) has permitted endothelial function to be

  1. High-Frequency Ultrasound for the Study of Early Mouse Embryonic Cardiovascular System.

    PubMed

    Greco, Adelaide; Coda, Anna Rita Daniela; Albanese, Sandra; Ragucci, Monica; Liuzzi, Raffaele; Auletta, Luigi; Gargiulo, Sara; Lamagna, Francesco; Salvatore, Marco; Mancini, Marcello

    2015-12-01

    An accurate diagnosis of congenital heart defects during fetal development is critical for interventional planning. Mice can be used to generate animal models with heart defects, and high-frequency ultrasound (HFUS) imaging enables in utero imaging of live mouse embryos. A wide range of physiological measurements is possible using Doppler-HFUS imaging; limitations of any single measurement warrant a multiparameter approach to characterize cardiovascular function. Doppler-HFUS was used to explore the embryonic (heart, aorta) and extraembryonic (umbilical blood flow) circulatory systems to create a database in normal mouse embryos between 9.5 and 16.5 days of gestation. Multivariate analyses were performed to explore correlations between gestational age and embryo echocardiographic parameters. Heart rate and peak velocity in the aorta were positively correlated with gestational time, whereas cardiac cycle length, isovolumetric relaxation time, myocardial performance index, and arterial deceleration time of the umbilical cord were negatively correlated with it. Doppler-HFUS facilitated detailed characterization of the embryonic mouse circulation and represents a useful tool for investigation of the early mouse embryonic cardiovascular system.

  2. [Hydrogen sulfide as a biologically active mediator in the cardiovascular system].

    PubMed

    Bełtowski, Jerzy

    2004-07-19

    Recent studies suggest that apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is another inorganic gaseous mediator in the cardiovascular system. H2S is synthesized from L-cysteine by either cystathionine beta-synthase (CBS) or cystathionin gamma--lyase (CSE), both using pyridoxal 5'-phosphate (vitamin B6) as a cofactor. CBS is the main H2S-producing enzyme in the brain and CSE is involved in H2S formation in the cardiovascular system. H2S induces hypotension in vivo and vasodilation vitro by opening KATP channels in vascular smooth muscle cells. Chronic administration of CSE inhibitor induces arterial hypertension in the rat. In addition, decreased H2S generation has been demonstrated in the vasculature of spontaneously hypertensive rat, in experimental hypertension induced by NO synthase blockade, and in hypoxia-induced pulmonary hypertension, and administration of exogenous H2S donor has significant therapeutic effects in these models. Deficiency of H2S may contribute to atherogenesis in some patients with hyperhomocysteinemia, in whom the metabolism of homocysteine to cysteine and H2S is compromised by vitamin B6 deficiency. Reduced H2S production in the brain was observed in patients with Alzheimer's disease. On the other hand, excess of H2S may lead to mental retardation in patients with Down's syndrome and may be involved in the pathogenesis of hypotension associated with septic shock.

  3. Cardiovascular Disease Risk Models and Longitudinal Changes in Cognition: A Systematic Review

    PubMed Central

    Harrison, Stephanie L.; Ding, Jie; Tang, Eugene Y. H.; Siervo, Mario; Robinson, Louise; Jagger, Carol; Stephan, Blossom C. M.

    2014-01-01

    Background Cardiovascular disease and its risk factors have consistently been associated with poor cognitive function and incident dementia. Whether cardiovascular disease prediction models, developed to predict an individual's risk of future cardiovascular disease or stroke, are also informative for predicting risk of cognitive decline and dementia is not known. Objective The objective of this systematic review was to compare cohort studies examining the association between cardiovascular disease risk models and longitudinal changes in cognitive function or risk of incident cognitive impairment or dementia. Materials and Methods Medline, PsychINFO, and Embase were searched from inception to March 28, 2014. From 3,413 records initially screened, 21 were included. Results The association between numerous different cardiovascular disease risk models and cognitive outcomes has been tested, including Framingham and non-Framingham risk models. Five studies examined dementia as an outcome; fourteen studies examined cognitive decline or incident cognitive impairment as an outcome; and two studies examined both dementia and cognitive changes as outcomes. In all studies, higher cardiovascular disease risk scores were associated with cognitive changes or risk of dementia. Only four studies reported model prognostic performance indices, such as Area Under the Curve (AUC), for predicting incident dementia or cognitive impairment and these studies all examined non-Framingham Risk models (AUC range: 0.74 to 0.78). Conclusions Cardiovascular risk prediction models are associated with cognitive changes over time and risk of dementia. Such models are easily obtainable in clinical and research settings and may be useful for identifying individuals at high risk of future cognitive decline and dementia. PMID:25478916

  4. Introduction: Cardiovascular physics

    NASA Astrophysics Data System (ADS)

    Wessel, Niels; Kurths, Jürgen; Ditto, William; Bauernschmitt, Robert

    2007-03-01

    The number of patients suffering from cardiovascular diseases increases unproportionally high with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop high-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Cardiovascular physics-which interconnects medicine, physics, biology, engineering, and mathematics-is based on interdisciplinary collaboration of specialists from the above scientific fields and attempts to gain deeper insights into pathophysiology and treatment options. This paper summarizes advances in cardiovascular physics with emphasis on a workshop held in Bad Honnef, Germany, in May 2005. The meeting attracted an interdisciplinary audience and led to a number of papers covering the main research fields of cardiovascular physics, including data analysis, modeling, and medical application. The variety of problems addressed by this issue underlines the complexity of the cardiovascular system. It could be demonstrated in this Focus Issue, that data analyses and modeling methods from cardiovascular physics have the ability to lead to significant improvements in different medical fields. Consequently, this Focus Issue of Chaos is a status report that may invite all interested readers to join the community and find competent discussion and cooperation partners.

  5. The effects of music on the cardiovascular system and cardiovascular health.

    PubMed

    Trappe, Hans-Joachim

    2010-12-01

    Music may not only improve quality of life but may also effect changes in heart rate and heart rate variability. It has been shown that cerebral flow was significantly lower when listening to 'Va pensiero' from Verdi's 'Nabucco' (70.4±3.3 cm/s) compared with 'Libiam nei lieti calici' from Verdi's 'La Traviata' (70.2±3.1 cm/s) (p<0.02) or Bach's Cantata No. 169 'Gott soll allein mein Herze haben' (70.9±2.9 cm/s) (p<0.02). There was no significant difference in cerebral flow during rest (67.6±3.3 cm/s) or when listening to Beethoven's Ninth Symphony (69.4±3.1 cm/s). It was reported that relaxing music significantly decreases the level of anxiety of patients in a preoperative setting (State-Trait Anxiety Inventory (STAI)-X-1 score 34)-to a greater extent even than orally administered midazolam (STAI-X-1 score 36) (p<0.001). In addition the score was better after surgery in the music group (STAI-X-1 score 30) compared with the midazolam group (STAI-X-1 score 34) (p<0.001). Higher effectiveness and absence of apparent adverse effects make relaxing, preoperative music a useful alternative to midazolam for premedication. In addition, there is sufficient practical evidence of stress reduction suggesting that a proposed regimen of listening to music while resting in bed after open-heart surgery is important in clinical use. After 30 min of bed rest, there was a significant difference in cortisol levels between the music (484.4 mmol/l) and the non-music group (618.8 mmol/l) (p<0.02). Vocal and orchestral music produce significantly better correlations between cardiovascular or respiratory signals compared with music with a more uniform emphasis (p<0.05). The greatest benefit on health is visible with classical music and meditation music, whereas heavy metal music or techno are not only ineffective but possibly dangerous and can lead to stress and/or life-threatening arrhythmias. The music of many composers most effectively improves quality of life, will increase health

  6. The effects of music on the cardiovascular system and cardiovascular health.

    PubMed

    Trappe, Hans-Joachim

    2010-12-01

    Music may not only improve quality of life but may also effect changes in heart rate and heart rate variability. It has been shown that cerebral flow was significantly lower when listening to 'Va pensiero' from Verdi's 'Nabucco' (70.4±3.3 cm/s) compared with 'Libiam nei lieti calici' from Verdi's 'La Traviata' (70.2±3.1 cm/s) (p<0.02) or Bach's Cantata No. 169 'Gott soll allein mein Herze haben' (70.9±2.9 cm/s) (p<0.02). There was no significant difference in cerebral flow during rest (67.6±3.3 cm/s) or when listening to Beethoven's Ninth Symphony (69.4±3.1 cm/s). It was reported that relaxing music significantly decreases the level of anxiety of patients in a preoperative setting (State-Trait Anxiety Inventory (STAI)-X-1 score 34)-to a greater extent even than orally administered midazolam (STAI-X-1 score 36) (p<0.001). In addition the score was better after surgery in the music group (STAI-X-1 score 30) compared with the midazolam group (STAI-X-1 score 34) (p<0.001). Higher effectiveness and absence of apparent adverse effects make relaxing, preoperative music a useful alternative to midazolam for premedication. In addition, there is sufficient practical evidence of stress reduction suggesting that a proposed regimen of listening to music while resting in bed after open-heart surgery is important in clinical use. After 30 min of bed rest, there was a significant difference in cortisol levels between the music (484.4 mmol/l) and the non-music group (618.8 mmol/l) (p<0.02). Vocal and orchestral music produce significantly better correlations between cardiovascular or respiratory signals compared with music with a more uniform emphasis (p<0.05). The greatest benefit on health is visible with classical music and meditation music, whereas heavy metal music or techno are not only ineffective but possibly dangerous and can lead to stress and/or life-threatening arrhythmias. The music of many composers most effectively improves quality of life, will increase health

  7. [The pneumoperitoneum course forecasting and surgery tactic in the group of patients with acute and chronic cholecystitis and concomitant pathology of cardiovascular system].

    PubMed

    Korotkyĭ, V M; Soliaryk, S O; Tsyganok, A M; Sysak, O M

    2012-01-01

    The share of elderly and senile patients with acute cholecystitis concomitant cardiovascular pathology whom the laparoscopic cholecystectomy has been provided is increased. The heightened intraabdominal pressure has negative influence at the cardiovascular system, so the alternative ways for treatment of this group of patients are used in clinic. We propose the pneumoperitoneum model using the pneumatic belt which is fixed at the abdomen in preoperative period in patients with an acute and chronic cholecystitis. This model is useful to forecast cardiovascular disorders during future laparoscopic cholecystectomy. The arterial pressure level, pulse score and ECG are monitored during the test (90 min). Myocardial ischemia appearance seems that the risk of laparoscopic cholecystectomy with pneumoperitoneum is high. The alternative method of surgery in such group of patients (no pneumoperitoneum is applied) is laparoscopic assisted cholecystectomya from miniaccess. This method allows to reducing frequency of intra- and postoperative complications connected with pneumoperitoneum negative influence at the patients with concomitant pathology of cardiovascular system.

  8. [Adverse effects of ultrafine particles on the cardiovascular system and its mechanisms].

    PubMed

    Yi, Tie-ci; Li, Jian-ping

    2014-12-18

    Cardiovascular disease is one of the major threats to human. Air pollution, which , as it become a problem too serious to be ignored in China, is known to be an important risk factor for cardiovascular disease. Among all pollutants, ultrafine particles ( UFPs) , defined as particles with their diameter less than 0. 1 f.Lm, are a specific composition. They are very small in size, large in quantity and surface area, and most important, capable of passing through the air-blood barrier. These unique features of UFPs make them special in their impact on cardiovascular system. Nowadays, the influence of UFPs on the cardiovascular system has become a hot topic. On the one side, studies have shown that UFPs can cause inflammation and oxidative stress in the lung, and then induce systemic inflammation by releasing cytokine and reactive oxygen species into the circulation. On the other side, UFPs themselves can "spillout"into the circulation and interact with their targets. By this way, UFPs directly affect endothelial cells, myocardial cells and the autonomic nervous system, which ultimately result in increased cardiovascular events. We intend to make an overview about the recent progress about the influence of UFPs on human cardiovascular disease and the related mechanisms, and argue for more attention to this issue.

  9. A universal number for wave reflection optimization of the mammalian cardiovascular system.

    NASA Astrophysics Data System (ADS)

    Pahlevan, Niema; Gharib, Morteza

    2015-11-01

    Quantifying the optimum arterial wave reflection and systemic arterial function is essential to the evaluation of optimal cardiovascular system (CVS) operation. The CVS function depends on both the dynamics of the heart and wave dynamics of the arterial network. Here, we are introducing a universal dimensionless number, called wave condition number (α) that quantifies the arterial wave reflection. An in-vitro experimental approach, utilizing a unique hydraulic model was used to quantify α in human aortas with a wide range of aortic rigidities. Our results indicate that the optimum value of the wave condition number is 0.1 at each level of aortic rigidity. Looking into mammals of various size (from mice to elephant), our results show that the optimum wave condition number remains 0.1 and is universal among all mammals. Clinical applications and the relevancy of the wave condition number will also be discussed.

  10. Zebrafish as a new model to study effects of periodontal pathogens on cardiovascular diseases

    PubMed Central

    Widziolek, Magdalena; Prajsnar, Tomasz K.; Tazzyman, Simon; Stafford, Graham P.; Potempa, Jan; Murdoch, Craig

    2016-01-01

    Porphyromonas gingivalis (Pg) is a keystone pathogen in the aetiology of chronic periodontitis. However, recent evidence suggests that the bacterium is also able to enter the bloodstream, interact with host cells and tissues, and ultimately contribute to the pathogenesis of cardiovascular disease (CVD). Here we established a novel zebrafish larvae systemic infection model showing that Pg rapidly adheres to and penetrates the zebrafish vascular endothelium causing a dose- and time-dependent mortality with associated development of pericardial oedemas and cardiac damage. The in vivo model was then used to probe the role of Pg expressed gingipain proteases using systemically delivered gingipain-deficient Pg mutants, which displayed significantly reduced zebrafish morbidity and mortality compared to wild-type bacteria. In addition, we used the zebrafish model to show efficacy of a gingipain inhibitor (KYT) on Pg-mediated systemic disease, suggesting its potential use therapeutically. Our data reveal the first real-time in vivo evidence of intracellular Pg within the endothelium of an infection model and establishes that gingipains are crucially linked to systemic disease and potentially contribute to CVD. PMID:27777406

  11. A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems

    PubMed Central

    Xu, Jiaxi; Mukerjee, Snigdha; Silva-Alves, Cristiane R. A.; Carvalho-Galvão, Alynne; Cruz, Josiane C.; Balarini, Camille M.; Braga, Valdir A.; Lazartigues, Eric; França-Silva, Maria S.

    2016-01-01

    ADAM17 is a metalloprotease and disintegrin that lodges in the plasmatic membrane of several cell types and is able to cleave a wide variety of cell surface proteins. It is somatically expressed in mammalian organisms and its proteolytic action influences several physiological and pathological processes. This review focuses on the structure of ADAM17, its signaling in the cardiovascular system and its participation in certain disorders involving the heart, blood vessels, and neural regulation of autonomic and cardiovascular modulation. PMID:27803674

  12. Computational modelling and evaluation of cardiovascular response under pulsatile impeller pump support

    PubMed Central

    Shi, Yubing; Brown, Alistair G.; Lawford, Patricia V.; Arndt, Andreas; Nuesser, Peter; Hose, D. Rodney

    2011-01-01

    This study presents a numerical simulation of cardiovascular response in the heart failure condition under the support of a Berlin Heart INCOR impeller pump-type ventricular assist device (VAD). The model is implemented using the CellML modelling language. To investigate the potential of using the Berlin Heart INCOR impeller pump to produce physiologically meaningful arterial pulse pressure within the various physiological constraints, a series of VAD-assisted cardiovascular cases are studied, in which the pulsation ratio and the phase shift of the VAD motion profile are systematically changed to observe the cardiovascular responses in each of the studied cases. An optimization process is proposed, including the introduction of a cost function to balance the importance of the characteristic cardiovascular variables. Based on this cost function it is found that a pulsation ratio of 0.35 combined with a phase shift of 200° produces the optimal cardiovascular response, giving rise to a maximal arterial pulse pressure of 12.6 mm Hg without inducing regurgitant pump flow while keeping other characteristic cardiovascular variables within appropriate physiological ranges. PMID:22670203

  13. Computational modelling and evaluation of cardiovascular response under pulsatile impeller pump support.

    PubMed

    Shi, Yubing; Brown, Alistair G; Lawford, Patricia V; Arndt, Andreas; Nuesser, Peter; Hose, D Rodney

    2011-06-01

    This study presents a numerical simulation of cardiovascular response in the heart failure condition under the support of a Berlin Heart INCOR impeller pump-type ventricular assist device (VAD). The model is implemented using the CellML modelling language. To investigate the potential of using the Berlin Heart INCOR impeller pump to produce physiologically meaningful arterial pulse pressure within the various physiological constraints, a series of VAD-assisted cardiovascular cases are studied, in which the pulsation ratio and the phase shift of the VAD motion profile are systematically changed to observe the cardiovascular responses in each of the studied cases. An optimization process is proposed, including the introduction of a cost function to balance the importance of the characteristic cardiovascular variables. Based on this cost function it is found that a pulsation ratio of 0.35 combined with a phase shift of 200° produces the optimal cardiovascular response, giving rise to a maximal arterial pulse pressure of 12.6 mm Hg without inducing regurgitant pump flow while keeping other characteristic cardiovascular variables within appropriate physiological ranges.

  14. Nonlinear effects of respiration on the crosstalk between cardiovascular and cerebrovascular control systems.

    PubMed

    Bari, Vlasta; Marchi, Andrea; De Maria, Beatrice; Rossato, Gianluca; Nollo, Giandomenico; Faes, Luca; Porta, Alberto

    2016-05-13

    Cardiovascular and cerebrovascular regulatory systems are vital control mechanisms responsible for guaranteeing homeostasis and are affected by respiration. This work proposes the investigation of cardiovascular and cerebrovascular control systems and the nonlinear influences of respiration on both regulations through joint symbolic analysis (JSA), conditioned or unconditioned on respiration. Interactions between cardiovascular and cerebrovascular regulatory systems were evaluated as well by performing correlation analysis between JSA indexes describing the two control systems. Heart period, systolic and mean arterial pressure, mean cerebral blood flow velocity and respiration were acquired on a beat-to-beat basis in 13 subjects experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non-SYNC) in supine resting condition and during head-up tilt test at 60° (TILT). Results showed that JSA distinguished conditions and groups, whereas time domain parameters detected only the effect of TILT. Respiration affected cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was able to modulate the interactions between the two control systems with different outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the impact of respiration on cardiovascular and cerebrovascular regulatory systems might improve our understanding of the mechanisms underpinning the development of postural-related syncope.

  15. Nonlinear effects of respiration on the crosstalk between cardiovascular and cerebrovascular control systems

    NASA Astrophysics Data System (ADS)

    Bari, Vlasta; Marchi, Andrea; De Maria, Beatrice; Rossato, Gianluca; Nollo, Giandomenico; Faes, Luca; Porta, Alberto

    2016-05-01

    Cardiovascular and cerebrovascular regulatory systems are vital control mechanisms responsible for guaranteeing homeostasis and are affected by respiration. This work proposes the investigation of cardiovascular and cerebrovascular control systems and the nonlinear influences of respiration on both regulations through joint symbolic analysis (JSA), conditioned or unconditioned on respiration. Interactions between cardiovascular and cerebrovascular regulatory systems were evaluated as well by performing correlation analysis between JSA indexes describing the two control systems. Heart period, systolic and mean arterial pressure, mean cerebral blood flow velocity and respiration were acquired on a beat-to-beat basis in 13 subjects experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non-SYNC) in supine resting condition and during head-up tilt test at 60° (TILT). Results showed that JSA distinguished conditions and groups, whereas time domain parameters detected only the effect of TILT. Respiration affected cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was able to modulate the interactions between the two control systems with different outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the impact of respiration on cardiovascular and cerebrovascular regulatory systems might improve our understanding of the mechanisms underpinning the development of postural-related syncope.

  16. Protective actions of melatonin and growth hormone on the aged cardiovascular system.

    PubMed

    Paredes, Sergio D; Forman, Katherine A; García, Cruz; Vara, Elena; Escames, Germaine; Tresguerres, Jesús A F

    2014-05-01

    Epidemiological studies indicate that certain aspects of lifestyle and genetics act as risk factors for a variety of cardiovascular disorders, including coronary disease, hypertension, heart failure and stroke. Aging, however, appears to be the major contributor for morbidity and mortality of the impaired cardiovascular system. Growth hormone (GH) and melatonin seem to prevent cardiac aging, as they contribute to the recovery of several physiological parameters affected by age. These hormones exhibit antioxidant properties and decrease oxidative stress and apoptosis. This paper summarizes a set of studies related to the potential role that therapy with GH and melatonin may play in the protection of the altered cardiac function due to aging, with a focus on experiments performed in our laboratory using the senescence-accelerated mouse as an aging model. In general, we observed significantly increased inflammation, oxidative stress and apoptosis markers in hearts from senescence-accelerated prone 10-month-old animals compared to 2-month-old controls, while anti-inflammatory and antiapoptotic markers as well as endothelial nitric oxide synthase were decreased. Senescence-accelerated resistant animals showed no significant changes with age. GH or melatonin treatment prevented the age-dependent cardiac alterations observed in the senescence-accelerated prone group. Combined administration of GH plus melatonin reduced the age-related changes in senescence-accelerated prone hearts in an additive fashion that was different to that displayed when administered alone. GH and melatonin may be potential agents for counteracting oxidative stress, apoptosis and inflammation in the aging heart.

  17. Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control

    PubMed Central

    de Kloet, Annette D.; Liu, Meng; Rodríguez, Vermalí; Krause, Eric G.

    2015-01-01

    Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin-angiotensin system (RAS) and of glial cell-mediated proinflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of antihypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, ANG II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent proinflammatory milieu within cardiovascular control centers. Another complexity is that the newly characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the prohypertensive ANG II type 1 receptor (AT1R)-mediated effects. That being said, the mechanism by which the RAS, glia, and neurons interact to regulate blood pressure is an active area of ongoing research. Here, we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function. PMID:26084692

  18. Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control.

    PubMed

    de Kloet, Annette D; Liu, Meng; Rodríguez, Vermalí; Krause, Eric G; Sumners, Colin

    2015-09-01

    Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin-angiotensin system (RAS) and of glial cell-mediated proinflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of antihypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, ANG II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent proinflammatory milieu within cardiovascular control centers. Another complexity is that the newly characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the prohypertensive ANG II type 1 receptor (AT1R)-mediated effects. That being said, the mechanism by which the RAS, glia, and neurons interact to regulate blood pressure is an active area of ongoing research. Here, we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function.

  19. Physiological interdependence of the cardiovascular and postural control systems under orthostatic stress.

    PubMed

    Garg, Amanmeet; Xu, Da; Laurin, Alexandre; Blaber, Andrew P

    2014-07-15

    The cardiovascular system has been observed to respond to changes in human posture and the environment. On the same lines, frequent fallers have been observed to suffer from cardiovascular deficits. The present article aims to demonstrate the existence of interactions between the cardiovascular and postural control systems. The behavior of the two systems under orthostatic challenge was studied through novel adaptations of signal processing techniques. To this effect, the interactions between the two systems were assessed with two metrics, coherence and phase lock value, based on the wavelet transform. Measurements from the cardiovascular system (blood pressure), lower limb muscles (surface electromyography), and postural sway (center of pressure) were acquired from young healthy adults (n = 28, men = 12, age = 20-28 yr) during quiet stance. The continuous wavelet transform was applied to decompose the representative signals on a time-scale basis in a frequency region of 0.01 to 0.1 Hz. Their linear coupling was quantified through a coherence metric, and the synchrony was characterized via the phase information. The outcomes of this study present evidence that the cardiovascular and postural control systems work together to maintain homeostasis under orthostatic challenge. The inferences open a new direction of study for effects under abnormalities and extreme environmental conditions.

