of nonlinearity and time delay. Steady and periodic solutions are studied with analytical tools, in a detailedA Delay Recruitment Model of the Cardiovascular Control System A.C. Fowler M.J. Mc by Springer. Abstract We develop a nonlinear delay-differential equation for the human cardiovascular control
A cardiovascular model for blood pressure control system is developed in this paper. This model is used to simulate hypertensive patients in order to design control systems for regulation of blood pressure. The stability of the model is also investigated. The model can accurately represent human arterial blood pressure and therefore, the control system designed and simulated based on the
P. C. A. Ang; B. W. Ang; K. Y. Zhu
Presents a model of the cardiovascular system which solves a set of interacting, possibly nonlinear, differential equations. Figures present a schematic diagram of the model and printouts that simulate normal conditions, exercise, hemorrhage, reduced contractility. The nine interacting equations used to describe the system are described in the…
Rothe, Carl F.
In this paper we consider the sensitivity analysis of a model of the cardiovascular system (CVS) simulating the transition to aerobic exercise and where the control for the system is implemented via an optimal control. Classical and generalized sensitivity analysis are discussed and compared and their application to the CVS model is analyzed
Franz Kappel; Jerry Batzel
The cardiovascular system is composed of the heart and the network of arteries, veins, and capillaries that transport blood throughout the ... carries waste products from the tissues to the systems of the body through which they are eliminated. ...
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)
Rothe, Carl F.
The study of the autonomic nervous system (ANS) function has shown to provide useful indicators for risk stratification and early detection on a variety of cardiovascular pathologies. However, data gathered during different tests of the ANS are difficult to analyse, mainly due to the complex mechanisms involved in the autonomic regulation of the cardiovascular system (CVS). Although model-based analysis of ANS data has been already proposed as a way to cope with this complexity, only a few models coupling the main elements involved have been presented in the literature. In this paper, a new model of the CVS, representing the ventricles, the circulatory system and the regulation of the CVS activity by the ANS, is presented. The models of the vascular system and the ventricular activity have been developed using the Bond Graph formalism, as it proposes a unified representation for all energetic domains, facilitating the integration of mechanic and hydraulic phenomena. In order to take into account the electro-mechanical behaviour of both ventricles, an electrophysiologic model of the cardiac action potential, represented by a set of ordinary differential equations, has been integrated. The short-term ANS regulation of heart rate, cardiac contractility and peripheral vasoconstriction is represented by means of continuous transfer functions. These models, represented in different continuous formalisms, are coupled by using a multi-formalism simulation library. Results are presented for two different autonomic tests, namely the Tilt Test and the Valsalva Manoeuvre, by comparing real and simulated signals. PMID:16583271
Le Rolle, Virginie; Hernandez, Alfredo I.; Richard, Pierre-Yves; Buisson, Jean; Carrault, Guy
A mathematical model, based on our previous pulsatile nonlinear multi-element cardiovascular model, was tested and improved to study cardiovascular response under graded exercise levels. Ten healthy subjects were studied using cycle-ergometry exercise test with constant workloads ranging from 25 Watt to 125 Watt. Breath by breath gas exchange, heart rate, cardiac output, stroke volume and blood pressure were measured at
Lu Wang; Steven W. Su; Gregory S. H. Chan; Branko G. Celler
Planning programs for the prevention and treatment of cardiovascular disease (CVD) is a challenge to every community that wants to make the best use of its limited resources. Selecting programs that provide the greatest impact is difficult because of the complex set of causal pathways and delays that link risk factors to CVD. We describe a system dynamics simulation model developed for a county health department that incorporates and tracks the effects of those risk factors over time on both first-time and recurrent events. We also describe how the model was used to evaluate the potential impacts of various intervention strategies for reducing the county's CVD burden and present the results of those policy tests. PMID:20167899
Homer, Jack; Evans, Elizabeth; Zielinski, Ann
\\u000a Nuclear medicine provides important information in the diagnosis and management of several cardiovascular disorders. It provides\\u000a a noninvasive means for evaluation of cardiac function. Radionuclide imaging of myocardial perfusion is a commonly performed\\u000a nuclear medicine examination to determine the adequacy of blood flow to the myocardium, especially in conjunction with exercise\\u000a or pharmacologic stress for the detection and evaluation of
Abdelhamid H. Elgazzar
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. PMID:23539439
Keith Sharp, M; Batzel, Jerry Joseph; Montani, Jean-Pierre
, and are certainly not applicable to the circulatory system as a whole1 from SIAM News, Volume 34, Number 6 Modeling the Cardiovascular System-- A Mathematical Adventure system, and the difficulty of coupling the different mathematical models appropriate for the different
delivered to the lungs on a first circulatory pass. Key words: Compartmental model, circulatory system, drugA Mathematical Model for the First-Pass Dynamics of Antibiotics Acting on the Cardiovascular System compounds to the lungs and heart. We use a compartmental mass balance approach to develop a system
. In this paper, a new model of the CVS, representing the ventricles, the circulatory system and the regulation activity, the circulatory system and evidently the autonomic baroreflex loop includingi) ii) iii) affereA bond graph model of the cardiovascular system Le Rolle Virginie 1 2 , Hernandez Alfredo I. 1
Cardiovascular system identification is a potentially powerful approach for intelligent patient monitoring of cardiovascular function. Rather than merely recording hemodynamic signals, the signals are mathematically analyzed ...
Mukkamala, Ramakrishna, 1971-
A dynamic model is developed through theoretical analysis and numerical solutions to approximate the response of human cardiovascular circulatory system. This system model has one critical time-varying parameter, the resistance of blood vessels. An parameter estimation scheme is derived to estimate this parameter, and the parameter estimate is used to implement an adaptive observer to estimate the aortic pressure for
Yi Wu; Paul Allaire; Gang Tao; Don Olsen
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.
Mitchell, B. A., Jr.; Giese, R. P.
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, and this application is also addressed. As an example of 0D cardiovascular modelling, a small selection of simple models have been represented in the CellML mark-up language and uploaded to the CellML model repository http://models.cellml.org/. They are freely available to the research and education communities. Conclusion Each published cardiovascular model has merit for particular applications. This review categorises 0D and 1D models, highlights their advantages and disadvantages, and thus provides guidance on the selection of models to assist various cardiovascular modelling studies. It also identifies directions for further development, as well as current challenges in the wider use of these models including service to represent boundary conditions for local 3D models and translation to clinical application. PMID:21521508
Confronting a Cardiovascular System Model with Heart Rate and Blood Pressure Data PE McSharry 1 fluctuations in the heart rate, blood pressure and rate of respiration. Its time evolution is governed the heart rate respectively. A nonlinear delayÂdifferential equation model is constructed to describe
McSharry, Patrick E.
Confronting a Cardiovascular System Model with Heart Rate and Blood Pressure Data PE McSharry1 fluctuations in the heart rate, blood pressure and rate of respiration. Its time evolution is governed the heart rate respectively. A nonlinear delay-differential equation model is constructed to describe
McSharry, Patrick E.
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.
Riedl, M.; Suhrbier, A.; Malberg, H.; Penzel, T.; Bretthauer, G.; Kurths, J.; Wessel, N.
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 JAVA version of the simulator which will be distributed amongst the cardiovascular team members. Future work on this project involves modifications of the model to represent a rodent (rat) model, further evaluation of the bedrest astronaut and animal data, and systematic investigation of specific countermeasures.
Kamm, Roger D.
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. PMID:22902782
Blanco, P J; Feijóo, R A
The cardiovascular portion of the InnerBody website is a road map to the human cardiovascular system. It displays all of the main veins and arteries of the human body allowing the user to click on various parts of body and dozens of links to the many different systems appear. Users can hover over the links to discover what each part is named, or click on the link to be brought to a thorough definition and description of the selected system. Users may also Ã¯Â¿Â½zoom inÃ¯Â¿Â½ on certain parts to view more detail. In addition to the interactive Ã¯Â¿Â½map,Ã¯Â¿Â½ InnerBody also has images and descriptions about common issues that arise within the cardiovascular system.
Background Previous research shows that the flow dynamics in the left ventricle (LV) reveal important information about cardiac health.\\u000a This information can be used in early diagnosis of patients with potential heart problems. The current study introduces a\\u000a patient-specific cardiovascular-modelling system (CMS) which simulates the flow dynamics in the LV to facilitate physicians\\u000a in early diagnosis of patients before heart failure.
Wee-Beng Tay; Yu-Heng Tseng; Liang-Yu Lin; Wen-Yih Tseng
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
Kim, Young-Tae; Lee, Jeong Sang; Youn, Chan-Hyun; Choi, Jae-Sung
After introduction on a new multislice computed tomography (MSCT) scanner, it has become possible to produce highspeed CT angiography (CTA) that selected preferred method for imaging in emergent vascular conditions. On the other hand, the imaging of blood vessels is often referred to as magnetic resonance angiography (MRA). Both of angiography offers the good quality of three-dimensional information of the vessels. In this study, patient specific model were reconstructed using multi-slice computed tomography (CT) and magnetic resonance imaging (MRI). The optimal transit time from intravenous injection to enhancement cardiovascular system was determined using a contrast bolus tracking technique with CT examination and phase contrast magnetic resonance angiography (PC-MRA). The purpose of this study was to describe a novel blood flow visualization and analysis in the human cardiovascular system in more detail by constructing actual three-dimensional (3D) flow and simulated model using Computational flow dynamics (CFD) methods. CFD streamlines were displayed using a special illumination technique with blood pressure display, which gives a much better spatial understanding of the field's structure than ordinary constant-colored lines. Real vector display using PC-MRA was also expressed to compare with the CFD simulation. On conclusion, Patient specific approach using actual blood flow with PC-MRA and CFD were effective to estimate blood flow state of the cardiovascular system.
Yamamoto, S.; Bartsch, H.; Maruyama, S.; Yoneyama, S.; Wada, S.; Yamaguchi, T.; Naito, H.
This paper presents a novel technique for evaluating the performance of ventricular assist devices in vitro, innovatively combining dynamic physical testing of assist devices with a mature, numerical human cardiovascular model. Based on this technique, one self-made direct mechanical ventricular assistance (DMVA) prototype is tested. With the true representation of device performance in vivo, the real-time interactions between DMVA and the cardiovascular system are captured and studied. Hemodynamic simulations under DMVA are performed. Experimental results demonstrate that it provides a useful tool for the study of device assist impact on the cardiovascular system as well as the improvement of device structure and effectiveness of control mechanism. PMID:20391921
Honglei, Li; Ming, Yang; Shiyang, Li
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.
Marsden, Alison L.
Studies investigating the integrative central control of the locomotor and cardiovascular system have mostly been conducted\\u000a in rats. These studies have shown that control of cardiovascular responses is located in neurons in close proximity, if not\\u000a overlapping or possibly identical to, neurons responsible for respiratory and locomotor control. In rats cardiorespiratory\\u000a and locomotor centers have been identified in the periaqueductal
David R. Gross
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
Fonoberova, Maria; Mezi?, Igor; Buckman, Jennifer F; Fonoberov, Vladimir A; Mezi?, Adriana; Vaschillo, Evgeny G; Mun, Eun-Young; Vaschillo, Bronya; Bates, Marsha E
This paper considers a model of the human cardiovascular-respiratory control system with one and two transport delays in the state equations describing the respiratory system. The effectiveness of the control of the ventilation rate is influenced by such transport delays because blood gases must be transported a physical distance from the lungs to the sensory sites where these gases are
Jerry J. Batzel; Franz Kappel; Susanne Timischl-Teschl
The cardiovascular system is a closed-loop system in which billions of vessels interact with each other, and it enables the\\u000a control of the systemic arterial pressure and varying organ flow through autoregulatory mechanisms. In this study, we describe\\u000a the development of mathematical models of autoregulatory mechanisms for systemic arterial pressure and coronary flow and discuss\\u000a the connection of these models
H. J. Kim; K. E. Jansen; C. A. Taylor
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. Copyright © 2011 John Wiley & Sons, Ltd. PMID:25365656
Blanco, P J; Trenhago, P R; Fernandes, L G; Feijóo, R A
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
Pironet, Antoine; Dauby, Pierre C.; Paeme, Sabine; Kosta, Sarah; Chase, J. Geoffrey; Desaive, Thomas
Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases. PMID:21403831
Zaragoza, Carlos; Gomez-Guerrero, Carmen; Martin-Ventura, Jose Luis; Blanco-Colio, Luis; Lavin, Begona; Mallavia, Benat; Tarin, Carlos; Mas, Sebastian; Ortiz, Alberto; Egido, Jesus
We developed a laboratory exercise that involves the construction and subsequent manipulation of a model of the cardiovascular system. The laboratory was designed to engage students in interactive, inquiry-based learning and to stimulate interest for future science study. The model presents a concrete means by which cardiovascular mechanics can be understood as well as a focal point for student interaction and discussion of cardiovascular principles. The laboratory contains directions for the construction of an inexpensive, easy-to-build model as well as an experimental protocol. From this experience students may gain an appreciation fo science that cannot be obtained by reading a book or interacting with a computer. Students not only learn the significant physiological concepts but also appreciate the importance of laboratory experimentation for understanding complex concepts. Model construction provides a hands-on experience that may substantially improve performance in science processes. We believe that model construction is an appropriate method for teaching advanced concepts. PMID:10644263
Rodenbaugh, D W; Collins, H L; Chen, C Y; DiCarlo, S E
Biofluid dynamics is characterized by the study of fluids in biological systems. Common biofluid systems include blood flow in the cardiovascular system and airflow in the lungs. The mathematical modeling of blood flow through the complex geometry of a prosthetic heart valve is a difficult task. In such a problem the complex geometries of the valve must be modeled properly so that they can be studied numerically. The present analysis is performed on a disk-type prosthetic heart valve. The valve is assumed to be in the aortic position and observed the structure of the valve cage influence the flow field near an aortic valve. For the purpose of mathematical modeling, the laminar incompressible two-dimensional steady flow of a homogeneous Newtonian fluid with constant viscosity is assumed. The flow is considered during the greater part of systole when the valve is fully open. Convergent numerical solutions are obtained for Reynolds numbers of 30, 180, 900 and 4500. Stream function, horizontal velocity, vertical velocity and shear stress solutions are computed at every grid point.
Chung, Hansol; Yoo, Su Jung; Kyung, Richard
The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction\\/oxidation (redox) status. The impairment of cell redox state alters multiple cell pathways, which may contribute to the pathogenesis of cardiovascular disorders including hypertension, atherosclerosis, and heart failure. In this manuscript, we review the essential roles that TRX plays by limiting oxidative
Hideyuki Yamawaki; Bradford C. Berk
As cardiovascular disorders have emerged as the primary cause of human mortality, quantitative modeling of cardiovascular system, including the dynamic coupling among its chemical, electrical and pulmonary mechanisms, has evoked keen interest in the recent years. The current dynamic models have little clinical relevance because they cannot be correlated with the real-time signals from a human heart. This research presents
Trung Q. Le; S. T. S. Bukkapatnam; A. Sangasoongsong; R. Komanduri
The primary role of the cardiovascular system is to deliver a required amount of oxygen to various organs. These needs vary with time and depend on the vascular site. To maintain a required diffusion level of oxygen in the capillary networks, the cardiovascular system is controlled by regulation processes that maintain pressure and blood flow to the required physiological levels.
Jean-Louis Lacaze; Etienne Menigault; Pierre Vieyres; B. Lepoivre; L. Pourcelot
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
Nerem, Robert M
A mathematical model of cardiovascular response to dynamic exercise is presented, The model includes the pulsating heart, the systemic and pulmonary, circulation, a functional description of muscle exercise hyperemia, the mechanical effects of muscle cont...
E. Magosso, A. Felicani, M. Ursino
Cardiovascular magnetic resonance (CMR) imaging is the modality of choice for clinical studies of the heart and vasculature, offering detailed images of both structure and function with high temporal resolution. Small animals are increasingly used for genetic and translational research, in conjunction with models of common pathologies such as myocardial infarction. In all cases, effective methods for characterising a wide range of functional and anatomical parameters are crucial for robust studies. CMR is the gold-standard for the non-invasive examination of these models, although physiological differences, such as rapid heart rate, make this a greater challenge than conventional clinical imaging. However, with the help of specialised magnetic resonance (MR) systems, novel gating strategies and optimised pulse sequences, high-quality images can be obtained in these animals despite their small size. In this review, we provide an overview of the principal CMR techniques for small animals for example cine, angiography and perfusion imaging, which can provide measures such as ejection fraction, vessel anatomy and local blood flow, respectively. In combination with MR contrast agents, regional dysfunction in the heart can also be identified and assessed. We also discuss optimal methods for analysing CMR data, particularly the use of semi-automated tools for parameter measurement to reduce analysis time. Finally, we describe current and emerging methods for imaging the developing heart, aiding characterisation of congenital cardiovascular defects. Advanced small animal CMR now offers an unparalleled range of cardiovascular assessments. Employing these methods should allow new insights into the structural, functional and molecular basis of the cardiovascular system. PMID:21331311
Price, Anthony N.; Cheung, King K.; Cleary, Jon O; Campbell, Adrienne E; Riegler, Johannes; Lythgoe, Mark F
Ultrafast computed tomography (CT) is a new imaging technique that relies on electron beam technology. Its rapid image acquisition speeds make it ideal for evaluating the cardiovascular system. The high-resolution, flow, and cine-modes are unique and provide complimentary information about cardiovascular anatomy, function, and flow dynamics. Ultrafast CT can provide quantitative measurements of cardiac output, ejection fraction, ventricular volumes, and
Mark S. Bleiweis; Demetrios Georgiou; Bruce H. Brundage
A global analysis of the mechanical function of the cardiovascular system that explains fundamental concepts, such as: The unique hydraulic characteristics of the heart as a pump and the cardiovascular system; the determinants of cardiac output; the mechanism that maintains blood volume equilibrium between the systemic and pulmonary circuits; and the primary contribution of the atria to circulation rate. Free downloadable text and online video available.
Dr. Robert M Anderson (University of Arizona)
Acromegaly is characterized by an increased cardiovascular morbidity and mortality. In fact, growth hormone and insulin-like growth factor-I excess induces a specific cardiomyopathy. The heart is involved from the very early stages of the disease in which the hyperkinetic syndrome (high heart rate and increased systolic output) takes place. Frequently, if the disease is untreated for many years or unsuccessfully
Gaetano Lombardi; Mariano Galdiero; Renata S. Auriemma; Rosario Pivonello; Annamaria Colao
Systemic hypertension is a highly prevalent potentially modifiable cardiovascular risk factor. Imaging plays an important role in the diagnosis of underlying causes for hypertension, in assessing cardiovascular complications of hypertension, and in understanding the pathophysiology of the disease process. Cardiovascular magnetic resonance (CMR) provides accurate and reproducible measures of ventricular volumes, mass, function and haemodynamics as well as uniquely allowing tissue characterization of diffuse and focal fibrosis. In addition, CMR is well suited for exclusion of common secondary causes for hypertension. We review the current and emerging clinical and research applications of CMR in hypertension. PMID:22559053
The cardiovascular application of gene transfer and therapy has three overlapping goals. First, it can be seen as a molecular\\u000a tool to probe pathways and mechanisms that are difficult to elucidate by other means. Second, it is widely used in preclinical\\u000a studies and a variety of cardiovascular disease models to find the most efficient and safe clinical applications. Lastly,\\u000a it
William H. Miller; Stuart A. Nicklin; Andrew H. Baker; Anna F. Dominiczak
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. PMID:22701195
Golbidi, Saeid; Laher, Ismail
Pulmonary vs. systemic circulations What are the primary functions of the cardiovascular system? How Respiration vs. Ventilation #12;ME498/599 Modeling the System Blood Velocity (Poiseuille's Law) CO = Q = (P1-P viscosity versus shear rate for blood of differing hematocrits (H). Note the Newtonian behavior of the fluid
Sniadecki, Nathan J.
The maintenance of an adequate cardiac output and systemic arterial blood pressure is a complex process with intricacies that are often difficult to understand. Cardiovascular Interactions is an active learning tool that demonstrates the interactions between the functions of the heart and peripheral circulation. This learning package consists of a Lab Book, a Model, and an Information file. The Lab Book is an interactive tutorial for exploring the relative influences of parameter changes on the cardiovascular system under normal, stressful, or pathophysiological conditions. The learners are guided to predict the direction and relative magnitude of changes of key variables in the cardiovascular system, evaluate the accuracy of their predictions, and describe the cause-and-effect mechanisms involved. Consequences of heart failure, hemorrhage, exercise, and changes in intrathoracic pressure can be explored. The results obtained in the Lab Book are based on a five-compartment mathematical Model, which reflects our current understanding of the basic control of the cardiovascular system. The Model was designed to be complex enough to be realistic, yet not so complex as to be overwhelming. An Information File contains definitions and descriptions of classical physiology about key concepts, including figures, and a detailed description of the Model. Hypertext tags embedded in the Lab Book are used to access the Information File. The Cardiovascular Interactions learning package was designed to run from its CD and so does not need to be installed.
PhD Carl F. Rothe (Indiana University School of Medicine Department of Cellular and Integrative Physiology); PhD John M. Gersting (Department of Computer Science)
Cheyne-Stokes respiration (CSR) is a periodic breathing pattern, characterized by short intervals of very little or no breathing (apnea), each followed by an interval of very heavy breathing (hyperpnea). This work presents a new compartmental model of the human cardio-respiratory system, simulating the factors that determine the concentrations of carbon dioxide in the compartments of the cardiovascular system and the lungs. The parameter set on which a Hopf bifurcation gives birth to stable CSR oscillations has been determined. The model predicts that the onset of CSR oscillations may result from an increase in any of: ventilation-perfusion ratio, feedback control gain, transport delay, left heart volume, lung congestion, or cardiovascular efficiency. The model is employed to investigate the relationship between CSR and serious cardiovascular pathologies, such as congestive heart failure and encephalitis, as well as the effects of acclimatization to higher altitudes. In all cases, the model is consistent with medical observations. PMID:18392825
Dong, Fang; Langford, William F
It was the hypothesis of this Project that the Simple lack of hydrostatic pressure in microgravity generates several purely physical reactions that underlie and may explain, in part, the cardiovascular response to weightlessness. For instance, hydrostatic pressure within the ventricles of the heart may improve cardiac performance by promoting expansion of ventricular volume during diastole. The lack of hydrostatic pressure in microgravity might, therefore, reduce diastolic filling and cardiac performance. The change in transmural pressure is possible due to the difference in hydrostatic pressure gradients between the blood inside the ventricle and the lung tissue surrounding the ventricle due to their different densities. On the other hand, hydrostatic pressure within the vasculature may reduce cardiac inlet pressures because of the typical location of the heart above the hydrostatic indifference level (the level at which pressure remains constant throughout changes in gravity). Additional physical responses of the body to changing gravitational conditions may influence cardiovascular performance. For instance, fluid shifts from the lower body to the thorax in microgravity may serve to increase central venous pressure (CVP) and boost cardiac output (CO). The concurrent release of gravitational force on the rib cage may tend to increase chest girth and decrease pedcardial pressure, augmenting ventricular filling. The lack of gravity on pulmonary tissue may allow an upward shifting of lung mass, causing a further decrease in pericardial pressure and increased CO. Additional effects include diuresis early in the flight, interstitial fluid shifts, gradual spinal extension and movement of abdominal mass, and redistribution of circulatory impedance because of venous distention in the upper body and the collapse of veins in the lower body. In this project, the cardiovascular responses to changes in intraventricular hydrostatic pressure, in intravascular hydrostatic 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.
Sharp, M. Keith
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
Pruett, William A.; Husband, Leland D.; Husband, Graham; Dakhlalla, Muhammad; Bellamy, Kyle; Coleman, Thomas G.; Hester, Robert L.
Human cardiovascular and/or cardio-respiratory systems are shown to exhibit both multifractal and synchronous dynamics, and we recently developed a nonlinear, physiologically plausible model for the synchronization between heartbeat and respiration (Kotani, et al. Phys. Rev. E 65: 051923, 2002). By using the same model, we now show the multifractality in the heart rate dynamics. We find that beat-to-beat monofractal noise (fractional Brownian motion) added to the brain stem cardiovascular areas results in significantly broader singularity spectra for heart rate through interactions between sympathetic and parasympathetic nervous systems. We conclude that the model proposed here would be useful in studying the complex cardiovascular and/or cardio- respiratory dynamics in humans.
Kotani, Kiyoshi; Takamasu, Kiyoshi; Safonov, Leonid; Yamamoto, Yoshiharu
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. PMID:22304473
Liu, Yi-Hong; Lu, Ming; Hu, Li-Fang; Wong, Peter T-H; Webb, George D; Bian, Jin-Song
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.
Lindsey, Thomas; Valsecchi, Pietro
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 dysfunction and this may represent a novel therapeutic strategy. Collectively, these data shed new insights into the likely mechanism of action through which the ACE2/Ang-(1-7)/Mas receptor axis prevents Type 1 diabetes-induced cardiovascular dysfunction. PMID:22580236
Yousif, Mariam H M; Dhaunsi, Gursev S; Makki, Batoul M; Qabazard, Bedour A; Akhtar, Saghir; Benter, Ibrahim F
Students learn about the heart and its role at the center of the human cardiovascular system. In the associated activity, students play out a scenario in which they are biomedical engineers asked to design artificial hearts. They learn about the path of blood flow through the heart and use that knowledge to evaluate designs of artificial hearts on the market.
Bio-Inspired Technology and Systems (BITS) RET,
Training of the cardiovascular system may effect several structural, chemical and functional changes. Some of the functional changes become manifest only during exercise, others are observable also at rest. To some extent changes due to training are independent of each other, and depend on the typo of training. For example, a decrease of the pulse rate during standard exercise is
M. J. KAKVONEN
Magnetic resonance imaging (MRI) has emerged as a powerful and reliable tool to noninvasively study the cardiovascular system in clinical practice. Because transgenic mouse models have assumed a critical role in cardiovascular research, technological advances in MRI have been extended to mice over the last decade. These have provided critical insights into cardiac and vascular morphology, function, and physiology/pathophysiology in many murine models of heart disease. Furthermore, magnetic resonance spectroscopy (MRS) has allowed the nondestructive study of myocardial metabolism in both isolated hearts and in intact mice. This article reviews the current techniques and important pathophysiological insights from the application of MRI/MRS technology to murine models of cardiovascular disease. PMID:23292717
Akki, Ashwin; Gupta, Ashish
The human cardiovascular system routinely encounters conditions that cause it to adapt. For example, when an astronaut enters microgravity, his/her cardiovascular system adapts rapidly to the weightless environment with ...
Zamanian, Sam Ahmad
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. PMID:8897409
Robertson, D; Jacob, G; Ertl, A; Shannon, J; Mosqueda-Garcia, R; Robertson, R M; Biaggioni, I
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
Campos, Luciana A.; Pereira, Valter L.; Muralikrishna, Amita; Albarwani, Sulayma; Bras, Susana; Gouveia, Sonia
Exfoliation syndrome (XFS) is a systemic condition. Intraocular alterations represent only a part of the exfoliation-related clinical signs. Exfoliation material has been identified in the visceral organs, skin, and vessel walls. This triggered several studies that investigated association between XFS and cardiovascular diseases. In many populations, significant associations between XFS and various systemic vascular diseases including elevated plasma homocysteine level, myocardial dysfunction, stroke, aortic aneurysm, and white matter lesions were found. Some of these XFS-associated vascular diseases are caused by elastosis of the vessel wall, which may be directly related to general extracellular dysfunction in XFS. Another part of the pathologic vascular alterations (reduced cutaneous capillary flow reactions, impaired baroreflex sensitivity, parasympathetic cardiovascular neuropathy, and pathologic heart rate variability indices), however, suggests that vascular dysregulation beyond the age-related normal decline may also play a role both in the development and worsening of the systemic cardiovascular diseases in XFS. The exact mechanism of the development of systemic vascular dysregulation associated with XFS is currently unknown. PMID:25275916
The effect of PUVA therapy on the cardiovascular system was studied in 2 groups of patients. The first group consisted of 9 otherwise healthy patients, who were treated without airconditioning. The second group was formed by 15 otherwise healthy psoriasis patients, who were treated with photochemotherapy, using airconditioning. In both groups the cabinet-skin and rectal temperature rose significantly. The most marked finding however was the rise in heart rate. By applying airconditioning, significantly smaller increases in the measured parameters occurred. In none of the patients changes in the electrocardiograms were observed. The effects on the cardiovascular system can evidently be limited by applying airconditioning and by keeping the time of light exposure as short as possible. PMID:6642037
Prens, E P; Smeenk, G
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 ?-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. PMID:24287310
Dassanayaka, Sujith; Jones, Steven P
Describes a model which gives realistic predictions of pulsatile pressure, flow, and volume events in the cardiovascular system. Includes computer oriented laboratory exercises for veterinary and graduate students; equations of the dynamic and algebraic models; and a flow chart for the cardiovascular teaching program. (JN)
Campbell, Kenneth; And Others
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.
Croston, R. C.
In this paper, the method of dynamic flow birefringence (DFB) have been studied extensively under the consideration of an application to cardiovascular models. The method utilises the optical interference patterns observed in the birefringent flow for determination of the fluid shear stress and velocity distribution. In order to measure a flow in a cardiovascular model, an assumption of a simplified stress-optical relation in a pulsatile flow is suggested and special experimental techniques such as birefringent fluid for simulating blood and new experimental system have been developed. Application studies focus on pulsatile flows in typical models, namely arterial bifurcation and mechanical heart valves. Experimental results are discussed and compared with those of other researchers.
Sun, Yong-Da; Sun, Yong-Fang; Sun, Yang; Xu, X. Y.; Collins, M. W.
This study established a numerical model to investigate the degradation mechanism and behavior of bioabsorbable cardiovascular stents. In order to generate the constitutive degradation material model, the degradation characteristics were characterized with user-defined field variables. The radial strength bench test and analysis were used to verify the material model. In order to validate the numerical degradation model, in vitro bench test and in vivo implantation studies were conducted under physiological and normal conditions. The results showed that six months of degradation had not influenced the thermodynamic properties and mechanical integrity of the stent while the molecular weight of the stents implanted in the in vivo and in vitro models had decreased to 61.8% and 68.5% respectively after six month's implantation. It was also found that the degradation rate, critical locations and changes in diameter of the stents in the numerical model were in good consistency in both in vivo and in vitro studies. It implies that the numerical degradation model could provide useful physical insights and prediction of the stent degradation behavior and evaluate, to some extent, the in-vivo performance of the stent. This model could eventually be used for design and optimization of bioabsorbable stent. PMID:25365310
Luo, Qiyi; Liu, Xiangkun; Li, Zhonghua; Huang, Chubo; Zhang, Wen; Meng, Juan; Chang, Zhaohua; Hua, Zezhao
The cardiovascular systems of Puget Sound king crabs, Lopholithodes mandtii, and brown box crabs, Lopholithodes foraminatus, were mapped using corrosion casting techniques. Both species have a similar external morphology and a very similar cardiovascular system. Seven arteries (five arterial systems) arise from the heart. The small anterior aorta exits from the anterior surface of the heart and supplies hemolymph to the eyestalks and brain region. The pathway of the two sets of paired arteries, the anterolateral arteries and hepatic arteries, is close, and they intertwine with one another during their initial course. The anterolateral arteries exit from the anterior dorsal surface of the heart and supply hemolymph to the hypodermis, cardiac stomach, antennal gland, and mandibular muscles, whereas the hepatic arteries branch profusely within the hepatopancreas. The lithodids are believed to have evolved from hermit crab ancestors; indicative of these evolutionary origins the posterior aorta is well developed and supplies hemolymph to the large abdomen and the gonads. Exiting from the ventral surface of the heart, the sternal artery is the largest in the system. It branches to supply the mouthparts, chelae, and pereiopods. The differing arrangement of this vessel compared with that of the pagurid anomurans is due to the more carcinized (crab-like) morphological features of the lithodid anomurans. The arrangement of vessels supplying the gills is different compared with that of brachyuran crabs; the infrabranchial sinus joins to the afferent gill vessels at their midpoint, rather than along the ventral edge. In general, the circulatory system of the lithodid crabs is somewhat simpler than that of brachyuran crabs, with fewer branching capillary-like networks. Nevertheless, it is still very complex. In accordance with anatomical descriptions of blue crabs and cancrid crabs it would also seem appropriate to classify the lithodid circulatory system as one that is incompletely closed. PMID:18553421
McGaw, Iain J; Duff, Stefanie D
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 ...
Choma, Michael A.
A study on circadian regulation of the cardiovascular system: dysfunction in the BACHD Huntington's Disease model and Vasoactive Intestinal Peptide-deficient mice and the use of scheduled exercise to rescue circadian deficits.
the cardiovascular system to respond to an exerciseexercise during the active phase leads to physiological hypertrophy of the heart, which is a beneficial adaptive response of the cardiovascular system (
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 ?m/s, that statistically significant (p
Gurfinkel, Yury; Breus, Tamara
There is considerable recent evidence that param- eters thought to reflect the complex interaction between the autonomic nervous system and the cardiovascular system during exercise testing can provide significant prognostic information. Specific variables of great importance include heart rate (HR) response to exercise (reserve), HR recovery after exercise, and multiple components of HR variability both at rest and with exercise.
James V. Freeman; Frederick E. Dewey; David M. Hadley; Jonathan Myers; Victor F. Froelicher
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.
Leonard, J. I.; Srinivasan, R.
Cardiovascular response to running exercise was studied with a simple pulsatile cardiovascular model. Published experimental data during graded exercise were used to tune the model parameters. Study results show that cardiac output is modulated by rhythmic muscle contractions during running. It oscillates when step rate and heart rate are not synchronised but stabilises when they are synchronised. A maximum cardiac
Daoming Zhang; Branko Celler
Management of SAS and cardiovascular disease risk should be closely linked. It is important to screen for cardiovascular disease risk in patients with SAS and vice versa. CSA/CSR may be improved by ventilation strategies in heart failure, but benefit remains to be proven. For OSA, although CPAP may reduce cardiovascular disease risk, its main benefit is symptom control. In the longer-term, CPAP should be used alongside standard cardiovascular risk reduction strategies including robust weight management programmes, with referral for bariatric surgery in appropriate cases. CPAP and NIV should be considered for acute admissions with decompensated cardiac failure. PMID:21902085
Pepperell, Justin C
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 arises from sources other than the caudal ventrolateral medulla. If similar alterations in control of the sympathetic nervous system occur in humans in response to cardiovascular deconditioning, it is likely that they play an important role in the observed tendency for orthostatic intolerance. Combined with potential changes in vascular function, cardiac function, and hypovolemia, the predisposition for orthostatic intolerance following cardiovascular deconditioning would be markedly enhanced by blunted ability to reflexly activate the sympathetic nervous system.
Hasser, E. M.; Moffitt, J. A.
