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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. 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.

  3. 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)

  4. 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.

  5. 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.

  6. QRAR models for cardiovascular system drugs using biopartitioning micellar chromatography.

    PubMed

    Wang, Sumin; Yang, Gengliang; Zhang, Hua; Liu, Haiyan; Li, Zhiwei

    2007-02-01

    The capability of biopartitioning micellar chromatography (BMC) to describe and estimate pharmacological parameters of cardiovascular system drugs has been studied. The retention of cardiovascular system drugs was studied using different pH of Brij-35 as micellar mobile phase in modified C(18) stationary phase. Quantitative retention-activity relationships (QRAR) in BMC were investigated for these compounds. An adequate correlation between the retention factors (log k) and the toxicity (LD(50)) of cardiovascular system drugs was obtained.

  7. 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.

  8. An integrated mathematical model of the cardiovascular and respiratory systems.

    PubMed

    Trenhago, Paulo Roberto; Fernandes, Luciano Gonçalves; Müller, Lucas Omar; Blanco, Pablo Javier; Feijóo, Raúl Antonino

    2016-01-01

    This study presents a lumped model for the human cardiorespiratory system. Specifically, we incorporate a sophisticated gas dissociation and transport system to a fully integrated cardiovascular and pulmonary model. The model provides physiologically consistent predictions in terms of hemodynamic variables such as pressure, flow rate, gas partial pressures, and pH. We perform numerical simulations to evaluate the behavior of the partial pressures of oxygen and carbon dioxide in different vascular and pulmonary compartments. For this, we design the rest condition with low oxygen requirements and carbon dioxide production and exercise conditions with high oxygen demand and carbon dioxide production. Furthermore, model sensitivity to more relevant model parameters is studied. Copyright © 2015 John Wiley & Sons, Ltd.

  9. 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.

  10. 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.

  11. 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.

  12. Experimental models of renal disease and the cardiovascular system.

    PubMed

    Grossman, Rebecca C

    2010-11-26

    Cardiovascular disease is a leading cause of death among patients with end stage renal failure. Animal models have played a crucial role in teasing apart the complex pathological processes involved. This review discusses the principles of using animal models, the history of their use in the study of renal hypertension, the controversies arising from experimental models of non-hypertensive uraemic cardiomyopathy and the lessons learned from these models, and highlights important areas of future research in this field, including de novo cardiomyopathy secondary to renal transplantation.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Modeling and simulation of the cardiovascular system: a review of applications, methods, and potentials.

    PubMed

    Brunberg, Anja; Heinke, Stefanie; Spillner, Jan; Autschbach, Rüdiger; Abel, Dirk; Leonhardt, Steffen

    2009-10-01

    Proper function of the cardiovascular system is indispensible to human survival. However, this system is dominated by complex interactions between different physiological processes and control mechanisms. A structured analysis and a mathematical description of this system can provide more insight, and a computer-based simulation of dynamic processes in the cardiovascular system could be applied in numerous tasks. This article gives a review of different approaches to cardio-circulatory modeling and discusses methodological aspects and fields of application for several classes of models.

  18. 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.

  19. 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%.

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

    PubMed

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

    1993-03-01

    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%.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Roadmap for cardiovascular circulation model.

    PubMed

    Safaei, Soroush; Bradley, Christopher P; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R; Omholt, Stig W; Chase, J Geoffrey; Müller, Lucas O; Watanabe, Sansuke M; Blanco, Pablo J; de Bono, Bernard; Hunter, Peter J

    2016-12-01

    Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well-established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo-skeletal system. The computational infrastructure for the cardiovascular model should provide for near real-time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model.

  7. 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.

  8. 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.

  9. Human cardiovascular model and applications.

    PubMed

    Zhu, K Y; Ang, Alvin; Acharya U, Rajendra; Lim, C M

    2011-10-01

    Cardiovascular diseases (CVDs) can be known as a class of diseases which affect different parts of the cardiovascular system such as the heart or blood vessels. Hemodynamic signals are an important tool used by doctors to diagnose the type of CVD occurred in a patient. Diagnosing the correct type of CVD in a patient early will allow the patient to have the suitable medical treatment. Some examples of CVDs include coronary heart disease, cerebrovascular disease and peripheral arterial disease. A human cardiovascular model is developed in order to simulate different hemodynamic signals of the cardiovascular system. The hemodynamic signals include the blood pressures, flow rates and volumes in various part of the cardiovascular system. This paper presents a model which is able to simulate hemodynamic signals and they are able to represent the human arterial blood pressure accurately. Hence this model can also be used to simulate hypertensive patients in order to design control systems for regulation of blood pressure. Signal verification has been performed and the stability of the model is being investigated. Applications of the human cardiovascular model are also presented.

  10. An Integrative Model of the Cardiovascular System Coupling Heart Cellular Mechanics with Arterial Network Hemodynamics

    PubMed Central

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

    2013-01-01

    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. PMID:23960442

  11. Laboratory model of the cardiovascular system for experimental demonstration of pulse wave propagation

    NASA Astrophysics Data System (ADS)

    Stojadinović, Bojana; Nestorović, Zorica; Djurić, Biljana; Tenne, Tamar; Zikich, Dragoslav; Žikić, Dejan

    2017-03-01

    The velocity by which a disturbance moves through the medium is the wave velocity. Pulse wave velocity is among the key parameters in hemodynamics. Investigation of wave propagation through the fluid-filled elastic tube has a great importance for the proper biophysical understanding of the nature of blood flow through the cardiovascular system. Here, we present a laboratory model of the cardiovascular system. We have designed an experimental setup which can help medical and nursing students to properly learn and understand basic fluid hemodynamic principles, pulse wave and the phenomenon of wave propagation in blood vessels. Demonstration of wave propagation allowed a real time observation of the formation of compression and expansion waves by students, thus enabling them to better understand the difference between the two waves, and also to measure the pulse wave velocity for different fluid viscosities. The laboratory model of the cardiovascular system could be useful as an active learning methodology and a complementary tool for understanding basic principles of hemodynamics.

  12. [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.

  13. 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.

  14. 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

  15. Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices.

    PubMed

    Kosta, S; Negroni, J; Lascano, E; Dauby, P C

    2017-02-01

    A multiscale model of the cardiovascular system is presented. Hemodynamics is described by a lumped parameter model, while heart contraction is described at the cellular scale. An electrophysiological model and a mechanical model were coupled and adjusted so that the pressure and volume of both ventricles are linked to the force and length of a half-sarcomere. Particular attention was paid to the extreme values of the sarcomere length, which must keep physiological values. This model is able to reproduce healthy behavior, preload variations experiments, and ventricular failure. It also allows to compare the relevance of standard cardiac contractility indices. This study shows that the theoretical gold standard for assessing cardiac contractility, namely the end-systolic elastance, is actually load-dependent and therefore not a reliable index of cardiac contractility.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Simulation of Left Atrial Function Using a Multi-Scale Model of the Cardiovascular System

    PubMed Central

    Pironet, Antoine; Dauby, Pierre C.; Paeme, Sabine; Kosta, Sarah; Chase, J. Geoffrey; Desaive, Thomas

    2013-01-01

    During a full cardiac cycle, the left atrium successively behaves as a reservoir, a conduit and a pump. This complex behavior makes it unrealistic to apply the time-varying elastance theory to characterize the left atrium, first, because this theory has known limitations, and second, because it is still uncertain whether the load independence hypothesis holds. In this study, we aim to bypass this uncertainty by relying on another kind of mathematical model of the cardiac chambers. In the present work, we describe both the left atrium and the left ventricle with a multi-scale model. The multi-scale property of this model comes from the fact that pressure inside a cardiac chamber is derived from a model of the sarcomere behavior. Macroscopic model parameters are identified from reference dog hemodynamic data. The multi-scale model of the cardiovascular system including the left atrium is then simulated to show that the physiological roles of the left atrium are correctly reproduced. This include a biphasic pressure wave and an eight-shaped pressure-volume loop. We also test the validity of our model in non basal conditions by reproducing a preload reduction experiment by inferior vena cava occlusion with the model. We compute the variation of eight indices before and after this experiment and obtain the same variation as experimentally observed for seven out of the eight indices. In summary, the multi-scale mathematical model presented in this work is able to correctly account for the three roles of the left atrium and also exhibits a realistic left atrial pressure-volume loop. Furthermore, the model has been previously presented and validated for the left ventricle. This makes it a proper alternative to the time-varying elastance theory if the focus is set on precisely representing the left atrial and left ventricular behaviors. PMID:23755183

  2. 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.

  3. [Thyroid and cardiovascular system].

    PubMed

    Gallowitsch, Hans-Jürgen

    2005-10-01

    The cardiocirculatory changes in hyperthyroidism seem to be an accommodation to the increased metabolic demands and lead to an increased perfusion of the peripheral tissues. Due to the influence of elevated thyroid hormone levels, contractility, stroke volume, resting heart rate, and contraction and relaxation velocity of the left ventricle increase. Caused by direct effect on the smooth vascular muscle, systemic vascular resistance is decreased with the consequence of a diminished afterload and an increased cardiac efficiency. The activation of the renin-angiotensin-aldosteron system and the increased production of erythropoietin additionally lead to an increased blood volume, which increases cardiac preload together with the increased venous backflow. Manifest hypothyroidism is characterized by bradycardia and diastolic dysfunction in rest and systolic dysfunction at stress. Despite a slight increase of diastolic blood pressure due to an increased systemic vascular resistance, blood pressure remains nearly stable because of diminished cardiac output. Hypercholesterinaemia and diastolic hypertension in hypothyroid patients can lead to the development of arteriosclerosis and coronary heart disease (CHD). Also subclinical hypothyroidism is associated with a significantly higher risk for arteriosclerosis and CHD, whereas subclinical hyperthyroidism seems to be associated with an increased mortality for all reasons, especially for cardiovascular diseases.

  4. 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.

  5. 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.

  6. Evaluation of mechanisms of postflight orthostatic intolerance with a simple cardiovascular system model.

    PubMed

    Broskey, Justin; Sharp, M Keith

    2007-10-01

    A significant fraction of astronauts experience postflight orthostatic intolerance (POI) during 10-min stand tests conducted on landing day. The average time that nonfinishers can stand is about 7 min. This phenomenon, including the delay in occurrence of presyncope, was studied with a five-compartment model of the cardiovascular system incorporating compartments for the heart/lungs, systemic arteries and cephalic, central, and caudal veins. The model included 28 independent parameters, including factors characterizing cardiac performance, vascular resistance, intrathoracic pressure, nonlinear venous compliance and circulating blood volume, and 13 dependent parameters, including cardiac output and cardiac and vascular compartment pressures and volumes. First, a sensitivity analysis of hemodynamic indicators of presyncope to independent parameters was performed. Results demonstrated that both cardiac output and arterial pressure were most sensitive to volume-related parameters, particularly total blood volume, and less sensitive to peripheral resistance. Next, a simulated postflight stand test confirmed that fluid loss due to capillary filtration, particularly from the caudal region where transmural pressure is high during standing, is a plausible mechanism of POI that also explains the delayed onset of symptoms in most astronauts. An accumulated drop in arterial pressure sufficient to compromise cerebral perfusion and, therefore, cause syncope was reached in about 7 min with a fluid loss of 280 mL. Finally, additional simulations showed that a 75% increase in peripheral resistance, similar to finishers of stand tests, was insufficient to overcome the loss of circulating fluid associated with capillary filtration, and extended the time that the modeled astronaut could stand by only about 1 min. It is therefore concluded that capillary filtration may play a key role in producing POI and that development of countermeasures should perhaps focus on reducing postflight

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

    PubMed Central

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

    2014-01-01

    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. PMID:25063789

  8. 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.

  9. [Cardiovascular system and aging].

    PubMed

    Saner, H

    2005-12-01

    Aging is one of the most important cardiovascular risk factors. Age-related morphologic changes in large resistance vessels include an intima-media-thickening and increased deposition of matrix substance, ultimately leading to a reduced compliance and an increased stiffness of the vessels. Aging of the heart is mainly characterized by an increase of the left ventricular mass in relation to the chamber volume and a decrease of diastolic function. There is some controversy in regard to the question if these changes in the vessel wall are the consequence of aging or if a decrease in physical activity is a major contributor of this process. With age the cardiovascular profile is changing. Whereas smoking is less prominent, arterial hypertension and diabetes mellitus are more often encountered. Primary and secondary prevention through cardiovascular risk factor management is also very important in the aging population due to the increased risk of acute vascular complications with age. Preventive measures have to include life style factor interventions as well as optimized drug therapy. There is no scientific evidence that vascular aging can be prevented by administration of supplements such as antioxidant vitamins. Aspirin is effective for cardiovascular prevention up to a higher age. Betablockers and ACE-inhibitors are generally underused in older patients after myocardial infarctions. Statins are effective in reducing cardiovascular complications up to an age of 80 years. Myocardial infarction in elderly patients is often characterized by atypical symptoms and may be even silent. Interventional therapy in elderly patients is as successful as in younger patients but has an increased complication rate. Ambulatory cardiac rehabilitation in elderly patients leads to significant improvements of physical capacity, well-being and quality of life and may help to prevent social isolation.

  10. Glucocorticoids and the Cardiovascular System.

    PubMed

    Goodwin, Julie E

    2015-01-01

    Glucocorticoids affect the developing and mature cardiovascular system in profound and, at times, contradictory ways. The glucocorticoid receptor is ubiquitous in most cell types and conserved across species, highlighting its importance in development and homeostasis. Despite the fact that the glucocorticoid receptor is widely expressed, tissue-specific effects of glucocorticoids may have pronounced effects on whole organism phenotypes. Here we will review the interactions between glucocorticoids and the cardiovascular system.

  11. Lymphatic System in Cardiovascular Medicine.

    PubMed

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

    2016-02-05

    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.

  12. 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.

  13. Nitric oxide and cardiovascular system.

    PubMed

    Cengel, Atiye; Sahinarslan, Asife

    2006-12-01

    Endothelium has many important functions including the control of blood-tissue permeability and vascular tonus, regulation of vascular surface properties for homeostasis and inflammation. Nitric oxide is the chief molecule in regulation of endothelial functions. Nitric oxide deficiency, which is also known as endothelial dysfunction, is the first step for the occurrence of many disease states in cardiovascular system including heart failure, hypertension, dyslipidemia, insulin resistance, diabetes mellitus, hyperhomocysteinemia and smoking. This review deals with the importance of nitric oxide for cardiovascular system. It also includes the latest improvements in the diagnosis and treatment of endothelial dysfunction.

  14. 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.

  15. 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.

  16. 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

  17. Simulation of hemodynamic responses to the valsalva maneuver: an integrative computational model of the cardiovascular system and the autonomic nervous system.

    PubMed

    Liang, Fuyou; Liu, Hao

    2006-02-01

    The Valsalva maneuver is a frequently used physiological test in evaluating the cardiovascular autonomic functions in human. Although a large pool of experimental data has provided substantial insights into different aspects of the mechanisms underlying the cardiovascular regulations during the Valsalva maneuver, so far a complete comprehension of these mechanisms and the interactions among them is unavailable. In the present study, a computational model of the cardiovascular system (CVS) and its interaction with the autonomic nervous system (ANS) was developed for the purpose of quantifying the individual roles of the CVS and the ANS in the hemodynamic regulations during the Valsalva maneuver. A detailed computational compartmental parameter model of the global CVS, a system of mathematical equations representing the autonomic nervous reflex regulatory functions, and an empirical cerebral autoregulation (CA) model formed the main body of the present model. Based on simulations of the Valsalva maneuvers at several typical postures, it was demonstrated that hemodynamic responses to the maneuver were not only determined by the ANS-mediated cardiovascular regulations, but also significantly affected by the postural-change-induced hemodynamic alterations preceding the maneuver. Moreover, the large-magnitude overshoot in cerebral perfusion immediately after the Valsalva maneuver was found to result from a combined effect of the circulatory autonomic functions, the CA, and the cerebral venous blood pressure.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. PET Radiotracers of the Cardiovascular System.

    PubMed

    Gropler, Robert J

    2009-01-01

    Cardiovascular PET provides exquisite measurements of key aspects of the cardiovascular system and as a consequence it plays central role in cardiovascular investigation. Moreover, PET is now playing an ever increasing role in the management of the cardiac patient. Central to the success of PET is the development and use of novel radiotracers that permit measurements of key aspects of cardiovascular health such as myocardial perfusion, metabolism, and neuronal function. Moreover, the development of molecular imaging radiotracers is now permitting the interrogation of cellular and sub cellular processes. This article highlights these various radiotracers and their role in both cardiovascular research and potential clinical applications.

  3. 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.

  4. KATP Channels in the Cardiovascular System

    PubMed Central

    Foster, Monique N.; Coetzee, William A.

    2015-01-01

    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. PMID:26660852

  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. Multiscale modeling of the cardiovascular system: application to the study of pulmonary and coronary perfusions in the univentricular circulation.

    PubMed

    Laganà, Katia; Balossino, Rossella; Migliavacca, Francesco; Pennati, Giancarlo; Bove, Edward L; de Leval, Marc R; Dubini, Gabriele

    2005-05-01

    The objective of this study is to compare the coronary and pulmonary blood flow dynamics resulting from two configurations of systemic-to-pulmonary artery shunts currently utilized during the Norwood procedure: the central (CS) and modified Blalock Taussig (MBTS) shunts. A lumped parameter model of the neonatal cardiovascular circulation and detailed 3-D models of the shunt based on the finite volume method were constructed. Shunt sizes of 3, 3.5 and 4 mm were considered. A multiscale approach was adopted to prescribe appropriate and realistic boundary conditions for the 3-D models of the Norwood circulation. Results showed that the average shunt flow rate is higher for the CS option than for the MBTS and that pulmonary flow increases with shunt size for both options. Cardiac output is higher for the CS option for all shunt sizes. Flow distribution between the left and the right pulmonary arteries is not completely balanced, although for the CS option the discrepancy is low (50-51% of the pulmonary flow to the right lung) while for the MBTS it is more pronounced with larger shunt sizes (51-54% to the left lung). The CS option favors perfusion to the right lung while the MBTS favors the left. In the CS option, a smaller percentage of aortic flow is distributed to the coronary circulation, while that percentage rises for the MBTS. These findings may have important implications for coronary blood flow and ventricular function.

  7. [Altitude and the cardiovascular system].

    PubMed

    Richalet, Jean-Paul

    2012-06-01

    A stay at high altitude exposes an individual to various environmental changes (cold, exercise, isolation) but the most stressful for the body is hypoxia. However, the cardiovascular system yields some efficient mechanisms of acclimatization to oxygen lack. Hypoxia activates the adrenergic system and induces a tachycardia that decreases during a prolonged stay at altitude. The desensitization of the adrenergic system leads to a decrease in maximal heart rate and a protection of the myocardium against an energy disequilibrium that could be potentially harmful for the heart. Hypoxia induces a peripheral vasodilation and a pulmonary vasoconstriction, leading to few changes in systemic blood pressure and an increase in pulmonary blood pressure (PHT) that can contribute to a high altitude pulmonary edema. Advice to a cardiac patient who plans to go to high altitude should take into account that all diseases aggravated by increased adrenergic activity or associated with a PHT or a hypoxemia (right-to-left shunt) will be aggravated at high altitude. As altitude increases, a patient with a coronary disease will present an ischemic threshold for a lower power output during an EKG exercise test. The only test allowing predicting the tolerance to high altitude is the hypoxia exercise test realized at 30% of maxVO(2)and at an equivalent altitude of 4,800m.

  8. A multi-scale cardiovascular system model can account for the load-dependence of the end-systolic pressure-volume relationship

    PubMed Central

    2013-01-01

    Background The end-systolic pressure-volume relationship is often considered as a load-independent property of the heart and, for this reason, is widely used as an index of ventricular contractility. However, many criticisms have been expressed against this index and the underlying time-varying elastance theory: first, it does not consider the phenomena underlying contraction and second, the end-systolic pressure volume relationship has been experimentally shown to be load-dependent. Methods In place of the time-varying elastance theory, a microscopic model of sarcomere contraction is used to infer the pressure generated by the contraction of the left ventricle, considered as a spherical assembling of sarcomere units. The left ventricle model is inserted into a closed-loop model of the cardiovascular system. Finally, parameters of the modified cardiovascular system model are identified to reproduce the hemodynamics of a normal dog. Results Experiments that have proven the limitations of the time-varying elastance theory are reproduced with our model: (1) preload reductions, (2) afterload increases, (3) the same experiments with increased ventricular contractility, (4) isovolumic contractions and (5) flow-clamps. All experiments simulated with the model generate different end-systolic pressure-volume relationships, showing that this relationship is actually load-dependent. Furthermore, we show that the results of our simulations are in good agreement with experiments. Conclusions We implemented a multi-scale model of the cardiovascular system, in which ventricular contraction is described by a detailed sarcomere model. Using this model, we successfully reproduced a number of experiments that have shown the failing points of the time-varying elastance theory. In particular, the developed multi-scale model of the cardiovascular system can capture the load-dependence of the end-systolic pressure-volume relationship. PMID:23363818

  9. A Multi-Branched Model of the Cardiovascular System: Application to G- Research

    DTIC Science & Technology

    1993-01-01

    model respectively. Because baboon and human physiology are different, we only expect qualitative similarities in the two. In this case, an increase...well as in the centrifuge. With human centrifuge data, we can improve our model and promote better understanding of human physiology under altered G

  10. Mathematical modelling of the human foetal cardiovascular system based on Doppler ultrasound data.

    PubMed

    Pennati, G; Bellotti, M; Fumero, R

    1997-06-01

    A lumped parameter model of the human foetal circulation primarily based on blood velocity data derived from the Doppler analysis was developed in this study. It consists of two major parts, the heart and the foetal vascular circulation. The heart model accounts for both ventricular and atrial contractility. The circulation was divided into 19 compliant vascular compartments in order to describe all of the clinically monitored sites. The model parameters refer to the final gestation period and were derived either from literature on foetal sheep circulation or from anatomical dimension monitoring of the human foetus. No control mechanism is incorporated into the model. The model was validated by comparing several index values of simulated velocity curves to those of the experimental Doppler waveforms. The mean and maximum percentual errors in the estimation of the experimental results by the model are 7.7% and 20.1%, respectively. Velocity and pressure tracings of the foetal circulation were investigated, as well as regional blood flow rate distribution.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Physics of the human cardiovascular system

    NASA Astrophysics Data System (ADS)

    Stefanovska, Aneta

    1999-01-01

    Contemporary measurement techniques permit the non-invasive observation of several cardiovascular functions, both from the central and peripheral points of view. We show that, within one cycle of blood through the cardiovascular system, the same dynamics characterizes heart function as well as blood flow in the capillary bed where cells exchange energy and matter. Analyses of several quite different signals derived from respiration, cardiac function and blood flow, all reveal the existence of five almost periodic frequency components. This result is interpreted as evidence that cardiovascular dynamics is governed by five coupled oscillators. The couplings provide co-ordination among the physiological processes involved, and are essential for efficient cardiovascular function. Understanding the dynamics of a system of five coupled oscillators not only represents a theoretical challenge, but also carries practical implications for diagnosis and for predicting the future behaviour of this life giving system.

  16. Exercise and the cardiovascular system.

    PubMed

    Golbidi, Saeid; Laher, Ismail

    2012-01-01

    There are alarming increases in the incidence of obesity, insulin resistance, type II diabetes, and cardiovascular disease. The risk of these diseases is significantly reduced by appropriate lifestyle modifications such as increased physical activity. However, the exact mechanisms by which exercise influences the development and progression of cardiovascular disease are unclear. In this paper we review some important exercise-induced changes in cardiac, vascular, and blood tissues and discuss recent clinical trials related to the benefits of exercise. We also discuss the roles of boosting antioxidant levels, consequences of epicardial fat reduction, increases in expression of heat shock proteins and endoplasmic reticulum stress proteins, mitochondrial adaptation, and the role of sarcolemmal and mitochondrial potassium channels in the contributing to the cardioprotection offered by exercise. In terms of vascular benefits, the main effects discussed are changes in exercise-induced vascular remodeling and endothelial function. Exercise-induced fibrinolytic and rheological changes also underlie the hematological benefits of exercise.

  17. 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.

  18. A reduced-order model-based study on the effect of intermittent pneumatic compression of limbs on the cardiovascular system.

    PubMed

    Maffiodo, Daniela; De Nisco, Giuseppe; Gallo, Diego; Audenino, Alberto; Morbiducci, Umberto; Ferraresi, Carlo

    2016-04-01

    This work investigates the effect that the application of intermittent pneumatic compression to lower limbs has on the cardiovascular system. Intermittent pneumatic compression can be applied to subjects with reduced or null mobility and can be useful for therapeutic purposes in sports recovery, deep vein thrombosis prevention and lymphedema drainage. However, intermittent pneumatic compression performance and the effectiveness are often difficult to predict. This study presents a reduced-order numerical model of the interaction between the cardiovascular system and the intermittent pneumatic compression device. The effect that different intermittent pneumatic compression operating conditions have on the overall circulation is investigated. Our findings confirm (1) that an overall positive effect on hemodynamics can be obtained by properly applying the intermittent pneumatic compression device and (2) that using intermittent pneumatic compression for cardiocirculatory recovery is feasible in subjects affected by lower limb disease.

  19. 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

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

    2013-01-01

    The purpose of this investigation is to use a computational model to compare a synchronized valveless pulsatile left ventricular assist device with 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 the 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 with 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 with 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.

  20. [Alcohol and the cardiovascular system].

    PubMed

    Frenzel, H; Roth, H; Schwartzkopff, B

    1988-10-01

    Because of the high frequency of cardiovascular diseases and a steadily increasing consumption of alcohol the potentially causal relationship between alcohol and cardiovascular diseases gains great interest for public health policy. Alcohol and its metabolites induce a toxic damage of myocardial metabolism with an injury of electromechanic coupling. As a consequence of acute alcoholic intake cardiac arrhythmias and a reduced contractility of the myocardium are found not only for chronic alcoholics but also in healthy non-drinkers. Chronic abuse of alcoholic beverages for many years can be the cause of alcoholic cardiomyopathy in a small percentage of patients, who have a bad prognosis. Atria and ventricles are dilated, light and electron microscopic changes of the myocardium are unspecific. The pathogenesis of alcoholic cardiomyopathy is unknown, modulations of cardiomyocytic membranes are discussed in the course of a toxic damage. In the genesis of atherosclerosis alcohol can approach from different sites: Changings on thrombocytes and an increase of HDL-cholesterin can be protective, however an increase in blood pressure support the process of atherosclerosis. In numerous investigations a smaller degree of atherosclerosis was found for little or moderate alcohol intake, while in chronic heavy abuse of alcohol a higher extent of atherosclerosis was observed. As the amount of alcohol, assumed to be protective against the development of atherosclerosis, is consumed already by the majority of the population, there is no reason to propagate a regulate consume of moderate amount of alcoholic beverages.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. [Cell polarity in the cardiovascular system].

    PubMed

    Haller, C; Kübler, W

    1999-05-01

    The importance of cell polarity as a fundamental biological principle is increasingly recognized in the cardiovascular system. Polar cell mechanisms underlie not only the development of the heart and blood vessels, but also play a major role in the adult organism for polarized endothelial functions such as the separation of the intra- and extravascular compartment and the vectorial exchange of substances between these compartments. Endothelial cells are connected through intercellular junctions which separate the functionally and structurally distinct luminal and abluminal cell surfaces. The luminal plasma membrane is in contact with the blood and takes part in the regulation of hemostasis. The abluminal cell membrane connects the endothelial cell with the basement membrane and modulates blood flow through the release of vasoactive substances. Results from epithelial model systems have shown that the polarized cell phenotype is generated by specific protein sorting and regulated protein trafficking between the trans-Golgi network and the cell surface. The polarized distribution of cell membrane proteins is maintained by anchorage with the cytoskeleton and limitation of lateral diffusion by tight junctions. Disturbances of cell polarity may contribute to the pathogenesis of disease states, including ischemic and radiocontrast-induced acute renal failure and carcinomas. Recent results have demonstrated the importance of cholesterol for protein traffic from the trans-Golgi network to the apical cell membrane. This novel intracellular function of cholesterol could point to a connection between cell polarity and the pathogenesis of arteriosclerosis. The polarity of the endothelium also has to be taken into account when developing gene-therapeutic strategies, since therapeutic success will not only depend on the efficient expression of the desired gene product, but also on its correct cellular location or secretion into the correct extracellular compartment. These

  6. 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.

  7. 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.

  8. 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

  9. [Cardiovascular disease and systemic inflammatory diseases].

    PubMed

    Cuende, José I; Pérez de Diego, Ignacio J; Godoy, Diego

    2016-01-01

    More than a century of research has shown that atherosclerosis is an inflammatory process more than an infiltrative or thrombogenic process. It has been demonstrated epidemiologically and by imaging techniques, that systemic inflammatory diseases (in particular, but not exclusively, rheumatoid arthritis and systemic lupus erythematosus) increase the atherosclerotic process, and has a demonstrated pathophysiological basis. Furthermore, treatments to control inflammatory diseases can modify the course of the atherosclerotic process. Although there are no specific scales for assessing cardiovascular risk in patients with these diseases, cardiovascular risk is high. A number of specific risk scales are being developed, that take into account specific factors such as the degree of inflammatory activity.

  10. 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.

  11. Acute pneumonia and the cardiovascular system.

    PubMed

    Corrales-Medina, Vicente F; Musher, Daniel M; Shachkina, Svetlana; Chirinos, Julio A

    2013-02-09

    Although traditionally regarded as a disease confined to the lungs, acute pneumonia has important effects on the cardiovascular system at all severities of infection. Pneumonia tends to affect individuals who are also at high cardiovascular risk. Results of recent studies show that about a quarter of adults admitted to hospital with pneumonia develop a major acute cardiac complication during their hospital stay, which is associated with a 60% increase in short-term mortality. These findings suggest that outcomes of patients with pneumonia can be improved by prevention of the development and progression of associated cardiac complications. Before this hypothesis can be tested, however, an adequate mechanistic understanding of the cardiovascular changes that occur during pneumonia, and their role in the trigger of various cardiac complications, is needed. In this Review, we summarise knowledge about the burden of cardiac complications in adults with acute pneumonia, the cardiovascular response to this infection, the potential effects of commonly used cardiovascular and anti-infective drugs on these associations, and possible directions for future research.