  20. Towards 3D in vitro models for the study of cardiovascular tissues and disease.

    PubMed

    Ryan, Alan J; Brougham, Claire M; Garciarena, Carolina D; Kerrigan, Steven W; O'Brien, Fergal J

    2016-09-01

    The field of tissue engineering is developing biomimetic biomaterial scaffolds that are showing increasing therapeutic potential for the repair of cardiovascular tissues. However, a major opportunity exists to use them as 3D in vitro models for the study of cardiovascular tissues and disease in addition to drug development and testing. These in vitro models can span the gap between 2D culture and in vivo testing, thus reducing the cost, time, and ethical burden of current approaches. Here, we outline the progress to date and the requirements for the development of ideal in vitro 3D models for blood vessels, heart valves, and myocardial tissue. PMID:27117348

  1. 2015 Guidelines for Establishing Genetically Modified Rat Models for Cardiovascular Research

    PubMed Central

    Flister, Michael J.; Prokop, Jeremy W.; Lazar, Jozef; Shimoyama, Mary; Dwinell, Melinda; Geurts, Aron

    2015-01-01

    The rat has long been a key physiological model for cardiovascular research; most of the inbred strains having been previously selected for susceptibility or resistance to various cardiovascular diseases (CVD). These CVD rat models offer a physiologically relevant background on which candidates of human CVD can be tested in a more clinically translatable experimental setting. However, a diverse toolbox for genetically modifying the rat genome to test molecular mechanisms has only recently become available. Here, we provide a high-level description of several strategies for developing genetically modified rat models of CVD. PMID:25920443

  2. Bushehr Elderly Health (BEH) Programme, phase I (cardiovascular system)

    PubMed Central

    Ostovar, Afshin; Nabipour, Iraj; Larijani, Bagher; Heshmat, Ramin; Darabi, Hossein; Vahdat, Katayoun; Ravanipour, Maryam; Mehrdad, Neda; Raeisi, Alireza; Heidari, Gholamreza; Shafiee, Gita; Haeri, Mohammadjavad; Pourbehi, Mohammadreza; Sharifi, Farshad; Noroozi, Azita; Tahmasebi, Rahim; Aghaei Meybodi, Hamidreza; Assadi, Majid; Farrokhi, Shokrollah; Nemati, Reza; Amini, Mohammad Reza; Barekat, Maryam; Amini, Abdullatif; Salimipour, Houman; Dobaradaran, Sina; Moshtaghi, Darab

    2015-01-01

    Purpose The main objective of the Bushehr Elderly Health Programme, in its first phase, is to investigate the prevalence of cardiovascular risk factors and their association with major adverse cardiovascular events. Participants Between March 2013 and October 2014, a total of 3000 men and women aged ≥60 years, residing in Bushehr, Iran, participated in this prospective cohort study (participation rate=90.2%). Findings to date Baseline data on risk factors, including demographic and socioeconomic status, smoking and medical history, were collected through a modified WHO MONICA questionnaire. Vital signs and anthropometric measures, including systolic and diastolic blood pressure, weight, height, and waist and hip circumference, were also measured. 12-lead electrocardiography and echocardiography were conducted on all participants, and total of 10 cc venous blood was taken, and sera was separated and stored at –80°C for possible future use. Preliminary data analyses showed a noticeably higher prevalence of risk factors among older women compared to that in men. Future plans Risk factor assessments will be repeated every 5 years, and the participants will be followed during the study to measure the occurrence of major adverse cardiac events. Moreover, the second phase, which includes investigation of bone health and cognition in the elderly, was started in September 2015. Data are available at the Persian Gulf Biomedical Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran, for any collaboration. PMID:26674503

  3. Changes in diet, cardiovascular risk factors and modelled cardiovascular risk following diagnosis of diabetes: 1-year results from the ADDITION-Cambridge trial cohort

    PubMed Central

    Savory, L A; Griffin, S J; Williams, K M; Prevost, A T; Kinmonth, A-L; Wareham, N J; Simmons, R K

    2014-01-01

    Aims To describe change in self-reported diet and plasma vitamin C, and to examine associations between change in diet and cardiovascular disease risk factors and modelled 10-year cardiovascular disease risk in the year following diagnosis of Type 2 diabetes. Methods Eight hundred and sixty-seven individuals with screen-detected diabetes underwent assessment of self-reported diet, plasma vitamin C, cardiovascular disease risk factors and modelled cardiovascular disease risk at baseline and 1 year (n = 736) in the ADDITION-Cambridge trial. Multivariable linear regression was used to quantify the association between change in diet and cardiovascular disease risk at 1 year, adjusting for change in physical activity and cardio-protective medication. Results Participants reported significant reductions in energy, fat and sodium intake, and increases in fruit, vegetable and fibre intake over 1 year. The reduction in energy was equivalent to an average-sized chocolate bar; the increase in fruit was equal to one plum per day. There was a small increase in plasma vitamin C levels. Increases in fruit intake and plasma vitamin C were associated with small reductions in anthropometric and metabolic risk factors. Increased vegetable intake was associated with an increase in BMI and waist circumference. Reductions in fat, energy and sodium intake were associated with reduction in HbA1c, waist circumference and total cholesterol/modelled cardiovascular disease risk, respectively. Conclusions Improvements in dietary behaviour in this screen-detected population were associated with small reductions in cardiovascular disease risk, independently of change in cardio-protective medication and physical activity. Dietary change may have a role to play in the reduction of cardiovascular disease risk following diagnosis of diabetes. PMID:24102972

  4. Emotional Stress and Cardiovascular Complications in Animal Models: A Review of the Influence of Stress Type.

    PubMed

    Crestani, Carlos C

    2016-01-01

    Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. The impact of stress on physiological and psychological processes is determined by characteristics of the stress stimulus. For example, distinct responses are induced by acute vs. chronic aversive stimuli. Additionally, the magnitude of stress responses has been reported to be inversely related to the degree of predictability of the aversive stimulus. Therefore, the purpose of the present review was to discuss experimental research in animal models describing the influence of stressor stimulus characteristics, such as chronicity and predictability, in cardiovascular dysfunctions induced by emotional stress. Regarding chronicity, the importance of cardiovascular and autonomic adjustments during acute stress sessions and cardiovascular consequences of frequent stress response activation during repeated exposure to aversive threats (i.e., chronic stress) is discussed. Evidence of the cardiovascular and autonomic changes induced by chronic stressors involving daily exposure to the same stressor (predictable) vs. different stressors (unpredictable) is reviewed and discussed in terms of the impact of predictability in cardiovascular dysfunctions induced by stress. PMID:27445843

  5. Emotional Stress and Cardiovascular Complications in Animal Models: A Review of the Influence of Stress Type

    PubMed Central

    Crestani, Carlos C.

    2016-01-01

    Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. The impact of stress on physiological and psychological processes is determined by characteristics of the stress stimulus. For example, distinct responses are induced by acute vs. chronic aversive stimuli. Additionally, the magnitude of stress responses has been reported to be inversely related to the degree of predictability of the aversive stimulus. Therefore, the purpose of the present review was to discuss experimental research in animal models describing the influence of stressor stimulus characteristics, such as chronicity and predictability, in cardiovascular dysfunctions induced by emotional stress. Regarding chronicity, the importance of cardiovascular and autonomic adjustments during acute stress sessions and cardiovascular consequences of frequent stress response activation during repeated exposure to aversive threats (i.e., chronic stress) is discussed. Evidence of the cardiovascular and autonomic changes induced by chronic stressors involving daily exposure to the same stressor (predictable) vs. different stressors (unpredictable) is reviewed and discussed in terms of the impact of predictability in cardiovascular dysfunctions induced by stress. PMID:27445843

  6. [Urine proteome study for the evaluation of cardiovascular system state after spaceflight in human].

    PubMed

    Pastukhova, L Kh; Kononikhin, A S; Tiĭs, E S; Popova, I A; Dobrokhotov, I V; Ivanisenko, V A; Nikolaev, E N; Larina, I M

    2013-08-01

    In order to find markers to assess the functional state of the cardiovascular system before and after spaceflight (first and seventh day after landing), we analyzed the urine proteome in ten cosmonauts aged of 35 to 51 years who have completed 169 to 199-day spaceflight onboard the ISS. A special sample preparation was performed, followed by liquid chromatography-mass spectrometry. Liquid chromatography-mass spectrometry of the minor proteins was performed on a nano-HPLC Agilent 1100 system (Agilent Technologies Inc., USA) in combination with a LTQ-FT Ultra mass spectrometer (Thermo, Germany). A total of 238 proteins was identified. According to the TIGER database, a tissue origin was established for 129 proteins. We identified 20 proteins related to the cardiovascular system. It was found that changes in cosmonauts' urine proteome comprehensively reflect the adaptive responses of cardiovascular, renal and neuroendocrine systems to long-term microgravity conditions.

  7. Regulators and effectors of bone morphogenetic protein signalling in the cardiovascular system.

    PubMed

    Luo, Jiang-Yun; Zhang, Yang; Wang, Li; Huang, Yu

    2015-07-15

    Bone morphogenetic proteins (BMPs) play key roles in the regulation of cell proliferation, differentiation and apoptosis in various tissues and organs, including the cardiovascular system. BMPs signal through both Smad-dependent and -independent cascades to exert a wide spectrum of biological activities. Cardiovascular disorders such as abnormal angiogenesis, atherosclerosis, pulmonary hypertension and cardiac hypertrophy have been linked to aberrant BMP signalling. To correct the dysregulated BMP signalling in cardiovascular pathogenesis, it is essential to get a better understanding of how the regulators and effectors of BMP signalling control cardiovascular function and how the dysregulated BMP signalling contributes to cardiovascular dysfunction. We hence highlight several key regulators of BMP signalling such as extracellular regulators of ligands, mechanical forces, microRNAs and small molecule drugs as well as typical BMP effectors like direct downstream target genes, mitogen-activated protein kinases, reactive oxygen species and microRNAs. The insights into these molecular processes will help target both the regulators and important effectors to reverse BMP-associated cardiovascular pathogenesis. PMID:25952563

  8. Regulators and effectors of bone morphogenetic protein signalling in the cardiovascular system.

    PubMed

    Luo, Jiang-Yun; Zhang, Yang; Wang, Li; Huang, Yu

    2015-07-15

    Bone morphogenetic proteins (BMPs) play key roles in the regulation of cell proliferation, differentiation and apoptosis in various tissues and organs, including the cardiovascular system. BMPs signal through both Smad-dependent and -independent cascades to exert a wide spectrum of biological activities. Cardiovascular disorders such as abnormal angiogenesis, atherosclerosis, pulmonary hypertension and cardiac hypertrophy have been linked to aberrant BMP signalling. To correct the dysregulated BMP signalling in cardiovascular pathogenesis, it is essential to get a better understanding of how the regulators and effectors of BMP signalling control cardiovascular function and how the dysregulated BMP signalling contributes to cardiovascular dysfunction. We hence highlight several key regulators of BMP signalling such as extracellular regulators of ligands, mechanical forces, microRNAs and small molecule drugs as well as typical BMP effectors like direct downstream target genes, mitogen-activated protein kinases, reactive oxygen species and microRNAs. The insights into these molecular processes will help target both the regulators and important effectors to reverse BMP-associated cardiovascular pathogenesis.

  9. Beta 3-adrenoreceptor regulation of nitric oxide in the cardiovascular system.

    PubMed

    Moens, An L; Yang, Ronghua; Watts, Vabren L; Barouch, Lili A

    2010-06-01

    The presence of a third beta-adrenergic receptor (beta 3-AR) in the cardiovascular system has challenged the classical paradigm of sympathetic regulation by beta1- and beta2-adrenergic receptors. While beta 3-AR's role in the cardiovascular system remains controversial, increasing evidence suggests that it serves as a "brake" in sympathetic overstimulation - it is activated at high catecholamine concentrations, producing a negative inotropic effect that antagonizes beta1- and beta2-AR activity. The anti-adrenergic effects induced by beta 3-AR were initially linked to nitric oxide (NO) release via endothelial NO synthase (eNOS), although more recently it has been shown under some conditions to increase NO production in the cardiovascular system via the other two NOS isoforms, namely inducible NOS (iNOS) and neuronal NOS (nNOS). We summarize recent findings regarding beta 3-AR effects on the cardiovascular system and explore its prospective as a therapeutic target, particularly focusing on its emerging role as an important mediator of NO signaling in the pathogenesis of cardiovascular disorders.

  10. The cardiovascular system in growth hormone excess and growth hormone deficiency.

    PubMed

    Lombardi, G; Di Somma, C; Grasso, L F S; Savanelli, M C; Colao, A; Pivonello, R

    2012-12-01

    The clinical conditions associated with GH excess and GH deficiency (GHD) are known to be associated with an increased risk for the cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GHD has been considered the under- lying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhood-onset or adulthood-onset GHD are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavorable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GHD is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular

  11. Modeling cardiovascular hemodynamics using the lattice Boltzmann method on massively parallel supercomputers

    NASA Astrophysics Data System (ADS)

    Randles, Amanda Elizabeth

    Accurate and reliable modeling of cardiovascular hemodynamics has the potential to improve understanding of the localization and progression of heart diseases, which are currently the most common cause of death in Western countries. However, building a detailed, realistic model of human blood flow is a formidable mathematical and computational challenge. The simulation must combine the motion of the fluid, the intricate geometry of the blood vessels, continual changes in flow and pressure driven by the heartbeat, and the behavior of suspended bodies such as red blood cells. Such simulations can provide insight into factors like endothelial shear stress that act as triggers for the complex biomechanical events that can lead to atherosclerotic pathologies. Currently, it is not possible to measure endothelial shear stress in vivo, making these simulations a crucial component to understanding and potentially predicting the progression of cardiovascular disease. In this thesis, an approach for efficiently modeling the fluid movement coupled to the cell dynamics in real-patient geometries while accounting for the additional force from the expansion and contraction of the heart will be presented and examined. First, a novel method to couple a mesoscopic lattice Boltzmann fluid model to the microscopic molecular dynamics model of cell movement is elucidated. A treatment of red blood cells as extended structures, a method to handle highly irregular geometries through topology driven graph partitioning, and an efficient molecular dynamics load balancing scheme are introduced. These result in a large-scale simulation of the cardiovascular system, with a realistic description of the complex human arterial geometry, from centimeters down to the spatial resolution of red-blood cells. The computational methods developed to enable scaling of the application to 294,912 processors are discussed, thus empowering the simulation of a full heartbeat. Second, further extensions to enable

  12. Ambient particle inhalation and the cardiovascular system: potential mechanisms.

    PubMed Central

    Donaldson, K; Stone, V; Seaton, A; MacNee, W

    2001-01-01

    Well-documented air pollution episodes throughout recent history have led to deaths among individuals with cardiovascular and respiratory disease. Although the components of air pollution that cause the adverse health effects in these individuals are unknown, a small proportion by mass but a large proportion by number of the ambient air particles are ultrafine, i.e., less than 100 nm in diameter. This ultrafine component of particulate matter with a mass median aerodynamic diameter less than 10 microm (PM(10) may mediate some of the adverse health effects reported in epidemiologic studies and for which there is toxicologic evidence to support this contention. The exact mechanism by which ultrafine particles have adverse effects is unknown, but these particles have recently been shown to enhance calcium influx on contact with macrophages. Oxidative stress is also to be anticipated at the huge particle surface; this can be augmented by oxidants generated by recruited inflammatory leukocytes. Atheromatous plaques form in the coronary arteries and are major causes of morbidity and death associated epidemiologically with particulate air pollution. In populations exposed to air pollution episodes, blood viscosity, fibrinogen, and C-reactive protein (CRP) were higher. More recently, increases in heart rate in response to rising air pollution have been described and are most marked in individuals who have high blood viscosity. In our study of elderly individuals, there were significant rises in CRP, an index of inflammation. In this present review, we consider the likely interactions between the ultrafine particles the acute phase response and cardiovascular disease. PMID:11544157

  13. The effects of exercise on blood flow with reference to the human cardiovascular system: a finite element study

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1992-01-01

    This paper reports on a theoretical investigation into the effects of vasomotion on blood through the human cardiovascular system. The finite element method has been used to analyse the model. Vasoconstriction and vasodilation may be effected either through the action of the central nervous system or autoregulation. One of the conditions responsible for vasomotion is exercise. The proposed model has been solved and quantitative results of flows and pressures due to changing the conductances of specific networks of arterioles, capillaries and venules comprising the arms, legs, stomach and their combinations have been obtained.

  14. [Analysis of mediastinal lymphadenopathy in sarcoidosis with transesophageal ultrasonic endoscopy; influences on cardiovascular system].

    PubMed

    Dambara, T; Ueki, J; Aiba, M; Tamaki, S; Saito, H; Matsuda, K; Nukiwa, T; Kira, S

    1989-01-01

    We studied influences of mediastinal lymphadenopathy on cardiovascular system in nine cases of sarcoidosis with transesophageal ultrasonic endoscopy. Chest x-ray films revealed bilateral hilar lymphadenopathy in all cases, whose diagnoses were made histologically with biopsies of peripheral lung through flexible fiber optic bronchoscope and/or of lymph nodes. These findings were typical in this disease. Many compartments of cardiovascular system in mediastinal and hilar regions were visible with this technique in all subjects. And enlarged lymph nodes changed dimensions in these compartments, especially in main pulmonary arteries, left atria, pulmonary veins and aorta. Furthermore, these phenomena were seen in azygos vein and superior caval vein in some cases. It is suggested that these lymph nodes may influence hemodynamics in above-mentioned compartments of cardiovascular system, if this phenomenon deteriorates more progressively. PMID:2657139

  15. The biological effect of endogenous sulfur dioxide in the cardiovascular system.

    PubMed

    Wang, Xin-Bao; Jin, Hong-Fang; Tang, Chao-Shu; Du, Jun-Bao

    2011-11-16

    Sulfur dioxide is considered a toxic gas in air pollution and detrimental to many organs, however, it can be generated endogenously in the cardiovascular system in vivo. Gaseous sulfur dioxide has an endothelium-dependent vasorelaxing effect at low concentrations, but is endothelium-independent at high concentrations and has a negative inotropic effect on cardiac function. This vasorelaxing effect is mediated by adenosine triphosphate-sensitive calcium channels and L-type calcium channels. Under pathophysiological conditions, sulfur dioxide increases anti-inflammatory response and antioxidant capacities in pulmonary hypertensive rats. Sulfur dioxide also attenuates increased blood pressure and vascular remodeling in spontaneously hypertensive and hypoxic pulmonary hypertensive rats. Recent studies suggest that endogenous sulfur dioxide is also involved in the process of myocardial ischemia-reperfusion injury and lipid metabolism. Therefore, the evidence suggests that endogenous sulfur dioxide may be a novel gasotransmitter in the cardiovascular system. The significance of sulfur dioxide on the cardiovascular system is intriguing and appealing.

  16. In vitro models for assessing the potential cardiovascular disease risk associated with cigarette smoking.

    PubMed

    Fearon, Ian M; Gaça, Marianna D; Nordskog, Brian K

    2013-02-01

    Atherosclerotic cardiovascular disease is a prevalent human disorder and a significant cause of human morbidity and mortality. A number of risk factors may predispose an individual to developing atherosclerosis, and of these factors, cigarette smoking is strongly associated with the development of cardiovascular disease. Current thinking suggests that exposure to toxicants found in cigarette smoke may be responsible for this elevated disease likelihood, and this gives rise to the idea that reductions in the levels of some smoke toxicants may reduce the harm associated with cigarette smoking. To assess the disease risk of individuals who smoke cigarettes with altered toxicant levels, a weight-of-evidence approach is required examining both exposure and disease-related endpoints. A key element of such an assessment framework are data derived from the use of in vitro models of cardiovascular disease, which when considered alongside other forms of data (e.g. from clinical studies) may support evidence of potential reduced risk. Importantly, such models may also be used to provide mechanistic insight into the effects of smoking and of smoke toxicant exposure in cardiovascular disease development. In this review the use of in vitro models of cardiovascular disease and one of the contributory factors, oxidative stress, is discussed in the context of assessing the risk potential of both conventional and modified cigarettes. Practical issues concerning the use of these models for cardiovascular disease understanding and risk assessment are highlighted and areas of development necessary to enhance the power and predictive capacity of in vitro disease models in risk assessment are discussed.

  17. Obesity and cardiovascular disease: role of adipose tissue, inflammation, and the renin-angiotensin-aldosterone system.

    PubMed

    Lastra, Guido; Sowers, James R

    2013-09-01

    Obesity is a leading contributor to morbidity and mortality worldwide. Chronic overnutrition and lack of physical activity result in excess deposition of adipose tissue and insulin resistance, which plays a key role in the pathophysiology of type 2 diabetes mellitus (DM2) and associated cardiovascular disease (CVD). Dysfunctional adipose tissue in obese individuals is characterized by chronic low-grade inflammation that spreads to several tissues as well as systemically and is able to impact the cardiovascular system, resulting in both functional and anatomical abnormalities. Inflammation is characterized by abnormalities in both innate and adaptive immunity including adipose tissue infiltration by CD4+ T lymphocytes, pro-inflammatory (M1) macrophages, and increased production of adipokines. The renin-angiotensin-aldosterone system (RAAS) is inappropriately activated in adipose tissue and contributes to originating and perpetuating inflammation and excessive oxidative stress by increasing production of reactive oxygen species (ROS). In turn, ROS and pro-inflammatory adipokines cause resistance to the metabolic actions of insulin in several tissues including cardiovascular and adipose tissue. Insulin resistance in cardiovascular tissues is characterized by impaired vascular reactivity and abnormal cardiac contractility as well as hypertrophy, fibrosis, and remodeling, which ultimately result in CVD. In this context, weight loss through caloric restriction, regular physical activity, and surgery as well as pharmacologic RAAS blockade all play a key role in reducing obesity-related cardiovascular morbidity and mortality.

  18. 77 FR 8117 - Medical Devices; Cardiovascular Devices; Classification of the Endovascular Suturing System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-14

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 870 Medical Devices; Cardiovascular Devices; Classification of the Endovascular Suturing System AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is classifying the endovascular suturing system into...

  19. An Adaptive and Implicit Immersed Boundary Method for Cardiovascular Device Modeling

    NASA Astrophysics Data System (ADS)

    Bhalla, Amneet Pal S.; Griffith, Boyce E.

    2015-11-01

    Computer models and numerical simulations are playing an increasingly important role in understanding the mechanics of fluid-structure interactions (FSI) in cardiovascular devices. To model cardiac devices realistically, there is a need to solve the classical fluid-structure interaction equations efficiently. Peskin's explicit immersed boundary method is one such approach to model FSI equations for elastic structures efficiently. However, in the presence of rigid structures the IB method faces a severe timestep restriction. To overcome this limitation, we are developing an implicit version of immersed boundary method on adaptive Cartesian grids. Higher grid resolution is employed in spatial regions occupying the structure while relatively coarser discretization is used elsewhere. The resulting discrete system is solved using geometric multigrid solver for the combined Stokes and elasticity operators. We use a rediscretization approach for standard finite difference approximations to the divergence, gradient, and viscous stress. In contrast, coarse grid versions of the Eulerian elasticity operator are constructed via a Galerkin approach. The implicit IB method is tested for a pulse duplicator cardiac device system that consists of both rigid mountings and elastic membrane.