We present an approach to deriving a real-time, lumped parameter cardiovascular dynamics model that uses features extracted from online electrocardiogram (ECG) signal recordings to generate certain surrogate hemodynamic signals. The model represents the coupled dynamics of the heart chambers, valves, and pulmonary and systemic blood circulation loops in the form of nonlinear differential equations. The features extracted from ECG signals were used to estimate the timings and amplitudes of the atrioventricular activation input functions as well as other model parameters that capture the effect of cardiac morphological and physiological characteristics. The model was tested using hemodynamic signals from the PhysioNet MGH/MF Waveform database. The results suggest that the model can capture the salient time and frequency patterns of the measured central venous pressure, pulmonary arterial pressure, and respiratory impedance signals (R(2) > 0.65). We have developed a method based on Anderson-Darling statistic and Kullback-Leibler divergence to compare the clinical measures (i.e., systolic and diastolic pressures) estimated from model waveform-extrema with those from actual measurements. The test statistics of the model waveform-extrema were statistically indistinguishable from the measured values with beat-to-beat rejection rates of 10%. The results indicate the potential of a virtual instrument that uses the model-derived signals for clinical diagnosis in lieu of expensive instrumentation. PMID:23559024
Le, Trung Q; Bukkapatnam, Satish T S; Komanduri, Ranga
Cardiovascular diseases involve the heart or blood vessels and remain a leading cause of morbidity and mortality in developed countries. A variety of animal models have been used to study cardiovascular diseases and have contributed to our understanding of their pathophysiology and treatment. However, mutations or abnormal expression of specific genes play important roles in the pathophysiology of some heart diseases, for which a closely similar animal model often is not naturally available. With the advent of techniques for specific genomic modification, several transgenic and knockout mouse models have been developed for cardiovascular conditions that result from spontaneous mutations. However, mouse and human heart show marked electrophysiologic differences. In addition, cardiac studies in mouse models are extremely difficult because of their small heart size and fast heart rate. Therefore, larger genetically engineered animal models are needed to overcome the limitations of the mouse models. This review summarizes the transgenic rabbit models that have been developed to study cardiovascular diseases. PMID:23561880
This work encompasses together a number of diverse disciplines (physiology, biomechanics, fluid mechanics and simulation)\\u000a in order to develop a predictive model of the behaviour of a prosthetic heart valve in vivo. The application of simulation,\\u000a for the study of other cardiovascular problems, such as blood clotting is also discussed. A commercial, finite volume, computational\\u000a fluid dynamics (CFD) code (ANSYS\\/CFX)
Vanessa Díaz-zuccarini; D. Rafirou; D. Rodney Hose; Patricia V. Lawford; A. J. Narracott
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 hyperthy- roidism 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
SERAFINO FAZIO; EMILIANO A. PALMIERI; GAETANO LOMBARDI; BERNADETTE BIONDI
\\u000a The renin angiotensin system (RAS) is an established regulator of intravascular volume and arterial pressure. It is now clear\\u000a that complete and partial RASs exist in multiple tissues, including the cardiovascular system, with the result that local\\u000a regulation of angiotensin can occur. In addition, newly identified factors such as ACE 2 and the (pro)renin receptor expand\\u000a the potential physiological actions
Richard N. Re
\\u000a One of the major concerns for both short- and long-duration spaceflight is the phenomenon of cardio-vascular deconditioning.\\u000a Exercise deconditioning during spaceflight may significantly affect a crewmember’s ability to perform strenuous or prolonged\\u000a tasks during and after a spaceflight mission, respond to an emergency situation, or assist a crewmate who might be incapacitated.\\u000a This chapter introduces the principles of cardio-vascular fluid
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.
Pendergast, D. R.; Olszowka, A. J.; Rokitka, M. A.; Farhi, L. E.
Oxidative stress and inflammation are two sides of the same coin that are intricately combined to elicit a chronic pathophysiological stress state, especially as seen in cardiovascular remodelling. In this review, we argue that administration of deoxycorticosterone acetate (DOCA) and sodium chloride to uninephrectomised rats, defined as DOCA-salt hypertensive rats, provides a reliable animal model of oxidative and inflammatory stress in the cardiovascular system. The supporting evidence includes pathophysiological and biochemical changes together with pharmacological responses to synthetic and natural compounds that lower the concentrations of reactive free radical species and that curtail inflammatory responses in the cardiovascular system. PMID:22043205
Iyer, Abishek; Chan, Vincent; Brown, Lindsay
Human exposure to particulate matter (PM) elicits a variety of responses on the cardiovascular system through both direct and indirect pathways. Indirect effects of PM on the cardiovascular system are mediated through the autonomic nervous system, which controls heart rate variability, and inflammatory responses, which augment acute cardiovascular events and atherosclerosis. Recent research demonstrates that PM also affects the cardiovascular system directly by entry into the systemic circulation. This process causes myocardial dysfunction through mechanisms of reactive oxygen species production, calcium ion interference, and vascular dysfunction. In this review, we will present key evidence in both the direct and indirect pathways, suggest clinical applications of the current literature, and recommend directions for future research. PMID:22119171
Nelin, Timothy D.; Joseph, Allan M.; Gorr, Matthew W.; Wold, Loren E.
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. PMID:24111539
Dangwal, Seema; Thum, Thomas
In this review, the role of wall shear stress in the chicken embryonic heart is analyzed to determine its effect on cardiac development through regulating gene expression. Therefore, background information is provided for fluid dynamics, normal chicken and human heart development, cardiac malformations, cardiac and vitelline blood flow, and a chicken model to induce cardiovascular anomalies. A set of endothelial shear stress-responsive genes coding for endothelin-1 (ET-1), lung KrÃÂ¼ppel-like factor (LKLF/KLF2), and endothelial nitric oxide synthase (eNOS/NOS-3) are active in development and are specifically addressed.
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.
Gallagher, R. R.
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
Lim, Einly; Chan, Gregory S. H.; Dokos, Socrates; Ng, Siew C.; Latif, Lydia A.; Vandenberghe, Stijn; Karunanithi, Mohan; Lovell, Nigel H.
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. PMID:23738043
Taverne, Yannick J. H. J.; Bogers, Ad J. J. C.; Duncker, Dirk J.; Merkus, Daphne
Pulmonary vs. systemic circulations What are the primary functions of the cardiovascular system? How Respiration vs. Ventilation #12;ME411/511 Hemodynamics #12; viscosity versus shear rate for blood of differing hematocrits (H). Note the Newtonian behavior of the fluid
Sniadecki, Nathan J.
Researchers at the Georgia Health Sciences University in Augusta have found that a master clock gene ÃÂ which regulates the cardiovascular system ÃÂ does not fluctuate regularly as it does in non-obese animals. This means that a key gene clock of the cardiovascular system does not work properly when obesity is present. These findings are believed to be the first of their kind. The study was conducted by Shuiqing Qiu, Eric Belin de Chantemele, James Mintz, David J. Fulton, R. Daniel Rudic and David W. Stepp.
APS Communications Office (American Physiological Society Communications Office)
Three portable prototype devices for cardiovascular biosensing based on reflection-type photoplethysmography (PPG) principle have been designed and clinically tested. The single-channel PPG finger sensor provides real-time measurements with fast calculation of the mean single-period PPG signal shape ("cardiovascular fingerprint", potentially useful for recognition). The dual-channel PPG system gives additional possibility to monitor on-line the arterial pulse wave transit time and its responses to physical exercises. The four-channel PPG system proved to be applicable for fast detection of cardiovascular pathologies, e.g. arterial occlusions in extremities. Design principles and software algorithms of the regarded devices will be discussed, as well as the results of recent clinical tests.
Erts, R.; Spigulis, J., Sr.; Ozols, M.
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.
Stamm, Christof; Klose, Kristin; Choi, Yeong-Hoon
of the human heart for a quantitative analysis of cyclical electrical conductance on the heart mem- brane [2, 3 such as lung nodules , coronary artery #12;2 Chandrajit Bajaj and Samrat Goswami Fig. 1. Cardiovascular and Right Ventricle and Atrium (colored differently). Bottom row illustrates the modeling of coronary artery
Texas at Austin, University of
The development of statistical models that accurately describe the stochastic structure of biological signals is a fast growing area in quantitative research. In developing a novel statistical paradigm based on Bayes’ theorem applied to point processes, we are focusing our recent research on characterizing the physiological mechanisms involved in cardiovascular control. Results from a tilt table study point at our
Riccardo Barbieri; Emery N. Brown
. For example, mean blood flow velocity and pressure show similar dynamics for healthy young and hyper- tensiveDevelopment of patient specific cardiovascular models predicting dynamics in response. Special attention is paid to the control of blood pressure, cerebral blood flow velocity, and heart rate
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 (?-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
The aim of the study was to get and analyse data on the changes in ECG, heart rate and blood pressure with the change in gravitational acceleration or g. Previous studies conducted in our laboratory showed that regular practice of Sheersasana (a Yogic posture) could possibly help in tuning the cardiovascular system to adapt easily to the accumulation of blood
Santosh Bhaskaran; Sayan Mondal; Sagar Jagtap; Pandit Vidyasagar
Although Hippocrates has been traditionally recognized as the father of medicine and one of the major early writers regarding the cardiovascular system, very little is known of about the knowledge of the cardiovascular system in the pre-Hippocratic period. We reviewed the literature and examined available references regarding the cardiovascular system in the pre-Hippocratic era of the Chinese, Indians, Egyptians, and Ancient Greeks including Asclepios, Alcmaeon, Empedocles and Diogenes. All pre-Hippocratic civilizations attributed the illnesses and the structures of the human body to divine powers. Pre-Hippocratic medicine was largely based on religious beliefs and not in scientific observations. Interestingly, despite these erroneous methods, the pre-Hippocratics were able to identify pipes carrying air into the body and name the air carriers (arteries). Unfortunately, the arteries were not associated with blood but rather with air, however, this ancient word still remains in use in our days. This paper reviews the evolution of thinking and discovery regarding the different aspects of the cardiovascular system in the pre-Hippocratic era. PMID:17316844
Loukas, Marios; Tubbs, R Shane; Louis, Robert G; Pinyard, Jeremy; Vaid, Sumreen; Curry, Brian
Dahl salt-sensitive (DS) and salt-resistant (DR) inbred rat strains represent a well established animal model for cardiovascular research. Upon prolonged administration of high-salt-containing diet, DS rats develop systemic hypertension, and as a consequence they develop left ventricular hypertrophy, followed by heart failure. The aim of this work was to explore whether this animal model is suitable to identify biomarkers that characterize defined stages of cardiac pathophysiological conditions. The work had to be performed in two stages: in the first part proteomic differences that are attributable to the two separate rat lines (DS and DR) had to be established, and in the second part the process of development of heart failure due to feeding the rats with high-salt-containing diet has to be monitored. This work describes the results of the first stage, with the outcome of protein expression profiles of left ventricular tissues of DS and DR rats kept under low salt diet. Substantial extent of quantitative and qualitative expression differences between both strains of Dahl rats in heart tissue was detected. Using Principal Component Analysis, Linear Discriminant Analysis and other statistical means we have established sets of differentially expressed proteins, candidates for further molecular analysis of the heart failure mechanisms. PMID:21338724
Grussenmeyer, Thomas; Meili-Butz, Silvia; Roth, Volker; Dieterle, Thomas; Brink, Marijke; Winkler, Bernhard; Matt, Peter; Carrel, Thierry P; Eckstein, Friedrich S; Lefkovits, Ivan; Grapow, Martin T R
This study develops a lumped cardiovascular-respiratory system-level model that incorporates patient-specific data to predict cardiorespiratory response to hyper-capnia (increased CO2 partial pressure) for a patient with congestive heart failure (CHF). In particular, the study focuses on predicting cerebral CO2 reactivity, which can be defined as the ability of vessels in the cerebral vasculature to expand or contract in response CO2 induced challenges. It is difficult to characterize cerebral CO2 reactivity directly from measurements, since no methods exist to dynamically measure vasomotion of vessels in the cerebral vasculature. In this study we show how mathematical modeling can be combined with available data to predict cerebral CO2 reactivity via dynamic predictions of cerebral vascular resistance, which can be directly related to vasomotion of vessels in the cerebral vasculature. To this end we have developed a coupled cardiovascular and respiratory model that predicts blood pressure, flow, and concentration of gasses (CO2 and O2) in the systemic, cerebral, and pulmonary arteries and veins. Cerebral vascular resistance is incorporated via a model parameter separating cerebral arteries and veins. The model was adapted to a specific patient using parameter estimation combined with sensitivity analysis and subset selection. These techniques allowed estimation of cerebral vascular resistance along with other cardiovascular and respiratory parameters. Parameter estimation was carried out during eucapnia (breathing room air), first for the cardiovascular model and then for the respiratory model. Then, hypercapnia was introduced by increasing inspired CO2 partial pressure. During eucapnia, 7 cardiovascular parameters and 4 respiratory parameters was be identified and estimated, including cerebral and systemic resistance. During the transition from eucapnia to hypercapnia, the model predicted a drop in cerebral vascular resistance consistent with cerebral vasodilation. PMID:23046704
Ellwein, L.M.; Pope, S.R.; Xie, A.; Batzel, J.J.; Kelley, C.T.; Olufsen, M.S.
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 (?s) 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 ?s 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 ? 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 hypertensive rats during the weeks after weaning CHAT precedes an elevation of the BP MESOR, a decadal overswing seems to precede the occurrence of high BP in two of the subjects here examined. Only around-the-clock monitoring in health for the collection of reference values will allow on their basis the differential diagnosis of the onsets of a circadian versus a circadecadal overswing in BP and the specification whether, and if so, when to initiate hypotensive non-drug or drug treatment. PMID:24860279
Halberg, Franz; Cornelissen, Germaine; Sothern, Robert B.; Hillman, Dewayne; Watanabe, Yoshihiko; Haus, Erhard; Schwartzkopff, Othild; Best, William R.
This paper reports the use of a magnetic resonance imaging (MRI) system to propel a ferromagnetic core. The concept was studied for future development of microdevices designed to perform minimally invasive interventions in remote sites accessible through the human cardiovascular system. A mathematical model is described taking into account various parameters such as the size of blood vessels, the velocities
Jean-Baptiste Mathieu; Gilles Beaudoin; Sylvain Martel
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.
White, Ronald J.; Leonard, Joel I.; Srinivasan, R. Srini; Charles, John B.
Vital spirits flow Air flow Nutrition This seemed absurd when compared to the amount of blood in a human Âµm) Â§ Capillaries (50 Âµm) Systemic Arteries #12;Arterioles and Capillaries #12;Pressure and Area Pressure Systolic pressure Pulse pressure Diastolic pressure L ventricle Aorta Arteries Arterioles Vessel
Olufsen, Mette Sofie
Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans. PMID:23691518
Lehnen, Alexandre M.; Rodrigues, Bruno; Irigoyen, Maria Claudia; De Angelis, Katia; Schaan, Beatriz D'Agord
Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans. PMID:23691518
Lehnen, Alexandre M; Rodrigues, Bruno; Irigoyen, Maria Cláudia; De Angelis, Kátia; Schaan, Beatriz D'Agord
In article covers theoretical preconditions for the hypothesis about helical (spiral or swirling) blood flow in cardiovascular system followed by its experimental corroboration. The role of the modern blood flow visualization methods--such as Color Doppler ultrasound and magnetic-resonance angiography--in registration and investigation of the regularities of the given phenomenon is described. The data describing the known parameters of helical blood flow--such as direction of the rotation and its quantitative parameters in large arteries--are given. The main hypotheses for flow screw mechanisms are considered from the point of view of cardiovascular system structural organization. Biological role of helical blood flow is discussed, in respect of which there are diametrically opposed points of view, which consider it as a physiological phenomenon on one side, and as a patogenetic factor of atherosclerosis development on the other. PMID:23789353
Kirsanov, R I; Kulikov, V P
The Nord-Pas-de-Calais region of France is under-served in terms of access to cardiovascular surgery services, as illustrated by relatively high levels of waiting list mortality. This prompted the decision to create a new surgical unit in the region's densely populated, former industrial heartland called the "Mining Basin". Geographical and epidemiological modelling was used prospectively to estimate the likely future level of activity of the existing public sector cardiovascular surgery units. Information on the regional population distribution and the likely pattern of service use enabled us to estimate the new unit's potential activity. Our simulations produced nine scenarios which describe variations in the existing public units' activity ranging from -54% to +95%. This type of approach should enable policy makers to improve the organization of healthcare provision. PMID:15774334
Quesnel-Barbet, Anne; Nuttens, Marie Christine; Aublet-Cuvellier, Bruno; Warembourg, Henri; Prat, Alain; Thumerelle, Pierre Jean; Beuscart, Régis
The human cardiovascular system is exposed to plasma 5-hydroxytryptamine (5-HT, serotonin), usually released from platelets. 5-HT can produce harmful acute and chronic effects. The acute cardiac effects of 5-HT consist of tachycardia (preceded on occasion by a brief reflex bradycardia), increased atrial contractility and production of atrial arrhythmias. Acute inotropic, lusitropic and arrhythmic effects of 5-HT on human ventricle become
Alberto J. Kaumann; Finn Olav Levy
\\u000a Regenerative medicine encompasses “tissue engineering” – the in vitro fabrication of tissues and\\/or organs using scaffold\\u000a material and viable cells – and “cell therapy” – the transplantation or manipulation of cells in diseased tissue in vivo.\\u000a In the cardiovascular system, tissue engineering strategies are being pursued for the development of viable replacement blood\\u000a vessels, heart valves, patch material, cardiac pacemakers
Christof Stamm; Kristin Klose; Yeong-Hoon Choi
In management of canine cardiac disorders, cardiac drugs are commonly administered with food, although the cardiovascular effects of feeding and frequency of feeding are unknown. This study investigated the cardiovascular effect of feeding and frequency of feeding using a telemetry monitoring system in unanesthetized and unrestrained dogs. Systolic and diastolic blood pressure, heart rate and double product were steeply elevated during the five minutes immediately before feeding. They showed a sharp fall within 60 min after feeding time, especially the systolic and diastolic blood pressure, which showed lower values than from before feeding time. There were no significant differences in the means of preprandial elevation, postprandial fall or 24-hr averages in the once- and twice-daily feeding periods. PMID:20009430
Nakagawa, Kiyoshi; Miyagawa, Yuichi; Takemura, Naoyuki; Hirose, Hisashi
The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions. PMID:11537147
White, R J; Leonard, J I; Srinivasan, R S; Charles, J 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.
White, Ronald J.; Leonard, Joel I.; Srinivasan, R. Srini; Charles, John B.
As in normal subjects, acute mental stress increases blood pressure measurements (sometimes to hypertensive levels) in subjects with cardiovascular disease. We found examples in the literature of acute mental stress increasing peripheral vascular resistance (as in isometric exercise) in patients with cardiovascular disease. We did not, however, find examples of acute mental stress decreasing peripheral vascular resistance (as in isotonic
W. Victor; R. Vieweg; Linda M. Dougherty; Christopher S. Nicholson
Conditional systems have proven to be efficient and powerful to delineate several aspects of cardiac pathophysiology and diseases. The possibility of addressing a particular time point in animal life is certainly an important breakthrough allowed by conditional strategies with temporal control of either transgene expression or gene modifications. The purpose of this review is to present various mouse models for
A. Nguyen Din Cat; Y. Sainte-Marie; F. Jaisser
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
V. K. Sud; R. S. Srinivasan; J. B. Charles; M. W. Bungo
In normal subjects, acute mental stress may alter baseline cardiovascular parameters. During this stimulation, blood pressure and heart rate commonly increase. Changes in peripheral vascular resistance are variable. Parameter responses during acute mental stress may be incorporated in the model of isotonic (dynamic or volume) exercise with increased blood pressure and decreased peripheral vascular resistance or in the model of
W. Victor R. Vieweg; Linda M. Dougherty; Christopher S. Nicholson
The ability to recognize and appreciate from a reproductive standpoint that males and females possess different attributes has been long standing. Only more recently have we begun to look more deeply into both the similarities and differences between men and women, as well as between boys and girls, with respect to the structure and function of other organ systems. This article focuses on the cardiovascular system, with examples of sex differences in the control of coronary function, blood pressure, and volume. Recognizing the differences between the sexes with respect to cardiovascular function facilitates understanding of the mechanisms whereby homeostasis can be achieved using different contributions or components of the living system. Furthermore, recognition of the differences as well as the similarities permits the design of appropriate diagnostic instruments, recognition of sex-specific pathophysiology, and implementation of appropriate treatment of cardiovascular disease in men and women.
PhD Virginia H. Huxley (University of Missouri School of Medicine Department of Medical Pharmacology and Physiology)
The role of chronotherapeutics--agents that match drug delivery to the natural circadian rhythms of the cardiovascular system--in antihypertensive and antianginal therapy is discussed. Hypertension and angina remain two of the most important risk factors for cardiovascular morbidity and mortality. Early-morning increases in blood pressure do not seem to be attenuated by many currently available sustained-release and extended-dosing formulations of anti-hypertensive agents, such as atenolol, enalapril, sustained-release verapamil, nitrendipine, nifedipine, diltiazem, and long-acting propranolol. A 24-hour controlled-onset, extended-release delivery system (COER-24) for verapamil hydrochloride has recently been developed to address the pharmacokinetic and circadian challenges to controlling blood pressure and angina. COER-24 for verapamil hydrochloride, the first chronopharmacologic agent approved for the treatment of both hypertension and angina, is designed for bedtime administration. It provides the highest concentration of drug in the blood during the early hours of the day, when blood pressure and heart rate are rising rapidly. COER-24 for verapamil hydrochloride has a more favorable adverse-effect profile than is seen with immediate-release verapamil. COER-24 for verapamil hydrochloride provides effective blood pressure reduction for 24 hours and protects against the early-morning increase in blood pressure; the drug has a more favorable adverse-effect profile than immediate-release verapamil. PMID:9825045
Carter, B L
One of the primary impediments to successful drug R&D is the frequent failure of successfully translating positive results obtained in animal models to human disease. To a large degree, this discrepancy is secondary to the substantial biological differences between species. Non-human primate models have the advantage of significant physiological, metabolic, biochemical and genetic similarity to humans. Despite this advantage, there has been a relative paucity of non-human primate models used in the study of disease states that currently underlie the most common causes of morbidity and mortality, such as chronic myocardial ischemia leading to heart failure. This review describes a primate model of heart failure that closely mimics the cardiomyopathic process observed in humans. The primary advantage of this non-human primate model is that, unlike existing heart failure models, it allows for continuous study during progressive stages of heart failure, including myocardial ischemia, progressive left ventricular remodeling and end-stage congestive heart failure. In addition to this model of heart failure, other non-human primate models for cardiovascular drug R&D are also reviewed. PMID:20730697
This paper considers a model developed to study the cardiovascular control system response to orthostatic stress as induced by two variations of lower body negative pressure (LBNP) experiments. This modeling approach has been previously applied to study control responses to transition from rest to aerobic exercise, to transition to non-REM sleep and to orthostatic stress as produced by the head
Franz Kappel; Martin Fink; Jerry J. Batzel
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
Roytvarf, Alexander; Shusterman, Vladimir
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. PMID:25192922
Scarsoglio, Stefania; Guala, Andrea; Camporeale, Carlo; Ridolfi, Luca
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. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24930810
Sentürk, Damla; Dalrymple, Lorien S; Mu, Yi; Nguyen, Danh V
Hormonal replacement therapy becomes frequently used in peri- and postmenopausal women. It causally affects the climacteric syndrome, positively stimulates psychics, improves quality of the skin, decreases dryness of mucous membranes and frequency of recurrent inflammations of eyes and vagina. The positive influence on the bone metabolism and therefore on the incidence of osteoporosis highly dominates among its long-term effects. Long lasting hormonal replacement reduces also the incidence of Alzheimer disease, colorectal carcinoma and it has particularly favourable effect on the cardiovascular system. Estrogens positive affect the lipid spectrum, however, more than 50% of their beneficial influence comes from their direct vasodilatory effect. Estrogene replacement becomes in many countries indicated for the primary prevention of the ischemic heart disease. The question of its application for the secondary prevention remains still open. PMID:11284420
...Criteria for the Respiratory System, Cardiovascular System, Hearing Impairment, and Ear...presentations made by subject matter experts. VA plans to use this information...pertain to the following four body systems: (1) Respiratory...
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 regulation alone cannot be responsible for orthostatic hypotension after spaceflight. All of the astronauts in our study had an increase in sympathetic nerve activity during upright tilting on Earth postflight. This increase was well calibrated for the reduction in stroke volume induced by the upright posture. The results obtained from stimulating the sympathetic nervous system using handgrip exercise or cold stress were also entirely normal during and after spaceflight. No astronaut had reduced cerebral blood flow during upright tilt, and cerebral autoregulation was normal or even enhanced inflight. These experiments show that the cardiovascular adaptation to spaceflight does not lead to a defect in the regulation of blood vessel constriction via sympathetic nerve activity. In addition, cerebral autoregulation is well-maintained. It is possible that despite the increased sympathetic nerve activity, blood vessels did not respond with a greater degree of constriction than occurred preflight, possibly uncovering a limit of vasoconstrictor reserve.
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.
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
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. PMID:22480517
Vignon-Zellweger, Nicolas; Heiden, Susi; Miyauchi, Takashi; Emoto, Noriaki
With the advent of high heat loading capacity x-ray tubes, high frequency inverter type generators, and the use of spectral shaping filters, the automatic brightness/exposure control (ABC) circuit logic employed in the new generation of angiographic imaging equipment has been significantly reprogrammed. These new angiographic imaging systems are designed to take advantage of the power train capabilities to yield higher contrast images while maintaining, or lower, the patient exposure. Since the emphasis of the imaging system design has been significantly altered, the system performance parameters one is interested and the phantoms employed for the quality assurance must also change in order to properly evaluate the imaging capability of the cardiovascular imaging systems. A quality assurance (QA) phantom has been under development in this institution and was submitted to various interested organizations such as American Association of Physicists in Medicine (AAPM), Society for Cardiac Angiography & Interventions (SCA&I), and National Electrical Manufacturers Association (NEMA) for their review and input. At the same time, in an effort to establish a unified standard phantom design for the cardiac catheterization laboratories (CCL), SCA&I and NEMA have formed a joint work group in early 1997 to develop a suitable phantom. The initial QA phantom design has since been accepted to serve as the base phantom by the SCA&I- NEMA Joint Work Group (JWG) from which a comprehensive QA Phantom is being developed.
Lin, Pei-Jan P.
ObjectiveEpidemiological and clinical evidence indicate that inflammatory processes play a pivotal role in a number of conditions associated with aging, including osteoporosis and cardiovascular diseases. The purpose of this study was to evaluate cardiovascular pathology and select inflammatory mediators of interest in a model of low-grade inflammation-induced osteopenia.
Brenda J. Smith; Stan A. Lightfoot; Megan R. Lerner; Kent D. Denson; Daniel L. Morgan; Jay S. Hanas; Michael S. Bronze; Russell G. Postier; Daniel J. Brackett
A multichannel telemetry system was developed for use with chronically instrumented unrestrained cats. This system can simultaneously record efferent and afferent cardiovascular neural signals, bioelectrical noise arising near the electrode recording the neural signals, EEG, ECG, and a standard calibration signal. The miniature (18 cm3), lightweight (24 g), telemeter is a five-channel, time-multiplexed, pulse width modulation (PWM)/FM device employing a high frequency subcarrier (60 kHz) and two sampling frequencies (30 kHz and 6 kHz). The device is powered by two small 120 mA . h silver oxide cells; it has an indoor transmission range of 10 m and can operate for 48 h. One channel transmits a standard signal (a square wave of 100 Hz and 200 mVp-p) used to monitor and regulate the system's performance. When the variation in either the amplitude or frequency of the standard signal is greater than 10% of the control value, the transmitted bioelectrical signals are automatically discarded. PMID:426088
Yonezawa, Y; Ninomiya, I; Nishiura, N
The cardiovascular response to changes in posture has been the focus of numerous investigations in the past. Yet despite considerable, targeted experimental effort, the mechanisms underlying orthostatic intolerance (OI) ...
Heldt, Thomas, 1972-
This brief review summarizes current knowledge on the neural mechanisms of cardiovascular regulation during exercise in space, with specific emphasis on the role of the arterial baroreflex and the muscle metaboreflex, with the attendant modifications in autonomic nervous system activity, in determining the cardiovascular responses to exercise in microgravity conditions. Available data suggest that the muscle metaboreflex is enhanced during
Massimo Pagani; Paolo Pizzinelli; Silvia Beltrami; Michele Massaro; Daniela Lucini; Ferdinando Iellamo
The goal of this review is to examine the events that led to discovery of blood circulation. The Ancient Greeks, including Hippocrates and Galen viewed the cardiovascular system as comprising two distinct networks of arteries and veins. Galen claimed that the liver produced blood that was then distributed to the body in a centrifugal manner, whereas air or pneuma was absorbed from the lung into the pulmonary veins and carried by arteries to the various tissues of the body. Arteries also contained blood, which passed from the venous side via invisible pores in the interventricular septum and peripheral anastomoses. This was an open-ended system in which blood and air simply dissipated at the ends of veins and arteries according to the needs of the local tissue. Blood was not seen to circulate but rather to slowly ebb and flow. This view would hold sway for 15 centuries until 1628 when William Harvey published his momentous 72-page book, On the Motion of the Heart and Blood in Animals. Harvey employed experiment and deductive logic to show that arteries and veins are functionally, if not structurally, connected in the lung and the peripheral tissues, and that blood circulates. The mechanical force of the heart replaced Galen's elusive attractive powers. Ultimately, Galenism would collapse under the weight of Harvey's evidence, and a new paradigm of blood circulation would prevail. PMID:21781247
Aird, W C
This thesis presents a new system identification approach to non-invasive central cardiovascular monitoring problem. For this objective, this thesis will develop and analyze blind system identification and input signal ...
Hahn, Jin-Oh, Ph. D. Massachusetts Institute of Technology
Both the sympathetic nervous system and the renin–angiotensin–aldosterone system (RAAS) have central roles in vascular adaptive processes. Stimulation of the 2 systems has been demonstrated in a range of cardiovascular disorders, including congestive heart failure and hypertension. However, elucidation regarding the interactions of the many factors involved in these 2 systems is lacking. Angiotensin-converting enzyme inhibitors have been used to
Robert J. Cody
Effect of on-line conductivity plasma ultrafiltrate kinetic modeling on cardiovascular stability of hemodialysis patients. The aim of this multicenter, prospective, randomized cross-over study was to clarify whether on-line conductivity ultrafiltrate kinetic modeling (treatment B), as a substitute for sodium kinetic modeling, is capable of reducing intradialytic cardiovascular instability in comparison with standard treatment (treatment A), by reducing the sodium balance
Francesco Locatelli; Simeone Andrulli; Salvatore Di Filippo; Bruno Redaelli; Stefano Mangano; Carlo Navino; Rosario Ariano; Marco Tagliaferri; Tommaso Fidelio; Mauro Corti; Silvia Civardi; Ciro Tetta
A previously developed nonlinear model of the pacemaker-cardiovascular system (G.F. Inbar et al. ibid., vol.35, p.679-90, 1988) is converted to a linear model using a Taylor's series expansion procedure. As the expansion is about a steady-state value, the linear model operates at specified exercise levels. Using the linear forward-loop transfer function a root locus plot of the closed-loop s-plane poles
G. K. Hung
Vasopressin (VP) and oxytocin (OT) are mainly synthesized in the magnocellular neurons of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. Axons from the magnocellular part of the PVN and SON project to neurohypophysis where VP and OT are released in blood to act like hormones. Axons from the parvocellular part of PVN project to extra-hypothalamic brain areas (median eminence, limbic system, brainstem and spinal cord) where VP and OT act like neurotransmitters/modulators. VP and OT act in complementary manner in cardiovascular control, both as hormones and neurotransmitters. While VP conserves water and increases circulating blood volume, OT eliminates sodium. Hyperactivity of VP neurons and quiescence of OT neurons in PVN underlie osmotic adjustment to pregnancy. In most vascular beds VP is a potent vasoconstrictor, more potent than OT, except in the umbilical artery at term. The vasoconstriction by VP and OT is mediated via V1aR. In some vascular beds, i.e. the lungs and the brain, VP and OT produce NO dependent vasodilatation. Peripherally, VP has been found to enhance the sensitivity of the baro-receptor while centrally, VP and OT increase sympathetic outflow, suppresse baro-receptor reflex and enhance respiration. Whilst VP is an important mediator of stress that triggers ACTH release, OT exhibits anti-stress properties. Moreover, VP has been found to contribute considerably to progression of hypertension and heart failure while OT has been found to decrease blood pressure and promote cardiac healing. PMID:23997756
Peroxisome proliferator-activated receptor (PPAR)s are a family of three nuclear hormone receptors, PPAR?, -?, and -?, which are members of the steriod receptor superfamily. The first member of the family (PPAR?) was originally discovered as the mediator by which a number of xenobiotic drugs cause peroxisome proliferation in the liver. Defined functions for all these receptors, until recently, mainly concerned their ability to regulate energy balance, with PPAR? being involved in ?-oxidation pathways, and PPAR? in the differentiation of adipocytes. Little is known about the functions of PPAR?, though it is the most ubiquitously expressed. Since their discovery, PPARs have been shown to be expressed in monocytes/macrophages, the heart, vascular smooth muscle cells, endothelial cells, and in atherosclerotic lesions. Furthermore, PPARs can be activated by a vast number of compounds including synthetic drugs, of the clofibrate, and anti-diabetic thiazoldinedione classes, polyunsaturated fatty acids, and a number of eicosanoids, including prostaglandins, lipoxygenase products, and oxidized low density lipoprotein. This review will aim to introduce the field of PPAR nuclear hormone receptors, and discuss the discovery and actions of PPARs in the cardiovascular system, as well as the source of potential ligands. PMID:10696077
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...
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...
Acoustic radiation force impulse (ARFI) imaging has been previously described for the visualization of the cardiovascular system, including assessment of cerebral and lower-limb vascular disease, myocardial function, and cardiac RF ablation monitoring. Given that plaque imposes a 3-dimensional burden on the artery and that accurate visualization of all lesion borders are important for ablation guidance, it would be convenient if an entire plaque or lesion volume could be acquired, either using a 3D system or 2D freehand scanning. Currently, ARFI imaging uses single-frame acquisition, with acquisition times ranging from 100-200ms. Such a system would be cumbersome for real-time, freehand scanning. In this work, we evaluate the feasibility of using ARFI for freehand, real-time scanning of the cardiovascular system. New techniques are presented which acquire B-mode / ARFI/ and Color-flow Doppler (BACD) information in less than 50 ms. Freehand feasibility is evaluated by sweeping the BACD system across lesion phantoms and vascular phantoms modeling a thin-cap fibroatheroma at sweep rates currently utilized in conventional B-mode systems. Stationary in vivo BACD images were then formed from the carotid artery of a canine model, demonstrating the system's potential. The results suggest that little loss in either ARFI or Doppler quality occurs during translational-stage controlled, quasi-freehand sweeps.
Dumont, Douglas M.; Lee, Seung-Yun; Doherty, Joshua R.; Trahey, Gregg E.