  12. Modulation of the cardiovascular system by leptin.

    PubMed

    Abel, E Dale; Sweeney, Gary

    2012-10-01

    It is well established that individuals with the metabolic syndrome have a significantly increased risk of cardiovascular disease and much effort has been expended to elicit the underlying mechanisms. Various studies have proposed that excessive or deficient physiological effects mediated by leptin make an important contribution, yet many paradoxical observations often preclude a clear definition of the role of leptin. This review article will briefly discuss principal and most recent evidence on direct and indirect regulation of the cardiovascular system by leptin, focusing on cardiac structural and functional as well as vascular effects.

  13. 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.

  14. 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

    2015-07-03

    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.

  15. Translational In Vivo Models for Cardiovascular Diseases.

    PubMed

    Fliegner, Daniela; Gerdes, Christoph; Meding, Jörg; Stasch, Johannes-Peter

    2016-01-01

    Cardiovascular diseases are still the first leading cause of death and morbidity in developed countries. Experimental cardiology research and preclinical drug development in cardiology call for appropriate and especially clinically relevant in vitro and in vivo studies. The use of animal models has contributed to expand our knowledge and our understanding of the underlying mechanisms and accordingly provided new approaches focused on the improvement of diagnostic and treatment strategies of various cardiac pathologies.Numerous animal models in different species as well as in small and large animals have been developed to address cardiovascular complications, including heart failure, pulmonary hypertension, and thrombotic diseases. However, a perfect model of heart failure or other indications that reproduces every aspect of the natural disease does not exist. The complexity and heterogeneity of cardiac diseases plus the influence of genetic and environmental factors limit to mirror a particular disease with a single experimental model.Thus, drug development in the field of cardiology is not only very challenging but also inspiring; therefore animal models should be selected that reflect as best as possible the disease being investigated. Given the wide range of animal models, reflecting critical features of the human pathophysiology available nowadays increases the likelihood of the translation to the patients. Furthermore, this knowledge and the increase of the predictive value of preclinical models help us to find more efficient and reliable solutions as well as better and innovative treatment strategies for cardiovascular diseases.

  16. 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.

  17. Cardiovascular remodeling and the peripheral serotonergic system.

    PubMed

    Ayme-Dietrich, Estelle; Aubertin-Kirch, Gaëlle; Maroteaux, Luc; Monassier, Laurent

    2017-01-01

    Plasma 5-hydroxytryptamine (5-HT; serotonin), released from blood platelets, plays a major role in the human cardiovascular system. Besides the effect of endogenous serotonin, many drugs targeting serotonergic receptors are widely used in the general population (antiobesity agents, antidepressants, antipsychotics, antimigraine agents), and may enhance the cardiovascular risk. Depending on the type of serotonin receptor activated and its location, the use of these compounds triggers acute and chronic effects. The acute cardiovascular response to 5-HT, named the Bezold-Jarish reflex, leads to intense bradycardia associated with atrioventricular block, and involves 5-HT3, 5-HT1B/1D, 5-HT7 and 5-HT2A/2B receptors. The chronic contribution of 5-HT and its receptors (5-HT4 and 5-HT2A/2B) in cardiovascular tissue remodeling, with a particular emphasis on cardiac hypertrophy, fibrosis and valve degeneration, will be explored in this review. Finally, through the analysis of the effects of sarpogrelate, some new aspects of 5-HT2A receptor pharmacology in vasomotor tone regulation and the interaction between endothelial and smooth muscle cells will also be discussed. The aim of this review is to emphasize the cardiac side effects caused by serotonin receptor activation, and to highlight their possible prevention by the development of new drugs targeting this system.

  18. Principal Component Analysis of HPLC Retention Data and Molecular Modeling Structural Parameters of Cardiovascular System Drugs in View of Their Pharmacological Activity

    PubMed Central

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

    2010-01-01

    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). PMID:20717530

  19. 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).

  20. 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

  1. Does the kinin system mediate in cardiovascular abnormalities? An overview.

    PubMed

    Sharma, Jagdish N

    2003-11-01

    All the components of the kallikrein-kinin system are located in the cardiac muscle, and its deficiency may lead to cardiac dysfunction. In recent years, numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischemia, myocardial infarction, and left ventricular hypertrophy have suggested that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular-related diseases. The cardioprotective property of the angiotensin-converting enzyme inhibitors is primarily mediated via the kinin-releasing pathway, which may cause regression of left ventricular hypertrophy in hypertensive situations. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating hypertension and cardiovascular and renal diseases. In addition, stable kinin agonists may also be available in the future as therapeutic agents for cardiovascular and renal disorders.

  2. 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.

  3. 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.

  4. Mathematical biomarkers for the autonomic regulation of cardiovascular system

    PubMed Central

    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

  5. Drug releasing systems in cardiovascular tissue engineering.

    PubMed

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

    2009-03-01

    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.

  6. 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

  7. Physiological Changes to the Cardiovascular System at High Altitude and Its Effects on Cardiovascular Disease.

    PubMed

    Riley, Callum James; Gavin, Matthew

    2017-03-15

    Riley, Callum James, and Matthew Gavin. Physiological changes to the cardiovascular system at high altitude and its effects on cardiovascular disease. High Alt Med Biol. 00:000-000, 2017.-The physiological changes to the cardiovascular system in response to the high altitude environment are well understood. More recently, we have begun to understand how these changes may affect and cause detriment to cardiovascular disease. In addition to this, the increasing availability of altitude simulation has dramatically improved our understanding of the physiology of high altitude. This has allowed further study on the effect of altitude in those with cardiovascular disease in a safe and controlled environment as well as in healthy individuals. Using a thorough PubMed search, this review aims to integrate recent advances in cardiovascular physiology at altitude with previous understanding, as well as its potential implications on cardiovascular disease. Altogether, it was found that the changes at altitude to cardiovascular physiology are profound enough to have a noteworthy effect on many forms of cardiovascular disease. While often asymptomatic, there is some risk in high altitude exposure for individuals with certain cardiovascular diseases. Although controlled research in patients with cardiovascular disease was largely lacking, meaning firm conclusions cannot be drawn, these risks should be a consideration to both the individual and their physician.

  8. Free radical biology of the cardiovascular system.

    PubMed

    Chen, Alex F; Chen, Dan-Dan; Daiber, Andreas; Faraci, Frank M; Li, Huige; Rembold, Christopher M; Laher, Ismail

    2012-07-01

    Most cardiovascular diseases (CVDs), as well as age-related cardiovascular alterations, are accompanied by increases in oxidative stress, usually due to increased generation and/or decreased metabolism of ROS (reactive oxygen species; for example superoxide radicals) and RNS (reactive nitrogen species; for example peroxynitrite). The superoxide anion is generated by several enzymatic reactions, including a variety of NADPH oxidases and uncoupled eNOS (endothelial NO synthase). To relieve the burden caused by this generation of free radicals, which also occurs as part of normal physiological processes, such as mitochondrial respiratory chain activity, mammalian systems have developed endogenous antioxidant enzymes. There is an increased usage of exogenous antioxidants such as vitamins C and E by many patients and the general public, ostensibly in an attempt to supplement intrinsic antioxidant activity. Unfortunately, the results of large-scale trails do not generate much enthusiasm for the continued use of antioxidants to mitigate free-radical-induced changes in the cardiovascular system. In the present paper, we review the clinical use of antioxidants by providing the rationale for their use and describe the outcomes of several large-scale trails that largely display negative outcomes. We also describe the emerging understanding of the detailed regulation of superoxide generation by an uncoupled eNOS and efforts to reverse eNOS uncoupling. SIRT1 (sirtuin 1), which regulates the expression and activity of multiple pro- and anti-oxidant enzymes, could be considered a candidate molecule for a 'molecular switch'.

  9. 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.

  10. Modelling the cardiovascular effects of ephedrine

    PubMed Central

    Persky, Adam M; Berry, N Seth; Pollack, Gary M; Brouwer, Kim L R

    2004-01-01

    Aims Recent reports have called into question the safety of ephedra supplements especially with regards to their cardiovascular effects. The purpose of this analysis was to characterize, via pharmacokinetic/pharmacodynamic modelling, the cardiovascular effects of ephedrine, the main active ingredient of ephedra, in apparently healthy, overweight volunteers. Methods In a randomized, double-blind, crossover, placebo-controlled study, eight subjects received either placebo, 0.25, 0.5 or 1.0 mg kg−1 ephedrine sulphate by mouth with a 7-day washout between treatments. Plasma ephedrine concentrations, heart rate and blood pressure were determined for 8 h postdose. Results The pharmacokinetics of ephedrine were best described by a one-compartment model with first-order absorption and elimination. The percentage change in heart rate was described by a linear model with a resulting slope of 0.14%·l µg−1 (CV = 59%). The percentage change in systolic blood pressure demonstrated clockwise hysteresis, and a sigmoidal tolerance model was used to describe the data. The mean maximum predicted effect (Emax) was 53.7% (CV = 41%) with an EC50 of 107 µg·l−1 (CV = 65%) and an inhibitory maximum (Imax) of 39.8% (CV = 60%). Tolerance developed with a mean half-life of 15 min (range 6–140 min). Conclusions This is the first study to apply a comprehensive pharmacokinetic/pharmacodynamic model to the cardiovascular effects of orally administered ephedrine. Although systolic blood pressure increases quickly after administration, the increase is nearly abolished by compensatory mechanisms. PMID:15089807

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

    PubMed

    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.

  12. 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

  13. 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

  14. Distribution of nitric oxide in cardiovascular system.

    PubMed

    Mesáros, S; Grunfeld, S

    1997-01-01

    We report here the in vitro measurements of nitric oxide in the cardiovascular system using a porphyrinic sensor specific for NO. Nitric oxide concentrations were measured directly in different parts of the heart and also in different arteries and veins, ranging from 100 microm to 5 mm in diameter. Highest NO. concentrations were found in the heart and particularly in the areas of aortic and pulmonary valves. The NO. concentration in the arteries was higher than in the veins. A clearcut positive correlation was obtained by plotting the vessel diameter and production of nitric oxide.

  15. 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.

  16. Targets of oxidative stress in cardiovascular system.

    PubMed

    Chakraborti, T; Ghosh, S K; Michael, J R; Batabyal, S K; Chakraborti, S

    1998-10-01

    Although oxidants such as superoxide (O2.) and hydrogen peroxide (H2O2) play a role in host-mediated destruction of foreign pathogens yet excessive generation of oxidants may lead to a variety of pathological complications in the cardiovascular system. An important mechanism by which oxidants cause dysfunction of the cardiovascular system appears to be due to the increase in intracellular free Ca2+ concentration. Oxidants cause cellular Ca2+ mobilization by modulating activities of a variety of regulators such as Na+/H+ and Na+/Ca2+ exchangers, Na+/K+ ATPase and Ca2+ ATPase and Ca2+ channels that are associated with Ca2+ transport in the plasma membrane and the sarco(endo)plasmic reticular membrane of myocardial cells. Recent research have suggested that the increase in Ca2+ level by oxidants plays a pivotal role in inducing several protein kinases such as protein kinase C, tyrosine kinase and mitogen activated protein kinases. Oxidant-mediated alteration of different signal transduction systems and their interations eventually regulate a variety of pathological conditions such as atherosclerosis, apoptosis and necrosis in the myocardium.

  17. 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

  18. Role of endothelin in the cardiovascular system.

    PubMed

    Rodríguez-Pascual, Fernando; Busnadiego, Oscar; Lagares, David; Lamas, Santiago

    2011-06-01

    The endothelin (ET) system consists of three peptide ligands (ET-1, ET-2 and ET-3) and two G-protein-coupled receptors, ET(A) and ET(B). In the cardiovascular system, ETs, particularly ET-1, are expressed in smooth muscle cells, cardiomyocytes, fibroblasts, and notably in vascular endothelial cells. Intense research over the last 10 years has changed the original view of ET-1 as mainly a vasoconstrictor regulating blood pressure, into a biological factor regulating processes such as vascular remodeling, angiogenesis or extracellular matrix synthesis. The advent of specific (and type-selective) ET receptor antagonists has greatly fostered our knowledge of the biological function of ET-1, and has offered a potential therapeutic approach for numerous diseases including hypertension, atherosclerosis or fibrosis. In this article, we review the regulation of the expression of vascular ET-1, as well as the contribution of ET-1 to endothelial, smooth muscle and fibroblast cell function, with particular interest in the role of ET-1 in the development of cardiovascular diseases.

  19. 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

  20. [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.

  1. 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.

  2. 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

  3. 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...

  4. 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.

  5. The brain norepinephrine system, stress and cardiovascular vulnerability.

    PubMed

    Wood, Susan K; Valentino, Rita J

    2017-03-01

    Chronic exposure to psychosocial stress has adverse effects on cardiovascular health, however the stress-sensitive neurocircuitry involved remains to be elucidated. The anatomical and physiological characteristics of the locus coeruleus (LC)-norepinephrine (NE) system position it to contribute to stress-induced cardiovascular disease. This review focuses on cardiovascular dysfunction produced by social stress and a major theme highlighted is that differences in coping strategy determine individual differences in social stress-induced cardiovascular vulnerability. The establishment of different coping strategies and cardiovascular vulnerability during repeated social stress has recently been shown to parallel a unique plasticity in LC afferent regulation, resulting in either excitatory or inhibitory input to the LC. This contrasting regulation of the LC would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The advances described suggest new directions for developing treatments and/or strategies for decreasing stress-induced cardiovascular vulnerability.

  6. 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.

  7. 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

  8. Common swine models of cardiovascular disease for research and training.

    PubMed

    Crisóstomo, Verónica; Sun, Fei; Maynar, Manuel; Báez-Díaz, Claudia; Blanco, Virginia; Garcia-Lindo, Monica; Usón-Gargallo, Jesús; Sánchez-Margallo, Francisco Miguel

    2016-02-01

    Cardiovascular diseases are a major health concern and therefore an important topic in biomedical research. Large animal models allow researchers to assess the safety and efficacy of new cardiovascular procedures in systems that resemble human anatomy; additionally, they can be used to emulate scenarios for training purposes. Among the many biomedical models that are described in published literature, it is important that researchers understand and select those that are best suited to achieve the aims of their research, that facilitate the humane care and management of their research animals and that best promote the high ethical standards required of animal research. In this resource the authors describe some common swine models that can be easily incorporated into regular practices of research and training at biomedical institutions. These models use both native and altered vascular anatomy of swine to carry out research protocols, such as testing biological reactions to implanted materials, surgically creating aneurysms using autologous tissue and inducing myocardial infarction through closed-chest procedures. Such models can also be used for training, where native and altered vascular anatomy allow medical professionals to learn and practice challenging techniques in anatomy that closely simulates human systems.

  9. 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.

  10. [Assessing the cardiovascular risk in patients with systemic lupus erythematosus].

    PubMed

    Arnaud, L; Mathian, A; Bruckert, E; Amoura, Z

    2014-11-01

    Multiple factors contribute to the increased cardiovascular risk observed in patients with systemic lupus erythematosus (SLE). Among these are the so-called classical cardiovascular risk factors, the disease itself through its activity, treatments, and complications, and the thrombotic risk due to antiphospholipid antibodies (aPL). Observational studies suggest that most classical cardiovascular risk factors are observed more frequently in SLE patients than in the general population, and that these are insufficient to explain the increased cardiovascular risk observed in most studies. Given this high risk, adequate management of cardiovascular risk factors should be recommended in SLE patients. Paradoxically, the benefit due to the anti-inflammatory properties of treatments such as corticosteroids may exceed, in certain cases, their pro-atherogenic effect. Importantly, the tools that were developed for the estimation of cardiovascular risk at the individual level among the general population cannot be used reliably in SLE patients, as these tools appear to underestimate the true cardiovascular risk. The adequate indications and targets of cardiovascular treatments are therefore not fully known in SLE. A better understanding of the determinants of the cardiovascular risk in SLE will allow the identification and more tailored management of these high-risk patients.

  11. 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.

  12. Aldosterone and the cardiovascular system: a dangerous association.

    PubMed

    Cachofeiro, Victoria; López-Andrés, Natalia; Miana, Maria; Martín-Fernández, Beatriz; de Las Heras, Natalia; Martínez, Ernesto; Lahera, Vicente; Fortuño, María Antonia

    2010-12-01

    Initial studies have focussed on the actions of aldosterone in renal electrolyte handling and, as a consequence, blood pressure control. More recently, attention has primarily been focussed on its actions on the heart and vascular system, where it is locally produced. Aldosterone by binding mineralocorticoid receptors causes oxidative stress, fibrosis and triggers an inflammatory response in the cardiovascular system. All these effects could be underlying the role of aldo-sterone on cardiac and vascular remodelling associated with different pathological situations. At the vascular level, aldo-sterone affects endothelial function because administration of aldosterone to rats impaired endothelium-dependent relaxations. In addition, the administration of mineralocorticoid receptor antagonists ameliorates endothelium-dependent relaxation in models of both hypertension and atherosclerosis, and in patients with heart failure. Several mechanisms can participate in this effect, including production of vasoconstrictor factors and a reduction in nitric oxide levels. This reduction can involve both a decrease in its production as well as an increase in its degradation by reactive oxygen species. Aldosterone can produce oxidative stress by the activation of transcription factors such as the NF-κB system, which can also trigger an inflammatory process through the production of different cytokines. At cardiac level, high levels of aldosterone can also adversely impact heart function by producing cardiac hypertrophy, diastolic dysfunction and electrical remodelling through changes in ionic channels. All these effects can explain the beneficial effect of mineralocorticoid blockade in the cardiovascular system.

  13. Mechanisms of Lipotoxicity in the Cardiovascular System

    PubMed Central

    Wende, Adam R.; Symons, J. David; Abel, E. Dale

    2012-01-01

    Cardiovascular diseases account for approximately one third of all deaths globally. Obese and diabetic patients have a high likelihood of dying from complications associated with cardiovascular dysfunction. Obesity and diabetes increase circulating lipids that upon tissue uptake, may be stored as triglyceride, or may be metabolized in other pathways, leading to the generation of toxic intermediates. Excess lipid utilization or activation of signaling pathways by lipid metabolites may disrupt cellular homeostasis and contribute to cell death, defining the concept of lipotoxicity. Lipotoxicity occurs in multiple organs, including cardiac and vascular tissues, and a number of specific mechanisms have been proposed to explain lipotoxic tissue injury. In addition, recent data suggests that increased tissue lipids may also be protective in certain contexts. This review will highlight recent progress toward elucidating the relationship between nutrient oversupply, lipotoxicity, and cardiovascular dysfunction. The review will focus in two sections on the vasculature and cardiomyocytes respectively. PMID:23054891

  14. 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

  15. [Effects of vitamin D on the cardiovascular system].

    PubMed

    Shoji, Tetsuo; Nishizawa, Yoshiki

    2006-07-01

    Active vitamin D plays important roles not only in bone and mineral metabolism but also in the cardiovascular system. Cohort studies in hemodialysis patients demonstrated that use of active vitamin D analogs was associated with reduced risk of death, particularly death from cardiovascular disease. Treatment with vitamin D had beneficial effects on cardiac and immune functions in dialysis patients, and inflammatory markers in non-renal subjects. Also, anti-proteinuric effect was recently shown in chronic kidney disease. Experimentally, active vitamin D inhibits atherogenic cellular behaviors and activation of the renin-angiotensin system. Thus, active vitamin D is a regulator of cardiovascular and kidney functions.

  16. Leukocytes Link Local and Systemic Inflammation in Ischemic Cardiovascular Disease: An Expanded “Cardiovascular Continuum”

    PubMed Central

    Libby, Peter; Nahrendorf, Matthias; Swirski, Filip K.

    2016-01-01

    We have traditionally viewed ischemic heart disease in a cardiocentric manner: plaques grow in arteries until they block blood flow, causing acute coronary and other ischemic syndromes. Recent research provides new insight into the integrative biology of inflammation as it contributes to ischemic cardiovascular disease. These results have revealed hitherto unsuspected inflammatory signaling networks at work in these disorders that link the brain, autonomic nervous system, bone marrow, and spleen to the atherosclerotic plaque and to the infarcting myocardium. A burgeoning clinical literature indicates that such inflammatory networks—far from a mere laboratory curiosity—operate in our patients and can influence aspects of ischemic cardiovascular disease that determine decisively clinical outcomes. These new findings enlarge the circle of the traditional “cardiovascular continuum” beyond the heart and vessels to include the nervous system, the spleen, and the bone marrow. PMID:26940931

  17. Tracking stem cells in the cardiovascular system.

    PubMed

    Chemaly, Elie R; Yoneyama, Ryuichi; Frangioni, John V; Hajjar, Roger J

    2005-11-01

    Stem cells are a promising approach to cardiovascular therapeutics. Animal experiments have assessed the fate of injected stem cells through ex vivo methods on sacrificed animals. Approaches are needed for in vivo tracking of stem cells. Various imaging techniques and contrast agents for stem cell tracking will be reviewed.

  18. microRNA therapeutics in cardiovascular disease models.

    PubMed

    Dangwal, Seema; Thum, Thomas

    2014-01-01

    Cardiovascular diseases are a major cause of human morbidity and mortality, posing a high socioeconomic burden on the health sector worldwide. microRNAs (miRNAs) constitute a new class of unique molecular regulators involved in the pathophysiology of a wide range of disorders. Studies in the past decade have identified miRNA signatures of various cardiovascular disorders and successfully validated miRNA-based therapeutic options in various small and a few large experimental cardiovascular disease models. In these models, researchers manipulate the expression of miRNAs and downstream signaling cascades, aiming to prevent and cure cardiovascular disease. Here, we review and discuss the recent reports on the in vivo use of miRNA animal models and miRNA therapeutic development as well as provide an outlook for clinical applications in the near future.

  19. Pharmacological effects of Chinese herb aconite (fuzi) on cardiovascular system.

    PubMed

    Zhao, Dandan; Wang, Jie; Cui, Yanjing; Wu, Xinfang

    2012-09-01

    Fuzi (aconite, Radix Aconiti praeparata), a widely used Chinese herb, plays a significant role in the cardiovascular system. This is mainly reflected by Fuzi's cardiotonic effect, its protective effect on myocardial cells, and its effect on heart rate and rhythm, blood pressure, and hemodynamics. In this article, the pharmacological effects and the corresponding mechanisms of Fuzi (aconite) and its active components on cardiovascular system are reviewed.

  20. Physiological adaptation of the cardiovascular system to high altitude.

    PubMed

    Naeije, Robert

    2010-01-01

    Altitude exposure is associated with major changes in cardiovascular function. The initial cardiovascular response to altitude is characterized by an increase in cardiac output with tachycardia, no change in stroke volume, whereas blood pressure may temporarily be slightly increased. After a few days of acclimatization, cardiac output returns to normal, but heart rate remains increased, so that stroke volume is decreased. Pulmonary artery pressure increases without change in pulmonary artery wedge pressure. This pattern is essentially unchanged with prolonged or lifelong altitude sojourns. Ventricular function is maintained, with initially increased, then preserved or slightly depressed indices of systolic function, and an altered diastolic filling pattern. Filling pressures of the heart remain unchanged. Exercise in acute as well as in chronic high-altitude exposure is associated with a brisk increase in pulmonary artery pressure. The relationships between workload, cardiac output, and oxygen uptake are preserved in all circumstances, but there is a decrease in maximal oxygen consumption, which is accompanied by a decrease in maximal cardiac output. The decrease in maximal cardiac output is minimal in acute hypoxia but becomes more pronounced with acclimatization. This is not explained by hypovolemia, acid-bases status, increased viscosity on polycythemia, autonomic nervous system changes, or depressed systolic function. Maximal oxygen uptake at high altitudes has been modeled to be determined by the matching of convective and diffusional oxygen transport systems at a lower maximal cardiac output. However, there has been recent suggestion that 10% to 25% of the loss in aerobic exercise capacity at high altitudes can be restored by specific pulmonary vasodilating interventions. Whether this is explained by an improved maximum flow output by an unloaded right ventricle remains to be confirmed. Altitude exposure carries no identified risk of myocardial ischemia in

  1. 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

  2. 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.

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

    PubMed

    Osadchii, Oleg E

    2015-09-05

    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.

  4. 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.

  5. 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

  6. Kinect system in home-based cardiovascular rehabilitation.

    PubMed

    Vieira, Ágata; Gabriel, Joaquim; Melo, Cristina; Machado, Jorge

    2017-01-01

    Cardiovascular diseases lead to a high consumption of financial resources. An important part of the recovery process is the cardiovascular rehabilitation. This study aimed to present a new cardiovascular rehabilitation system to 11 outpatients with coronary artery disease from a Hospital in Porto, Portugal, later collecting their opinions. This system is based on a virtual reality game system, using the Kinect sensor while performing an exercise protocol which is integrated in a home-based cardiovascular rehabilitation programme, with a duration of 6 months and at the maintenance phase. The participants responded to a questionnaire asking for their opinion about the system. The results demonstrated that 91% of the participants (n = 10) enjoyed the artwork, while 100% (n = 11) agreed on the importance and usefulness of the automatic counting of the number of repetitions, moreover 64% (n = 7) reported motivation to continue performing the programme after the end of the study, and 100% (n = 11) recognized Kinect as an instrument with potential to be an asset in cardiovascular rehabilitation. Criticisms included limitations in motion capture and gesture recognition, 91% (n = 10), and the lack of home space, 27% (n = 3). According to the participants' opinions, the Kinect has the potential to be used in cardiovascular rehabilitation; however, several technical details require improvement, particularly regarding the motion capture and gesture recognition.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. A Cardiovascular Mathematical Model of Graded Head-Up Tilt

    PubMed Central

    Lim, Einly; Chan, Gregory S. H.; Dokos, Socrates; Ng, Siew C.; Latif, Lydia A.; Vandenberghe, Stijn; Karunanithi, Mohan; Lovell, Nigel H.

    2013-01-01

    A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to . The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting. PMID:24204817

  13. Arterial branching in various parts of the cardiovascular system.

    PubMed

    Zamir, M; Brown, N

    1982-04-01

    Angiographic pictures of vascular beds in various parts of the cardiovascular system were analyzed to study the geometrical structure of arterial bifurcations. The sites of arterial bifurcations were enlarged individually, and measurements were made of the branching angles and branch diameters at each site. Results from various parts of the cardiovascular system of man, and some from rabbit and pig, were compared with each other. The measurements were also compared with "optimum" values of branching angles and branch diameters which have been predicted by various theoretical studies. In general the measurements were found to give support to the theoretical premise that branching angles and branch diameters in the cardiovascular system are dictated by certain optimality principles which aim to maximize the efficiency of the system in its fluid-conducting function. In some parts of the system, however, the measured angles and diameters were found to be decidedly lower than those predicted by theory.

  14. 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.

  15. Cardiovascular risk assessment and treatment in systemic lupus erythematosus.

    PubMed

    Elliott, Jennifer R; Manzi, Susan

    2009-08-01

    With improved treatment modalities and survival rates, patients with systemic lupus erythematosus live longer and their co-morbidities have become more apparent. Of great concern is cardiovascular disease, which has become a leading cause of death. Lupus patients prematurely develop atherosclerosis, which likely arises from an interaction among traditional cardiovascular risk factors, factors specific to lupus itself and inflammatory mediators. Despite these findings, lupus patients are not always adequately evaluated for traditional risk factors, many of which are treatable and reversible. We propose that lupus patients be assessed and managed regarding cardiovascular risk factors in the same manner as patients with known cardiovascular disease. As a result, preventive cardiology should be considered an essential component of the care for patients with lupus.

  16. Stabilizing control for a pulsatile cardiovascular mathematical model.

    PubMed

    de los Reyes, Aurelio A; Jung, Eunok; Kappel, Franz

    2014-06-01

    In this paper, we develop a pulsatile model for the cardiovascular system which describes the reaction of this system to a submaximal constant workload imposed on a person at a bicycle ergometer test after a period of rest. Furthermore, the model should allow to use measurements for the pulsatile pressure in fingertips which provide information on the diastolic and the systolic pressure for parameter estimation. Based on the assumption that the baroreceptor loop is the essential control loop in this case, we design a stabilizing feedback control for the pulsatile model which is obtained by solving a linear-quadratic regulator problem for the linearization of a non-pulsatile counterpart of the pulsatile model. We also investigate the behavior of the model with respect to changes in the weight of the term in the cost functional for the linear-quadratic regulator problem which penalizes the deviation of the momentary pressure in the aorta from the pressure at the stationary situation which should be obtained.

  17. 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.

  18. Leptin and the cardiovascular system: a review.

    PubMed

    Ashwin, Patel J; Dilipbhai, Patel J

    2007-06-01

    Obesity is an increasing health problem not only in the industrialized western countries but, also in the developing countries like India. The adipose tissue specific obese (ob) gene and its peptide product leptin were discovered in 1994. Leptin binding to specific receptors in the hypothalamus results in altered expression of orexigenic and anorexigenic neuropeptides that regulate neuroendocrine functions and energy homeostasis. Recent patents and experimental evidence suggest that leptin plays an important role in the pathogenesis of obesity and eating disorders. Central leptin action also includes regulation of blood pressure, bone mass, and immune function. Peripherally also, leptin plays an important role in direct regulation of immune cells, pancreatic beta cells, adipocytes and muscle cells. Leptin receptors are present on human endothelial cells, and it has been shown to induce angiogenesis both in vitro and in vivo. Further, leptin appears to be a potential pressure and volume regulating factor and may function pathophysiologically as a common link to obesity and hypertension. Obesity is also a risk factor for several other cardiovascular diseases like myocardial hypertrophy, myocardial infarction, coronary atherosclerosis and increased cardiovascular morbidity and mortality. Recent progress in understanding central and peripheral leptin receptor signaling pathways may provide potential new targets to combat obesity, hypertension etc.