  20. Job strain (demands and control model) as a predictor of cardiovascular risk factors among petrochemical personnel

    PubMed Central

    Habibi, Ehsanollah; Poorabdian, Siamak; Shakerian, Mahnaz

    2015-01-01

    Background: One of the practical models for the assessment of stressful working conditions due to job strain is job demand and control model, which explains how physical and psychological adverse consequences, including cardiovascular risk factors can be established due to high work demands (the amount of workload, in addition to time limitations to complete that work) and low control of the worker on his/her work (lack of decision making) in the workplace. The aim of this study was to investigate how certain cardiovascular risk factors (including body mass index [BMI], heart rate, blood pressure, cholesterol and smoking) and the job demand and job control are related to each other. Materials and Methods: This prospective cohort study was conducted on 500 workers of the petrochemical industry in south of Iran, 2009. The study population was selected using simple random statistical method. They completed job demand and control questionnaire. The cardiovascular risk factors data was extracted from the workers hygiene profiles. Chi-square (χ2) test and hypothesis test (η) were used to assess the possible relationship between different quantified variables, individual demographic and cardiovascular risk factors. Results: The results of this study revealed that a significant relationship can be found between job demand control model and cardiovascular risk factors. Chi-square test result for the heart rate showed the highest (χ2 = 145.078) relationship, the corresponding results for smoking and BMI were χ2 = 85.652 and χ2 = 30.941, respectively. Subsequently, hypothesis testing results for cholesterol and hypertension was 0.469 and 0.684, respectively. Discussion: Job strain is likely to be associated with an increased risk of cardiovascular risk factors among male staff in a petrochemical company in Iran. The parameters illustrated in the Job demands and control model can act as acceptable predictors for the probability of job stress occurrence followed by showing

  1. Implementation strategies of Systems Medicine in clinical research and home care for cardiovascular disease patients.

    PubMed

    Montecucco, Fabrizio; Carbone, Federico; Dini, Frank Lloyd; Fiuza, Manuela; Pinto, Fausto J; Martelli, Antonietta; Palombo, Domenico; Sambuceti, Gianmario; Mach, François; De Caterina, Raffaele

    2014-11-01

    Insights from the "-omics" science have recently emphasized the need to implement an overall strategy in medical research. Here, the development of Systems Medicine has been indicated as a potential tool for clinical translation of basic research discoveries. Systems Medicine also gives the opportunity of improving different steps in medical practice, from diagnosis to healthcare management, including clinical research. The development of Systems Medicine is still hampered however by several challenges, the main one being the development of computational tools adequate to record, analyze and share a large amount of disparate data. In addition, available informatics tools appear not yet fully suitable for the challenge because they are not standardized, not universally available, or with ethical/legal concerns. Cardiovascular diseases (CVD) are a very promising area for translating Systems Medicine into clinical practice. By developing clinically applied technologies, the collection and analysis of data may improve CV risk stratification and prediction. Standardized models for data recording and analysis can also greatly broaden data exchange, thus promoting a uniform management of CVD patients also useful for clinical research. This advance however requires a great organizational effort by both physicians and health institutions, as well as the overcoming of ethical problems. This narrative review aims at providing an update on the state-of-art knowledge in the area of Systems Medicine as applied to CVD, focusing on current critical issues, providing a road map for its practical implementation.

  2. P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease.

    PubMed

    Ralevic, Vera

    2015-01-01

    This review considers the expression and roles of P2X receptors in the cardiovascular system in health and disease and their potential as therapeutic targets. P2X receptors are ligand gated ion channels which are activated by the endogenous ligand ATP. They are formed from the assembly of three P2X subunit proteins from the complement of seven (P2X1-7), which can associate to form homomeric or heteromeric P2X receptors. The P2X1 receptor is widely expressed in the cardiovascular system, being located in the heart, in the smooth muscle of the majority of blood vessels and in platelets. P2X1 receptors expressed in blood vessels can be activated by ATP coreleased with noradrenaline as a sympathetic neurotransmitter, leading to smooth muscle depolarisation and contraction. There is evidence that the purinergic component of sympathetic neurotransmission is increased in hypertension, identifying P2X1 receptors as a possible therapeutic target in this disorder. P2X3 and P2X2/3 receptors are expressed on cardiac sympathetic neurones and may, through positive feedback of neuronal ATP at this prejunctional site, amplify sympathetic neurotransmission. Activation of P2X receptors expressed in the heart increases cardiac myocyte contractility, and an important role of the P2X4 receptor in this has been identified. Deletion of P2X4 receptors in the heart depresses contractile performance in models of heart failure, while overexpression of P2X4 receptors has been shown to be cardioprotective, thus P2X4 receptors may be therapeutic targets in the treatment of heart disease. P2X receptors have been identified on endothelial cells. Although immunoreactivity for all P2X1-7 receptor proteins has been shown on the endothelium, relatively little is known about their function, with the exception of the endothelial P2X4 receptor, which has been shown to mediate endothelium-dependent vasodilatation to ATP released during shear stress. The potential of P2X receptors as therapeutic targets

  3. Predictors of the first cardiovascular event in patients with systemic lupus erythematosus - a prospective cohort study

    PubMed Central

    2009-01-01

    Introduction Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients. Methods A total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression. Results Follow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE. Conclusions In addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation

  4. Introduction to the series on microRNAs in the cardiovascular system.

    PubMed

    van Rooij, Eva

    2012-02-01

    Until recently, microRNAs (miRNAs) were considered to be relatively small players in biological systems by having a balancing function through moderate effects on gene expression levels. However, it has become appreciated that miRNAs are actually much more relevant during both development and disease, which is underscored by the attention they have been receiving. The goal of this thematic review series is to highlight current knowledge of miRNA function during cardiovascular development, their dysregulation under disease conditions and the disease modifying functions they have been shown to exert in the cardiovascular system. These reviews, in addition to discussing the recent advancements in using miRNAs as circulating biomarkers or therapeutic modalities, will hopefully be able to provide a strong basis for future research to further expand our insights into miRNA function in cardiovascular biology.

  5. Iron, oxidative stress, and redox signaling in the cardiovascular system.

    PubMed

    Gudjoncik, Aurélie; Guenancia, Charles; Zeller, Marianne; Cottin, Yves; Vergely, Catherine; Rochette, Luc

    2014-08-01

    The redox state of the cell is predominantly dependent on an iron redox couple and is maintained within strict physiological limits. Iron is an essential metal for hemoglobin synthesis in erythrocytes, for oxidation-reduction reactions, and for cellular proliferation. The maintenance of stable iron concentrations requires the coordinated regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. The absorption of dietary iron, which is present in heme or nonheme form, is carried out by mature villus enterocytes of the duodenum and proximal jejunum. Multiple physiological processes are involved in maintaining iron homeostasis. These include its storage at the intracellular and extracellular level. Control of iron balance in the whole organism requires communication between sites of uptake, utilization, and storage. Key protein transporters and the molecules that regulate their activities have been identified. In this field, ferritins and hepcidin are the major regulator proteins. A variety of transcription factors may be activated depending on the level of oxidative stress, leading to the expression of different genes. Major preclinical and clinical trials have shown advances in iron-chelation therapy for the treatment of iron-overload disease as well as cardiovascular and chronic inflammatory diseases.

  6. Iron, oxidative stress, and redox signaling in the cardiovascular system.

    PubMed

    Gudjoncik, Aurélie; Guenancia, Charles; Zeller, Marianne; Cottin, Yves; Vergely, Catherine; Rochette, Luc

    2014-08-01

    The redox state of the cell is predominantly dependent on an iron redox couple and is maintained within strict physiological limits. Iron is an essential metal for hemoglobin synthesis in erythrocytes, for oxidation-reduction reactions, and for cellular proliferation. The maintenance of stable iron concentrations requires the coordinated regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. The absorption of dietary iron, which is present in heme or nonheme form, is carried out by mature villus enterocytes of the duodenum and proximal jejunum. Multiple physiological processes are involved in maintaining iron homeostasis. These include its storage at the intracellular and extracellular level. Control of iron balance in the whole organism requires communication between sites of uptake, utilization, and storage. Key protein transporters and the molecules that regulate their activities have been identified. In this field, ferritins and hepcidin are the major regulator proteins. A variety of transcription factors may be activated depending on the level of oxidative stress, leading to the expression of different genes. Major preclinical and clinical trials have shown advances in iron-chelation therapy for the treatment of iron-overload disease as well as cardiovascular and chronic inflammatory diseases. PMID:24888568

  7. Cardiovascular physiology in space flight

    NASA Technical Reports Server (NTRS)

    Charles, John B.; Bungo, Michael W.

    1991-01-01

    The effects of space flight on the cardiovascular system have been studied since the first manned flights. In several instances, the results from these investigations have directly contradicted the predictions based on established models. Results suggest associations between space flight's effects on other organ systems and those on the cardiovascular system. Such findings provide new insights into normal human physiology. They must also be considered when planning for the safety and efficiency of space flight crewmembers.

  8. Estrogen receptor β actions in the female cardiovascular system: A systematic review of animal and human studies.

    PubMed

    Muka, Taulant; Vargas, Kris G; Jaspers, Loes; Wen, Ke-xin; Dhana, Klodian; Vitezova, Anna; Nano, Jana; Brahimaj, Adela; Colpani, Veronica; Bano, Arjola; Kraja, Bledar; Zaciragic, Asija; Bramer, Wichor M; van Dijk, Gaby M; Kavousi, Maryam; Franco, Oscar H

    2016-04-01

    Five medical databases were searched for studies that assessed the role of ERβ in the female cardiovascular system and the influence of age and menopause on ERβ functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERβ signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERβ signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERβ may be vessel specific and may differ by age and menopause status. ERβ seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERβ-ligands might contribute to cardiovascular disease prevention.

  9. Estrogen receptor β actions in the female cardiovascular system: A systematic review of animal and human studies.

    PubMed

    Muka, Taulant; Vargas, Kris G; Jaspers, Loes; Wen, Ke-xin; Dhana, Klodian; Vitezova, Anna; Nano, Jana; Brahimaj, Adela; Colpani, Veronica; Bano, Arjola; Kraja, Bledar; Zaciragic, Asija; Bramer, Wichor M; van Dijk, Gaby M; Kavousi, Maryam; Franco, Oscar H

    2016-04-01

    Five medical databases were searched for studies that assessed the role of ERβ in the female cardiovascular system and the influence of age and menopause on ERβ functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERβ signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERβ signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERβ may be vessel specific and may differ by age and menopause status. ERβ seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERβ-ligands might contribute to cardiovascular disease prevention. PMID:26921926

  10. Klinefelter syndrome, cardiovascular system, and thromboembolic disease: review of literature and clinical perspectives.

    PubMed

    Salzano, Andrea; Arcopinto, Michele; Marra, Alberto M; Bobbio, Emanuele; Esposito, Daniela; Accardo, Giacomo; Giallauria, Francesco; Bossone, Eduardo; Vigorito, Carlo; Lenzi, Andrea; Pasquali, Daniela; Isidori, Andrea M; Cittadini, Antonio

    2016-07-01

    Klinefelter syndrome (KS) is the most frequently occurring sex chromosomal aberration in males, with an incidence of about 1 in 500-700 newborns. Data acquired from large registry-based studies revealed an increase in mortality rates among KS patients when compared with mortality rates among the general population. Among all causes of death, metabolic, cardiovascular, and hemostatic complication seem to play a pivotal role. KS is associated, as are other chromosomal pathologies and genetic diseases, with cardiac congenital anomalies that contribute to the increase in mortality. The aim of the current study was to systematically review the relationships between KS and the cardiovascular system and hemostatic balance. In summary, patients with KS display an increased cardiovascular risk profile, characterized by increased prevalence of metabolic abnormalities including Diabetes mellitus (DM), dyslipidemia, and alterations in biomarkers of cardiovascular disease. KS does not, however, appear to be associated with arterial hypertension. Moreover, KS patients are characterized by subclinical abnormalities in left ventricular (LV) systolic and diastolic function and endothelial function, which, when associated with chronotropic incompetence may led to reduced cardiopulmonary performance. KS patients appear to be at a higher risk for cardiovascular disease, attributing to an increased risk of thromboembolic events with a high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism with higher risk of deep venous thrombosis or pulmonary embolism. It appears that cardiovascular involvement in KS is mainly due to chromosomal abnormalities rather than solely on low serum testosterone levels. On the basis of evidence acquisition and authors' own experience, a flowchart addressing the management of cardiovascular function and prognosis of KS patients has been developed for clinical use.

  11. Variability in Ozone-Induced Pulmonary Injury and Inflammation in Healthy and Cardiovascular Compromised Rat Models

    EPA Science Inventory

    The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure depe...

  12. Role Models and the Psychological Characteristics That Buffer Low-Socioeconomic-Status Youth from Cardiovascular Risk

    ERIC Educational Resources Information Center

    Chen, Edith; Lee, William K.; Cavey, Lisa; Ho, Amanda

    2013-01-01

    Little is understood about why some youth from low-socioeconomic-status (SES) environments exhibit good health despite adversity. This study tested whether role models and "shift-and-persist" approaches (reframing stressors more benignly while persisting with future optimism) protect low-SES youth from cardiovascular risk. A total of 163…

  13. Strain Differences in Antioxidants in Rat Models of Cardiovascular Disease Exposed to Ozone

    EPA Science Inventory

    We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to 03 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH ...

  14. Health system challenges of cardiovascular disease and diabetes in four Eastern Mediterranean countries.

    PubMed

    Phillimore, Peter; Zaman, Shahaduz; Ahmad, Balsam; Shoaibi, Azza; Khatib, Rasha; Khatib, Rana; Husseini, Abdullatif; Fouad, Fouad; Elias, Madonna; Maziak, Wasim; Tlili, Faten; Tinsa, Francine; Ben Romdhane, Habiba; Kılıç, Bülent; Kalaça, Sibel; Ünal, Belgin; Critchley, Julia

    2013-01-01

    This paper presents evidence from research into health system challenges of cardiovascular disease (CVD) and diabetes in four Eastern Mediterranean countries: the occupied Palestinian territory, Syria, Tunisia and Turkey. We address two questions. How has the health system in each country been conceptualised and organised to manage the provision of care for those with CVD or diabetes? And what were key concerns about the institutional ability to address this challenge? Research took place from 2009 to 2010, shortly before the political upheavals in the region, and notably in Syria and Tunisia. Data collection involved a review of key documents, interviews with key informants and brief data collection in clinics. In analysing the data, we adopted the analytical schema proposed by Walt and Gilson, distinguishing content, actors, context and process. Key findings from each country highlighted concerns about fragmented provision and a lack of coordination. Specific concerns included: the lack of patient referral pathways, functioning health information systems and investment in staff. Regarding issues underlying these 'visible' problems in managing these diseases, we highlight implications of the wider systemic pressure for reform of health-sector finance in each country, based on neoliberal models.

  15. The insular cortex and cardiovascular system: a new insight into the brain-heart axis.

    PubMed

    Nagai, Michiaki; Hoshide, Satoshi; Kario, Kazuomi

    2010-01-01

    The classical literature on neurocardiology has focused mainly on the subcortical regions of the central autonomic nervous system. However, recent studies have supported the notion that the cardiovascular system is regulated by cortical modulation. Modern neuroimaging data, including positron emission tomography and functional magnetic resonance imaging, have revealed that a network consisting of the insular cortex, anterior cingulate gyrus, and amygdala plays a crucial role in the regulation of central autonomic nervous system. Because the insular cortex is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease. The insular cortex damage has been associated with arrhythmia, diurnal blood pressure variation disruption (eg, a non-dipper or riser pattern), myocardial injury, and sleep disordered breathing, as well as higher plasma levels of brain natriuretic peptide, catecholamine, and glucose. This review article focuses on the role of the insular cortex as a mediator for the cardiovascular system and summarizes current knowledge on the relationships between cerebrovascular disease and cardiovascular system dysregulation. Finally, a hypothesis of the neural network involved in cortical cardiovascular modulation, including modulation of the insular cortex, is provided. PMID:20655502

  16. Interactions between immune, stress-related hormonal and cardiovascular systems following strenuous physical exercise.

    PubMed

    Menicucci, Danilo; Piarulli, Andrea; Mastorci, Francesca; Sebastiani, Laura; Laurino, Marco; Garbella, Erika; Castagnini, Cinzia; Pellegrini, Silvia; Lubrano, Valter; Bernardi, Giulio; Metelli, Maria; Bedini, Remo; L'abbate, Antonio; Pingitore, Alessandro; Gemignani, Angelo

    2013-09-01

    Physical exercise represents a eustress condition that promotes rapid coordinated adjustments in the immune, stress-related hormonal and cardiovascular systems, for maintaining homeostasis in response to increased metabolic demands. Compared to the tight multisystem coordination during exercise, evidence of between-systems cross talk in the early post exercise is still lacking. This study was aimed at identifying possible interactions between multiple systems following strenuous physical exercise (Ironman race) performed by twenty well-trained triathletes. Cardiac hemodynamics, left ventricle systolic and diastolic function and heart rate variability were measured along with plasma concentrations of immune messengers (cytokines and C-reactive protein) and stress-related hormones (catecholamines and cortisol) both 24h before and within 20 min after the race. Observed changes in antiinflammatory pathways, stress-related hormones and cardiovascular function were in line with previous findings; moreover, correlating parameters' changes (post versus pre-race) highlighted a dependence of cardiovascular function on the post-race biohumoral milieu: in particular, individual post-race variations of heart rate and diastolic function were strongly correlated with individual variations of anti-inflammatory cytokines, while individual baroreflex sensitivity changes were linked to IL-8 increase. Multiple correlations between anti-inflammatory cytokines and catecholamines were also found according with the autonomic regulation of immune function. Observed post-race cytokine and hormone levels were presumptively representative of the increases reached at the effort end while the cardiovascular parameters after the race were measured during the cardiovascular recovery; thus, results suggest that sustained strenuous exercise produced a stereotyped cardiovascular early recovery, whose speed could be conditioned by the immune and stress-related hormonal milieu.

  17. Influence of mitochondrion-toxic agents on the cardiovascular system.

    PubMed

    Finsterer, Josef; Ohnsorge, Peter

    2013-12-01

    Cardiovascular disease may be induced or worsened by mitochondrion-toxic agents. Mitochondrion-toxic agents may be classified as those with or without a clinical effect, those which induce cardiac disease only in humans or animals or both, as prescribed drugs, illicit drugs, exotoxins, or nutritiants, as those which affect the heart exclusively or also other organs, as those which are effective only in patients with a mitochondrial disorder or cardiac disease or also in healthy subjects, or as solid, liquid, or volatile agents. In humans, cardiotoxic agents due to mitochondrial dysfunction include anthracyclines (particularly doxorubicin), mitoxantrone, cyclophosphamide, cisplatin, fluorouracil, imatinib, bortezomib, trastuzumab, arsenic trioxide, cyclosporine-A, zidovudine, lamotrigine, glycosides, lidocain, isoproterenol, nitroprusside, pivalic acid, alcohol, cocaine, pesticides, cadmium, mycotoxins, cyanotoxins, meat meal, or carbon monoxide. Even more agents exhibit cardiac abnormalities due to mitochondrion-toxicity only in animals or tissue cultures. The mitochondrion-toxic effect results from impairment of the respiratory chain, the oxidative phosphorylation, the Krebs cycle, or the β-oxidation, from decrease of the mitochondrion-membrane potential, from increased oxidative stress, reduced anti-oxidative capacity, or from induction of apoptosis. Cardiac abnormalities induced via these mechanisms include cardiomyopathy, myocarditis, coronary heart disease, arrhythmias, heart failure, or Takotsubo syndrome. Discontinuation of the cardiotoxic agent results in complete recovery in the majority of the cases. Antioxidants and nutritiants may be of additional help. Particularly coenzyme-Q, riboflavin, vitamin-E, vitamin-C, L-carnitine, vitamin-D, thiamin, folic acid, omega-3 fatty acids, and D-ribose may alleviate mitochondrial cardiotoxic effects.

  18. Systemic Hemodynamic Atherothrombotic Syndrome and Resonance Hypothesis of Blood Pressure Variability: Triggering Cardiovascular Events.

    PubMed

    Kario, Kazuomi

    2016-07-01

    Blood pressure (BP) exhibits different variabilities and surges with different time phases, from the shortest beat-by-beat to longest yearly changes. We hypothesized that the synergistic resonance of these BP variabilites generates an extraordinarily large dynamic surge in BP and triggers cardiovascular events (the resonance hypothesis). The power of pulses is transmitted to the peripheral sites without attenuation by the large arteries, in individuals with stiffened arteries. Thus, the effect of a BP surge on cardiovascular risk would be especially exaggerated in high-risk patients with vascular disease. Based on this concept, our group recently proposed a new theory of systemic hemodynamic atherothromboltic syndrome (SHATS), a vicious cycle of hemodynamic stress and vascular disease that advances organ damage and triggers cardiovascular disease. Clinical phenotypes of SHATS are large-artery atherothombotic diseases such as stroke, coronary artery disease, and aortic and pheripheral artery disease; small-artery diseases, and microcirculation-related disease such as vascular cognitive dysfunction, heart failure, and chronic kidney disease. The careful consideration of BP variability and vascular diseases such as SHATS, and the early detection and management of SHATS, will achieve more effective individualized cardiovascular protection. In the near future, information and communication technology-based 'anticipation medicine' predicted by the changes of individual BP values could be a promising approach to achieving zero cardiovascular events. PMID:27482253

  19. Systemic Hemodynamic Atherothrombotic Syndrome and Resonance Hypothesis of Blood Pressure Variability: Triggering Cardiovascular Events

    PubMed Central

    2016-01-01

    Blood pressure (BP) exhibits different variabilities and surges with different time phases, from the shortest beat-by-beat to longest yearly changes. We hypothesized that the synergistic resonance of these BP variabilites generates an extraordinarily large dynamic surge in BP and triggers cardiovascular events (the resonance hypothesis). The power of pulses is transmitted to the peripheral sites without attenuation by the large arteries, in individuals with stiffened arteries. Thus, the effect of a BP surge on cardiovascular risk would be especially exaggerated in high-risk patients with vascular disease. Based on this concept, our group recently proposed a new theory of systemic hemodynamic atherothromboltic syndrome (SHATS), a vicious cycle of hemodynamic stress and vascular disease that advances organ damage and triggers cardiovascular disease. Clinical phenotypes of SHATS are large-artery atherothombotic diseases such as stroke, coronary artery disease, and aortic and pheripheral artery disease; small-artery diseases, and microcirculation-related disease such as vascular cognitive dysfunction, heart failure, and chronic kidney disease. The careful consideration of BP variability and vascular diseases such as SHATS, and the early detection and management of SHATS, will achieve more effective individualized cardiovascular protection. In the near future, information and communication technology-based 'anticipation medicine' predicted by the changes of individual BP values could be a promising approach to achieving zero cardiovascular events. PMID:27482253

  20. Therapeutic targeting of two-pore-domain potassium (K(2P)) channels in the cardiovascular system.

    PubMed

    Wiedmann, Felix; Schmidt, Constanze; Lugenbiel, Patrick; Staudacher, Ingo; Rahm, Ann-Kathrin; Seyler, Claudia; Schweizer, Patrick A; Katus, Hugo A; Thomas, Dierk

    2016-05-01

    The improvement of treatment strategies in cardiovascular medicine is an ongoing process that requires constant optimization. The ability of a therapeutic intervention to prevent cardiovascular pathology largely depends on its capacity to suppress the underlying mechanisms. Attenuation or reversal of disease-specific pathways has emerged as a promising paradigm, providing a mechanistic rationale for patient-tailored therapy. Two-pore-domain K(+) (K(2P)) channels conduct outward K(+) currents that stabilize the resting membrane potential and facilitate action potential repolarization. K(2P) expression in the cardiovascular system and polymodal K2P current regulation suggest functional significance and potential therapeutic roles of the channels. Recent work has focused primarily on K(2P)1.1 [tandem of pore domains in a weak inwardly rectifying K(+) channel (TWIK)-1], K(2P)2.1 [TWIK-related K(+) channel (TREK)-1], and K(2P)3.1 [TWIK-related acid-sensitive K(+) channel (TASK)-1] channels and their role in heart and vessels. K(2P) currents have been implicated in atrial and ventricular arrhythmogenesis and in setting the vascular tone. Furthermore, the association of genetic alterations in K(2P)3.1 channels with atrial fibrillation, cardiac conduction disorders and pulmonary arterial hypertension demonstrates the relevance of the channels in cardiovascular disease. The function, regulation and clinical significance of cardiovascular K(2P) channels are summarized in the present review, and therapeutic options are emphasized.

  1. System identification of closed-loop cardiovascular control: effects of posture and autonomic blockade

    NASA Technical Reports Server (NTRS)

    Mullen, T. J.; Appel, M. L.; Mukkamala, R.; Mathias, J. M.; Cohen, R. J.

    1997-01-01

    We applied system identification to the analysis of fluctuations in heart rate (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize quantitatively the physiological mechanisms responsible for the couplings between these variables. We characterized two autonomically mediated coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the blood pressure wavelet generated with each cardiac contraction (circulatory mechanics) and the direct mechanical effects of respiration on blood pressure (ILV-->ABP)]. We evaluated the method in humans studied in the supine and standing postures under control conditions and under conditions of beta-sympathetic and parasympathetic pharmacological blockades. Combined beta-sympathetic and parasympathetic blockade abolished the autonomically mediated couplings while preserving the mechanically mediated coupling. Selective autonomic blockade and postural changes also altered the couplings in a manner consistent with known physiological mechanisms. System identification is an "inverse-modeling" technique that provides a means for creating a closed-loop model of cardiovascular regulation for an individual subject without altering the underlying physiological control mechanisms.