A hallmark feature of Williams-Beuren Syndrome (WBS) is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH-oxidase (NOX)-mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated with elevated angiotensin II (angII), oxidative stress parameters, and Ncf1 expression. Genetic (by crossing with Ncf1 mutant) and/or pharmacological (with ang II type 1 receptor blocker, losartan, or NOX inhibitor apocynin) reduction of NOX activity controlled hormonal and biochemical parameters in DD mice, resulting in normalized blood pressure and improved cardiovascular histology. We provide strong evidence for implication of the redox system in the pathophysiology of the cardiovascular disease in a mouse model of WBS. The phenotype of these mice can be ameliorated by either genetic or pharmacological intervention reducing NOX activity, likely through reduced angII-mediated oxidative stress. Therefore, anti-NOX therapy merits evaluation to prevent the potentially serious cardiovascular complications of WBS, as well as in other cardiovascular disorders mediated by similar pathogenic mechanism. PMID:22319452
Campuzano, Victoria; Segura-Puimedon, Maria; Terrado, Verena; Sánchez-Rodríguez, Carolina; Coustets, Mathilde; Menacho-Márquez, Mauricio; Nevado, Julián; Bustelo, Xosé R; Francke, Uta; Pérez-Jurado, Luis A
Conventional risk factors (abnormal lipids, hypertension, etc.) are independent predictors of atherosclerosis and cardiovascular events; however, these factors are not specific since about half patients with acute myocardial infarction paradoxically result at low cardiovascular risk. Recent prospective studies provide convincing evidence that some psychosocial factors are independent predictors of atherosclerosis and cardiovascular events, as well. Psychosocial factors that promote atherosclerosis can be divided into two general categories: chronic stressors, including social isolation/low social support and work stress (subordination without job control) and emotional factors, including affective disorders such as depression, severe anxiety and hostility/anger. The emotional factors, such as the chronic stressors, activate the biological mechanisms of chronic stress: increased activity of the hypothalamic-pituitary-adrenal axis, sympathetic system and inflammation processes, which have atherogenic effects, and an increase in blood coagulation. In spite of the amount of published data, psychosocial factors receive little attention in the medical setting. About 30 years ago, Kuller defined the criteria for a causal relation between a risk factor and atherosclerosis and cardiac events. The first of these criteria states that experimental research should demonstrate that any new factor would increase the extent of atherosclerosis or its complications in suitable animal models. We carried out a bibliographic research in order to investigate whether the results of the studies dealing with animal examination and experimentation support the psychosocial factors as predictors of atherosclerosis. Contributions related to some of the psychosocial factors such as social isolation, subordination and hostility/anger have been found. In these studies atherosclerotic extension has been evaluated at necroscopy; however, the incidence of cardiovascular events has not been investigated. As regards the biological mechanisms of chronic stress, the hypothalamic-pituitary-adrenal axis and the sympathetic system have been investigated. The studies have mainly been carried out on primates, and, to a less extent, on other mammals such as rabbit and wolf and on some species of birds. In the animals under social isolation, subordination or hostility/anger, a significantly more severe atherosclerosis was present, besides an increased activity of the hypothalamic-pituitary-adrenal axis and sympathetic system. In conclusion, the results offered by animal models seem to satisfy the first of Kuller's criteria, as for the three above-mentioned psychosocial factors. PMID:17216916
Alboni, Paolo; Alboni, Marco
Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint. PMID:24903268
Dos Reis, Daniel Gustavo; Fortaleza, Eduardo Albino Trindade; Tavares, Rodrigo Fiacadori; Corrêa, Fernando Morgan Aguiar
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
Kunapuli, S P; Daniel, J L
Epidemiological studies show that adverse cardiovascular events peak in the morning (i.e., between 6 AM and noon) and that shift work is associated with cardiovascular disease, obesity, and diabetes. The endogenous circadian timing system modulates certain cardiovascular risk markers to be highest (e.g., cortisol, nonlinear dynamic heart rate control, and platelet activation) or to respond most unfavorably to stressors such as exercise (e.g., epinephrine, norepinephrine, and vagal cardiac modulation) at an internal body time corresponding to the time of day when adverse cardiovascular events most likely occur. This indicates that the circadian timing system and its interaction with external cardiovascular stressors (e.g., physical activity) could contribute to the morning peak in adverse cardiovascular events. Moreover, circadian misalignment and simulated night work have adverse effects on cardiovascular and metabolic function. This suggests that misalignment between the behavioral cycle and the circadian timing system in shift workers contributes to that population’s increased risk for cardiometabolic disease. PMID:22877674
Morris, Christopher J.; Yang, Jessica N.; Scheer, Frank A. J. L.
\\u000a Oxidative stress results from an imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant\\u000a systems, which detoxify the reactive intermediates. Diseases of the cardiovascular system, including atherosclerosis, diabetes,\\u000a cardiac hypertrophy, and congestive heart disease are characterized by enhanced production of ROS. In these conditions ROS\\u000a promote cardiovascular pathology in part by activating inflammatory signaling pathways. One
Bradford C. Berk
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
Guido Lastra; Sonal Dhuper; Megan S. Johnson; James R. Sowers
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.
Krutz, R. W.; Rader, R. D.; Meehan, J. P.; Henry, J. P.
Angiotensin II (Ang II), an endogenous peptide hormone, plays critical roles in the pathophysiological modulation of cardiovascular functions. Ang II is the principle effector of the renin-angiotensin system for maintaining homeostasis in the cardiovascular system, as well as a potent stimulator of NAD(P)H oxidase, which is the major source and primary trigger for reactive oxygen species (ROS) generation in various tissues. Recent accumulating evidence has demonstrated the importance of oxidative stress in Ang II-induced heart diseases. Here, we review the recent progress in the study on oxidative stress-mediated effects of Ang II in the cardiovascular system. In particular, the involvement of Ang II-induced ROS generation in arrhythmias, cell death/heart failure, ischemia/reperfusion injury, cardiac hypertrophy and hypertension are discussed. Ca2+/calmodulin-dependent protein kinase II is an important molecule linking Ang II, ROS and cardiovascular pathological conditions. PMID:24587981
Wen, Hairuo; Gwathmey, Judith K; Xie, Lai-Hua
??A cardio-protective adaptation associated with aerobic fitness may be an attenuated sympathetic nervous system (SNS) and cardiovascular response to stress. The hypothesis that the cardiovascular… (more)
Raymond, Duncan A
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 and probably prolong life, particularly music by Bach, Mozart or Italian composers. PMID:21062776
Background Humans and other organisms are equipped with a set of responses that can prevent damage from exposure to a multitude of endogenous and environmental stressors. If these stress responses are overwhelmed, this can result in pathogenesis of diseases, which is reflected by an increased development of, e.g., pulmonary and cardiac diseases in humans exposed to chronic levels of environmental stress, including inhaled cigarette smoke (CS). Systems biology data sets (e.g., transcriptomics, phosphoproteomics, metabolomics) could enable comprehensive investigation of the biological impact of these stressors. However, detailed mechanistic networks are needed to determine which specific pathways are activated in response to different stressors and to drive the qualitative and eventually quantitative assessment of these data. A current limiting step in this process is the availability of detailed mechanistic networks that can be used as an analytical substrate. Results We have built a detailed network model that captures the biology underlying the physiological cellular response to endogenous and exogenous stressors in non-diseased mammalian pulmonary and cardiovascular cells. The contents of the network model reflect several diverse areas of signaling, including oxidative stress, hypoxia, shear stress, endoplasmic reticulum stress, and xenobiotic stress, that are elicited in response to common pulmonary and cardiovascular stressors. We then tested the ability of the network model to identify the mechanisms that are activated in response to CS, a broad inducer of cellular stress. Using transcriptomic data from the lungs of mice exposed to CS, the network model identified a robust increase in the oxidative stress response, largely mediated by the anti-oxidant NRF2 pathways, consistent with previous reports on the impact of CS exposure in the mammalian lung. Conclusions The results presented here describe the construction of a cellular stress network model and its application towards the analysis of environmental stress using transcriptomic data. The proof-of-principle analysis described here, coupled with the future development of additional network models covering distinct areas of biology, will help to further clarify the integrated biological responses elicited by complex environmental stressors such as CS, in pulmonary and cardiovascular cells. PMID:22011616
Most cardiovascular activities show a circadian rhythm, as do electrophysiological phenomenon. Under theinfluence of both external stimuli and endogenous homoeostatic mechanisms, cardiac electrophysiologicalproperties change diurnally and enable the cardiovascular system adapt to rest-exercise cycles. According torecent reports, almost all non-invasive electrophysiological phenomena, such as electrocardiographic indices,cardiac refractoriness and conduction, pacing and defibrillation threshold, heart rate variability indices, andeven Q-T dispersion
Yi-Fang Guo; Phyllis K. Stein
\\u000a The purpose of this chapter is to introduce the reader to cardiovascular physiology and pathology. These are vast, complex\\u000a subjects, each filling large tomes and severely exercising the memory of medical students. By necessity, this will be a very\\u000a brief and, in places, simplistic introduction to the subject. Despite its simplicity, it can be very daunting to the newcomer\\u000a who
Marc Thiriet; Kim H. Parker
Abuse of anabolic androgenic steroids (AAS) has been linked to a variety of different cardiovascular side effects. In case reports, acute myocardial infarction is the most common event presented, but other adverse cardiovascular effects such as left ventricular hypertrophy, reduced left ventricular function, arterial thrombosis, pulmonary embolism and several cases of sudden cardiac death have also been reported. However, to date there are no prospective, randomized, interventional studies on the long-term cardiovascular effects of abuse of AAS. In this review we have studied the relevant literature regarding several risk factors for cardiovascular disease where the effects of AAS have been scrutinized:(1) Echocardiographic studies show that supraphysiologic doses of AAS lead to both morphologic and functional changes of the heart. These include a tendency to produce myocardial hypertrophy (Fig. 3), a possible increase of heart chamber diameters, unequivocal alterations of diastolic function and ventricular relaxation, and most likely a subclinically compromised left ventricular contractile function. (2) AAS induce a mild, but transient increase of blood pressure. However, the clinical significance of this effect remains modest. (3) Furthermore, AAS confer an enhanced pro-thrombotic state, most prominently through an activation of platelet aggregability. The concomitant effects on the humoral coagulation cascade are more complex and include activation of both pro-coagulatory and fibrinolytic pathways. (4) Users of AAS often demonstrate unfavorable measurements of vascular reactivity involving endothelial-dependent or endothelial-independent vasodilatation. A degree of reversibility seems to be consistent, though. (5) There is a comprehensive body of evidence documenting that AAS induce various alterations of lipid metabolism. The most prominent changes are concomitant elevations of LDL and decreases of HDL, effects that increase the risk of coronary artery disease. And finally, (6) the use of AAS appears to confer an increased risk of life-threatening arrhythmia leading to sudden death, although the underlying mechanisms are still far from being elucidated. Taken together, various lines of evidence involving a variety of pathophysiologic mechanisms suggest an increased risk for cardiovascular disease in users of anabolic androgenic steroids. PMID:20020375
Vanberg, Paul; Atar, Dan
Aims To describe change in self-reported diet and plasma vitamin C, and to examine associations between change in diet and cardiovascular disease risk factors and modelled 10-year cardiovascular disease risk in the year following diagnosis of Type 2 diabetes. Methods Eight hundred and sixty-seven individuals with screen-detected diabetes underwent assessment of self-reported diet, plasma vitamin C, cardiovascular disease risk factors and modelled cardiovascular disease risk at baseline and 1 year (n = 736) in the ADDITION-Cambridge trial. Multivariable linear regression was used to quantify the association between change in diet and cardiovascular disease risk at 1 year, adjusting for change in physical activity and cardio-protective medication. Results Participants reported significant reductions in energy, fat and sodium intake, and increases in fruit, vegetable and fibre intake over 1 year. The reduction in energy was equivalent to an average-sized chocolate bar; the increase in fruit was equal to one plum per day. There was a small increase in plasma vitamin C levels. Increases in fruit intake and plasma vitamin C were associated with small reductions in anthropometric and metabolic risk factors. Increased vegetable intake was associated with an increase in BMI and waist circumference. Reductions in fat, energy and sodium intake were associated with reduction in HbA1c, waist circumference and total cholesterol/modelled cardiovascular disease risk, respectively. Conclusions Improvements in dietary behaviour in this screen-detected population were associated with small reductions in cardiovascular disease risk, independently of change in cardio-protective medication and physical activity. Dietary change may have a role to play in the reduction of cardiovascular disease risk following diagnosis of diabetes. PMID:24102972
Savory, L A; Griffin, S J; Williams, K M; Prevost, A T; Kinmonth, A-L; Wareham, N J; Simmons, R K
Nitric Oxide (NO) is a small molecule that continues to attract much attention from the scientific community. Since its discovery, it has been evident that NO has a crucial role in the modulation of vascular tone. Moreover, NO is involved in multiple signal transduction pathways thus contributing to the regulation of many cellular functions. NO effects can be either dependent or independent on cGMP, and rely also upon several mechanisms such as the amount of NO, the compartmentalization of the enzymes responsible for its biosynthesis (NOS), and the local redox conditions. Several evidences highlighted the correlation among adrenoreceptors activity, vascular redox status and NO bioavailability. It was suggested a possible crosstalk between NO and oxidative stress hallmarks in the endothelium function and adaptation, and in sympathetic vasoconstriction control. Adrenergic vasoconstriction is a balance between a direct vasoconstrictive effect on smooth muscle and an indirect vasorelaxant action caused by ?2- and ?-adrenergic endothelial receptor-triggered NO release. An increased oxidative stress and a reduction of NO bioavailability shifts this equilibrium causing the enhanced vascular adrenergic responsiveness observed in hypertension. The activity of NOS contributes to manage the adrenergic pathway, thus supporting the idea that the endothelium might control or facilitate ?-adrenergic effects on the vessels and the polymorphic variants in ?2-receptors and NOS isoforms could influence aging, some pathological conditions and individual responses to drugs. This seems to be dependent, almost in part, on differences in the control of vascular tone exerted by NO. Given its involvement in such important mechanisms, the NO pathway is implicated in aging process and in both cardiovascular and non-cardiovascular conditions. Thus, it is essential to pinpoint NO involvement in the regulation of vascular tone for the effective clinical/therapeutic management of cardiovascular diseases (CVD). PMID:24223559
Conti, Valeria; Russomanno, Giusy; Corbi, Graziamaria; Izzo, Viviana; Vecchione, Carmine; Filippelli, Amelia
Narrative ReviewGiven the prevalence of cardiovascular and pulmonary (CV-P) disease, it is likely that a substantial portion of patients seeking services from hand therapists have diagnosed or yet to be diagnosed disease in one or both of these systems. Pain originating from these systems is more common in the chest, shoulder, and scapular regions, but both systems can refer pain
Mark D. Weber
The renin-angiotensin system is central to the pathophysiology of a number of cardiovascular disorders. Most obviously this is so with renin secreting tumours, but the system is of central importance in other disorders such as scleroderma renal crisis and most cases of malignant hypertension. Activation of the renin-angiotensin system in unilateral renal artery stenosis is pivotal to the development of
MG Nicholls; AM Richards; M Agarwal
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 ...
Scarsoglio, Stefania; Camporeale, Carlo; Ridolfi, Luca
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.
Charles, John B.; Bungo, Michael W.
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 the modeling of fluids in vessels with smaller diameters and a method for introducing the deformational forces exerted on the arterial flows from the movement of the heart by borrowing concepts from cosmodynamics are presented. These additional forces have a great impact on the endothelial shear stress. Third, the fluid model is extended to not only recover Navier-Stokes hydrodynamics, but also a wider range of Knudsen numbers, which is especially important in micro- and nano-scale flows. The tradeoffs of many optimizations methods such as the use of deep halo level ghost cells that, alongside hybrid programming models, reduce the impact of such higher-order models and enable efficient modeling of extreme regimes of computational fluid dynamics are discussed. Fourth, the extension of these models to other research questions like clogging in microfluidic devices and determining the severity of co-arctation of the aorta is presented. Through this work, a validation of these methods by taking real patient data and the measured pressure value before the narrowing of the aorta and predicting the pressure drop across the co-arctation is shown. Comparison with the measured pressure drop in vivo highlights the accuracy and potential impact of such patient specific simulations. Finally, a method to enable the simulation of longer trajectories in time by discretizing both spatially and temporally is presented. In this method, a serial coarse iterator is used to initialize data at discrete time steps for a fine model that runs in parallel. This coarse solver is based on a larger time step and typically a coarser discretization in space. Iterative refinement enables the compute-intensive fine iterator to be modeled with temporal parallelization. The algorithm consists of a series of prediction-corrector iterations completing when the results have converged within a certain tolerance. Combined, these developments allow large fluid models to be simulated for longer time durations than previously possible.
Randles, Amanda Elizabeth
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.
Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.
A bidirectional association between mood disorders and cardiovascular diseases has been described in humans, yet the precise neurobiological mechanisms that underlie this association are not fully understood. This article is focused on neurobiological processes and mediators in mood and cardiovascular disorders, with an emphasis on common mechanisms including stressor reactivity, neuroendocrine and neurohumoral changes, immune alterations, autonomic and cardiovascular dysregulation, and central neurotransmitter and neuropeptide dysfunction. A discussion of the utility of experimental investigations with rodent models, including those in rats and prairie voles (Microtus ochrogaster), is presented. Specific studies using these models are reviewed, focusing on the analysis of behavioral, physiological and neural mechanisms underlying depressive disorders and cardiovascular disease. Considered in combination with studies using human samples, the investigation of mechanisms underlying depressive behaviors and cardiovascular regulation using animal models will enhance our understanding of the association of depression and cardiovascular disease, and will promote the development of improved interventions for individuals with these detrimental disorders. PMID:18703084
Grippo, Angela J
The cardiovascular effects of levocarnitine chloride (LC-80) were investigated in in vitro and in vivo experiments, and the following results were obtained: (1) In isolated rabbit cardiac muscle preparations, LC-80 at the high concentration of 10(-2) M had little influence on the atrial rate of spontaneously beating right atria, while it caused a gradual increase in the contractile tension of both spontaneously beating right atria and electrically driven papillary muscle that reached a maximum level after 10 min of administration and lasted for 20-30 min. However, the LC-80-induced positive inotropic effect may be negligible in whole animal experiments or clinical trials, since it was elicited only after the administration of LC-80 in an extremely large dose. Furthermore, LC-80 in a high concentration (10(-2) M) had no influence on the isoproterenol-induced positive inotropic effect in electrically driven papillary muscles. (2) LC-80 in high concentrations of 10(-3)-10(-2) M did not affect the high K+-induced contraction in isolated canine left circumflex coronary artery and saphenous vein. (3) In anesthetized dogs, intraarterial injection of LC-80 in high doses of up to 10 mg did not change the blood flow of coronary, femoral, renal, mesenteric or vertebral arteries and on the adenosine-induced vasodilator action. (4) In anesthetized dogs, intravenous injection of LC-80 in doses of 100-300 mg/kg did not modify the blood pressure responses induced by norepinephrine, acetylcholine, carotid occlusion and vagal stimulation. These results suggest that the cardiovascular effects of LC-80 are extremely mild or negligible. Therefore, LC-80 may be a drug having a new pharmacological feature in its mechanism which enables it to exert a beneficial effect in the treatment of ischemic heart disease, being different from the commonly used antianginal drugs. PMID:2731806
Kirimoto, T; Morikawa, Y; Yamada, H; Fujisawa, S; Hironaka, Y
2006-1968: TEACHING BASIC CARDIO-VASCULAR MECHANICS WITH LEGO MODELS: A HIGH SCHOOL CASE STUDY worked with LEGO to develop ROBOLAB, a robotic approach to learning science and math. Â© American Society for Engineering Education, 2006 #12;Teaching Basic Cardio-Vascular Mechanics With LEGO Models: A High School Case
Cardiovascular disease (CVD) is the leading cause of death for Latinos living in the United States. This population is generally unaware of important lifestyle or behavioral changes that can prevent CVD. The National Heart, Lung, and Blood Institute (NHLBI) designed and implemented Salud para su Corazón (Health for Your Heart), a culturally appropriate, community-based, theory-driven intervention model. NHLBI's goals were:
Rina Alcalay; Matilde Alvarado; Hector Balcazar; Eileen Newman; Elmer Huerta
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…
Chen, Edith; Lee, William K.; Cavey, Lisa; Ho, Amanda
Rationale Depression is associated with medical comorbidities, particularly cardiovascular disease. However, mechanisms linking depression and cardiovascular disease remain unclear. Objectives This study investigated whether the rat resident–intruder model of social stress would elicit behavioral dysfunctions and autonomic changes characteristic of psychiatric/cardiovascular comorbidity. Furthermore, the efficacy of the corticotropin-releasing factor-1 (CRF1) receptor antagonist, NBI-30775 (NBI), or the tricyclic antidepressant, desipramine (DMI), to prevent social stress-induced behavioral, neuroendocrine, and cardiovascular changes were evaluated. Methods Adult male rats were exposed to resident–intruder stress (seven consecutive days) and systemically administered NBI (10 mg/kg/7 days), DMI (10 mg/kg/14 days), or vehicle. The efficacy of NBI and DMI to alter the behavioral and neuroendocrine responses to social stress was assessed. Furthermore, their effects on stress-induced forced swim behavior (FST), bladder and adrenal weight, and heart rate variability (HRV) were examined. Results NBI, but not DMI, increased time spent in an upright, defensive posture and the latency to submit to the resident. Additionally, only NBI reduced social stress-induced adrenocorticotropic hormone and corticosterone release. Social stress increased FST immobility, caused bladder and adrenal hypertrophy, and decreased HRV. Both NBI and DMI blocked stress-induced increases in immobility during the FST. However, only NBI inhibited social stress-induced adrenal and bladder hypertrophy and decreases in heart rate variability. Conclusions Rat resident–intruder stress paradigm models aspects of psychiatric/medical comorbidity. Furthermore, the CRF system may contribute to both the behavioral response during social stress and its behavioral and autonomic consequences, offering insight into potential therapy to treat these comorbid conditions. PMID:22322324
McFadden, Kile V.; Grigoriadis, Dimitri; Bhatnagar, Seema; Valentino, Rita J.
A compelling association has been observed between cardiovascular disease (CVD) and depression, suggesting individuals with depression to be at significantly higher risk for CVD and CVD-related mortality. Systemic immune activation, hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, arterial stiffness and endothelial dysfunction have been frequently implicated in this relationship. Although a differential epidemiological association between CVD and depression subtypes is evident, it has not been determined if this indicates subtype specific biological mechanisms. A comprehensive systematic literature search was conducted using PubMed and PsycINFO databases yielding 147 articles for this review. A complex pattern of systemic immune activation, endothelial dysfunction and HPA axis hyperactivity is suggestive of the biological relationship between CVD and depression subtypes. The findings of this review suggest that diagnostic subtypes rather than a unifying model of depression should be considered when investigating the bidirectional biological relationship between CVD and depression. The suggested model of a subtype-specific biological relationship between depression and CVDs has implications for future research and possibly for diagnostic and therapeutic processes. PMID:22832857
Baune, B T; Stuart, M; Gilmour, A; Wersching, H; Heindel, W; Arolt, V; Berger, K
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…
Ahopelto, Ilona; Mikkila-Erdmann, Mirjamaija; Olkinuora, Erkki; Kaapa, Pekka
Background\\/Purpose: Endothelin is a potent biological vasoactive mediator in the cardiovascular and renal systems. Little is known of the effects of endothelin antagonism on the developing heart and kidney, and we hope to show that endothelin does have an important role in the cardiovascular and renal systems of the developing neonate. In this study the authors have examined the effects
Anthony Chin; Jayant Radhakrishnan; Linda Fornell; Eunice John
The aim was to study the effects of C-type natriuretic peptide (CNP) on mean arterial pressure (MAP) and the cardiovascular nitric oxide (NO) system in spontaneously hypertensive rats (SHR), and to investigate the signaling pathways involved in this interaction. SHR and WKY rats were infused with saline or CNP. MAP and nitrites and nitrates excretion (NOx) were determined. Catalytic NO
Carolina Caniffi; Rosana Elesgaray; Mariela Gironacci; Cristina Arranz
The aims were to evaluate the role of cardiovascular nitric oxide (NO)-system in C-type natriuretic peptide (CNP) actions and to investigate receptor types and signaling pathways involved in this interaction. Wistar rats were infused with saline or CNP. Mean arterial pressure (MAP) and nitrites and nitrates (NOx) excretion were determined. NO synthase (NOS) activity and NOS expression (Western blot) were
Rosana Elesgaray; Carolina Caniffi; Andrea Fellet; Cristina Arranz
PurposePolycystic ovary syndrome (PCOS) is frequently accompanied by the presence of cardiovascular risk factors. It has also been recognized that there is a significant relationship between the autonomic nervous system and adverse cardiac events. Heart rate recovery (HRR) after exercise is a marker of parasympathetic activity and attenuation of this parameter has been shown to be associated with increased cardiac
Göknur Tekin; Abdullah Tekin; Esra B. K?l?çarslan; Bülent Haydardedeo?lu; Tuna Kat?rc?ba??; Tolga Koçum; Tansel Erol; Yücel Çölkesen; Alpay T. Sezgin; Haldun Müderriso?lu
Halothane attenuates the alterations in arterial pressure (BP) and heart rate (HR) produced by central nervous system (CNS) stimulation. We examined the effects of the a2-adrenergic agonist dexmedetomidine, with and without halothane, on cardiovascular regulation dur- ing CNS pressor site stimulation in chronically instru- mented cats. Stimuli trains via bipolar stimulating elec- trodes in the hypothalamus and reticular formation elicited
Neil E. Farber; Enric Samso; Michael Staunton; David Schwabe; William T. Schmeling
A direct, continuous, and independent relation between blood pressure and the incidence of various cardiovascular events, such as stroke and myocardial infarction, is now well accepted. The increase in risk can be attributed to structural and functional changes in target organs. Central to many of these pathophysiologic processes is the renin-angiotensin system (RAS), specifically, angiotensin II. Binding of angiotensin II
Abstract Significance: Oxidants were once principally considered perpetrators of injury and disease. However, this has become an antiquated view, with cumulative evidence showing that the oxidant hydrogen peroxide serves as a signaling molecule. Hydrogen peroxide carries vital information about the redox state of the cell and is crucial for homeostatic regulation during health and adaptation to stress. Recent Advances: In this review, we examine the contemporary concepts for how hydrogen peroxide is sensed and transduced into a biological response by introducing post-translational oxidative modifications on select proteins. Oxidant sensing and signaling by kinases are of particular importance as they integrate oxidant signals into phospho-regulated pathways. We focus on CAMKII, PKA, and PKG, kinases whose redox regulation has notable impact on cardiovascular function. Critical Issues: In addition, we examine the mechanism for regulating intracellular hydrogen peroxide, considering the net concentrations that may accumulate. The effects of endogenously generated oxidants are often modeled by applying exogenous hydrogen peroxide to cells or tissues. Here we consider whether model systems exposed to exogenous hydrogen peroxide have relevance to systems where the oxidant is generated endogenously, and if so, what concentration can be justified in terms of relevance to health and disease. Future Directions: Improving our understanding of hydrogen peroxide signaling and the sensor proteins that it can modify will help us develop new strategies to regulate intracellular signaling to prevent disease. Antioxid. Redox Signal. 18, 1042–1052. PMID:22867279
Burgoyne, Joseph R.; Oka, Shin-ichi; Ale-Agha, Niloofar
\\u000a In this chapter we summarize the commonly used animal models employed in the study of cardiovascular diseases and diabetes,\\u000a two of the most prevalent oxidative stress-induced diseases. A number of animal models of atherosclerosis support the notion\\u000a that reactive oxygen and nitrogen species have a causal role in atherosclerosis and other vascular diseases. Experimental\\u000a atherosclerosis is induced by specific lipid-rich
Maria D. Mesa; Concepcion M. Aguilera; Angel Gil
Objective To use measures of CSF 5HIAA and MAOA-uVNTR genotype to study the role of central nervous system (CNS) serotonin in clustering of hostility, and other psychosocial, metabolic and cardiovascular endophenotypes. Methods In 86 healthy men, we evaluated cerebrospinal fluid (CSF) levels of the primary serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA) and genotype on a functional promoter polymorphism of the monoamine oxidase A gene (M-uVNTR) for association with 29 variables assessing hostility, other psychosocial, metabolic, neuroendocrine and cardiovascular endophenotypes. Results The correlations of 5HIAA with these endophenotypes in men with more active MAOA-uVNTR alleles were significantly different from those with less active alleles for 15 of 29 endophenotypes. MAOA-uVNTR phenotype and CSF 5HIAA interacted to explain 20% and 22% of the variance, respectively, in scores on one factor wherein high scores reflected a less healthy psychosocial profile and a second factor wherein high score reflected increased insulin resistance, BMI, blood pressure and hostility. In men with less active alleles, higher 5HIAA was associated with more favorable profiles of hostility, other psychosocial, metabolic and cardiovascular endophenotypes; in men with more active alleles, higher 5HIAA was associated with less favorable profiles. Conclusions These findings indicate that in men indices of CNS serotonin function influence the expression and clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes that have been shown to increase risk of developing cardiovascular disease. The findings are consistent with the hypothesis that increased CNS serotonin is associated with a more favorable psychosocial/metabolic/cardiovascular profile, while decreased CNS serotonin function is associated with a less favorable profile. PMID:20595415
Williams, Redford B.; Surwit, Richard S.; Siegler, Ilene C.; Ashley-Koch, Allison E.; Collins, Ann L.; Helms, Michael J.; Georiades, Anastasia; Boyle, Stephen H.; Brummett, Beverly H.; Barefoot, John C.; Grichnik, Katherine; Stafford-Smith, Mark; Kuhn, Cynthia M.
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.
Samsonov, S. N.
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. PMID:15320794
Sanz-González, Silvia M; Cano, Antonio; Valverde, M A; Hermenegildo, Carlos; Andrés, Vicente
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.
Little, Mark; Vandoolaeghe, Wendy; Gola, Anna; Tzoulaki, Ioanna
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.
Tipton, David A.
In its classical definition, the renin-angiotensin system (RAS) acts predominantly by endocrine mechanisms. This view has been modified since several components of the RAS and their mRNAs were found in peripheral tissues. These findings gave rise to the concept of local tissue renin-angiotensin systems. Although no cells of cardiovascular organs containing a complete RAS have been identified as of this
Philippe Stock; Lutz Liefeldt; Martin Paul; Detlev Ganten
Congenital heart defects (CHDs) impact in utero embryonic viability, children, and surviving adults. Since the first transfer of genes into mice, transgenic mouse models have enabled researchers to experimentally study and genetically test the roles of genes in development, physiology, and disease progression. Transgenic mice have become a bona fide human CHD pathology model and their use has dramatically increased within the past two decades. Now that the entire mouse and human genomes are known, it is possible to knock out, mutate, misexpress, and/or replace every gene. Not only have transgenic mouse models changed our understanding of normal development, CHD processes, and the complex interactions of genes and pathways required during heart development, but they are also being used to identify new avenues for medical therapy. PMID:21377625
Snider, Paige; Conway, Simon J.
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).
Hooker, John C.
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
Watts, Stephanie W
SOMETIMES, differences are, simply, annoying. Sometimes, they are illuminating and provide insight into hitherto hidden mech- anisms. So it appears to be when considering the cardiovascu- lar function and dysfunction of women and men. The purpose of this article is to highlight the features of cardiovascular function (e.g., pumping of the heart, blood flow control, pres- sure regulation, and solute
Virginia H. Huxley
This paper reports the use of a magnetic resonance imaging (MRI) system to propel a ferromagnetic core. The concept was studied for future development of microdevices designed to perform minimally invasive interventions in remote sites accessible through the human cardiovascular system. A mathematical model is described taking into account various parameters such as the size of blood vessels, the velocities and viscous properties of blood, the magnetic properties of the materials, the characteristics of MRI gradient coils, as well as the ratio between the diameter of a spherical core and the diameter of the blood vessels. The concept of magnetic propulsion by MRI is validated experimentally by measuring the flow velocities that magnetized spheres (carbon steel 1010/1020) can withstand inside cylindrical tubes under the different magnetic forces created with a Siemens Magnetom Vision 1.5 T MRI system. The differences between the velocities predicted by the theoretical model and the experiments are approximately 10%. The results indicate that with the technology available today for gradient coils used in clinical MRI systems, it is possible to generate sufficient gradients to propel a ferromagnetic sphere in the larger sections of the arterial system. In other words, the results show that in the larger blood vessels where the diameter of the microdevices could be as large as a couple a millimeters, the few tens of mT/m of gradients required for displacement against the relatively high blood flow rate is well within the limits of clinical MRI systems. On the other hand, although propulsion of a ferromagnetic core with diameter of approximately 600 microm may be possible with existing clinical MRI systems, gradient amplitudes of several T/m would be required to propel a much smaller ferromagnetic core in small vessels such as capillaries and additional gradient coils would be required to upgrade existing MRI systems for operations at such a scale. PMID:16485758
Mathieu, Jean-Baptiste; Beaudoin, Gilles; Martel, Sylvain
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 inc...