  19. Reactive oxygen species and the cardiovascular system.

    PubMed

    Taverne, Yannick J H J; Bogers, Ad J J C; Duncker, Dirk J; Merkus, Daphne

    2013-01-01

    Ever since the discovery of free radicals, many hypotheses on the deleterious actions of reactive oxygen species (ROS) have been proposed. However, increasing evidence advocates the necessity of ROS for cellular homeostasis. ROS are generated as inherent by-products of aerobic metabolism and are tightly controlled by antioxidants. Conversely, when produced in excess or when antioxidants are depleted, ROS can inflict damage to lipids, proteins, and DNA. Such a state of oxidative stress is associated with many pathological conditions and closely correlated to oxygen consumption. Although the deleterious effects of ROS can potentially be reduced by restoring the imbalance between production and clearance of ROS through administration of antioxidants (AOs), the dosage and type of AOs should be tailored to the location and nature of oxidative stress. This paper describes several pathways of ROS signaling in cellular homeostasis. Further, we review the function of ROS in cardiovascular pathology and the effects of AOs on cardiovascular outcomes with emphasis on the so-called oxidative paradox.

  20. Effects of thyroid hormone on the cardiovascular system.

    PubMed

    Fazio, Serafino; Palmieri, Emiliano A; Lombardi, Gaetano; Biondi, Bernadette

    2004-01-01

    Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that overt hyperthyroidism induces a hyperdynamic cardiovascular state (high cardiac output with low systemic vascular resistance), which is associated with a faster heart rate, enhanced left ventricular (LV) systolic and diastolic function, and increased prevalence of supraventricular tachyarrhythmias - namely, atrial fibrillation - whereas overt hypothyroidism is characterized by the opposite changes. However, whether changes in cardiac performance associated with overt thyroid dysfunction are due mainly to alterations of myocardial contractility or to loading conditions remains unclear. Extensive evidence indicates that the cardiovascular system responds to the minimal but persistent changes in circulating thyroid hormone levels, which are typical of individuals with subclinical thyroid dysfunction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased LV mass, impaired ventricular relaxation, reduced exercise performance, and increased risk of cardiovascular mortality. Subclinical hypothyroidism is associated with impaired LV diastolic function and subtle systolic dysfunction and an enhanced risk for atherosclerosis and myocardial infarction. Because all cardiovascular abnormalities are reversed by restoration of euthyroidism ("subclinical hypothyroidism") or blunted by beta-blockade and L-thyroxine (L-T4) dose tailoring ("subclinical hyperthyroidism"), timely treatment is advisable in an attempt to avoid adverse cardiovascular effects. Interestingly, some data indicate that patients with acute and chronic cardiovascular disorders and those undergoing cardiac surgery may have altered peripheral thyroid hormone metabolism that, in turn, may contribute to altered cardiac function. Preliminary clinical investigations suggest that administration of

  1. Cardiovascular involvement in pediatric systemic autoimmune diseases: the emerging role of noninvasive cardiovascular imaging.

    PubMed

    Mavrogeni, Sophie; Servos, George; Smerla, Roubini; Markousis-Mavrogenis, George; Grigoriadou, Georgia; Kolovou, Genovefa; Papadopoulos, George

    2015-01-01

    Cardiac involvement in pediatric systemic autoimmune diseases has a wide spectrum of presentation ranging from asymptomatic to severe clinically overt involvement. Coronary artery disease, pericardial, myocardial, valvular and rythm disturbances are the most common causes of heart lesion in pediatric systemic autoimmune diseases and cannot be explained only by the traditional cardiovascular risk factors. Therefore, chronic inflammation has been considered as an additive causative factor of cardiac disease in these patients. Rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, ankylosing spondylitis/spondyloarthritides, juvenile scleroderma, juvenile dermatomyositis/polymyositis, Kawasaki disease and other autoimmune vasculitides are the commonest pediatric systemic autoimmune diseases with heart involvement. Noninvasive cardiovascular imaging is an absolutely necessary adjunct to the clinical evaluation of these patients. Echocardiography is the cornerstone of this assessment, due to excellent acoustic window in children, lack of radiation, low cost and high availability. However, it can not detect disease acuity and pathophysiologic background of cardiac lesions. Recently, the development of cardiovascular magnetic resonance imaging holds the promise for early detection of subclinical heart disease and detailed serial evaluation of myocardium (function, inflammation, stress perfusion-fibrosis) and coronary arteries (assessment of ectasia and aneurysms).

    .

  2. Inorganic nitrate and the cardiovascular system.

    PubMed

    Kapil, V; Webb, A J; Ahluwalia, A

    2010-11-01

    Fruit and vegetable-rich diets reduce blood pressure and risk of ischaemic stroke and ischaemic heart disease. While the cardioprotective effects of a fruit and vegetable-rich diet are unequivocal, the exact mechanisms of this effect remain uncertain. Recent evidence has highlighted the possibility that dietary nitrate, an inorganic anion found in large quantities in vegetables (particularly green leafy vegetables), may have a part to play. This beneficial activity lies in the processing in vivo of nitrate to nitrite and thence to the pleiotropic molecule nitric oxide. In this review, recent preclinical and clinical evidence identifying the mechanisms involved in nitrate bioactivity, and the evidence supporting the potential utility of exploitation of this pathway for the prevention and/or treatment of cardiovascular diseases are discussed.

  3. Purinergic Signaling in the Cardiovascular System.

    PubMed

    Burnstock, Geoffrey

    2017-01-06

    There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y1, P2Y12, and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine.

  4. 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.…

  5. 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.

  6. Multifractality in the peripheral cardiovascular system from pointwise holder exponents of laser Doppler flowmetry signals.

    PubMed

    Humeau, Anne; Chapeau-Blondeau, François; Rousseau, David; Tartas, Maylis; Fromy, Bérengère; Abraham, Pierre

    2007-12-15

    We study the dynamics of skin laser Doppler flowmetry signals giving a peripheral view of the cardiovascular system. The analysis of Hölder exponents reveals that the experimental signals are weakly multifractal for young healthy subjects at rest. We implement the same analysis on data generated by a standard theoretical model of the cardiovascular system based on nonlinear coupled oscillators with linear couplings and fluctuations. We show that the theoretical model, although it captures basic features of the dynamics, is not complex enough to reflect the multifractal irregularities of microvascular mechanisms.

  7. 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.

  8. O-GlcNAc Signaling in the Cardiovascular System

    PubMed Central

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

    2010-01-01

    Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of post-translational 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 (i.e. O-GlcNAc) to cellular proteins, this unique monosaccharide is involved in a diverse array of physiologic and pathologic functions. This Review will introduce 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 will focus on the emerging evidence of its involvement in the cardiovascular system. In particular, we will highlight evidence of protein O-GlcNAcylation as an autoprotective alarm or stress response. We will discuss recent literature supporting the idea that promoting O-GlcNAcylation improves cell survival during acute stress (e.g. 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 will 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. PMID:20651294

  9. 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.

  10. 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.

  11. 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

  12. 76 FR 62164 - VASRD Improvement Forum-Updating Disability Criteria for the Respiratory System, Cardiovascular...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-06

    ... AFFAIRS VASRD Improvement Forum--Updating Disability Criteria for the Respiratory System, Cardiovascular...) Improvement Forum-- Updating Disability Criteria for the Respiratory System, Cardiovascular System, Hearing... four body systems: (1) Respiratory System (38 CFR 4.96-4.97), (2) the Cardiovascular System (38 CFR...

  13. Molecular Mechanisms of Autophagy in the Cardiovascular System

    PubMed Central

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

    2014-01-01

    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 in order 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 widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells and vascular smooth muscle cells. In all cases, a window of optimal autophagic activity appears 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. PMID:25634969

  14. 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.

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

    PubMed

    Pacher, Pál; Steffens, Sabine

    2009-06-01

    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 CB(1) and CB(2). 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 CB(1) receptors. Furthermore, tonic activation of CB(1) 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 CB(2) receptors in immune cells exerts various immunomodulatory effects, and the CB(2) 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.

  16. Aldosterone and mineralocorticoid receptors in the cardiovascular system.

    PubMed

    Funder, John W

    2010-01-01

    Aldosterone is currently thought to exert its physiologic effects by activating epithelial mineralocorticoid receptors, and its pathologic effects on the cardiovascular system via mineralocorticoid receptors in the heart and blood vessels. Recent studies have extended this understanding to include a reevaluation of the roles of aldosterone and mineralocorticoid receptor activation in blood pressure control; the rapid, nongenomic effects of aldosterone; the role of cortisol as a mineralocorticoid receptor agonist under conditions of redox change/tissue damage/reactive oxygen species generation; the growing consensus that primary aldosteronism accounts for approximately 10% of all essential hypertension; recent new insights into the cardioprotective role of spironolactone; and the development of third- and fourth-generation mineralocorticoid receptor antagonists for use in cardiovascular and other inflammatory disease. These findings on aldosterone action and mineralocorticoid receptor blockade are analyzed in the context of the prevention and treatment of cardiovascular disease.

  17. [Serotonin and its receptors in the cardiovascular system].

    PubMed

    Nadeev, A D; Zharkikh, I L; Avdonin, P V; Goncharov, N V

    2014-01-01

    Serotonin in cardiovascular system plays an important role in blood coagulation, allergy, and inflammation, as well as in blood vessel tone regulation. In this review, the mechanisms of serotonin effects upon the cells of blood vessels are considered and the list of main agonists and antagonists is presented. The signaling pathways activated by serotonin and their interaction in normal and pathological states are described.

  18. 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

  19. 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.

  20. 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.

  1. 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...

  2. Effects of exercise training on the cardiovascular system: pharmacological approaches.

    PubMed

    Zanesco, Angelina; Antunes, Edson

    2007-06-01

    Physical exercise promotes beneficial health effects by preventing or reducing the deleterious effects of pathological conditions, such as arterial hypertension, coronary artery disease, atherosclerosis, diabetes mellitus, osteoporosis, Parkinson's disease, and Alzheimer disease. Human movement studies are becoming an emerging science in the epidemiological area and public health. A great number of studies have shown that exercise training, in general, reduces sympathetic activity and/or increases parasympathetic tonus either in human or laboratory animals. Alterations in autonomic nervous system have been correlated with reduction in heart rate (resting bradycardia) and blood pressure, either in normotensive or hypertensive subjects. However, the underlying mechanisms by which physical exercise produce bradycardia and reduces blood pressure has not been fully understood. Pharmacological studies have particularly contributed to the comprehension of the role of receptor and transduction signaling pathways on the heart and blood vessels in response to exercise training. This review summarizes and examines the data from studies using animal models and human to determine the effect of exercise training on the cardiovascular system.

  3. 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

  4. 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.

  5. Optimizing cardiovascular benefits of exercise: a review of rodent models.

    PubMed

    Davis, Brittany; Moriguchi, Takeshi; Sumpio, Bauer

    2013-03-01

    Although research unanimously maintains that exercise can ward off cardiovascular disease (CVD), the optimal type, duration, intensity, and combination of forms are yet not clear. In our review of existing rodent-based studies on exercise and cardiovascular health, we attempt to find the optimal forms, intensities, and durations of exercise. Using Scopus and Medline, a literature review of English language comparative journal studies of cardiovascular benefits and exercise was performed. This review examines the existing literature on rodent models of aerobic, anaerobic, and power exercise and compares the benefits of various training forms, intensities, and durations. The rodent studies reviewed in this article correlate with reports on human subjects that suggest regular aerobic exercise can improve cardiac and vascular structure and function, as well as lipid profiles, and reduce the risk of CVD. Findings demonstrate an abundance of rodent-based aerobic studies, but a lack of anaerobic and power forms of exercise, as well as comparisons of these three components of exercise. Thus, further studies must be conducted to determine a truly optimal regimen for cardiovascular health.

  6. Protease-activated receptor-2 (PAR2) in cardiovascular system.

    PubMed

    Bucci, Mariarosaria; Roviezzo, Fiorentina; Cirino, Giuseppe

    2005-10-01

    Vascular system is constituted by a complex and articulate network, e.g. arteries, arterioles, venules and veins, that requires a high degree of coordination between different elemental cell types. Proteinase-activated receptors (PARs) constitute a recent described family of 7-transmembrane G protein-coupled receptors that are activated by proteolysis. In recent years several evidence have been accumulated for an involvement of this receptor in the response to endothelial injury in vitro and in vivo experimental settings suggesting a role for PAR2 in the pathophysiology of cardiovascular system. This review will deal with the role of PAR2 receptor in the cardiovascular system analyzing both in vivo and in vitro published data. In particular this review will deal with the role of this receptor in vascular reactivity, ischemia/reperfusion injury, coronary atherosclerotic lesions and angiogenesis.

  7. Role of tissue kallikrein-kininogen-kinin pathways in the cardiovascular system.

    PubMed

    Sharma, Jagdish N

    2006-04-01

    All the components of the kallikrein-kinin system are located in the cardiac muscle, and its deficiency may lead to cardiac dysfunction. In recent years, numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischemia, myocardial infarction and left ventricular hypertrophy have suggested that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular-related diseases. The cardioprotective property of the angiotensin converting enzyme inhibitors is primarily mediated via kinin-releasing pathway, which may cause regression of the left ventricular hypertrophy in hypertensive situations. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating hypertension, cardiovascular and renal diseases. In addition, stable kinin agonists may also be available in the future as therapeutic agents for cardiovascular and renal disorders.

  8. 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.

  9. CaMKII in the cardiovascular system: sensing redox states.

    PubMed

    Erickson, Jeffrey R; He, B Julie; Grumbach, Isabella M; Anderson, Mark E

    2011-07-01

    The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease. CaMKII is a multimeric serine-threonine kinase that is initially activated by binding calcified calmodulin (Ca(2+)/CaM). Under conditions of sustained exposure to elevated Ca(2+)/CaM, CaMKII transitions into a Ca(2+)/CaM-autonomous enzyme by two distinct but parallel processes. Autophosphorylation of threonine-287 in the CaMKII regulatory domain "traps" CaMKII into an open configuration even after Ca(2+)/CaM unbinding. More recently, our group identified a pair of methionines (281/282) in the CaMKII regulatory domain that undergo a partially reversible oxidation which, like autophosphorylation, prevents CaMKII from inactivating after Ca(2+)/CaM unbinding. Here we review roles of CaMKII in cardiovascular disease with an eye to understanding how CaMKII may act as a transduction signal to connect pro-oxidant conditions into specific downstream pathological effects that are relevant to rare and common forms of cardiovascular disease.

  10. 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.

  11. Physiological role of ROCKs in the cardiovascular system.

    PubMed

    Noma, Kensuke; Oyama, Naotsugu; Liao, James K

    2006-03-01

    Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. [Radionuclide evaluation of the cardiovascular system in arterial hypertension].

    PubMed

    Oganesian, N M; Babaian, A S; Mikaelian, R S; Mnatsakanian, E L

    1986-08-01

    Proceeding from a study of the nature of changes in hemodynamics during development of hypertensive disease (HD) at its different stages it was shown that hemodynamic changes in 42.1% of the patients with Stage I-IIA HD were of hypertensive type, in the patients with Stage IIB-III HD normal and hypokinetic types of the blood circulation prevailed. After bicycle ergometry exercise the reactivity of the cardiovascular system was revealed more completely. The transition of one hemodynamic type into another and its detection acquired a great importance. The definition of the types of hemodynamics at rest and of effort was very important in terms of adequate antihypertensive therapy and the prediction of a subsequent course of disease. The most complete information on function of the cardiovascular system and myocardial contractility can be obtained with the help of radio-angiocardiography and radionuclide ventriculography. However in the absence of a gamma-chamber radiocardiography can provide necessary information on function of the cardiovascular system in case it is used in one and the same patient over time using bicycle ergometry testing.

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

    PubMed

    Elder, Andrew; Japp, Alan; Verghese, Abraham

    2016-07-27

    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.

  3. 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.

  4. 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."

  5. 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

  6. Glucocorticoids and the cardiovascular system: state of the art.

    PubMed

    Nussinovitch, Udi; de Carvalho, Jozélio Freire; Pereira, Rosa Maria R; Shoenfeld, Yehuda

    2010-01-01

    Glucocorticoids (GC) are drugs commonly used, by approximately 1% of the total adult population as anti-inflammatory and immunosuppressive therapies for asthma, inflammatory bowel disease, dermatological, ophthalmic, neurological, and rheumatic autoimmune diseases. Supporting evidence exists of GC use in both immune mediated and non-immune mediated heart disease. The molecular mechanisms by which GC induces immune-modulation and direct cardioprotection, are complex and not fully understood. We review herein, the current knowledge of GC use in various immune-mediated or non-immune mediated cardiovascular conditions. GC have been investigated in autoimmune, inflammatory and idiopathic heart diseases such as atrio-ventricular conduction abnormalities, rheumatic fever, myocarditis, dilated cardiomyopathy, Churg-Strauss syndrome, Kawasaki disease and sarcoidosis. GC therapy has been studied in non-autoimmune and non-inflammatory indications such as acute myocardial infarction, angina, postpericardiotomy syndrome and other pericardial diseases, endocarditis and cardiac amyloidosis, as well as in invasive cardiology, coronary interventions, and cardiopulmonary-bypass surgery. Despite GC's role as natural, physiologic regulators of the immune system, cardiovascular adverse outcomes may occur. Some of the well-known side effects of GC therapy involve bone, metabolic, and cardiovascular systems and include osteoporosis, fractures, dyslipidemia, diabetes, obesity, and hypertension.

  7. 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.

  8. Nicotine effect on cardiovascular system and ion channels.

    PubMed

    Hanna, Salma Toma

    2006-03-01

    Smoking is a leading cause of cardiovascular disease, hypertension, myocardial infarction, and stroke. Nicotine is one of the components of cigarette smoke. Nicotine effects on the cardiovascular system reflect the activity of the nicotine receptors centrally and on peripheral autonomic ganglia. It has been found that cigarette smoke extract-induced contraction of porcine coronary arteries is related to superoxide anion-mediated degradation of nitric oxide. Treatment of rabbit aortas with an oxygen free radicals scavenger attenuated cigarette smoke impairment of arterial relaxation. Treatment of smokers with vitamin C, an antioxidant, improved impaired endothelium-dependent reactivity of large peripheral arteries. Thus it appears that chronic smoking and acute exposure to cigarette smoke extract may alter endothelium-dependent reactivity via the production of oxygen derived free radicals. This review discusses the effects of nicotine on resistance arterioles, compliance arteries, smooth muscle cells, and ion channels in the cardiovascular system. We discuss studies performed on humans, nicotine-exposed animals, and cell cultures yielding varying and inconsistent results that may be due to differences in experimental design, species, and the dose of exposure. Nicotine exposure appears to induce a combination of free radical production, vascular wall adhesion, and a reduction of fibrinolytic activity in the plasma.

  9. 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.

  10. Exercise protects the cardiovascular system: effects beyond traditional risk factors.

    PubMed

    Joyner, Michael J; Green, Daniel J

    2009-12-01

    In humans, exercise training and moderate to high levels of physical activity are protective against cardiovascular disease. In fact they are 40% more protective than predicted based on the changes in traditional risk factors (blood lipids, hypertension, diabetes etc.) that they cause. In this review, we highlight the positive effects of exercise on endothelial function and the autonomic nervous system. We also ask if these effects alone, or in combination, might explain the protective effects of exercise against cardiovascular disease that appear to be independent of traditional risk factor modification. Our goal is to use selected data from our own work and that of others to stimulate debate on the nature and cause of the 'risk factor gap' associated with exercise and physical activity.

  11. Molecular mechanism of vitamin D in the cardiovascular system.

    PubMed

    Li, Yan Chun

    2011-08-01

    Vitamin D deficiency is a global health problem that has various adverse consequences. Vitamin D is mainly synthesized in the skin by sunlight (UV light) irradiation; therefore, vitamin D status is influenced by geographic locations, seasonal changes, and skin pigmentations. The kidney is involved in the biosynthesis of 1,25-dihydroxyvitamin D and the reuptake of filtered 25-hydroxyvitamin D from the proximal tubules, thus, vitamin D deficiency is highly prevalent in patients with kidney disease who have renal insufficiency. There is a growing body of epidemiological and clinical evidence in the literature that links vitamin D deficiency to cardiovascular disease. The discovery of the vitamin D hormone functioning as an endocrine inhibitor of the renin-angiotensin system provides an explanation for this association. This review will discuss the mechanism underlying the connection between vitamin D and cardiovascular disease and its physiological and therapeutic implications.

  12. Analysis of Cardiovascular Instability by a Mathematical Model of Baroreflex Control

    DTIC Science & Technology

    2007-11-02

    of 41 ANALYSIS OF CARDIOVASCULAR INSTABILITY BY A MATHEMATICAL MODEL OF BAROREFLEX CONTROL E. Magosso, V. Biavati, and M. Ursino Department of...arterial pressure (arterial baroreflex ) and in right atrial pressure (cardiopulmonary baroreflex ) and work on systemic resistance, systemic venous...A sensitivity analysis on the parameters of feedback mechanisms revealed that a significant increase in the gains and time delays (up to 9 s) of all

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

    PubMed Central

    Stapleton, Phoebe A.; Abukabda, Alaeddin B.; Hardy, Steven L.

    2015-01-01

    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

  14. 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.

  15. 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

  16. A coupling method for a cardiovascular simulation model which includes the Kalman filter.

    PubMed

    Hasegawa, Yuki; Shimayoshi, Takao; Amano, Akira; Matsuda, Tetsuya

    2012-01-01

    Multi-scale models of the cardiovascular system provide new insight that was unavailable with in vivo and in vitro experiments. For the cardiovascular system, multi-scale simulations provide a valuable perspective in analyzing the interaction of three phenomenons occurring at different spatial scales: circulatory hemodynamics, ventricular structural dynamics, and myocardial excitation-contraction. In order to simulate these interactions, multiscale cardiovascular simulation systems couple models that simulate different phenomena. However, coupling methods require a significant amount of calculation, since a system of non-linear equations must be solved for each timestep. Therefore, we proposed a coupling method which decreases the amount of calculation by using the Kalman filter. In our method, the Kalman filter calculates approximations for the solution to the system of non-linear equations at each timestep. The approximations are then used as initial values for solving the system of non-linear equations. The proposed method decreases the number of iterations required by 94.0% compared to the conventional strong coupling method. When compared with a smoothing spline predictor, the proposed method required 49.4% fewer iterations.

  17. The endocannabinoid system: a new approach to control cardiovascular disease.

    PubMed

    Cannon, Christopher P

    2005-01-01

    The endocannabinoid (EC) system consists of 2 types of G-protein-coupled cannabinoid receptors--cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2)--and their natural ligands. The EC system plays a key role in the regulation of food intake and fat accumulation, as well as glucose and lipid metabolism. When overactivated, the EC system triggers dyslipidemia, thrombotic and inflammatory states, and insulin resistance. Blocking CB1 receptors centrally and peripherally in adipose tissue can help normalize an overactivated EC system. CB1 blockade helps regulate food intake and adipose tissue metabolism, contributing to improved insulin sensitivity and other features of the metabolic syndrome. Visceral adipose tissue is most closely associated with the metabolic syndrome, which is a constellation of conditions that place people at high risk for coronary artery disease. Targeting the EC system represents a new approach to treating visceral obesity and reducing cardiovascular risk factors.

  18. 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.

  19. 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.

  20. [An analysis of the cardiovascular responses under hyper- and hypo-gravity environments using a mathematical model].

    PubMed

    Hirata, Y; Yoshimura, K; Nakatomi, T; Toda, N; Usui, S; Nagaoka, S

    1999-06-01

    Gravity affects cardiovascular control system remarkably. Internal control mechanism responsible for such cardiovascular changes under hypo- and hyper-gravity have not yet been fully understood, although many biological and physiological measurements as to cardiovascular system have been conducted since man's first exploration to space. One reason for this arises from the difficulty in continuous and simultaneous measurements of hemodynamics of many parts of the body. To overcome this difficulty, a mathematical model was constructed based on animal and human physiological evidence in our previous study. In the present study, the model is used for explaining hemodynamics during hyper- and hypo-gravity environments obtained during parabolic flight. The parabolic flight experiment was conducted by a small rear-jet MU300. Three university male students volunteered as subjects. Five to eleven parabolic flights per day were performed for 6 days. The subjects sat on a chair either in an upright position or a 45 degree reclining position. Electrocardiogram and finger blood pressure were measured continuously during the flights. Variable parameters of the model were adjusted so that heart rate and blood pressure of the model fit to those of the experiment. It was shown that the model can quantitatively reproduce and predict experimental heart rate and blood pressure during a parabolic flight. Analysis of internal property of the model revealed hemodynamics of the human cardiovascular system during a parabolic flight which explains the mechanisms of cardiovascular responses under hyper- and hypo-gravitational environments.

  1. 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.

  2. 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.

  3. [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)

  4. 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.

  5. 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

  6. Possible Muscle Repair in the Human Cardiovascular System.

    PubMed

    Sommese, Linda; Zullo, Alberto; Schiano, Concetta; Mancini, Francesco P; Napoli, Claudio

    2017-04-01

    The regenerative potential of tissues and organs could promote survival, extended lifespan and healthy life in multicellular organisms. Niches of adult stemness are widely distributed and lead to the anatomical and functional regeneration of the damaged organ. Conversely, muscular regeneration in mammals, and humans in particular, is very limited and not a single piece of muscle can fully regrow after a severe injury. Therefore, muscle repair after myocardial infarction is still a chimera. Recently, it has been recognized that epigenetics could play a role in tissue regrowth since it guarantees the maintenance of cellular identity in differentiated cells and, therefore, the stability of organs and tissues. The removal of these locks can shift a specific cell identity back to the stem-like one. Given the gradual loss of tissue renewal potential in the course of evolution, in the last few years many different attempts to retrieve such potential by means of cell therapy approaches have been performed in experimental models. Here we review pathways and mechanisms involved in the in vivo repair of cardiovascular muscle tissues in humans. Moreover, we address the ongoing research on mammalian cardiac muscle repair based on adult stem cell transplantation and pro-regenerative factor delivery. This latter issue, involving genetic manipulations of adult cells, paves the way for developing possible therapeutic strategies in the field of cardiovascular muscle repair.

  7. 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

  8. 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.

  9. 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.

  10. Physio-pathological effects of alcohol on the cardiovascular system: its role in hypertension and cardiovascular disease.

    PubMed

    Kawano, Yuhei

    2010-03-01

    Alcohol has complex effects on the cardiovascular system. The purpose of this article is to review physio-pathological effects of alcohol on cardiovascular and related systems and to describe its role in hypertension and cardiovascular disease. The relationship between alcohol and hypertension is well known, and a reduction in the alcohol intake is widely recommended in the management of hypertension. Moreover, alcohol has both pressor and depressor actions. The latter actions are clear in Oriental subjects, especially in those who show alcohol flush because of the genetic variation in aldehyde dehydrogenase activity. Repeated alcohol intake in the evening causes an elevation in daytime and a reduction in nighttime blood pressure (BP), with little change in the average 24-h BP in Japanese men. Thus, the hypertensive effect of alcohol seems to be overestimated by the measurement of casual BP during the day. Heavy alcohol intake seems to increase the risk of several cardiovascular diseases, such as hemorrhagic stroke, arrhythmia and heart failure. On the other hand, alcohol may act to prevent atherosclerosis and to decrease the risk of ischemic heart disease, mainly by increasing HDL cholesterol and inhibiting thrombus formation. A J- or U-shaped relationship has been observed between the level of alcohol intake and risk of cardiovascular mortality and total mortality. It is reasonable to reduce the alcohol intake to less than 30 ml per day for men and 15 ml per day for women in the management of hypertension. As a small amount of alcohol seems to be beneficial, abstinence from alcohol is not recommended to prevent cardiovascular disease.

  11. 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.

  12. Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

    PubMed Central

    Eklund, Lauri; Kangas, Jaakko; Saharinen, Pipsa

    2016-01-01

    Endothelial cells that form the inner layer of blood and lymphatic vessels are important regulators of vascular functions and centrally involved in the pathogenesis of vascular diseases. In addition to the vascular endothelial growth factor (VEGF) receptor pathway, the angiopoietin (Ang)–Tie system is a second endothelial cell specific ligand–receptor signalling system necessary for embryonic cardiovascular and lymphatic development. The Ang–Tie system also regulates postnatal angiogenesis, vessel remodelling, vascular permeability and inflammation to maintain vascular homoeostasis in adult physiology. This system is implicated in numerous diseases where the vasculature has an important contribution, such as cancer, sepsis, diabetes, atherosclerosis and ocular diseases. Furthermore, mutations in the TIE2 signalling pathway cause defects in vascular morphogenesis, resulting in venous malformations and primary congenital glaucoma. Here, we review recent advances in the understanding of the Ang–Tie signalling system, including cross-talk with the vascular endothelial protein tyrosine phosphatase (VE-PTP) and the integrin cell adhesion receptors, focusing on the Ang–Tie system in vascular development and pathogenesis of vascular diseases. PMID:27941161

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Influence of exposure to electromagnetic field on the cardiovascular system.

    PubMed

    Jeong, J H; Kim, J S; Lee, B C; Min, Y S; Kim, D S; Ryu, J S; Soh, K S; Seo, K M; Sohn, U D

    2005-01-01

    1 We examined whether extremely low frequency electromagnetic fields (ELF-EMF) affect the basal level of cardiovascular parameters and influence of drugs acting on the sympathetic nervous system. 2 Male rats were exposed to sham control and EMF (60 Hz, 20 G) for 1 (MF-1) or 5 days (MF-5). We evaluated the alterations of blood pressure (BP), pulse pressure (PP), heart rate (HR), and the PR interval, QRS interval and QT interval on the electrocardiogram and dysrhythmic ratio in basal level and dysrhythmia induced by beta-adrenoceptor agonists. 3 In terms of the basal levels, there were no statistically significant differences among control, MF-1 and MF-5 in PR interval, QRS interval, mean BP, HR and PP. However, the QT interval, representing ventricular repolarization, was significantly reduced by MF-1 (P < 0.05). 4 (-)-Dobutamine (beta1-adrenoceptor-selective agonist)-induced tachycardia was significantly suppressed by ELF-EMF exposure in MF-1 for the increase in HR (DeltaHR), the decrease in QRS interval (DeltaQRS) and the decrease in QT (DeltaQT) interval. Adrenaline (nonselective beta-receptor agonist)-induced dysrhythmia was also significantly suppressed by ELF-EMF in MF-1 for the number of missing beats, the dysrhythmic ratio, and the increase in BP and PP. 5 These results indicated that 1-day exposure to ELF-EMF (60 Hz, 20 G) could suppress the increase in HR by affecting ventricular repolarization and may have a down-regulatory effect on responses of the cardiovascular system induced by sympathetic agonists.