  2. Regulation of signal transduction by reactive oxygen species in the cardiovascular system.

    PubMed

    Brown, David I; Griendling, Kathy K

    2015-01-30

    Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species (ROS) in normal physiological signaling has been elucidated. Signaling pathways modulated by ROS are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here, we review the current literature on ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases, including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy, and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis, and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress.

  3. Small G proteins in the cardiovascular system: physiological and pathological aspects.

    PubMed

    Loirand, Gervaise; Sauzeau, Vincent; Pacaud, Pierre

    2013-10-01

    Small G proteins exist in eukaryotes from yeast to human and constitute the Ras superfamily comprising more than 100 members. This superfamily is structurally classified into five families: the Ras, Rho, Rab, Arf, and Ran families that control a wide variety of cell and biological functions through highly coordinated regulation processes. Increasing evidence has accumulated to identify small G proteins and their regulators as key players of the cardiovascular physiology that control a large panel of cardiac (heart rhythm, contraction, hypertrophy) and vascular functions (angiogenesis, vascular permeability, vasoconstriction). Indeed, basal Ras protein activity is required for homeostatic functions in physiological conditions, but sustained overactivation of Ras proteins or spatiotemporal dysregulation of Ras signaling pathways has pathological consequences in the cardiovascular system. The primary object of this review is to provide a comprehensive overview of the current progress in our understanding of the role of small G proteins and their regulators in cardiovascular physiology and pathologies.

  4. Regulation of signal transduction by reactive oxygen species in the cardiovascular system

    PubMed Central

    Brown, David I.; Griendling, Kathy K.

    2015-01-01

    Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species in normal physiological signaling has been elucidated. Signaling pathways modulated by reactive oxygen species (ROS) are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here we review the current literature regarding ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress. PMID:25634975

  5. Magnetic Resonance Cardiorhythmography as a Method of Study of Human's Cardiovascular System Condition

    NASA Astrophysics Data System (ADS)

    Protasov, E. A.; Ryzhkova, A. V.

    In this article a highly sensitive method for graphic recording of cardiogram by detecting the signal of nuclear magnetic resonance (NMR) of human finger has been developed and signals directly related to movement of blood ejected by the heart into the vessels have been studied. Changes in the behavior of signals depending on the condition of the cardiovascular system of person have been discovered.

  6. TEMPORAL ASSOCIATION BETWEEN PULMONARY AND SYSTEMIC EFFECTS OF PARTICULATE MATTER IN HEALTHY AND CARDIOVASCULAR COMPROMISED RATS

    EPA Science Inventory

    Temporal association between pulmonary and systemic effects of particulate matter in healthy and cardiovascular compromised rats

    Urmila P. Kodavanti, Mette C. Schladweiler, Allen D. Ledbetter, Russ Hauser*, David C. Christiani*, John McGee, Judy R. Richards, Daniel L. Co...

  7. Role of ventrolateral medulla in regulation of respiratory and cardiovascular systems.

    PubMed

    Millhorn, D E; Eldridge, F L

    1986-10-01

    It is now widely accepted that the ventrolateral aspect of the medulla oblongata (VLM) plays an important role in regulation of the respiratory and cardiovascular systems. The VLM has been implicated as being involved in a number of different physiological functions, including central chemoreception, integration of afferent inputs from certain sense organs to the respiratory and cardiovascular controllers, the source of excitatory input to preganglionic sympathetic neurons in the spinal cord, and location of synaptic relay between the higher brain defense areas and spinal cord sympathetic elements. In recent years there have been a number of important findings concerning both the anatomical substrate and neurophysiological characteristics of VLM neurons involved in regulation of the respiratory and cardiovascular systems. New anatomical findings show that neuronal networks located in the VLM send projections to and receive projections from brain stem nuclei that have traditionally been associated with respiratory and cardiovascular regulation. Nevertheless, there are still many important questions concerning the role of the VLM in control of these vital systems that have yet to be answered. For instance, are the same VLM neurons involved in control of both systems? Is the VLM the only site for central respiratory chemoreception? This review will endeavor to examine new findings and to reexamine some older findings concerning the VLM. PMID:3536832

  8. The role of the histaminergic system in the central cardiovascular regulation in haemorrhagic hypotension.

    PubMed

    Jochem, Jerzy; Kasperska-Zajac, Alicja

    2012-01-01

    The histaminergic system consists of neurons located in tuberomammillary nucleus of the posterior hypothalamus. It affects many functions of the central nervous system, including regulation of the brainstem cardiovascular center. In this paper, we present current review of the literature concerning the role of the histaminergic system in the cardiovascular regulation in haemorrhagic hypotension. Experimental studies demonstrate that in both, normotension and critical hemorrhagic hypotension, histamine, acting as a central neurotransmitter, evokes the pressor effect. Interestingly, increases in mean arterial pressure are significantly higher in hypovolaemic than in normovolaemic animals. Many lines of evidence support the hypothesis that in haemorrhagic shock, the histaminergic system is able to activate neural and humoral compensatory mechanisms involving the sympathetic nervous and renin-angiotensin systems, arginine vasopressin and proopiomelanocortin-derived peptides. We suggest that the histaminergic system could be a new target for treatment of hemorrhagic hypotension.

  9. A Follow-Up Study of Medical Students' Biomedical Understanding and Clinical Reasoning Concerning the Cardiovascular System

    ERIC Educational Resources Information Center

    Ahopelto, Ilona; Mikkila-Erdmann, Mirjamaija; Olkinuora, Erkki; Kaapa, Pekka

    2011-01-01

    Novice medical students usually hold initial conceptions concerning medical domains, such as the cardiovascular system, which may contradict scientific explanations and thus hinder learning. The purpose of this study was to investigate which kinds of biomedical representations medical students constructed of the central cardiovascular system in…

  10. Altered Nitric Oxide System in Cardiovascular and Renal Diseases

    PubMed Central

    Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

    2016-01-01

    Nitric oxide (NO) is synthesized by a family of NO synthases (NOS), including neuronal, inducible, and endothelial NOS (n/i/eNOS). NO-mediated effects can be beneficial or harmful depending on the specific risk factors affecting the disease. In hypertension, the vascular relaxation response to acetylcholine is blunted, and that to direct NO donors is maintained. A reduction in the activity of eNOS is mainly responsible for the elevation of blood pressure, and an abnormal expression of iNOS is likely to be related to the progression of vascular dysfunction. While eNOS/nNOS-derived NO is protective against the development of atherosclerosis, iNOS-derived NO may be proatherogenic. eNOS-derived NO may prevent the progression of myocardial infarction. Myocardial ischemia/reperfusion injury is significantly enhanced in eNOS-deficient animals. An important component of heart failure is the loss of coronary vascular eNOS activity. A pressure-overload may cause severer left ventricular hypertrophy and dysfunction in eNOS null mice than in wild-type mice. iNOS-derived NO has detrimental effects on the myocardium. NO plays an important role in regulating the angiogenesis and slowing the interstitial fibrosis of the obstructed kidney. In unilateral ureteral obstruction, the expression of eNOS was decreased in the affected kidney. In triply n/i/eNOS null mice, nephrogenic diabetes insipidus developed along with reduced aquaporin-2 abundance. In chronic kidney disease model of subtotal-nephrectomized rats, treatment with NOS inhibitors decreased systemic NO production and induced left ventricular systolic dysfunction (renocardiac syndrome). PMID:27231671

  11. Increasing blood flow to exercising muscle attenuates systemic cardiovascular responses during dynamic exercise in humans.

    PubMed

    Ichinose, Masashi; Ichinose-Kuwahara, Tomoko; Kondo, Narihiko; Nishiyasu, Takeshi

    2015-11-15

    Reducing blood flow to working muscles during dynamic exercise causes metabolites to accumulate within the active muscles and evokes systemic pressor responses. Whether a similar cardiovascular response is elicited with normal blood flow to exercising muscles during dynamic exercise remains unknown, however. To address that issue, we tested whether cardiovascular responses are affected by increases in blood flow to active muscles. Thirteen healthy subjects performed dynamic plantarflexion exercise for 12 min at 20%, 40%, and 60% of peak workload (EX20, EX40, and EX60) with their lower thigh enclosed in a negative pressure box. Under control conditions, the box pressure was the same as the ambient air pressure. Under negative pressure conditions, beginning 3 min after the start of the exercise, the box pressure was decreased by 20, 45, and then 70 mmHg in stepwise fashion with 3-min step durations. During EX20, the negative pressure had no effect on blood flow or the cardiovascular responses measured. However, application of negative pressure increased blood flow to the exercising leg during EX40 and EX60. This increase in blood flow had no significant effect on systemic cardiovascular responses during EX40, but it markedly attenuated the pressor responses otherwise seen during EX60. These results demonstrate that during mild exercise, normal blood flow to exercising muscle is not a factor eliciting cardiovascular responses, whereas it elicits an important pressor effect during moderate exercise. This suggests blood flow to exercising muscle is a major determinant of cardiovascular responses during dynamic exercise at higher than moderate intensity.

  12. Increasing blood flow to exercising muscle attenuates systemic cardiovascular responses during dynamic exercise in humans.

    PubMed

    Ichinose, Masashi; Ichinose-Kuwahara, Tomoko; Kondo, Narihiko; Nishiyasu, Takeshi

    2015-11-15

    Reducing blood flow to working muscles during dynamic exercise causes metabolites to accumulate within the active muscles and evokes systemic pressor responses. Whether a similar cardiovascular response is elicited with normal blood flow to exercising muscles during dynamic exercise remains unknown, however. To address that issue, we tested whether cardiovascular responses are affected by increases in blood flow to active muscles. Thirteen healthy subjects performed dynamic plantarflexion exercise for 12 min at 20%, 40%, and 60% of peak workload (EX20, EX40, and EX60) with their lower thigh enclosed in a negative pressure box. Under control conditions, the box pressure was the same as the ambient air pressure. Under negative pressure conditions, beginning 3 min after the start of the exercise, the box pressure was decreased by 20, 45, and then 70 mmHg in stepwise fashion with 3-min step durations. During EX20, the negative pressure had no effect on blood flow or the cardiovascular responses measured. However, application of negative pressure increased blood flow to the exercising leg during EX40 and EX60. This increase in blood flow had no significant effect on systemic cardiovascular responses during EX40, but it markedly attenuated the pressor responses otherwise seen during EX60. These results demonstrate that during mild exercise, normal blood flow to exercising muscle is not a factor eliciting cardiovascular responses, whereas it elicits an important pressor effect during moderate exercise. This suggests blood flow to exercising muscle is a major determinant of cardiovascular responses during dynamic exercise at higher than moderate intensity. PMID:26377556

  13. System-level multi-target drug discovery from natural products with applications to cardiovascular diseases.

    PubMed

    Zheng, Chunli; Wang, Jinan; Liu, Jianling; Pei, Mengjie; Huang, Chao; Wang, Yonghua

    2014-08-01

    The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug-target and target-target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.

  14. Space Weather and a State of Cardiovascular System of Human Being with a Weakened Adaptation System

    NASA Astrophysics Data System (ADS)

    Samsonov, S. N.

    As has been shown in [Samsonov et al., 2013] even at the considerable disturbances of space weather parameters a healthy human being did not undergo painful symptoms although measurements of objective physiological indices showed their changes. At the same time the state of health of people with the weakened adaptation system under the same conditions can considerably be deteriorated up to fatal outcome. The analysis of results of the project "Heliomed" and the number of calls for the emergency medical care (EMC) around Yakutsk as to cardiovascular diseases (CVD) has shown:- the total number of calls for EMC concerning myocardial infarction (MI) per year near the geomagnetic disturbance maximum (1992) exceeds the number of calls per year near the geomagnetic activity minimum (1998) by a factor of 1,5 and concerning to strokes - by a factor of 1,8.- maxima of MI are observed during spring and autumn periods coinciding with maxima of geophysical disturbance;- the coincidence of 30-32 daily periods in a power spectrum of MI with the same periods in power spectra of space weather parameters (speeds and density of the solar wind, interplanetary magnetic field, geophysical disturbance);- the existence of 3 maxima of the number of calls for EMC: a) at the moment of disturbance on the Sun; during a geophysical disturbance (in 2-4 days after a disturbance on the Sun); in 2-4 days after a geophysical disturbance;- the availability of coincidence of insignificant disturbances of space weather parameters with changes of the functional state of cardiovascular system of a human being with the weakened adaptation system and the occurrence of MI and strokes at considerable values of such disturbances is explained by a quasi-logarithmic dependence of the response of human being organisms to the environment disturbance intensity.

  15. A role for the central histaminergic system in the leptin-mediated increase in cardiovascular dynamics.

    PubMed

    Rao, Sumangala P; Dunbar, Joseph C

    2005-01-15

    The central nervous system (CNS) histaminergic neurons have been shown to regulate feeding behavior and are a target of leptin in the brain. The present study aimed to examine the involvement of the histaminergic system in the leptin-mediated regulation of cardiovascular dynamics. We investigated the cardiovascular responses to the CNS administration of histamine, leptin and alpha-melanocyte stimulating hormone (alpha-MSH) both in the presence and absence of the histamine H1 antagonist, chlorpheniramine. The intracerebroventricular (i.c.v.) administration of histamine resulted in an immediate increase in both mean arterial pressure (MAP) and heart rate (HR) and vasoconstricted the iliac, renal and superior mesenteric vessels. The i.c.v. pretreatment with chlorpheniramine attenuated the histamine-induced increase in MAP, HR and decreased vascular conductance. The i.c.v. administration of leptin increased MAP and HR and decreased vascular conductance. The i.c.v. pretreatment with chlorpheniramine decreased the leptin-induced increase in MAP and the leptin-mediated iliac vasoconstriction. The i.c.v. administration of alpha-MSH also increased MAP, HR and decreased vascular conductance. However, pretreatment with chlorpheniramine did not influence the central alpha-MSH-mediated increase in MAP, HR and decreased vascular conductance. These results indicate that the central histaminergic system mediated by H1 receptors have a role in the central signaling pathway and is involved in leptin's regulation of cardiovascular dynamics. It appears that leptin directly or indirectly stimulates histaminergic neurons that lead to increased cardiovascular activity.

  16. Cardiovascular cast model fabrication and casting effectiveness evaluation in fetus with severe congenital heart disease or normal heart.

    PubMed

    Wang, Yu; Cao, Hai-yan; Xie, Ming-xing; He, Lin; Han, Wei; Hong, Liu; Peng, Yuan; Hu, Yun-fei; Song, Ben-cai; Wang, Jing; Wang, Bin; Deng, Cheng

    2016-04-01

    To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease (control group) and 18 specimens with severe congenital heart disease (case group) from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels (including overall level, atrioventricular and great vascular system, left-sided and right-sided heart), as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group (P=0.027). Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group (P=0.046), while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.

  17. Adenosinergic regulation of the cardiovascular system in the red-eared slider Trachemys scripta.

    PubMed

    Joyce, William; Wang, Tobias

    2014-08-01

    Few studies have investigated adenosinergic regulation of the cardiovascular system in reptiles. The haemodynamic effect of a bolus intra-arterial adenosine injection (2.5 μM kg⁻¹) was investigated in nine anaesthetised red-eared sliders (Trachemys scripta). Adenosine caused a transient bradycardia, which was accompanied by systemic vasodilatation as evidenced by an increase in systemic flow and a decrease in systemic pressure. Meanwhile, pulmonary flow fell significantly. Both the bradycardia and increase in systemic conductance were significantly attenuated by theophylline (4 mg kg⁻¹), demonstrating an involvement of P₁ receptors. These results suggest that adenosine is likely to play a significant role in reptile cardiovascular physiology. In turtles specifically, adenosinergic regulation may be particularly relevant during periods of apnoea.

  18. A Reporting System for Non-Invasive Cardiovascular Investigations

    PubMed Central

    Covvey, H.D.; Van Horik, M.; Hum, J.; Sole, M.J.; Schwartz, L.; Rakowski, H.; Wigle, E.D.

    1978-01-01

    A computer-based system has been developed to support the collection, reporting and storage of data acquired during non-invasive cardiac investigations. Currently the system serves 1-D echocardiography and graded exercise testing. Optical mark forms are used to record information in computer-readable form. A terminal station consisting of a CRT terminal, an optical mark reader and a printer is used for input and output from a central minicomputer database management system. Even when the costs associated with database storage are included, the overall cost of the system compares favorably with the option of using typists to produce reports.

  19. Cardiovascular toxicity evaluation of silica nanoparticles in endothelial cells and zebrafish model.

    PubMed

    Duan, Junchao; Yu, Yongbo; Li, Yang; Yu, Yang; Sun, Zhiwei

    2013-07-01

    Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and as a result, nanotoxicity research is gaining attention. However, most investigators focus on the evaluation of overall toxicity instead of a certain organism system. In this regard, the evaluation of cardiovascular effects of silica nanoparticles was preformed in vitro and in vivo. It's worth noting that silica nanoparticles induced cytotoxicity as well as oxidative stress and apoptosis. ROS and apoptosis were considered as major factor to endothelial cells dysfunction, involved in several molecular mechanisms of cardiovascular diseases. In vivo study, mortality, malformation, heart rate and whole-embryo cellular death were measured in zebrafish embryos. Results showed that silica nanoparticles induced pericardia toxicity and caused bradycardia. We also examined the expression of cardiovascular-related proteins in embryos by western blot analysis. Silica nanoparticles inhibited the expression of p-VEGFR2 and p-ERK1/2 as well as the downregulation of MEF2C and NKX2.5, revealed that silica nanoparticles could inhibit the angiogenesis and disturb the heart formation and development. In summary, our results suggest that exposure to silica nanoparticles is a possible risk factor to cardiovascular system.

  20. Some peculiar effects of NO-synthase inhibition on the structure and function of cardiovascular system.

    PubMed

    Kristek, Frantisek

    2011-09-01

    Long-term increase of blood pressure represents one of the most important risk factors triggering many cardiovascular diseases, and via counter-regulatory mechanisms it is itself modulated by them. Adequate perfusion of the respective areas with nutrients requires appropriate production of vasodilatory and vasoconstrictory agents. Disharmony among them has an important impact on mechanical properties of the arteries, resulting in pathological alterations in the cardiovascular system. Defective production of the vasodilatory agent nitric oxide (NO) has a pronounced effect on this delicate balance and can evoke functional and structural changes in the cardiovascular system leading to hypertension. This review is focused mainly on changes in the cardiovascular system of newborn and adult Wistar rats after long-term administration of two different types of NO-synthase inhibitors: nonspecific inhibitor NG-nitro-L-arginine methylester and specific inhibitor of neuronal NO-synthase 7-nitroindazole. A possible supplementation of decreased endogenous NO production by NO donors is discussed. Particular attention is given to the complex interplay among blood pressure, arterial geometry, including arterial wall thickness, cross-sectional area, inner diameter, and individual components of the arterial wall, as extracellular matrix, endothelial and smooth muscle cell trophicity. Some methodological remarks for determination of the arterial geometry are also presented. Better understanding of the interrelationship among the factors involved can help in explaining more accurately differences in functional manifestations of vessels in various types of hypertension. The review indicates that the current concept of NO production, effect of NO deficiency, substitution of the missing NO in failing NO production in the cardiovascular system appears to be oversimplified.

  1. Sinapic Acid Prevents Hypertension and Cardiovascular Remodeling in Pharmacological Model of Nitric Oxide Inhibited Rats

    PubMed Central

    Silambarasan, Thangarasu; Manivannan, Jeganathan; Krishna Priya, Mani; Suganya, Natarajan; Chatterjee, Suvro; Raja, Boobalan

    2014-01-01

    Objectives Hypertensive heart disease is a constellation of abnormalities that includes cardiac fibrosis in response to elevated blood pressure, systolic and diastolic dysfunction. The present study was undertaken to examine the effect of sinapic acid on high blood pressure and cardiovascular remodeling. Methods An experimental hypertensive animal model was induced by L-NAME intake on rats. Sinapic acid (SA) was orally administered at a dose of 10, 20 and 40 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system and organ bath studies, respectively. Fibrotic remodeling of heart and aorta was assessed by histopathologic analyses. Oxidative stress was measured by biochemical assays. mRNA and protein expressions were assessed by RT-qPCR and western blot, respectively. In order to confirm the protective role of SA on endothelial cells through its antioxidant property, we have utilized the in vitro model of H2O2-induced oxidative stress in EA.hy926 endothelial cells. Results Rats with hypertension showed elevated blood pressure, declined myocardial performance associated with myocardial hypertrophy and fibrosis, diminished vascular response, nitric oxide (NO) metabolites level, elevated markers of oxidative stress (TBARS, LOOH), ACE activity, depleted antioxidant system (SOD, CAT, GPx, reduced GSH), aberrant expression of TGF-β, β-MHC, eNOS mRNAs and eNOS protein. Remarkably, SA attenuated high blood pressure, myocardial, vascular dysfunction, cardiac fibrosis, oxidative stress and ACE activity. Level of NO metabolites, antioxidant system, and altered gene expression were also repaired by SA treatment. Results of in vitro study showed that, SA protects endothelial cells from oxidative stress and enhance the production of NO in a concentration dependent manner. Conclusions Taken together, these results suggest that SA may have beneficial role in the

  2. Meeting report from the 2nd International Symposium on New Frontiers in Cardiovascular Research. Protecting the cardiovascular system from ischemia: between bench and bedside.

    PubMed

    Cabrera-Fuentes, Hector A; Alba-Alba, Corina; Aragones, Julian; Bernhagen, Jürgen; Boisvert, William A; Bøtker, Hans E; Cesarman-Maus, Gabriela; Fleming, Ingrid; Garcia-Dorado, David; Lecour, Sandrine; Liehn, Elisa; Marber, Michael S; Marina, Nephtali; Mayr, Manuel; Perez-Mendez, Oscar; Miura, Tetsuji; Ruiz-Meana, Marisol; Salinas-Estefanon, Eduardo M; Ong, Sang-Bing; Schnittler, Hans J; Sanchez-Vega, Jose T; Sumoza-Toledo, Adriana; Vogel, Carl-Wilhelm; Yarullina, Dina; Yellon, Derek M; Preissner, Klaus T; Hausenloy, Derek J

    2016-01-01

    Recent advances in basic cardiovascular research as well as their translation into the clinical situation were the focus at the last "New Frontiers in Cardiovascular Research meeting". Major topics included the characterization of new targets and procedures in cardioprotection, deciphering new players and inflammatory mechanisms in ischemic heart disease as well as uncovering microRNAs and other biomarkers as versatile and possibly causal factors in cardiovascular pathogenesis. Although a number of pathological situations such as ischemia-reperfusion injury or atherosclerosis can be simulated and manipulated in diverse animal models, also to challenge new drugs for intervention, patient studies are the ultimate litmus test to obtain unequivocal information about the validity of biomedical concepts and their application in the clinics. Thus, the open and bidirectional exchange between bench and bedside is crucial to advance the field of ischemic heart disease with a particular emphasis of understanding long-lasting approaches in cardioprotection.

  3. Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging

    PubMed Central

    Belliere, Julie; Martinez de Lizarrondo, Sara; Choudhury, Robin P.; Quenault, Aurélien; Le Béhot, Audrey; Delage, Christine; Chauveau, Dominique; Schanstra, Joost P.; Bascands, Jean-Loup; Vivien, Denis; Gauberti, Maxime

    2015-01-01

    Endothelial activation is a hallmark of cardiovascular diseases, acting either as a cause or a consequence of organ injury. To date, we lack suitable methods to measure endothelial activation in vivo. In the present study, we developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping in the vasculature of the main organs affected during cardiovascular diseases. In clinically relevant contexts in mice (including systemic inflammation, acute and chronic kidney diseases, diabetes mellitus and normal aging), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation of organ failure in the brain, kidney and heart with an exceptional sensitivity. In particular, we demonstrated that diabetes mellitus induces chronic endothelial cells activation in the kidney and heart. Moreover, aged mice presented activated endothelial cells in the kidneys and the cerebrovasculature. Interestingly, depending on the underlying condition, the temporospatial patterns of endothelial activation in the vascular beds of the cardiovascular system were different. These results demonstrate the feasibility of detecting silent endothelial activation occurring in conditions associated with high cardiovascular risk using molecular MRI. PMID:26379785

  4. Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography

    PubMed Central

    Boppart, Stephen A.; Tearney, Gary J.; Bouma, Brett E.; Southern, James F.; Brezinski, Mark E.; Fujimoto, James G.