B. D. Levine, J. A. Pawelczyk, J. Zuckerman, R. Zhang, Q. Fu K. Iwasaki, C. Ray, C. G. Blomqvist, L. D. Lane, C. A. Giller
Background Cardiovascular disease is the leading cause of death worldwide. Like many countries, Australia is currently changing its guidelines for cardiovascular disease prevention from drug treatment for everyone with ‘high blood pressure’ or ‘high cholesterol’, to prevention based on a patient’s absolute risk. In this research, we model cost-effectiveness of cardiovascular disease prevention with blood pressure and lipid drugs in Australia under three different scenarios: (1) the true current practice in Australia; (2) prevention as intended under the current guidelines; and (3) prevention according to proposed absolute risk levels. We consider the implications of changing to absolute risk-based cardiovascular disease prevention, for the health of the Australian people and for Government health sector expenditure over the long term. Methods We evaluate cost-effectiveness of statins, diuretics, ACE inhibitors, calcium channel blockers and beta-blockers, for Australian men and women, aged 35 to 84?years, who have never experienced a heart disease or stroke event. Epidemiological changes and health care costs are simulated by age and sex in a discrete time Markov model, to determine total impacts on population health and health sector costs over the lifetime, from which we derive cost-effectiveness ratios in 2008 Australian dollars per quality-adjusted life year. Results Cardiovascular disease prevention based on absolute risk is more cost-effective than prevention under the current guidelines based on single risk factor thresholds, and is more cost-effective than the current practice, which does not follow current clinical guidelines. Recommending blood pressure-lowering drugs to everyone with at least 5% absolute risk and statin drugs to everyone with at least 10% absolute risk, can achieve current levels of population health, while saving $5.4 billion for the Australian Government over the lifetime of the population. But savings could be as high as $7.1 billion if Australia could match the cheaper price of statin drugs in New Zealand. Conclusions Changing to absolute risk-based cardiovascular disease prevention is highly recommended for reducing health sector spending, but the Australian Government must also consider measures to reduce the cost of statin drugs, over and above the legislated price cuts of November 2010. PMID:22657090
Background The purpose of the present study was to develop and evaluate a risk score to predict people at high risk of cardiovascular autonomic dysfunction neuropathy (CAN) in Chinese population. Methods and Materials A population-based sample of 2,092 individuals aged 30–80 years, without previously diagnosed CAN, was surveyed between 2011 and 2012. All participants underwent short-term HRV test. The risk score was derived from an exploratory set. The risk score was developed by stepwise backward multiple logistic regression. The coefficients from this model were transformed into components of a CAN score. This score was tested in a validation and entire sample. Results The final risk score included age, body mass index, hypertension, resting hear rate, items independently and significantly (P<0.05) associated with the presence of previously undiagnosed CAN. The area under the receiver operating curve was 0.726 (95% CI 0.686–0.766) for exploratory set, 0.784 (95% CI 0.749–0.818) for validation set, and 0.756 (95% CI 0.729–0.782) for entire sample. In validation set, at optimal cutoff score of 5 of 10, the risk score system has the sensitivity, specificity, and percentage that needed subsequent testing were 69, 78, and 30%, respectively. Conclusion We developed a CAN risk score system based on a set of variables not requiring laboratory tests. The score system is simple fast, inexpensive, noninvasive, and reliable tool that can be applied to early intervention to delay or prevent the disease in China. PMID:24621478
Zeng, Fangfang; Tang, Zi-Hui; Wang, Ying-Wei
Abstract The transient receptor potential (TRP) family of ion channels is a large family of cation selective ion channels, which are expressed and functional in a variety of tissues. In this review we focus on the most recent results detailing the role of TRP channels in the cardiovascular system. The presented results underscore the role of TRP channels in cardiomyocytes, smooth cells and endothelium, and in disease states such as hypertension, cardiac conduction block and cardiac hypertrophy. PMID:21173080
In children five to seven years of age, the adaptation of their cardiovascular system to a high physical activity as related\\u000a to their individual somatic characteristics was studied. The methods of rheography and bicycle ergometry were used under physical\\u000a loads with the power increasing from 1 and 1.5 W\\/kg body weight. During exercises, load grading according to the body’s somatic
V. I. Kuznetsov; V. N. Prokofieva
Background: We wished to investigate potential causes of dialysis-induced hypotension (DIH), including the attenuated cardiovascular response to sympathetic system activation during exercise and myocardial dysfunction. Methods: This study included 26 end-stage renal disease (ESRD) patients with DIH, 30 ESRD patients without DIH (Non-DIH), and 30 control subjects. Each patient was evaluated with echocardiography and a symptom-limited treadmill stress test. The
Hakan Fotbolcu; Dursun Duman; Vecih Oduncu; Cihan Cevik; Kursat Tigen; Emre Özker; Yelda Basaran
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.
Yu, Zong-Han; Wu, Chun-Ming; Lin, Yo-Wei; Chuang, Ming-Lung; Tsai, Jui-che; Sun, Chia-Wei
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.
Baker, J. T.
Development of novel drugs relies on research to discover new drugs. Testing and evaluating new drugs on human subjects are usually impossible because of ethical concerns. Therefore, for drug discovery research, it is essential to establish animal models of human diseases. Numerous animal models have been developed and used in drug discovery and evaluation studies. Such animal models have had important roles in developing new drugs as well as understanding the etiologies of diseases. In the field of cardiovascular drugs, several interesting animal models are currently in use. These include, transgenic mice carrying both human renin and human angiotensinogen genes, Watanabe's heritable hyperlipidemic rabbits, rats with pulmonary hypertension induced by monocrotaline, myocardial infarction model, cardial hypertrophy model and photochemical thrombosis models. It is envisaged that for drug discovery and development, the search for more physiological animal models will continue in the future. PMID:8406232
Nakashima, M; Umemura, K; Takiguchi, Y
In heart failure (HF), exercise has been shown to modulate cardiac sympathetic hyperactivation which is one of the earliest features of neurohormonal derangement in this syndrome and correlates with adverse outcome. An important molecular alteration related to chronic sympathetic overstimulation in HF is represented by cardiac ?-adrenergic receptor (?-AR) dysfunction. It has been demonstrated that exercise reverses ?-AR dysfunction by restoring cardiac receptor membrane density and G-protein-dependent adenylyl cyclase activation. In particular, several evidence indicate that exercise reduces levels of cardiac G-protein coupled receptor kinase-2 (GRK2) which is known to be involved in both ?1-AR and ?2-AR dysregulation in HF. Similar alterations of ?-AR system have been described also in the senescent heart. It has also been demonstrated that exercise training restores adrenal GRK2/?-2AR/catecholamine (CA) production axis. At vascular level, exercise shows a therapeutic effect on age-related impairment of vascular reactivity to adrenergic stimulation and restores ?-AR-dependent vasodilatation by increasing vascular ?-AR responsiveness and reducing endothelial GRK2 activity. Sympathetic nervous system overdrive is thought to account for >50% of all cases of hypertension and a lack of balance between parasympathetic and sympathetic modulation has been observed in hypertensive subjects. Non-pharmacological, lifestyle interventions have been associated with reductions in SNS overactivity and blood pressure in hypertension. Several evidence have highlighted the blood pressure lowering effects of aerobic endurance exercise in patients with hypertension and the significant reduction in sympathetic neural activity has been reported as one of the main mechanisms explaining the favorable effects of exercise on blood pressure control. PMID:24348425
Leosco, Dario; Parisi, Valentina; Femminella, Grazia D.; Formisano, Roberto; Petraglia, Laura; Allocca, Elena; Bonaduce, Domenico
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.
Sheridan, P.J.; McGill, H.C. Jr.
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.
Li, Xing D.; Stamper, Debra L.; Patel, Nirlep A.; Saunders, Kathleen; Plummer, Sam; Schenck, John; Rogowska, Ika; Fujimoto, James G.; Brezinski, Mark E.
Background The aim of this study was to determine the hemodynamic effects of various support modes of continuous flow left ventricular assist devices (CF-LVADs) on the cardiovascular system using a numerical cardiovascular system model. Material/Methods Three support modes were selected for controlling the CF-LVAD: constant flow mode, constant speed mode, and constant pressure head mode of CF-LVAD. The CF-LVAD is established between the left ventricular apex and the ascending aorta, and was incorporated into the numerical model. Various parameters were evaluated, including the blood assist index (BAI), the left ventricular external work (LVEW), the energy of blood flow (EBF), pulsatility index (PI), and surplus hemodynamic energy (SHE). Results The results show that the constant flow mode, when compared to the constant speed mode and the constant pressure head mode, increases LVEW by 31% and 14%, and EBF by 21% and 15%, respectively, indicating that this mode achieved the best ventricular unloading among the 3 support modes. As BAI is increased, PI and SHE are gradually decreased, whereas PI of the constant pressure head reaches the maximum value. Conclusions The study demonstrates that the continuous flow control mode of the CF-LVAD may achieve the highest ventricular unloading. In contrast, the constant rotational speed mode permits the optimal blood perfusion. Finally, the constant pressure head strategy, permitting optimal pulsatility, should optimize the vascular function. PMID:24793178
Song, Zhiming; Gu, Kaiyun; Gao, Bin; Wan, Feng; Chang, Yu; Zeng, Yi
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
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
Batzel, Jerry; Baselli, Giuseppe; Mukkamala, Ramakrishna; Chon, Ki H
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.
Solomon, M.; Srinivasan, R.
State-of-the-art magnetic resonance imaging (MRI) generates high-resolution images of the cardiovascular system. Conventional MRI techniques provide images in six to ten minutes per tomographic slice. New strategies have substantially improved the speed of imaging. The technology is relatively expensive, and its cost-effectiveness remains to be defined in relation to other effective, less expensive, and noninvasive technologies, such as echocardiography and nuclear medicine. The ultimate role of MRI will depend on several factors, including the development of specific applications such as (1) noninvasive angiography, especially of the coronary arteries;(2) noninvasive, high-resolution assessment of regional myocardial blood flow distribution (e.g., using paramagnetic contrast agents); (3) characterization of myocardial diseases using proton-relaxation property changes; and (4) evaluation of in vivo myocardial biochemistry. The three-dimensional imaging capability and the ability to image cardiovascular structures without contrast material give MRI a potential advantage over existing noninvasive diagnostic imaging techniques. This report analyzes current applications of MRI to the cardiovascular system and speculates on their future.
We have recently proposed a correlated model to provide a Gaussian mixture representation of the cardiovascular signals, with promising results in identifying rhythm disturbances. The approach provides a transformation of the data into a set of integrable Gaussians distributed over time. Looking into the model from a new joint modeling perspective, it is capable of assembling a filtered estimation, and can be used to derive temporal information of the waveforms. In this paper, we present a step-by-step derivation of the joint model putting correlation assumptions together to conclude a minimal joint description for a pair of ECG-ABP signals. We then probe novel applications of this model, including Kalman filter based denoising and fiducial point detection. In particular, we use the joint model for denoising and employ the denoised signals for pulse transit time (PTT) estimation. We analyzed more than 70 h of data from 76 patients from the MIMIC database to illustrate the accuracy of the algorithm. We have found that this method can be effectively used for robust joint ECG-ABP noise suppression, with mean signal-to-noise ratio (SNR) improvement up to 23.2 (12.0) dB and weighted diagnostic distortion measures as low as 2.1 (3.3)% for artificial (real) noises, respectively. In addition, we have estimated the error distributions for QT interval, systolic and diastolic blood pressure before and after filtering to demonstrate the maximal preservation of morphological features (?QT: mean ± std = 2.2 ± 6.1 ms; ?SBP: mean ± std = 2.3 ± 1.9 mmHg; ?DBP: mean ± std = 1.9 ± 1.4 mmHg). Finally, we have been able to present a systematic approach for robust PTT estimation (r = 0.98, p <; 0.001, mean ± std of error = -0.26 ± 2.93 ms). These findings may have important implications for reliable monitoring and estimation of clinically important features in clinical settings. In conclusion, the proposed framework opens the door to the possibility of deploying a hybrid system that integrates these algorithmic approaches for index estimation and filtering scenarios with high output SNRs and low distortion. PMID:25055317
Sayadi, Omid; Shamsollahi, Mohammad Bagher
\\u000a More than half of all new pediatric patients with malignancies will receive therapy with cardiotoxic agents (van Dalen et\\u000a al. 2007). As the number of survivors increases, the number of survivors developing cardiotoxicity also increases. Cardiac\\u000a toxicity occurs primarily as a result of treatment with anthracyclines. Doxorubicin and daunorubicin are cited as having the\\u000a greatest cardiotoxicity, though this may be
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. PMID:25204470
Fardet, Laurence; Fève, Bruno
There is growing evidence that the altered production and/or spatiotemporal distribution of reactive oxygen and nitrogen species creates oxidative and/or nitrosative stresses in the failing heart and vascular tree, which contribute to the abnormal cardiac and vascular phenotypes that characterize the failing cardiovascular system. These derangements at the integrated system level can be interpreted at the cellular and molecular levels in terms of adverse effects on signaling elements in the heart, vasculature, and blood that subserve cardiac and vascular homeostasis. PMID:15765132
Hare, Joshua M.; Stamler, Jonathan S.
Chronic RAS (renin-angiotensin system) activation by both AngII (angiotensin II) and aldosterone leads to hypertension and perpetuates a cascade of pro-hypertrophic, pro-inflammatory, pro-thrombotic and atherogenic effects associated with cardiovascular damage. In 2000, a new pathway consisting of ACE2 (angiotensin-converting enzyme2), Ang-(1-9) [angiotensin-(1-9)], Ang-(1-7) [angiotensin-(1-7)] and the Mas receptor was discovered. Activation of this novel pathway stimulates vasodilation, anti-hypertrophy and anti-hyperplasia. For some time, studies have focused mainly on ACE2, Ang-(1-7) and the Mas receptor, and their biological properties that counterbalance the ACE/AngII/AT1R (angiotensin type 1 receptor) axis. No previous information about Ang-(1-9) suggested that this peptide had biological properties. However, recent data suggest that Ang-(1-9) protects the heart and blood vessels (and possibly the kidney) from adverse cardiovascular remodelling in patients with hypertension and/or heart failure. These beneficial effects are not modified by the Mas receptor antagonist A779 [an Ang-(1-7) receptor blocker], but they are abolished by the AT2R (angiotensin type 2 receptor) antagonist PD123319. Current information suggests that the beneficial effects of Ang-(1-9) are mediated via the AT2R. In the present review, we summarize the biological effects of the novel vasoactive peptide Ang-(1-9), providing new evidence of its cardiovascular-protective activity. We also discuss the potential mechanism by which this peptide prevents and ameliorates the cardiovascular damage induced by RAS activation. PMID:25029123
Ocaranza, Maria Paz; Michea, Luis; Chiong, Mario; Lagos, Carlos F; Lavandero, Sergio; Jalil, Jorge E
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
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.
Cardiovascular disease (CVD) is the leading cause of death worldwide, and due to the lack of early detection techniques, the incidence of CVD is increasing day by day. In order to address this limitation, a knowledge based system with embedded intelligent heart sound analyser (KBHSA) has been developed to diagnose cardiovascular disorders at early stages. The system analyses digitized heart sounds that are recorded from an electronic stethoscope using advanced digital signal processing and artificial intelligence techniques. KBHSA takes into account data including the patient's personal and past medical history, clinical examination, auscultation findings, chest x-ray and echocardiogram, and provides a list of diseases that it has diagnosed. The system can assist the general physician in making more accurate and reliable diagnosis under emergency conditions where expert cardiologists and advanced equipment are not readily available. To test the validity of the system, abnormal heart sound samples and medical data from 40 patients were recorded and analysed. The diagnoses made by the system were counter checked by four senior cardiologists in Malaysia. The results show that the findings of KBHSA coincide with those of cardiologists. PMID:17701779
Javed, F; Venkatachalam, P A; Hani, A F M
The authors conducted a 2-year follow-up of 40 cardiovascular disease patients (mean age = 65.6 years (standard deviation, 5.8)) who underwent repeated measurements of cardiovascular response before and during the 2008 Beijing Olympics (Beijing, China), when air pollution was strictly controlled. Ambient levels of particulate matter with an aerodynamic diameter less than 2.5 µm (PM(2.5)), black carbon, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide were measured continuously, with validation of concurrent real-time measurements of personal exposure to PM(2.5) and carbon monoxide. Linear mixed-effects models were used with adjustment for individual risk factors, time-varying factors, and meteorologic effects. Significant heart rate variability reduction and blood pressure elevation were observed in association with exposure to air pollution. Specifically, interquartile-range increases of 51.8 µg/m(3), 2.02 µg/m(3), and 13.7 ppb in prior 4-hour exposure to PM(2.5), black carbon, and nitrogen dioxide were associated with significant reductions in the standard deviation of the normal-to-normal intervals of 4.2% (95% confidence interval (CI): 1.9, 6.4), 4.2% (95% CI: 1.8, 6.6), and 3.9% (95% CI: 2.2, 5.7), respectively. Greater heart rate variability declines were observed among subjects with C-reactive protein values above the 90th percentile, subjects with a body mass index greater than 25, and females. The authors conclude that autonomic and vascular dysfunction may be one of the mechanisms through which air pollution exposure can increase cardiovascular disease risk, especially among persons with systemic inflammation and overweight. PMID:22763390
Huang, Wei; Zhu, Tong; Pan, Xiaochuan; Hu, Min; Lu, Shou-En; Lin, Yong; Wang, Tong; Zhang, Yuanhang; Tang, Xiaoyan
Loeys-Dietz syndrome (LDS) is an autosomal dominant arterial aneurysm disease belonging to the spectrum of transforming growth factor ? (TGF?)-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 TGF? receptor 1 and 2 (TGFBR1 and -2), which lead to a paradoxical increase in TGF? 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
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
Long-term mechanical circulatory assistance opened new problems in ventricular assist device-patient interaction, especially in relation to autonomic controls. Modeling studies, based on adequate models, could be a feasible approach of investigation. The aim of this work is the exploitation of a hybrid (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo experimental data acquired during a continuous flow left ventricular assistance. The hybrid cardiovascular simulator embeds three submodels: a computational cardiovascular submodel, a computational baroreflex submodel, and a hydronumerical interface submodel. The last one comprises two impedance transformers playing the role of physical interfaces able to provide a hydraulic connection with specific cardiovascular sites (in this article, the left atrium and the ascending/descending aorta). The impedance transformers are used to connect a continuous flow pump for partial left ventricular support (Synergy Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular simulator. Data collected from five animals in physiological, pathological, and assisted conditions were reproduced using the hybrid cardiovascular simulator. All parameters useful to characterize and tune the hybrid cardiovascular simulator to a specific hemodynamic condition were extracted from experimental data. Results show that the simulator is able to reproduce animal-specific hemodynamic status both in physiological and pathological conditions, to reproduce cardiovascular left ventricular assist device (LVAD) interaction and the progressive unloading of the left ventricle for different pump speeds, and to investigate the effects of the LVAD on baroreflex activity. Results in chronic heart failure conditions show that an increment of LVAD speed from 20?000 to 22?000?rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3?L/min). Thanks to its flexibility and modular structure, the simulator is a platform potentially useful to test different assist devices, thus providing clinicians additional information about LVAD therapy strategy. PMID:24117988
Fresiello, Libera; Zieli?ski, Krzysztof; Jacobs, Steven; Di Molfetta, Arianna; Pa?ko, Krzysztof Jakub; Bernini, Fabio; Martin, Michael; Claus, Piet; Ferrari, Gianfranco; Trivella, Maria Giovanna; Górczy?ska, Krystyna; Darowski, Marek; Meyns, Bart; Kozarski, Maciej
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 events becomes extremely high, even in the presence of minor environmental stimuli that could be usually harmless, and circadian rhythms of cardiovascular events are observed. This implies that one cannot afford to miss what happens during day but also night. Moreover, the requirement for preventive and therapeutic interventions varies predictably during the 24 h, suggesting that the delivery of protective or preventive medications should be synchronized in time in proportion to need, as determined by established rhythmic patterns in cardiovascular function as well as risk, in a manner that will avert or minimize their undesired side effects. PMID:24851400
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
Rothman, Sarah M; Griffioen, Kathleen J; Wan, Ruiqian; Mattson, Mark P
The term "space weather" characterizes a state of the near-Earth environmental space. An organism of human being represents an open system so the change of conditions in the environment including the near-Earth environmental space influences the health state of a human being.In recent years many works devoted to the effect of space weather on the life on the Earth, and the degree of such effect has been represented from a zero-order up to apocalypse. To reveal a real effect of space weather on the health of human being the international Russian- Ukrainian experiment "Geliomed" is carried out since 2005 (http://geliomed.immsp.kiev.ua) [Vishnevsky et al., 2009]. The analysis of observational set of data has allowed to show a synchronism and globality of such effect (simultaneous manifestation of space weather parameters in a state of cardiovascular system of volunteer groups removed from each other at a distance over 6000 km). The response of volunteer' cardiovascular system to the changes of space weather parameters were observed even at insignificant values of the Earth's geomagnetic field. But even at very considerable disturbances of space weather parameters a human being healthy did not feel painful symptoms though measurements of objective physiological indices showed their changes.
Samsonov, S. N.; Manykina, V. I.; Krymsky, G. F.; Petrova, P. G.; Palshina, A. M.; Vishnevsky, V. V.
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. PMID:23949656
Pfenniger, Alois; Jonsson, Magnus; Zurbuchen, Adrian; Koch, Volker M; Vogel, Rolf
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. PMID:24292907
Tune, Johnathan D; Sturek, Michael; Basile, David P
A mini-microscope-based system for multisite detection of cardiovascular toxicity was developed. The mini-microscope consisted of an image sensor and lens module extracted from an inexpensive webcam. The flipped lens module enabled cells to be magnified and monitored during testing. The portability and compactness of this system enables short-term and potential long-term experimentation inside a conventional incubator. The toxicity test results demonstrated that the normalized beating rates of cardiac muscle cells selected from multiple regions increased over time when treated with 100 nM isoprenaline. The presented system could be a promising cost-effective cell-based testing tool for discovering and screening drugs. PMID:24563288
Koo, Kyo-in; Kim, Sang Bok; Kim, Keekyoung; Oh, Jonghyun
Activation of the renin–angiotensin–aldosterone system (RAAS) results in vasoconstriction, muscular (vascular and cardiac) hypertrophy and fibrosis. Established arterial stiffness and cardiac dysfunction are key factors contributing to subsequent cardiovascular and renal complications. Blockade of RAAS has been shown to be beneficial in patients with hypertension, acute myocardial infarction, chronic systolic heart failure, stroke and diabetic renal disease. An aggressive approach for more extensive RAAS blockade with combination of two commonly used RAAS blockers [ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)] yielded conflicting results in different patient populations. Combination therapy is also associated with more side effects, in particular hypotension, hyperkalaemia and renal impairment. Recently published ONTARGET study showed ACEI/ARB combination therapy was associated with more adverse effects without any increase in benefit. The Canadian Hypertension Education Program responded with a new warning: ‘Do not use ACEI and ARB in combination’. However, the European Society of Cardiology in their updated heart failure treatment guidelines still recommended ACEI/ARB combo as a viable option. This apparent inconsistency among guidelines generates debate as to which approach of RAAS inhibition is the best. The current paper reviews the latest evidence of isolated ACEI or ARB use and their combination in cardiovascular diseases, and makes recommendations for their prescriptions in specific patient populations. PMID:20590619
Ma, Terry KW; Kam, Kevin KH; Yan, Bryan P; Lam, Yat-Yin
Aging is associated with immunosenescence and accompanied by a chronic inflammatory state which contributes to metabolic syndrome, diabetes and their cardiovascular consequences. Risk factors for cardiovascular diseases (CVDs) and diabetes overlap, leading to the hypothesis that both share an inflammatory basis. Obesity is increased in the elderly population, and adipose tissue induces a state of systemic inflammation partially induced by adipokines. The liver plays a pivotal role in the metabolism of nutrients and exhibits alterations in the expression of genes associated with inflammation, cellular stress and fibrosis. Hepatic steatosis and its related inflammatory state (steatohepatitis) are the main hepatic complications of obesity and metabolic diseases. Aging-linked declines in expression and activity of endoplasmic reticulum molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the unfolded protein response. These changes predispose aged individuals to CVDs. CVDs and endothelial dysfunction are characterized by a chronic alteration of inflammatory function and markers of inflammation and the innate immune response, including C-reactive protein, interleukin-6, TNF-?, and several cell adhesion molecules are linked to the occurrence of myocardial infarction and stroke in healthy elderly populations and patients with metabolic diseases. © 2015 S. Karger AG, Basel. PMID:25341516
Guarner, Verónica; Rubio-Ruiz, Maria Esther
We applied cardiovascular system identification (CSI) to characterize closed-loop cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN). The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize four physiological coupling mechanisms, two of which are autonomically mediated (the heart rate baroreflex and the coupling of respiration, measured in terms of ILV, to heart rate) and two of which are mechanically mediated (the coupling of ventricular contraction to the generation of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control and 60 diabetic subjects who were classified as having minimal, moderate, or severe DAN on the basis of standard autonomic tests. The autonomically mediated couplings progressively decreased with increasing severity of DAN, whereas the mechanically mediated couplings were essentially unchanged. CSI identified differences between the minimal DAN and control groups, which were indistinguishable based on the standard autonomic tests. CSI may provide a powerful tool for assessing DAN.
Mukkamala, R.; Mathias, J. M.; Mullen, T. J.; Cohen, R. J.; Freeman, R.
Vascular peroxidase 1 (VPO1) is a recently identified novel family member of peroxidases in cardiovascular system. As an enzyme that is downstream of NADPH oxidases (NOX), VPO1 functions to utilize NOX - derived hydrogen peroxide (H2O2) to produce hypochlorous acid (HOCl), a strong oxidant which is believed to greatly promote oxidative stress. Under multiple conditions, NOX is activated concomitantly with an increase in superoxide anion (O2(.-)) and H2O2 production. The latter is converted to HOCl by VPO1. In this process (O2(.-) ? H2O2 ? HOCl), the oxidant reactivities of reactive oxygen species (ROS) are significantly increased and therefore the oxidative stress is dramatically amplified. Several lines of evidence suggest that the NOX/VPO1 pathway - mediated oxidative stress plays an important role in myocardial ischemia-reperfusion injury, endothelial cell apoptosis and/or smooth muscle cell proliferation. In addition, VPO1 can be secreted into the extracellular space to participate in extracellular matrix formation, suggesting that VPO1 may also play a role in cardiovascular remodeling (such as fibrosis). This function is independent of the peroxidase activity of VPO1. PMID:23357484
Ma, Qi-Lin; Zhang, Guo-Gang; Peng, Jun
Since its discovery in 1988, the endothelin system has been employed in multiple physiological and pathological roles. Endothelin-1 (ET-1) is not only a major regulator of vascular tone and cardiac contractility but also exerts mitogenic effects and is involved in inflammatory responses. ET-1 acts via two endothelin receptors located mainly on smooth muscle and endothelial cells through complex intracellular pathways differing between receptors and cell types. Polymorphisms of the endothelin receptor A have been associated not only with the risk in pulmonary arterial hypertension (PAH), systolic heart failure and systemic hypertension but are also of prognostic significance in dilated cardiomyopathy. Polymorphisms of endothelin receptors might lead to altered endothelin signaling and influence the response to endothelin receptor antagonist therapy in PAH in light of pharmacogenetics. This review will summarize the role of ET-1 within major cardiovascular pathologies and discuss endothelin receptor polymorphisms with special emphasis on potential therapeutic and screening implications. PMID:24570333
Holzhauser, Luise; Zolty, Ronald
Introduction: Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder characterized by generalized fragmentation of elastic fibers and progressive calcification of elastic tissue, affecting the skin, the eyes and the vascular system.Typically these patients present arteriosclerosis, hypertension, ischemic attacks and occlusive vascular changes at young ages.Objective: The aim of our study was to specify the cardiovascular changes in a case of
Elena Sanchez-Largo; Martin Fabregate; David Coca; Rosa Fabregate; Begonia Monge; Eva Fernandez; Judith Marquez; Jose Saban-Ruiz
Background: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species.Objective: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be incre...
The escalating epidemic of obesity has increased the incidence of obesity-induced complications to historically high levels. Adipose tissue is a dynamic energy depot, which stores energy and mobilizes it during nutrient deficiency. Excess nutrient intake resulting in adipose tissue expansion triggers lipid release and aberrant adipokine, cytokine and chemokine production, and signaling that ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low-grade chronic inflammation is thought to link obesity to insulin resistance and the associated comorbidities of metabolic syndrome such as dyslipidemia and hypertension, which increase risk of type 2 diabetes and cardiovascular disease. In this review, we focus on and discuss members of the chemokine system for which there is clear evidence of participation in the development of obesity and obesity-induced pathologies. PMID:24741577
Yao, Longbiao; Herlea-Pana, Oana; Heuser-Baker, Janet; Chen, Yitong; Barlic-Dicen, Jana
Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain tissue structure. ECM is also important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Among ECM molecules, increased attention has been focused on matricellular proteins. Matricellular proteins are a growing group of non-structural ECM proteins highly up-regulated at active tissue remodeling, serving as biological mediators. Tenascin-C (TNC) is a typical matricellular protein, which is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion. The expression is tightly regulated, dependent on the microenvironment, including various growth factors, cytokines and mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted manner during early stages of development, sparsely detected in normal adults, but transiently re-expressed at restricted sites associated with tissue injury and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated during embryonic development and under pathological conditions with an increase in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular system develops normally in TNC knockout mice. However, deletion of TNC causes acute aortic dissection under strong mechanical and humoral stress. Accumulating reports suggest that TNC may modulate the inflammatory response and contribute to elasticity of the tissue, so that it may protect cardiovascular tissue from destructive stress responses. TNC may be a key molecule to control cellular activity during development, adaptation or pathological tissue remodeling.
Imanaka-Yoshida, Kyoko; Aoki, Hiroki
In order to allow for a comparative evaluation of the in vivo degeneration of biological and tissue-engineered heart valves and vascular grafts, a small animal model of accelerated cardiovascular calcification is desired. Wistar rats (n = 102; 6 groups) were fed ad libitum with regular chow and 5 different regimens of pro-calcific diet supplemented with combinations of vitamin D (VD), cholesterol (CH) and dicalcium phosphate (PH). Moreover, cryopreserved (n = 7) or detergent-decellularized rat aortic conduit grafts (n = 6) were infrarenally implanted in Wistar rats under severely pro-calcific conditions. The follow-up lasted up to 12 weeks. High-dose application of VD (300,000 IU/kg), CH (2%) and PH (1.5%) resulted in elevated serum calcium and cholesterol levels as well as LDL/HDL ratio. It increased the tissue MMP activity visualized by in situ zymography and caused significantly aggravated calcification of the native aortic valve as well as the aortic wall as assessed by histology and micro-computed tomography. (Immuno)histology and quantitative real-time PCR revealed chondro-osteogenic cell transformation, lipid deposition, nitrosative stress and low-level inflammation to be involved in the formation of calcific lesions. Despite pro-calcific in vivo conditions, decellularization significantly reduced calcification, inflammation and intimal hyperplasia in aortic conduit implants. A well balanced dietary trigger for pathologic metabolic conditions may represent an appropriate mid-term treatment to induce calcifying degeneration of aortic valves as well as vascular structures in the systemic circulation in rats. With respect to experimental investigation focusing on calcifying degeneration of native or prosthetic tissue, this regimen may serve as a valuable tool with a rapid onset and multi-facetted character of cardiovascular degeneration. PMID:24917029
Assmann, Alexander; Zwirnmann, Kai; Heidelberg, Friederike; Schiffer, Franziska; Horstkötter, Kim; Munakata, Hiroshi; Gremse, Felix; Barth, Mareike; Lichtenberg, Artur; Akhyari, Payam
Currently, augmentation of sympathetic nervous system function produced by cocaine is thought to be due primarily to stimulation of sympathetic centers in the brain (central effect) and to inhibition of catecholamine uptake into postganglionic sympathetic nerve terminals (peripheral effect). In this review of our work, we present the following evidence that cocaine-induced changes in cardiovascular function, particularly those that peak
Richard A. Gillis; Yvonne M. Hernandez; Hashim K. Erzouki; Victor F. C. Raczkowski; Aloke K. Mandal; Frederick E. Kuhn; Kenneth L. Dretchen
Intermittent fasting (IF; reduced meal frequency) and caloric restriction (CR) extend lifespan and increase resistance to age-related diseases in rodents and monkeys and improve the health of overweight humans. Both IF and CR enhance cardiovascular and brain functions and improve several risk factors for coronary artery disease and stroke including a reduction in blood pressure and increased insulin sensitivity. Cardiovascular
Mark P. Mattson; Ruiqian Wan
Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent disease and is recognised as a major public health burden. Large-scale epidemiological studies have demonstrated an independent relationship between OSAS and various cardiovascular disorders. The pathogenesis of cardiovascular complications in OSAS is not completely understood but a multifactorial aetiology is likely. Inflammatory processes have emerged as critical in the pathogenesis of
S Ryan; C T Taylor; W T McNicholas
Modeling of the vascular system and its capillary networks is con- sidered within the context of associated scaling laws relating measurements of cardiovascular variables of mammals ranging in size from the mouse to the human and onward to the elephant. Topics include competing effects of viscous and iner- tial resistances to blood flow in the system and their appropriate separation
THOMAS H. DAWSON
Background Diabetes mellitus brings an increased risk for cardiovascular complications and patients profit from prevention. This prevention also suits the general population. The question arises what is a better strategy: target the general population or diabetes patients. Methods A mathematical programming model was developed to calculate optimal allocations for the Dutch population of the following interventions: smoking cessation support, diet and exercise to reduce overweight, statins, and medication to reduce blood pressure. Outcomes were total lifetime health care costs and QALYs. Budget sizes were varied and the division of resources between the general population and diabetes patients was assessed. Results Full implementation of all interventions resulted in a gain of 560,000 QALY at a cost of €640 per capita, about €12,900 per QALY on average. The large majority of these QALY gains could be obtained at incremental costs below €20,000 per QALY. Low or high budgets (below €9 or above €100 per capita) were predominantly spent in the general population. Moderate budgets were mostly spent in diabetes patients. Conclusions Major health gains can be realized efficiently by offering prevention to both the general and the diabetic population. However, a priori setting a specific distribution of resources is suboptimal. Resource allocation models allow accounting for capacity constraints and program size in addition to efficiency. PMID:21974836
??Using the allostatic load model of disease processes, this study investigated gender differences on cardiovascular risk and cardiovascular disease among PTSD and MDD veterans. Cross-sectional… (more)
Frazier, Elizabeth C.
Background Estimation of cardiovascular disease risk is increasingly used to inform decisions on interventions, such as the use of antihypertensives and statins, or to communicate the risks of smoking. Crude 10-year cardiovascular disease risk risks may not give a realistic view of the likely impact of an intervention over a lifetime and will underestimate of the risks of smoking. A validated model of survival to act as a decision aid in the consultation may help to address these problems. This study aims to describe the development of such a model for use with people free of cardiovascular disease and evaluates its accuracy against data from a United Kingdom cohort. Methods A Markov cycle tree evaluated using cohort simulation was developed utilizing Framingham estimates of cardiovascular risk, 1998 United Kingdom mortality data, the relative risk for smoking related non-cardiovascular disease risk and changes in systolic blood pressure and serum total cholesterol total cholesterol with age. The model's estimates of survival at 20 years for 1391 members of the Whickham survey cohort between the ages of 35 and 65 were compared with the observed survival at 20-year follow-up. Results The model estimate for survival was 75% and the observed survival was 75.4%. The correlation between estimated and observed survival was 0.933 over 39 subgroups of the cohort stratified by estimated survival, 0.992 for the seven 5-year age bands from 35 to 64, 0.936 for the ten 10 mmHg systolic blood pressure bands between 100 mmHg and 200 mmHg, and 0.693 for the fifteen 0.5 mmol/l total cholesterol bands between 3.0 and 10.0 mmol/l. The model significantly underestimated mortality in those people with a systolic blood pressure greater than or equal to 180 mmHg (p = 0.006). The average gain in life expectancy from the elimination of cardiovascular disease risk as a cause of death was 4.0 years for all the 35 year-old men in the sample (n = 24), and 1.8 years for all the 35 year-old women in the sample (n = 32). Conclusions This model accurately estimates 20-year survival in subjects from the Whickham cohort with a systolic blood pressure below 180 mmHg. PMID:15157279
Martin, Chris; Vanderpump, Mark; French, Joyce
Purpose Although elevated cardiovascular disease (CVD) risk factors are associated with a higher risk of developing heart conditions across all ethnic groups, variations exist between groups in the distribution and association of risk factors, and also risk levels. This study assessed the 10-year predicted risk in a multiethnic cohort of women and compared the differences in risk between Asian and Caucasian women. Methods Information on demographics, medical conditions and treatment, smoking behavior, dietary behavior, and exercise patterns were collected. Physical measurements were also taken. The 10-year risk was calculated using the Framingham model, SCORE (Systematic COronary Risk Evaluation) risk chart for low risk and high risk regions, the general CVD, and simplified general CVD risk score models in 4,354 females aged 20–69 years with no heart disease, diabetes, or stroke at baseline from the third Australian Risk Factor Prevalence Study. Country of birth was used as a surrogate for ethnicity. Nonparametric statistics were used to compare risk levels between ethnic groups. Results Asian women generally had lower risk of CVD when compared to Caucasian women. The 10-year predicted risk was, however, similar between Asian and Australian women, for some models. These findings were consistent with Australian CVD prevalence. Conclusion In summary, ethnicity needs to be incorporated into CVD risk assessment. Australian standards used to quantify risk and treat women could be applied to Asians in the interim. The SCORE risk chart for low-risk regions and Framingham risk score model for incidence are recommended. The inclusion of other relevant risk variables such as obesity, poor diet/nutrition, and low levels of physical activity may improve risk estimation. PMID:24648770
Goh, Louise GH; Dhaliwal, Satvinder S; Welborn, Timothy A; Thompson, Peter L; Maycock, Bruce R; Kerr, Deborah A; Lee, Andy H; Bertolatti, Dean; Clark, Karin M; Naheed, Rakhshanda; Coorey, Ranil; Della, Phillip R
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.