  18. Numerical simulation of the blood flow in the human cardiovascular system.

    PubMed

    Zácek, M; Krause, E

    1996-01-01

    This paper describes a numerical model of the human cardiovascular system. The model is composed of 15 elements connected in series representing the main parts of the system. Each element is composed of a rigid connecting tube and an elastic reservoir. The blood flow is described by a one-dimensional time-dependent Bernoulli equation. The action of the ventricles is simulated with a Hill's three-element model, adapted for the left and right heart. The closing of the four heart valves is simulated with the aid of time-dependent drag coefficients. Closing is achieved by letting the drag coefficient approach infinity. The resulting system of 32 non-linear ordinary differential equations is solved numerically with the Runge-Kutta method. The results of the simulation (pressure-time and volume-time dependence for the atria and ventricles and pressure forms in the aorta at a heart rate of 70 beats per minute) agree with the physiological data given in the literature. The model's input aortic impedance is 31.5 dyn s cm-5 which agrees with literature data given for aortic input impedance in man 26-80 dyn s cm-5). Long-term stability of the system was achieved. The cardiovascular system presented here can also be simulated at higher and varying heart rates--up to 200 beats per minute. The results of calculations for some pathological changes (e.g. valvular abnormalities) are discussed.

  19. Regulation of chromatin structure in the cardiovascular system.

    PubMed

    Rosa-Garrido, Manuel; Karbassi, Elaheh; Monte, Emma; Vondriska, Thomas M

    2013-01-01

    It has been appreciated for some time that cardiovascular disease involves large-scale transcriptional changes in various cell types. What has become increasingly clear only in the past few years, however, is the role of chromatin remodeling in cardiovascular phenotypes in normal physiology, as well as in development and disease. This review summarizes the state of the chromatin field in terms of distinct mechanisms to regulate chromatin structure in vivo, identifying when these modes of regulation have been demonstrated in cardiovascular tissues. We describe areas in which a better understanding of chromatin structure is leading to new insights into the fundamental biology of cardiovascular disease. 

  20. Red blood cell flow in the cardiovascular system: a fluid dynamics perspective.

    PubMed

    AlMomani, Thakir D; Vigmostad, Sarah C; Chivukula, Venkat Keshav; Al-zube, Loay; Smadi, Othman; BaniHani, Suleiman

    2012-01-01

    The dynamics of red blood cells (RBCs) is one of the major aspects of the cardiovascular system that has been studied intensively in the past few decades. The dynamics of biconcave RBCs are thought to have major influences in cardiovascular diseases, the problems associated with cardiovascular assistive devices, and the determination of blood rheology and properties. This article provides an overview of the works that have been accomplished in the past few decades and aim to study the dynamics of RBCs under different flow conditions. While significant progress has been made in both experimental and numerical studies, a detailed understanding of the behavior of RBCs is still faced with many challenges. Experimentally, the size of RBCs is considered to be a major limitation that allows measurements to be performed under conditions similar to physiological conditions. In numerical computations, researchers still are working to develop a model that can cover the details of the RBC mechanics as it deforms and moves in the bloodstream. Moreover, most of reported computational models have been confined to the behavior of a single RBC in 2-dimensional domains. Advanced models are yet to be developed for accurate description of RBC dynamics under physiological flow conditions in 3-dimensional regimes.

  1. 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

  2. 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

  3. 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

  4. Endothelin and endothelin receptors in the renal and cardiovascular systems.

    PubMed

    Vignon-Zellweger, Nicolas; Heiden, Susi; Miyauchi, Takashi; Emoto, Noriaki

    2012-10-15

    Endothelin-1 (ET-1) is a multifunctional hormone which regulates the physiology of the cardiovascular and renal systems. ET-1 modulates cardiac contractility, systemic and renal vascular resistance, salt and water renal reabsorption, and glomerular function. ET-1 is responsible for a variety of cellular events: contraction, proliferation, apoptosis, etc. These effects take place after the activation of the two endothelin receptors ET(A) and ET(B), which are present - among others - on cardiomyocytes, fibroblasts, smooth muscle and endothelial cells, glomerular and tubular cells of the kidney. The complex and numerous intracellular pathways, which can be contradictory in term of functional response depending on the receptor type, cell type and physiological situation, are described in this review. Many diseases share an enhanced ET-1 expression as part of the pathophysiology. However, the use of endothelin blockers is currently restricted to pulmonary arterial hypertension, and more recently to digital ulcer. The complexity of the endothelin system does not facilitate the translation of the molecular knowledge to clinical applications. Endothelin antagonists can prevent disease development but secondary undesirable effects limit their usage. Nevertheless, the increasing understanding of the effects of ET-1 on the cardiac and renal physiology maintains the endothelin system as a promising therapeutic target.

  5. Weighted hurdle regression method for joint modeling of cardiovascular events likelihood and rate in the US dialysis population.

    PubMed

    Sentürk, Damla; Dalrymple, Lorien S; Mu, Yi; Nguyen, Danh V

    2014-11-10

    We propose a new weighted hurdle regression method for modeling count data, with particular interest in modeling cardiovascular events in patients on dialysis. Cardiovascular disease remains one of the leading causes of hospitalization and death in this population. Our aim is to jointly model the relationship/association between covariates and (i) the probability of cardiovascular events, a binary process, and (ii) the rate of events once the realization is positive-when the 'hurdle' is crossed-using a zero-truncated Poisson distribution. When the observation period or follow-up time, from the start of dialysis, varies among individuals, the estimated probability of positive cardiovascular events during the study period will be biased. Furthermore, when the model contains covariates, then the estimated relationship between the covariates and the probability of cardiovascular events will also be biased. These challenges are addressed with the proposed weighted hurdle regression method. Estimation for the weighted hurdle regression model is a weighted likelihood approach, where standard maximum likelihood estimation can be utilized. The method is illustrated with data from the United States Renal Data System. Simulation studies show the ability of proposed method to successfully adjust for differential follow-up times and incorporate the effects of covariates in the weighting.

  6. 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…

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

    PubMed

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

    2015-11-11

    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.

  8. [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.

  9. 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

  10. An integrative model of respiratory and cardiovascular control in sleep-disordered breathing

    PubMed Central

    Cheng, Limei; Ivanova, Olga; Fan, Hsing-Hua; Khoo, Michael C. K.

    2010-01-01

    While many physiological control models exist in the literature, none thus far has focused on characterizing the interactions among the respiratory, cardiovascular and sleep-wake regulation systems that occur in sleep-disordered breathing. The model introduced in this study integrates the autonomic control of the cardiovascular system, chemoreflex and state-related control of respiration, including respiratory and upper airway mechanics, along with a model of circadian and sleep-wake regulation. The integrative model provides realistic predictions of the physiological responses under a variety of conditions including: the sleep-wake cycle, hypoxia-induced periodic breathing, Cheyne-Stokes respiration in chronic heart failure, and obstructive sleep apnoea (OSA). It can be used to investigate the effects of a variety of interventions, such as isocapnic and hypercapnic and/or hypoxic gas administration, the Valsalva and Mueller maneuvers, and the application of continuous positive airway pressure on OSA subjects. By being able to delineate the influences of the various interacting physiological mechanisms, the model is useful in providing a more lucid understanding of the complex dynamics that characterize state-cardiorespiratory control in the different forms of sleep-disordered breathing. PMID:20542148

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Development and validation of a cardiovascular risk prediction model for Japanese: the Hisayama study.

    PubMed

    Arima, Hisatomi; Yonemoto, Koji; Doi, Yasufumi; Ninomiya, Toshiharu; Hata, Jun; Tanizaki, Yumihiro; Fukuhara, Masayo; Matsumura, Kiyoshi; Iida, Mitsuo; Kiyohara, Yutaka

    2009-12-01

    The objective of this paper is to develop a new risk prediction model of cardiovascular disease and to validate its performance in a general population of Japanese. The Hisayama study is a population-based prospective cohort study. A total of 2634 participants aged 40 years or older were followed up for 14 years for incident cardiovascular disease (stroke and coronary heart disease (myocardial infarction, coronary revascularization and sudden cardiac death)). We used data among a random two-thirds (the derivation cohort, n=1756) to develop a new risk prediction model that was then tested to compare observed and predicted outcomes in the remaining one-third (the validation cohort, n=878). A multivariable cardiovascular risk prediction model was developed that incorporated age, sex, systolic blood pressure, diabetes, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and smoking. We assessed the performance of the model for predicting individual cardiovascular event among the validation cohort. The risk prediction model demonstrated good discrimination (c-statistic=0.81; 95% confidence interval, 0.77 to 0.86) and calibration (Hosmer-Lemeshow chi(2)-statistic=6.46; P=0.60). A simple risk score sheet based on the cardiovascular risk prediction model was also presented. We developed and validated a new cardiovascular risk prediction model in a general population of Japanese. The risk prediction model would provide a useful guide to estimate absolute risk of cardiovascular disease and to treat individual risk factors.

  17. Application of cardiovascular models in comparative physiology and blood pressure variability.

    PubMed

    Avolio, Alberto P; Xu, Ke; Butlin, Mark

    2013-01-01

    The usefulness of cardiovascular models is determined by their intended function with respect to elucidating underlying hemodynamic concepts and to enable simulations that will assist in understanding the effects of specific parameters. Models can take different forms, including mock circulatory constructs with physical components, mathematical representations of parameter space relations employing constitutive equations, or closed form representations of electrical circuit analogs described in the time or frequency domain. This investigation describes the use of cardiovascular models based on electrical analogs of mechanical hydrodynamic systems to elucidate two different physiologic concepts: (i) the use of distributed vascular impedance to investigate comparative physiology of optimal design and features related to body size across a broad range of animal species; (ii) use of lumped parameter models to assess the role of arterial stiffness in blood pressure variability. The impedance model shows that an allometric relationship between body weight and aortic effective length can be determined by using the frequency of minimum input impedance and aortic pulse wave velocity. This concept provides a background for optimal matching of body size and hemodynamic load on the heart. The lumped parameter model indicates that arterial stiffness, simulated by the total arterial compliance term, has a significant impact on variability of arterial pressure when changes are due to dynamic alterations of peripheral resistance. In addition, the known pressure dependency of arterial stiffness results in a curvilinear relationship between blood pressure variability and mean pressure. This has implications in hypertensive treatment where there are marked changes in arterial stiffness, as occurs with aging.

  18. Nanoparticles and the cardiovascular system: a critical review.

    PubMed

    Donaldson, Ken; Duffin, Rodger; Langrish, Jeremy P; Miller, Mark R; Mills, Nicholas L; Poland, Craig A; Raftis, Jennifer; Shah, Anoop; Shaw, Catherine A; Newby, David E

    2013-03-01

    Nanoparticles (NPs) are tiny particles with a diameter of less than 100 nm. Traffic exhaust is a major source of combustion-derived NPs (CDNPs), which represent a significant component in urban air pollution. Epidemiological, panel and controlled human chamber studies clearly demonstrate that exposure to CDNPs is associated with multiple adverse cardiovascular effects in both healthy individuals and those with pre-existing cardiovascular disease. NPs are also manufactured from a large range of materials for industrial use in a vast array of products including for use as novel imaging agents for medical use. There is currently little information available on the impacts of manufactured NPs in humans, but experimental studies demonstrate similarities to the detrimental cardiovascular actions of CDNPs. This review describes the evidence for these cardiovascular effects and attempts to resolve the paradox between the adverse effects of the unintentional exposure of CDNPs and the intentional delivery of manufactured NPs for medical purposes.

  19. 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

  20. The CD40-CD40L system in cardiovascular disease.

    PubMed

    Pamukcu, Burak; Lip, Gregory Y H; Snezhitskiy, Viktor; Shantsila, Eduard

    2011-08-01

    The CD40-CD40L system is a pathway which is associated with both prothrombotic and proinflammatory effects. CD40 and its ligand were first discovered on the surface of activated T cells, but its presence on B cells, antigen-presenting cells, mast cells, and finally platelets, is evident. The soluble form of CD40L (sCD40L) is derived mainly from activated platelets and contributes to the pathophysiology of atherosclerosis and atherothrombosis. Indeed, sCD40L has autocrine, paracrine, and endocrine activities, and it enhances platelet activation, aggregation, and platelet-leucocyte conjugation that may lead to atherothrombosis. It has even been suggested that sCD40L may play a pathogenic role in triggering acute coronary syndromes. Conversely, blockade of this pathway with anti-CD40L antibodies may prevent or delay the progression of atherosclerosis. Concentrations of sCD40L also predict risk of future cardiovascular disease in healthy women and clinical outcomes in patients with acute coronary syndromes. However, there are controversial and uncertain points over the application of this biomarker to clinical cardiology. In this review, we provide an overview of potential implications of CD40-CD40L signalling and sCD40L as a biomarker in patients with atherosclerotic vascular diseases.

  1. How did Haly Abbas look at the cardiovascular system?

    PubMed

    Dalfardi, Behnam; Mahmoudi Nezhad, Golnoush Sadat; Mehdizadeh, Alireza

    2014-03-01

    Persian scholars, especially those who lived during the Golden Age of Islamic Medicine (9th-12th century AD), made significant contributions to the healing arts and secured a place of honor for themselves in the history of this science. Abū l-Ḥasan Alī ibn al-'Abbās al-Majūsī Ahvazi (? 930-994AD), with the Latinized name of Haly Abbas, was a scientist from this part of the world who contributed to the advancement of medicine. He is the author of Kāmil al-Sinā'ah al-Tibbīyah (The Perfect Book of the Art of Medicine), also commonly known as al-Kitāb al-Malikī (The Royal Book), a medical encyclopedia renowned for its systematic and precise content. This textbook covers a wide variety of medical issues, among them topics related to the science of cardiology. This paper reviews the main points of Haly Abbas' knowledge of the cardiovascular system, of which little has been written until now.

  2. 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.

  3. 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

  4. TRPV1 channels in cardiovascular system: A double edged sword?

    PubMed

    Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

    2017-02-01

    Apart from modulating nociception, there is vital role of TRPV1 channels in modulating atherosclerosis, congestive heart failure, systemic hypertension, pulmonary hypertension, hemorrhagic shock and vascular remodeling. TRPV1 channel activation has shielding effect against the development of atherosclerosis and systemic hypertension. TRPV1 channel activation alleviates the formation of atherosclerotic lesions via increasing the expression of cholesterol efflux regulatory protein, UCP 2 and enhancing autophagy. Furthermore, activation of these channels enhances Na(+) excretion and NO release to reduce the blood pressure. TRPV1 channel activation in the cardiac sensory neurons and subsequent CGRP release reduces ischemia-reperfusion injury. Activation of these channels during conditioning enhances CGRP and SP release from the sensory nerve fibers innervating the heart to induce cardioprotection. However, activation of these channels may elicit detrimental effects in pulmonary hypertension, hemorrhage and vascular remodeling. Activation of TRPV1 channels enhances smooth muscle cell proliferation to promote pulmonary hypertension. Moreover, TRPV1 channel inhibition reduces massive catecholamine release, improves survival during hemorrhage. Activation of these channels enhances vascular remodeling via enhancing NO release. Furthermore, dual role of TRPV1 channels has been reported in the perpetuation of congestive heart failure. On one hand, TRPV1 channel activation increases the expression of UCP2, PPAR- δ and mitochondrial sirtuin 3 to decrease oxidative stress and reduce heart injury. On the other hand, activation of these channels may enhance the expression of hypertrophic fibrotic proteins viz. GATA4, MMP to promote cardiac fibrosis. The present review discusses the dual role of activation of TRPV1 channels in diseases associated with cardiovascular system.

  5. Model-based cardiovascular disease diagnosis: a preliminary in-silico study.

    PubMed

    Ebrahimi Nejad, Shiva; Carey, Jason P; McMurtry, M Sean; Hahn, Jin-Oh

    2017-04-01

    In this study, we developed and examined the feasibility of a model-based system identification approach to cardiovascular disease diagnosis. The basic premise of the approach is that it may be possible to diagnose cardiovascular disease from disease-induced alterations in the arterial mechanical properties manifested in the proximal and distal arterial blood pressure waveforms. It first individualizes the lumped-parameter model of wave propagation and reflection in the artery using the measurement of proximal and distal arterial blood pressure waveforms. Then, it employs a diagnosis logic, in the form of disease-specific patterns in model parameters, referred as [Formula: see text] and pulse transit time. The longitudinal change in these parameters is used to diagnose the presence of peripheral artery disease and arterial stiffening. We illustrated the feasibility of the proposed approach by testing it in a full-scale in-silico arterial tree simulation. The results showed that the approach exhibited superior sensitivity to ankle-brachial index and convenience to carotid-femoral pulse wave velocity: The model parameters [Formula: see text] and [Formula: see text] responded with up to 100 and 40 % changes to peripheral artery disease with up to 50 % arterial blockage whereas the change in ankle-brachial index was [Formula: see text]; the same parameters responded with up to 300 and 40 % changes to up to 100 % arterial stiffening while pulse transit time changed by up to 24 %. Together with the development of more convenient techniques for the measurement of arterial blood pressure waveforms, the proposed approach may evolve into a viable alternative to the state-of-the-art techniques for cardiovascular disease diagnosis.

  6. Systemic Inflammation in Cardiovascular and Periodontal Disease: Comparative Study

    PubMed Central

    Glurich, Ingrid; Grossi, Sara; Albini, Boris; Ho, Alex; Shah, Rashesh; Zeid, Mohamed; Baumann, Heinz; Genco, Robert J.; De Nardin, Ernesto

    2002-01-01

    Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, α1-acid-glycoprotein (AAG), α1-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes. PMID:11874889

  7. 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

  8. Cardiovascular system identification: Simulation study using arterial and central venous pressures.

    PubMed

    Karamolegkos, Nikolaos; Vicario, Francesco; Chbat, Nicolas W

    2015-08-01

    The paper presents a study of the identifiability of a lumped model of the cardiovascular system. The significance of this work from the existing literature is in the potential advantage of using both arterial and central venous (CVP) pressures, two signals that are frequently monitored in the critical care unit. The analysis is done on the system's state-space representation via control theory and system identification techniques. Non-parametric state-space identification is preferred over other identification techniques as it optimally assesses the order of a model, which best describes the input-output data, without any prior knowledge about the system. In particular, a recent system identification algorithm, namely Observer Kalman Filter Identification with Deterministic Projection, is used to identify a simplified version of an existing cardiopulmonary model. The outcome of the study highlights the following two facts. In the deterministic (noiseless) case, the theoretical indicators report that the model is fully identifiable, whereas the stochastic case reveals the difficulty in determining the complete system's dynamics. This suggests that even with the use of CVP as an additional pressure signal, the identification of a more detailed (high order) model of the circulatory system remains a challenging task.

  9. Protective effects of AMP-activated protein kinase in the cardiovascular system.

    PubMed

    Xu, Qiang; Si, Liang-Yi

    2010-11-01

    Cardiovascular diseases remain the leading cause of mortality worldwide. Recent studies of AMP-activated protein kinase (AMPK), a highly conserved sensor of cellular energy status, suggest that there might be therapeutic value in targeting the AMPK signaling pathway. AMPK is found in most mammalian tissues, including those of the cardiovascular system. As cardiovascular diseases are typically associated with blood flow occlusion and blood occlusion may induce rapid energy deficit, AMPK activation may occur during the early phase upon nutrient deprivation in cardiovascular organs. Therefore, investigation of AMPK in cardiovascular organs may help us to understand the pathophysiology of defence mechanisms in these organs. Recent studies have provided proof of concept for the idea that AMPK is protective in heart as well as in vascular endothelial and smooth muscle cells. Moreover, dysfunction of the AMPK signalling pathway is involved in the genesis and development of various cardiovascular diseases, including atherosclerosis, hypertension and stroke. The roles of AMPK in the cardiovascular system, as they are currently understood, will be presented in this review. The interaction between AMPK and other cardiovascular signalling pathways such as nitric oxide signalling is also discussed.

  10. 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.

  11. P2 receptor subtypes in the cardiovascular system.

    PubMed Central

    Kunapuli, S P; Daniel, J L

    1998-01-01

    Extracellular nucleotides have been implicated in a number of physiological functions. Nucleotides act on cell-surface receptors known as P2 receptors, of which several subtypes have been cloned. Both ATP and ADP are stored in platelets and are released upon platelet activation. Furthermore, nucleotides are also released from damaged or broken cells. Thus during vascular injury nucleotides play an important role in haemostasis through activation of platelets, modulation of vascular tone, recruitment of neutrophils and monocytes to the site of injury, and facilitation of adhesion of leucocytes to the endothelium. Nucleotides also moderate these functions by generating nitric oxide and prostaglandin I2 through activation of endothelial cells, and by activating different receptor subtypes on vascular smooth muscle cells. In the heart, P2 receptors regulate contractility through modulation of L-type Ca2+ channels, although the molecular mechanisms involved are still under investigation. Classical pharmacological studies have identified several P2 receptor subtypes in the cardiovascular system. Molecular pharmacological studies have clarified the nature of some of these receptors, but have complicated the picture with others. In platelets, the classical P2T receptor has now been resolved into three P2 receptor subtypes: the P2Y1, P2X1 and P2TAC receptors (the last of these, which is coupled to the inhibition of adenylate cyclase, is yet to be cloned). In peripheral blood leucocytes, endothelial cells, vascular smooth muscle cells and cardiomyocytes, the effects of classical P2X, P2Y and P2U receptors have been found to be mediated by more than one P2 receptor subtype. However, the exact functions of these multiple receptor subtypes remain to be understood, as P2-receptor-selective agonists and antagonists are still under development. PMID:9841859

  12. 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...

  13. 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...

  14. 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...

  15. Biochemistry, Physiology and Pathophysiology of NADPH Oxidases in the Cardiovascular System

    PubMed Central

    Lassègue, Bernard; San Martín, Alejandra; Griendling, Kathy K.

    2012-01-01

    The NADPH oxidase (Nox) enzymes are critical mediators of cardiovascular physiology and pathophysiology. These proteins are expressed in virtually all cardiovascular cells, and regulate such diverse functions as differentiation, proliferation, apoptosis, senescence, inflammatory responses and oxygen sensing. They target a number of important signaling molecules, including kinases, phosphatases, transcription factors, ion channels and proteins that regulate the cytoskeleton. Nox enzymes have been implicated in many different cardiovascular pathologies: atherosclerosis, hypertension, cardiac hypertrophy and remodeling, angiogenesis and collateral formation, stroke and heart failure. In this review, we discuss in detail the biochemistry of Nox enzymes expressed in the cardiovascular system (Nox1, 2, 4 and 5), their roles in cardiovascular cell biology, and their contributions to disease development. PMID:22581922

  16. Invited review-Computed tomographic angiography (CTA) of the thoracic cardiovascular system in companion animals.

    PubMed

    Drees, Randi; François, Christopher J; Saunders, Jimmy H

    2014-01-01

    Computed tomographic angiography (CTA) of the thoracic cardiovascular system is offering new diagnostic opportunities in companion animal patients with the increasing availability of multidetector-row computed tomographic (MDCT) units in veterinary facilities. Optimal investigation of the systemic, pulmonary, and coronary circulation provides unique challenges due to the constant movement of the heart, the small size of several of the structures of interest, and the dependence of angiographic quality on various contrast bolus design and patient factors. Technical and practical aspects of thoracic cardiovascular CTA are reviewed in light of the currently available veterinary literature and future opportunities given utilizing MDCT in companion animal patients with suspected thoracic cardiovascular disease.

  17. 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

  18. 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.

  19. 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.

  20. Usefulness of serum interleukin-18 in predicting cardiovascular mortality in patients with chronic kidney disease--systems and clinical approach.

    PubMed

    Formanowicz, Dorota; Wanic-Kossowska, Maria; Pawliczak, Elżbieta; Radom, Marcin; Formanowicz, Piotr

    2015-12-16

    The aim of this study was to check if serum interleukin-18 (IL-18) predicts 2-year cardiovascular mortality in patients at various stages of chronic kidney disease (CKD) and history of acute myocardial infarction (AMI) within the previous year. Diabetes mellitus was one of the key factors of exclusion. It was found that an increase in serum concentration of IL-18 above the cut-off point (1584.5 pg/mL) was characterized by 20.63-fold higher risk of cardiovascular deaths among studied patients. IL-18 serum concentration was found to be superior to the well-known cardiovascular risk parameters, like high sensitivity C-reactive protein (hsCRP), carotid intima media thickness (CIMT), glomerular filtration rate, albumins, ferritin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in prognosis of cardiovascular mortality. The best predictive for IL-18 were 4 variables, such as CIMT, NT-proBNP, albumins and hsCRP, as they predicted its concentration at 89.5%. Concluding, IL-18 seems to be important indicator and predictor of cardiovascular death in two-year follow-up among non-diabetic patients suffering from CKD, with history of AMI in the previous year. The importance of IL-18 in the process of atherosclerotic plaque formation has been confirmed by systems analysis based on a formal model expressed in the language of Petri nets theory.

  1. Usefulness of serum interleukin-18 in predicting cardiovascular mortality in patients with chronic kidney disease – systems and clinical approach

    PubMed Central

    Formanowicz, Dorota; Wanic-Kossowska, Maria; Pawliczak, Elżbieta; Radom, Marcin; Formanowicz, Piotr

    2015-01-01

    The aim of this study was to check if serum interleukin-18 (IL-18) predicts 2-year cardiovascular mortality in patients at various stages of chronic kidney disease (CKD) and history of acute myocardial infarction (AMI) within the previous year. Diabetes mellitus was one of the key factors of exclusion. It was found that an increase in serum concentration of IL-18 above the cut-off point (1584.5 pg/mL) was characterized by 20.63-fold higher risk of cardiovascular deaths among studied patients. IL-18 serum concentration was found to be superior to the well-known cardiovascular risk parameters, like high sensitivity C-reactive protein (hsCRP), carotid intima media thickness (CIMT), glomerular filtration rate, albumins, ferritin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in prognosis of cardiovascular mortality. The best predictive for IL-18 were 4 variables, such as CIMT, NT-proBNP, albumins and hsCRP, as they predicted its concentration at 89.5%. Concluding, IL-18 seems to be important indicator and predictor of cardiovascular death in two-year follow-up among non-diabetic patients suffering from CKD, with history of AMI in the previous year. The importance of IL-18 in the process of atherosclerotic plaque formation has been confirmed by systems analysis based on a formal model expressed in the language of Petri nets theory. PMID:26669254

  2. [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.

  3. [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.

  4. Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases.

    PubMed

    Tobaldini, Eleonora; Costantino, Giorgio; Solbiati, Monica; Cogliati, Chiara; Kara, Tomas; Nobili, Lino; Montano, Nicola

    2017-03-01

    Sleep deprivation (SD) has become a relevant health problem in modern societies. We can be sleep deprived due to lifestyle habits or due to sleep disorders, such as insomnia, obstructive sleep apnea (OSA) and neurological disorders. One of the common element of sleep disorders is the condition of chronic SD, which has complex biological consequences. SD is capable of inducing different biological effects, such as neural autonomic control changes, increased oxidative stress, altered inflammatory and coagulatory responses and accelerated atherosclerosis. All these mechanisms links SD and cardiovascular and metabolic disorders. Epidemiological studies have shown that short sleep duration is associated with increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities. Thus, an early assessment of a condition of SD and its treatment is clinically relevant to prevent the harmful consequences of a very common condition in adult population.

  5. Pathophysiology of the Cardiovascular System and Neonatal Hypotension.

    PubMed

    Shead, Sandra L

    2015-01-01

    Hypotension is common in low birth weight neonates and less common in term newborns and is associated with significant morbidity and mortality. Determining an adequate blood pressure in neonates remains challenging for the neonatal nurse because of the lack of agreed-upon norms. Values for determining norms for blood pressure at varying gestational and postnatal ages are based on empirical data. Understanding cardiovascular pathophysiology, potential causes of hypotension, and assessment of adequate perfusion in the neonatal population is important and can assist the neonatal nurse in the evaluation of effective blood pressure. This article reviews cardiovascular pathophysiology as it relates to blood pressure and discusses potential causes of hypotension in the term and preterm neonate. Variation in management of hypotension across centers is discussed. Underlying causes and pathophysiology of hypotension in the neonate are described.

  6. Cardiovascular symptoms in patients with systemic mast cell activation disease.

    PubMed

    Kolck, Ulrich W; Haenisch, Britta; Molderings, Gerhard J

    2016-08-01

    Traditionally, mast cell activation disease (MCAD) has been considered as just one rare (neoplastic) disease, mastocytosis, focused on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, the MC activation syndrome, has been recognized featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. Increasing expertise and appreciation has been established for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic theme. We describe the pathogenesis of MCAD with a particular focus on clinical cardiovascular symptoms and the therapeutic options for MC mediator-induced cardiovascular symptoms.

  7. 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

  8. Cardiovascular system and microgravity simulation and inflight results

    NASA Astrophysics Data System (ADS)

    Pottier, J. M.; Patat, F.; Arbeille, P.; Pourcelot, L.; Massabuau, P.; Guell, A.; Gharib, C.

    Main results of cardiovascular investigation, performed with ultrasound methods during the common French/Soviet flight aboard Salyut VII in June 1982, are compared to variations of the same parameters studied during ground-based simulations on the same subject or observed by other investigators during various ground-based experiences. The antiorthostatic bed rest simulation partly reproduces microgravity conditions and seems to be better adaptated to cardiac hemodynamics, despite some differences, and to the cerebral circulation, than to the inferior limb circulation.