    1997-01-01

    Studies investigating normal and abnormal cardiac development are frequently limited by an inability to assess cardiovascular function within the intact organism. In this work, optical coherence tomography (OCT), a new method of micron-scale, noninvasive imaging based on the measurement of backscattered infrared light, was introduced for the high resolution assessment of structure and function in the developing Xenopus laevis cardiovascular system. Microstructural details, such as ventricular size and wall positions, were delineated with OCT at 16-μm resolution and correlated with histology. Three-dimensional representation of the cardiovascular system also was achieved by repeated cross-sectional imaging at intervals of 25 μm. In addition to structural information, OCT provides high speed in vivo axial ranging and imaging, allowing quantitative dynamic activity, such as ventricular ejection fraction, to be assessed. The sensitivity of OCT for dynamic assessment was demonstrated with an inotropic agent that altered cardiac function and dimensions. Optical coherence tomography is an attractive new technology for assessing cardiovascular development because of its high resolution, its ability to image through nontransparent structures, and its inexpensive portable design. In vivo and in vitro imaging are performed at a resolution approaching that of histopathology without the need for animal killing. PMID:9113976

  5. Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging.

    PubMed

    Belliere, Julie; Martinez de Lizarrondo, Sara; Choudhury, Robin P; Quenault, Aurélien; Le Béhot, Audrey; Delage, Christine; Chauveau, Dominique; Schanstra, Joost P; Bascands, Jean-Loup; Vivien, Denis; Gauberti, Maxime

    2015-01-01

    Endothelial activation is a hallmark of cardiovascular diseases, acting either as a cause or a consequence of organ injury. To date, we lack suitable methods to measure endothelial activation in vivo. In the present study, we developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping in the vasculature of the main organs affected during cardiovascular diseases. In clinically relevant contexts in mice (including systemic inflammation, acute and chronic kidney diseases, diabetes mellitus and normal aging), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation of organ failure in the brain, kidney and heart with an exceptional sensitivity. In particular, we demonstrated that diabetes mellitus induces chronic endothelial cells activation in the kidney and heart. Moreover, aged mice presented activated endothelial cells in the kidneys and the cerebrovasculature. Interestingly, depending on the underlying condition, the temporospatial patterns of endothelial activation in the vascular beds of the cardiovascular system were different. These results demonstrate the feasibility of detecting silent endothelial activation occurring in conditions associated with high cardiovascular risk using molecular MRI.

  6. TRPM4 channels in the cardiovascular system: physiology, pathophysiology, and pharmacology.

    PubMed

    Abriel, Hugues; Syam, Ninda; Sottas, Valentin; Amarouch, Mohamed Yassine; Rougier, Jean-Sébastien

    2012-10-01

    The transient receptor potential channel (TRP) family comprises at least 28 genes in the human genome. These channels are widely expressed in many different tissues, including those of the cardiovascular system. The transient receptor potential channel melastatin 4 (TRPM4) is a Ca(2+)-activated non-specific cationic channel, which is impermeable to Ca(2+). TRPM4 is expressed in many cells of the cardiovascular system, such as cardiac cells of the conduction pathway and arterial and venous smooth muscle cells. This review article summarizes the recently described roles of TRPM4 in normal physiology and in various disease states. Genetic variants in the human gene TRPM4 have been linked to several cardiac conduction disorders. TRPM4 has also been proposed to play a crucial role in secondary hemorrhage following spinal cord injuries. Spontaneously hypertensive rats with cardiac hypertrophy were shown to over-express the cardiac TRPM4 channel. Recent studies suggest that TRPM4 plays an important role in cardiovascular physiology and disease, even if most of the molecular and cellular mechanisms have yet to be elucidated. We conclude this review article with a brief overview of the compounds that have been shown to either inhibit or activate TRPM4 under experimental conditions. Based on recent findings, the TRPM4 channel can be proposed as a future target for the pharmacological treatment of cardiovascular disorders, such as hypertension and cardiac arrhythmias.

  7. Energy Drinks and Their Impact on the Cardiovascular System: Potential Mechanisms.

    PubMed

    Grasser, Erik Konrad; Miles-Chan, Jennifer Lynn; Charrière, Nathalie; Loonam, Cathríona R; Dulloo, Abdul G; Montani, Jean-Pierre

    2016-09-01

    Globally, the popularity of energy drinks is steadily increasing. Scientific interest in their effects on cardiovascular and cerebrovascular systems in humans is also expanding and with it comes a growing number of case reports of adverse events associated with energy drinks. The vast majority of studies carried out in the general population report effects on blood pressure and heart rate. However, inconsistencies in the current literature render it difficult to draw firm conclusions with regard to the effects of energy drinks on cardiovascular and cerebrovascular variables. These inconsistencies are due, in part, to differences in methodologies, volume of drink ingested, and duration of postconsumption measurements, as well as subject variables during the test. Recent well-controlled, randomized crossover studies that used continuous beat-to-beat measurements provide evidence that cardiovascular responses to the ingestion of energy drinks are best explained by the actions of caffeine and sugar, with little influence from other ingredients. However, a role for other active constituents, such as taurine and glucuronolactone, cannot be ruled out. This article reviews the potentially adverse hemodynamic effects of energy drinks, particularly on blood pressure and heart rate, and discusses the mechanisms by which their active ingredients may interact to adversely affect the cardiovascular system. Research areas and gaps in the literature are discussed with particular reference to the use of energy drinks among high-risk individuals. PMID:27633110

  8. Energy Drinks and Their Impact on the Cardiovascular System: Potential Mechanisms.

    PubMed

    Grasser, Erik Konrad; Miles-Chan, Jennifer Lynn; Charrière, Nathalie; Loonam, Cathríona R; Dulloo, Abdul G; Montani, Jean-Pierre

    2016-09-01

    Globally, the popularity of energy drinks is steadily increasing. Scientific interest in their effects on cardiovascular and cerebrovascular systems in humans is also expanding and with it comes a growing number of case reports of adverse events associated with energy drinks. The vast majority of studies carried out in the general population report effects on blood pressure and heart rate. However, inconsistencies in the current literature render it difficult to draw firm conclusions with regard to the effects of energy drinks on cardiovascular and cerebrovascular variables. These inconsistencies are due, in part, to differences in methodologies, volume of drink ingested, and duration of postconsumption measurements, as well as subject variables during the test. Recent well-controlled, randomized crossover studies that used continuous beat-to-beat measurements provide evidence that cardiovascular responses to the ingestion of energy drinks are best explained by the actions of caffeine and sugar, with little influence from other ingredients. However, a role for other active constituents, such as taurine and glucuronolactone, cannot be ruled out. This article reviews the potentially adverse hemodynamic effects of energy drinks, particularly on blood pressure and heart rate, and discusses the mechanisms by which their active ingredients may interact to adversely affect the cardiovascular system. Research areas and gaps in the literature are discussed with particular reference to the use of energy drinks among high-risk individuals.

  9. The autonomic nervous system and cardiovascular disease: role of n-3 PUFAs.

    PubMed

    La Rovere, Maria Teresa; Christensen, Jeppe Hagstrup

    2015-08-01

    In the last decades, a large body of experimental and clinical evidence has been accumulated showing that cardiovascular diseases are often accompanied by an imbalance in the sympathetic-vagal outflow to the heart, resulting in a chronic adrenergic activation. The arterial baroreceptor system is a key component of mechanisms contributing to the neural regulation of the cardiovascular system. Several methods have been proposed to assess autonomic activity by analyzing heart rate and blood pressure changes either spontaneously occurring or following provocations. The autonomic nervous system has been regarded as one of the putative mechanisms involved into the beneficial effects of exposure to n-3 fatty acids observed in epidemiological studies. The aim of the present review is to provide an update on the clinical evidence proposed so far linking exposure to n-3 fatty acids to autonomic nervous system modulation.

  10. Cardiovascular and other dynamic systems in long-term space flight

    NASA Technical Reports Server (NTRS)

    Tipton, David A.

    1987-01-01

    The paper examines the physiology of the cardiovascular system, and to a lesser extent the endocrine, renal, and hematopoietic systems. The paper highlights the aspects of these areas that are most pertinent to space manufacturing, i.e., working in space. Areas covered include the physiological costs of working in microgravity and partial gravity (e.g., the moon or Mars), countermeasures to potentially adverse physiological adaptations, and problems associated with return to earth after long periods of weightlessness.

  11. Characterization of Coherent Structures in the Cardiovascular System

    PubMed Central

    Shadden, Shawn C.; Taylor, Charles A.

    2013-01-01

    Recent advances in blood flow modeling have provided highly resolved, four-dimensional data of fluid mechanics in large vessels. The motivation for such modeling is often to better understand how flow conditions relate to health and disease, or to evaluate interventions that affect, or are affected by, blood flow mechanics. Vessel geometry and the pulsatile pumping of blood leads to complex flow, which is often difficult to characterize. This article discusses a computational method to better characterize blood flow kinematics. In particular, we compute Lagrangian coherent structures (LCS) to study flow in large vessels. We demonstrate that LCS can be used to characterize flow stagnation, flow separation, partitioning of fluid to downstream vasculature, and mechanisms governing stirring and mixing in vascular models. This perspective allows valuable under-standing of flow features in large vessels beyond methods traditionally considered. PMID:18437573

  12. A plausible radiobiological model of cardiovascular disease at low or fractionated doses

    NASA Astrophysics Data System (ADS)

    Little, Mark; Vandoolaeghe, Wendy; Gola, Anna; Tzoulaki, Ioanna

    Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally-exposed groups receiving small daily radia-tion doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis, and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1) concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and can-cer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapo-lation would be appropriate for this endpoint.

  13. Cardiovascular Development and Survival During Gestation in the TS65DN Mouse Model for Down Syndrome

    PubMed Central

    Lorandeau, Candice G.; Hakkinen, Lauren A.; Moore, Clara S.

    2011-01-01

    The Ts65Dn mouse model for Down syndrome (DS) exhibits many phenotypes seen in human DS. Previous research has revealed a reduced rate of transmission of the T65Dn marker chromosome in neonates. To analyze potential fetal loss, litters from trisomic females at 10.5dpc through 14.5dpc were genotyped. No significant differences from the expected Mendelian ratio were found in transmission of T65Dn at any stage. Cardiovascular defects found in trisomic neonates are associated with formation of pharyngeal arch arteries. Vessel tracing was used to identify anomalies in 10.5dpc, 11.5dpc, and 13.5dpc embryos. Comparison of trisomic versus euploid embryos injected with India ink revealed delay and abnormality in cardiovascular development in trisomic embryos at each stage. Through the analysis of transmission rate and cardiovascular development in embryonic mice, we learn more about prenatal mortality and the origins of cardiac abnormality in the Ts65Dn mice to assist in understanding cardiovascular malformation associated with DS. PMID:21157920

  14. What Research Says: The Cardiovascular System: Children's Conceptions and Misconceptions.

    ERIC Educational Resources Information Center

    Arnaudin, Mary W.; Mintzes, Joel J.

    1986-01-01

    Reports findings of a study on children's perceptions and alternate conceptions about the human circulatory system. Summarizes the responses of fifth and eighth grade students on questions dealing with the heart and blood. Offers examples of hands-on activities and confrontation strategies that address common misconceptions on circulation. (ML)

  15. Method of propulsion of a ferromagnetic core in the cardiovascular system through magnetic gradients generated by an MRI system.

    PubMed

    Mathieu, Jean-Baptiste; Beaudoin, Gilles; Martel, Sylvain

    2006-02-01

    This paper reports the use of a magnetic resonance imaging (MRI) system to propel a ferromagnetic core. The concept was studied for future development of microdevices designed to perform minimally invasive interventions in remote sites accessible through the human cardiovascular system. A mathematical model is described taking into account various parameters such as the size of blood vessels, the velocities and viscous properties of blood, the magnetic properties of the materials, the characteristics of MRI gradient coils, as well as the ratio between the diameter of a spherical core and the diameter of the blood vessels. The concept of magnetic propulsion by MRI is validated experimentally by measuring the flow velocities that magnetized spheres (carbon steel 1010/1020) can withstand inside cylindrical tubes under the different magnetic forces created with a Siemens Magnetom Vision 1.5 T MRI system. The differences between the velocities predicted by the theoretical model and the experiments are approximately 10%. The results indicate that with the technology available today for gradient coils used in clinical MRI systems, it is possible to generate sufficient gradients to propel a ferromagnetic sphere in the larger sections of the arterial system. In other words, the results show that in the larger blood vessels where the diameter of the microdevices could be as large as a couple a millimeters, the few tens of mT/m of gradients required for displacement against the relatively high blood flow rate is well within the limits of clinical MRI systems. On the other hand, although propulsion of a ferromagnetic core with diameter of approximately 600 microm may be possible with existing clinical MRI systems, gradient amplitudes of several T/m would be required to propel a much smaller ferromagnetic core in small vessels such as capillaries and additional gradient coils would be required to upgrade existing MRI systems for operations at such a scale.

  16. The Applicability of Nonlinear Systems Dynamics Chaos Measures to Cardiovascular Physiology Variables

    NASA Technical Reports Server (NTRS)

    Hooker, John C.

    1991-01-01

    Three measures of nonlinear chaos (fractal dimension, Approximate Entropy (ApEn), and Lyapunov exponents) were studied as potential measures of cardiovascular condition. It is suggested that these measures have potential in the assessment of cardiovascular condition in environments of normal cardiovascular stress (normal gravity on the Earth surface), cardiovascular deconditioning (microgravity of space), and increased cardiovascular stress (lower body negative pressure (LBNP) treatments).

  17. Distribution of Urocortins and Corticotropin-Releasing Factor Receptors in the Cardiovascular System

    PubMed Central

    Takahashi, Kazuhiro

    2012-01-01

    Urocortins are human homologues of urotensin I, a fish corticotropin-releasing-factor- (CRF-) like peptide secreted from the urophysis. There are three urocortins: urocortin 1, urocortin 2, and urocortin 3 in mammals. We have shown that urocortin 1 and urocortin 3 are endogenously synthesized in the myocardial cells of human heart and may act on CRF type 2 receptor (CRFR2) expressed in the heart. Expression levels of urocortin 1 in the heart and plasma urocortin 1 levels are elevated in patients with heart failure. Recent studies have shown that urocortins have various biological actions in the cardiovascular system, such as a vasodilator action, a positive inotropic action, a cardioprotective action against ischemia/reperfusion injury, and suppressive actions against the renin angiotensin system and the sympathetic nervous system. Urocortins and CRFR2 may therefore be a potential therapeutic target for cardiovascular diseases, such as congestive heart failure, hypertension, and myocardial infarction. PMID:22675352

  18. Protein O-GlcNAcylation: a new signaling paradigm for the cardiovascular system.

    PubMed

    Laczy, Boglarka; Hill, Bradford G; Wang, Kai; Paterson, Andrew J; White, C Roger; Xing, Dongqi; Chen, Yiu-Fai; Darley-Usmar, Victor; Oparil, Suzanne; Chatham, John C

    2009-01-01

    The posttranslational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide beta-N-acetylglucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification. Protein O-GlcNAcylation is rapidly emerging as a key regulator of critical biological processes including nuclear transport, translation and transcription, signal transduction, cytoskeletal reorganization, proteasomal degradation, and apoptosis. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are both major hallmarks of diabetes mellitus and diabetes-related cardiovascular complications. Conversely, there is a growing body of data demonstrating that the acute activation of O-GlcNAc levels is an endogenous stress response designed to enhance cell survival. Reports on the effect of altered O-GlcNAc levels on the heart and cardiovascular system have been growing rapidly over the past few years and have implicated a role for O-GlcNAc in contributing to the adverse effects of diabetes on cardiovascular function as well as mediating the response to ischemic injury. Here, we summarize our present understanding of protein O-GlcNAcylation and its effect on the regulation of cardiovascular function. We examine the pathways regulating protein O-GlcNAcylation and discuss, in more detail, our understanding of the role of O-GlcNAc in both mediating the adverse effects of diabetes as well as its role in mediating cellular protective mechanisms in the cardiovascular system. In addition, we also explore the parallels between O-GlcNAc signaling and redox signaling, as an alternative paradigm for understanding the role of O-GlcNAcylation in regulating cell function.

  19. S-Nitrosothiols and the S-Nitrosoproteome of the Cardiovascular System

    PubMed Central

    Maron, Bradley A.; Tang, Shiow-Shih

    2013-01-01

    Abstract Significance: Since their discovery in the early 1990's, S-nitrosylated proteins have been increasingly recognized as important determinants of many biochemical processes. Specifically, S-nitrosothiols in the cardiovascular system exert many actions, including promoting vasodilation, inhibiting platelet aggregation, and regulating Ca2+ channel function that influences myocyte contractility and electrophysiologic stability. Recent Advances: Contemporary developments in liquid chromatography–mass spectrometry methods, the development of biotin- and His-tag switch assays, and the availability of cyanide dye-labeling for S-nitrosothiol detection in vitro have increased significantly the identification of a number of cardiovascular protein targets of S-nitrosylation in vivo. Critical Issues: Recent analyses using modern S-nitrosothiol detection techniques have revealed the mechanistic significance of S-nitrosylation to the pathophysiology of numerous cardiovascular diseases, including essential hypertension, pulmonary hypertension, ischemic heart disease, stroke, and congestive heart failure, among others. Future Directions: Despite enhanced insight into S-nitrosothiol biochemistry, translating these advances into beneficial pharmacotherapies for patients with cardiovascular diseases remains a primary as-yet unmet goal for investigators within the field. Antioxid. Redox Signal. 18, 270–287. PMID:22770551

  20. Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors

    PubMed Central

    Zeller, Carlos Borelli; Appenzeller, Simone

    2008-01-01

    Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). SLE is an autoimmune disease that may affect any organ. Premature coronary heart disease has emerged as a major cause of morbidity and mortality in SLE. In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as SLE and that of atherosclerosis. We will review traditional risk factors for CVD in SLE. We will also discuss the role of inflammation in atherosclerosis, as well as possible treatment strategies in these patients. PMID:19936286

  1. Systolic time interval data acquisition system. Specialized cardiovascular studies

    NASA Technical Reports Server (NTRS)

    Baker, J. T.

    1976-01-01

    The development of a data acquisition system for noninvasive measurement of systolic time intervals is described. R-R interval from the ECG determines instantaneous heart rate prior to the beat to be measured. Total electromechanical systole (Q-S2) is measured from the onset of the ECG Q-wave to the onset of the second heart sound (S2). Ejection time (ET or LVET) is measured from the onset of carotid upstroke to the incisure. Pre-ejection period (PEP) is computed by subtracting ET from Q-S2. PEP/ET ratio is computed directly.

  2. Advancing cardiovascular tissue engineering

    PubMed Central

    Truskey, George A.

    2016-01-01

    Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function. iPSC technology holds great promise, but robust methods are needed to further promote differentiation. Differentiation can be further enhanced with chemical, electrical, or mechanical stimuli. PMID:27303643

  3. Minimizing risk of nephrogenic systemic fibrosis in cardiovascular magnetic resonance.

    PubMed

    Reiter, Theresa; Ritter, Oliver; Prince, Martin R; Nordbeck, Peter; Wanner, Christoph; Nagel, Eike; Bauer, Wolfgang Rudolf

    2012-05-20

    Nephrogenic Systemic Fibrosis is a rare condition appearing only in patients with severe renal impairment or failure and presents with dermal lesions and involvement of internal organs. Although many cases are mild, an estimated 5% have a progressive debilitating course. To date, there is no known effective treatment thus stressing the necessity of ample prevention measures. An association with the use of Gadolinium based contrast agents (GBCA) makes Nephrogenic Systemic Fibrosis a potential side effect of contrast enhanced magnetic resonance imaging and offers the opportunity for prevention by limiting use of gadolinium based contrast agents in renal failure patients. In itself toxic, Gadolinium is embedded into chelates that allow its safe use as a contrast agent. One NSF theory is that Gadolinium chelates distribute into the extracellular fluid compartment and set Gadolinium ions free, depending on multiple factors among which the duration of chelates exposure is directly related to the renal function. Major medical societies both in Europe and in North America have developed guidelines for the usage of GBCA. Since the establishment of these guidelines and the increased general awareness of this condition, the occurrence of NSF has been nearly eliminated. Giving an overview over the current knowledge of NSF pathobiochemistry, pathogenesis and treatment options this review focuses on the guidelines of the European Medicines Agency, the European Society of Urogenital Radiology, the FDA and the American College of Radiology from 2008 up to 2011 and the transfer of this knowledge into every day practice.

  4. Minimizing Risk of Nephrogenic systemic fibrosis in Cardiovascular Magnetic Resonance

    PubMed Central

    2012-01-01

    Nephrogenic Systemic Fibrosis is a rare condition appearing only in patients with severe renal impairment or failure and presents with dermal lesions and involvement of internal organs. Although many cases are mild, an estimated 5 % have a progressive debilitating course. To date, there is no known effective treatment thus stressing the necessity of ample prevention measures. An association with the use of Gadolinium based contrast agents (GBCA) makes Nephrogenic Systemic Fibrosis a potential side effect of contrast enhanced magnetic resonance imaging and offers the opportunity for prevention by limiting use of gadolinium based contrast agents in renal failure patients. In itself toxic, Gadolinium is embedded into chelates that allow its safe use as a contrast agent. One NSF theory is that Gadolinium chelates distribute into the extracellular fluid compartment and set Gadolinium ions free, depending on multiple factors among which the duration of chelates exposure is directly related to the renal function. Major medical societies both in Europe and in North America have developed guidelines for the usage of GBCA. Since the establishment of these guidelines and the increased general awareness of this condition, the occurrence of NSF has been nearly eliminated. Giving an overview over the current knowledge of NSF pathobiochemistry, pathogenesis and treatment options this review focuses on the guidelines of the European Medicines Agency, the European Society of Urogenital Radiology, the FDA and the American College of Radiology from 2008 up to 2011 and the transfer of this knowledge into every day practice. PMID:22607376

  5. Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms.

    PubMed

    Ayers, Lisa; Nieuwland, Rienk; Kohler, Malcolm; Kraenkel, Nicolle; Ferry, Berne; Leeson, Paul

    2015-12-01

    Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies.

  6. Interaction of Hydrogen Sulfide with Nitric Oxide in the Cardiovascular System

    PubMed Central

    Nagpure, B. V.; Bian, Jin-Song

    2016-01-01

    Historically acknowledged as toxic gases, hydrogen sulfide (H2S) and nitric oxide (NO) are now recognized as the predominant members of a new family of signaling molecules, “gasotransmitters” in mammals. While H2S is biosynthesized by three constitutively expressed enzymes (CBS, CSE, and 3-MST) from L-cysteine and homocysteine, NO is generated endogenously from L-arginine by the action of various isoforms of NOS. Both gases have been transpired as the key and independent regulators of many physiological functions in mammalian cardiovascular, nervous, gastrointestinal, respiratory, and immune systems. The analogy between these two gasotransmitters is evident not only from their paracrine mode of signaling, but also from the identical and/or shared signaling transduction pathways. With the plethora of research in the pathophysiological role of gasotransmitters in various systems, the existence of interplay between these gases is being widely accepted. Chemical interaction between NO and H2S may generate nitroxyl (HNO), which plays a specific effective role within the cardiovascular system. In this review article, we have attempted to provide current understanding of the individual and interactive roles of H2S and NO signaling in mammalian cardiovascular system, focusing particularly on heart contractility, cardioprotection, vascular tone, angiogenesis, and oxidative stress. PMID:26640616

  7. Interaction of Hydrogen Sulfide with Nitric Oxide in the Cardiovascular System.

    PubMed

    Nagpure, B V; Bian, Jin-Song

    2016-01-01

    Historically acknowledged as toxic gases, hydrogen sulfide (H2S) and nitric oxide (NO) are now recognized as the predominant members of a new family of signaling molecules, "gasotransmitters" in mammals. While H2S is biosynthesized by three constitutively expressed enzymes (CBS, CSE, and 3-MST) from L-cysteine and homocysteine, NO is generated endogenously from L-arginine by the action of various isoforms of NOS. Both gases have been transpired as the key and independent regulators of many physiological functions in mammalian cardiovascular, nervous, gastrointestinal, respiratory, and immune systems. The analogy between these two gasotransmitters is evident not only from their paracrine mode of signaling, but also from the identical and/or shared signaling transduction pathways. With the plethora of research in the pathophysiological role of gasotransmitters in various systems, the existence of interplay between these gases is being widely accepted. Chemical interaction between NO and H2S may generate nitroxyl (HNO), which plays a specific effective role within the cardiovascular system. In this review article, we have attempted to provide current understanding of the individual and interactive roles of H2S and NO signaling in mammalian cardiovascular system, focusing particularly on heart contractility, cardioprotection, vascular tone, angiogenesis, and oxidative stress.