Cellier, Francois E.
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 radiation 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 cancer 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 extrapolation would be appropriate for this endpoint. PMID:19851450
Little, Mark P.; Gola, Anna; Tzoulaki, Ioanna
Increased oxidative stress and compromised antioxidant status are common pathologic factors of cardiovascular diseases (CVD). It is hypothesized that individuals with chronic CVD are more susceptible to environmental exposures due to underlying oxidative stress. To determine the ...
Introduction: Fe homeostasis can be disrupted in human cardiovascular diseases (CVD). We addressed how dysregulation of Fe homeostasis affected the pulmonary inflammation/oxidative stress response and disease progression after exposure to Libby amphibole (LA), an asbestifonn mine...
One of NASA's objectives is to be able to perform a complete, pre-flight, evaluation of cardiovascular changes in astronauts scheduled for prolonged space missions. Computational fluid dynamics (CFD) has shown promise as a method for estimating cardiovascular function during reduced gravity conditions. For this purpose, MRI can provide geometrical information, to reconstruct vessel geometries, and measure all spatial velocity components, providing location specific boundary conditions. The objective of this study was to investigate the reliability of MRI-based model reconstruction and measured boundary conditions for CFD simulations. An aortic arch model and a carotid bifurcation model were scanned in a 1.5T Siemens MRI scanner. Axial MRI acquisitions provided images for geometry reconstruction (slice thickness 3 and 5 mm; pixel size 1x1 and 0.5x0.5 square millimeters). Velocity acquisitions provided measured inlet boundary conditions and localized three-directional steady-flow velocity data (0.7-3.0 L/min). The vessel walls were isolated using NIH provided software (ImageJ) and lofted to form the geometric surface. Constructed and idealized geometries were imported into a commercial CFD code for meshing and simulation. Contour and vector plots of the velocity showed identical features between the MRI velocity data, the MRI-based CFD data, and the idealized-geometry CFD data, with less than 10% differences in the local velocity values. CFD results on models reconstructed from different MRI resolution settings showed insignificant differences (less than 5%). This study illustrated, quantitatively, that reliable CFD simulations can be performed with MRI reconstructed models and gives evidence that a future, subject-specific, computational evaluation of the cardiovascular system alteration during space travel is feasible.
Chatzimavroudis, George P.; Spirka, Thomas A.; Setser, Randolph M.; Myers, Jerry G.
Background For the patient-oriented medical services, it is important to assist the patient in understanding the management of cardiovascular diseases. The strategy of medication instruction is particularly important to enhance medication adherence. Objective and methods The original model was newly constructed and covers multiple factors, including those related to renin–angiotensin, metabolism of glucose and lipids, blood coagulation, and the organic basis of the disease. The four factors of cardiovascular diseases and their relationship with the disease state are expressed in the form of a tetrahedral model. Results and discussion This disease model illustrates in points, lines, surfaces, and spaces that the factors combine with each other and result in a pathological condition, as determined by the degree of involvement of each factor in a discontinuous manner. The model helps cardiovascular patients to understand visually that there is more than one pathological condition. Our model allowed patients to quickly comprehend the complex pharmacotherapy of cardiovascular diseases by presenting the information in the form of a three-dimensional structure. Lifestyle-related diseases, including cardiovascular diseases, involve complicated factors and require careful pharmacotherapy which is tailored to individual patient needs. In this regard, the development of instructional tools is particularly effective. Conclusion The three-dimensional model shows optimum treatment by correctly considering both the quantity and quality of the four pathological factors associated with cardiovascular diseases. Appropriate patient compliance instruction based on life guidance is thought to be essential in the treatment of cardiovascular diseases. PMID:23836964
Nakano, Masuyo; Shirotake, Shoichi
Background We simulated tobacco control and pharmacological strategies for preventing cardiovascular deaths in India, the country that is expected to experience more cardiovascular deaths than any other over the next decade. Methods and Findings A microsimulation model was developed to quantify the differential effects of various tobacco control measures and pharmacological therapies on myocardial infarction and stroke deaths stratified by age, gender, and urban/rural status for 2013 to 2022. The model incorporated population-representative data from India on multiple risk factors that affect myocardial infarction and stroke mortality, including hypertension, hyperlipidemia, diabetes, coronary heart disease, and cerebrovascular disease. We also included data from India on cigarette smoking, bidi smoking, chewing tobacco, and secondhand smoke. According to the model's results, smoke-free legislation and tobacco taxation would likely be the most effective strategy among a menu of tobacco control strategies (including, as well, brief cessation advice by health care providers, mass media campaigns, and an advertising ban) for reducing myocardial infarction and stroke deaths over the next decade, while cessation advice would be expected to be the least effective strategy at the population level. In combination, these tobacco control interventions could avert 25% of myocardial infarctions and strokes (95% CI: 17%–34%) if the effects of the interventions are additive. These effects are substantially larger than would be achieved through aspirin, antihypertensive, and statin therapy under most scenarios, because of limited treatment access and adherence; nevertheless, the impacts of tobacco control policies and pharmacological interventions appear to be markedly synergistic, averting up to one-third of deaths from myocardial infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological therapies could also be considerably more potent with further health system improvements. Conclusions Smoke-free laws and substantially increased tobacco taxation appear to be markedly potent population measures to avert future cardiovascular deaths in India. Despite the rise in co-morbid cardiovascular disease risk factors like hyperlipidemia and hypertension in low- and middle-income countries, tobacco control is likely to remain a highly effective strategy to reduce cardiovascular deaths. Please see later in the article for the Editors' Summary PMID:23874160
Basu, Sanjay; Glantz, Stanton; Bitton, Asaf; Millett, Christopher
The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l-NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from our laboratory on three other species of reptiles: pythons (), rattlesnakes () and turtles (). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies on reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast, the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity. PMID:15982914
Skovgaard, Nini; Galli, Gina; Abe, Augusto; Taylor, Edwin W; Wang, Tobias
Low-dose X-ray imaging, diagnosis by image analysis and multi-modal medical imaging are example aspects that lead to more advanced image processing algorithms and the corresponding platforms on which they have to be executed. In this paper, we investigate the applicability of commercially available off-the-shelf components for a new computing platform. In the analysis, we will comply to some specific use cases. In cardiovascular minimal invasive surgery, physicians require low-latency imaging applications, as their actions must be directly visible on the screen. Typical image-processing algorithms in this domain are based on multi-resolution decomposition, noise reduction, image analysis and enhancement techniques. We have compared various solutions for possible processing architectures. The most interesting technology areas for constituting a new architecture are presented and we discuss the mapping of the use cases onto the various architectural proposals. Results show that a heterogeneous architecture gives the highest potential for current and upcoming image-processing applications. However, hardware and software solutions to support low-latency, high-bandwidth image streaming and an efficient concurrent distribution of functionality still need further development. This validates a clear direction for the future, which is based on modeling streaming computing architectures and special interconnect infrastructures.
Albers, Rob; Boosten, Marcel; de With, Peter H. N.
Background A number of studies have evaluated the educational contents of videos on YouTube. However, little analysis has been done on videos about physical examination. Objective This study aimed to analyze YouTube videos about physical examination of the cardiovascular and respiratory systems. It was hypothesized that the educational standards of videos on YouTube would vary significantly. Methods During the period from November 2, 2011 to December 2, 2011, YouTube was searched by three assessors for videos covering the clinical examination of the cardiovascular and respiratory systems. For each video, the following information was collected: title, authors, duration, number of viewers, and total number of days on YouTube. Using criteria comprising content, technical authority, and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-useful videos. Results A total of 1920 videos were screened. Only relevant videos covering the examination of adults in the English language were identified (n=56). Of these, 20 were found to be relevant to cardiovascular examinations and 36 to respiratory examinations. Further analysis revealed that 9 provided useful information on cardiovascular examinations and 7 on respiratory examinations: scoring mean 14.9 (SD 0.33) and mean 15.0 (SD 0.00), respectively. The other videos, 11 covering cardiovascular and 29 on respiratory examinations, were not useful educationally, scoring mean 11.1 (SD 1.08) and mean 11.2 (SD 1.29), respectively. The differences between these two categories were significant (P<.001 for both body systems). The concordance between the assessors on applying the criteria was 0.89, with a kappa score >.86. Conclusions A small number of videos about physical examination of the cardiovascular and respiratory systems were identified as educationally useful; these videos can be used by medical students for independent learning and by clinical teachers as learning resources. The scoring system utilized by this study is simple, easy to apply, and could be used by other researchers on similar topics. PMID:24225171
Venues for informal science education are usually those sought out by people who are specifically looking for an educational experience. Whether planning a trip to a museum or choosing a television program, these individuals are actively seeking an informal educational experience; they are a self-selected group. This paper investigates whether members of the public will respond to an informal science activity that is placed in a location where learning about science would be unexpected. This project developed and used an activity about the cardiovascular system in which participants were able to walk the path of blood flow through the heart, body, and lungs. This activity was tested in two types of settings: where science was either expected or unexpected. A non-traditional assessment method was used to evaluate the effectiveness of the activity in the unexpected versus the expected settings. Ultimately, the activity was found to be equally effective in both settings, providing evidence for success in bringing informal science education to the general population in non-traditional venues.
Monzack, Elyssa Lynne; Petersen, Greta M. Zenner
The authors used male New Zealand white rabbits to study the effects of zinc-deficient diets on the cardiovascular system. These 10 week-old rabbits were fed semi-purified diets containing either 50 ppm or less than 1 ppm zinc for 12 weeks. Serum samples were analyzed at 3,6,9 and 12 weeks. Body weight and food consumption were measured weekly. At necropsy the liver and heart were removed and weighed. Then the heart was perfused at 100 mm Hg with 10% buffered formalin via the ascending aorta. Coronary arteries were block-dissected and processed for light microscopy. Food consumption and body weights were not significantly altered throughout the study. Relative heart weights were not different; however, the relative liver weight of the zinc-deficient group was elevated by 11%. Neither total serum cholesterol or HDL-cholesterol were changed at any time. After 6 weeks treatment, serum zinc levels were depressed by 29% in the zinc-deficient group; no changes were observed for serum copper or calcium. Morphometric analysis of coronary arteries revealed a decreased combined thickness of the tunica intima and tunica media and a decreased area per unit length in the left coronary circumflex arteries of zinc-deficient rabbits. Significant changes reported here are probably related to possible alterations in lipoproteins metabolism and will be investigated in future studies.
Carter, J.W.; Koo, S.I.
modeling system. Also noteworthy is the representation of regional circulatory beds with related short term and system extensibility. The coordination framework relies on the autonomous object paradigm underlying indigenous and a more integrated system representation. Dynamic simulation control serves to interject new
California at Irvine, University of
A priority of NASA is to identify and study possible risks to astronauts health during prolonged space missions [l]. The goal is to develop a procedure for a preflight evaluation of the cardiovascular system of an astronaut and to forecast how it will be affected during the mission. To predict these changes, a computational cardiovascular model must be constructed. Although physiology data can be used to make a general model, a more desirable subject-specific model requires anatomical, functional, and flow data from the specific astronaut. MRI has the unique advantage of providing images with all of the above information, including three-directional velocity data which can be used as boundary conditions in a computational fluid dynamics (CFD) program [2,3]. MRI-based CFD is very promising for reproduction of the flow patterns of a specific subject and prediction of changes in the absence of gravity. The aim of this study was to test the feasibility of this approach by reconstructing the geometry of MRI-scanned arterial models and reproducing the MRI-measured velocities using CFD simulations on these geometries.
Spirka, T. A.; Myers, J. G.; Setser, R. M.; Halliburton, S. S.; White, R. D.; Chatzimavroudis, G. P.
Adequate characterization of hemodynamic and autonomic responses to physical and mental stress can elucidate underlying mechanisms of cardiovascular disease or anxiety disorders. We developed a physiological signal processing system for analysis of continuously recorded ECG, arterial blood pressure (BP), and respiratory signals using the programming language Matlab. Data collection devices are a 16-channel digital, physiological recorder (Vitaport), a finger arterial pressure transducer (Finapres), and a respiratory inductance plethysmograph (Respitrace). Besides the conventional analysis of the physiological channels, power spectral density and transfer functions of respiration, heart rate, and blood pressure variability are used to characterize respiratory sinus arrhythmia (RSA), 0.10-Hz BP oscillatory activity (Mayer-waves), and baroreflex sensitivity. The arterial pressure transducer waveforms permit noninvasive estimation of stroke volume, cardiac output, and systemic vascular resistance. Time trends in spectral composition of indices are assessed using complex demodulation. Transient dynamic changes of cardiovascular parameters at the onset of stress and recovery periods are quantified using a regression breakpoint model that optimizes piecewise linear curve fitting. Approximate entropy (ApEn) is computed to quantify the degree of chaos in heartbeat dynamics. Using our signal processing system we found distinct response patterns in subgroups of patients with coronary artery disease or anxiety disorders, which were related to specific pharmacological and behavioral factors. PMID:11143335
Wilhelm, F H; Grossman, P; Roth, W T
The relationship between sympathetic nervous system activity and cardiovascular responses to head-up tilt in patients with spinal cord injuries and in able-bodied subjects was studied. Twenty-seven adults, nine in each of the three groups (tetraplegia, paraplegia, and able-bodied subjects) were tilted 70°, head up, for 12 minutes after 20 minutes supine rest. Differences between steady-state measurements of mean arterial pressure,
Sibrand Houtman; Berend Oeseburg; Richard L. Hughson; Maria T. E. Hopman
Study design:Measurement of haemodynamic responses and cutaneous blood flow during an inspiratory-capacity apnoea following spinal cord injury (SCI).Objective:To assess the capacity of the sympathetic nervous system to respond to a cardiovascular challenge following SCI.Setting:Prince of Wales Medical Research Institute, Australia.Subjects:Thirteen spinal cord injured subjects with injuries ranging from C5-T8 and eight able-bodied control subjects.Methods:Continuous blood pressure, an electrocardiogram, respiration and
R Brown; V G Macefield
In rabbits, mean arterial pressure (MAP) increases in response to fat feeding, but does not increase further with progressive weight gain. We documented the progression of adiposity and the alterations in endocrine/cardiovascular function in response to fat feeding in rabbits, to determine whether stabilization of MAP after 3 weeks could be explained by stabilization of neurohormonal factors. Rabbits were fed a control diet or high-fat diet for 9 weeks (n=23). Fat feeding progressively increased body mass and adiposity. Heart rate (HR) was elevated by week 3 (15±3%) but changed little thereafter. The effects of fat feeding on MAP were dependent on baseline MAP and peaked at 3 weeks. From baseline, MAP ?80?mm?Hg, MAP had increased by 8.1±1.3, 4.7±1.7 and 5.6±1.2 mm Hg, respectively, 3, 6 and 9 weeks after commencing the high-fat diet, but by only 2.6±1.5, 3.0±1.7 and 3.9±1.4 mm Hg, respectively, in control rabbits. Fat feeding did not increase MAP from a baseline >80 mm Hg. Plasma concentrations of leptin and insulin increased during the first 3-6 weeks of fat feeding and then stabilized (increasing by 111±17% and 731±302% by week 9, respectively), coinciding with the pattern of changes in MAP and HR. Plasma total cholesterol, triglycerides, renin activity, aldosterone and atrial natriuretic peptide were not significantly altered by fat feeding. Given that the changes in plasma leptin and insulin mirrored the changes in MAP and HR, leptin and insulin may be important factors in the development of hypertension and tachycardia in the rabbit model of obesity. PMID:23407240
Eppel, Gabriela A; Armitage, James A; Eikelis, Nina; Head, Geoffrey A; Evans, Roger G
Objective Incorporation of novel plasma protein biomarkers may improve current models for prediction of atherosclerotic cardiovascular disease (ASCVD) risk. Approach and Results We utilized discovery mass spectrometry (MS) to determine plasma concentrations of 861 proteins in 135 myocardial infarction (MI) cases and 135 matched controls. We then measured 59markers by targeted MS in 336 ASCVD case-control pairs. Associations with MI or ASCVD were tested in single marker and multimarker analyses adjusted for established ASCVD risk factors. Twelve single markers from discovery MS were associated with MI incidence (at p<0.01) adjusting for clinical risk factors. Seven proteins in aggregate (cyclophilin A, CD5 antigen-like, cell surface glycoprotein MUC18, collagen-alpha 1 [XVIII] chain, salivary alpha-amylase 1, C-reactive protein, and multimerin-2) were highly associated with MI (p<0.0001) and significantly improved its prediction compared to a model with clinical risk factors alone (C-statistic of 0.71 vs. 0.84). Through targeted MS, twelve single proteins were predictors of ASCVD (at p<0.05) after adjusting for established risk factors. In multimarker analyses, four proteins in combination (alpha-1-acid glycoprotein 1, paraoxonase 1, tetranectin, and CD5 antigen-like, predicted incident ASCVD (p<0.0001) and moderately improved the C-statistic from the model with clinical covariates alone (C-statistic of 0.69 vs. 0.73). Conclusions Proteomics profiling identified single and multimarker protein panels that are associated with new onset ASCVD and may lead to a better understanding of underlying disease mechanisms. Our findings include many novel protein biomarkers that, if externally validated, may improve risk assessment for MI and ASCVD. PMID:24526693
Yin, Xiaoyan; Subramanian, Subha; Hwang, Shih-Jen; O'Donnell, Christopher J.; Fox, Caroline S.; Courchesne, Paul; Muntendam, Pieter; Adourian, Aram; Juhasz, Peter; Larson, Martin G.; Levy, Daniel
This paper proposes a model for a miniaturized signal conditioning system for biopotential and ion-selective electrode arrays. The system consists of three main components: sensors, interconnections, and signal conditioning chip. The model for this system is based on SPICE. Transmission-line based equivalent circuits are used to represent the sensors, lumped resistance-capacitance circuits describe the interconnections, and a model for the signal conditioning chip is extracted from its layout. A system for measurements of biopotentials and ionic activities can be miniaturized and optimized for cardiovascular applications based on the development of an integrated SPICE system model of its electrochemical, interconnection, and electronic components.
Mundt, C. W.; Nagle, H. T.
This paper proposes a model for a miniaturized signal conditioning system for biopotential and ion-selective electrode arrays. The system consists of three main components: sensors, interconnections, and signal conditioning chip. The model for this system is based on SPICE. Transmission-line based equivalent circuits are used to represent the sensors, lumped resistance-capacitance circuits describe the interconnections, and a model for the signal conditioning chip is extracted from its layout. A system for measurements of biopotentials and ionic activities can be miniaturized and optimized for cardiovascular applications based on the development of an integrated SPICE system model of its electrochemical, interconnection, and electronic components. PMID:10721621
Mundt, C W; Nagle, H T
Purpose Many patients treated for dyslipidemia do not achieve recommended cholesterol goals despite the widespread availability of effective statins. Pharmaceutical claims show a strong tendency for patients to remain on their initially assigned treatment. With computer simulations, the impact of initial statin treatment decisions on medium- and long-term cardiovascular outcomes were examined. Patients and methods Using the Archimedes Model, three treatment scenarios were simulated. Patients initiated treatment with simvastatin (20, 40, or 80 mg), atorvastatin (10, 20, 40, or 80 mg), or rosuvastatin (10, 20, or 40 mg), and periodically intensified treatment. The simulated population consisted of 50,025 patients, aged 45–70 years, with low-density lipoprotein cholesterol exceeding goal. The proportion of patients initiating each dose was calibrated to United States pharmacy claims. Patients not reaching goal intensified the dose of their current statin or switched to an appropriate dose of rosuvastatin at rates matching pharmacy claims. Biomarkers and major adverse cardiovascular events (MACE) were tracked for 10 years and several high-risk subpopulations were analyzed. Statin models used biomarker effects from the STELLAR (Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin) trial and outcomes data from various trials. Results Initiating therapy with rosuvastatin reduced MACE more than simvastatin or atorvastatin. The 5- year relative risk of MACE was 0.906 (95% confidence interval: 0.888–0.923; P < 0.001) for initial treatment with atorvastatin rather than simvastatin, 0.831 (0.812–0.850; P < 0.001) for rosuvastatin rather than simvastatin, and 0.918 (0.898–0.938; P < 0.001) for rosuvastatin rather than atorvastatin. Subgroups with higher MACE incidence experienced greater absolute benefit. Conclusion Considering observed rates of treatment intensification, initial treatment choices appear to significantly impact medium- and long-term cardiovascular risk. Patients at high cardiovascular risk are good candidates for aggressive initial therapy. PMID:23180970
van Herick, Andrew; Schuetz, C Andy; Alperin, Peter; Bullano, Michael F; Balu, Sanjeev; Gandhi, Sanjay
Background and purpose: Studies have shown that the angiotensin II AT1 receptor antagonist, losartan, accentuates the hypotensive response in the orthostatic stress test (tilt) performed in anaesthetized rats. The same effect was not reported with other AT1 antagonists. The aim of this study was to re-evaluate the effects of AT1 receptor blockade on the cardiovascular response to tilt in a model developed for conscious rats. Experimental approach: Rats (n=5–7 per group) were instrumented for infusion of drugs and recording of cardiovascular parameters and, after recovery, placed in a plastic tube positioned over the tilt board. The tilt test was conducted by raising the head side of the tilt board from horizontal position to 75° head up position for 15?min. Key results: Compared with control group (NaCl 0.9%, 1?ml?kg?1), oral treatment with 1?mg?kg?1 per day of losartan or telmisartan did not alter the blood pressure response during tilt. With the 10?mg?kg?1 dose, both antagonists altered the blood pressure response during tilt (mean maximum changes ?11±3?mm?Hg; P<0.01). A post-tilt hypotension was observed with both doses in losartan and telmisartan groups (?13±1 and ?9±2?mm?Hg, respectively; P<0.01). Conclusions and implications: The present results indicate that the effect of losartan on the cardiovascular reactivity to tilt shares a similar profile to that of other AT1 antagonists. Evidence discussed addresses the importance of using a conscious model for testing the influence of antihypertensive drugs on the cardiovascular reactivity to orthostatic challenges. PMID:18193073
Bedette, D; Santos, R A S; Fontes, M A P
The Earth System Model is the natural evolution of current climate models and will be the ultimate embodiment of our geophysical understanding of the planet. These models are constructed from components - atmosphere, ocean, ice, land, chemistry, solid ear...
M. Schoeberl, R. B. Rood, P. Hildebrand, C. Raymond
Objective To model the long term effectiveness and cost effectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease. Design Best case scenario analysis using a Markov model. Setting Australian Diabetes, Obesity and Lifestyle study. Participants 2013 people with hypertension who met the criteria for metabolic syndrome, with no history of cardiovascular disease and not receiving antihypertensive therapy. Main outcome measures Treatment effects associated with dark chocolate consumption derived from published meta-analyses were used to determine the absolute number of cardiovascular events with and without treatment. Costs associated with cardiovascular events and treatments were applied to determine the potential amount of funding required for dark chocolate therapy to be considered cost effective. Results Daily consumption of dark chocolate (polyphenol content equivalent to 100 g of dark chocolate) can reduce cardiovascular events by 85 (95% confidence interval 60 to 105) per 10?000 population treated over 10 years. $A40 (£25; €31; $42) could be cost effectively spent per person per year on prevention strategies using dark chocolate. These results assume 100% compliance and represent a best case scenario. Conclusions The blood pressure and cholesterol lowering effects of dark chocolate consumption are beneficial in the prevention of cardiovascular events in a population with metabolic syndrome. Daily dark chocolate consumption could be an effective cardiovascular preventive strategy in this population. PMID:22653982
Although cardiovascular disease (CVD) is considered a risk factor for the exacerbation of air pollution health effects, no studies have been done assessing the influence of the disease on the development of lung injury induced by asbestos exposure. In this study we examined lung ...
Cardiovascular diseases (CVD) are the number one cause for human mortality and nearly 25% of the population develops chronic CVD at an age of 65 years or older. Environmental and genetic interactions govern pathogenesis. Increased oxidative stress and compromised antioxidant stat...
Background/Aim Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy. Methods/Results Male C57BL/6 mice were fed with a standardized high-fat diet (obese) or regular diet (normal) for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method) and by hemodynamic parameters (invasive method). Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction), and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study. Conclusions Mice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy. PMID:23593350
Calligaris, Sebastian D.; Lecanda, Manuel; Solis, Felipe; Ezquer, Marcelo; Gutierrez, Jaime; Brandan, Enrique; Leiva, Andrea; Sobrevia, Luis; Conget, Paulette
The specific features of the psychophysiological regulation of the cardiovascular system in healthy 8-to 9-year-old children\\u000a and in children of the same age with impairments of intellectual development are considered. An analysis of the functional\\u000a heart rhythm values after mental and physical exercise is given. The directions of correctional influence on the mechanisms\\u000a of functional optimization of the cardiovascular system
S. K. Bystrushkin; R. I. Aizman
Background Patients with diabesity have a significantly increased risk of developing cardiovascular disease. Therefore, therapy addressing the multiple metabolic abnormalities linked with diabesity and leading to further reduction of cardiovascular risk is highly desirable. Activation of the TGR5 receptor holds therapeutic potential for diabesity. In the present study, we evaluated the efficacy of TRC210258, a novel TGR5 agonist, in clinically relevant animal models of diabesity. Methods A novel small molecule, TRC210258 (N-(4-chlorophenyl)-2-(4-fluorophenoxy)-N-methylimidazo (1, 2-a) pyrimidine-3-carboxamide), was synthesized. The in vitro TGR5 receptor activation potential of TRC210258 was assessed by cyclic adenosine monophosphate (cAMP) assay and cAMP-responsive element reporter assay using cells overexpressing the human TGR5 receptor. The effect of TRC210258 on glucagon-like peptide-1 release was evaluated in vitro using a human enteroendocrine cell line. The effect of TRC210258 on energy expenditure and glycemic control was evaluated in high-fat diet-induced obese mice. Additionally, the effect of TRC210258 on dyslipidemic parameters was determined in high fat-fed hamsters. Results TRC210258 demonstrated potent TGR5 agonist activity, with enhanced glucagon-like peptide-1 release and energy expenditure. Treatment with TRC210258 resulted in better glycemic control and improved parameters of dyslipidemia such as plasma triglyceride, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol levels. Treatment with TRC210258 also improved emerging dyslipidemic cardiovascular risk parameters, including remnant cholesterol and triglyceride clearance. Conclusion This study highlights the potential of TRC210258, a novel TGR5 agonist, to improve dyslipidemic cardiovascular risk beyond glycemic control in patients with type 2 diabetes. PMID:24379686
Zambad, Shitalkumar P; Tuli, Davinder; Mathur, Anoop; Ghalsasi, Sameer A; Chaudhary, Anita R; Deshpande, Shailesh; Gupta, Ramesh C; Chauthaiwale, Vijay; Dutt, Chaitanya
parameters describing the results of the function of these systems like heart rate, arterial pressure, cardiac output, or breathing frequency, concentration of O2 and CO2 , etc. Missing significant changes of these parameters during weightlessness supports the hypothesis that adaptational and compensatory mechanisms are sufficient and guarantee cardiovascular homeostasis under changing environmental conditions. characteristic changes of the vegetative balance and of the activity of different regulatory elements at the brainstem and subcortical level. This changes guaranteed the adaptation to long term weightlessness. However, it remains unclear to what extent the different levels are involved. Moreover, the criteria describing the efficacy of cardiorespiratory interaction for the different functional states are not defined yet. The investigation of this problems is highly relevant in order to improve the medical control, especially if considering that the disruption of regulatory systems mostly precedes dangerous destruction of homeostasis. cardiovascular and respiratory function on Board the International Space Station (ISS) aiming to obtain new insights into the interaction between different regulatory elements. "Puls" is measures ECG, photoplethysmogram (PPG), and the pneumotachogram (PTG). The ECG is used to measure time series of R-R intervals and to analyse HRV. PPG is used to define the pulse wave velocity, phases of the cardiac cycle, and an estimate of the filling of finger vessels. The variability of these parameters is also calculated and compared to HRV. The analysis of the PTG allows to describe the interaction of the regulatory parameters of the cardiovascular and respiratory systems. Hence, an important feature of the experiment "Puls" is the investigation of regulatory mechanisms rather than of cardiovascular homeostasis. cardiography) and left ventricular contractility (seismocardiography) will be obtained. This expansion is of major importance because, it allows us to get deeper insight into regulatory mechanisms of the cardiorespiratory system and into the state of cardiovascular homeostasis. have the same size (90 x 60 x 20 mm), identical technology, and identical interfaces with the computer. the onboard experiment and to store the obtained data; 2) "Editor": to archive and dearchive the obtained data, to edit them and to insert necessary comments and markers; 3) "Earth": to edit and analyse the data under laboratory conditions.The subprogram "Earth" is an original software package for data analysis, peak detection, calculation of a variety of parameters, time series forming and editing, statistical and spectral time series analysis. Furthermore, a specialized data base is designated for storing of the biosignals, results of analysis, information about the investigated subjects and comments of simple autonomic function tests will allow to assess different elements of the regulatory mechanisms. Special interest will be given to respiratory tests in order to evaluate the interaction between the cardiovascular system and respiration. volunteers and in patients with different cardiovascular diseases. The results were used to establish normal values and criteria for the prognosis of pathologic changes. These materials will be used at valuation the data obtained during researches on ISS. respiratory systems onboard the ISS are the following: 1) definition of the most important parameters, which can be measured simple and reliable during weightlessness; 2) development of miniaturized devices which can be kept on the astronauts body and which could be used in future as an autonomic system of operational medical control; 3) development of original software packages which allow to detect prognostic changes of the regulatory pattern preceding diseases and based on time series analysis of a large number of cardiorespiratory parameters.
Baranov, V. M.; Baevsky, R. M.; Drescher, J.; Tank, J.
A system and method of modeling a circulatory system including a regulatory mechanism parameter. In one embodiment, a regulatory mechanism parameter in a lumped parameter model is represented as a logistic function. In another embodiment, the circulatory system model includes a compliant vessel, the model having a parameter representing a change in pressure due to contraction of smooth muscles of a wall of the vessel.
Lakin, William D. (Inventor); Stevens, Scott A. (Inventor)
Our objective was to identify the sites of interaction of cannabinoids with cardiovascular sympathetic regulation in the rat. Effects on sympathetic tone were first determined in anaesthetised animals following i.v. administration of the drugs. Central effects were evaluated in anaesthetised rats receiving microinjections of cannabinoids into brain stem nuclei. Peripheral effects were identified in pithed rats with electrically stimulated sympathetic
Nathalie Niederhoffer; Karin Schmid; Bela Szabo
In humans, a chronically increased circulating level of C-reactive protein (CRP), a positive acute-phase reactant, is an independent risk factor for cardiovascular disease. This observation has led to considerable interest in the role of inflammatory proteins in atherosclerosis. In this review, after discussing CRP, we focus on the potential role in the pathogenesis of human vascular disease of inflammation-induced proteins that are carried by lipoproteins. Serum amyloid A (SAA) is transported predominantly on HDL, and levels of this protein increase markedly during acute and chronic inflammation in both animals and humans. Increased SAA levels predict the risk of cardiovascular disease in humans. Recent animal studies support the proposal that SAA plays a role in atherogenesis. Evidence is accruing that secretory phospholipase A(2), an HDL-associated protein, and platelet-activating factor acetylhydrolase, a protein associated predominantly with LDL in humans and HDL in mice, might also play roles both as markers and mediators of human atherosclerosis. In contrast to positive acute-phase proteins, which increase in abundance during inflammation, negative acute-phase proteins have received less attention. Apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, decreases during inflammation. Recent studies also indicate that HDL is oxidized by myeloperoxidase in patients with established atherosclerosis. These alterations may limit the ability of apoA-I to participate in reverse cholesterol transport. Paraoxonase-1 (PON1), another HDL-associated protein, also decreases during inflammation. PON1 is atheroprotective in animal models of hypercholesterolemia. Controversy over its utility as a marker of human atherosclerosis may reflect the fact that enzyme activity rather than blood level (or genotype) is the major determinant of cardiovascular risk. Thus, multiple lipoprotein-associated proteins that change in concentration during acute and chronic inflammation may serve as markers of cardiovascular disease. In future studies, it will be important to determine whether these proteins play a causal role in atherogenesis. PMID:15722558
Chait, Alan; Han, Chang Yeop; Oram, John F; Heinecke, Jay W
Oxidative stress has been implicated in the pathophysiology of several types of cardiovascular disease (CVD). Statins are widely used to inhibit the progression of atherosclerosis and reduce the incidence of CVD. Certain over-the-counter products, including resveratrol, show similar effects to statins and may thus be used in conjunction with statins for the treatment of the majority of patients with CVD. The aim of the present study was to evaluate the effects of atorvastatin, resveratrol and resveratrol + atorvastatin (R+A) pretreatment on myocardial contractions and vascular endothelial functions in the presence of H2O2 as an experimental model of oxidative stress in rats. Four groups were established and referred to as the control, atorvastatin, resveratrol and R+A groups. Atorvastatin (40 mg/kg, per oral) and/or resveratrol (30 mg/kg, intraperitoneal) treatments were administered for 14 days. On the 15th day, the thoracic aortas and hearts of the rats were dissected and placed into isolated organ baths. Vascular responses to cumulative doses of H2O2 (1×10?8–1×10?4 M H2O2) with and without N (G)-nitro-L-arginine methyl ester (L-NAME) incubation were measured. In addition, myocardial electrical stimulation (ES) responses to various H2O2 concentrations (1×10?7–1×10?5 M H2O2) were evaluated. In the control and atorvastatin groups, H2O2 application caused a significant dose-dependent decrease in the ES-induced contractions in the myocardial tissue of rats. In the resveratrol and R+A groups, H2O2 application did not significantly affect myocardial contraction at any dose. In all groups, incubation with L-NAME caused a significant augmentation in the H2O2 response, revealing that this effect was mediated via the vascular endothelium. In conclusion, pretreatment with R+A for CVD appears to be superior to pretreatment with either agent alone.