  9. Aerobic vs anaerobic exercise training effects on the cardiovascular system.

    PubMed

    Patel, Harsh; Alkhawam, Hassan; Madanieh, Raef; Shah, Niel; Kosmas, Constantine E; Vittorio, Timothy J

    2017-02-26

    Physical exercise is one of the most effective methods to help prevent cardiovascular (CV) disease and to promote CV health. Aerobic and anaerobic exercises are two types of exercise that differ based on the intensity, interval and types of muscle fibers incorporated. In this article, we aim to further elaborate on these two categories of physical exercise and to help decipher which provides the most effective means of promoting CV health.

  10. Aerobic vs anaerobic exercise training effects on the cardiovascular system

    PubMed Central

    Patel, Harsh; Alkhawam, Hassan; Madanieh, Raef; Shah, Niel; Kosmas, Constantine E; Vittorio, Timothy J

    2017-01-01

    Physical exercise is one of the most effective methods to help prevent cardiovascular (CV) disease and to promote CV health. Aerobic and anaerobic exercises are two types of exercise that differ based on the intensity, interval and types of muscle fibers incorporated. In this article, we aim to further elaborate on these two categories of physical exercise and to help decipher which provides the most effective means of promoting CV health. PMID:28289526

  11. Introduction: Cardiovascular physics.

    PubMed

    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.

  12. 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.

  13. [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.

  14. [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.

  15. 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

  16. 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

  17. 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.

  18. [Postmenopausal hormone replacement therapy and the cardiovascular system].

    PubMed

    Yildirir, Aylin

    2010-03-01

    Women suffer from cardiovascular diseases 10 years later than men, therefore female sex has been considered to be a 'protective factor'. However, the risk in women increases rapidly after menopause and the declining levels of endogenous estrogen is thought to be responsible. Postmenopausal hormone replacement therapy (HRT) decreases the severity and intensity of menopausal symptoms and improves women's quality of life. Until the last 10 years, based on the results of observational studies, postmenopausal HRT was thought to protect women against cardiovascular events and decrease the risk of coronary artery disease by 35-50%. However, recent randomized primary and secondary prevention trials did not support the cardioprotective effect of HRT. The different results of observational and randomized controlled trials are discussed to be related to the differences in the study population. The study population in observational and prospective cohort studies included relatively young women at the earlier stages of menopause, whereas studies showing neutral or negative effects of HRT included women older than 50 years old at least 10 years in menopause. Furthermore, the effects of estrogen depend on the state of vascular pathology. In relatively healthy vessels with no or early signs of atherosclerosis, estrogen prevent the development or progression of atherosclerotic lesions, whereas in the presence of established atherosclerotic lesions, estrogen promotes atherosclerosis or may even trigger acute events. Therefore, it is critically important to predict which women can safely receive HRT and which are at increased risk from HRT. Under the light of current knowledge, HRT should not be used for prevention from cardiovascular disease in postmenopausal women and the many other preventive strategies, (diet, exercise, blood pressure or cholesterol control) that are proven to be effective but underused, should be kept in mind.

  19. 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.

  20. Nprl3 is required for normal development of the cardiovascular system.

    PubMed

    Kowalczyk, Monika S; Hughes, Jim R; Babbs, Christian; Sanchez-Pulido, Luis; Szumska, Dorota; Sharpe, Jacqueline A; Sloane-Stanley, Jacqueline A; Morriss-Kay, Gillian M; Smoot, Leslie B; Roberts, Amy E; Watkins, Hugh; Bhattacharya, Shoumo; Gibbons, Richard J; Ponting, Chris P; Wood, William G; Higgs, Douglas R

    2012-08-01

    C16orf35 is a conserved and widely expressed gene lying adjacent to the human α-globin cluster in all vertebrate species. In-depth sequence analysis shows that C16orf35 (now called NPRL3) is an orthologue of the yeast gene Npr3 (nitrogen permease regulator 3) and, furthermore, is a paralogue of its protein partner Npr2. The yeast Npr2/3 dimeric protein complex senses amino acid starvation and appropriately adjusts cell metabolism via the TOR pathway. Here we have analysed a mouse model in which expression of Nprl3 has been abolished using homologous recombination. The predominant effect on RNA expression appears to involve genes that regulate protein synthesis and cell cycle, consistent with perturbation of the mTOR pathway. Embryos homozygous for this mutation die towards the end of gestation with a range of cardiovascular defects, including outflow tract abnormalities and ventriculoseptal defects consistent with previous observations, showing that perturbation of the mTOR pathway may affect development of the myocardium. NPRL3 is a candidate gene for harbouring mutations in individuals with developmental abnormalities of the cardiovascular system.

  1. Comprehensive physiological cardiovascular model enables automatic correction of hemodynamics in patients with acute life-threatening heart failure.

    PubMed

    Uemura, Kazunori; Kamiya, Atsunori; Shimizu, Shuji; Shishido, Toshiaki; Sugimachi, Masaru; Sunagawa, Kenji

    2006-01-01

    Saving life of patients with acute life-threatening heart failure is a major challenge. One has to correct several fatal hemodynamic abnormalities at the same time within a limited time frame. The formulation of such complicated treatments enables the development of a system that can be used to save automatically lives of patients with acute heart failure, an autopilot system. To accomplish this, we established a comprehensive physiological cardiovascular model, on which we based the design of the autopilot system. By translating hemodynamics into cardiovascular parameters (pumping ability, vascular resistance, blood volume), and by controlling each of these with individual drugs, we were able to correct blood pressure, cardiac output, and left atrial pressure to the target values rapidly (5.2 +/- 6.6, 6.8 +/- 4.6, and 11.7 +/- 9.8 minutes), stably, and simultaneously.

  2. Regulation of Rho proteins by phosphorylation in the cardiovascular system.

    PubMed

    Loirand, Gervaise; Guilluy, Christophe; Pacaud, Pierre

    2006-08-01

    The small G protein Rho signaling pathways are recognized as major regulators of cardiovascular functions, and activation of Rho proteins appears to be a common component for the pathogenesis of hypertension and vascular proliferative disorders. Rho proteins are tightly regulated, and recent evidence suggests that modulation of Rho protein signaling by phosphorylation of Rho proteins provides an additional simple mechanism for coordinating Rho protein functions. This regulation by phosphorylation is particularly important in the arterial wall, where RhoA protein expressed in vascular smooth muscle cells is controlled by the endothelium through the nitric oxide/cGMP-dependent kinase pathway.

  3. Cutaneous lupus erythematosus and systemic lupus erythematosus are associated with clinically significant cardiovascular risk: a Danish nationwide cohort study.

    PubMed

    Hesselvig, J Halskou; Ahlehoff, O; Dreyer, L; Gislason, G; Kofoed, K

    2017-01-01

    Systemic lupus erythematosus (SLE) is a well-known cardiovascular risk factor. Less is known about cutaneous lupus erythematosus (CLE) and the risk of developing cardiovascular disease (CVD). Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients diagnosed with SLE and CLE. We conducted a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular endpoint and all-cause mortality, for patients with SLE and CLE. A total of 3282 patients with CLE and 3747 patients with SLE were identified and compared with 5,513,739 controls. The overall HR for the composite CVD endpoint was 1.31 (95% CI 1.16-1.49) for CLE and 2.05 (95% CI 1.15-3.44) for SLE. The corresponding HRs for all-cause mortality were 1.32 (95% CI 1.20-1.45) for CLE and 2.21 (95% CI 2.03-2.41) for SLE. CLE and SLE were associated with a significantly increased risk of CVD and all-cause mortality. Local and chronic inflammation may be the driver of low-grade systemic inflammation.

  4. 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.

  5. The Learning Healthcare System and Cardiovascular Care: A Scientific Statement From the American Heart Association.

    PubMed

    Maddox, Thomas M; Albert, Nancy M; Borden, William B; Curtis, Lesley H; Ferguson, T Bruce; Kao, David P; Marcus, Gregory M; Peterson, Eric D; Redberg, Rita; Rumsfeld, John S; Shah, Nilay D; Tcheng, James E

    2017-03-02

    The learning healthcare system uses health information technology and the health data infrastructure to apply scientific evidence at the point of clinical care while simultaneously collecting insights from that care to promote innovation in optimal healthcare delivery and to fuel new scientific discovery. To achieve these goals, the learning healthcare system requires systematic redesign of the current healthcare system, focusing on 4 major domains: science and informatics, patient-clinician partnerships, incentives, and development of a continuous learning culture. This scientific statement provides an overview of how these learning healthcare system domains can be realized in cardiovascular disease care. Current cardiovascular disease care innovations in informatics, data uses, patient engagement, continuous learning culture, and incentives are profiled. In addition, recommendations for next steps for the development of a learning healthcare system in cardiovascular care are presented.

  6. 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.

  7. Individual differences in the locus coeruleus-norepinephrine system: Relevance to stress-induced cardiovascular vulnerability.

    PubMed

    Wood, Christopher S; Valentino, Rita J; Wood, Susan K

    2017-04-01

    Repeated exposure to psychosocial stress is a robust sympathomimetic stressor and as such has adverse effects on cardiovascular health. While the neurocircuitry involved remains unclear, the physiological and anatomical characteristics of the locus coeruleus (LC)-norepinephrine (NE) system suggest that it is poised to contribute to stress-induced cardiovascular vulnerability. A major theme throughout is to review studies that shed light on the role that the LC may play in individual differences in vulnerability to social stress-induced cardiovascular dysfunction. Recent findings are discussed that support a unique plasticity in afferent regulation of the LC, resulting in either excitatory or inhibitory input to the LC during establishment of different stress coping strategies. This contrasting regulation of the LC by either afferent regulation, or distinct differences in stress-induced neuroinflammation would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The goal of this review is to highlight recent developments in the interplay between the LC-NE and cardiovascular systems during repeated stress in an effort to advance therapeutic treatments for the development of stress-induced cardiovascular vulnerability.

  8. Preclinical safety assessments of nano-sized constructs on cardiovascular system toxicity: A case for telemetry.

    PubMed

    Cheah, Hoay Yan; Kiew, Lik Voon; Lee, Hong Boon; Japundžić-Žigon, Nina; Vicent, Marίa J; Hoe, See Ziau; Chung, Lip Yong

    2017-02-06

    While nano-sized construct (NSC) use in medicine has grown significantly in recent years, reported unwanted side effects have raised safety concerns. However, the toxicity of NSCs to the cardiovascular system (CVS) and the relative merits of the associated evaluation methods have not been thoroughly studied. This review discusses the toxicological profiles of selected NSCs and provides an overview of the assessment methods, including in silico, in vitro, ex vivo and in vivo models and how they are related to CVS toxicity. We conclude the review by outlining the merits of telemetry coupled with spectral analysis, baroreceptor reflex sensitivity analysis and echocardiography as an appropriate integrated strategy for the assessment of the acute and chronic impact of NSCs on the CVS. Copyright © 2017 John Wiley & Sons, Ltd.

  9. 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

  10. 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.

  11. 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.

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

    PubMed Central

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

    2015-01-01

    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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Complementary role of cardiovascular imaging and laboratory indices in early detection of cardiovascular disease in systemic lupus erythematosus.

    PubMed

    Mavrogeni, S; Koutsogeorgopoulou, L; Dimitroulas, T; Markousis-Mavrogenis, G; Kolovou, G

    2017-03-01

    Background Cardiovascular disease (CVD) has been documented in >50% of systemic lupus erythematosus (SLE) patients, due to a complex interplay between traditional risk factors and SLE-related factors. Various processes, such as coronary artery disease, myocarditis, dilated cardiomyopathy, vasculitis, valvular heart disease, pulmonary hypertension and heart failure, account for CVD complications in SLE. Methods Electrocardiogram (ECG), echocardiography (echo), nuclear techniques, cardiac computed tomography (CT), cardiovascular magnetic resonance (CMR) and cardiac catheterization (CCa) can detect CVD in SLE at an early stage. ECG and echo are the cornerstones of CVD evaluation in SLE. The routine use of cardiac CT and nuclear techniques is limited by radiation exposure and use of iodinated contrast agents. Additionally, nuclear techniques are also limited by low spatial resolution that does not allow detection of sub-endocardial and sub-epicardial lesions. CCa gives definitive information about coronary artery anatomy and pulmonary artery pressure and offers the possibility of interventional therapy. However, it carries the risk of invasive instrumentation. Recently, CMR was proved of great value in the evaluation of cardiac function and the detection of myocardial inflammation, stress-rest perfusion defects and fibrosis. Results An algorithm for CVD evaluation in SLE includes clinical, laboratory, ECG and echo assessment as well as CMR evaluation in patients with inconclusive findings, persistent cardiac symptoms despite normal standard evaluation, new onset of life-threatening arrhythmia/heart failure and/or as a tool to select SLE patients for CCa. Conclusions A non-invasive approach including clinical, laboratory and imaging evaluation is key for early CVD detection in SLE.

  18. 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.

  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. Biotypes of Candida albicans isolated from cardiovascular system and skin surveillance cultures of hospitalized patients.

    PubMed

    Vazić-Babić, Verica; Mlinarić-Missoni, Emilija; Kalenić, Smilja

    2006-01-01

    The aim of the study was to biotype 59 isolates of Candida (C.) albicans from cardiovascular system samples (blood and intravenous catheter) and 123 isolates of the same species from skin surveillance cultures (swabs of the armpit, groins and intravenous catheter insertion sites) of hospitalized patients using the Odds and Abbott biotyping method. Biotyping of 59 isolates of C. albicans taken from the cardiovascular system samples revealed the presence of 16 biotypes. Biotype 355 was the most common biotype, accounting for 35.6% of all biotype isolates from this system. Biotyping of 123 C. albicans isolates from skin surveillance cultures detected 21 biotypes. Biotype 355 was most common, accounting for 17.9% of all biotype isolates from these samples. The two systems had 10 biotypes in common: 355, 155, 257, 305, 105, 315, 300, 015, 157, and 345. These biotypes accounted for 88.3% and 81.4% of all C. albicans biotypes isolated from the cardiovascular system and skin surveillance cultures, respectively. Biotypes 355, 155, and 257 were the biotypes most frequently shared in isolates from the two systems. These biotypes accounted for 57.7% and 43.1% of all C. albicans biotypes isolated from the cardiovascular system and skin surveillance cultures, respectively.

  1. 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

  2. Introduction to the series on microRNAs in the cardiovascular system.

    PubMed

    van Rooij, Eva

    2012-02-03

    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.

  3. TREK-1 K(+) channels in the cardiovascular system: their significance and potential as a therapeutic target.

    PubMed

    Goonetilleke, Lakshman; Quayle, John

    2012-02-01

    Potassium (K(+) ) channels are important in cardiovascular disease both as drug targets and as a cause of underlying pathology. Voltage-dependent K(+) (K(V) ) channels are inhibited by the class III antiarrhythmic agents. Certain vasodilators work by opening K(+) channels in vascular smooth muscle cells (VSMCs), and K(+) channel activation may also be a route to improving endothelial function. The two-pore domain K(+) (K(2P) ) channels form a group of 15 known channels with an expanding list of functions in the cardiovascular system. One of these K(2P) channels, TREK-1, is the focus of this review. TREK-1 channel activity is tightly regulated by intracellular and extracellular pH, membrane stretch, polyunsaturated fatty acids (PUFAs), temperature, and receptor-coupled second messenger systems. TREK-1 channels are also activated by volatile anesthetics and some neuroprotectant agents, and they are inhibited by selective serotonin reuptake inhibitors (SSRIs) as well as amide local anesthetics. Some of the clinical cardiovascular effects and side effects of these drugs may be through their actions on TREK-1 channels. It has recently been suggested that TREK-1 channels have a role in mechano-electrical coupling in the heart. They also seem important in the vascular responses to PUFAs, and this may underlie some of the beneficial cardiovascular effects of the essential dietary fatty acids. Development of selective TREK-1 openers and inhibitors may provide promising routes for intervention in cardiovascular diseases.

  4. Pediatric computed tomographic angiography: imaging the cardiovascular system gently.

    PubMed

    Hellinger, Jeffrey C; Pena, Andres; Poon, Michael; Chan, Frandics P; Epelman, Monica

    2010-03-01

    Whether congenital or acquired, timely recognition and management of disease is imperative, as hemodynamic alterations in blood flow, tissue perfusion, and cellular oxygenation can have profound effects on organ function, growth and development, and quality of life for the pediatric patient. Ensuring safe computed tomographic angiography (CTA) practice and "gentle" pediatric imaging requires the cardiovascular imager to have sound understanding of CTA advantages, limitations, and appropriate indications as well as strong working knowledge of acquisition principles and image post processing. From this vantage point, CTA can be used as a useful adjunct along with the other modalities. This article presents a summary of dose reduction CTA methodologies along with techniques the authors have employed in clinical practice to achieve low-dose and ultralow-dose exposure in pediatric CTA. CTA technical principles are discussed with an emphasis on the low-dose methodologies and safe contrast medium delivery strategies. Recommended parameters for currently available multidetector-row computed tomography scanners are summarized alongside recommended radiation and contrast medium parameters. In the second part of the article an overview of pediatric CTA clinical applications is presented, illustrating low-dose and ultra-low dose techniques, with an emphasis on the specific protocols.

  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. Cardiovascular and autonomic modulation by the central nervous system after aerobic exercise training.

    PubMed

    Martins-Pinge, M C

    2011-09-01

    The autonomic nervous system plays a key role in maintaining homeostasis under normal and pathological conditions. The sympathetic tone, particularly for the cardiovascular system, is generated by sympathetic discharges originating in specific areas of the brainstem. Aerobic exercise training promotes several cardiovascular adjustments that are influenced by the central areas involved in the output of the autonomic nervous system. In this review, we emphasize the studies that investigate aerobic exercise training protocols to identify the cardiovascular adaptations that may be the result of central nervous system plasticity due to chronic exercise. The focus of our study is on some groups of neurons involved in sympathetic regulation. They include the nucleus tractus solitarii, caudal ventrolateral medulla and the rostral ventrolateral medulla that maintain and regulate the cardiac and vascular autonomic tonus. We also discuss studies that demonstrate the involvement of supramedullary areas in exercise training modulation, with emphasis on the paraventricular nucleus of the hypothalamus, an important area of integration for autonomic and neuroendocrine responses. The results of these studies suggest that the beneficial effects of physical activity may be due, at least in part, to reductions in sympathetic nervous system activity. Conversely, with the recent association of physical inactivity with chronic disease, these data may also suggest that increases in sympathetic nervous system activity contribute to the increased incidence of cardiovascular diseases associated with a sedentary lifestyle.

  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. 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.

  10. 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 ...

  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. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Design and utilization of macrophage and vascular smooth muscle cell co-culture systems in atherosclerotic cardiovascular disease investigation.

    PubMed

    Zuniga, Mary C; White, Sharla L Powell; Zhou, Wei

    2014-10-01

    Atherosclerotic cardiovascular disease has been acknowledged as a chronic inflammatory condition. Monocytes and macrophages lead the inflammatory pathology of atherosclerosis whereas changes in atheromatous plaque thickness and matrix composition are attributed to vascular smooth muscle cells. Because these cell types are key players in atherosclerosis progression, it is crucial to utilize a reliable system to investigate their interaction. In vitro co-culture systems are useful platforms to study specific molecular mechanisms between cells. This review aims to summarize the various co-culture models that have been developed to investigate vascular smooth muscle cell and monocyte/macrophage interactions, focusing on the monocyte/macrophage effects on vascular smooth muscle cell function.

  19. 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.

  20. 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.

  1. 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

  2. [Capacity and resistance parameters of the athlete's cardiovascular system and their dynamics in regular training].

    PubMed

    Epifanov, V A; Suvorova, S S

    2001-01-01

    Viscosity and elasticity of the cardiovascular system are assessed by a new method based on evaluation of correlations between deposit properties of the left ventricular chamber, aortic wall and vascular resistance in different parts of the arterial tree. This method examines individual hemodynamic characteristics of healthy untrained persons and hemodynamic changes due to regular training.

  3. The heart and cardiovascular system in the Qur'an and Hadeeth.

    PubMed

    Loukas, Marios; Saad, Yousuf; Tubbs, R Shane; Shoja, Mohamadali M

    2010-04-01

    Descriptions of the human anatomy derived from religious texts are often omitted from the medical literature. The present review aims to discuss the comments and commentaries made regarding the heart and cardiovascular system as found in the Qur'an and Hadeeth. Based on this review, it is clear that these early sources both had a good comprehension of these parts of the body.

  4. 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...

  5. Hydrogen sulphide in cardiovascular system: A cascade from interaction between sulphur atoms and signalling molecules.

    PubMed

    Wang, Ming-Jie; Cai, Wen-Jie; Zhu, Yi-Chun

    2016-05-15

    As a gasotransmitter, hydrogen sulphide exerts its extensive physiological and pathophysiological effects in mammals. The interaction between sulphur atoms and signalling molecules forms a cascade that modulates cellular functions and homeostasis. In this review, we focus on the signalling mechanism underlying the effect of hydrogen sulphide in the cardiovascular system and metabolism as well as the biological relevance to human diseases.

  6. 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

  7. 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…

  8. Physics of the cardiovascular system: An intrinsic control mechanism of the human heart

    NASA Astrophysics Data System (ADS)

    Uehara, Mituo; Sakane, Kumiko K.

    2003-04-01

    Differential equations for the cardiovascular system are derived by applying the continuity equation of fluid mechanics to the rate of blood flow and variation of blood volume in different parts of the system. The equations are used to explain the Frank-Starling mechanism, which plays an important role in the maintenance of the stability of the distribution of blood in the system. This treatment can be easily understood by undergraduate physics students with no previous knowledge of human physiology.

  9. 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.

  10. 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.

  11. 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.

  12. [Significance of endogenous sulfur dioxide in the regulation of cardiovascular system].

    PubMed

    Jin, Hong Fang; DU, Shu Xu; Zhao, Xia; Zhang, Su Qing; Tian, Yue; Bu, Ding Fang; Tang, Chao Shu; DU, Jun Bao

    2007-08-18

    Since the 1980's nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H(2)S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the regulation of body homeostasis and to play important roles under physiological and pathophysiological conditions. The researches on these endogenous gas signal molecules opened a new avenue in life science. To explore the new member of gasotransmitter family, other endogenous gas molecules which have been regarded as metabolic waste up to date, and their biological regulatory effects have been paid close attention to in the current fields of life science and medicine. Sulfur dioxide (SO(2)) can be produced endogenously from normal metabolism of sulfur-containing amino acids. L-cysteine is oxidized via cysteine dioxygenase to L-cysteinesulfinate, and the latter can proceed through transamination by glutamate oxaloacetate transaminase (GOT) to beta-sulfinyl pyruvate which decomposes spontaneously to pyruvate and SO(2). In mammals, activated neutrophils by oxidative stress can convert H(2)S to sulfite through a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent process. The authors detected endogenous production of SO(2) in all cardiovascular tissues, including in heart, aorta, pulmonary artery, mesenteric artery, renal artery, tail artery and the plasma SO(2) content. As the key enzyme producing SO(2), GOT mRNA in cardiovascular system was detected and found to be located enriched in endothelial cells and vascular smooth muscle cells near the endothelial layer. When the normal rats were treated with hydroxamate(HDX), a GOT inhibitor, at a dose of 3.7 mg/kg body weight, the blood pressure (BP) went high markedly, the ratio of wall thickness to lumen radius was increased by 18.34%, and smooth muscle cell proliferation was enhanced. The plasma SO(2) level in the rats injected with 125 micromol/kg body weight SO(2) donor was

  13. A Bionic Approach to Cardiovascular Regulation: Bionic Arterial Baroreflex System

    DTIC Science & Technology

    2007-11-02

    micromanometer and by stimulating celiac with the knowledge of system characteristics. succeeded in functionally identifying the native arterial...system was obtained. Similarly we recorded blood pressure while stimulating sympathetic nerves at the celiac ganglia randomly. We A BIONIC APPROACH TO...baroreflex was realized by stimulating the celiac ganglia according to the stimulation command. The stimulation command was calculated by convolving the

  14. Nighttime instabilities of neurophysiological, cardiovascular, and respiratory activity: integrative modeling and preliminary results

    PubMed Central

    Shusterman, Vladimir; Troy, William C.; Abdelmessih, Medhat; Hoffman, Stacy; Nemec, Jan; Strollo, Patrick J.; London, Barry; Lampert, Rachel

    2015-01-01

    Unstable (cyclical alternating pattern, or CAP) sleep is associated with surges of sympathetic nervous system activity, increased blood pressure and vasoconstriction, heightened baroreflex sensitivity, and unstable heart rhythm and breathing. In susceptible persons, CAP sleep provokes clinically significant events, including hypertensive crises, sleep-disordered breathing, and cardiac arrhythmias. Here we explore the neurophysiology of CAP sleep and its impact on cardiovascular and respiratory functions. We show that: (i) an increase in neurophysiological recovery rate can explain the emergence of slow, self-sustained, hypersynchronized A1 CAP-sleep pattern and its transition to the faster A2-A3 CAP-sleep patterns; (ii) in a two-dimensional, continuous model of cardiac tissue with heterogeneous action potential duration (APD) distribution, heart rate accelerations during CAP sleep may encounter incompletely recovered electrical excitability in cell clusters with longer APD. If the interaction between short cycle length and incomplete, spatially heterogeneous repolarization persists over multiple cycles, irregularities and asymmetry of depolarization front may accumulate and ultimately lead to a conduction block, retrograde conduction, breakup of activation waves, reentrant activity, and arrhythmias; and (iii) these modeling results are consistent with the nighttime data obtained from patients with structural heart disease (N=13) that show clusters of atrial and ventricular premature beats occurring during the periods of unstable heart rhythm and respiration that accompany CAP sleep. In these patients, CAP sleep is also accompanied by delayed adaptation of QT intervals and T-wave alternans. PMID:26341647

  15. 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.

  16. 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

  17. The Cardiovascular Intensive Care Unit-An Evolving Model for Health Care Delivery.

    PubMed

    Loughran, John; Puthawala, Tauqir; Sutton, Brad S; Brown, Lorrel E; Pronovost, Peter J; DeFilippis, Andrew P

    2017-02-01

    Prior to the advent of the coronary care unit (CCU), patients having an acute myocardial infarction (AMI) were managed on the general medicine wards with reported mortality rates of greater than 30%. The first CCUs are believed to be responsible for reducing mortality attributed to AMI by as much as 40%. This drastic improvement can be attributed to both advances in medical technology and in the process of health care delivery. Evolving considerably since the 1960s, the CCU is now more appropriately labeled as a cardiac intensive care unit (CICU) and represents a comprehensive system designed for the care of patients with an array of advanced cardiovascular disease, an entity that reaches far beyond its early association with AMI. Grouping of patients by diagnosis to a common physical space, dedicated teams of health care providers, as well as the development and implementation of evidence-based treatment algorithms have resulted in the delivery of safer, more efficient care, and most importantly better patient outcomes. The CICU serves as a platform for an integrated, team-based patient care delivery system that addresses a broad spectrum of patient needs. Lessons learned from this model can be broadly applied to address the urgent need to improve outcomes and efficiency in a variety of health care settings.

  18. Response of the Cardiovascular System to Vibration and Combined Stresses

    DTIC Science & Technology

    1982-11-30

    ACCELERATION FREQUENCY. Hz Figure A12. Comparison of +2 Gy and ;2 G~ values of left ventricular end diastolic l*vol umi in 6 normally Innervated animls lb...induced regulatory process. METHODS •" Anlzal Andel, The animal model was one in which the artrio-ventricular L node was destroyed using the technique of...standard instruments for measuring aortic flow and right and left ventricular and aortic pressure. This model allows investigator control of heart rate

  19. 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.

  20. Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

    PubMed Central

    Ramachandran, Deepa; Luo, Chuan; Ma, Tony S; Clark, John W

    2009-01-01

    Background Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow. Methods We integrate a new pericardial model into our previously developed H-CRS model based on a fit to patient pressure data. Virtual experiments are designed to simulate pericardial effusion and study mechanisms of pulsus paradoxus, focusing particularly on the role of the interventricular septum. Model differential equations programmed in C are solved using a 5th-order Runge-Kutta numerical integration scheme. MATLAB is employed for waveform analysis. Results The H-CRS model simulates hemodynamic and respiratory changes associated with tamponade clinically. Our model predicts effects of effusion-generated pericardial constraint on chamber and septal mechanics, such as altered right atrial filling, delayed leftward septal motion, and prolonged left ventricular pre-ejection period, causing atrioventricular interaction and ventricular desynchronization. We demonstrate pericardial constraint to markedly accentuate normal ventricular interactions associated with respiratory effort, which we show to be the distinct mechanisms of pulsus paradoxus, namely, series and parallel ventricular interaction. Series ventricular interaction represents respiratory variation in right ventricular stroke volume carried over to the left ventricle via the pulmonary vasculature, whereas parallel interaction (via the septum and pericardium) is a result of

  1. Serotonin and Sensory Nerves: Meeting in the Cardiovascular System

    PubMed Central

    Watts, Stephanie W.

    2014-01-01

    Blood pressure regulation by 5-HT has proven to be a complex story to unravel. The work by Cuesta et al in this issue of Vascular Pharmacology adds another layer of complexity by providing sound in vivo data that 5-HT, through the 5-HT7 receptor, can inhibit the vasodepressor actions of the sensory nervous system and thereby promote blood pressure maintenance. This interaction of 5-HT with the sensory nervous system is inhibitory, whereas 5-HT is understood to be stimulatory in other systems. Moreover, activation of the 5-HT7 receptor has been linked to both reduction and elevation of blood pressure. These interactions are discussed in this mini-review, as are potential steps forward in understanding the interplay of 5-HT, the sensory nervous system and blood pressure. PMID:25181552

  2. 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.

  3. 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.