  8. Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

    PubMed Central

    Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton

    2012-01-01

    Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

  9. [CARDIOVASCULAR SYSTEM REACTIVITY IN PRENATALLY STRESSED RATS DURING THE LATE PERIOD OF ONTOGENESIS].

    PubMed

    Khudaverdyan, A; Saroyan, M; Khudaverdyan, D

    2015-09-01

    Systolic, diastolic blood pressure and heart rate were determined in normal rats and those exposed to influence of chronic stress during gestation. Data were registered six months after the birth and in 5, 24 and 48 hours after their immobilization. Analysis of the data showed that in rats undergoing stress, recorded systolic, diastolic blood pressure and heart rate both before and during all periods of immobilization were significantly below than in control group. It is concluded that the maximum limit of motor activity in the prenatally stressed rats accompanied by a decrease in the values ​​recorded performance of the cardiovascular system, which is reflecting the decrease in these animals reactivity of the cardiovascular system, and thus the adaptive capacity for action of stress factors.

  10. Neutrophil gelatinase-associated lipocalin is a novel mineralocorticoid target in the cardiovascular system.

    PubMed

    Latouche, Celine; El Moghrabi, Soumaya; Messaoudi, Smail; Nguyen Dinh Cat, Aurélie; Hernandez-Diaz, Ivan; Alvarez de la Rosa, Diego; Perret, Claudine; López Andrés, Natalia; Rossignol, Patrick; Zannad, Faiez; Farman, Nicolette; Jaisser, Frederic

    2012-05-01

    Mineralocorticoid receptor (MR) activation may be deleterious to the cardiovascular system, and MR antagonists improve morbidity and mortality of patients with heart failure. However, mineralocorticoid signaling in the heart remains largely unknown. Using a pan-genomic transcriptomic analysis, we identified neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) as a strongly induced gene in the heart of mice with conditional and targeted MR overexpression in cardiomyocytes (whereas induction was low in glucocorticoid receptor-overexpressing mice). NGAL mRNA levels were enhanced after hormonal stimulation by the MR ligand aldosterone in cultured cardiac cells and in the heart of wild-type mice. Mineralocorticoid pathological challenge induced by nephrectomy/aldosterone/salt treatment upregulated NGAL expression in the heart and aorta and its plasma levels. We show evidence for MR binding to an NGAL promoter, providing a mechanism for NGAL regulation. We propose that NGAL may be a marker of mineralocorticoid-dependent injury in the cardiovascular system in mice.

  11. The effects of sympathomimetics on the cardiovascular system of sheep.

    PubMed

    Pack, R J; Alley, M R; Davie, P S; Kealey, A S; Baxter, S; Allen, R; Dallimore, J A; Lapwood, K R; Crane, J; Burgess, C

    1994-10-01

    1. Sheep hearts have been used to study the effects of beta-adrenoceptor (beta-AR) agonists in order to better understand the effects of common asthma treatment drugs on heart rate, cardiac power output and cardiac pathology. Hearts have been examined both in vivo and in vitro. 2. In whole anaesthetized sheep, isoprenaline, fenoterol and salbutamol induced dose-dependent increases in heart rate. Hypokalaemia in response to salbutamol was accentuated in hypoxia. Many of these hearts showed significant myocardial lesions. Hypoxia alone caused no significant cardiac response. 3. As expected, the beta 1-AR agonist dobutamine caused dose-dependent increases in heart performance (heart rate and cardiac power output). Both responses were blocked by metoprolol and propranolol. The beta 2-AR agonist salbutamol caused dose-dependent increases in heart rate and although cardiac output increased, cardiac power output remained unchanged as a consequence of the fall in peripheral resistance. The heart rate changes were blocked by metoprolol. Importantly, propranolol blocked both the heart rate response and the fall in peripheral resistance. 4. Isolated atrial strips showed a right shift of their dose-response curve to isoprenaline in the presence of the highly selective beta 2-AR antagonist ICI 118,551 at concentrations above 1 x 10(-8) mol/L. 5. We conclude that the sheep heart shows many pharmacological characteristics of the human heart which makes it a good pharmacological model in addition to its being amenable to many common techniques available for humans.

  12. OCT imaging of the musculoskeletal and cardiovascular systems

    NASA Astrophysics Data System (ADS)

    Li, Xing D.; Stamper, Debra L.; Patel, Nirlep A.; Saunders, Kathleen; Plummer, Sam; Schenck, John; Rogowska, Ika; Fujimoto, James G.; Brezinski, Mark E.

    2002-07-01

    In this presentation, the application of optical coherence tomography (OCT) to the prevention of myocardial infarction and early identification of osteoarthritis is discussed. Myocardial infarction or a heart attack is the leading cause of death worldwide. It results from an acute loss of blood flow to a region of the heart resulting in death to that heart tissue. Most heart attacks are caused by small, thin walled lipid filled plaques which can not be detected by currently available imaging technologies. This paper outlines some of the advances demonstrating the potential of OCT for the identification of high risk plaque. Osteoarthritis is a major cause of mobility in the industrialized world. The hallmark of the disease is a degradation of articular cartilage. As new therapeutics have been shown to be effective in animal models, there effectiveness in humans remains unclear as there is no effective method for accurate monitoring changes in cartilage. In the second part of this manuscript, the effectiveness of OCT for monitoring articular cartilage is described.

  13. Nonlinear systems dynamics in cardiovascular physiology: The heart rate delay map and lower body negative pressure

    NASA Technical Reports Server (NTRS)

    Hooker, John C.

    1990-01-01

    A preliminary study of the applicability of nonlinear dynamic systems analysis techniques to low body negative pressure (LBNP) studies. In particular, the applicability of the heart rate delay map is investigated. It is suggested that the heart rate delay map has potential as a supplemental tool in the assessment of subject performance in LBNP tests and possibly in the determination of susceptibility to cardiovascular deconditioning with spaceflight.

  14. [Baseball during the growing years: repercussions on the cardiovascular system (echocardiographic evaluation)].

    PubMed

    Zuliani, U; Dei Cas, L; Manca, C

    1985-01-01

    The influence upon the cardiovascular system of a period (21 months) of physical training program for baseball was studied in 40 normal children (aged 8 to 10 years) in an experimental (20) and control (20) group. The echocardiographic changes observed at the end of the period proved to be substantially alike in both groups. The physiopathological involvements linked to the baseball training in the prepubescent age are discussed.

  15. In vitro cardiovascular system emulator (bioreactor) for the simulation of normal and diseased conditions with and without mechanical circulatory support.

    PubMed

    Ruiz, Paula; Rezaienia, Mohammad Amin; Rahideh, Akbar; Keeble, Thomas R; Rothman, Martin T; Korakianitis, Theodosios

    2013-06-01

    This article presents a new device designed to simulate in vitro flow rates, pressures, and other parameters representing normal and diseased conditions of the human cardiovascular system. Such devices are sometimes called bioreactors or "mock" simulator of cardiovascular loops (SCVLs) in literature. Most SCVLs simulate the systemic circulation only and have inherent limitations in studying the interaction of left and right sides of circulation. Those SCVLs that include both left and right sides of the circulation utilize header reservoirs simulating cycles with constant atrial pressures. The SCVL described in this article includes models for all four chambers of the heart, and the systemic and pulmonary circulation loops. Each heart chamber is accurately activated by a separate linear motor to simulate the suction and ejection stages, thus capturing important features in the perfusion waveforms. Four mechanical heart valves corresponding to mitral, pulmonary, tricuspid, and aortic are used to control the desired unidirectional flow. This SCVL can emulate different physiological and pathological conditions of the human cardiovascular system by controlling the different parameters of blood circulation through the vascular tree (mainly the resistance, compliance, and elastance of the heart chambers). In this study, four cases were simulated: healthy, congestive heart failure, left ventricular diastolic dysfunction conditions, and left ventricular dysfunction with the addition of a mechanical circulatory support (MCS) device. Hemodynamic parameters including resistance, pressure, and flow have been investigated at aortic sinus, carotid artery, and pulmonary artery, respectively. The addition of an MCS device resulted in a significant reduction in mean blood pressure and re-establishment of cardiac output. In all cases, the experimental results are compared with human physiology and numerical simulations. The results show the capability of the SCVL to replicate various

  16. Combined toxicity of silica nanoparticles and methylmercury on cardiovascular system in zebrafish (Danio rerio) embryos.

    PubMed

    Duan, Junchao; Hu, Hejing; Li, Qiuling; Jiang, Lizhen; Zou, Yang; Wang, Yapei; Sun, Zhiwei

    2016-06-01

    This study was to investigate the combined toxicity of silica nanoparticles (SiNPs) and methylmercury (MeHg) on cardiovascular system in zebrafish (Danio rerio) embryos. Ultraviolet absorption analysis showed that the co-exposure system had high absorption and stability. The dosages used in this study were based on the NOAEL level. Zebrafish embryos exposed to the co-exposure of SiNPs and MeHg did not show any cardiovascular malformation or atrioventricular block, but had an inhibition effect on bradycardia. Using o-Dianisidine for erythrocyte staining, the cardiac output of zebrafish embryos was decreased gradually in SiNPs, MeHg, co-exposure groups, respectively. Co-exposure of SiNPs and MeHg enhanced the vascular endothelial damage in Tg(fli-1:EGFP) transgenic zebrafish line. Moreover, the co-exposure significantly activated the oxidative stress and inflammatory response in neutrophils-specific Tg(mpo:GFP) transgenic zebrafish line. This study suggested that the combined toxic effects of SiNPs and MeHg on cardiovascular system had more severe toxicity than the single exposure alone.

  17. Chronic contamination of rats with 137 cesium radionuclide: impact on the cardiovascular system.

    PubMed

    Guéguen, Yann; Lestaevel, Philippe; Grandcolas, Line; Baudelin, Cédric; Grison, Stéphane; Jourdain, Jean-René; Gourmelon, Patrick; Souidi, Maâmar

    2008-03-01

    Cardiovascular system impairment has been observed in children and in liquidators exposed to the Chernobyl nuclear power plant accident. No experimental studies of animals have analyzed whether these disorders might be attributed to chronic ingestion of low levels of cesium 137 ((137)Cs). Biochemical, physiological, and molecular markers of the cardiovascular system were analyzed in rats exposed through drinking water to (137)Cs at a dose of 500 Bq kg(-1) (6500 Bq l(-1)). Plasma concentrations of CK and CK-MB were higher (+52%, P < 0.05) in contaminated rats. No histological alteration of the heart was observed, but gene expression was modified in the atria. Specifically, levels of ACE (angiotensin converting enzyme) and BNP (brain natriuretic peptide) gene expression increased significantly (P < 0.05). ECG analysis did not disclose any arrhythmia except ST- and RT-segment shortening (-9% and -11%, respectively, P < 0.05) in rats exposed to (137)Cs. Mean blood pressure decreased (-10%, P < 0.05), and its circadian rhythm disappeared. Overall, chronic contamination by an extreme environmental dose of (137)Cs for 3 months did not result in cardiac morphological changes, but the cardiovascular system impairments we observed could develop into more significant changes in sensitive animals or after longer contamination.

  18. Nnuclear uptake and retention of a synthetic progestin in the cardiovascular system of the baboon

    SciTech Connect

    Sheridan, P.J.; McGill, H.C. Jr.

    1984-06-01

    It has long been known that there is a sexual dimorphism in the incidence of coronary heart disease. This observation, together with more recent reports of increased cardiovascular disease associated with the use of oral contraceptives, led to a search for steroid receptors in the cardiovascular system. In this study the nuclear uptake and retention of a synthetic progestin was examined in the cardiovascular system of the baboons. Long term oophorectomized baboons were primed with estradiol benzoate for 3 days before the experiment (50 micrograms/kg, im) and adrenalectomized 2 days before the experiment. On the day of the experiment, the animals were injected under anesthesia with 2.5 micrograms/kg BW (/sup 3/H)ORG 2058 (16 alpha-ethyl-21-hydroxy-19-nor-(6,7-/sup 3/H)pregn-4-ene-3,20-dione) or with (/sup 3/H) ORG 2058 plus a 1000-fold excess of unlabeled progesterone (control). One hour after the injection, the animals were rapidly exsanguinated, and parts of the cardiovascular system were removed and processed for autoradiography. Localization of the synthetic progestin was found in nuclei of between 25-75% of all smooth muscle cells of the media of all arteries examined and to a lesser extent in the nuclei of the fibroblasts and others cells of the adventitia. Localization of the synthetic progestin in the heart was limited to approximately 1% of the myocardial cells and less than 5% of interstitial cell nuclei. The pattern of localization found differs from that for estrogen and androgen and suggests the possible presence of estrogen-independent progesterone receptors in smooth muscle cells of the media of the aorta and coronary arteries.

  19. Palm oil taxes and cardiovascular disease mortality in India: economic-epidemiologic model

    PubMed Central

    Babiarz, Kim S; Ebrahim, Shah; Vellakkal, Sukumar; Stuckler, David; Goldhaber-Fiebert, Jeremy D

    2013-01-01

    Objective To examine the potential effect of a tax on palm oil on hyperlipidemia and on mortality due to cardiovascular disease in India. Design Economic-epidemiologic model. Modeling methods A microsimulation model of mortality due to myocardial infarction and stroke among Indian populations was constructed, incorporating nationally representative data on systolic blood pressure, total cholesterol, tobacco smoking, diabetes, and cardiovascular event history, and stratified by age, sex, and urban/rural residence. Household expenditure data were used to estimate the change in consumption of palm oil following changes in oil price and the potential substitution of alternative oils that might occur after imposition of a tax. A 20% excise tax on palm oil purchases was simulated over the period 2014-23. Main outcome measures The model was used to project future mortality due to myocardial infarction and stroke, as well as the potential effect of a tax on food insecurity, accounting for the effect of increased food prices. Results A 20% tax on palm oil purchases would be expected to avert approximately 363 000 (95% confidence interval 247 000 to 479 000) deaths from myocardial infarctions and strokes over the period 2014-23 in India (1.3% reduction in cardiovascular deaths) if people do not substitute other oils for reduced palm oil consumption. Given estimates of substitution of palm oil with other oils following a 20% price increase for palm oil, the beneficial effects of increased polyunsaturated fat consumption would be expected to enhance the projected reduction in deaths to as much as 421 000 (256 000 to 586 000). The tax would be expected to benefit men more than women and urban populations more than rural populations, given differential consumption and cardiovascular risk. In a scenario incorporating the effect of taxation on overall food expenditures, the tax may increase food insecurity by <1%, resulting in 16 000 (95% confidence interval 12 000

  20. Modelling and disentangling physiological mechanisms: linear and nonlinear identification techniques for analysis of cardiovascular regulation.

    PubMed

    Batzel, Jerry; Baselli, Giuseppe; Mukkamala, Ramakrishna; Chon, Ki H

    2009-04-13

    Cardiovascular (CV) regulation is the result of a number of very complex control interactions. As computational power increases and new methods for collecting experimental data emerge, the potential for exploring these interactions through modelling increases as does the potential for clinical application of such models. Understanding these interactions requires the application of a diverse set of modelling techniques. Several recent mathematical modelling techniques will be described in this review paper. Starting from Granger's causality, the problem of closed-loop identification is recalled. The main aspects of linear identification and of grey-box modelling tailored to CV regulation analysis are summarized as well as basic concepts and trends for nonlinear extensions. Sensitivity analysis is presented and discussed as a potent tool for model validation and refinement. The integration of methods and models is fostered for a further physiological comprehension and for the development of more potent and robust diagnostic tools.

  1. Novel aspects of the roles of Rac1 GTPase in the cardiovascular system.

    PubMed

    Sawada, Naoki; Li, Yuxin; Liao, James K

    2010-04-01

    Rac1 GTPase is an established master regulator of cell motility through cortical actin re-organization and of reactive oxygen species generation through regulation of NADPH oxidase activity. Numerous molecular and cellular studies have implicated Rac1 in various cardiovascular pathologies: vascular smooth muscle proliferation, cardiomyocyte hypertrophy, and endothelial cell shape change. The physiological relevance of these in vitro findings, however, is just beginning to be reassessed with the newly developed, conditional mouse mutagenesis technology. Conditional gene targeting has also revealed unexpected, cell type-specific roles of Rac1. The aim of this review is to summarize the recent advance made in Rac1 research in the cardiovascular system, with special focus on its novel roles in the regulation of endothelial function, angiogenesis, and endothelium-mediated neuroprotection.

  2. Sensing pressure in the cardiovascular system: Gq-coupled mechanoreceptors and TRP channels.

    PubMed

    Sharif-Naeini, Reza; Folgering, Joost H A; Bichet, Delphine; Duprat, Fabrice; Delmas, Patrick; Patel, Amanda; Honoré, Eric

    2010-01-01

    Despite the central physiological importance of cardiovascular mechanotransduction, the molecular identities of the sensors and the signaling pathways have long remained elusive. Indeed, how pressure is transduced into cellular excitation has only recently started to emerge. In both arterial and cardiac myocytes, the diacylglycerol-sensitive canonical transient receptor potential (TRPC) subunits are proposed to underlie the stretch-activated depolarizing cation channels. An indirect mechanism of activation through a ligand-independent conformational switch of Gq-coupled receptors by mechanical stress is invoked. Such a mechanism involving the angiotensin type 1 receptor and TRPC6 is proposed to trigger the arterial myogenic response to intraluminal pressure. TRPC6 is also involved in load-induced cardiac hypertrophy. In this review, we will focus on the molecular basis of pressure sensing in the cardiovascular system and associated disease states.

  3. Physical activity ameliorates cardiovascular health in elderly subjects: the functional role of the β adrenergic system

    PubMed Central

    Santulli, Gaetano; Ciccarelli, Michele; Trimarco, Bruno; Iaccarino, Guido

    2013-01-01

    Aging is a complex process characterized by a gradual decline in organ functional reserves, which eventually reduces the ability to maintain homeostasis. An exquisite feature of elderly subjects, which constitute a growing proportion of the world population, is the high prevalence of cardiovascular disorders, which negatively affect both the quality of life and the life expectancy. It is widely acknowledged that physical activity represents one of the foremost interventions capable in reducing the health burden of cardiovascular disease. Interestingly, the benefits of moderate-intensity physical activity have been established both in young and elderly subjects. Herein we provide a systematic and updated appraisal of the literature exploring the pathophysiological mechanisms evoked by physical activity in the elderly, focusing on the functional role of the β adrenergic system. PMID:23964243

  4. Protective effects of red wine polyphenolic compounds on the cardiovascular system

    PubMed Central

    Zenebe, Woineshet; Pechánová, Olga; Bernátová, Iveta

    2001-01-01

    Phenolic phytochemicals are widely distributed in the plant kingdom. In terms of protective effects on organisms, the group of polyphenols is the most important. In various experiments, it has been shown that selected polyphenols, mainly flavonoids, confer protective effects on the cardiovascular system and have anti-cancer, antiviral and antiallergic properties. In coronary artery disease, the protective effects are due mainly to antithrombic, antioxidant, anti-ischemic and vasorelaxant properties of flavonoids. Flavonoids are low molecular weight compounds composed of a three-ring structure with various substitutions, which appear to be responsible for the antioxidant and antiproliferative properties. It has been hypothesized that the low incidence of coronary artery disease in the French population may be partially related to the pharmacological properties of polyphenolic compounds present in red wine. Many epidemiological studies have shown that regular flavonoid intake is associated with reduced risk of cardiovascular diseases. PMID:20428452

  5. Magnetic resonance imaging of the cardiovascular system: present state of the art and future potential

    SciTech Connect

    Jacobson, H.G.

    1988-01-08

    State-of-the-art magnetic resonance imaging (MRI) generates high-resolution images of the cardiovascular system. Conventional MRI techniques provide images in six to ten minutes per tomographic slice. New strategies have substantially improved the speed of imaging. The technology is relatively expensive, and its cost-effectiveness remains to be defined in relation to other effective, less expensive, and noninvasive technologies, such as echocardiography and nuclear medicine. The ultimate role of MRI will depend on several factors, including the development of specific applications such as (1) noninvasive angiography, especially of the coronary arteries;(2) noninvasive, high-resolution assessment of regional myocardial blood flow distribution (e.g., using paramagnetic contrast agents); (3) characterization of myocardial diseases using proton-relaxation property changes; and (4) evaluation of in vivo myocardial biochemistry. The three-dimensional imaging capability and the ability to image cardiovascular structures without contrast material give MRI a potential advantage over existing noninvasive diagnostic imaging techniques. This report analyzes current applications of MRI to the cardiovascular system and speculates on their future.

  6. Cardiovascular prevention model from Kenyan slums to migrants in the Netherlands.

    PubMed

    van de Vijver, Steven; Oti, Samuel; Moll van Charante, Eric; Allender, Steven; Foster, Charlie; Lange, Joep; Oldenburg, Brian; Kyobutungi, Catherine; Agyemang, Charles

    2015-01-01

    Cardiovascular diseases (CVD) are the main cause of morbidity and mortality worldwide. As prevention and treatment of CVD often requires active screening and lifelong follow up it is a challenge for health systems both in high-income and low and middle-income countries to deliver adequate care to those in need, with efficient use of resources.We developed a health service model for primary prevention of CVD suitable for implementation in the Nairobi slums, based on best practices from public health and the private sectors. The model consists of four key intervention elements focusing on increasing awareness, incentives for promoting access to screening and treatment, and improvement of long-term adherence to prescribed medications. More than 5,000 slum dwellers aged ≥35 years and above have been screened in the study resulting in more than 1000 diagnosed with hypertension and referred to the clinic.Some marginalized groups in high-income countries like African migrants in the Netherlands also have low rates of awareness, treatment and control of hypertension as the slum population in Nairobi. The parallel between both groups is that they have a combination of risky lifestyle, are prone to chronic diseases such as hypertension, have limited knowledge about hypertension and its complications, and a tendency to stay away from clinics partly due to cultural beliefs in alternative forms of treatment, and lack of trust in health providers. Based on these similarities it was suggested by several policymakers that the model from Nairobi can be applied to other vulnerable populations such as African migrants in high-income countries. The model can be contextualized to the local situation by adapting the key steps of the model to the local settings.The involvement and support of African communities' infrastructures and health care staff is crucial, and the most important enabler for successful implementation of the model in migrant communities in high-income countries

  7. Cardiovascular system

    MedlinePlus

    ... the network of arteries, veins, and capillaries that transport blood throughout the body. The average adult male has between 5 to 6 liters of blood or blood volume, while the average adult female has between 4 to 5 liters. The blood carries oxygen and essential nutrients to all of the living ...

  8. Simulation of a G-tolerance curve using the pulsatile cardiovascular model

    NASA Technical Reports Server (NTRS)

    Solomon, M.; Srinivasan, R.

    1985-01-01

    A computer simulation study, performed to assess the ability of the cardiovascular model to reproduce the G tolerance curve (G level versus tolerance time) is reported. A composite strength duration curve derived from experimental data obtained in human centrifugation studies was used for comparison. The effects of abolishing automomic control and of blood volume loss on G tolerance were also simulated. The results provide additional validation of the model. The need for the presence of autonomic reflexes even at low levels of G is pointed out. The low margin of safety with a loss of blood volume indicated by the simulation results underscores the necessity for protective measures during Shuttle reentry.