SONER, BURAK CEM; SAHIN, AYSE SAIDE
The paper deals with the justification and description of clinical and organizational approaches to preventing cardiovascular diseases (CVD) in the primary health care system (PHCS) under the present conditions of health care modernization in Russia. It formulates the basic directions of systematic measures in integration strategies for the prevention of noncommunicable diseases (mainly CVD) at a federal level, in which practical measures are presented to improve a system for the early detection of high-risk individuals and to carry out measures for risk factor correction in PHCS, i.e. to implement high-risk strategies, including clinical and organizational approaches to reconstituting the medical prevention infrastructure in PHCS. This is favored by the new normative documents adopted by the Ministry of Health of Russia on the follow-up and prophylactic medical examinations of the adult population. The paper substantiates the objective need for such examinations and characterizes the main clinical and organizational approaches promoted in medical examinations, which is aimed at introducing the current science-based and economically expedient methods in the real practice of PHCS for the early identifications of atherosclerosis-induced major CVDs and, what is particularly important, a risk for their development. Prophylactic counseling as a compulsory component is first being introduced in medical examination procedures. The key clinical and organizational principle of effective CVD prevention in public health is the implementation of the relationship and continuity of preventive measures, which becomes realistic with the adoption of new regulations of clinical examinations, prophylactic medical examinations, and follow-ups. The improvement of CVD prevention is associated not only with the introduction of organizational innovation changes, but also with the need to create a prevention ideology in physicians at all levels. It is emphasized that a comprehensive approach and all integrated CVD prevention strategies both at the population level and in the PHCS facilities are the most efficient and cost-effective procedure to reduce premature deaths from CVD in the population and to improve the demographic situation in our country. PMID:24137958
Bo?tsov, S A; Kalinina, A M; Ipatov, P V
As part of the series on Controversies in Cardiovascular Research, the article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize anti-arrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders such as long QT syndrome, Brugada Syndrome or Catecholaminergic Polymorphic Ventricular Tachycardia. PMID:23569106
Knollmann, Bjorn C
During the last decade the use of numerical modeling for geothermal resource evaluation has grown significantly, and new modeling approaches have been developed. In this paper we present a summary of the present status in numerical modeling of geothermal systems, emphasizing recent developments. Different modeling approaches are described and their applicability discussed. The various modeling tasks, including natural-state, exploitation, injection, multi-component and subsidence modeling, are illustrated with geothermal field examples. 99 refs., 14 figs.
Bodvarsson, G.S.; Pruess, K.; Lippmann, M.J.
Introduction Cardiovascular disease (CVD) is a leading cause of death in sub-Saharan Africa (SSA), with annual deaths expected to increase to 2 million by 2030. Currently, most national health systems in SSA are not adequately prepared for this epidemic. This is especially so in slum settlements where access to formal healthcare and resources is limited. Objective To develop and introduce a model of cardiovascular prevention in the slums of Nairobi by integrating public health and private sector approaches. Study design Two non-profit organizations that conduct public health research, Amsterdam Institute for Global Health and Development (AIGHD) and African Population and Health Research Center (APHRC), collaborated with private-sector Boston Consulting Group (BCG) to develop a service delivery package for CVD prevention in slum settings. A theoretic model was designed based on the integration of public and private sector approaches with the focus on costs and feasibility. Results The final model includes components that aim to improve community awareness, a home-based screening service, patient and provider incentives to seek and deliver treatment specifically for hypertension, and adherence support. The expected outcomes projected by this model could prove potentially cost effective and affordable (1 USD/person/year). The model is currently being implemented in a Nairobi slum and is closely followed by key stakeholders in Kenya including the Ministry of Health, the World Health Organization (WHO), and leading non-governmental organizations (NGOs). Conclusion Through the collaboration of public health and private sectors, a theoretically cost-effective model was developed for the prevention of CVD and is currently being implemented in the slums of Nairobi. If results are in line with the theoretical projections and first impressions on the ground, scale-up of the service delivery package could be planned in other poor urban areas in Kenya by relevant policymakers and NGOs. PMID:24149078
van de Vijver, Steven; Oti, Samuel; Tervaert, Thijs Cohen; Hankins, Catherine; Kyobutungi, Catherine; Gomez, Gabriela B.; Brewster, Lizzy; Agyemang, Charles; Lange, Joep
NADPH oxidase family enzymes (or NOXs) are the major sources of reactive oxygen species (ROS) that are implicated in the pathophysiology\\u000a of many cardiovascular diseases. These enzymes appear to be especially important in the modulation of redox-sensitive signalling\\u000a pathways that underlie key cellular functions such as growth, differentiation, migration and proliferation. Seven distinct\\u000a members of the family have been identified
Alexander Sirker; Min Zhang; Ajay M. Shah
Athletes who abuse recombinant human erythropoietin (rhEPO) consider only the benefit to performance and usually ignore the potential short and long-term liabilities. Elevated haematocrit and dehydratation associated with intense exercise may reveal undetected cardiovascular risk, but the mechanisms underlying it remain to be fully explained. This study aimed to evaluate the cardiovascular effects of rhEPO in rats under chronic aerobic exercise. A ten week protocol was performed in four male Wistar rat groups: control--sedentary; rhEPO--50 IU kg(-1), 3 times/wk; exercised (EX)--swimming for 1 h, 3 times/wk; EX + rhEPO. One rat of the EX + rhEPO group suffered a sudden death episode during the week 8. rhEPO in trained rats promoted erythrocyte count increase, hypertension, heart hypertrophy, sympathetic and serotonergic overactivation. The suddenly died rat's tissues presented brain with vascular congestion; left ventricular hypertrophy, together with a "cardiac-liver", suggesting the hypothesis of heart failure as cause of sudden death. In conclusion, rhEPO doping in rats under chronic exercise promotes not only the expected RBC count increment, suggesting hyperviscosity, but also other serious deleterious cardiovascular and thromboembolic modifications, including mortality risk, which might be known and assumed by all sports authorities, including athletes and their physicians. PMID:19859831
Piloto, Nuno; Teixeira, Helena M; Teixeira-Lemos, Edite; Parada, Belmiro; Garrido, Patrícia; Sereno, José; Pinto, Rui; Carvalho, Lina; Costa, Elísio; Belo, Luís; Santos-Silva, Alice; Teixeira, Frederico; Reis, Flávio
The metabolic syndrome (MetS) is associated with an increased risk of cardiac mortality, as it is characterised by the clustering of multiple cardiovascular risk factors. Studies have shown that capsaicin (red pepper) may be useful as a nutraceutical, ameliorating metabolic profile and cardiovascular function. The aim of the present study was to investigate the cardiovascular and metabolic effects of orally administered capsaicin in rats with the MetS. Neonate spontaneously hypertensive rats were injected with monosodium glutamate and subjected to one of the following three treatments by oral administration for 14 d, between 27 and 30 weeks: low-dose capsaicin (CAP05, n 18, synthetic capsaicin powder diluted in a vehicle (10 % ethyl alcohol) plus 0·5 mg/kg body weight (BW) of capsaicin); high-dose capsaicin (CAP1, n 19, synthetic capsaicin powder diluted in a vehicle (10 % ethyl alcohol) plus 1 mg/kg BW of capsaicin); control (C, n 18, vehicle). Lee's index, lipid/metabolic profile, and cardiovascular parameters with the rats being conscious, including arterial pressure (AP) and heart rate (HR) variability, as well as aortic wall thickness (haematoxylin and eosin staining) and CD68 (cluster of differentiation 68) antibody levels (monocyte/macrophage immunostaining) were evaluated. Weight, Lee's index, and lipid and metabolic parameters, as well as AP and HR and aortic wall thickness, were similar between the groups. Capsaicin determined HR variability improvement (16·0 (sem 9·0), 31·0 (sem 28·2) and 31·3 (sem 19·0) ms2 for the C, CAP05 and CAP1 groups, respectively, P= 0·003), increased vascular sympathetic drive (low-frequency component of systolic AP variability: 3·3 (sem 2·8), 8·2 (sem 7·7) and 12·1 (sem 8·8) mmHg2 for the C, CAP05 and CAP1 groups, respectively, P< 0·001) and increased ?-index (spontaneous baroreflex sensitivity). The present data show that capsaicin did not improve lipid and glucose abnormalities in rats with the MetS. However, beneficial cardiovascular effects were observed with this nutraceutical. PMID:23968579
Tremarin, Camila da Silva; Casali, Karina Rabello; Meurer, Luise; Schaan, Beatriz D'Agord
The race for a cure to cancer continues, fueled by unprecedented discoveries of fundamental biology underlying carcinogenesis and tumorogenesis. The expansion of the target list and tools to approach them is moving the oncology community extraordinarily rapidly to clinical trials, bringing new hope for cancer victims. This effort is also propelling biological discoveries in cardiovascular research as many of the targets being explored in cancer play fundamental roles in the heart and vasculature. The combined efforts of cardiovascular and cancer biologists, along with clinical investigators in these fields, will be needed to understand how to safely exploit these efforts. Here we discuss a few of the many research foci in oncology where we believe such collaboration will be particularly important. PMID:20360265
Peng, Xuyang; Pentassuglia, Laura; Sawyer, Douglas B.
Candidate gene association studies in cardiovascular diseases have provided evidence on the molecular basis of phenotypic\\u000a differences between individuals. The comprehension of how inherited genetic variants are able to affect protein functions\\u000a has increased the knowledge of how genes interact with environment in order to modulate a particular phenotype. Although it\\u000a is known that the human genome contains more than
Rodrigo Gonçalves Dias; Márcia Maria Gowdak; Alexandre Costa Pereira
Adipose tissue modifies the development of cardiovascular disease in a complex manner: obesity is a major risk factor, but particularly when accompanied with a central fat distribution. For that reason the characteristics of visceral adipose tissue attracted the majority of research interest thus far and measurement of waist circumference is now recommended for everyday clinical practice. However, the direct, causative role of visceral fat in cardiometabolic disease remains to be established. Epidemiological and clinical studies show that accumulation of fat subcutaneously, in the gluteo-femoral area, is protective for cardiovascular disease, but the exact molecular mechanisms remain again unclear. In the last few years, imaging allowed the study of smaller fat depots that may interact locally with important tissues: epicardial fat with the myocardium, perivascular fat with the vessel wall and the developing atherosclerotic plaque, renal sinus fat with the renal artery. Unraveling the heterogeneous fat distribution and metabolic phenotypes in human obesity will facilitate optimal assessment of cardiovascular risk in overweight and obese individuals. PMID:23982264
Karastergiou, Kalypso; Fried, Susan K.
Atherosclerotic cardiovascular disease (ASCVD) contributes to morbidity and mortality in systemic lupus erythematosus (SLE).\\u000a Immunologic derangements may disrupt cholesterol balance in vessel wall monocytes\\/macrophages and endothelium. We determined\\u000a whether lupus plasma impacts expression of cholesterol 27-hydroxylase, an anti-atherogenic cholesterol-degrading enzyme that\\u000a promotes cellular cholesterol efflux, in THP-1 human monocytes and primary human aortic endothelial cells (HAEC). THP-1 monocytes\\u000a and HAEC
Allison B. Reiss; Kamran Anwar; Joan T. Merrill; Edwin S. L. Chan; Nahel W. Awadallah; Bruce N. Cronstein; H. Michael Belmont; Elise Belilos; Gary Rosenblum; Kristina Belostocki; Lois Bonetti; Kowser Hasneen; Steven E. Carsons
It is accepted that oxidative stress and inflammation play an integral role in the pathophysiology of many chronic diseases including atherosclerotic cardiovascular disease. The xanthophyll carotenoid dietary supplement astaxanthin has demonstrated potential as an antioxidant and anti-inflammatory therapeutic agent in models of cardiovascular disease. There have been at least eight clinical studies conducted in over 180 humans using astaxanthin to assess its safety, bioavailability and clinical aspects relevant to oxidative stress, inflammation or the cardiovascular system. There have been no adverse outcomes reported. Studies have demonstrated reduced markers of oxidative stress and inflammation and improved blood rheology. A larger number of experimental studies have been performed using astaxanthin. In particular, studies in a variety of animals using a model of myocardial ischemia and reperfusion have demonstrated protective effects from prior administration of astaxanthin both intravenously and orally. Future clinical studies and trials will help determine the efficacy of antioxidants such as astaxanthin on vascular structure, function, oxidative stress and inflammation in a variety of patients at risk of, or with, established cardiovascular disease. These may lead to large intervention trials assessing cardiovascular morbidity and mortality. PMID:19656058
Fassett, Robert G; Coombes, Jeff S
There are several computer-based systems, currently in various phases of development at KSC, which encompass some component, aspect, or function of workforce modeling. These systems may offer redundant capabilities and/or incompatible interfaces. A systems approach to workforce modeling is necessary in order to identify and better address user requirements. This research has consisted of two primary tasks. Task 1 provided an assessment of existing and proposed KSC workforce modeling systems for their functionality and applicability to the workforce planning function. Task 2 resulted in the development of a proof-of-concept design for a systems approach to workforce modeling. The model incorporates critical aspects of workforce planning, including hires, attrition, and employee development.
Moynihan, Gary P.
. In this paper we show how numerical solutions of human cardiovascular system may be devised by coupling models having different\\u000a physical dimensions. One of the aspects of circulatory system is indeed its multiscale nature. Local flow features may have\\u000a a global effect on circulation. For instance, a stenosis caused by an atherosclerotic plaque may change the overall characteristic\\u000a of
Luca Formaggia; Fabio Nobile; Alfio Quarteroni; Alessandro Veneziani
The increasing prevalence of cardiovascular disease (CVD) has prompted leading cardiovascular organizations to advocate utilization of a team approach to patient care that includes nonphysician providers. In spite of that, the American College of Cardiology reported that nonphysician providers are underutilized in the management of patients with CVD. A survey of cardiologists revealed that the underutilization is a result of lack of understanding of how best to involve nonphysician providers in the health care team. Clinical pharmacists are one category of nonphysician providers that have recognized effectiveness in managing patients with CVD. No example of a comprehensive model of collaboration between cardiologists and clinical pharmacists is described in the literature that could serve to close this gap in understanding. The objective of this report is to describe a model of cardiologist-clinical pharmacist collaboration in the longitudinal management of patients with CVD that has been successfully implemented in 2 diverse settings. The implementation, evolution, scope of practice, required pharmacist training, logistical elements needed for success, and implementation barriers are reviewed. A summary of the patients referred to the clinic are examined as well. PMID:24321852
Ripley, Toni L; Adamson, Philip B; Hennebry, Thomas A; Van Tuyl, Joseph S; Harrison, Donald L; Rathbun, R Chris
Cardiovascular disease (CVD) is largely the product of interactions among modifiable risk factors that are common in developed nations and increasingly of concern in developing countries. Hypertension is an important precursor to the development of CVD, and although detection and treatment rates have improved in recent years in some jurisdictions, effective strategies and policies supporting a shift in distribution of risk factors at the population level remain paramount. Challenges in managing cardiovascular health more effectively include factors at the patient, provider, and system level. Strategies to reduce hypertension and CVD should be population based, incorporate multilevel, multicomponent, and socioenvironmental approaches, and integrate community resources with public health and clinical care. There is an urgent need to improve monitoring and management of risk factors through community-wide, primary care-linked initiatives, increase the evidence base for community-based prevention strategies, further develop and evaluate promising program components, and develop new approaches to support healthy lifestyle behaviors in diverse age, socioeconomic, and ethnocultural groups. Policy and system changes are critical to reduce risk in populations, including legislation and public education to reduce dietary sodium and trans-fatty acids, food pricing policies, and changes to health care delivery systems to explicitly support prevention and management of CVD. PMID:22312217
Karwalajtys, Tina; Kaczorowski, Janusz
Increased endocannabinoid (EC) system activity promotes excessive food intake and obesity in animals and humans. The EC system regulates food intake and hedonic reward through central mechanisms located within the hypothalamus and limbic forebrain. In rodent models, cannabinoid1 (CB1) receptor blockade reduces appetite and weight and prevents obesity and insulin resistance. The EC system also regulates food intake and metabolic factors through peripheral CB1 receptors located at multiple sites throughout the body, including adipose tissue, skeletal muscle, liver, and the gastrointestinal (GI) tract. In rodent models, CB1 receptor antagonists act in the liver to decrease lipogenesis, act in the GI tract to increase satiety, and function in adipose tissue to normalize adiponectin levels and reduce fat storage. The CB1 receptor antagonist rimonabant has been shown to reduce food intake and improve metabolic parameters, such as insulin resistance and fatty liver, in animal models of obesity. In preliminary human studies, upregulation of the EC system has been linked to obesity through mechanisms that include high-fat diet, insulin resistance, and genetic malfunction of an EC inactivation enzyme. Evidence suggests that CB1 receptor blockade is a novel therapeutic strategy that addresses the underlying mechanisms of both obesity and cardiometabolic risk. PMID:17320518
Woods, Stephen C
Purpose This article provides an update on cardiovascular genomics using three clinically relevant exemplars, including myocardial infarction (MI) and coronary artery disease (CAD), stroke, and sudden cardiac death (SCD). Organizational Construct Recent advances in cardiovascular genomic research, testing, and clinical implications are presented. Methods Genomic nurse experts reviewed and summarized recent salient literature to provide updates on three selected cardiovascular genomic conditions. Findings Research is ongoing to discover comprehensive genetic markers contributing to many common forms of cardiovascular disease (CVD), including MI and stroke. However, genomic technologies are increasingly being used clinically, particularly in patients with long QT syndrome (LQTS) or hypertrophic cardiomyopathy (HCM) who are at risk for SCD. Conclusions Currently, there are no clinically recommended genetic tests for many common forms of CVD even though direct-to-consumer genetic tests are being marketed to healthcare providers and the general public. On the other hand, genetic testing for patients with certain single gene conditions, including channelopathies (e.g., LQTS) and cardiomyopathies (e.g., HCM), is recommended clinically. Clinical Relevance Nurses play a pivotal role in cardiogenetics and are actively engaged in direct clinical care of patients and families with a wide variety of heritable conditions. It is important for nurses to understand current development of cardiovascular genomics and be prepared to translate the new genomic knowledge into practice. PMID:23368089
Wung, Shu-Fen; Hickey, Kathleen T.; Taylor, Jacquelyn Y.; Gallek, Matthew J.
The Earth System Model is the natural evolution of current climate models and will be the ultimate embodiment of our geophysical understanding of the planet. These models are constructed from components - atmosphere, ocean, ice, land, chemistry, solid earth, etc. models and merged together through a coupling program which is responsible for the exchange of data from the components. Climate models and future earth system models will have standardized modules, and these standards are now being developed by the ESMF project funded by NASA. The Earth System Model will have a variety of uses beyond climate prediction. The model can be used to build climate data records making it the core of an assimilation system, and it can be used in OSSE experiments to evaluate. The computing and storage requirements for the ESM appear to be daunting. However, the Japanese ES theoretical computing capability is already within 20% of the minimum requirements needed for some 2010 climate model applications. Thus it seems very possible that a focused effort to build an Earth System Model will achieve succcss.
Schoeberl, Mark; Rood, Richard B.; Hildebrand, Peter; Raymond, Carol
Purpose of the work was to study the cardiovascular effects of simulated factors in a 520-day crewed mission to Mars, and to validate the diagnostic value of the ultrasonic investigation of microcirculation and endothelium-dependent dilation of the right brachial artery in 6 male volunteers at the age of 28 to 39 years. It appears that 520-d isolation affected intracardiac hemodynamics and endothelium function more dramatically compared with 105-d isolation, increasing the risk of atherosclerosis. These findings add insight into the "cost of human adaptation" to very long isolation. PMID:25365873
Stepanova, G P; Bu?lov, S P; Eshchenko, A I; Skedina, M A; Voronkov, Iu I
Hepatocytes play a central and crucial role in cholesterol and lipid homeostasis, and their proper function is of key importance for cardiovascular health. In particular, hepatocytes (especially periportal hepatocytes) endogenously synthesize large amounts of cholesterol and secrete it into circulating blood via apolipoprotein particles. Cholesterol-secreting hepatocytes are also the clinically-relevant cells targeted by statin treatment in vivo. The study of cholesterol homeostasis is largely restricted to the use of animal models and immortalized cell lines that do not recapitulate those key aspects of normal human hepatocyte function that result from genetic variation of individuals within a population. Hepatocyte-like cells (HLCs) derived from human embryonic and induced pluripotent stem cells can provide a cell culture model for the study of cholesterol homeostasis, dyslipidemias, the action of statins and other pharmaceuticals important for cardiovascular health. We have analyzed expression of core components for cholesterol homeostasis in untreated human iPS cells and in response to pravastatin. Here we show the production of differentiated cells resembling periportal hepatocytes from human pluripotent stem cells. These cells express a broad range of apolipoproteins required for secretion and elimination of serum cholesterol, actively secrete cholesterol into the medium, and respond functionally to statin treatment by reduced cholesterol secretion. Our research shows that HLCs derived from human pluripotent cells provide a robust cell culture system for the investigation of the hepatic contribution to human cholesterol homeostasis at both cellular and molecular levels. Importantly, it permits for the first time to also functionally assess the impact of genetic polymorphisms on cholesterol homeostasis. Finally, the system will also be useful for mechanistic studies of heritable dyslipidemias, drug discovery, and investigation of modes of action of cholesterol-modulatory drugs. PMID:23874411
Krueger, Winfried H.; Tanasijevic, Borko; Barber, Vanessa; Flamier, Anthony; Gu, Xinsheng; Manautou, Jose; Rasmussen, Theodore P.
Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901
Dai, Dao-Fu; Ungvari, Zoltan
In order to improve the intraoperative applications, this paper presents the advantages of using Guyton's model in hypotensive control system development. In this system, the mean arterial pressure is decreased and maintained at a low level during anaesthesia by controlling sodium nitroprusside infusion rate. The key of the study is to develop a physiological model of cardiovascular dynamics to present
Chi-ngon Nguyen; Olaf Simanski; Ralf Kähler; Agnes Schubert; Matthias Janda; Jörn Bajorat; Bernhard Lampe
Cardiovascular complications (CVC) are the most common causes of death in patients with type 2 diabetes (T2D). However the pathophysiological determinants and molecular mechanisms involved in the progression of CVC in T2D are poorly understood. We have undertaken the challenging task of identifying some of the genetic and clinical determinants of CVC through a unique multidisciplinary approach involving Canadian and Finnish investigators. We are studying novel animal models combining atherosclerosis, diet-induced obesity and T2D to understand the molecular basis of CVC in obesity-linked T2D. We are also conducting clinical studies to identify key determinants of CVC in T2D patients and to determine whether a lifestyle modification program targeting loss of visceral adipose tissue/ectopic fat could be associated with clinical benefits in these patients. Together, we strongly believe that we can fill some gaps in our understanding of the CVC pathogenesis in T2D and identify novel therapeutic targets and hope that this new knowledge may be translated into the design of effective clinical interventions to optimally reduce cardiovascular risk in T2D subjects. PMID:24500564
Kohen Avramoglu, Rita; Laplante, Marc-André; Le Quang, Khai; Deshaies, Yves; Després, Jean-Pierre; Larose, Eric; Mathieu, Patrick; Poirier, Paul; Pérusse, Louis; Vohl, Marie-Claude; Sweeney, Gary; Ylä-Herttuala, Seppo; Laakso, Markku; Uusitupa, Matti; Marette, André
Cyclooxygenase-2 (COX-2) has been found to be activated in diabetes. We investigated whether nimesulide (selective COX-2 inhibitor) alters cardiovascular responses to adrenaline in 2 rat models of diabetes. Wistar rats (5-week old) were continuously fed a normal or high-fructose diet (60% of caloric intake). At week 2, half of the rats in each diet regimen were given streptozotocin (STZ) (60 mg/kg, intravenously). At week 6, cardiovascular effects of adrenaline (6 and 16 × 10 mol·kg·min, intravenously) were measured in 4 groups of thiobutabarbital-anesthetized rats (control, fructose, STZ, and fructose-streptozotocin [F-STZ]) before and after the injection of nimesulide (3 mg/kg, intravenously). Both the STZ and F-STZ groups exhibited hyperglycemia and significantly (P < 0.05) reduced left ventricular contractility, mean arterial pressure, arterial and venous resistance, and mean circulatory filling pressure (index of venous tone) responses to adrenaline, relative to the control and fructose groups. Nimesulide did not affect responses in the control and fructose groups but increased the venous and, to a less extent, arterial constriction to adrenaline in both the groups of diabetic rats. The cardiac contractile responses, however, were not altered after nimesulide treatment. The results show that nimesulide partially restored arterial and venous constriction to adrenaline in rats with STZ- and F-STZ-induced diabetes. PMID:24621649
Leung, Joanne Y T; Pang, Catherine C Y
Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPAR? agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPAR? agonists, and more recently dual PPAR?/? coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPAR? receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease. PMID:18288280
Calkin, Anna C.; Thomas, Merlin C.
Pre-conception or gestationally-induced diabetes increases morbidities and elevates long-term cardiovascular disease risks in women and their children. Spontaneously hyperglycemic (d)-NOD/ShiLtJ females, a type 1 diabetes model, develop bradycardia and hypotension after midpregnancy compared with normoglycemic, age and gestation day (gd)-matched controls (c-NOD). We hypothesized that onset of the placental circulation at gd9–10 and rapid fetal growth from gd14 correlate with aberrant hemodynamic outcomes in d-NOD females. To develop further gestational time course correlations between maternal cardiac and renal parameters, high-frequency ultrasonography was applied to virgin and gd8–16 d- and c-NODs. Cardiac output and left ventricular (LV) mass increased in c- but not d-NODs. Ultrasound and postmortem histopathology showed overall greater LV dilation in d- than c-NOD mice in mid-late gestation. These changes suggest blunted remodeling and altered functional adaptation of d-NOD hearts. Umbilical cord ultrasounds revealed lower fetal heart rates from gd12 and lower umbilical flow velocities at gd14 and 16 in d- versus c-NOD pregnancies. From gd14–16, d-NOD fetal losses exceeded those of c-NOD. Similar aberrant responses in human diabetic pregnancies may elevate postpartum maternal and child cardiovascular risk, particularly if mothers lack adequate prenatal care or have poor glycemic control over gestation. PMID:23636813
Aasa, Kristiina L.; Kwong, Kenneth K.; Adams, Michael A.; Croy, B. Anne
Summary As cocaine use has become prevalent, an increasing number of reports of cocaine-associated morbidity and mortality, largely because of central nervous system and cardiovascular toxicity, appeared. Cardiovascular toxicity is broad, and it may also lead to neurological, psychiatric and other organ-specific symptoms. Cocaine may induce myocardial ischemia by increasing myocardial oxygen demand while simultaneously decreasing myocardial oxygen supply. Most
The management of cardiovascular risk through lifestyle modification and pharmacotherapy is paramount to the prevention of cardiovascular disease. Epidemiological studies have identified obesity, dyslipidemia, diabetes, and hypertension as interrelated factors that negatively affect cardiovascular health. Recently, genetic and pharmacological evidence in model systems has implicated microRNAs as dynamic modifiers of disease pathogenesis. An expanded understanding of the function of microRNAs in gene regulatory networks associated with cardiovascular risk will enable identification of novel genetic mechanisms of disease and inform the development of innovative therapeutic strategies. PMID:23281405
Quiat, Daniel; Olson, Eric N
Background and Purpose Mitochondria are a drug target in mitochondrial dysfunction diseases and in antiparasitic chemotherapy. While zebrafish is increasingly used as a biomedical model, its potential for mitochondrial research remains relatively unexplored. Here, we perform the first systematic analysis of how mitochondrial respiratory chain inhibitors affect zebrafish development and cardiovascular function, and assess multiple quinones, including ubiquinone mimetics idebenone and decylubiquinone, and the antimalarial atovaquone. Experimental Approach Zebrafish (Danio rerio) embryos were chronically and acutely exposed to mitochondrial inhibitors and quinone analogues. Concentration-response curves, developmental and cardiovascular phenotyping were performed together with sequence analysis of inhibitor-binding mitochondrial subunits in zebrafish versus mouse, human and parasites. Phenotype rescuing was assessed in co-exposure assays. Key Results Complex I and II inhibitors induced developmental abnormalities, but their submaximal toxicity was not additive, suggesting active alternative pathways for complex III feeding. Complex III inhibitors evoked a direct normal-to-dead transition. ATP synthase inhibition arrested gastrulation. Menadione induced hypochromic anaemia when transiently present following primitive erythropoiesis. Atovaquone was over 1000-fold less lethal in zebrafish than reported for Plasmodium falciparum, and its toxicity partly rescued by the ubiquinone precursor 4-hydroxybenzoate. Idebenone and decylubiquinone delayed rotenone- but not myxothiazol- or antimycin-evoked cardiac dysfunction. Conclusion and Implications This study characterizes pharmacologically induced mitochondrial dysfunction phenotypes in zebrafish, laying the foundation for comparison with future studies addressing mitochondrial dysfunction in this model organism. It has relevant implications for interpreting zebrafish disease models linked to complex I/II inhibition. Further, it evidences zebrafish's potential for in vivo efficacy or toxicity screening of ubiquinone analogues or antiparasitic mitochondria-targeted drugs. PMID:23758163
Pinho, Brigida R; Santos, Miguel M; Fonseca-Silva, Anabela; Valentao, Patricia; Andrade, Paula B; Oliveira, Jorge M A
This teaching resource was developed by a K-12 science teacher in the American Physiologycal Society's 2006 Frontiers in Physiology Program. For more information on this program, please visit www.frontiersinphys.org. The purpose of this activity is to investigate and develop a model of the normal anatomy of the human heart/circulatory system and then to explore and model the effects of several cardiovascular disease processes. Students should understand basic cellular respiration. Upon completion of this activity, students will be able to: plan and design a model of a human heart with basic systemic circulation and evaluate impact of cardiovascular diseases on normal circulation.
Cynthia Pfirrmann (Scotch Plains-Fanwood High School)
Devices and techniques for measuring and analyzing systolic time intervals and quantitative phonocardiograms were initiated during Apollo 17. The data show that the systolic time interval from Apollo 17 crewmen remained elevated longer postflight than the response criteria of heart rate, blood pressure, and percent change in leg volume all of which had returned to preflight levels by the second day postflight. Although the systolic time interval values were only slightly outside the preflight fiducial limits, this finding suggested that: the analysis of systolic time intervals may help to identify the mechanisms of postflight orthostatic intolerance by virtue of measuring ventricular function more directly and, the noninvasive technique may prove useful in determining the extent and duration of cardiovascular instability after long duration space flight. The systolic time intervals obtained on the Apollo 17 crewmen during lower body negative pressure were similar to those noted in patients with significant heart disease.
Bergman, S. A., Jr.; Johnson, R. L.; Hoffler, G. W.
Chronically heightened physiological reactivity to or delayed recovery from stress may contribute to cardiovascular (CV) risk and mortality. Long-term stability of physiological stress responses has received little attention. Our objectives were to evaluate the 3-year stability of reactivity and recovery change scores across CV and autonomic parameters and assess whether sex and age moderate stability. A total of 134 healthy participants underwent two laboratory stress protocols, including four 5-min interpersonal stressors, each followed by a 5-min recovery period. Heart rate (HR), blood pressure (BP), and HR variability (high frequency, low frequency, very low frequency [VLF]) were obtained. Spearman rank correlations and linear regressions were performed. Significant correlations emerged for all physiological measures except diastolic BP and VLF recovery. No significant sex or age differences were found. Stress responses represent stable individual traits little affected by sex or age. PMID:24853995
Dragomir, Anda I; Gentile, Christina; Nolan, Robert P; D'Antono, Bianca
Imbalance between production and scavenging of superoxide anion results in hypertension by the inactivation of nitric oxide, and the increased oxidative stress from the resultant peroxynitrite that is produced promotes inflammatory processes such as atherosclerosis. Induction of phase 2 proteins promotes oxidant scavenging. We hypothesized that intake of dietary phase 2 protein inducers would ameliorate both hypertension and atherosclerotic changes in the spontaneously hypertensive stroke-prone rat. For 5 days/week for 14 weeks, we fed rats 200 mg/day of dried broccoli sprouts that contained glucoraphanin, which is metabolized into the phase 2 protein-inducer sulforaphane (Group A), sprouts in which most of the glucoraphanin was destroyed (Group B), or no sprouts (Group C). After 14 weeks of treatment, no significant differences were seen between rats in Groups B and C. Rats in Group A had significantly decreased oxidative stress in cardiovascular and kidney tissues, as shown by increased glutathione (GSH) content and decreased oxidized GSH, decreased protein nitrosylation, as well as increased GSH reductase and GSH peroxidase activities. Decreased oxidative stress correlated with better endothelial-dependent relaxation of the aorta and significantly lower (20 mm Hg) blood pressure. Tissues from Groups B and C had considerable numbers of infiltrating activated macrophages, indicative of inflammation, whereas animals in Group A had few detectable infiltrating macrophages. There is interest in dietary phase 2 protein inducers as means of reducing cancer incidence. We conclude that a diet containing phase 2 protein inducers also reduces the risk of developing cardiovascular problems of hypertension and atherosclerosis. PMID:15103025
Wu, Lingyun; Ashraf, M. Hossein Noyan; Facci, Marina; Wang, Rui; Paterson, Phyllis G.; Ferrie, Alison; Juurlink, Bernhard H. J.
Microalbuminuria is a marker for generalized vascular dysfunction. Its prevalence in United States and European general population surveys ranges from 6% to 10%. Increased risk for cardiovascular morbidity and mortality begins with albumin excretion rates that are well within normal limits. Although microalbuminuria interacts with the traditional cardiovascular risk factors, it has an independent relationship to renal and cardiovascular outcomes. For example, microalbuminuria doubles the risk for a cardiovascular event in patients with type 2 diabetes mellitus even after adjusting for the usual risk factors. Elevated rates of urinary albumin excretion predict target organ damage, notably renal disease, but are also related to left ventricular dysfunction, stroke, and myocardial infarction. Screening for microalbuminuria, which is recommended by several expert committees and associations, has become a readily accessible procedure. Screening can give clinicians prognostic information concerning cardiovascular risk and assist in guiding therapy. The goal of treatment is to prevent progression of, and even to reverse, microalbuminuria. Abundant evidence demonstrates that antihypertensive therapy is an important key to the control of urinary albumin excretion, and blockade of the renin-angiotensin system (with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) is the treatment of choice. These drugs have successfully halted or delayed the progression to nephropathy and have reversed elevated rates of albumin excretion to normal values, even when blood pressure reduction has been minimal. PMID:15485765
Karalliedde, Janaka; Viberti, Giancarlo
The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1? and IL-1? antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases. PMID:25119884
Yamanaka, Keiichi; Nakanishi, Takehisa; Saito, Hiromitsu; Maruyama, Junko; Isoda, Kenichi; Yokochi, Ayumu; Imanaka-Yoshida, Kyoko; Tsuda, Kenshiro; Kakeda, Masato; Okamoto, Ryuji; Fujita, Satoshi; Iwakura, Yoichiro; Suzuki, Noboru; Ito, Masaaki; Maruyama, Kazuo; Gabazza, Esteban C.; Yoshida, Toshimichi; Shimaoka, Motomu; Mizutani, Hitoshi
The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1? and IL-1? antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases. PMID:25119884
Yamanaka, Keiichi; Nakanishi, Takehisa; Saito, Hiromitsu; Maruyama, Junko; Isoda, Kenichi; Yokochi, Ayumu; Imanaka-Yoshida, Kyoko; Tsuda, Kenshiro; Kakeda, Masato; Okamoto, Ryuji; Fujita, Satoshi; Iwakura, Yoichiro; Suzuki, Noboru; Ito, Masaaki; Maruyama, Kazuo; Gabazza, Esteban C; Yoshida, Toshimichi; Shimaoka, Motomu; Mizutani, Hitoshi
CSU Research Colloquium Cardiovascular Research at CSU: Molecules, Models and Mankind Hilton Fort 10:00 AM Break 10:30 AM Session I: Basic Cardiovascular Science Chair, Adam Chicco, PhD, Director that focuses on understanding the cellular and molecular bases of cardiovascular function in health and disease
Stephens, Graeme L.