  4. Drug targeting of estrogen receptor signaling in the cardiovascular system: preclinical and clinical studies.

    PubMed

    Sanz-González, Silvia M; Cano, Antonio; Valverde, M A; Hermenegildo, Carlos; Andrés, Vicente

    2004-04-01

    Atherosclerosis and associated coronary heart disease events have lower prevalence in women than in men, especially during young adult years. Although multiple lines of evidence suggest that estrogens contribute to this difference, the efficacy of hormone replacement therapy for the prevention of cardiovascular disease in postmenopausal women is controversial. The protective action of estrogen in the cardiovascular system appears to be mediated indirectly by an effect on serum lipoprotein and triglyceride profiles and on the expression of coagulant and fibrinolytic proteins, and by a direct effect on the vessel wall itself. Estrogen has both rapid effects involving alteration of membrane ionic permeability and activation of membrane-bound enzymes and increases in endothelial cell nitric oxide synthase activity, as well as longer-term effects on gene expression that are mediated, at least in part, by the ligand-activated transcription factors, estrogen receptor alpha and beta. Compounds with pure antiestrogenic activity and selective estrogen receptor modulators that regulate estrogen receptor function in a tissue-specific manner have been developed in an attempt to achieve the cardioprotective effects of estrogens while minimizing the undesirable risks associated with hormone replacement therapy (e.g., endometrial and breast cancer). In this review, we will discuss recent developments on the mechanisms of estrogen action in the cardiovascular system. The results of clinical trials testing the long-term efficacy of hormone replacement therapy for the treatment of cardiovascular disease will also be discussed.

  5. Intra- and Interorgan Communication in the Cardiovascular System: A Special View on Redox Regulation.

    PubMed

    Gödecke, Axel; Haendeler, Judith

    2017-02-07

    Intraorgan communication in the cardiovascular system is exerted not only by direct cell-cell contacts but also by locally released factors, which modulate neighboring cells by paracrine signals (e.g., NO, vascular endothelial growth factor, adenosine, reactive oxygen species). Moreover, cells in close proximity to the typical cardiovascular cells such as fibroblasts, red blood cells, as well as resident and invading immune cells must be considered in attempts to understand cardiovascular function in physiology and pathology. The second level of communication is the interorgan communication, which may be distinguished from intraorgan communication, since it involves signaling from remote organs to the heart and circulation. Therefore, mediators released by, for example, the kidney or skeletal muscle reach the heart and modulate its function. This is not only the case under physiological conditions, because there is increasing evidence that the organ-specific response to a primary insult may affect also the function of remote organs by the release of factors. This Forum will summarize novel mechanisms involved in intraorgan and interorgan communication of the cardiovascular system, with a special view on the remote organs, skeletal muscle and kidney.

  6. 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.

  7. Characterization of coherent structures in the cardiovascular system.

    PubMed

    Shadden, Shawn C; Taylor, Charles A

    2008-07-01

    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 understanding of flow features in large vessels beyond methods traditionally considered.

  8. Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep.

    PubMed

    Wang, Qiming; Gold, Nathan; Frasch, Martin G; Huang, Huaxiong; Thiriet, Marc; Wang, Xiaogang

    2015-12-01

    Fetal acidemia during labor is associated with an increased risk of brain injury and lasting neurological deficits. This is in part due to the repetitive occlusions of the umbilical cord (UCO) induced by uterine contractions. Whereas fetal heart rate (FHR) monitoring is widely used clinically, it fails to detect fetal acidemia. Hence, new approaches are needed for early detection of fetal acidemia during labor. We built a mathematical model of the UCO effects on FHR, mean arterial blood pressure (MABP), oxygenation and metabolism. Mimicking fetal experiments, our in silico model reproduces salient features of experimentally observed fetal cardiovascular and metabolic behavior including FHR overshoot, gradual MABP decrease and mixed metabolic and respiratory acidemia during UCO. Combined with statistical analysis, our model provides valuable insight into the labor-like fetal distress and guidance for refining FHR monitoring algorithms to improve detection of fetal acidemia and cardiovascular decompensation.

  9. Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep

    PubMed Central

    Wang, Qiming; Gold, Nathan; Frasch, Martin G.; Thiriet, Marc; Wang, Xiaogang

    2017-01-01

    Fetal acidemia during labor is associated with an increased risk of brain injury and lasting neurological deficits. This is in part due to the repetitive occlusions of the umbilical cord (UCO) induced by uterine contractions. Whereas fetal heart rate (FHR) monitoring is widely used clinically, it fails to detect fetal acidemia. Hence, new approaches are needed for early detection of fetal acidemia during labor. We built a mathematical model of the UCO effects on FHR, mean arterial blood pressure (MABP), oxygenation and metabolism. Mimicking fetal experiments, our in silico model reproduces salient features of experimentally observed fetal cardiovascular and metabolic behavior including FHR overshoot, gradual MABP decrease and mixed metabolic and respiratory acidemia during UCO. Combined with statistical analysis, our model provides valuable insight into the labor-like fetal distress and guidance for refining FHR monitoring algorithms to improve detection of fetal acidemia and cardiovascular decompensation. PMID:26582358

  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. An integrated mathematical model of the human cardiopulmonary system: model development.

    PubMed

    Albanese, Antonio; Cheng, Limei; Ursino, Mauro; Chbat, Nicolas W

    2016-04-01

    Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics.

  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. 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)

  14. Effects of air pollution caused by sugarcane burning in Western São Paulo on the cardiovascular system

    PubMed Central

    Pestana, Paula Roberta da Silva; Braga, Alfésio Luís Ferreira; Ramos, Ercy Mara Cipulo; de Oliveira, Ariadna Ferraz; Osadnik, Christian Robert; Ferreira, Aline Duarte; Ramos, Dionei

    2017-01-01

    ABSTRACT OBJECTIVE To evaluate the effects of acute exposure to air pollutants (NO2 and PM10) on hospitalization of adults and older people with cardiovascular diseases in Western São Paulo. METHODS Daily cardiovascular-related hospitalization data (CID10 – I00 to I99) were acquired by the Department of Informatics of the Brazilian Unified Health System (DATASUS) from January 2009 to December 2012. Daily levels of NO2 and PM10 and weather data were obtained from Companhia Ambiental do Estado de São Paulo (CETESB – São Paulo State Environmental Agency). To estimate the effects of air pollutants exposure on hospital admissions, generalized linear Poisson regression models were used. RESULTS During the study period, 6,363 hospitalizations were analysed. On the day of NO2 exposure, an increase of 1.12% (95%CI 0.05–2.20) was observed in the interquartile range along with an increase in hospital admissions. For PM10, a pattern of similar effect was observed; however, results were not statistically significant. CONCLUSIONS Even though with values within established limits, NO2 is an important short-term risk factor for cardiovascular morbidity. PMID:28273230

  15. [Current concepts of the origin of circadian changes in the cardiovascular system under normal and pathological conditions].

    PubMed

    Arushanyan, E B

    2012-01-01

    The importance of circadian rhythms for the function of the cardiovascular system and its pharmacotherapy is discussed The central mechanisms regulating these rhythms at the level of suprachiasmatic hypothalamic nucleus and pineal gland are considered in conjunction with the approaches to modulating their activity for optimization of chronopharmnacotherapy of cardiovascular diseases.

  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. Protein O-GlcNAcylation: a new signaling paradigm for the cardiovascular system

    PubMed Central

    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 β-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. PMID:19028792

  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. System identification: a multi-signal approach for probing neural cardiovascular regulation.

    PubMed

    Xiao, Xinshu; Mullen, Thomas J; Mukkamala, Ramakrishna

    2005-06-01

    Short-term, beat-to-beat cardiovascular variability reflects the dynamic interplay between ongoing perturbations to the circulation and the compensatory response of neurally mediated regulatory mechanisms. This physiologic information may be deciphered from the subtle, beat-to-beat variations by using digital signal processing techniques. While single signal analysis techniques (e.g., power spectral analysis) may be employed to quantify the variability itself, the multi-signal approach of system identification permits the dynamic characterization of the neural regulatory mechanisms responsible for coupling the variability between signals. In this review, we provide an overview of applications of system identification to beat-to-beat variability for the quantitative characterization of cardiovascular regulatory mechanisms. After briefly summarizing the history of the field and basic principles, we take a didactic approach to describe the practice of system identification in the context of probing neural cardiovascular regulation. We then review studies in the literature over the past two decades that have applied system identification for characterizing the dynamical properties of the sinoatrial node, respiratory sinus arrhythmia, and the baroreflex control of sympathetic nerve activity, heart rate and total peripheral resistance. Based on this literature review, we conclude by advocating specific methods of practice and that future research should focus on nonlinear and time-varying behaviors, validation of identification methods, and less understood neural regulatory mechanisms. Ultimately, we hope that this review stimulates such future investigations by both new and experienced system identification researchers.

  20. Nano-constructed Carriers Loaded With Antioxidant: Boon For Cardiovascular System.

    PubMed

    Jain, Ashay; Kesharwani, Prashant; Garg, Neeraj Kumar; Jain, Atul; Nirbhavane, Pradip; Dwivedi, Nitin; Banerjee, Sanjeev; Iyer, Arun K; Iqbal Mohd Amin, Mohd Cairul

    2015-01-01

    In the last couple of decades antioxidant agents have entered the health market as an easy and attractive means of managing diseases. These agents are of enormous interest for an increasingly health-concerned society, and may be particularly relevant for prophylaxis of a number of diseases i.e. arthritis, cancer, metabolic and cardiovascular diseases, osteoporosis, cataracts, brain disorders, etc. Antioxidants are also favorable to vascular healthiness and symbolize useful compounds because they are able to diminish overall cardiovascular risk by acting analogous to first line therapy or as adjuvants in case of failure or in situations where first line therapy cannot be used. Furthermore, well-designed trials are indeed needed to improve the therapeutic efficacy and health benefits of antioxidants. Numerous in vivo proof-of-concepts studies are offered to underline the feasibility of nanostructure system in order to optimizing the delivery of cardiovascular drugs. The present review highlights the recent approaches for management of cardiovascular disease using different vesicular and particulate carriers, including liposomes, nanoparticles, and nanoemulsions, with a primary emphasis on those which are expected to enhance the antioxidants level.

  1. Diagnosis of cardiovascular diseases based on diffuse optical tomography system

    NASA Astrophysics Data System (ADS)

    Yu, Zong-Han; Wu, Chun-Ming; Lin, Yo-Wei; Chuang, Ming-Lung; Tsai, Jui-che; Sun, Chia-Wei

    2008-02-01

    Diffuse optical tomography (DOT) is a technique to assess the spatial variation in absorption and scattering properties of the biological tissues. DOT provides the measurement of changes in concentrations of oxy-hemoglobin and deoxy-hemoglobin. The oxygenation images are reconstructed by the measured optical signals with nearest-neighbor pairs of sources and detectors. In our study, a portable DOT system is built with optode design on a flexible print circuit board (FPCB). In experiments, the hemodynamics temporal evolution of exercises and vessel occlusions are observed with in vivo measurements form normal subjects and some patients in intensive care unit.

  2. 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.

  3. A new oxidative stress model, 2,2-azobis(2-amidinopropane) dihydrochloride induces cardiovascular damages in chicken embryo.

    PubMed

    He, Rong-Rong; Li, Yan; Li, Xiao-Di; Yi, Ruo-Nan; Wang, Xiao-Yu; Tsoi, Bun; Lee, Kenneth Ka Ho; Abe, Keiichi; Yang, Xuesong; Kurihara, Hiroshi

    2013-01-01

    It is now well established that the developing embryo is very sensitive to oxidative stress, which is a contributing factor to pregnancy-related disorders. However, little is known about the effects of reactive oxygen species (ROS) on the embryonic cardiovascular system due to a lack of appropriate ROS control method in the placenta. In this study, a small molecule called 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH), a free radicals generator, was used to study the effects of oxidative stress on the cardiovascular system during chick embryo development. When nine-day-old (stage HH 35) chick embryos were treated with different concentrations of AAPH inside the air chamber, it was established that the LD50 value for AAPH was 10 µmol/egg. At this concentration, AAPH was found to significantly reduce the density of blood vessel plexus that was developed in the chorioallantoic membrane (CAM) of HH 35 chick embryos. Impacts of AAPH on younger embryos were also examined and discovered that it inhibited the development of vascular plexus on yolk sac in HH 18 embryos. AAPH also dramatically repressed the development of blood islands in HH 3+ embryos. These results implied that AAPH-induced oxidative stress could impair the whole developmental processes associated with vasculogenesis and angiogenesis. Furthermore, we observed heart enlargement in the HH 40 embryo following AAPH treatment, where the left ventricle and interventricular septum were found to be thickened in a dose-dependent manner due to myocardiac cell hypertrophy. In conclusion, oxidative stress, induced by AAPH, could lead to damage of the cardiovascular system in the developing chick embryo. The current study also provided a new developmental model, as an alternative for animal and cell models, for testing small molecules and drugs that have anti-oxidative activities.

  4. 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

  5. [The marmoset in biomedical research. Value of this primate model for cardiovascular studies].

    PubMed

    Michel, J B; Mahouy, G

    1990-03-01

    Because of its small size, low cost of maintenance, breeding capabilities in captivity, the marmoset, a New World monkey, appears well suited for clinical and fundamental investigations. The contribution of this laboratory animal in the main areas of biomedical research is succinctly described: viral oncology, infections diseases, immunology, reproduction, toxicology and teratology, odontology, behaviour and neuro-psychopathology. Emphasis is put upon the exceptional interest of the use of marmoset as a biological model in cardiovascular studies.

  6. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system.

    PubMed

    Nagatomo, Takafumi; Rashid, Mamunur; Abul Muntasir, Habib; Komiyama, Tadazumi

    2004-10-01

    The serotonin (5-hydroxytryptamine, 5-HT) receptors have conventionally been divided into seven subfamilies, most of which have several subtypes. Among them, 5-HT(2A) receptor is associated with the contraction of vascular smooth muscle, platelet aggregation and thrombus formation and coronary artery spasms. Accordingly, selective 5-HT(2A) antagonists may have potential in the treatment of cardiovascular diseases. Sarpogrelate, a selective 5-HT(2A) antagonist, has been introduced clinically as a therapeutic agent for the treatment of ischemic diseases associated with thrombosis. Molecular modeling studies also suggest that sarpogrelate is a 5-HT(2A) selective antagonist and is likely to have pharmacological effects beneficial in the treatment of cardiovascular diseases. This review describes the above findings as well as the signaling linkages of the 5-HT(2A) receptors and the mode of agonist binding to 5-HT(2A) receptor using data derived from molecular modeling and site-directed mutagenesis.

  7. 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.

  8. A Systems Biology Approach to Uncovering Pharmacological Synergy in Herbal Medicines with Applications to Cardiovascular Disease

    PubMed Central

    Wang, Xia; Xu, Xue; Tao, Weiyang; Li, Yan; Wang, Yonghua; Yang, Ling

    2012-01-01

    Background. Clinical trials reveal that multiherb prescriptions of herbal medicine often exhibit pharmacological and therapeutic superiority in comparison to isolated single constituents. However, the synergistic mechanisms underlying this remain elusive. To address this question, a novel systems biology model integrating oral bioavailability and drug-likeness screening, target identification, and network pharmacology method has been constructed and applied to four clinically widely used herbs Radix Astragali Mongolici, Radix Puerariae Lobatae, Radix Ophiopogonis Japonici, and Radix Salviae Miltiorrhiza which exert synergistic effects of combined treatment of cardiovascular disease (CVD). Results. The results show that the structural properties of molecules in four herbs have substantial differences, and each herb can interact with significant target proteins related to CVD. Moreover, the bioactive ingredients from different herbs potentially act on the same molecular target (multiple-drug-one-target) and/or the functionally diverse targets but with potentially clinically relevant associations (multiple-drug-multiple-target-one-disease). From a molecular/systematic level, this explains why the herbs within a concoction could mutually enhance pharmacological synergy on a disease. Conclusions. The present work provides a new strategy not only for the understanding of pharmacological synergy in herbal medicine, but also for the rational discovery of potent drug/herb combinations that are individually subtherapeutic. PMID:23243453

  9. 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.

  10. Autonomic nervous system abnormalities in spinocerebellar ataxia type 2: a cardiovascular neurophysiologic study.

    PubMed

    De Joanna, G; De Rosa, A; Salvatore, E; Castaldo, I; De Luca, N; Izzo, R; Manzo, V; Filla, A; De Michele, G

    2008-12-15

    Autonomic nervous system dysfunction is part of the spinocerebellar ataxia (SCA) clinical picture, but few data are available on this topic. The present study is aimed to report a detailed investigation of autonomic nervous system in patients with molecular diagnosis of SCA type 2, one of the most frequent forms and the commonest in Italy. Nine patients with a mild to moderate form of SCA2 underwent a questionnaire about dysautonomic symptoms and a complete cardiovascular neurophysiologic evaluation of both sympathetic and parasympathetic system, comprising head-up tilt, standing, isometric hand grip, cold pressure, mental arithmetic, Valsalva manoeuvre, deep breathing, and hyperventilation tests. An echocardiographic study and Holter-ECG recording were also performed. All patients complained dysautonomic problems regarding urinary tract, cardiovascular system, or gastrointestinal dysfunction. The neurophysiologic study showed both sympathetic and parasympathetic involvement, with highly variable degree and pattern of dysautonomia. The present study results show that the autonomic dysfunction is common in SCA2 representing a significant component of the complex picture of the disease. We found a wide spectrum of cardiovascular autonomic abnormalities, without a typical pattern of dysfunction and without correlation with clinical variables.

  11. 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

  12. Golden ratio: A subtle regulator in our body and cardiovascular system?

    PubMed

    Ozturk, Selcuk; Yalta, Kenan; Yetkin, Ertan

    2016-11-15

    Golden ratio, which is an irrational number and also named as the Greek letter Phi (φ), is defined as the ratio between two lines of unequal length, where the ratio of the lengths of the shorter to the longer is the same as the ratio between the lengths of the longer and the sum of the lengths. The so-called formula is a mathematical ratio and there exist a variety of examples in natural and man-made structures of great beauty. Moreover, golden ratio is expressed throughout the human body in some ways, including digits, uterus, teeth, and cardiovascular system. Although the association of Fibonacci series or golden ratio with systems and organs of human being has not been assessed in depth yet, the mainstream regulation of cardiovascular system seems to be associated with golden ratio. This raises the idea that there might have been a fine and subtle regulator in our body. In this article, we aimed to elaborate the relationship between the existence of golden ratio and the human body and to discuss the golden ratio and its association with cardiovascular system.

  13. 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.

  14. Cardiovascular Surgery Residency Program: Training Coronary Anastomosis Using the Arroyo Simulator and UNIFESP Models

    PubMed Central

    Maluf, Miguel Angel; Gomes, Walter José; Bras, Ademir Massarico; de Araújo, Thiago Cavalcante Vila Nova; Mota, André Lupp; Cardoso, Caio Cesar; Coutinho, Rafael Viana dos S.

    2015-01-01

    OBJECTIVE Engage the UNIFESP Cardiovascular Surgery residents in coronary anastomosis, assess their skills and certify results, using the Arroyo Anastomosis Simulator and UNIFESP surgical models. METHODS First to 6th year residents attended a weekly program of technical training in coronary anastomosis, using 4 simulation models: 1. Arroyo simulator; 2. Dummy with a plastic heart; 3. Dummy with a bovine heart; and 4. Dummy with a beating pig heart. The assessment test was comprised of 10 items, using a scale from 1 to 5 points in each of them, creating a global score of 50 points maximum. RESULTS The technical performance of the candidate showed improvement in all items, especially manual skill and technical progress, critical sense of the work performed, confidence in the procedure and reduction of the time needed to perform the anastomosis after 12 weeks practice. In response to the multiplicity of factors that currently influence the cardiovascular surgeon training, there have been combined efforts to reform the practices of surgical medical training. CONCLUSION 1 - The four models of simulators offer a considerable contribution to the field of cardiovascular surgery, improving the skill and dexterity of the surgeon in training. 2 - Residents have shown interest in training and cooperate in the development of innovative procedures for surgical medical training in the art. PMID:26735604

  15. 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

  16. 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.

  17. Natriuretic peptide receptor B signaling in the cardiovascular system: protection from cardiac hypertrophy.

    PubMed

    Pagel-Langenickel, Ines; Buttgereit, Jens; Bader, Michael; Langenickel, Thomas H

    2007-08-01

    Natriuretic peptides (NP) represent a family of structurally homologous but genetically distinct peptide hormones involved in regulation of fluid and electrolyte balance, blood pressure, fat metabolism, cell proliferation, and long bone growth. Recent work suggests a role for natriuretic peptide receptor B (NPR-B) signaling in regulation of cardiac growth by either a direct effect on cardiomyocytes or by modulation of other signaling pathways including the autonomic nervous system. The research links NPR-B for the first time to a cardiac phenotype in vivo and underlines the importance of the NP in the cardiovascular system. This manuscript will focus on the role of NPR-B and its ligand C-type natriuretic peptide in cardiovascular physiology and disease and will evaluate these new findings in the context of the known function of this receptor, with a perspective on how future research might further elucidate NPR-B function.

  18. Investigating autonomic control of the cardiovascular system: a battery of simple tests.

    PubMed

    Johnson, Christopher D; Roe, Sean; Tansey, Etain A

    2013-12-01

    Sympathetic and parasympathetic divisions of the autonomic nervous system constantly control the heart (sympathetic and parasympathetic divisions) and blood vessels (predominantly the sympathetic division) to maintain appropriate blood pressure and organ blood flow over sometimes widely varying conditions. This can be adversely affected by pathological conditions that can damage one or both branches of autonomic control. The set of teaching laboratory activities outlined here uses various interventions, namely, 1) the heart rate response to deep breathing, 2) the heart rate response to a Valsalva maneuver, 3) the heart rate response to standing, and 4) the blood pressure response to standing, that cause fairly predictable disturbances in cardiovascular parameters in normal circumstances, which serve to demonstrate the dynamic control of the cardiovascular system by autonomic nerves. These tests are also used clinically to help investigate potential damage to this control.

  19. Physiology and pharmacology of the cardiovascular adrenergic system.

    PubMed

    Lymperopoulos, Anastasios

    2013-09-04

    Heart failure (HF), the leading cause of death in the western world, ensues in response to cardiac injury or insult and represents the inability of the heart to adequately pump blood and maintain tissue perfusion. It is characterized by complex interactions of several neurohormonal mechanisms that get activated in the syndrome in order to try and sustain cardiac output in the face of decompensating function. The most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are greatly elevated in HF. Acutely, provided that the heart still works properly, this activation of the ANS will promptly restore cardiac function according to the fundamental Frank-Starling law of cardiac function. However, if the cardiac insult persists over time, this law no longer applies and ANS will not be able to sustain cardiac function. This is called decompensated HF, and the hyperactive ANS will continue to "push" the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, and, finally, the molecular alterations in heart physiology that occur in HF along with their pharmacological and therapeutic implications for the failing heart.

  20. Skeletal Muscle Pump Drives Control of Cardiovascular and Postural Systems

    PubMed Central

    Verma, Ajay K.; Garg, Amanmeet; Xu, Da; Bruner, Michelle; Fazel-Rezai, Reza; Blaber, Andrew P.; Tavakolian, Kouhyar

    2017-01-01

    The causal interaction between cardio-postural-musculoskeletal systems is critical in maintaining postural stability under orthostatic challenge. The absence or reduction of such interactions could lead to fainting and falls often experienced by elderly individuals. The causal relationship between systolic blood pressure (SBP), calf electromyography (EMG), and resultant center of pressure (COPr) can quantify the behavior of cardio-postural control loop. Convergent cross mapping (CCM) is a non-linear approach to establish causality, thus, expected to decipher nonlinear causal cardio-postural-musculoskeletal interactions. Data were acquired simultaneously from young participants (25 ± 2 years, n = 18) during a 10-minute sit-to-stand test. In the young population, skeletal muscle pump was found to drive blood pressure control (EMG → SBP) as well as control the postural sway (EMG → COPr) through the significantly higher causal drive in the direction towards SBP and COPr. Furthermore, the effect of aging on muscle pump activation associated with blood pressure regulation was explored. Simultaneous EMG and SBP were acquired from elderly group (69 ± 4 years, n = 14). A significant (p = 0.002) decline in EMG → SBP causality was observed in the elderly group, compared to the young group. The results highlight the potential of causality to detect alteration in blood pressure regulation with age, thus, a potential clinical utility towards detection of fall proneness. PMID:28345674

  1. Physiology and pharmacology of the cardiovascular adrenergic system

    PubMed Central

    Lymperopoulos, Anastasios

    2013-01-01

    Heart failure (HF), the leading cause of death in the western world, ensues in response to cardiac injury or insult and represents the inability of the heart to adequately pump blood and maintain tissue perfusion. It is characterized by complex interactions of several neurohormonal mechanisms that get activated in the syndrome in order to try and sustain cardiac output in the face of decompensating function. The most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are greatly elevated in HF. Acutely, provided that the heart still works properly, this activation of the ANS will promptly restore cardiac function according to the fundamental Frank-Starling law of cardiac function. However, if the cardiac insult persists over time, this law no longer applies and ANS will not be able to sustain cardiac function. This is called decompensated HF, and the hyperactive ANS will continue to “push” the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, and, finally, the molecular alterations in heart physiology that occur in HF along with their pharmacological and therapeutic implications for the failing heart. PMID:24027534

  2. Could a high-fat diet rich in unsaturated fatty acids impair the cardiovascular system?

    PubMed Central

    Medei, Emiliano; Lima-Leopoldo, Ana Paula; Pereira-Junior, Pedro Paulo; Leopoldo, André Soares; Campos, Dijon Henrique Salomé; Raimundo, Juliana Montani; Sudo, Roberto Takashi; Zapata-Sudo, Gisele; Bruder-Nascimento, Thiago; Cordellini, Sandra; Nascimento, José Hamilton Matheus; Cicogna, Antonio Carlos

    2010-01-01

    BACKGROUND: Dyslipidemia results from consumption of a diet rich in saturated fatty acids and is usually associated with cardiovascular disease. A diet rich in unsaturated fatty acids is usually associated with improved cardiovascular condition. OBJECTIVE: To investigate whether a high-fat diet rich in unsaturated fatty acids (U-HFD) – in which fatty acid represents approximately 45% of the total calories – impairs the cardiovascular system. METHODS: Male, 30-day-old Wistar rats were fed a standard (control) diet or a U-HFD containing 83% unsaturated fatty acid for 19 weeks. The in vivo electrocardiogram, the spectral analysis of heart rate variability, and the vascular reactivity responses to phenylephrine, acetylcholine, noradrenaline and prazosin in aortic ring preparations were analyzed to assess the cardiovascular parameters. RESULTS: After 19 weeks, the U-HFD rats had increased total body fat, baseline glucose levels and feed efficiency compared with control rats. However, the final body weight, systolic blood pressure, area under the curve for glucose, calorie intake and heart weight/final body weight ratio were similar between the groups. In addition, both groups demonstrated no alteration in the electrocardiogram or cardiac sympathetic parameters. There was no difference in the responses to acetylcholine or the maximal contractile response of the thoracic aorta to phenylephrine between groups, but the concentration necessary to produce 50% of maximal response showed a decrease in the sensitivity to phenylephrine in U-HFD rats. The cumulative concentration-effect curve for noradrenaline in the presence of prazosin was shifted similarly in both groups. CONCLUSIONS: The present work shows that U-HFD did not impair the cardiovascular parameters analyzed. PMID:21165364

  3. Inverse problems in reduced order models of cardiovascular haemodynamics: aspects of data assimilation and heart rate variability.

    PubMed

    Pant, Sanjay; Corsini, Chiara; Baker, Catriona; Hsia, Tain-Yen; Pennati, Giancarlo; Vignon-Clementel, Irene E

    2017-01-01

    Inverse problems in cardiovascular modelling have become increasingly important to assess each patient individually. These problems entail estimation of patient-specific model parameters from uncertain measurements acquired in the clinic. In recent years, the method of data assimilation, especially the unscented Kalman filter, has gained popularity to address computational efficiency and uncertainty consideration in such problems. This work highlights and presents solutions to several challenges of this method pertinent to models of cardiovascular haemodynamics. These include methods to (i) avoid ill-conditioning of the covariance matrix, (ii) handle a variety of measurement types, (iii) include a variety of prior knowledge in the method, and (iv) incorporate measurements acquired at different heart rates, a common situation in the clinic where the patient state differs according to the clinical situation. Results are presented for two patient-specific cases of congenital heart disease. To illustrate and validate data assimilation with measurements at different heart rates, the results are presented on a synthetic dataset and on a patient-specific case with heart valve regurgitation. It is shown that the new method significantly improves the agreement between model predictions and measurements. The developed methods can be readily applied to other pathophysiologies and extended to dynamical systems which exhibit different responses under different sets of known parameters or different sets of inputs (such as forcing/excitation frequencies).

  4. The influence of selective vitamin D receptor activator paricalcitol on cardiovascular system and cardiorenal protection.

    PubMed

    Duplancic, Darko; Cesarik, Marijan; Poljak, Nikola Kolja; Radman, Maja; Kovacic, Vedran; Radic, Josipa; Rogosic, Veljko

    2013-01-01

    The ubiquitous distribution of vitamin D receptors in the human body is responsible for the pleiotropic effects of vitamin D-receptor activation. We discuss the possible beneficial effects of a selective activator of vitamin D receptor, paricalcitol, on the cardiovascular system in chronic heart failure patients and chronic kidney patients, in light of new trials. Paricalcitol should provide additional clinical benefits over the standard treatment for chronic kidney and heart failure, especially in cases of cardiorenal syndrome.

  5. 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.

  6. 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

  7. [Cardiovascular manifestations in systemic lupus erythematosus in Dakar: Descriptive study about 50 cases].