  9. Cardiovascular Effects of Shock and Trauma in Experimental Models. A Review

    PubMed Central

    Rocha-e-Silva, Mauricio

    2016-01-01

    Experimental models of human pathology are useful guides to new approaches towards improving clinical and surgical treatments. A systematic search through PubMed using the syntax (shock) AND (trauma) AND (animal model) AND (cardiovascular) AND ("2010/01/01"[PDat]: "2015/12/31"[PDat]) found 88 articles, which were reduced by manual inspection to 43 entries. These were divided into themes and each theme is subsequently narrated and discussed conjointly. Taken together, these articles indicate that valuable information has been developed over the past 5 years concerning endothelial stability, mesenteric lymph, vascular reactivity, traumatic injuries, burn and sepsis. A surviving interest in hypertonic saline resuscitation still exists. PMID:27074274

  10. [Study on mechanism of Salvia miltiorrhiza treating cardiovascular disease through auxiliary mechanism elucidation system for Chinese medicine].

    PubMed

    He, Shuai-bing; Zhang, Bai-xia; Wang, Hui-hui; Wang, Yun; Qiao, Yan-jiang

    2015-10-01

    Salvia miltiorrhiza is a traditional Chinese medicine (TCM) and is widely used as a clinically medication for its efficiency in treating cardiovascular disease. Due to TCM is a comprehensive system, the mechanism of S. miltiorrhiza treating cardiovascular disease through integrated multiple pathways are still unclear in some aspects. With the rapid progress of bioinformatics and systems biology, network pharmacology is considered as a promising approach toward reveal the underlying complex relationship between an herb and the disease. In order to discover the mechanism of S. miltiorrhiza treating cardiovascular disease systematically, we use the auxiliary mechanism elucidation system for Chinese medicine, built up a molecule interaction network on the active component targets of S. miltiorrhiza and the therapeutic targets of cardiovascular disease to offer an opportunity for deep understanding the mechanism of S. miltiorrhiza treating cardiovascular disease from the perspective of network pharmacology. The results showed that S. miltiorrhiza treating cardiovascular disease through ten pathways as follows: improve lipid metabolism, anti-inflammation, regulate blood pressure, negatively regulates blood coagulation factor and antithrombotic, regulate cell proliferation, anti-stress injury, promoting angiogenesis, inhibited apoptosis, adjust vascular systolic and diastolic, promoting wound repair. The results of this paper provide theoretical guidance for the development of new drugs to treat cardiovascular disease and the discovery of new drugs through component compatibility.

  11. [Study on mechanism of Salvia miltiorrhiza treating cardiovascular disease through auxiliary mechanism elucidation system for Chinese medicine].

    PubMed

    He, Shuai-bing; Zhang, Bai-xia; Wang, Hui-hui; Wang, Yun; Qiao, Yan-jiang

    2015-10-01

    Salvia miltiorrhiza is a traditional Chinese medicine (TCM) and is widely used as a clinically medication for its efficiency in treating cardiovascular disease. Due to TCM is a comprehensive system, the mechanism of S. miltiorrhiza treating cardiovascular disease through integrated multiple pathways are still unclear in some aspects. With the rapid progress of bioinformatics and systems biology, network pharmacology is considered as a promising approach toward reveal the underlying complex relationship between an herb and the disease. In order to discover the mechanism of S. miltiorrhiza treating cardiovascular disease systematically, we use the auxiliary mechanism elucidation system for Chinese medicine, built up a molecule interaction network on the active component targets of S. miltiorrhiza and the therapeutic targets of cardiovascular disease to offer an opportunity for deep understanding the mechanism of S. miltiorrhiza treating cardiovascular disease from the perspective of network pharmacology. The results showed that S. miltiorrhiza treating cardiovascular disease through ten pathways as follows: improve lipid metabolism, anti-inflammation, regulate blood pressure, negatively regulates blood coagulation factor and antithrombotic, regulate cell proliferation, anti-stress injury, promoting angiogenesis, inhibited apoptosis, adjust vascular systolic and diastolic, promoting wound repair. The results of this paper provide theoretical guidance for the development of new drugs to treat cardiovascular disease and the discovery of new drugs through component compatibility. PMID:26975090

  12. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

    PubMed Central

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L.; Potthoff, Sebastian A.; Kelm, Malte; Schurgers, Leon J.; Westenfeld, Ralf

    2015-01-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  13. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification.

    PubMed

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L; Potthoff, Sebastian A; Kelm, Malte; Schurgers, Leon J; Westenfeld, Ralf

    2015-08-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  14. Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

    PubMed

    Sharma, Arun; Wu, Joseph C; Wu, Sean M

    2013-12-24

    Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

  15. Ozone and cardiovascular injury.

    PubMed

    Srebot, Vera; Gianicolo, Emilio A L; Rainaldi, Giuseppe; Trivella, Maria Giovanna; Sicari, Rosa

    2009-06-24

    Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular diseases in urban communities. The potential detrimental effects are both acute and chronic having a strong impact on morbidity and mortality. The acute exposure to pollutants has been linked to adverse cardiovascular events such as myocardial infarction, heart failure and life-threatening arrhythmias. The long-terms effects are related to the lifetime risk of death from cardiac causes. The WHO estimates that air pollution is responsible for 3 million premature deaths each year. The evidence supporting these data is very strong nonetheless, epidemiologic and observational data have the main limitation of imprecise measurements. Moreover, the lack of clinical experimental models makes it difficult to demonstrate the individual risk. The other limitation is related to the lack of a clear mechanism explaining the effects of pollution on cardiovascular mortality. In the present review we will explore the epidemiological, clinical and experimental evidence of the effects of ozone on cardiovascular diseases. The pathophysiologic consequences of air pollutant exposures have been extensively investigated in pulmonary systems, and it is clear that some of the major components of air pollution (e.g. ozone and particulate matter) can initiate and exacerbate lung disease in humans 1. It is possible that pulmonary oxidant stress mediated by particulate matter and/or ozone (O3) exposure can result in downstream perturbations in the cardiovasculature, as the pulmonary and cardiovascular systems are intricately associated, and it is well documented that specific environmental toxins (such as tobacco smoke 2) introduced through the lungs can initiate and/or accelerate cardiovascular disease development. Indeed, several epidemiologic studies have proved that there is an association between PM and O3 and the increased incidence of cardiovascular morbidity and mortality 3. Most of the

  16. Investigating properties of the cardiovascular system using innovative analysis algorithms based on ensemble empirical mode decomposition.

    PubMed

    Yeh, Jia-Rong; Lin, Tzu-Yu; Chen, Yun; Sun, Wei-Zen; Abbod, Maysam F; Shieh, Jiann-Shing

    2012-01-01

    Cardiovascular system is known to be nonlinear and nonstationary. Traditional linear assessments algorithms of arterial stiffness and systemic resistance of cardiac system accompany the problem of nonstationary or inconvenience in practical applications. In this pilot study, two new assessment methods were developed: the first is ensemble empirical mode decomposition based reflection index (EEMD-RI) while the second is based on the phase shift between ECG and BP on cardiac oscillation. Both methods utilise the EEMD algorithm which is suitable for nonlinear and nonstationary systems. These methods were used to investigate the properties of arterial stiffness and systemic resistance for a pig's cardiovascular system via ECG and blood pressure (BP). This experiment simulated a sequence of continuous changes of blood pressure arising from steady condition to high blood pressure by clamping the artery and an inverse by relaxing the artery. As a hypothesis, the arterial stiffness and systemic resistance should vary with the blood pressure due to clamping and relaxing the artery. The results show statistically significant correlations between BP, EEMD-based RI, and the phase shift between ECG and BP on cardiac oscillation. The two assessments results demonstrate the merits of the EEMD for signal analysis.

  17. Significance of the development of a cardiovascular disease surveillance and reporting system in India.

    PubMed

    Coelho, Ken Russell

    2013-09-01

    Cardiovascular disease (CVD) is the single largest cause of global morbidity and mortality and is the leading cause of death in the Indian subcontinent projected to contribute to deaths expected to double by 2015. The social and economic impact of these staggering projections highlight the need for a centralized effort to monitor and evaluate behavioral and physiological risk factors for CVD. Limited evidence on existing surveillance systems suggest that the key to an effective monitoring and evaluation (M and E) program for CVD surveillance in India relies upon the World Health Organization's STEP-wise model. Key recommendations for the Ministry of Health include the development of a national CVD surveillance program with expertise and a quality-improvement mechanism to receive continuous input from similar surveillance programs in likeminded countries. Structure of the surveillance system would include; (1) the development of process measures for CVD risk factor' based surveillance M and E systems for early detection of CVD at the local-level, (2) the development of trigger based data reporting responsibilities to State-based monitoring teams including incentives for accuracy in data reporting and the use of data-driven evidence to target risk specific intervention and prevention on Central Government monitoring teams with reporting feedback to the State and local-levels and (3) the creation of health policy to require the use of data to target risk specific prevention for intervention and developing local technical capacity. Such a system would provide significant cost and social benefits, presenting an evidence based data driven cost-effective business case for scale-up and potential use in areas comprising similar demographics. Future research should focus on the inclusion of a systematic critique of the reported data for the challenges to surveillance systems in India and the examination of the effect of an incentivized reporting system on the states. Further

  18. Cardiovascular modeling in pulmonary arterial hypertension: focus on mechanisms and treatment of right heart failure using the CircAdapt model.

    PubMed

    Lumens, Joost; Delhaas, Tammo

    2012-09-15

    In recent years, increased understanding of cardiovascular system dynamics has led to the development of mathematical models of the heart and circulation. Models that enable realistic simulation of ventricular mechanics and interactions under a range of conditions have the potential to provide an ideal method with which to investigate the effects of pulmonary arterial hypertension and its treatment on cardiac mechanics and hemodynamics. Such mathematical models have the potential to contribute to a personalized, patient-specific treatment approach and allow more objective diagnostic decision-making, patient monitoring, and assessment of treatment outcome. This review discusses the development of mathematical models of the heart and circulation, with particular reference to the closed-loop CircAdapt model, and how the model performs under both normal and pathophysiological (pulmonary hypertensive) conditions.

  19. NO/redox disequilibrium in the failing heart and cardiovascular system

    PubMed Central

    Hare, Joshua M.; Stamler, Jonathan S.

    2005-01-01

    There is growing evidence that the altered production and/or spatiotemporal distribution of reactive oxygen and nitrogen species creates oxidative and/or nitrosative stresses in the failing heart and vascular tree, which contribute to the abnormal cardiac and vascular phenotypes that characterize the failing cardiovascular system. These derangements at the integrated system level can be interpreted at the cellular and molecular levels in terms of adverse effects on signaling elements in the heart, vasculature, and blood that subserve cardiac and vascular homeostasis. PMID:15765132

  20. Activation of the central histaminergic system mediates arachidonic-acid-induced cardiovascular effects.

    PubMed

    Altinbas, Burcin; Topuz, Bora Burak; İlhan, Tuncay; Yilmaz, Mustafa Sertac; Erdost, Hatice; Yalcin, Murat

    2014-08-01

    The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague-Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3-H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.

  1. Recent insights and therapeutic perspectives of angiotensin-(1-9) in the cardiovascular system.

    PubMed

    Ocaranza, Maria Paz; Michea, Luis; Chiong, Mario; Lagos, Carlos F; Lavandero, Sergio; Jalil, Jorge E

    2014-11-01

    Chronic RAS (renin-angiotensin system) activation by both AngII (angiotensin II) and aldosterone leads to hypertension and perpetuates a cascade of pro-hypertrophic, pro-inflammatory, pro-thrombotic and atherogenic effects associated with cardiovascular damage. In 2000, a new pathway consisting of ACE2 (angiotensin-converting enzyme2), Ang-(1-9) [angiotensin-(1-9)], Ang-(1-7) [angiotensin-(1-7)] and the Mas receptor was discovered. Activation of this novel pathway stimulates vasodilation, anti-hypertrophy and anti-hyperplasia. For some time, studies have focused mainly on ACE2, Ang-(1-7) and the Mas receptor, and their biological properties that counterbalance the ACE/AngII/AT1R (angiotensin type 1 receptor) axis. No previous information about Ang-(1-9) suggested that this peptide had biological properties. However, recent data suggest that Ang-(1-9) protects the heart and blood vessels (and possibly the kidney) from adverse cardiovascular remodelling in patients with hypertension and/or heart failure. These beneficial effects are not modified by the Mas receptor antagonist A779 [an Ang-(1-7) receptor blocker], but they are abolished by the AT2R (angiotensin type 2 receptor) antagonist PD123319. Current information suggests that the beneficial effects of Ang-(1-9) are mediated via the AT2R. In the present review, we summarize the biological effects of the novel vasoactive peptide Ang-(1-9), providing new evidence of its cardiovascular-protective activity. We also discuss the potential mechanism by which this peptide prevents and ameliorates the cardiovascular damage induced by RAS activation.

  2. Recent insights and therapeutic perspectives of angiotensin-(1-9) in the cardiovascular system.

    PubMed

    Ocaranza, Maria Paz; Michea, Luis; Chiong, Mario; Lagos, Carlos F; Lavandero, Sergio; Jalil, Jorge E

    2014-11-01

    Chronic RAS (renin-angiotensin system) activation by both AngII (angiotensin II) and aldosterone leads to hypertension and perpetuates a cascade of pro-hypertrophic, pro-inflammatory, pro-thrombotic and atherogenic effects associated with cardiovascular damage. In 2000, a new pathway consisting of ACE2 (angiotensin-converting enzyme2), Ang-(1-9) [angiotensin-(1-9)], Ang-(1-7) [angiotensin-(1-7)] and the Mas receptor was discovered. Activation of this novel pathway stimulates vasodilation, anti-hypertrophy and anti-hyperplasia. For some time, studies have focused mainly on ACE2, Ang-(1-7) and the Mas receptor, and their biological properties that counterbalance the ACE/AngII/AT1R (angiotensin type 1 receptor) axis. No previous information about Ang-(1-9) suggested that this peptide had biological properties. However, recent data suggest that Ang-(1-9) protects the heart and blood vessels (and possibly the kidney) from adverse cardiovascular remodelling in patients with hypertension and/or heart failure. These beneficial effects are not modified by the Mas receptor antagonist A779 [an Ang-(1-7) receptor blocker], but they are abolished by the AT2R (angiotensin type 2 receptor) antagonist PD123319. Current information suggests that the beneficial effects of Ang-(1-9) are mediated via the AT2R. In the present review, we summarize the biological effects of the novel vasoactive peptide Ang-(1-9), providing new evidence of its cardiovascular-protective activity. We also discuss the potential mechanism by which this peptide prevents and ameliorates the cardiovascular damage induced by RAS activation. PMID:25029123

  3. Recent advances in iPSC technologies involving cardiovascular and neurodegenerative disease modeling.

    PubMed

    Csöbönyeiová, Mária; Danišovič, Ľuboš; Polák, Štefan

    2016-01-01

    Cardiovascular and neurodegenerative diseases are the most common health threats in developed countries. Limited cell derivation and cell number in cardiac tissue makes it difficult to study the cardiovascular disease using the existing cardiac cell model. Regarding the neurodegenerative disorders, the most potential sources of cell therapeutics such as fetal-derived primary neurons and human embryonic stem cells (ESCs) are associated with ethical or technical limitations. The successful derivation of human-induced pluripotent stem cells (iPSCs) by de-differentiation of somatic cells offers significant potential to overcome hurdles in the field of the replacement therapy. Human iPSCs are functionally similar to human embryonic stem cells, and can be derived autologously without the ethical challenges associated with human ESCs. The iPSCs can, in turn, be differentiated into all cell types including neurons, cardiac cells, blood and liver cells, etc. Recently, target tissues derived from human iPSCs such as cardiomyocytes (CMs) or neurons have been used for new disease modeling and regenerative medicine therapies. Diseases models could be advantageous in the development of personalized medicine of various pathological conditions. This paper reviews efforts aimed at both the practical development of iPSCs, differentiation to neural/cardiac lineages, and the further use of these iPSCs-derived cells for disease modeling, as well as drug toxicity testing. PMID:26492069

  4. Recent advances in iPSC technologies involving cardiovascular and neurodegenerative disease modeling.

    PubMed

    Csöbönyeiová, Mária; Danišovič, Ľuboš; Polák, Štefan

    2016-01-01

    Cardiovascular and neurodegenerative diseases are the most common health threats in developed countries. Limited cell derivation and cell number in cardiac tissue makes it difficult to study the cardiovascular disease using the existing cardiac cell model. Regarding the neurodegenerative disorders, the most potential sources of cell therapeutics such as fetal-derived primary neurons and human embryonic stem cells (ESCs) are associated with ethical or technical limitations. The successful derivation of human-induced pluripotent stem cells (iPSCs) by de-differentiation of somatic cells offers significant potential to overcome hurdles in the field of the replacement therapy. Human iPSCs are functionally similar to human embryonic stem cells, and can be derived autologously without the ethical challenges associated with human ESCs. The iPSCs can, in turn, be differentiated into all cell types including neurons, cardiac cells, blood and liver cells, etc. Recently, target tissues derived from human iPSCs such as cardiomyocytes (CMs) or neurons have been used for new disease modeling and regenerative medicine therapies. Diseases models could be advantageous in the development of personalized medicine of various pathological conditions. This paper reviews efforts aimed at both the practical development of iPSCs, differentiation to neural/cardiac lineages, and the further use of these iPSCs-derived cells for disease modeling, as well as drug toxicity testing.

  5. Noise, sleep and poor health: Modeling the relationship between road traffic noise and cardiovascular problems.

    PubMed

    Fyhri, Aslak; Aasvang, Gunn Marit

    2010-10-01

    Several adverse effects have been associated with exposure to traffic noise. Studies supporting a noise-stress-health model have suggested links between noise level and increased noradrenalin concentrations in urine, hypertension and myocardial infarction. Among the more commonly documented effects, sleep disturbances have been regarded as being the most serious. Both noise annoyance and sleep disturbance have been proposed as important mediators of the impact of noise on health. The present paper investigates the relationships among long-term noise exposure, annoyance, sleeping problems and subjective health complaints by the use of a structural equation model. Further, it aims at giving insight into how noise sensitivity is related to sleep disturbances from road traffic noise. Finally, it examines whether any effect of noise exposure or response to noise can be detected on prevalence of cardiovascular problems, when information on sleep disturbances is included in a model. Data from a questionnaire survey conducted among a population sample in Oslo (N=2786) are combined with nighttime noise levels calculated from outside each respondents dwelling, at the bedroom façade. The results of the analysis showed significant relationships between noise annoyance at night and sleeping problems. The model also showed strong links among pseudoneurological complaints, annoyance and sleeping problems, thus pointing to the importance of including information on psychosomatic disorders and mild psychological problems in future studies looking at potential health effects of noise. The analysis showed no relationship between neither noise exposure nor response to noise and cardiovascular problems.

  6. Methods for establishing a surveillance system for cardiovascular diseases in Indian industrial populations.

    PubMed Central

    Reddy, K. S.; Prabhakaran, D.; Chaturvedi, V.; Jeemon, P.; Thankappan, K. R.; Ramakrishnan, L.; Mohan, B. V. M.; Pandav, C. S.; Ahmed, F. U.; Joshi, P. P.; Meera, R.; Amin, R. B.; Ahuja, R. C.; Das, M. S.; Jaison, T. M.

    2006-01-01

    OBJECTIVE: To establish a surveillance network for cardiovascular diseases (CVD) risk factors in industrial settings and estimate the risk factor burden using standardized tools. METHODS: We conducted a baseline cross-sectional survey (as part of a CVD surveillance programme) of industrial populations from 10 companies across India, situated in close proximity to medical colleges that served as study centres. The study subjects were employees (selected by age and sex stratified random sampling) and their family members. Information on behavioural, clinical and biochemical determinants was obtained through standardized methods (questionnaires, clinical measurements and biochemical analysis). Data collation and analyses were done at the national coordinating centre. FINDINGS: We report the prevalence of CVD risk factors among individuals aged 20-69 years (n = 19 973 for the questionnaire survey, n = 10 442 for biochemical investigations); mean age was 40 years. The overall prevalence of most risk factors was high, with 50.9% of men and 51.9% of women being overweight, central obesity was observed among 30.9% of men and 32.8% of women, and 40.2% of men and 14.9% of women reported current tobacco use. Self-reported prevalence of diabetes (5.3%) and hypertension (10.9%) was lower than when measured clinically and biochemically (10.1% and 27.7%, respectively). There was marked heterogeneity in the prevalence of risk factors among the study centres. CONCLUSION: There is a high burden of CVD risk factors among industrial populations across India. The surveillance system can be used as a model for replication in India as well as other developing countries. PMID:16799730

  7. Generation and Characterization of Patient-Specific iPSC Model for Cardiovascular Disease.

    PubMed

    Lee, Yee Ki; Ran, X; Lai, K W H; Lau, V Y M; Siu, D C W; Tse, H F

    2016-01-01

    Advances in differentiation of cardiomyocytes from human induced pluripotent stem cell (hiPSC) were emerged as a tool for modeling of cardiovascular disease that recapitulates the phenotype for the purpose of drug screening, biomarker discovery, and testing of single-nucleotide polymorphism (SNP) as a modifier for disease stratification. Here, we describe the (1) retroviral reprogramming strategies in the generation of human iPSC, (2) methodology in characterization of iPSC in order to identify the stem cell clones with the best quality, and (3) protocol of cardiac differentiation by modulation of Wnt signaling and β-catenin pathway.

  8. Development of Diagnostic Reference Levels Using a Real-Time Radiation Dose Monitoring System at a Cardiovascular Center in Korea.

    PubMed

    Kim, Jungsu; Seo, Deoknam; Choi, Inseok; Nam, Sora; Yoon, Yongsu; Kim, Hyunji; Her, Jae; Han, Seonggyu; Kwon, Soonmu; Park, Hunsik; Yang, Dongheon; Kim, Jungmin

    2015-12-01

    Digital cardiovascular angiography accounts for a major portion of the radiation dose among the examinations performed at cardiovascular centres. However, dose-related information is neither monitored nor recorded systemically. This report concerns the construction of a radiation dose monitoring system based on digital imaging and communications in medicine (DICOM) data and its use at the cardiovascular centre of the University Hospitals in Korea. The dose information was analysed according to DICOM standards for a series of procedures, and the formulation of diagnostic reference levels (DRLs) at our cardiovascular centre represents the first of its kind in Korea. We determined a dose area product (DAP) DRL for coronary angiography of 75.6 Gy cm(2) and a fluoroscopic time DRL of 318.0 s. The DAP DRL for percutaneous transluminal coronary intervention was 213.3 Gy cm(2), and the DRL for fluoroscopic time was 1207.5 s.

  9. Development of Diagnostic Reference Levels Using a Real-Time Radiation Dose Monitoring System at a Cardiovascular Center in Korea.

    PubMed

    Kim, Jungsu; Seo, Deoknam; Choi, Inseok; Nam, Sora; Yoon, Yongsu; Kim, Hyunji; Her, Jae; Han, Seonggyu; Kwon, Soonmu; Park, Hunsik; Yang, Dongheon; Kim, Jungmin

    2015-12-01

    Digital cardiovascular angiography accounts for a major portion of the radiation dose among the examinations performed at cardiovascular centres. However, dose-related information is neither monitored nor recorded systemically. This report concerns the construction of a radiation dose monitoring system based on digital imaging and communications in medicine (DICOM) data and its use at the cardiovascular centre of the University Hospitals in Korea. The dose information was analysed according to DICOM standards for a series of procedures, and the formulation of diagnostic reference levels (DRLs) at our cardiovascular centre represents the first of its kind in Korea. We determined a dose area product (DAP) DRL for coronary angiography of 75.6 Gy cm(2) and a fluoroscopic time DRL of 318.0 s. The DAP DRL for percutaneous transluminal coronary intervention was 213.3 Gy cm(2), and the DRL for fluoroscopic time was 1207.5 s. PMID:25700616

  10. Air pollution and autonomic and vascular dysfunction in patients with cardiovascular disease: interactions of systemic inflammation, overweight, and gender.