1. In the duck systemic arterial baroreceptors which cause bradycardia in response to induced hypertension are located in the walls of the ascending aorta, innervated by the depressor nerves. 2. The location of the baroreceptors was confirmed both histologically and by recording activity from the depressor nerve. Stimulation of the central cut end of a depressor nerve caused transient bradycardia and a fall in blood pressure which was maintained throughout the period of stimulation. 3. Cardiovascular adjustments to submergence of 2 min duration were monitored in intact, sham-operated and denervated ducks. The sham-operated and denervated ducks were used in the experiments some 20-50 days post-operation. The denervations were checked at post-mortem. 4. In the first series of experiments on young ducks mean arterial pressure during a 2 min dive fell by 30% in intact, 17·5% in sham-operated, and 48% in denervated ducks. In all ducks heart rate was reduced by 84-85%. 5. In a second series of experiments on older ducks sciatic artery blood flow was also recorded and mean arterial blood pressure fell by 9·2% in intact and by 53% in denervated animals, although there were no significant differences in heart rate during the 2 min dives. In normal animals sciatic vascular resistance increased after 2 min submergence by 7·86 ± 1·7 times, whereas in denervated ducks it increased by only 2·32 ± 0·5 times. 6. The role of systemic arterial baroreceptors in generation of the cardiovascular responses to submergence in ducks is discussed in terms of the input supplied by the baroreceptors to the central nervous system. ImagesPlate 1 PMID:4764429
Jones, D. R.
An integrated modeling capability that provides the tools by which entire optical systems and instruments can be simulated and optimized is a key technology development, applicable to all mission classes, especially astrophysics. Many of the future missions require optical systems that are physically much larger than anything flown before and yet must retain the characteristic sub-micron diffraction limited wavefront accuracy of their smaller precursors. It is no longer feasible to follow the path of 'cut and test' development; the sheer scale of these systems precludes many of the older techniques that rely upon ground evaluation of full size engineering units. The ability to accurately model (by computer) and optimize the entire flight system's integrated structural, thermal, and dynamic characteristics is essential. Two distinct integrated modeling capabilities are required. These are an initial design capability and a detailed design and optimization system. The content of an initial design package is shown. It would be a modular, workstation based code which allows preliminary integrated system analysis and trade studies to be carried out quickly by a single engineer or a small design team. A simple concept for a detailed design and optimization system is shown. This is a linkage of interface architecture that allows efficient interchange of information between existing large specialized optical, control, thermal, and structural design codes. The computing environment would be a network of large mainframe machines and its users would be project level design teams. More advanced concepts for detailed design systems would support interaction between modules and automated optimization of the entire system. Technology assessment and development plans for integrated package for initial design, interface development for detailed optimization, validation, and modeling research are presented.
Shannon, Robert R.; Laskin, Robert A.; Brewer, SI; Burrows, Chris; Epps, Harlan; Illingworth, Garth; Korsch, Dietrich; Levine, B. Martin; Mahajan, Vini; Rimmer, Chuck
Traditional cardiovascular proteomics includes the comparative large-scale determination of protein profiles and the identification\\u000a of individual proteins of myocardial tissue from different species including humans. The goal of these studies consisted,\\u000a and still consists, in the establishment of comprehensive proteome databases. By comparison with protein profiles from diseased\\u000a tissues such databases will enable to an increasing degree the fast identification
Rainer Klocke; Sergiu Scobioala; Sigrid Nikol
CVSim is a lumped-parameter model of the human cardiovascular system that has been developed and used for research and for teaching quantitative physiology courses at MIT and Harvard Medical School since 1984. We present ...
The Ejs Copernican System model illustrates Copernicus' system of planetary motions. The entire system is centered on the center of Earth's uniform, circular orbit. Sun is placed near, but not at, this center point. The orbit of each planet (other than Earth) consists of a deferent circle, centered on a point some distance from the center (at the eccentric point). Attached to this deferent is the center of a much smaller circle, the epicycle (or epicyclet). The radius of the epicycle is 1/3 the eccentricity of the deferent. The planet moves along the epicycle at a constant angular speed equal to twice the angular speed along the deferent. This model produces retrograde motion and changes in brightness that are always properly correlated with the location of Sun. In this simulation, the planet is assumed to move in the plane of the ecliptic, so its latitude is always zero. You can modify this simulation if you have Ejs installed by right-clicking within the plot and selecting "Open Ejs Model" from the pop-up menu item. Ejs Copernican System model was created using the Easy Java Simulations (Ejs) modeling tool. It is distributed as a ready-to-run (compiled) Java archive. Double clicking the ejs_astronomy_CopernicanSystem.jar file will run the program if Java is installed. Ejs is a part of the Open Source Physics Project and is designed to make it easier to access, modify, and generate computer models. Additional Ejs models for astronomy are available. They can be found by searching ComPADRE for Open Source Physics, OSP, or Ejs.
In the Japanese workplace, employers are required to provide annual health checkups for workers in accordance with the "Industrial Safety and Health Law," which also mandates that an occupational physician be assigned to companies employing at least 50 workers. The annual medical examination includes testing for the early detection of cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, and the metabolic syndrome. This approach has successfully contributed to the extremely low incidence of coronary artery disease among Japanese workers. However, problems such as poor health and the low rate of participation in health checkups among small-scale companies still persist. Furthermore, although most wellness delivery systems in Japan employ strategies targeting high-risk individuals, instituting a strategy addressing the broader population irrespective of screening may be effective in reducing disease risk in the overall population. As a future direction, we should therefore develop practical methods for implementing a population strategy. PMID:24607016
Okamura, Tomonori; Sugiyama, Daisuke; Tanaka, Taichiro; Dohi, Seitaro
Cardiovascular disease remains a major cause of morbidity and mortality worldwide. Current medical practice takes into account information based on population studies and benefits observed in large populations or cohorts. However, individual patients present great differences in both toxicity and clinical efficacy that can be explained by variations in adherence, unknown drug to drug interactions and genetic variability. The latter seems to explain from 20% up to 95% of patient to patient variability. Treating patients with cardiovascular disorders faces the clinician with the challenge to include genomic analysis into daily practice. There are several examples within cardiovascular disease of treatments that can vary in toxicity or clinical usefulness based on genetic changes. One of the main factors affecting the efficacy of Clopidogrel is the phenotype associated with polymorphisms in the gene CYP 2C9. Furthermore, regarding oral anticoagulants, changes in CYP2C9 and VKORC1 play an important role in changing the clinical response to anticoagulation. When analyzing statin treatment, one of their main toxicities (myopathy) can be predicted by the SLCO1B1 polymorphism. The potential for prediction of toxicity and clinical efficacy from the use of genetic analysis warrants further studies aiming towards its inclusion in daily clinical practice. PMID:24636047
Scibona, Paula; Angriman, Federico; Simonovich, Ventura; Heller, Martina M; Belloso, Waldo H
The goal of the development of the Earth System Model Data Information System (ESMDIS) are to provide Earth scientists with: 1) an output management system of Earth System Model (ESM) to browse the metadata and retrieve a desired subset of ESM output; 2) an analysis system of ESM output and other related datasets; 3) an automated pipelining system for ESM
Yuechen Chi; Carlos R. Mechoso; Michael Stonebraker; Keith Sklower; Richard Troy; Richard R. Muntz; Edmond Mesrobian
The Climate System Modeling Project is a component activity of NSF's Climate Modeling, Analysis and Prediction Program, supported by the Atmospheric Sciences Program, Geosciences Directorate. Its objective is to accelerate progress toward reliable prediction of global and regional climate changes in the decades ahead. CSMP operates through workshops, support for post-docs and graduate students and other collaborative activities designed to promote interdisciplinary and strategic work in support of the overall objective (above) and specifically in three areas, (1) Causes of interdecadal variability in the climate system, (2) Interactions of regional climate forcing with global processes, and (3) Scientific needs of climate assessment.
The 1990 Global Change Institute (GCI) on Earth System Modeling is the third of a series organized by the Office for Interdisciplinary Earth Studies to look in depth at particular issues critical to developing a better understanding of the earth system. The 1990 GCI on Earth System Modeling was organized around three themes: defining critical gaps in the knowledge of the earth system, developing simplified working models, and validating comprehensive system models. This book is divided into three sections that reflect these themes. Each section begins with a set of background papers offering a brief tutorial on the subject, followed by working group reports developed during the institute. These reports summarize the joint ideas and recommendations of the participants and bring to bear the interdisciplinary perspective that imbued the institute. Since the conclusion of the 1990 Global Change Institute, research programs, nationally and internationally, have moved forward to implement a number of the recommendations made at the institute, and many of the participants have maintained collegial interactions to develop research projects addressing the needs identified during the two weeks in Snowmass.
Ojima, D. [ed.
The paper describes a visiting nurse led intervention model for the primary and secondary prevention of cardiovascular diseases (CVD) and specificities of its application. Although CVD burden is high in Croatia, the visiting nurse services have not been specifically focused on CVD prevention in the population until now. The intervention model described here is being implemented alongside the second cycle of the Croatian Adult Health Survey (2008 CAHS). The model includes an objective evaluation of respondents' CVD risk factors through quantitative and qualitative analyses, as well as respondents' self-evaluation of risk factors and motivation to change. At the same time, respondents are educated and intervention is evaluated. A 'health booklet' was specifically designed for documentation during one year's follow-up, where both the user and the visiting nurse keep copies of the negotiated targets and strategies set to achieve them. This intervention model has the potential to mobilize the service towards permanent incorporation of primary and secondary CVD prevention into routine care and, due to work specificities of the visiting nurse services, to cover the entire population in an organized CVD prevention. PMID:19563151
Pavi?, Jadranka; Zupani?, Mara; Milanovi?, Sanja Musi?; Fister, Kristina
Cardiac pathologies are among the leading causes of mortality and morbidity in industrialized countries, with myocardial infarction (MI) representing one of the major conditions leading to heart failure (HF). Hitherto, the development of consistent, stable, and reproducible models of closed-chest MI in large animals, meeting the clinical realism of a patient with HF subsequent to chronic ischemic necrosis, has not been successful. We hereby report the design and ensuing application of a novel porcine experimental model of closed-chest chronic ischemia suitable for biomedical research, mimicking post-MI HF. We also emphasize the key procedural steps involved in replicating this unprecedented model, from femoral artery and vein catheterization to MI induction by permanent occlusion of the left anterior descending coronary artery through superselective deployment of platinum-nylon coils, as well as endomyocardial biopsy sampling for histologic analysis and cell harvesting. Our model could indeed represent a valuable contribution and tool for translational research, providing precious insights to understand and overcome the many hurdles concerning, and currently quenching, the preclinical steps mandatory for the clinical translation of new cardiovascular technologies for personalized HF treatments. PMID:24151600
De Falco, Elena; Peruzzi, Mariangela; Cavarretta, Elena; Mancone, Massimo; Leoni, Omar; Caristo, Maria Emiliana; Lotrionte, Marzia; Marullo, Antonino G. M.; Amodeo, Antonio; Pacini, Luca; Calogero, Antonella; Petrozza, Vincenzo; D'Ascenzo, Fabrizio; Frati, Giacomo
Using embryonic chickens (Gallus gallus domesticus), we examined the role of the renin-angiotensin system (RAS) in cardiovascular and osmotic homeostasis through chronic captopril, an angiotensin-converting enzyme (ACE) inhibitor. Captopril (5mgkg(-1) embryo wet mass) or saline (control) was delivered via the egg air cell daily from embryonic day 5-18. Mean arterial pressure (MAP), heart rate (ƒH), fluid osmolality and ion concentration, and embryonic and organ masses were measured on day 19. Exogenous angiotensin I (ANG I) injection did not change MAP or ƒH in captopril-treated embryos, confirming ACE inhibition. Captopril-treated embryos were significantly hypotensive, with MAP 15% lower than controls, which we attributed to the loss of vasoconstrictive ANG II action. Exogenous ANG II induced a relatively greater hypertensive response in captopril-treated embryos compared to controls. Changes in response to ANG II following pre-treatment with phentolamine (?-adrenergic antagonist) indicated a portion of the ANG II response was due to circulating catecholamines in captopril-treated embryos. An increase in MAP and ƒH in response to hexamethonium indicated vagal tone was also increased in the absence of ACE activity. Captopril-treated embryos had lower osmolality, lower Na(+) and higher K(+) concentration in the blood, indicating osmoregulatory changes. Larger kidney mass in captopril-treated embryos suggests disrupting the RAS may stimulate kidney growth by decreasing resistance at the efferent arteriole and increasing the fraction of cardiac output to the kidneys. This study suggests that the RAS, most likely through ANG II action, influences the development of the cardiovascular and osmoregulatory systems. PMID:25149042
Mueller, Casey A; Crossley, Dane A; Burggren, Warren W
Background: Periodontitis is a local inflammatory process mediating destruction of periodontium triggered by bacterial insult leading to systemic inflammatory mayhem in the host. Epidemiologically, it has been modestly associated with cardiovascular diseases (CVD) with elevated acute-phase reactant C-reactive protein (CRP) and rheological variables such as total leukocyte count and differential leukocyte count (TLC and DLC), which are potential predictors of CVD. Aim: The aim of this study was to investigate the serum CRP level, leukocyte count in chronic periodontitis patients and their relation to the severity of chronic periodontitis. Subjects and Methods: This cross-sectional study comprised 30 subjects, of which 20 were diagnosed as chronic periodontitis based on the Gingival index, probing depth and clinical attachment levels and 10 healthy subjects as controls. Following, which peripheral blood samples were drawn and serum CRP, TLC and DLC were quantified using the turbidimetric immunoassay. Data was analyzed using Intercooled Stata 9.2 version, (Stata corporation, LP, USA) ANOVA, Mann Whitney U test and Newman-Keuls post hoc procedures. P values less than) 0.05 were considered as significant Results: The mean serum CRP levels were statistically significant (P < 0.05) in severe and moderate periodontitis subjects when compared with healthy controls. Leukocytes were significantly elevated in severe periodontitis compared with moderate periodontitis and controls; this finding was primarily explained by the increase in number of neutrophils. Conclusion: The increased serum CRP levels and neutrophils in chronic periodontitis subjects suggest an addition to the inflammatory burden of the individual potentially striking toward an increasing risk for cardiovascular events. Further research is needed to determine the specificity of these markers and their role in the inflammatory burden of one's systemic health. PMID:24971214
Kalburgi, V; Sravya, L; Warad, S; Vijayalaxmi, K; Sejal, P; Hazeil, DJ
Intraocular pressure (IOP) varies quasi-periodically due to blood pulsation in vessels inside the eye globe. This variations cause the eye deformations and displacements of the outer surface of the eye. The aim of this paper is to calculate the correlation between longitudinal corneal apex displacement and cardiovascular activity. Using ultrasound transducer at sampling frequency of 100Hz we have measured longitudinal corneal apex displacement (LCAD) of the left eye for 5 subjects. Synchronically we have registered ECG and blood pulsation signals at the same sampling frequency. Cross-correlation function was applied to investigate dependencies between these signals. To find time shift between LCAD and ECG or pulse, the time window of 3 seconds length have been chosen from all signals and had been shifting with the step of 0.01 seconds from 0 to 7s. For each shift the cross-correlation function and its extrema were calculated in the window area. We have obtained information about extrema position of cross-correlation function and its stability in time for particular subjects. The time shift between LCAD and ECG or pulse is individual feature of each subject. Such calculations may lead us to better understanding of pulse propagation in human eye and creation a non invasive method of eye hemodynamics and ocular diagnosis.
Danielewska, M.; Kowalska, M.; Kasprzak, H.
The 1982-1988 aspirin component of the Physicians' Health Study, a randomized trial of aspirin and ?- carotene in primary prevention of cardiovascular disease and cancer among 22,071 US male physicians, was terminated early primarily because of a statistically extreme 44% reduction in first myocardial infarction, with inadequate precision and no apparent effect on the primary endpoint, cardiovascular death. Because of
Nancy R. Cook; Stephen R. Cole; Charles H. Hennekens
A prototype of a fiber-optic, multi-analyte, immunobiosensing system was developed to simultaneously quantify disease-representing biomarkers in blood plasma. This system was for simultaneous quantification of two different groups of multi-biomarkers related to cardiovascular diseases (CVD): anticoagulants (protein C, protein S, antithrombin III, and plasminogen) for deficiency diagnosis; and cardiac markers (B-type natriuretic peptide, cardiac troponin I, myoglobin, and C-reactive protein) for coronary heart disease diagnosis. As an initial effort towards the development of a disposable and easy-to-use sensing cartridge as a rapid diagnostic tool for CVD related diseases, a prototype of a flow control system was also developed to automatically perform simultaneous four-analyte quantification. Currently, the system is capable of quantifying the multiple anticoagulants in their clinically significant sensing ranges within 5 minutes, at an average signal-to-noise (S/N) ratio of 25. A simultaneous assay of the four cardiac markers can be performed within 10 min, at an average S/N ratio of 20. When this highly portable multi-analyte sensing system is completed and successfully tested for CVD patient's plasma, it can provide rapid (<10 min) and reliable diagnostic and prognostic information at a patient's bedside.
Tang, Liang; Ren, Yongjie; Hong, Bin; Kang, Kyung A.
The MIT Integrated Global System Model (IGSM) is designed for simulating the global environmental changes that may arise as a result of anthropogenic causes, the uncertainties associated with the projected changes, and the effect of proposed policies on such changes. As described...
in cognitive modeling ÂReadings ÂTeam work / interaction ÂStudent presentations ÂHands-on lab exercises #12;2 Cognitive Systems: Topics Â· Introduction Â· Perception Â· Memory and Reasoning Â· Learning Â· Maximum is 28 points #12;8 On Grading Â· Exercises ÂExercise 1 is worth 5 points each ÂExercises 2 Â 6
Cardiovascular disease (CVD) models are used for identification of mechanisms of susceptibility to air pollution. We hypothesized that baseline systemic biomarkers and cardiac gene expression in CVD rat models will have influence on their ozone-induced lung inflammation. Male 12-...
Ang II, the primary effector pleiotropic hormone of the renin-angiotensin system (RAS) cascade, mediates physiological control of blood pressure and electrolyte balance through its action on vascular tone, aldosterone secretion, renal sodium absorption, water intake, sympathetic activity and vasopressin release. It affects the function of most of the organs far beyond blood pressure control including heart, blood vessels, kidney and brain, thus, causing both beneficial and deleterious effects. However, the protective axis of the RAS composed of ACE2, Ang (1-7), alamandine, and Mas and MargD receptors might oppose some harmful effects of Ang II and might promote beneficial cardiovascular effects. Newly identified RAS family peptides, Ang A and angioprotectin, further extend the complexities in understanding the cardiovascular physiopathology of RAS. Most of the diverse actions of Ang II are mediated by AT1 receptors, which couple to classical Gq/11 protein and activate multiple downstream signals, including PKC, ERK1/2, Raf, tyrosine kinases, receptor tyrosine kinases (EGFR, PDGF, insulin receptor), nuclear factor ?B and reactive oxygen species (ROS). Receptor activation via G12/13 stimulates Rho-kinase, which causes vascular contraction and hypertrophy. The AT1 receptor activation also stimulates G protein-independent signaling pathways such as ?-arrestin-mediated MAPK activation and Src-JAK/STAT. AT1 receptor-mediated activation of NADPH oxidase releases ROS, resulting in the activation of pro-inflammatory transcription factors and stimulation of small G proteins such as Ras, Rac and RhoA. The components of the RAS and the major Ang II-induced signaling cascades of AT1 receptors are reviewed. PMID:25007996
Balakumar, Pitchai; Jagadeesh, Gowraganahalli
Previous studies have established the effects of orthostatic challenge on the cardiovascular and postural control systems, but the interdependent behavior of the systems under such condition is unclear. In the present study we examined the simultaneous changes in posture muscle electromyography (EMG) and systolic blood pressure (SBP) during quiet standing in healthy young individuals. Photoplethysmography based SBP, surface EMG, electrocardiogram (Lead II ECG) and posturography data were acquired during the experiment. Wavelet transform coherence (WTC) analysis was applied to identify the zones of interdependent behavior of the systems. The WTC thresholds were identified for the specific data under investigation. The coherence was analyzed in three frequency bands namely, LF (0.05 - 0.1 Hz), VLF (0.01-0.05 Hz) and ULF (0.005 - 0.01 Hz). WTC estimates for the EMG - SBP comparison showed greater than threshold values in all three frequency bands (LF: 0.31 ± 0.02; VLF: 0.41 ± 0.01; ULF: 0.45 ± 0.01). In conclusion this study showed the existence of relationship between the posture muscle EMG and blood pressure during natural orthostatic stress, by validation based on wavelet transform coherence. Further validation is required to objectively characterize this relationship between the two systems during orthostatic stress. PMID:23366703
Garg, Amanmeet; Blaber, Andrew P
A computer program is described for the analysis of several cardiovascular parameters frequently measured or derived in the chronically instrumented dog model. Data are stored on magnetic tape and are subsequently analyzed with the Apple IIe microcomputer equipped with the ADALAB (Interactive Microware, Inc.) analog-to-digital convertor. Not limited to the chronically instrumented animal model, the program is capable of analyzing left ventricular pressure, three channels of regional myocardial segment length, coronary flow velocity as measured by the Doppler ultrasonic flow technique, and two channels of systemic arterial pressure. Derived data include: left ventricular dP/dtmax, left ventricular pressure-heart rate product, left ventricular ejection time, tension time index; percent segment length shortening and velocity of shortening, dL/dt(s)max, regional stroke work and power, duration of systole and diastole; mean coronary flow velocity, peak diastolic and systolic flow velocity, and true mean systemic arterial pressure. PMID:3581809
Mass, H J; Gean, J T; Gwirtz, P A
The Kepler System model simulates Kepler's final theory of planetary motion. In this theory the planets orbit in ellipses with Sun at one focus (Kepler's First law). These elliptical orbits are not necessarily all in the same plane. A line from Sun to the planet sweeps out equal areas in equal times (Kepler's Second law). The square a planet's period is directly proportional to the cube of the semimajor axis of its elliptical orbit (Kepler's Third law). The simulation shows Earth's orbit around Sun, as well as the orbit of one other planet. The user can choose to show one of the five visible planets (Mercury, Venus, Mars, Jupiter, or Saturn), or a fictitious planet. The top window shows the orbits of the planets around Sun. The view can be changed by clicking and dragging in the window and a zoom slider is provided to zoom in or out. The bottom window shows the view of Sun and planet against the background stars as seen from Earth. The Kepler System model was created using the Easy Java Simulations (EJS) modeling tool. It is distributed as a ready-to-run (compiled) Java archive. Double clicking the ejs_astronomy_KeplerSystem.jar file will run the program if Java is installed. EJS is a part of the Open Source Physics Project and is designed to make it easier to access, modify, and generate computer models.
cognitive loss, falls, and syncope, which are major causes of morbidity and mortality in elderly people-term cardiovascular regulation of blood flow to the brain is essential for development of new strategies to prevent
Olufsen, Mette Sofie
Comparative gene expression profiling of multiple tissues from rat strains with genetic predisposition to diverse cardiovascular diseases (CVD) can help decode the transcriptional program that governs organ-specific functions. We examined expressions of CVD genes in the lungs of ...
Rationale: Individuals suffering from cardiovascular disease (CVD) develop iron dysregulation which may influence pulmonary toxicity and injury upon exposure to asbestos. We hypothesized spontaneously hypertensive (SH) and spontaneously hypertensive heart failure (SHHF) rats woul...
On the Track of Syncope induced by Orthostatic Stress - Feedback Mechanisms Regulating-to-stand and head-up-tilt experiments are encapsulated by the model. The model may be used in studies of syncope-to-stand, head-up-tilt, syncope 1. INTRODUCTION During postural change in sit-to-stand (STS) and head
Olufsen, Mette Sofie
The quality management of an organization can be defined as the ability to identify, plan and implement programs of measure, analysis, verification and control that allow to monitor management, resources, activities, processes and output/outcome of the same organization, including the satisfaction of the customers. Whatever the model used, it is demonstrated that the management-quality system, either for professional quality or for organization, turns out to be effective even in the health organizations within and to any level of organizational-structural complexity. The present paper concerns the experience of the Italian Society of Cardiovascular Echography (SIEC) on quality certification, both as a scientific society compared to other health organizations and to cardiovascular echo laboratories, and the definition of minimum requirements for the accreditation of the same laboratories. The model most frequently used for quality management is represented by the ISO 9000: Vision 2000, that is a management model with specific reference to the organization and the customer satisfaction. The model applied to the health structure needs a rapid change in mentality that addresses the operators to define, share and achieve objectives to be brought on by means of an active collaboration, group activity and deep sense of belonging necessary to the attainment of expected objectives. When the model is applied by a scientific society, it is necessary to take into account the different structural and functional organization, the constitution and the operators differing on the point of view of origin, experiences, mentality, and roles. The ISO 9000: Vision 2000 model can be applied also to the cardiovascular echo laboratory which may be compared to a simple organization; for its corrected functioning, SIEC has defined minimal requirements for the accreditation, realization and modalities to carry out and manage quality. The quality system represents a new way of operating of an organization that enhances capability and performance of the operators, stimulates their creativity and facilitates the activities of all, to guarantee both the quality of the product and the satisfaction of operators and customers at the same time. PMID:12611211
A long and productive history in biomedical research defines the chick as a model for human biology. Fundamental discoveries, including the description of directional circulation propelled by the heart and the link between oncogenes and the formation of cancer, indicate its utility in cardiac biology and cancer. Despite the more recent arrival of several vertebrate and invertebrate animal models during the last century, the chick embryo remains a commonly used model for vertebrate biology and provides a tractable biological template. With new molecular and genetic tools applied to the avian genome, the chick embryo is accelerating the discovery of normal development and elusive disease processes. Moreover, progress in imaging and chick culture technologies is advancing real-time visualization of dynamic biological events, such as tissue morphogenesis, angiogenesis, and cancer metastasis. A rich background of information, coupled with new technologies and relative ease of maintenance, suggest an expanding utility for the chick embryo in cardiac biology and cancer research. PMID:24357262
Kain, Kristin H; Miller, James W I; Jones-Paris, Celestial R; Thomason, Rebecca T; Lewis, John D; Bader, David M; Barnett, Joey V; Zijlstra, Andries
A long and productive history in biomedical research defines the chick as a model for human biology. Fundamental discoveries, including the description of directional circulation propelled by the heart and the link between oncogenes and the formation of cancer, indicate its utility in cardiac biology and cancer. Despite the more recent arrival of several vertebrate and invertebrate animal models during the last century, the chick embryo remains a commonly used model for vertebrate biology and provides a tractable biological template. With new molecular and genetic tools applied to the avian genome the chick embryo is accelerating the discovery of normal development and elusive disease processes. Moreover, progress in imaging and chick culture technologies is advancing real-time visualization of dynamic biological events, such as tissue morphogenesis, angiogenesis and cancer metastasis. A rich background of information, coupled with new technologies and relative ease of maintenance suggest an expanding utility for the chick embryo in cardiac biology and cancer research. PMID:24357262
Kain, Kristin H.; Miller, James W.I.; Jones-Paris, Celestial R.; Thomason, Rebecca T.; Lewis, John D.; Bader, David M.; Barnett, Joey V.; Zijlstra, Andries
This report documents the results of an LDRD program entitled 'System of Systems Modeling and Analysis' that was conducted during FY 2003 and FY 2004. Systems that themselves consist of multiple systems (referred to here as System of Systems or SoS) introduce a level of complexity to systems performance analysis and optimization that is not readily addressable by existing capabilities. The objective of the 'System of Systems Modeling and Analysis' project was to develop an integrated modeling and simulation environment that addresses the complex SoS modeling and analysis needs. The approach to meeting this objective involved two key efforts. First, a static analysis approach, called state modeling, has been developed that is useful for analyzing the average performance of systems over defined use conditions. The state modeling capability supports analysis and optimization of multiple systems and multiple performance measures or measures of effectiveness. The second effort involves time simulation which represents every system in the simulation using an encapsulated state model (State Model Object or SMO). The time simulation can analyze any number of systems including cross-platform dependencies and a detailed treatment of the logistics required to support the systems in a defined mission.
Campbell, James E.; Anderson, Dennis James; Longsine, Dennis E. (Intera, Inc., Austin, TX); Shirah, Donald N.
Frequency domain analysis by power spectrum density (PSD) estimate has proven to be an effective method of investigation for studying the influence of the automatic nervous system on the systemic and coronary hemodynamics. Since the problem is intrinsically multichannel it should be studied by some proper multichannel PSD estimates. Parametric autoregressive spectral methods were used and in particular the Nuttal-Strand
A. Macerata; M. Fusilli; F. Conforti; M. Niccolai; H. Emdin; M. G. Trivella; C. Marchesi
Interventional cardiovascular magnetic resonance imaging (iCMR) is potentially revolutionary because of the exquisite tissue\\u000a and blood imaging afforded to guide therapeutic procedures. By making small compromises in spatial or temporal resolution,\\u000a and with little or no modifications to commercial high-performance magnetic resonance imaging (MRI) systems, images can be\\u000a acquired and displayed almost instantaneously to operators. This may be useful simply
Robert J. Lederman
The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E) 2-related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis). The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases. PMID:23691261
Several adverse effects have been associated with exposure to traffic noise. Studies supporting a noise–stress–health model have suggested links between noise level and increased noradrenalin concentrations in urine, hypertension and myocardial infarction. Among the more commonly documented effects, sleep disturbances have been regarded as being the most serious. Both noise annoyance and sleep disturbance have been proposed as important mediators
Aslak Fyhri; Gunn Marit Aasvang
The assessment of cardiovascular function is becoming increasingly important for the care of patients with single-ventricle defects. However, most measurement methods available in the clinical setting cannot provide a separate measure of cardiac function and loading conditions. In the present study, a numerical method has been proposed to compensate for the limitations of clinical measurements. The main idea was to estimate the parameters of a cardiovascular model by fitting model simulations to patient-specific clinical data via parameter optimization. Several strategies have been taken to establish a well-posed parameter optimization problem, including clinical data-matched model development, parameter selection based on an extensive sensitivity analysis, and proper choice of parameter optimization algorithm. The numerical experiments confirmed the ability of the proposed parameter optimization method to uniquely determine the model parameters given an arbitrary set of clinical data. The method was further tested in four patients undergoing the Fontan operation. Obtained results revealed a prevalence of ventricular abnormalities in the patient cohort and at the same time demonstrated the presence of marked inter-patient differences and preoperative to postoperative changes in cardiovascular function. Because the method allows a quick assessment and makes use of clinical data available in clinical practice, its clinical application is promising. PMID:24753499
Liang, Fuyou; Sughimoto, Koichi; Matsuo, Kozo; Liu, Hao; Takagi, Shu
This chapter surveys the field of user modeling in artificial intelligence dialog systems. First, reasons why user modeling has become so important in the last few years are pointed out, and definitions are proposed for the terms 'user model' and 'user modeling component'. Research within and outside of artificial intelligence which is related to user modeling in dialog systems is
Wolfgang Wahlster; Alfred Kobsa
Mock circulatory systems (MCS) are often used for the development of cardiovascular devices and for the study of the dynamics of blood flow through the cardiovascular system. However, conventional MCS suffer from the repeatability, flexibility, and precision problems because they are typically built up with passive and linear fluidic elements such as compliance chamber, manual valve, and tube. To solve these limitations, we have developed an impedance simulator, comprised of a feedback-controlled positive displacement pump that is capable of generating analogous dynamic characteristics as the conventional fluidic elements would generate, thereby replacing the conventional passive fluidic elements that often cause problems. The impedance simulator is experimentally proven to reproduce the impedance of the various discrete elements, such as resistance and compliance of the cardiovascular system model, as well as the combined impedances of them. PMID:19709951
Gwak, Kwan-Woong; Paden, Brad E; Antaki, James F; Ahn, Ihn-Seok
Rationale: Acute pulmonary injury and chronic disease can impact systemic vasculature because the lung capillary network can release inflammogenic and vasoactive mediators into the circulation. Occupational exposure to Libby amphibole (LA) type asbestos is associated with increas...
Aims: The Williams-Beuren syndrome (WBS) is a genetic disorder caused by a heterozygous ?1.5-Mb deletion. The aim of this study was to determine how the genetic changes in a Wbs mouse model alter Eln expression, blood pressure, vessel structure, and abdominal aortic wall dynamics in vivo. Methods: Elastin (ELN) transcript levels were quantified by qRT-PCR and blood pressure was measured
Craig J. Goergen; Hong-Hua Li; Uta Francke; Charles A. Taylor
The T-wave of an electrocardiogram (ECG) represents the ventricular repolarization that is critical in restoration of the heart muscle to a pre-contractile state prior to the next beat. Alterations in the T-wave reflect various cardiac conditions; and links between abnormal (prolonged) ventricular repolarization and malignant arrhythmias have been documented. Cardiac safety testing prior to approval of any new drug currently relies on two points of the ECG waveform: onset of the Q-wave and termination of the T-wave; and only a few beats are measured. Using functional data analysis, a statistical approach extracts a common shape for each subject (reference curve) from a sequence of beats, and then models the deviation of each curve in the sequence from that reference curve as a four-dimensional vector. The representation can be used to distinguish differences between beats or to model shape changes in a subject's T-wave over time. This model provides physically interpretable parameters characterizing T-wave sh...
Zhou, Yingchun; 10.1214/09-AOAS273
Spinal muscular atrophy (SMA) is a leading genetic cause of infantile death. Loss of a gene called Survival Motor Neuron 1 (SMN1) and, as a result, reduced levels of the Survival Motor Neuron (SMN) protein leads to SMA development. SMA is characterized by the loss of functional motor neurons in the spinal cord. However, accumulating evidence suggest the contribution of other organs to the composite SMA phenotype and disease progression. A growing number of congenital heart defects have been identified in severe SMA patients. Consistent with the clinical cases, we have recently identified developmental and functional heart defects in two SMA mouse models, occurring at embryonic stage in a severe SMA model and shortly after birth in a less severe model (SMN?7). Our goal was to examine the late stage cardiac abnormalities in untreated SMN?7 mice and to determine whether gene replacement therapy restores cardiac structure/function in rescued SMN?7 model. To reveal the extent of the cardiac structural/functional repair in the rescued mice, we analyzed the heart of untreated and treated SMN?7 model using self-complementary Adeno-associated virus (serotype 9) expressing the full-length SMN cDNA. We examined the characteristics of the heart failure such as remodeling, fibrosis, oxidative stress, and vascular integrity in both groups. Our results clearly indicate that fibrosis, oxidative stress activation, vascular remodeling, and a significant decrease in the number of capillaries exist in the SMA heart. The cardiac structural defects were improved drastically in the rescued animals, however, the level of impairment was still significant compared to the age-matched wildtype littermates. Furthermore, functional analysis by in vivo cardiac magnetic resonance imaging (MRI) revealed that the heart of the treated SMA mice still exhibit functional defects. In conclusion, cardiac abnormalities are only partially rescued in post-birth treated SMA animals and these abnormalities may contribute to the premature death of vector-treated SMA animals with seemingly rescued motor function but an average life span of less than 70 days as reported in several studies. PMID:22285962
Shababi, Monir; Habibi, Javad; Ma, Lixin; Glascock, Jacqueline; Sowers, James R.; Lorson, Christian L.
Aim. To evaluate the effects of bosentan, sildenafil, and combined therapy on the cardiovascular system using impedance cardiography (ICG) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Methods. Seventy male Wistar-albino rats were randomized into five groups. A single dose of MCT was given to all rats, except to the control group. After 4 weeks, bosentan, sildenafil, and combined treatment was started and lasted for 3 weeks. The last group that developed PAH did not receive any medication. Echocardiographic evaluation was performed to determine the PAH development. Thoracic fluid content index (TFCI), stroke volume index (SI), heart rate (HR), cardiac index (CI), and myocardial contractility index (IC) were determined. All procedures were performed at the baseline and after 4 and 7 weeks. Results. Echocardiographic parameters showed that the all MCT-injected rats developed PAH. There were no significant inter- and intra-group differences in TFCI, SI, and IC (P>0.05), but at the 7th week, CI value in the sildenafil-treated PAH rats was significantly higher than in other groups and HR of PAH rats with combined therapy was significantly lower than in other groups. Conclusion. PAH did not have an effect on LV function of rats, or if it did, the effect was compensated by physiological processes. Also, sildenafil treatment deteriorated the LV cardiac index. PMID:25358882
Buyukakilli, Belgin; Gurgul, Serkan; C?t?r?k, Derya; Hallioglu, Olgu; Ozeren, Murat; Tasdelen, Bahar
Objective. This study was performed to determine the prevalence of and associated risk factors for cardiovascular disease (CVD) in Latin American (LA) patients with systemic lupus erythematosus (SLE). Methods. First, a cross-sectional analytical study was conducted in 310 Colombian patients with SLE in whom CVD was assessed. Associated factors were examined by multivariate regression analyses. Second, a systematic review of the literature on CVD in SLE in LA was performed. Results. There were 133 (36.5%) Colombian SLE patients with CVD. Dyslipidemia, smoking, coffee consumption, and pleural effusion were positively associated with CVD. An independent effect of coffee consumption and cigarette on CVD was found regardless of gender and duration of disease. In the systematic review, 60 articles fulfilling the eligibility criteria were included. A wide range of CVD prevalence was found (4%–79.5%). Several studies reported ancestry, genetic factors, and polyautoimmunity as novel risk factors for such a condition. Conclusions. A high rate of CVD is observed in LA patients with SLE. Awareness of the observed risk factors should encourage preventive population strategies for CVD in patients with SLE aimed at facilitating the suppression of cigarette smoking and coffee consumption as well as at the tight control of dyslipidemia and other modifiable risk factors. PMID:24294522
Amaya-Amaya, Jenny; Caro-Moreno, Julian; Molano-Gonzalez, Nicolas; Mantilla, Ruben D.; Rojas-Villarraga, Adriana; Anaya, Juan-Manuel
Aim To evaluate the effects of bosentan, sildenafil, and combined therapy on the cardiovascular system using impedance cardiography (ICG) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Methods Seventy male Wistar-albino rats were randomized into five groups. A single dose of MCT was given to all rats, except to the control group. After 4 weeks, bosentan, sildenafil, and combined treatment was started and lasted for 3 weeks. The last group that developed PAH did not receive any medication. Echocardiographic evaluation was performed to determine the PAH development. Thoracic fluid content index (TFCI), stroke volume index (SI), heart rate (HR), cardiac index (CI), and myocardial contractility index (IC) were determined. All procedures were performed at the baseline and after 4 and 7 weeks. Results Echocardiographic parameters showed that the all MCT-injected rats developed PAH. There were no significant inter- and intra-group differences in TFCI, SI, and IC (P?>?0.05), but at the 7th week, CI value in the sildenafil-treated PAH rats was significantly higher than in other groups and HR of PAH rats with combined therapy was significantly lower than in other groups. Conclusion PAH did not have an effect on LV function of rats, or if it did, the effect was compensated by physiological processes. Also, sildenafil treatment deteriorated the LV cardiac index. PMID:25358882
Buyukakilli, Belgin; Gurgul, Serkan; C?t?r?k, Derya; Hallioglu, Olgu; Ozeren, Murat; Tasdelen, Bahar
Circulatory and tissue renin-angiotensin systems (RAS) play a central role in cardiovascular (CV) and renal pathophysiology, making RAS inhibition a logical therapeutic approach in the prevention of CV and renal disease in patients with hypertension. The cardio- and renoprotective effects observed with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) monotherapy, together with the availability of a direct renin inhibitor (DRI), led to the investigation of the potential benefits of dual RAS inhibition. In small studies, ARB and ACE inhibitor combinations were shown to be beneficial in patients with CV or renal disease, with improvement in surrogate markers. However, in larger outcome trials, involving combinations of ACE inhibitors, ARBs or DRIs, dual RAS inhibition did not show reduction in mortality in patients with diabetes, heart failure, coronary heart disease or after myocardial infarction, and was in fact, associated with increased harm. A recent meta-analysis of all major trials conducted over the past 22 years involving dual RAS inhibition has clearly shown that the risk-benefit ratio argues against the use of dual RAS inhibition. Hence, the recent evidence clearly advocates against the use of dual RAS inhibition, and single RAS inhibition appears to be the most suitable approach to controlling blood pressure and improving patient outcomes. PMID:23866091
Variability in drug responsiveness is a sine qua non of modern therapeutics, and the contribution of genomic variation is increasingly recognized. Investigating the genomic basis for variable responses to cardiovascular therapies has been a model for pharmacogenomics in general and has established critical pathways and specific loci modulating therapeutic responses to commonly used drugs such as clopidogrel, warfarin, and statins. In addition, genomic approaches have defined mechanisms and genetic variants underlying important toxicities with these and other drugs. These findings have not only resulted in changes to the product labels but also have led to development of initial clinical guidelines that consider how to facilitate incorporating genetic information to the bedside. This review summarizes the state of knowledge in cardiovascular pharmacogenomics and considers how variants described to date might be deployed in clinical decision making. PMID:23689943
Weeke, Peter; Roden, Dan M.
Despite its status as a world leader in treatment innovation and medical education, a quality chasm exists in American health care. Care fragmentation and poor coordination contribute to expensive care with highly variable quality in the United States. The rising costs of health care since 1990 have had a huge impact on individuals, families, businesses, the federal and state governments, and the national budget deficit. The passage of the Affordable Care Act represents a large shift in how health care is financed and delivered in the United States. The objective of this review is to describe some of the economic and social forces driving health care reform, provide an overview of the Patient Protection and Affordable Care Act (ACA), and review model cardiovascular quality improvement programs underway in the state of Michigan. As health care reorganization occurs at the federal level, local and regional efforts can serve as models to accelerate improvement toward achieving better population health and better care at lower cost. Model programs in Michigan have achieved this goal in cardiovascular care through the systematic application of evidence-based care, the utilization of regional quality improvement collaboratives, community-based childhood wellness promotion, and medical device-based competitive bidding strategies. These efforts are examples of the direction cardiovascular care delivery will need to move in this era of the Affordable Care Act. PMID:25120917
Alyeshmerni, Daniel; Froehlich, James B; Lewin, Jack; Eagle, Kim A
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…
Johnson, Christopher D.; Roe, Sean; Tansey, Etain A.
The baroreflex is an internal feedback mechanism that stabilizes the blood pressure in the circulatory system. Its function in patients with congestive heart failure is preserved fairly well. When these patients are implanted with a left ventricular assist device (LVAD), the baroreflex plays an important role in interacting with the controller that regulates the pump speed. In this paper, we
Shaohui Chen; A. Ferreira; M. A. Simaan; J. R. Boston; J. F. Antaki
Background: increasing age affects aerobic capacity, with an average loss of 10% or more per decade. Aim: to determine the effect of ageing on the circulatory system in middle-aged men during 33 years of physical training. Methods: 15 men initially aged 45 years took part in an exercise training programme for 25-33 years. Nine serial measurements were made at rest
FRED W. K ASCH; OHN L. BOYER; AUL K. SCHMIDT; R USSELL H. WELLS; ANET P. W ALLACE
This article reviews recent flight and ground-based studies of cardiovascular adaptation to spaceflight. Prominent features of microgravity exposure include loss of gravitational pressures, relatively low venous pressures, headward fluid shifts, plasma volume loss, and postflight orthostatic intolerance and reduced exercise capacity. Many of these short-term responses to microgravity extend themselves during long-duration microgravity exposure and may be explained by altered pressures (blood and tissue) and fluid balance in local tissues nourished by the cardiovascular system. In this regard, it is particularly noteworthy that tissues of the lower body (e.g., foot) are well adapted to local hypertension on Earth, whereas tissues of the upper body (e.g., head) are not as well adapted to increase in local blood pressure. For these and other reasons, countermeasures for long-duration flight should include reestablishment of higher, Earth-like blood pressures in the lower body.
Hargens, A. R.; Watenpaugh, D. E.
Data are presented on the rate of adaptation of the human cardiovascular system to conditions of spaceflight, with particular attention given to data obtained during spaceflight in the U.S. Space Shuttle Program. It is pointed out that many of the cardiovascular changes that occurred during spaceflights that lasted from 2 to 11 days can be traced directly to changes in the body fluid volume. The beneficial effects of a fluid loading countermeasure (oral rehydration) and of the supine body position on the heart rate during the spaceflight are demonstrated. It is noted that, after hours or a few days of spaceflight, a state of adaptation is reached, in which the subject is well adapted and appropriately hydrated for the weightless environment. However, the return to the normal gravity of the earth leaves the individual especially sensitive to orthostatic stress.
Charles, John B.; Lathers, Claire M.
The loss of cardiac pump function accounts for a significant increase in both mortality and morbidity in Western society, where there is currently a one in four lifetime risk, and costs associated with acute and long-term hospital treatments are accelerating. The significance of cardiac disease has motivated the application of state-of-the-art clinical imaging techniques and functional signal analysis to aid diagnosis and clinical planning. Measurements of cardiac function currently provide high-resolution datasets for characterizing cardiac patients. However, the clinical practice of using population-based metrics derived from separate image or signal-based datasets often indicates contradictory treatments plans owing to inter-individual variability in pathophysiology. To address this issue, the goal of our work, demonstrated in this study through four specific clinical applications, is to integrate multiple types of functional data into a consistent framework using multi-scale computational modelling. PMID:22670205
Smith, Nic; de Vecchi, Adelaide; McCormick, Matthew; Nordsletten, David; Camara, Oscar; Frangi, Alejandro F.; Delingette, Herve; Sermesant, Maxime; Relan, Jatin; Ayache, Nicholas; Krueger, Martin W.; Schulze, Walther H. W.; Hose, Rod; Valverde, Israel; Beerbaum, Philipp; Staicu, Cristina; Siebes, Maria; Spaan, Jos; Hunter, Peter; Weese, Juergen; Lehmann, Helko; Chapelle, Dominique; Rezavi, Reza
Personalized medicine is a novel medical model with all decisions and practices being tailored to individual patients in whatever ways possible. In the era of genomics, personalized medicine combines the genetic information for additional benefit in preventive and therapeutic strategies. Personalized medicine may allow the physician to provide a better therapy for patients in terms of efficiency, safety and treatment length to reduce the associated costs. There was a remarkable growth in scientific publication on personalized medicine within the past few years in the cardiovascular field. However, so far, only very few cardiologists in the USA are incorporating personalized medicine into clinical treatment. We review the concepts, strengths, limitations and challenges of personalized medicine with a particular focus on cardiovascular diseases (CVDs). There are many challenges from both scientific and policy perspectives to personalized medicine, which can overcome them by comprehensive concept and understanding, clinical application, and evidence based practices. Individualized medicine serves a pivotal role in the evolution of national and global healthcare reform, especially, in the CVDs fields. Ultimately, personalized medicine will affect the entire landscape of health care system in the near future. PMID:23091501
Lee, Moo-Sik; Flammer, Andreas J.; Lerman, Lilach O.
Background—Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular disease 2- to 3- fold. The factors responsible for this association remain largely unknown. Methods and Results—We analyzed data from participants, 50 years of age, of the Third National Health and Nutrition Examination Survey (n6629) to determine whether C-reactive protein (CRP) and other systemic inflammatory markers are present in participants
Don D. Sin; S. F. Paul Man
A device suitable for the continuous measurement of physiological activity in large, conscious monkeys has permitted the direct recording of systemic arterial blood pressure and heart rate in caged baboons. The device comprises a lightweight fiberglass backpack, retained in place on the baboon by a thoracic elastic band and shoulder straps, and a flexible stainless steel tether connecting the pack to an electrocannular slip-ring in the top center of the baboon's cage. A chronically indwelling arterial catheter inserted retrograde into the abdominal aorta via the internal iliac artery and connected to a small pressure transducer on the pack provides direct measurement of blood pressure and heart rate. Body fluids can be sampled or drugs administered via an indwelling catheter in the inferior vena cava. Electrical and fluid connections between the fiberglass pack and recording and infusion equipment located outside the cage pass through the flexible tether and remain protected from the subject. The reliability of the tethering system has been demonstrated in physiological, pharmacological, and behavioral experiments with baboons.
Byrd, L. D.
The time course of metabolic and cardiovascular changes with weight gain and subsequent weight loss has not been elucidated. The goal of the present study was to determine how weight gain, weight loss and altered body fat distribution affected metabolic and cardiovascular changes in an obese dog model. Testing was performed when the dogs were lean (scores 4-5 on a nine-point scale), after ad libitum feeding for 12 and 32 weeks to promote obesity (>5 score), and after weight loss. Measurements included serum glucose and insulin, plasma leptin, adiponectin and C-reactive protein, echocardiography, flow-mediated dilation and blood pressure. Body fat distribution was assessed by computed tomography. Fasting serum glucose concentrations increased significantly with obesity (P< 0·05). Heart rate increased by 22 (SE 5) bpm after 12 weeks of obesity (P= 0·003). Systolic left ventricular free wall thickness increased after 12 weeks of obesity (P= 0·002), but decreased after weight loss compared with that observed in the lean phase (P= 0·03). Ventricular free wall thickness was more strongly correlated with visceral fat (r 0·6, P= 0·001) than with total body fat (r 0·4, P= 0·03) and was not significantly correlated with subcutaneous body fat (r 0·3, P= 0·1). The present study provides evidence that metabolic and cardiovascular alterations occur within only 12 weeks of obesity in an obese dog model and are strongly predicted by visceral fat. These results emphasise the importance of obesity prevention, as weight loss did not result in the return of all metabolic indicators to their normal levels. Moreover, systolic cardiac muscle thickness was reduced after weight loss compared with the pre-obesity levels, suggesting possible acute adverse cardiovascular effects. PMID:24877650
Adolphe, Jennifer L; Silver, Tawni I; Childs, Helene; Drew, Murray D; Weber, Lynn P
Cardiovascular diseases, including hypertension and heart failure, are associated with activation of the renin-angiotensin system (RAS) and increased circulating and tissue levels of ANG II, a primary effector peptide of the RAS. Through its actions on various cell types and organ systems, ANG II contributes to the pathogenesis of cardiovascular diseases by inducing cardiac and vascular hypertrophy, vasoconstriction, sodium and water reabsorption in kidneys, sympathoexcitation, and activation of the immune system. Cardiovascular research over the past 15-20 years has clearly implicated an important role for elevated levels of reactive oxygen species (ROS) in mediating these pathophysiological actions of ANG II. As such, the use of antioxidants, to reduce the elevated levels of ROS, as potential therapies for various ANG II-associated cardiovascular diseases has been intensely investigated. Although some antioxidant-based therapies have shown therapeutic impact in animal models of cardiovascular disease and in human patients, others have failed. In this review, we discuss the benefits and limitations of recent strategies, including gene therapy, dietary sources, low-molecular-weight free radical scavengers, polyethylene glycol conjugation, and nanomedicine-based technologies, which are designed to deliver antioxidants for the improved treatment of cardiovascular diseases. Although much work has been completed, additional research focusing on developing specific antioxidant molecules or proteins and identifying the ideal in vivo delivery system for such antioxidants is necessary before the use of antioxidant-based therapies for cardiovascular diseases become a clinical reality. PMID:23552499
Rosenbaugh, Erin G; Savalia, Krupa K; Manickam, Devika S; Zimmerman, Matthew C
Cardiovascular diseases, including hypertension and heart failure, are associated with activation of the renin-angiotensin system (RAS) and increased circulating and tissue levels of ANG II, a primary effector peptide of the RAS. Through its actions on various cell types and organ systems, ANG II contributes to the pathogenesis of cardiovascular diseases by inducing cardiac and vascular hypertrophy, vasoconstriction, sodium and water reabsorption in kidneys, sympathoexcitation, and activation of the immune system. Cardiovascular research over the past 15–20 years has clearly implicated an important role for elevated levels of reactive oxygen species (ROS) in mediating these pathophysiological actions of ANG II. As such, the use of antioxidants, to reduce the elevated levels of ROS, as potential therapies for various ANG II-associated cardiovascular diseases has been intensely investigated. Although some antioxidant-based therapies have shown therapeutic impact in animal models of cardiovascular disease and in human patients, others have failed. In this review, we discuss the benefits and limitations of recent strategies, including gene therapy, dietary sources, low-molecular-weight free radical scavengers, polyethylene glycol conjugation, and nanomedicine-based technologies, which are designed to deliver antioxidants for the improved treatment of cardiovascular diseases. Although much work has been completed, additional research focusing on developing specific antioxidant molecules or proteins and identifying the ideal in vivo delivery system for such antioxidants is necessary before the use of antioxidant-based therapies for cardiovascular diseases become a clinical reality. PMID:23552499
Rosenbaugh, Erin G.; Savalia, Krupa K.; Manickam, Devika S.
Familial dysautonomia (FD) is a profound sensory and autonomic nervous system disorder associated with an increased risk for sudden death. While bradycardia resulting from loss of sympathetic tone has been hypothesized to play a role in this mortality, extended in-home monitoring has failed to find evidence of low heart rates in children with FD. In order to better characterize the specific cardio-respiratory pathophysiology and autonomic dysregulation in patients with FD, 25 affected children and matched controls were studied with in-home technology, during day and night. Respiratory and heart rate timing and variability metrics were derived from inductance plethysmography and electrocardiogram signals. Selective shortening of inspiratory time produced an overall increase in respiratory frequency in children with FD, with higher daytime respiratory variability (vs. controls), suggesting alterations in central rhythm generating circuits that may contribute to the heightened risk for sudden death. Overall heart rate was increased and variability reduced in FD cases, with elevated heart rates during 20% of study time. Time and frequency domain measures of autonomic tone indicated lower parasympathetic drive in FD patients (vs. controls). These results suggest withdrawal of vagal, rather than sympathetic tone, as a cause for the sustained increase and dramatic lability in respiration and heart rates that characterize this disorder. PMID:22170819
Carroll, Michael S; Kenny, Anna S; Patwari, Pallavi P; Ramirez, Jan-Marino; Weese-Mayer, Debra E
The glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide, liraglutide and lixisenatide have been shown to improve glycaemic control and beta-cell function with a low risk of hypoglycaemia in people with type 2 diabetes. GLP-1 receptors are also expressed in extra-pancreatic tissues and trial data suggest that GLP-1RAs also have effects beyond their glycaemic actions. Preclinical studies using native GLP-1 or GLP-1RAs provide substantial evidence for cardioprotective effects, while clinical trial data have shown beneficial actions on hypertension and dyslipidaemia in people with type 2 diabetes. Significant weight loss has been reported with GLP-1RAs in both people with type 2 diabetes and obese people without diabetes. GLP-1RAs also slow down gastric emptying, but preclinical data suggest that the main mechanism behind GLP-1RA-induced weight loss is more likely to involve their effects on appetite signalling in the brain. GLP-1RAs have also been shown to exert a neuroprotective role in rodent models of stroke, Alzheimer's disease and Parkinson's disease. These extra-pancreatic effects of GLP-1RAs could provide multi-factorial benefits to people with type 2 diabetes. Potential adverse effects of GLP-1RA treatment are usually manageable but may include gastrointestinal effects, increased heart rate and renal injury. While extensive further research is still required, early data suggest that GLP-1RAs may also have the potential to favourably impact cardiovascular disease, obesity or neurological disorders in people without diabetes in the future. PMID:24373150
Seufert, J; Gallwitz, B
Endothelin-2 [ET-2; also known as vasoactive intestinal contractor (VIC), in rodents] differs from endothelin-1 (ET-1) by only two amino acids, and unlike the third isoform, endothelin-3 (ET-3), it has the same affinity as ET-1 for both ETA and ETB receptors. It is often assumed that ET-2 would mimic the actions of the more abundant ET-1 and current pharmacological interventions used to inhibit the ET system would also block the actions of ET-2. These assumptions have focused research on ET-1 with ET-2 studied in much less detail. Recent research suggests that our understanding of the ET family requires re-evaluation. Although ET-2 is very similar in structure as well as pharmacology to ET-1, and may co-exist in the same tissue compartments, there is converging evidence for an important and distinct ET-2 pathway. Specifically is has been demonstrated that ET-2 has a key role in ovarian physiology, with ET-2-mediated contraction proposed as a final signal facilitating ovulation. Furthermore, ET-2 may also have a pathophysiological role in heart failure, immunology and cancer. Comparison of ET-2 versus ET-1 mRNA expression suggests this may be accomplished at the level of gene expression but differences may also exist in peptide synthesis by enzymes such as endothelin converting enzymes (ECEs) and chymase, which may allow the two pathways to be distinguished pharmacologically and become separate drug targets. LINKED ARTICLES This article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.168.issue-1 PMID:22118774
Ling, Lowell; Maguire, Janet J; Davenport, Anthony P
Aim Arteriovenous fistula-formation remains critical for the provision of hemodialysis in end-stage renal failure patients. Its creation results in a significant increase in cardiac output, with resultant alterations in cardiac stroke volume, systemic blood flow, and vascular resistance. The impact of fistula-formation on cardiac and vascular structure and function has not yet been evaluated via “gold standard” imaging techniques in the modern era of end-stage renal failure care. Methods A total of 24 patients with stage 5 chronic kidney disease undergoing fistula-creation were studied in a single-arm pilot study. Cardiovascular magnetic resonance imaging was undertaken at baseline, and prior to and 6 months following fistula-creation. This gold standard imaging modality was used to evaluate, via standard brachial flow-mediated techniques, cardiac structure and function, aortic distensibility, and endothelial function. Results At follow up, left ventricular ejection fraction remained unchanged, while mean cardiac output increased by 25.0% (P<0.0001). Significant increases in left and right ventricular end-systolic volumes (21% [P=0.014] and 18% [P<0.01]), left and right atrial area (11% [P<0.01] and 9% [P<0.01]), and left ventricular mass were observed (12.7% increase) (P<0.01). Endothelial-dependent vasodilation was significantly decreased at follow up (9.0%±9% vs 3.0%±6%) (P=0.01). No significant change in aortic distensibility was identified. Conclusion In patients with end-stage renal failure, fistula-formation is associated with an increase in cardiac output, dilation of all cardiac chambers and deterioration in endothelial function. PMID:25258554
Dundon, Benjamin K; Torpey, Kim; Nelson, Adam J; Wong, Dennis TL; Duncan, Rae F; Meredith, Ian T; Faull, Randall J; Worthley, Stephen G; Worthley, Matthew I
The analysis of the ambulance calls in Moscow, related to myocardial infarction (85.000 events), sudden death (71.700 events), and hypertension crises (165.500 events) over the period of 1979-1981 demonstrated their clear seasonal variations with a profound summer minimum and a winter maximum. The same results were obtained in the analysis of statistical monthly data on sudden death from infarction in Bulgaria over the period of 15 years (1970-1985). However, there are a great number of clinical and statistical studies confirming the rises in the incidence of myocardial infarction, hypertension crise, and sudden death during geomagnetic disturbances, which have maximum occurrence near equinox, not in winter. In order to explain this contradiction, we suggested that one of critical factors that affect the human cardiovascular system is geomagnetic micropulsations Pc1 having the frequency comparable with the frequency of heart rate beatings and winter maximum in their occurrence. The results of a comparative analysis of data of ambulance calls in Moscow related to myocardial infarction and sudden death and the catalog of Pc1 observations at the geophysical observatory "Borok" (Yaroslavl region) are presented. It is shown that in approximately 70% of days with an anomalously large number of ambulance calls related to myocardial infarction, Pc1 micropulsations have been registered. The probability of simultaneous occurrence of myocardial infarction and Pc1 in the winter season was 1.5 times greater than their accidental coincidence. Moreover, it was found that in winter the effects of magnetic storms and Pc1 IM(A) were much higher than in summer. We suggested that one of possible reasons for the seasonal variations in the occurrence of myocardial infarction is an increase in the production of the pineal hormone melatonin in winter which leads to an unstable state of the human organism and an increase in its sensitivity to the effect of geomagnetic pulsations. PMID:18225664
Kle?menova, N G; Kozyreva, O V; Breus, T K; Rapoport, S I
Frequency spectrum analysis of circulatory signals has been proposed as a potential method for clinical risk assessment of preterm infants by previous studies. In this study, we examined the relationships between various spectral measures derived from systemic and cerebral cardiovascular variabilities and the clinical risk index for babies (CRIB II). Physiological data collected from 17 early low birth weight infants within 1-3 h after birth were analysed. Spectral and cross-spectral analyses were performed on heart rate variability, blood pressure variability and cerebral near-infrared spectroscopy measures such as oxygenated and deoxygenated haemoglobins (HbO(2) and HHb) and tissue oxygenation index (TOI). In addition, indices related to cardiac baroreflex sensitivity and cerebral autoregulation were derived from the very low, low- and mid-frequency ranges (VLF, LF and MF). Moderate correlations with CRIB II were identified from mean arterial pressure (MAP) normalized MF power (r = 0.61, P = 0.009), LF MAP-HHb coherence (r = 0.64, P = 0.006), TOI VLF percentage power (r = 0.55, P = 0.023) and LF baroreflex gain (r = -0.61, P = 0.01 after logarithmic transformation), with the latter two parameters also highly correlated with gestational age (r = -0.75, P = 0.0005 and r = 0.70, P = 0.002, respectively). The relationships between CRIB II and various spectral measures of arterial baroreflex and cerebral autoregulation functions have provided further justification for these measures as possible markers of clinical risks and predictors of adverse outcome in preterm infants. PMID:22048689
Zhang, Ying; Chan, Gregory S H; Tracy, Mark B; Lee, Qim Y; Hinder, Murray; Savkin, Andrey V; Lovell, Nigel H
Transition metal ion-mediated oxidation is a commonly used model system for studies of the chemical, structural, and functional modifications of low-density lipoprotein (LDL). The physiological relevance of studies using free metal ions is unclear and has led to an exploration of free metal ion-independent mechanisms of oxidation. We and others have investigated the role of human ceruloplasmin (Cp) in oxidative processes because it the principal copper-containing protein in serum. There is an abundance of epidemiological data that suggests that serum Cp may be an important risk factor predicting myocardial infarction and cardiovascular disease. Biochemical studies have shown that Cp is a potent catalyst of LDL oxidation in vitro. The pro-oxidant activity of Cp requires an intact structure, and a single copper atom at the surface of the protein, near His(426), is required for LDL oxidation. Under conditions where inhibitory protein (such as albumin) is present, LDL oxidation by Cp is optimal in the presence of superoxide, which reduces the surface copper atom of Cp. Cultured vascular endothelial and smooth muscle cells also oxidize LDL in the presence of Cp. Superoxide release by these cells is a critical factor regulating the rate of oxidation. Cultured monocytic cells, when activated by zymosan, can oxidize LDL, but these cells are unique in their secretion of Cp. Inhibitor studies using Cp-specific antibodies and antisense oligonucleotides show that Cp is a major contributor to LDL oxidation by these cells. The role of Cp in lipoprotein oxidation and atherosclerotic lesion progression in vivo has not been directly assessed and is an important area for future studies.
Fox, P. L.; Mazumder, B.; Ehrenwald, E.; Mukhopadhyay, C. K.
In this paper, the problem of approximating a linear time-invariant stable system by a finite weighted sum of given exponentials is considered. System identification schemes using Laguerre models are extended and generalized to Kautz models, which correspond to representations using several different possible complex exponentials. In particular, linear regression methods to estimate this sort of model from measured data are
A mathematical model is presented of the VHF ranging system to analyze the performance of the Apollo-Soyuz test project (ASTP). The system was adapted for use in the ASTP. The ranging system mathematical model is presented in block diagram form, and a brief description of the overall model is also included. A procedure for implementing the math model is presented along with a discussion of the validation of the math model and the overall summary and conclusions of the study effort. Detailed appendices of the five study tasks are presented: early late gate model development, unlock probability development, system error model development, probability of acquisition and model development, and math model validation testing.
Ellis, M. R.; Robinson, L. H.
This contribution proposes a universal, intelligent information storage and management system for autonomous systems, e. g., robots. The proposed system uses a three pillar information architecture consisting of three distinct components: prior knowledge, environment model, and real world. In the center of the architecture, the environment model is situated, which constitutes the fusion target for prior knowledge and sensory information
Ioana Gheta; Michael Heizmann; Andrey Belkin; Jurgen Beyerer
In a healthy individual both during exercise aswell as at rest all four heart chambers contract in a coordinated fashion,\\u000a the valves function normally and the heartmuscle is perfused uniformly by the coronary arteries. Disease states can result\\u000a in abnormalities of valves, ventricular contraction, and reduced perfusion of the heart muscle. Nuclear cardiology is a very\\u000a useful clinical tool which
Malcolm J. Metcalfe
Although electrocardiography is frequently used as an initial test to detect or rule out previous myocardial infarction (MI), the diagnostic performance of commonly used electrocardiographic scoring systems is not well described. We aimed to determine the diagnostic accuracy of (1) the Universal Definition, (2) Minnesota ECG Code (MC), (3) Selvester QRS Score, and (4) assessment by cardiologists using late gadolinium enhancement cardiovascular magnetic resonance imaging as the reference standard. Additionally, the effect of electrocardiographic patterns and infarct characteristics on detecting previous MI was evaluated. The 3-month follow-up electrocardiograms of 78 patients with first-time reperfused ST elevation MI were pooled with electrocardiograms of 36 healthy controls. All 114 electrocardiograms were randomly analyzed, blinded to clinical and LGE-CMR data. The sensitivity of the Universal Definition, MC, Selvester QRS Score, and cardiologists to detect previous MI was 33%, 79%, 90%, and 67%, respectively; specificity 97%, 72%, 31%, and 89%, respectively; diagnostic accuracy 54%, 77%, 71%, and 74%, respectively. Probability of detecting MI by cardiologists increased with an increasing number (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.30 to 3.09), width (OR 1.02, 95% CI 1.01 to 1.03), and depth (OR 1.16, 95% CI 1.07 to 1.27) of Q waves as well as increasing infarct size (OR 1.15, 95% CI 1.06 to 1.25) and transmurality (OR 1.05, 95% CI 1.01 to 1.08; p <0.05 for all). The time-consuming MC and rapid visual assessment by cardiologists achieved the best and similar diagnostic accuracies to detect previous MI. The diagnostic performance of all 4 electrocardiographic scoring systems was modest and related to the number, depth, and width of Q waves as well as increasing infarct size and transmurality. In conclusion, the exclusion of a previous MI based solely on electrocardiographic findings should be done with caution. Future studies are needed to define which patients should be referred to additional diagnostic testing. PMID:23827406
Jaarsma, Caroline; Bekkers, Sebastiaan C; Haidari, Zaki; Smulders, Martijn W; Nelemans, Patricia J; Gorgels, Anton P; Crijns, Harry J; Wildberger, Joachim E; Schalla, Simon
The purpose of dynamic modeling and simulation of Advanced Life Support (ALS) systems is to help design them. Static steady state systems analysis provides basic information and is necessary to guide dynamic modeling, but static analysis is not sufficient to design and compare systems. ALS systems must respond to external input variations and internal off-nominal behavior. Buffer sizing, resupply scheduling, failure response, and control system design are aspects of dynamic system design. We develop two dynamic mass flow models and use them in simulations to evaluate systems issues, optimize designs, and make system design trades. One model is of nitrogen leakage in the space station, the other is of a waste processor failure in a regenerative life support system. Most systems analyses are concerned with optimizing the cost/benefit of a system at its nominal steady-state operating point. ALS analysis must go beyond the static steady state to include dynamic system design. All life support systems exhibit behavior that varies over time. ALS systems must respond to equipment operating cycles, repair schedules, and occasional off-nominal behavior or malfunctions. Biological components, such as bioreactors, composters, and food plant growth chambers, usually have operating cycles or other complex time behavior. Buffer sizes, material stocks, and resupply rates determine dynamic system behavior and directly affect system mass and cost. Dynamic simulation is needed to avoid the extremes of costly over-design of buffers and material reserves or system failure due to insufficient buffers and lack of stored material.
Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps as a result, fully effective countermeasures have yet to be developed. The National Space Biomedical Research Institute Cardiovascular Alterations Team is currently conducting a head-down tilt bed rest study in Boston. These studies involve the application of two powerful new methodologies developed at the NASA Center for Quantitative Cardiovascular Physiology, Modeling and Data Analysis at the Massachusetts Institute of Technology-cardiovascular system identification and T Wave Alternans analysis-for the study of the effects of simulated microgravity on the cardiovascular system. This study is being used as a basis for developing effective countermeasures against microgravity induced orthostatic hypotension and ventricular arrhythmias. .
Ramsdell, Craig D.; Sundby, Grete H.; Sherman, Derin; Maa, Ming; Baskin, Jacquelyn L.; Williams, Gordon H.; Cohen, Richard J.