    PubMed

    Ngaïdé, A A; Ly, F; Ly, K; Diao, M; Kane, Ad; Mbaye, A; Lèye, M; Aw, F; Sarr, S A; Dioum, M; Ndao, C T; Gaye, N D; Ndiaye, M B; Bodian, M; Bah, M B; Ndiaye, M; Cissé, A F; Kouamé, I; Tabane, A; Mingou, J S; Thiombiano, P; Kane, A; Bâ, S A

    2016-12-01

    Systemic lupus erythematosus is a non-specific inflammatory disorder of an organ of unknown cause and autoimmune origin. Visceral injuries, including those cardiovascular, determine the prognosis of this disease primarily affecting women. The objectives of this study were to determine the frequency and describe the cardiovascular manifestations in systemic lupus erythematosus in a lupus population of the Dakar region. This is a multicenter prospective study descriptive and analytical conducted in the region of Dakar (Senegal) from 14 February 2011 to 2 July 2012. Patients were either hospitalized or monitored as outpatients. Included were all patients with lupus and meeting at least four criteria of the American College of Rheumatology of lupus disease classification 1997. All patients underwent physical examination, an electrocardiogram and an echocardiogram looking for cardiovascular damage. The collected data were entered into the Epi Info version 3.5.1 and processed with SPSS 16.0 software. Quantitative variables are described in the median and the qualitative workforce, percentage and frequency. We have included 50 patients. The average age of the population was 36.18 years. A female predominance is noted with a sex ratio man/woman of 0.09. Cardiovascular functional symptoms were dominated by dyspnea stage II to IV NYHA (26%) and palpitations (22%). The physical signs we have found were mainly tachycardia (40%), spontaneous turgor of the jugular veins (29%), a muffling of the heart sounds (29%) and a infandibulopulmonairy shock (18%). The frequency of cardiovascular events was 46%. Electrical cardiac events were dominated by sinus tachycardia (40%) of repolarization disorders (16.3%) type of ischemia, injury, ischemia injury, necrosis and hypertrophy with 18% atrial and left ventricular hypertrophy each. Furthermore, one case of BAV first degree at 280 ms was recorded. We found 19 cases of pericarditis including 2 tamponade, 3 cases of dilated cardiomyopathy

  8. The nuclear uptake and retention of a synthetic progestin in the cardiovascular system of the baboon.

    PubMed

    Sheridan, P J; McGill, H C

    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 we examined the nuclear uptake and retention of a synthetic progestin 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 [3H]ORG 2058 (16 alpha-ethyl-21-hydroxy-19-nor-[6,7-3H]pregn-4-ene-3,20-dione) or with [3H] 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.

  9. 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.

  10. Impact of the human circadian system, exercise, and their interaction on cardiovascular function.

    PubMed

    Scheer, Frank A J L; Hu, Kun; Evoniuk, Heather; Kelly, Erin E; Malhotra, Atul; Hilton, Michael F; Shea, Steven A

    2010-11-23

    The risk of adverse cardiovascular events peaks in the morning (≈9:00 AM) with a secondary peak in the evening (≈8:00 PM) and a trough at night. This pattern is generally believed to be caused by the day/night distribution of behavioral triggers, but it is unknown whether the endogenous circadian system contributes to these daily fluctuations. Thus, we tested the hypotheses that the circadian system modulates autonomic, hemodynamic, and hemostatic risk markers at rest, and that behavioral stressors have different effects when they occur at different internal circadian phases. Twelve healthy adults were each studied in a 240-h forced desynchrony protocol in dim light while standardized rest and exercise periods were uniformly distributed across the circadian cycle. At rest, there were large circadian variations in plasma cortisol (peak-to-trough ≈85% of mean, peaking at a circadian phase corresponding to ≈9:00 AM) and in circulating catecholamines (epinephrine, ≈70%; norepinephrine, ≈35%, peaking during the biological day). At ≈8:00 PM, there was a circadian peak in blood pressure and a trough in cardiac vagal modulation. Sympathetic variables were consistently lowest and vagal markers highest during the biological night. We detected no simple circadian effect on hemostasis, although platelet aggregability had two peaks: at ≈noon and ≈11:00 PM. There was circadian modulation of the cardiovascular reactivity to exercise, with greatest vagal withdrawal at ≈9:00 AM and peaks in catecholamine reactivity at ≈9:00 AM and ≈9:00 PM. Thus, the circadian system modulates numerous cardiovascular risk markers at rest as well as their reactivity to exercise, with resultant profiles that could potentially contribute to the day/night pattern of adverse cardiovascular events.

  11. Injected nanoparticles: the combination of experimental systems to assess cardiovascular adverse effects.

    PubMed

    Vlasova, Maria A; Tarasova, Olga S; Riikonen, Joakim; Raula, Janne; Lobach, Anatoly S; Borzykh, Anna A; Smirin, Boris V; Kauppinen, Esko I; Eletskii, Alexander V; Herzig, Karl-Heinz; Salonen, Jarno; Tavi, Pasi; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-05-01

    When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.

  12. [Cyclic nucleotide phosphodiesterase IV expression, activity and targeting in cells of cardiovascular system].

    PubMed

    Yan, Jun; Zhu, Hai-Bo

    2007-06-01

    Cyclic nucleotide second messages (cAMP and cGMP) play a central role in signal transduction and regulation of physiologic responses. The only way to inactivate them is to degrade them through the action of phosphodiesterases (PDEs). Recent advances show that PDE4, a cAMP specific phosphodiesterase, has specific functions in regulating the activities of the cardiovascular system. PDE4 is expressed in the cells of cardiovascular systems including cardiomyocytes, vascular smooth muscle cells, and vascular endothelial cells. The expression level of PDE4 is shown to be downregulated in the failure hearts, while it is upregulated in hypertrophied hearts. And PDE4 deficiency in mice is associated with a cardiac phenotype comprised of a progressive, age-related cardiomyopathy, accelerated heart failure after myocardial infarction and exercise-induced arrhythmias. Local levels of cAMP regulate the precise opening of the ryanodine receptor complex (RyR2) which releases calcium at the start of a heartbeat. Loss or inhibition of PDE4 activity increases calcium flow through RyR2, and causes leakiness and heart failure in mice. These finding may show us a new target for treating cardiovascular diseases.

  13. PHYSIOLAB: a new laboratory for the study of the cardio-vascular system.

    PubMed

    Marsal, O; Andre-Deshays, C; Cauquil, D; Kotovskaya, A; Gratchev, V; Noskin, A

    1995-01-01

    On the basis of the experience gained during the previous french-russian missions on board MIR about the adaptation processes of the cardio-vascular system, a new laboratory has been designed. The objective of this "PHYSIOLAB" is to have a better understanding of the mechanisms underlying the changes in the cardio-vascular system, with a special emphasis on the phenomenon of cardio-vascular deconditioning after landing. Beyond these scientific objectives, it is also intended to use PHYSIOLAB to help in the medical monitoring on-board MIR, during functional tests such as LBNP. PHYSIOLAB will be set up in MIR by the French cosmonaut during the next french-russian CASSIOPEE mission in 1996. Its architecture is based on a central unit, which controls the experimental protocols, records the results and provides an interface for transmission to the ground via telemetry. Different specific modules are used for the acquisition of various physiological parameters. This PHYSIOLAB under development for the CASSIOPEE mission should evolve towards a more ambitious laboratory, whose definition would take into account the results obtained with the first version of PHYSIOLAB. This "second generation" laboratory should be developed in the frame of wide International cooperation.

  14. Systems biology—opportunities and challenges: the application of proteomics to study the cardiovascular extracellular matrix

    PubMed Central

    Barallobre-Barreiro, Javier; Lynch, Marc; Yin, Xiaoke; Mayr, Manuel

    2016-01-01

    Systems biology approaches including proteomics are becoming more widely used in cardiovascular research. In this review article, we focus on the application of proteomics to the cardiac extracellular matrix (ECM). ECM remodelling is a hallmark of many cardiovascular diseases. Proteomic techniques using mass spectrometry (MS) provide a platform for the comprehensive analysis of ECM proteins without a priori assumptions. Proteomics overcomes various constraints inherent to conventional antibody detection. On the other hand, studies that use whole tissue lysates for proteomic analysis mask the identification of the less abundant ECM constituents. In this review, we first discuss decellularization-based methods that enrich for ECM proteins in cardiac tissue, and how targeted MS allows for accurate protein quantification. The second part of the review will focus on post-translational modifications including hydroxylation and glycosylation and on the release of matrix fragments with biological activity (matrikines), all of which can be interrogated by proteomic techniques. PMID:27635058

  15. Mechanosensitive channels in striated muscle and the cardiovascular system: not quite a stretch anymore.

    PubMed

    Stiber, Jonathan A; Seth, Malini; Rosenberg, Paul B

    2009-08-01

    Stretch-activated or mechanosensitive channels transduce mechanical forces into ion fluxes across the cell membrane. These channels have been implicated in several aspects of cardiovascular physiology including regulation of blood pressure, vasoreactivity, and cardiac arrhythmias, as well as the adverse remodeling associated with cardiac hypertrophy and heart failure. This review discusses mechanosensitive channels in skeletal muscle and the cardiovascular system and their role in disease pathogenesis. We describe the regulation of gating of mechanosensitive channels including direct mechanisms and indirect activation by signaling pathways, as well as the influence on activation of these channels by the underlying cytoskeleton and scaffolding proteins. We then focus on the role of transient receptor potential channels, several of which have been implicated as mechanosensitive channels, in the pathogenesis of adverse cardiac remodeling and as potential therapeutic targets in the treatment of heart failure.

  16. Pain perception and cardiovascular system response among athletes playing contact sports.

    PubMed

    Leźnicka, Katarzyna; Pawlak, Matthias; Białecka, Monika; Safranow, Krzysztof; Cięszczyk, Paweł

    2017-04-10

    The aim of this study was to determine whether the contact sports change the perception of pain as assessed by the cold pressor test (CPT), and if the test induces the same reaction of the cardiovascular system in contact athletes and non-athletes. The study involved 321 healthy men; 140 contact athletes and 181 students of the University of Szczecin (control). Pain threshold and pain tolerance were evaluated using CPT. Cardiovascular measurements were made during CPT. The contact athletes showed a much higher tolerance to pain than the control group (median time 120 vs. 94 s, respectively, p = 0.0002). The thresholds of pain in both groups did not differ significantly between the groups. Systolic blood pressure measured before and during the test in all three measurements was statistically significantly higher in athletes compared with the control group. Heart rate and diastolic blood pressure did not differ significantly between the studied groups.

  17. 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.

  18. Protein kinase d in the cardiovascular system: emerging roles in health and disease.

    PubMed

    Avkiran, Metin; Rowland, Alexandra J; Cuello, Friederike; Haworth, Robert S

    2008-02-01

    The protein kinase D (PKD) family is a recent addition to the calcium/calmodulin-dependent protein kinase group of serine/threonine kinases, within the protein kinase complement of the mammalian genome. Relative to their alphabetically superior cousins in the AGC group of kinases, namely the various isoforms of protein kinase A, protein kinase B/Akt, and protein kinase C, PKD family members have to date received limited attention from cardiovascular investigators. Nevertheless, increasing evidence now points toward important roles for PKD-mediated signaling pathways in the cardiovascular system, particularly in the regulation of myocardial contraction, hypertrophy and remodeling. This review provides a primer on PKD signaling, using information gained from studies in multiple cell types, and discusses recent data that suggest novel functions for PKD-mediated pathways in the heart and the circulation.

  19. Modelling and disentangling physiological mechanisms: linear and nonlinear identification techniques for analysis of cardiovascular regulation

    PubMed Central

    Batzel, Jerry; Baselli, Giuseppe; Mukkamala, Ramakrishna; Chon, Ki H

    2009-01-01

    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. PMID:19324714

  20. Multifractality, sample entropy, and wavelet analyses for age-related changes in the peripheral cardiovascular system: preliminary results.

    PubMed

    Humeau, Anne; Chapeau-Blondeau, François; Rousseau, David; Rousseau, Pascal; Trzepizur, Wojciech; Abraham, Pierre

    2008-02-01

    Using signal processing measures we evaluate the effect of aging on the peripheral cardiovascular system. Laser Doppler flowmetry (LDF) signals, reflecting the microvascular perfusion, are recorded on the forearm of 27 healthy subjects between 20-30, 40-50, or 60-70 years old. Wavelet-based representations, Hölder exponents, and sample entropy values are computed for each time series. The results indicate a possible modification of the peripheral cardiovascular system with aging. Thus, the endothelial-related metabolic activity decreases, but not significantly, with aging. Furthermore, LDF signals are more monofractal for elderly subjects than for young people for whom LDF signals are weakly multifractal: the average range of Holder exponents computed with a parametric generalized quadratic variation based estimation method is 0.13 for subjects between 20 and 30 years old and 0.06 for subjects between 60 and 70 years old. Moreover, the average mean sample entropy value of LDF signals slightly decreases with age: it is 1.34 for subjects between 20 and 30 years old and 1.19 for subjects between 60 and 70 years old. Our results could assist in gaining knowledge on the relationship between microvascular system status and age and could also lead to a more accurate age-related nonlinear modeling.

  1. 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.

  2. 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

  3. Cardiovascular Effects of Shock and Trauma in Experimental Models. A Review.

    PubMed

    Rocha-e-Silva, Mauricio

    2016-02-01

    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.

  4. Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

    NASA Astrophysics Data System (ADS)

    Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

    2017-02-01

    Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

  5. [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.

  6. 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

    2015-08-18

    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.

  7. 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

  8. Effects of acute and chronic systemic methamphetamine on respiratory, cardiovascular and metabolic function, and cardiorespiratory reflexes

    PubMed Central

    Hassan, Sarah F.; Wearne, Travis A.; Cornish, Jennifer L.

    2016-01-01

    Key points Methamphetamine (METH) abuse is escalating worldwide, with the most common cause of death resulting from cardiovascular failure and hyperthermia; however, the underlying physiological mechanisms are poorly understood.Systemic administration of METH in anaesthetised rats reduced the effectiveness of some protective cardiorespiratory reflexes, increased central respiratory activity independently of metabolic function, and increased heart rate, metabolism and respiration in a pattern indicating that non‐shivering thermogenesis contributes to the well‐described hyperthermia.In animals that showed METH‐induced behavioural sensitisation following chronic METH treatment, no changes were evident in baseline cardiovascular, respiratory and metabolic measures and the METH‐evoked effects in these parameters were similar to those seen in saline‐treated or drug naïve animals.Physiological effects evoked by METH were retained but were neither facilitated nor depressed following chronic treatment with METH.These data highlight and identify potential mechanisms for targeted intervention in patients vulnerable to METH overdose. Abstract Methamphetamine (METH) is known to promote cardiovascular failure or life‐threatening hyperthermia; however, there is still limited understanding of the mechanisms responsible for evoking the physiological changes. In this study, we systematically determined the effects on both autonomic and respiratory outflows, as well as reflex function, following acute and repeated administration of METH, which enhances behavioural responses. Arterial pressure, heart rate, phrenic nerve discharge amplitude and frequency, lumbar and splanchnic sympathetic nerve discharge, interscapular brown adipose tissue and core temperatures, and expired CO2 were measured in urethane‐anaesthetised male Sprague‐Dawley rats. Novel findings include potent increases in central inspiratory drive and frequency that are not dependent on METH

  9. Systemic glucocorticoid therapy: a review of its metabolic and cardiovascular adverse events.

    PubMed

    Fardet, Laurence; Fève, Bruno

    2014-10-01

    The prevalence of use of long-term systemic glucocorticoid therapy in the general adult population is 1 %. This figure increases to up to 3 % in elderly women. Metabolic (i.e. diabetes mellitus, dyslipidemia, weight gain, lipodystrophy) and cardiovascular (i.e. hypertension, cardiovascular events) adverse events are commonly observed in these patients and can be life threatening. Paradoxically, there is very few data on some of these adverse events and many of the available studies remain inconclusive. Incidence of and risk factors for dyslipidemia, weight gain and lipodystrophy are poorly defined. The optimal treatment plan for patients diagnosed with glucocorticoid-induced diabetes or hypertension is undetermined. Finally, there is no medical consensus on the best strategies for the prevention and detection of these complications. However, certain of these questions can be answered by looking at available data on patients with endogenous hypercortisolism (i.e. Cushing's syndrome). This article reviews the pathophysiology, incidence, risk factors, screening, and treatment of glucocorticoid-induced weight gain, lipodystrophy, diabetes, dyslipidemia, hypertension, and cardiovascular events. It also focuses on the possible prevention of these adverse events by targeting the glucocorticoid receptor using selective glucocorticoid receptor modulators.

  10. Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease.

    PubMed

    Robinson, Emma; Grieve, David J

    2009-06-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that belong to the nuclear receptor superfamily. Three isoforms of PPAR have been identified, alpha, delta and gamma, which play distinct roles in the regulation of key metabolic processes, such as glucose and lipid redistribution. PPARalpha is expressed predominantly in the liver, kidney and heart, and is primarily involved in fatty acid oxidation. PPARgamma is mainly associated with adipose tissue, where it controls adipocyte differentiation and insulin sensitivity. PPARdelta is abundantly and ubiquitously expressed, but as yet its function has not been clearly defined. Activators of PPARalpha (fibrates) and gamma (thiazolidinediones) have been used clinically for a number of years in the treatment of hyperlipidaemia and to improve insulin sensitivity in diabetes. More recently, PPAR activation has been found to confer additional benefits on endothelial function, inflammation and thrombosis, suggesting that PPAR agonists may be good candidates for the treatment of cardiovascular disease. In this regard, it has been demonstrated that PPAR activators are capable of reducing blood pressure and attenuating the development of atherosclerosis and cardiac hypertrophy. This review will provide a detailed discussion of the current understanding of basic PPAR physiology, with particular reference to the cardiovascular system. It will also examine the evidence supporting the involvement of the different PPAR isoforms in cardiovascular disease and discuss the current and potential future clinical applications of PPAR activators.

  11. Insulin-like growth factor-2 regulates early neural and cardiovascular system development in zebrafish embryos.

    PubMed

    Hartnett, Lori; Glynn, Catherine; Nolan, Catherine M; Grealy, Maura; Byrnes, Lucy

    2010-01-01

    The insulin-like growth factor (IGF) family is essential for normal embryonic growth and development and it is highly conserved through vertebrate evolution. However, the roles that the individual members of the IGF family play in embryonic development have not been fully elucidated. This study focuses on the role of IGF-2 in zebrafish embryonic development. Two igf-2 genes, igf-2a and igf-2b, are present in the zebrafish genome. Antisense morpholinos were designed to knock down both igf-2 genes. The neural and cardiovascular defects in IGF-2 morphant embryos were then examined further using wholemount in situ hybridisation, TUNEL analysis and O-dianisidine staining. Knockdown of igf-2a or igf-2b resulted in ventralised embryos with reduced growth, reduced eyes, disrupted brain structures and a disrupted cardiovascular system, with igf-2b playing a more significant role in development. During gastrulation, igf-2a and igf-2b are required for development of anterior neural structures and for regulation of genes critical to dorsal-ventral patterning. As development proceeds, igf-2a and igf-2b play anti-apoptotic roles. Gene expression analysis demonstrates that igf-2a and igf-2b play overlapping roles in angiogenesis and cardiac outflow tract development. Igf-2b is specifically required for cardiac valve development and cardiac looping. Injection of a dominant negative IGF-1 receptor led to similar defects in angiogenesis and cardiac valve development, indicating IGF-2 signals through this receptor to regulate cardiovascular development. This is the first study describing two functional igf-2 genes in zebrafish. This work demonstrates that igf-2a and igf-2b are critical to neural and cardiovascular development in zebrafish embryos. The finding that igf-2a and igf-2b do not act exclusively in a redundant manner may explain why both genes have been stably maintained in the genome.

  12. 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.

  13. 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

  14. The effects of a 50-Hz magnetic field on the cardiovascular system in rats

    PubMed Central

    Zhou, Ling; Wan, Baoquan; Liu, Xingfa; Zhang, Yemao; Lai, Jinsheng; Ruan, Guoran; He, Mengying; Chen, Chen; Wang, Dao Wen

    2016-01-01

    A 50-Hz magnetic field (MF) is a potential health-risk factor. Its effects on the cardiovascular system have not been fully investigated. This study was conducted to explore the effects of long-term exposure to a 50-Hz MF on the cardiovascular system. In the study, an exposure system was constructed, and the distribution of the 50-Hz MF was determined. Sixty-four Sprague-Dawley (SD) rats were exposed to a 50-Hz MF at 100 μT for 24 weeks, 20 h per day, while another 64 rats were sham exposed. During the exposure, blood pressure was measured every 4 weeks. After 24 weeks, echocardiography, cardiac catheterization and electrocardiography were performed. Moreover, heart and body weight were recorded, and haematoxylin–eosin staining and real-time PCR were conducted. The results showed that compared with the sham group, exposure to a 50-Hz MF did not exert any effects on blood pressure, pulse rate, heart rate or cardiac rhythm. Furthermore, echocardiography and cardiac catheterization showed that there were no significant differences in the cardiac morphology or haemodynamics. In addition, histopathological examination showed that exposure to a 50-Hz MF had no effects on the structure of the heart. Finally, expression of the cardiac hypertrophy–related genes did not show any significant differences between the 50-Hz MF exposure group and the sham group. Taken together, in SD rats, exposure to a 50-Hz/100 μT MF for 24 weeks did not show any obvious effects on the cardiovascular system. PMID:27694282

  15. 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.

  16. Can oral vitamin D prevent the cardiovascular diseases among migrants in Australia? Provider perspective using Markov modelling.

    PubMed

    Ruwanpathirana, Thilanga; Owen, Alice; Renzaho, Andre M N; Zomer, Ella; Gambhir, Manoj; Reid, Christopher M

    2015-06-01

    The study was designed to model the effectiveness and cost effectiveness of oral Vitamin D supplementation as a primary prevention strategy for cardiovascular disease among a migrant population in Australia. It was carried out in the Community Health Service, Kensington, Melbourne. Best-case scenario analysis using a Markov model was employed to look at the health care providers' perspective. Adult migrants who were vitamin D deficient and free from cardiovascular disease visiting the medical centre at least once during the period from 1 January 2010 to 31 December 2012 were included in the study. The blood pressure-lowering effect of vitamin D was taken from a published meta-analysis and applied in the Framingham 10 year cardiovascular risk algorithm (with and without oral vitamin D supplements) to generate the probabilities of cardiovascular events. A Markov decision model was used to estimate the provider costs associated with the events and treatments. Uncertainties were derived by Monte Carlo simulation. Vitamin D oral supplementation (1000 IU/day) for 10 years could potentially prevent 31 (interquartile range (IQR) 26 to 37) non-fatal and 11 (IQR 10 to 15) fatal cardiovascular events in a migrant population of 10,000 assuming 100% compliance. The provider perspective incremental cost effectiveness per year of life saved was AU$3,992 (IQR 583 to 8558). This study suggests subsidised supplementation of oral vitamin D may be a cost effective intervention to reduce non-fatal and fatal cardiovascular outcomes in high-risk migrant populations.

  17. 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

  18. Absence of Cardiovascular Manifestations in a Haploinsufficient Tgfbr1 Mouse Model

    PubMed Central

    Renard, Marjolijn; Trachet, Bram; Casteleyn, Christophe; Campens, Laurence; Cornillie, Pieter; Callewaert, Bert; Deleye, Steven; Vandeghinste, Bert; van Heijningen, Paula M.; Dietz, Harry; De Vos, Filip; Essers, Jeroen; Staelens, Steven; Segers, Patrick; Loeys, Bart; Coucke, Paul; De Paepe, Anne; De Backer, Julie

    2014-01-01

    Loeys-Dietz syndrome (LDS) is an autosomal dominant arterial aneurysm disease belonging to the spectrum of transforming growth factor β (TGFβ)-associated vasculopathies. In its most typical form it is characterized by the presence of hypertelorism, bifid uvula/cleft palate and aortic aneurysm and/or arterial tortuosity. LDS is caused by heterozygous loss of function mutations in the genes encoding TGFβ receptor 1 and 2 (TGFBR1 and −2), which lead to a paradoxical increase in TGFβ signaling. To address this apparent paradox and to gain more insight into the pathophysiology of aneurysmal disease, we characterized a new Tgfbr1 mouse model carrying a p.Y378* nonsense mutation. Study of the natural history in this model showed that homozygous mutant mice die during embryonic development due to defective vascularization. Heterozygous mutant mice aged 6 and 12 months were morphologically and (immuno)histochemically indistinguishable from wild-type mice. We show that the mutant allele is degraded by nonsense mediated mRNA decay, expected to result in haploinsufficiency of the mutant allele. Since this haploinsufficiency model does not result in cardiovascular malformations, it does not allow further study of the process of aneurysm formation. In addition to providing a comprehensive method for cardiovascular phenotyping in mice, the results of this study confirm that haploinsuffciency is not the underlying genetic mechanism in human LDS. PMID:24587008

  19. The utility of superparamagnetic contrast agents in MRI: theoretical consideration and applications in the cardiovascular system.

    PubMed

    Bjørnerud, Atle; Johansson, Lars

    2004-11-01

    This review will discuss the in vivo physical chemical relaxation properties of superparamagnetic iron oxide particles. Various parameters such as size, magnetization, compartmentalization and water exchange effects and how these alter the behavior of the iron oxide particles in an in vitro vs an in vivo situation with special reference to the cardiovascular system will be exemplified. Furthermore, applications using iron oxide particles for vascular, perfusion and viability imaging as well as assessment of the inflammatory status of a given tissue will be discussed.

  20. The circadian organization of the cardiovascular system in health and disease.

    PubMed

    Portaluppi, Francesco

    2014-05-01

    In normal conditions, the temporal organization of blood pressure (BP) is mainly controlled by neuroendocrine mechanisms. Above all, the monoaminergic systems (including variations in activity of the autonomous nervous system, and in secretion of biogenic amines) appear to integrate the major driving factors of temporal variability, but evidence is available also for a role of the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, opioid, renin-angiotensin-aldosterone, and endothelial systems, as well as other vasoactive peptides. Many hormones with established actions on the cardiovascular system (arginine vasopressin, vasoactive intestinal peptide, melatonin, somatotropin, insulin, steroids, serotonin, CRF, ACTH, TRH, endogenous opioids, and prostaglandin E2) are also involved in sleep induction or arousal, which in turn affects BP regulation. Hence, physical, mental, and pathological stimuli which may drive activation or inhibition of these neuroendocrine effectors of biological rhythmicity, may also interfere with the temporal BP structure. On the other hand, the immediate adaptation of the exogenous components of BP rhythms to the demands of the environment are modulated by the circadian-time-dependent responsiveness of the biological oscillators and their neuroendocrine effectors. These notions may contribute to a better understanding of the pathophysiology and therapeutics of hypertension, myocardial ischemia and infarction, cardiac arrhythmias and all kind of acute cardiovascular accidents. For instance, the normal temporal balance between external stimuli and neurohumoral influences with endogenous rhythmicity is preserved in uncomplicated, essential hypertension, whereas it is frequently lost in complicated and secondary forms of hypertension where gross alterations are found in the circadian profile of BP. When all the gates of the critical physiologic functions are aligned at the same time, the susceptibility, and thus risk, of adverse

  1. Long-term consequences of drugs on the paediatric cardiovascular system.

    PubMed

    Hausner, Elizabeth; Fiszman, Monica L; Hanig, Joseph; Harlow, Patricia; Zornberg, Gwen; Sobel, Solomon

    2008-01-01

    Many pharmacological and toxicological actions of drugs in children cannot be fully predicted from adult clinical experience or from standard non-clinical toxicology studies. Numerous drugs have direct or indirect pharmacological effects on the heart and are prescribed for children of all ages. Toxicity or secondary effects may be immediate or delayed for years after drug exposure has ceased. Originally, the aim of this review was to compile information on the effect of specific drugs on the post-natal development of the cardiovascular system and to examine long-term follow-up of the use of cardio-active drugs in children. The limited database of published information caused the original question to evolve into an examination of the medical literature for three areas of information: (i) whether vulnerable developmental windows have been identified that reflect the substantial functional development that the cardiovascular system undergoes after birth; (ii) what is known about pharmacological perturbation of development; and (iii) what the likelihood is of drug exposure during childhood. We examined different scenarios for exposure including random, isolated exposure, conditions historically associated with adults, primary or secondary cardiac disease, psychiatric and neurological conditions, asthma, cancer and HIV. Except for random, isolated drug exposures, each category of possible exposure contained numerous drugs known to have either primary or secondary effects on the cardiovascular system or to influence factors associated with atherosclerosis. It is likely that a significant number of children will be prescribed drugs having either direct or indirect effects upon the immature cardiovascular system. A confounding factor is the simultaneous use of over-the-counter medications and herbal or nutraceutical preparations that a patient, parent or guardian does not mention to a prescribing physician. Metabolism is also important in assessing drug effects in children

  2. [Functional state of cardiovascular system by progressive absences--epilepsy and its treatment].

    PubMed

    Mamalyga, M L

    2014-05-01

    Age-dependent increase of seizure activity at absence epilepsy exacerbates hemodynamic and autonomic regulation of heart rate. Cardiac dysfunction is accompanied by an increasing duration of intervals repolarization left ventricular QTc, which causes the risk of life-threatening arrhythmias, increases the threat of sudden cardiac death. Anticonvulsant drug therapy provides an opportunity to improve the functional state of the cardiovascular system, if not exceeded a certain level of seizure activity of the brain. This possibility remains as long as the progressive seizure activity isn't reaches a certain level. Later anticonvulsant drug therapy reduces seizure activity of the brain, but does not improve the functional state of heart.

  3. Phosphodiesterases and subcellular compartmentalized cAMP signaling in the cardiovascular system.

    PubMed

    Stangherlin, Alessandra; Zaccolo, Manuela

    2012-01-01

    Phosphodiesterases are key enzymes in the cAMP signaling cascade. They convert cAMP in its inactive form 5'-AMP and critically regulate the intensity and the duration of cAMP-mediated signals. Multiple isoforms exist that possess different intracellular distributions, different affinities for cAMP, and different catalytic and regulatory properties. This complex repertoire of enzymes provides a multiplicity of ways to modulate cAMP levels, to integrate more signaling pathways, and to respond to the specific needs of the cell within distinct subcellular domains. In this review we summarize key findings on phosphodiesterase compartmentalization in the cardiovascular system.

  4. [Diabetic neuropathies. IV. Autonomous neuropathy. Peripheral sympathetic innervation and the cardiovascular system].