    PubMed

    Huang, Wei; Zhu, Tong; Pan, Xiaochuan; Hu, Min; Lu, Shou-En; Lin, Yong; Wang, Tong; Zhang, Yuanhang; Tang, Xiaoyan

    2012-07-15

    The authors conducted a 2-year follow-up of 40 cardiovascular disease patients (mean age = 65.6 years (standard deviation, 5.8)) who underwent repeated measurements of cardiovascular response before and during the 2008 Beijing Olympics (Beijing, China), when air pollution was strictly controlled. Ambient levels of particulate matter with an aerodynamic diameter less than 2.5 µm (PM(2.5)), black carbon, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide were measured continuously, with validation of concurrent real-time measurements of personal exposure to PM(2.5) and carbon monoxide. Linear mixed-effects models were used with adjustment for individual risk factors, time-varying factors, and meteorologic effects. Significant heart rate variability reduction and blood pressure elevation were observed in association with exposure to air pollution. Specifically, interquartile-range increases of 51.8 µg/m(3), 2.02 µg/m(3), and 13.7 ppb in prior 4-hour exposure to PM(2.5), black carbon, and nitrogen dioxide were associated with significant reductions in the standard deviation of the normal-to-normal intervals of 4.2% (95% confidence interval (CI): 1.9, 6.4), 4.2% (95% CI: 1.8, 6.6), and 3.9% (95% CI: 2.2, 5.7), respectively. Greater heart rate variability declines were observed among subjects with C-reactive protein values above the 90th percentile, subjects with a body mass index greater than 25, and females. The authors conclude that autonomic and vascular dysfunction may be one of the mechanisms through which air pollution exposure can increase cardiovascular disease risk, especially among persons with systemic inflammation and overweight. PMID:22763390

  11. The influence of whole body vibration on the central and peripheral cardiovascular system.

    PubMed

    Robbins, Dan; Yoganathan, Priya; Goss-Sampson, Mark

    2014-09-01

    The purpose of this study was to investigate the physiological changes of the cardiovascular system in response to whole body vibration during quiet standing and identify whether there is a greater influence on the central or peripheral cardiovascular system. Twenty healthy participants (12 male and 8 female) were assessed over two separate testing sessions for changes in peripheral skin temperature, peripheral venous function, blood flow velocity in the dorsalis pedis artery, blood pressure and heart rate during quiet standing with 40 Hz 1·9 mm synchronous vibration. Vibration exposure totalled 5 min in 1 min increments with 5 min recovery during each testing session. There were no significant changes in heart rate, blood pressure or peripheral skin temperature. Significant results were obtained for blood flow velocity with increases from 0·5 + 0·2 cm·s(-1) at baseline to 1 + 0·2 cm·s(-1) during vibration, returning to baseline levels during the recovery period. Due to the absence of changes in heart rate, blood pressure or lower leg and foot temperature, the change in blood flow velocity can be attributed to changes in peripheral vascular function. The results suggest a high level of sensitivity of the peripheral vascular system to vibration exposure; therefore, further studies should be completed to ascertain the physiological mechanisms underlying the effects of vibration on the peripheral vascular system.

  12. An experimental ovine Theileriosis: The effect of Theileria lestoquardi infection on cardiovascular system in sheep.

    PubMed

    Yaghfoori, Saeed; Razmi, Gholam Reza; Mohri, Mehrdad; Razavizadeh, Ali Reza Taghavi; Movassaghi, Ahmad Reza

    2016-09-01

    The malignant ovine theileriosis is caused by Theileria lestoquardi, which is highly pathogenic in sheep. Theileriosis involves different organs in ruminants, but the effect of the disease on the cardiovascular system is unclear. To understand the pathogenesis of T. lestoquardi on the cardiovascular system, Baluchi breed sheep were infected with the mentioned parasite by releasing unfed adults of Hyalomma anatolicum anatolicum, which were infected with T. lestoquardi. The infected sheep were clinically examined on days 0, 2, 5, 7, 10, 12, 14, 17, and 21, and the blood samples were collected for biochemical parameters measurement. At termination of the experiment, the infected sheep were euthanized and pathological examinations of heart tissue were conducted. During experimental infection of sheep with T. lestoquardi, activities of cardiac troponin I (cTnI), lactate dehydrogenase, and aspartate aminotransferase, were significantly increased (P˂0.05), while a conspicuous decrease (P˂0.05) was observed in creatine phosphokinase activities. Alterations made in biochemical factors almost coincided with the presence of piroplasm in the blood and schizont in lymph nodes. Maximum and minimum of parasitemia in the sheep stood between 3.3% and 0.28%, respectively. In addition, electrocardiography revealed sinus tachycardia, sinus arrhythmia, sino-atrial block and ST-elevation, atrial premature beat, and alteration in QRS and in T waves' amplitude. Heart histopathological examination showed hyperemia, infiltration of mononuclear inflammatory cells into interstitial tissue, endocarditis, and focal necrosis of cardiac muscle cells. In addition, in one of the sheep, definite occurrence of infarction was observed. The results indicate that T. lestoquardi infection has devastating pathological impacts on the cardiovascular system of sheep. Furthermore, measurement of the cTnI amount is a useful biochemical factor for diagnosis and for better understanding of the severity and

  13. An experimental ovine Theileriosis: The effect of Theileria lestoquardi infection on cardiovascular system in sheep.

    PubMed

    Yaghfoori, Saeed; Razmi, Gholam Reza; Mohri, Mehrdad; Razavizadeh, Ali Reza Taghavi; Movassaghi, Ahmad Reza

    2016-09-01

    The malignant ovine theileriosis is caused by Theileria lestoquardi, which is highly pathogenic in sheep. Theileriosis involves different organs in ruminants, but the effect of the disease on the cardiovascular system is unclear. To understand the pathogenesis of T. lestoquardi on the cardiovascular system, Baluchi breed sheep were infected with the mentioned parasite by releasing unfed adults of Hyalomma anatolicum anatolicum, which were infected with T. lestoquardi. The infected sheep were clinically examined on days 0, 2, 5, 7, 10, 12, 14, 17, and 21, and the blood samples were collected for biochemical parameters measurement. At termination of the experiment, the infected sheep were euthanized and pathological examinations of heart tissue were conducted. During experimental infection of sheep with T. lestoquardi, activities of cardiac troponin I (cTnI), lactate dehydrogenase, and aspartate aminotransferase, were significantly increased (P˂0.05), while a conspicuous decrease (P˂0.05) was observed in creatine phosphokinase activities. Alterations made in biochemical factors almost coincided with the presence of piroplasm in the blood and schizont in lymph nodes. Maximum and minimum of parasitemia in the sheep stood between 3.3% and 0.28%, respectively. In addition, electrocardiography revealed sinus tachycardia, sinus arrhythmia, sino-atrial block and ST-elevation, atrial premature beat, and alteration in QRS and in T waves' amplitude. Heart histopathological examination showed hyperemia, infiltration of mononuclear inflammatory cells into interstitial tissue, endocarditis, and focal necrosis of cardiac muscle cells. In addition, in one of the sheep, definite occurrence of infarction was observed. The results indicate that T. lestoquardi infection has devastating pathological impacts on the cardiovascular system of sheep. Furthermore, measurement of the cTnI amount is a useful biochemical factor for diagnosis and for better understanding of the severity and

  14. Study of nanosensor systems for hypertension associated cerebrovascular and cardiovascular disorders

    NASA Astrophysics Data System (ADS)

    Ramasamy, Mouli; Varadan, Vijay K.

    2015-04-01

    Hypertension and hypertension associated cerebrovascular and cardiovascular diseases are on a rise. At-least 970 million people in the world and Seventy percent of the American adults are affected by high blood pressure, also known as hypertension. Even though blood pressure monitoring systems are readily available, the number of people being affected has been increasing. Most of the blood pressure monitoring systems require cumbersome approaches. Even the noninvasive techniques have not lowered the number of people affected nor did at-least increase the user base of these systems. Uncontrolled or untreated hypertension may lead to various cerebrovascular disorders including stroke, hypertensive crisis, lacunar infarcts intracerebral damage, microaneurysm, and cardiovascular disorders including heart failure, myocardial infraction, and ischemic heart disease. Hypertension is rated as the one of the most important causes of premature death in spite of the technical advances in biomedical technology. This paper briefs a review of the widely adopted blood pressure monitoring methods, research techniques, and finally, proposes a concept of implementing nanosensors and wireless communication for real time non-invasive blood pressure monitoring.

  15. The effects of phthalates in the cardiovascular and reproductive systems: A review.

    PubMed

    Mariana, Melissa; Feiteiro, Joana; Verde, Ignacio; Cairrao, Elisa

    2016-09-01

    Every year millions of tons of plastic are produced around the world and humans are increasingly exposed to them. This constant exposure to plastics has raised some concerns against human health, particularly when it comes to phthalates. These compounds have endocrine-disrupting properties, as they have the ability to bind molecular targets in the body and interfere with hormonal function and quantity. The main use of phthalates is to give flexibility to polyvinyl chloride (PVC) polymers. Phthalates are found in a variety of industrial and consumer products, and as they are not covalently bound to the plastic, phthalates contaminate the environment from which human exposure occurs. Studies in human and animal populations suggest a correlation between phthalate exposure and adverse health outcomes, particularly at the reproductive and cardiovascular systems, however there is much less information about the phthalate toxicity of the later. Thus, the main purpose of this review is to present the studies relating the effects already stated of phthalates on the cardiovascular and reproductive systems, and also present the link between these two systems. PMID:27424259

  16. Space Weather and the State of Cardiovascular System of a Healthy Human Being

    NASA Astrophysics Data System (ADS)

    Samsonov, S. N.; Manykina, V. I.; Krymsky, G. F.; Petrova, P. G.; Palshina, A. M.; Vishnevsky, V. V.

    The term "space weather" characterizes a state of the near-Earth environmental space. An organism of human being represents an open system so the change of conditions in the environment including the near-Earth environmental space influences the health state of a human being.In recent years many works devoted to the effect of space weather on the life on the Earth, and the degree of such effect has been represented from a zero-order up to apocalypse. To reveal a real effect of space weather on the health of human being the international Russian- Ukrainian experiment "Geliomed" is carried out since 2005 (http://geliomed.immsp.kiev.ua) [Vishnevsky et al., 2009]. The analysis of observational set of data has allowed to show a synchronism and globality of such effect (simultaneous manifestation of space weather parameters in a state of cardiovascular system of volunteer groups removed from each other at a distance over 6000 km). The response of volunteer' cardiovascular system to the changes of space weather parameters were observed even at insignificant values of the Earth's geomagnetic field. But even at very considerable disturbances of space weather parameters a human being healthy did not feel painful symptoms though measurements of objective physiological indices showed their changes.

  17. The effects of phthalates in the cardiovascular and reproductive systems: A review.

    PubMed

    Mariana, Melissa; Feiteiro, Joana; Verde, Ignacio; Cairrao, Elisa

    2016-09-01

    Every year millions of tons of plastic are produced around the world and humans are increasingly exposed to them. This constant exposure to plastics has raised some concerns against human health, particularly when it comes to phthalates. These compounds have endocrine-disrupting properties, as they have the ability to bind molecular targets in the body and interfere with hormonal function and quantity. The main use of phthalates is to give flexibility to polyvinyl chloride (PVC) polymers. Phthalates are found in a variety of industrial and consumer products, and as they are not covalently bound to the plastic, phthalates contaminate the environment from which human exposure occurs. Studies in human and animal populations suggest a correlation between phthalate exposure and adverse health outcomes, particularly at the reproductive and cardiovascular systems, however there is much less information about the phthalate toxicity of the later. Thus, the main purpose of this review is to present the studies relating the effects already stated of phthalates on the cardiovascular and reproductive systems, and also present the link between these two systems.

  18. Reproduction of continuous flow left ventricular assist device experimental data by means of a hybrid cardiovascular model with baroreflex control.

    PubMed

    Fresiello, Libera; Zieliński, Krzysztof; Jacobs, Steven; Di Molfetta, Arianna; Pałko, Krzysztof Jakub; Bernini, Fabio; Martin, Michael; Claus, Piet; Ferrari, Gianfranco; Trivella, Maria Giovanna; Górczyńska, Krystyna; Darowski, Marek; Meyns, Bart; Kozarski, Maciej

    2014-06-01

    Long-term mechanical circulatory assistance opened new problems in ventricular assist device-patient interaction, especially in relation to autonomic controls. Modeling studies, based on adequate models, could be a feasible approach of investigation. The aim of this work is the exploitation of a hybrid (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo experimental data acquired during a continuous flow left ventricular assistance. The hybrid cardiovascular simulator embeds three submodels: a computational cardiovascular submodel, a computational baroreflex submodel, and a hydronumerical interface submodel. The last one comprises two impedance transformers playing the role of physical interfaces able to provide a hydraulic connection with specific cardiovascular sites (in this article, the left atrium and the ascending/descending aorta). The impedance transformers are used to connect a continuous flow pump for partial left ventricular support (Synergy Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular simulator. Data collected from five animals in physiological, pathological, and assisted conditions were reproduced using the hybrid cardiovascular simulator. All parameters useful to characterize and tune the hybrid cardiovascular simulator to a specific hemodynamic condition were extracted from experimental data. Results show that the simulator is able to reproduce animal-specific hemodynamic status both in physiological and pathological conditions, to reproduce cardiovascular left ventricular assist device (LVAD) interaction and the progressive unloading of the left ventricle for different pump speeds, and to investigate the effects of the LVAD on baroreflex activity. Results in chronic heart failure conditions show that an increment of LVAD speed from 20 000 to 22 000 rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3 L/min). Thanks to its flexibility and modular structure, the

  19. Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health.

    PubMed

    Rothman, Sarah M; Griffioen, Kathleen J; Wan, Ruiqian; Mattson, Mark P

    2012-08-01

    Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise- and DER-induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders.

  20. Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health

    PubMed Central

    Rothman, Sarah M; Griffioen, Kathleen J; Wan, Ruiqian; Mattson, Mark P

    2012-01-01

    Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise- and DER-induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders. PMID:22548651

  1. The cardiovascular effects of salidroside in the Goto-Kakizaki diabetic rat model.

    PubMed

    Alameddine, A; Fajloun, Z; Bourreau, J; Gauquelin-Koch, G; Yuan, M; Gauguier, D; Derbre, S; Ayer, A; Custaud, M A; Navasiolava, N

    2015-04-01

    Many factors, including hyperglycemia, hypertension, obesity, dyslipidemia, and a sedentary lifestyle, contribute to a high prevalence of cardiovascular disease. Specific vascular impairment treatments in the context of diabetes and vascular risk need to be improved. Salidroside is the primary active component of Rhodiola rosea and has documented antioxidative, cardioprotective, and vasculoprotective properties. The aim of this study was to test the hypothesis that salidroside has protective effects against hyperglycemia, hypertension, and vasodilation impairment in the Goto-Kakizaki (GK) rat model of diabetes. We evaluated cardiovascular parameters (e.g., daytime/nighttime systolic and diastolic blood pressure, heart rate, and activity), metabolic parameters (e.g., body weight, food and water consumption, serum fructosamine level, glucose tolerance), eNOS / phospho-eNOS expression level and in vitro vascular reactivity of aorta and second-order mesenteric arteries in Wistar-Kyoto (control) and GK (diabetic) rats treated with salidroside (40 mg/kg) or placebo (water) for 5 weeks. GK rats showed hypertension, marked glucose intolerance, and impaired endothelium-dependent and endothelium-independent vasodilation capacity. Salidroside showed beneficial effects on endothelial and non-endothelial vasodilation and likely acts on the endothelium and smooth muscle cells through the soluble guanylyl cyclase pathway. Despite its vascular effects, salidroside had no effect on blood pressure and heart rate in GK and control rats, it did not improve glucose metabolism or limit hypertension in the GK model of type 2 diabetes.

  2. Cardiovascular Dysfunction Following Burn Injury: What We Have Learned from Rat and Mouse Models.

    PubMed

    Guillory, Ashley N; Clayton, Robert P; Herndon, David N; Finnerty, Celeste C

    2016-01-02

    Severe burn profoundly affects organs both proximal and distal to the actual burn site. Cardiovascular dysfunction is a well-documented phenomenon that increases morbidity and mortality following a massive thermal trauma. Beginning immediately post-burn, during the ebb phase, cardiac function is severely depressed. By 48 h post-injury, cardiac function rebounds and the post-burn myocardium becomes tachycardic and hyperinflammatory. While current clinical trials are investigating a variety of drugs targeted at reducing aspects of the post-burn hypermetabolic response such as heart rate and cardiac work, there is still a paucity of knowledge regarding the underlying mechanisms that induce cardiac dysfunction in the severely burned. There are many animal models of burn injury, from rodents, to sheep or swine, but the majority of burn related cardiovascular investigations have occurred in rat and mouse models. This literature review consolidates the data supporting the prevalent role that β-adrenergic receptors play in mediating post-burn cardiac dysfunction and the idea that pharmacological modulation of this receptor family is a viable therapeutic target for resolving burn-induced cardiac deficits.

  3. The impact of haemodialysis arteriovenous fistula on haemodynamic parameters of the cardiovascular system

    PubMed Central

    Basile, Carlo; Vernaglione, Luigi; Casucci, Francesco; Libutti, Pasquale; Lisi, Piero; Rossi, Luigi; Vigo, Valentina; Lomonte, Carlo

    2016-01-01

    Background Satisfactory vascular access flow (Qa) of an arteriovenous fistula (AVF) is necessary for haemodialysis (HD) adequacy. The aim of the present study was to further our understanding of haemodynamic modifications of the cardiovascular system of HD patients associated with an AVF. The main objective was to calculate using real data in what way an AVF influences the load of the left ventricle (LLV). Methods All HD patients treated in our dialysis unit and bearing an AVF were enrolled into the present observational cross-sectional study. Fifty-six patients bore a lower arm AVF and 30 an upper arm AVF. Qa and cardiac output (CO) were measured by means of the ultrasound dilution Transonic Hemodialysis Monitor HD02. Mean arterial pressure (MAP) was calculated; total peripheral vascular resistance (TPVR) was calculated as MAP/CO; resistance of AVF (AR) and systemic vascular resistance (SVR) are connected in parallel and were respectively calculated as AR = MAP/Qa and SVR = MAP/(CO − Qa). LLV was calculated on the principle of a simple physical model: LLV (watt) = TPVR·CO2. The latter was computationally divided into the part spent to run Qa through the AVF (LLVAVF) and that part ensuring the flow (CO − Qa) through the vascular system. The data from the 86 AVFs were analysed by categorizing them into lower and upper arm AVFs. Results Mean Qa, CO, MAP, TPVR, LLV and LLVAVF of the 86 AVFs were, respectively, 1.3 (0.6 SD) L/min, 6.3 (1.3) L/min, 92.7 (13.9) mmHg, 14.9 (3.9) mmHg·min/L, 1.3 (0.6) watt and 19.7 (3.1)% of LLV. A statistically significant increase of Qa, CO, LLV and LLVAVF and a statistically significant decrease of TPVR, AR and SVR of upper arm AVFs compared with lower arm AVFs was shown. A third-order polynomial regression model best fitted the relationship between Qa and LLV for the entire cohort (R2 = 0.546; P < 0.0001) and for both lower (R2 = 0.181; P < 0.01) and upper arm AVFs (R2 = 0.663; P < 0.0001). LLVAVF calculated as % of LLV rose with

  4. The impact of haemodialysis arteriovenous fistula on haemodynamic parameters of the cardiovascular system

    PubMed Central

    Basile, Carlo; Vernaglione, Luigi; Casucci, Francesco; Libutti, Pasquale; Lisi, Piero; Rossi, Luigi; Vigo, Valentina; Lomonte, Carlo

    2016-01-01

    Background Satisfactory vascular access flow (Qa) of an arteriovenous fistula (AVF) is necessary for haemodialysis (HD) adequacy. The aim of the present study was to further our understanding of haemodynamic modifications of the cardiovascular system of HD patients associated with an AVF. The main objective was to calculate using real data in what way an AVF influences the load of the left ventricle (LLV). Methods All HD patients treated in our dialysis unit and bearing an AVF were enrolled into the present observational cross-sectional study. Fifty-six patients bore a lower arm AVF and 30 an upper arm AVF. Qa and cardiac output (CO) were measured by means of the ultrasound dilution Transonic Hemodialysis Monitor HD02. Mean arterial pressure (MAP) was calculated; total peripheral vascular resistance (TPVR) was calculated as MAP/CO; resistance of AVF (AR) and systemic vascular resistance (SVR) are connected in parallel and were respectively calculated as AR = MAP/Qa and SVR = MAP/(CO − Qa). LLV was calculated on the principle of a simple physical model: LLV (watt) = TPVR·CO2. The latter was computationally divided into the part spent to run Qa through the AVF (LLVAVF) and that part ensuring the flow (CO − Qa) through the vascular system. The data from the 86 AVFs were analysed by categorizing them into lower and upper arm AVFs. Results Mean Qa, CO, MAP, TPVR, LLV and LLVAVF of the 86 AVFs were, respectively, 1.3 (0.6 SD) L/min, 6.3 (1.3) L/min, 92.7 (13.9) mmHg, 14.9 (3.9) mmHg·min/L, 1.3 (0.6) watt and 19.7 (3.1)% of LLV. A statistically significant increase of Qa, CO, LLV and LLVAVF and a statistically significant decrease of TPVR, AR and SVR of upper arm AVFs compared with lower arm AVFs was shown. A third-order polynomial regression model best fitted the relationship between Qa and LLV for the entire cohort (R2 = 0.546; P < 0.0001) and for both lower (R2 = 0.181; P < 0.01) and upper arm AVFs (R2 = 0.663; P < 0.0001). LLVAVF calculated as % of LLV rose with

  5. Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model.

    PubMed

    Trifilieff, Alexandre; Ethell, Brian T; Sykes, David A; Watson, Kenny J; Collingwood, Steve; Charlton, Steven J; Kent, Toby C

    2015-08-15

    Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED50 values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1h; >200 fold at 6h) than with tiotropium (1.5 and 4.2 fold at 1h; 4.6 and 5.5 fold at 6h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M2 muscarinic receptor occupancy, which predicted significantly higher M2 receptor blockade at ED50 doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. PMID:26026369

  6. Development of a multivariable model to predict vulnerability in older American patients hospitalised with cardiovascular disease

    PubMed Central

    Bell, Susan P; Schnelle, John; Nwosu, Samuel K; Schildcrout, Jonathan; Goggins, Kathryn; Cawthon, Courtney; Mixon, Amanda S; Vasilevskis, Eduard E; Kripalani, Sunil

    2015-01-01

    Objectives To identify vulnerable cardiovascular patients in the hospital using a self-reported function-based screening tool. Participants Prospective observational cohort study of 445 individuals aged ≥65 years admitted to a university medical centre hospital within the USA with acute coronary syndrome and/or decompensated heart failure. Methods Participants completed an inperson interview during hospitalisation, which included vulnerable functional status using the Vulnerable Elders Survey (VES-13), sociodemographic, healthcare utilisation practices and clinical patient-specific measures. A multivariable proportional odds logistic regression model examined associations between VES-13 and prior healthcare utilisation, as well as other coincident medical and psychosocial risk factors for poor outcomes in cardiovascular disease. Results Vulnerability was highly prevalent (54%) and associated with a higher number of clinic visits, emergency room visits and hospitalisations (all p<0.001). A multivariable analysis demonstrating a 1-point increase in VES-13 (vulnerability) was independently associated with being female (OR 1.55, p=0.030), diagnosis of heart failure (OR 3.11, p<0.001), prior hospitalisations (OR 1.30, p<0.001), low social support (OR 1.42, p=0.007) and depression (p<0.001). A lower VES-13 score (lower vulnerability) was associated with increased health literacy (OR 0.70, p=0.002). Conclusions Vulnerability to functional decline is highly prevalent in hospitalised older cardiovascular patients and was associated with patient risk factors for adverse outcomes and an increased use of healthcare services. PMID:26316650

  7. Prediction models for cardiovascular disease risk in the general population: systematic review

    PubMed Central

    Hooft, Lotty; Schuit, Ewoud; Debray, Thomas P A; Collins, Gary S; Tzoulaki, Ioanna; Lassale, Camille M; Siontis, George C M; Chiocchia, Virginia; Roberts, Corran;