    PubMed

    Gentile, S; Marmo, R; Costume, A; Persico, M; Bronzino, P; Contaldi, P; Stroffolini, T

    1984-04-28

    The clinical conditions due to damage to the peripheral sympathetic nervous system during diabetic neuropathy mainly involve alterations to subcutaneous vasomotility , temperature body regulation and exudation, which may take form of hyper or hypoactivity. Gustatory exudation and local anhydrosis are described in detail as well as the connection with aggravating factors like long duration, poor balance and early onset of diabetes mellitus . Change in the relevant cardiovascular reflexes, commonly used in diagnosing diabetic neuropathy, are also analysed with a discussion of their physiopathological background and clinical significance. Finally the painless infarct, sudden death and abnormal response to hypoglycaemia, that are the common features of diabetic neuropathy, are also described.

  5. Integrated Metabolomics and Genomics: Systems Approaches to Biomarkers and Mechanisms of Cardiovascular Disease

    PubMed Central

    Shah, Svati H.; Newgard, Christopher B.

    2015-01-01

    The genetic architecture underlying the heritability of cardiovascular disease (CVD) is incompletely understood. Metabolomics is an emerging technology platform that has shown early success in identifying biomarkers and mechanisms of common, chronic diseases. Integration of metabolomics, genetics and other ‘omics’ platforms in a systems biology approach holds potential for elucidating novel genetic markers and mechanisms for CVD. We review important studies that have utilized metabolomic profiling in cardiometabolic diseases, approaches for integrating metabolomics with genetics and other molecular profiling platforms, and key studies showing the potential for such studies in deciphering CVD genetics, biomarkers and mechanisms. PMID:25901039

  6. Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems.

    PubMed

    Trifirò, Gianluca; Spina, Edoardo

    2011-09-01

    Aging is characterized by progressive impairment of functional capacities of all system organs, reduction in homeostatic mechanisms, and altered response to receptor stimulation. These age-related physiologic changes influence both pharmacokinetics and pharmacodynamics of drugs in elderly patients. Pharmacokinetic and pharmacodynamics changes as well as polypharmacy and comorbidities may alter significantly the effect of pharmacological treatment with advancing age. With the same drug concentration at the site of action, significant differences in the response to several drugs have been observed in older patients as compared to younger patients. Elderly patients are particularly suceptibles to the effects of frequently prescribed drugs acting on central nervous system, such as benzodiazepines, antidepressants, antipsychotics and lithium, with high potential for adverse drug reactions. Moreover, in older patients increased sensitivity to warfarin resulting in increased risk of bleeding has been previously documented. On the other hand, reduced effectiveness of conventional doses of cardiovascular drugs, such as diuretics and β-blockers, has been observed. Due to pharmacodynamic changes, therefore, dose adjustment of the above mentioned cardiovascular and psychotropic drugs is recommended in elderly. Clinicians should be aware of the age-related physiologic changes affecting several organ systems and their implications on the effect of drugs that are commonly prescribed to elderly patients.

  7. 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.

  8. Effects of perinatal, late foetal, and early embryonic insults on the cardiovascular phenotype in experimental animal models and humans.

    PubMed

    Meister, Theo Arthur; Rexhaj, Emrush; Rimoldi, Stefano Flavio; Scherrer, Urs; Sartori, Claudio

    2016-11-01

    Cardiovascular diseases are the main cause of mortality and morbidity in Western countries, but the underlying mechanisms are still poorly understood. Genetic polymorphisms, once thought to represent a major determinant of cardiovascular risk, individually and collectively, only explain a tiny fraction of phenotypic variation and disease risk in humans. It is now clear that non-genetic factors, i.e., factors that modify gene activity without changing the DNA sequence and that are sensitive to the environment can cause important alterations of the cardiovascular phenotype in experimental animal models and humans. Here, we will review recent studies demonstrating that distinct pathological events during the perinatal (transient perinatal hypoxemia), late foetal (preeclampsia), and early embryonic (assisted reproductive technologies) periods induce profound alterations of the cardiovascular phenotype in humans and experimental animals. Moreover, we will provide evidence that epigenetic modifications are contributing importantly to this problem and are conferring the potential for its transmission to subsequent generations.

  9. 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

  10. 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.

  11. 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

  12. Model-based parameter estimation using cardiovascular response to orthostatic stress

    NASA Technical Reports Server (NTRS)

    Heldt, T.; Shim, E. B.; Kamm, R. D.; Mark, R. G.

    2001-01-01

    This paper presents a cardiovascular model that is capable of simulating the short-term (< or approximately equal to 3 min) transient hemodynamic response to gravitational stress and a gradient-based optimization method that allows for the automated estimation of model parameters from simulated or experimental data. We perform a sensitivity analysis of the transient heart rate response to determine which parameters of the model impact the heart rate dynamics significantly. We subsequently include only those parameters in the estimation routine that impact the transient heart rate dynamics substantially. We apply the estimation algorithm to both simulated and real data and showed that restriction to the 20 most important parameters does not impair our ability to match the data.

  13. Cardiovascular dysfunction associated with neurodegeneration in an experimental model of Parkinson's disease.

    PubMed

    Falquetto, Barbara; Tuppy, Marina; Potje, Simone R; Moreira, Thiago S; Antoniali, Cristina; Takakura, Ana C

    2017-02-15

    Patients with Parkinson's disease (PD) exhibit both motor and non-motor symptoms. Among the non-motor symptoms, cardiovascular autonomic dysfunction is frequently observed. Here, we evaluated baroreflex function, vascular reactivity and neuroanatomical changes in brainstem regions involved in the neural control of circulation in the 6-hydroxydopamine (6-OHDA) model of PD. Male Wistar rats received a bilateral injection of 6-OHDA or vehicle into the striatum. After 61days, baroreflex function and vascular reactivity were assessed. The 6-OHDA and vehicle groups showed similar increases in mean arterial pressure (MAP) in response to phenylephrine (PE). However, the bradycardia observed in the vehicle group was blunted in the 6-OHDA-treated rats. Injection of sodium nitroprusside (SNP) decreased hypotension, tachycardia and vascular relaxation in 6-OHDA-treated rats. Bilateral intrastriatal 6-OHDA led to massive degeneration of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra and to reductions in the numbers of A1/C1 and A5 catecholaminergic neurons while sparing A2 neurons within the nucleus of the solitary tract (NTS). 6-OHDA-treated rats also showed decreases in Phox2b-expressing neurons in the NTS and in choline acetyltransferase (ChAT) immunoreactivity in the nucleus ambiguus. Altogether, our data suggest that this model of PD includes neuroanatomical and functional changes that lead to cardiovascular impairment.

  14. 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.

  15. Cardiovascular risk

    PubMed Central

    Payne, Rupert A

    2012-01-01

    Cardiovascular disease is a major, growing, worldwide problem. It is important that individuals at risk of developing cardiovascular disease can be effectively identified and appropriately stratified according to risk. This review examines what we understand by the term risk, traditional and novel risk factors, clinical scoring systems, and the use of risk for informing prescribing decisions. Many different cardiovascular risk factors have been identified. Established, traditional factors such as ageing are powerful predictors of adverse outcome, and in the case of hypertension and dyslipidaemia are the major targets for therapeutic intervention. Numerous novel biomarkers have also been described, such as inflammatory and genetic markers. These have yet to be shown to be of value in improving risk prediction, but may represent potential therapeutic targets and facilitate more targeted use of existing therapies. Risk factors have been incorporated into several cardiovascular disease prediction algorithms, such as the Framingham equation, SCORE and QRISK. These have relatively poor predictive power, and uncertainties remain with regards to aspects such as choice of equation, different risk thresholds and the roles of relative risk, lifetime risk and reversible factors in identifying and treating at-risk individuals. Nonetheless, such scores provide objective and transparent means of quantifying risk and their integration into therapeutic guidelines enables equitable and cost-effective distribution of health service resources and improves the consistency and quality of clinical decision making. PMID:22348281

  16. 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; Schlüssel, Michael Maia; Gerry, Stephen; Black, James A; Heus, Pauline; van der Schouw, Yvonne T; Peelen, Linda M; Moons, Karel G M

    2016-01-01

    Objective To provide an overview of prediction models for risk of cardiovascular disease (CVD) in the general population. Design Systematic review. Data sources Medline and Embase until June 2013. Eligibility criteria for study selection Studies describing the development or external validation of a multivariable model for predicting CVD risk in the general population. Results 9965 references were screened, of which 212 articles were included in the review, describing the development of 363 prediction models and 473 external validations. Most models were developed in Europe (n=167, 46%), predicted risk of fatal or non-fatal coronary heart disease (n=118, 33%) over a 10 year period (n=209, 58%). The most common predictors were smoking (n=325, 90%) and age (n=321, 88%), and most models were sex specific (n=250, 69%). Substantial heterogeneity in predictor and outcome definitions was observed between models, and important clinical and methodological information were often missing. The prediction horizon was not specified for 49 models (13%), and for 92 (25%) crucial information was missing to enable the model to be used for individual risk prediction. Only 132 developed models (36%) were externally validated and only 70 (19%) by independent investigators. Model performance was heterogeneous and measures such as discrimination and calibration were reported for only 65% and 58% of the external validations, respectively. Conclusions There is an excess of models predicting incident CVD in the general population. The usefulness of most of the models remains unclear owing to methodological shortcomings, incomplete presentation, and lack of external validation and model impact studies. Rather than developing yet another similar CVD risk prediction model, in this era of large datasets, future research should focus on externally validating and comparing head-to-head promising CVD risk models that already exist, on tailoring or even combining these models to local

  17. Energy harvesting from the cardiovascular system, or how to get a little help from yourself.

    PubMed

    Pfenniger, Alois; Jonsson, Magnus; Zurbuchen, Adrian; Koch, Volker M; Vogel, Rolf

    2013-11-01

    Human energy harvesting is envisioned as a remedy to the weight, the size, and the poor energy density of primary batteries in medical implants. The first implant to have necessarily raised the idea of a biological power supply was the pacemaker in the early 1960s. So far, review articles on human energy harvesting have been rather unspecific and no tribute has been given to the early role of the pacemaker and the cardiovascular system in triggering research in the field. The purpose of the present article is to provide an up-to-date review of research efforts targeting the cardiovascular system as an alternative energy source for active medical implants. To this end, a chronological survey of the last 14 most influential publications is proposed. They include experimental and/or theoretical studies based on electromagnetic, piezoelectric, or electrostatic transducers harnessing various forms of energy, such as heart motion, pressure gradients, and blood flow. Technical feasibility does not imply clinical applicability: although most of the reported devices were shown to harvest an interesting amount of energy from a physiological environment, none of them were tested in vivo for a longer period of time.

  18. Functional plasticity of the developing cardiovascular system: examples from different vertebrates.

    PubMed

    Pelster, Bernd; Gittenberger-de Groot, A C; Poelmann, R E; Rombough, Peter; Schwerte, Thorsten; Thompson, Michael B

    2010-01-01

    Technical advances that have made it possible to perform physiological measurements on very small organisms, including those in embryonic and larval stages, have resulted in the formation of the discipline of developmental physiology. The transparency and size of developing organisms in some areas permit insights into physiological processes that cannot be obtained with opaque, adult organisms. On the other hand, it is widely accepted that without eggs, there are no chickens, so physiological adaptations during early life are just as important to species survival as those manifested by adults. Physiological adaptations of early developmental stages, however, are not always the same as patterns known in adults; they often follow their own rules. The adaptability of early developmental stages demonstrates that development is not stereotyped and a phenotype is not just the result of genetic information and the expression of a certain series of genes. Environmental factors influence phenotype production, and this in turn results in flexibility and plasticity in physiological processes. This article comprises exemplary studies presented at the Fourth International Conference in Africa for Comparative Physiology and Biochemistry (Maasai Mara, Kenya, 2008). It includes a brief introduction into technical advances, discusses the developing cardiovascular system of various vertebrates, and demonstrates the flexibility and plasticity of early developmental stages. Fluid forces, oxygen availability, ionic homeostasis, and the chemical environment (including, e.g., hormone concentrations or cholesterol levels) all contribute to the shaping and performance of the cardiovascular system.

  19. Cardiovascular and systemic effects of gastric dilatation and volvulus in dogs.

    PubMed

    Sharp, Claire R; Rozanski, Elizabeth A

    2014-09-01

    Gastric dilatation and volvulus (GDV) is a common emergency condition in large and giant breed dogs that is associated with high morbidity and mortality. Dogs with GDV classically fulfill the criteria for the systemic inflammatory response syndrome (SIRS) and can go on to develop multiple organ dysfunction syndrome (MODS). Previously reported organ dysfunctions in dogs with GDV include cardiovascular, respiratory, gastrointestinal, coagulation and renal dysfunction. Cardiovascular manifestations of GDV include shock, cardiac arrhythmias and myocardial dysfunction. Respiratory dysfunction is also multifactorial, with contributory factors including decreased respiratory excursion due to gastric dilatation, decreased pulmonary perfusion and aspiration pneumonia. Gastrointestinal dysfunction includes gastric necrosis and post-operative gastrointestinal upset such as regurgitation, vomiting, and ileus. Coagulation dysfunction is another common feature of MODS in dogs with GDV. Disseminated intravascular coagulation can occur, putting them at risk of complications associated with thrombosis in the early hypercoagulable state and hemorrhage in the subsequent hypocoagulable state. Acute kidney injury, acid-base and electrolyte disturbances are also reported in dogs with GDV. Understanding the potential for systemic effects of GDV allows the clinician to monitor patients astutely and detect such complications early, facilitating early intervention to maximize the chance of successful management.

  20. Role of the endocannabinoid system in abdominal obesity and the implications for cardiovascular risk.

    PubMed

    Rosenson, Robert S

    2009-01-01

    Several cardiometabolic factors present in obese and insulin-resistant individuals represent a continuum of increasing risk for the development of type 2 diabetes and cardiovascular disease. The importance of abdominal obesity as an independent risk factor is underscored by its association with adverse endocrine function. Recent evidence from animal and human studies has shown a role for the endocannabinoid system in maintaining energy balance and glucose and lipoprotein metabolism, with overactivity linked to aberrant glycemic and lipoprotein control, and a link to adiposity. Modulation of this system through endocannabinoid-receptor blockade has resulted in an improvement in a number of important risk factors in clinical trials, including visceral and subcutaneous abdominal adipose tissue, glucose tolerance, dyslipidemia and measures of inflammation. These findings may have significant implications for the management of patients at risk of developing cardiovascular and metabolic disease; however, the occurrence of psychiatric adverse events with rimonabant may preclude further development of centrally active endocannabinoid receptor antagonists for the treatment of cardiometabolic disorders. Future research is needed to explore the role of selective peripheral CB(1) receptor antagonists in the treatment of patients at high cardiometabolic risk.

  1. Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system

    NASA Astrophysics Data System (ADS)

    Luo, Wei; Marks, Daniel L.; Ralston, Tyler S.; Boppart, Stephen A.

    2006-03-01

    Optical coherence tomography (OCT) is an emerging high-resolution real-time biomedical imaging technology that has potential as a novel investigational tool in developmental biology and functional genomics. In this study, murine embryos and embryonic hearts are visualized with an OCT system capable of 2-µm axial and 15-µm lateral resolution and with real-time acquisition rates. We present, to our knowledge, the first sets of high-resolution 2- and 3-D OCT images that reveal the internal structures of the mammalian (murine) embryo (E10.5) and embryonic (E14.5 and E17.5) cardiovascular system. Strong correlations are observed between OCT images and corresponding hematoxylin- and eosin-stained histological sections. Real-time in vivo embryonic (E10.5) heart activity is captured by spectral-domain optical coherence tomography, processed, and displayed at a continuous rate of five frames per second. With the ability to obtain not only high-resolution anatomical data but also functional information during cardiovascular development, the OCT technology has the potential to visualize and quantify changes in murine development and in congenital and induced heart disease, as well as enable a wide range of basic in vitro and in vivo research studies in functional genomics.

  2. Histamine H3 receptors--general characterization and their function in the cardiovascular system.

    PubMed

    Malinowska, B; Godlewski, G; Schlicker, E

    1998-06-01

    The histamine H3 receptor was initially identified as a presynaptic autoreceptor controlling histamine release and synthesis in the brain. It belongs to the superfamily of G protein-coupled receptors. The existence of the H3 receptor which has not yet been cloned was definitely established by the design of highly potent and selective agonists (R-(-)-alpha-methylhistamine, imetit) and antagonists (thioperamide, clobenpropit). These receptors also occur as heteroreceptors both in the central nervous system and on peripheral neurons of the gastrointestinal and bronchial tract, where they regulate the release of a variety of neurotransmitters. In the cardiovascular system, histamine H3 receptors are mainly located presynaptically on the postganglionic sympathetic nerve fibers innervating the blood vessels and the heart. Their activation leads to the inhibition of noradrenaline release and consequently to the reduction of the neurogenic vasopressor and cardiostimulatory responses. The presence of such receptors has been shown both in vitro (human, pig, guinea-pig, rabbit, rat isolated tissues) and in vivo (rat, guinea-pig). The vascular and cardiac presynaptic H3 receptors may be activated by endogenous histamine. The vascular H3 receptors appear to be operative in hypertension and interact with presynaptic alpha 2-adrenoceptors. Postsynaptic vasodilatatory H3 receptors have been detected in several vascular beds as well. H3 receptor ligands affect basal cardiovascular parameters in conscious and anesthetized guinea-pigs but not rats. Presynaptic H3 receptors may play a role in the pathophysiology of headache and cardiac ischemia.

  3. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.

    PubMed

    Mehta, Puja K; Griendling, Kathy K

    2007-01-01

    The renin-angiotensin system is a central component of the physiological and pathological responses of cardiovascular system. Its primary effector hormone, angiotensin II (ANG II), not only mediates immediate physiological effects of vasoconstriction and blood pressure regulation, but is also implicated in inflammation, endothelial dysfunction, atherosclerosis, hypertension, and congestive heart failure. The myriad effects of ANG II depend on time (acute vs. chronic) and on the cells/tissues upon which it acts. In addition to inducing G protein- and non-G protein-related signaling pathways, ANG II, via AT(1) receptors, carries out its functions via MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases [PDGF, EGFR, insulin receptor], and nonreceptor tyrosine kinases [Src, JAK/STAT, focal adhesion kinase (FAK)]. AT(1)R-mediated NAD(P)H oxidase activation leads to generation of reactive oxygen species, widely implicated in vascular inflammation and fibrosis. ANG II also promotes the association of scaffolding proteins, such as paxillin, talin, and p130Cas, leading to focal adhesion and extracellular matrix formation. These signaling cascades lead to contraction, smooth muscle cell growth, hypertrophy, and cell migration, events that contribute to normal vascular function, and to disease progression. This review focuses on the structure and function of AT(1) receptors and the major signaling mechanisms by which angiotensin influences cardiovascular physiology and pathology.

  4. Design and implementation of multimedia display system for electronic cardiovascular conferences with radiological consultation services

    NASA Astrophysics Data System (ADS)

    Zhang, Jianguo; Stahl, Johannes N.; Li, Gaoping; Huang, H. K.; Liu, Jun; Li, Jian; Zhou, Peng

    2000-04-01

    We present a networked multimedia display system based on component technologies for the electronic cardiovascular conferences with radiological consultation services. The system consists of two parts: a data acquisition gateway and a multimedia display workstation. The acquisition gateway is used to collect digital data from difference modalities and authorize them in different sessions for conference presentation. The display workstation is used to display static/dynamic radiographic images, or video sequences, ECG and other text information. The display program is designed with functions of image processing, multimedia data manipulation and visualization. In addition, the workstation also integrates with a real time tele-consultation component for the necessary consultation between cardiologists and remote radiologists equipped with a tele-consultation workstation. Finally, we discuss the system clinical performance and the applications.

  5. Relation of Total and Cardiovascular Death Rates to Climate System, Temperature, Barometric Pressure, and Respiratory Infection.

    PubMed

    Schwartz, Bryan G; Qualls, Clifford; Kloner, Robert A; Laskey, Warren K

    2015-10-15

    A distinct seasonal pattern in total and cardiovascular death rates has been reported. The factors contributing to this pattern have not been fully explored. Seven locations (average total population 71,354,000) were selected where data were available including relatively warm, cold, and moderate temperatures. Over the period 2004 to 2009, there were 2,526,123 all-cause deaths, 838,264 circulatory deaths, 255,273 coronary heart disease deaths, and 135,801 ST-elevation myocardial infarction (STEMI) deaths. We used time series and multivariate regression modeling to explore the association between death rates and climatic factors (temperature, dew point, precipitation, barometric pressure), influenza levels, air pollution levels, hours of daylight, and day of week. Average seasonal patterns for all-cause and cardiovascular deaths were very similar across the 7 locations despite differences in climate. After adjusting for multiple covariates and potential confounders, there was a 0.49% increase in all-cause death rate for every 1°C decrease. In general, all-cause, circulatory, coronary heart disease and STEMI death rates increased linearly with decreasing temperatures. The temperature effect varied by location, including temperature's linear slope, cubic fit, positional shift on the temperature axis, and the presence of circulatory death increases in locally hot temperatures. The variable effect of temperature by location suggests that people acclimatize to local temperature cycles. All-cause and circulatory death rates also demonstrated sizable associations with influenza levels, dew point temperature, and barometric pressure. A greater understanding of how climate, temperature, and barometric pressure influence cardiovascular responses would enhance our understanding of circulatory and STEMI deaths.

  6. Continuous system modeling

    NASA Technical Reports Server (NTRS)

    Cellier, Francois E.

    1991-01-01

    A comprehensive and systematic introduction is presented for the concepts associated with 'modeling', involving the transition from a physical system down to an abstract description of that system in the form of a set of differential and/or difference equations, and basing its treatment of modeling on the mathematics of dynamical systems. Attention is given to the principles of passive electrical circuit modeling, planar mechanical systems modeling, hierarchical modular modeling of continuous systems, and bond-graph modeling. Also discussed are modeling in equilibrium thermodynamics, population dynamics, and system dynamics, inductive reasoning, artificial neural networks, and automated model synthesis.

  7. Risk stratification in cardiovascular disease primary prevention - scoring systems, novel markers, and imaging techniques.

    PubMed

    Zannad, Faiez; De Backer, Guy; Graham, Ian; Lorenz, Matthias; Mancia, Giuseppe; Morrow, David A; Reiner, Zeljko; Koenig, Wolfgang; Dallongeville, Jean; Macfadyen, Robert J; Ruilope, Luis M; Wilhelmsen, Lars

    2012-04-01

    The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low-density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost-effectiveness and benefit-to-risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C-reactive protein, lipoprotein-associated phospholipase A(2) , genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High-resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk-guided therapy in CVD prevention.

  8. Milan PM1 Induces Adverse Effects on Mice Lungs and Cardiovascular System

    PubMed Central

    Farina, Francesca; Sancini, Giulio; Longhin, Eleonora; Mantecca, Paride; Camatini, Marina; Palestini, Paola

    2013-01-01

    Recent studies have suggested a link between inhaled particulate matter (PM) exposure and increased mortality and morbidity associated with cardiorespiratory diseases. Since the response to PM1 has not yet been deeply investigated, its impact on mice lungs and cardiovascular system is here examined. A repeated exposure to Milan PM1 was performed on BALB/c mice. The bronchoalveolar lavage fluid (BALf) and the lung parenchyma were screened for markers of inflammation (cell counts, tumor necrosis factor-α (TNF-α); macrophage inflammatory protein-2 (MIP-2); heme oxygenase-1 (HO-1); nuclear factor kappa-light-chain-enhancer of activated B cells p50 subunit (NFκB-p50); inducible nitric oxide synthetase (iNOS); endothelial-selectin (E-selectin)), cytotoxicity (lactate dehydrogenase (LDH); alkaline phosphatase (ALP); heat shock protein 70 (Hsp70); caspase-8-p18), and a putative pro-carcinogenic marker (cytochrome 1B1 (Cyp1B1)). Heart tissue was tested for HO-1, caspase-8-p18, NFκB-p50, iNOS, E-selectin, and myeloperoxidase (MPO); plasma was screened for markers of platelet activation and clot formation (soluble platelet-selectin (sP-selectin); fibrinogen; plasminogen activator inhibitor 1 (PAI-1)). PM1 triggers inflammation and cytotoxicity in lungs. A similar cytotoxic effect was observed on heart tissues, while plasma analyses suggest blood-endothelium interface activation. These data highlight the importance of lung inflammation in mediating adverse cardiovascular events following increase in ambient PM1 levels, providing evidences of a positive correlation between PM1 exposure and cardiovascular morbidity. PMID:23509745

  9. D Modelling and Rapid Prototyping for Cardiovascular Surgical Planning - Two Case Studies

    NASA Astrophysics Data System (ADS)

    Nocerino, E.; Remondino, F.; Uccheddu, F.; Gallo, M.; Gerosa, G.

    2016-06-01

    In the last years, cardiovascular diagnosis, surgical planning and intervention have taken advantages from 3D modelling and rapid prototyping techniques. The starting data for the whole process is represented by medical imagery, in particular, but not exclusively, computed tomography (CT) or multi-slice CT (MCT) and magnetic resonance imaging (MRI). On the medical imagery, regions of interest, i.e. heart chambers, valves, aorta, coronary vessels, etc., are segmented and converted into 3D models, which can be finally converted in physical replicas through 3D printing procedure. In this work, an overview on modern approaches for automatic and semiautomatic segmentation of medical imagery for 3D surface model generation is provided. The issue of accuracy check of surface models is also addressed, together with the critical aspects of converting digital models into physical replicas through 3D printing techniques. A patient-specific 3D modelling and printing procedure (Figure 1), for surgical planning in case of complex heart diseases was developed. The procedure was applied to two case studies, for which MCT scans of the chest are available. In the article, a detailed description on the implemented patient-specific modelling procedure is provided, along with a general discussion on the potentiality and future developments of personalized 3D modelling and printing for surgical planning and surgeons practice.

  10. Flipped classroom model improves graduate student performance in cardiovascular, respiratory, and renal physiology.

    PubMed

    Tune, Johnathan D; Sturek, Michael; Basile, David P

    2013-12-01

    The purpose of this study was to assess the effectiveness of a traditional lecture-based curriculum versus a modified "flipped classroom" curriculum of cardiovascular, respiratory, and renal physiology delivered to first-year graduate students. Students in both courses were provided the same notes and recorded lectures. Students in the modified flipped classroom were required to watch the prerecorded lectures before class and then attend class, where they received a quiz or homework covering material in each lecture (valued at 25% of the final grade) followed by a question and answer/problem-solving period. In the traditional curriculum, attending lectures was optional and there were no quizzes. Evaluation of effectiveness and student performance was achieved by having students in both courses take the same multiple-choice exams. Within a comparable group of graduate students, participants in the flipped course scored significantly higher (P ≤ 0.05) on the cardiovascular, respiratory, and weighted cumulative sections by an average of >12 percentage points. Exam averages for students in the flipped course also tended to be higher on the renal section by ∼11 percentage points (P = 0.06). Based on our experience and responses obtained in blinded student surveys, we propose that the use of homework and in-class quizzes were critical motivating factors that likely contributed to the increase in student exam performance. Taken together, our findings support that the flipped classroom model is a highly effective means in which to disseminate key physiological concepts to graduate students.

  11. A mini-network balance model for evaluating the progression of cardiovascular complications in Goto-Kakizaki rats

    PubMed Central

    Jiang, Hao; Wang, Yu-hao; Wei, Chun-xiang; Zhang, Xue; Liu, Hao-chen; Liu, Xiao-quan

    2017-01-01

    Cardiovascular complications represent a leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). During such complicated progression, subtle variations in the cardiovascular risk (CVR)-related biomarkers have been used to identify cardiovascular disease at the incipient stage. In this study we attempt to integrally characterize the progression of cardiovascular complications and to assess the beneficial effects of metformin combined with salvianolic acid A (Sal A), in Goto-Kakizaki (GK) rats with spontaneous T2DM. The rats were treated with metformin (200 mg·kg−1·d−1, ig) alone or in combination with Sal A (1 mg·kg−1·d−1, ip) at ages from 8 to 22 weeks. During the treatment, the levels of asymmetric dimethylarginine, L-arginine, superoxide dismutase, malondialdehyde, glucose, high density lipoprotein and low density lipoprotein were assessed. Based on alterations in these biomarkers, a mini-network balance model was established using matrixes and vectors. Radar charts were created to visually depict the disruption of CVR-related modules (endothelial function, oxidative stress, glycation and lipid profiles). The description for the progression of cardiovascular disorder was quantitatively represented by u, the dynamic parameter of the model. The modeling results suggested that untreated GK rats tended to have more severe cardiovascular complications than the treatment groups. Metformin monotherapy retarded disease deterioration, whereas the combination treatment ameliorated the disease progression via restoring the balance. The current study, which focused on the balance of the mini-network and interactions among CVR-related modules, proposes a novel method for evaluating the progression of cardiovascular complications in T2DM as well as a more beneficial intervention strategy. PMID:28042873

  12. The effect of blood volume loss on cardiovascular response to lower body negative pressure using a mathematical model

    NASA Technical Reports Server (NTRS)

    Karam, E. H.; Srinivasan, R. S.; Charles, J. B.; Fortney, S. M.

    1994-01-01

    Different mathematical models of varying complexity have been proposed in recent years to study the cardiovascular (CV) system. However, only a few of them specifically address the response to lower body negative pressure (LBNP), a stress that can be applied in weightlessness to predict changes in orthostatic tolerance. Also, the simulated results produced by these models agree only partially with experimental observations. In contrast, the model proposed by Melchior et al., and modified by Karam et al. is a simple representation of the CV system capable of accurately reproducing observed LBNP responses up to presyncopal levels. There are significant changes in LBNP response due to a loss of blood volume and other alterations that occur in weightlessness and related one-g conditions such as bedrest. A few days of bedrest can cause up to 15% blood volume loss (BVL), with consequent decreases in both stroke volume and cardiac output, and increases in heart rate, mean arterial pressure, and total peripheral resistance. These changes are more pronounced at higher levels of LBNP. This paper presents the results of a simulation study using our CV model to examine the effect of BVL on LBNP response.

  13. Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models

    PubMed Central

    Folkesson, Maggie; Sadowska, Natalia; Vikingsson, Svante; Karlsson, Matts; Carlhäll, Carl-Johan; Länne, Toste; Wågsäter, Dick

    2016-01-01

    ABSTRACT Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding