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A novel approach to modeling and diagnosing the cardiovascular system  

SciTech Connect

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

Keller, P.E.; Kangas, L.J.; Hashem, S.; Kouzes, R.T. [Pacific Northwest Lab., Richland, WA (United States); Allen, P.A. [Life Link, Richland, WA (United States)



Fractal model for blood flow in cardiovascular system.  


Blood flow in the cardiovascular system is the central point of experimental and theoretical investigation. The objective of the study is to determine the blood flow in the cardiovascular system using Darcy's law, Reynold's number and Poiseuille's equation. A possible way of modeling of self-similar biological tree-like structure is proposed. Special attention is paid to the blood vessel system, with elaboration on a model with certain spatial arrangement of the vessels and reasonable dependence of the blood pressure on the vessels diameter such that the organism has a homogeneous oxygen supply. Flow analysis in the above systems is analyzed by invasion percolation. The blood flow in the cardiovascular system has been numerically calculated for both normal and abnormal patients. A new algorithm has been introduced to visit the blood vessels in a robust manner which avoids loops and provides us the results in a simple manner. PMID:18471808

Jayalalitha, G; Shanthoshini Deviha, V; Uthayakumar, R



Reintrepreting the cardiovascular system as a mechanical model  

NASA Astrophysics Data System (ADS)

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

Lemos, Diogo; Machado, José; Minas, Graça; Soares, Filomena; Barros, Carla; Lea~o, Celina Pinto



Mathematical modelling of flow distribution in the human cardiovascular system.  


The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite-element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes. PMID:1453803

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



Experimental Models of Renal Disease and the Cardiovascular System  

PubMed Central

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

Grossman, Rebecca C.



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


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



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

SciTech Connect

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

Kangas, L.J.; Keller, P.E.; Hashem, S. [and others



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

NASA Astrophysics Data System (ADS)

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.



Confronting a cardiovascular system model with heart rate and blood pressure data  

Microsoft Academic Search

The cardiovascular system may be investigated by observing fluctuations in the heart rate, blood pressure and rate of respiration. Its time evolution is governed by the baroreflex control mechanism, where the sympathetic and vagal nerves compete to increase and decrease the heart rate respectively. A nonlinear delay-differential equation model is constructed to describe this control mechanism and to explore the

P. E. McSharry; M. J. McGuinness; A. C. Fowler



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

Microsoft Academic Search

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



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

PubMed Central

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.

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



A Functional Cardiovascular Model with Disorders  

Microsoft Academic Search

This paper introduces a functional model of the cardiovascular system that is capable of describing its behavior in normal as well as pathologic cases. The developed model includes all the main compartments of the circulatory system and also the baroreflex-feedback regulatory mechanism. The model response to the incorporation of two critical cardiovascular disorders namely hypertension and acute congestive heart failure

M. E. Hassan; M. A. El-Brawany; M. M. Sharaf



Study of ventricular interaction during pulmonary embolism using clinical identification in a minimum cardiovascular system model.  


Cardiovascular disturbances are difficult to diagnose and treat because of the large range of possible underlying dysfunctions combined with regulatory reflex mechanisms that can result in conflicting clinical data. Thus, medical professionals often rely on experience and intuition to optimize hemodynamics in the critically ill. This paper combines an existing minimal cardiovascular system model with an extended integral based parameter identification method to track the evolution of induced pulmonary embolism in porcine data. The model accounts for ventricular interaction dynamics and is shown to predict an increase in the right ventricle expansion index and a decrease in septum volume consistent with known physiological response to pulmonary embolism. The full range of hemodynamic responses was captured with mean prediction errors of 4.1% in the pressures and 3.1% in the volumes for 6 sets of clinical data. Pulmonary resistance increased significantly with the onset of embolism in all cases, as expected, with the percentage increase ranging from 89.98% to 261.44% of the initial state. These results are an important first step towards model-based cardiac diagnosis in the Intensive Care Unit. PMID:18002620

Desaive, Thomas; Ghuysen, Alexandre; Lambermont, Bernard; Kolh, Philippe; Dauby, Pierre C; Starfinger, Christina; Hann, Christopher E; Chase, J; Shaw, Geoffrey M



Velocity profile method for time varying resistance in minimal cardiovascular system models  

NASA Astrophysics Data System (ADS)

This paper investigates the fluid dynamics governing arterial flow used in lumped parameter cardiovascular system (CVS) models, particularly near the heart where arteries are large. Assumptions made in applying equations conventionally used in lumped parameter models are investigated, specifically that of constant resistance to flow. The Womersley number is used to show that the effects of time varying resistance must be modelled in the pulsatile flow through the large arteries near the heart. It is shown that the equation commonly used to include inertial effects in fluid flow calculations is inappropriate for including time varying resistance. A method of incorporating time varying resistance into a lumped parameter model is developed that uses the Navier-Stokes equations to track the velocity profile. Tests on a single-chamber model show a 17.5% difference in cardiac output for a single-chamber ventricle model when comparing constant resistance models with the velocity profile tracking method modelling time varying resistance. This increase in precision can be achieved using 20 nodes with only twice the computational time required. The method offers a fluid dynamically and physiologically accurate method of calculating large Womersley number pulsatile fluid flows in large arteries around the heart and valves. The proposed velocity profile tracking method can be easily incorporated into existing lumped parameter CVS models, improving their clinical application by increasing their accuracy.

Smith, Bram W.; Chase, J. Geoffrey; Nokes, Roger I.; Shaw, Geoffrey M.; David, Tim



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

Microsoft Academic Search

A computational model of the entire cardiovascular system is established based on multi-scale modeling, where the arterial\\u000a tree is described by a one-dimensional model coupled with a lumped parameter description of the remainder. The resultant multi-scale\\u000a model forms a closed loop, thus placing arterial wave propagation into a global hemodynamic environment. The model is applied\\u000a to study the global hemodynamic

Fuyou Liang; Shu Takagi; Ryutaro Himeno; Hao Liu



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

PubMed Central

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



Animal Models of Cardiovascular Diseases  

PubMed Central

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.

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



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

PubMed Central

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



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


Because of the large number of interaction factors involved, the effects of the intra-aortic balloon pump (IABP) have not been investigated deeply. To enhance its clinical efficiency and to better define indications for use, advanced models are required to test the interaction between the IABP and the cardiovascular system. A patient with mild blood pressure depression and a lowered cardiac output is modeled in a lumped parameter computational model, developed with physiologically representative elements for relevant components of circulation and device. IABP support is applied, and the moments of balloon inflation and deflation are varied around their conventional timing modes. For validation purposes, timing is adapted within acceptable ranges in ten patients undergoing IABP therapy for typical clinical indications. In both model and patients, the IABP induces a diastolic blood pressure augmentation as well as a systolic reduction in afterload. The support capabilities of the IABP benefit the most when the balloon is deflated simultaneously with ventricular contraction, whereas inflation before onset of diastole unconditionally interferes with ejection. The physiologic response makes the model an excellent tool for testing the interaction between the IABP and the cardiovascular system, and how alterations of specific IABP parameters (i.e., timing) affect this coupling. PMID:23263334

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


PPARs and the Cardiovascular System  

PubMed Central

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

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



A closed-loop model of the canine cardiovascular system that includes ventricular interaction.  


A closed-loop model of cardiopulmonary circulation has been developed for the study of right-left ventricular interaction under physiologically normal and altered conditions. The core model provides insight into the effects of ventricular interaction and pericardial mechanics on hemodynamics. The complete model contains realistic descriptions of (a) the interacting ventricular free walls and septum, (b) the atria, (c) the pericardium, and (d) the systemic and pulmonary vascular loads. The current analysis extends previous work on ventricular interaction and pericardial influence under isolated heart conditions to loading conditions imposed by a closed-loop model of the circulation. A nonlinear least-squares parameter identification method (Levenberg-Marquardt algorithm) is used, together with parameter sensitivity analysis, to estimate the values of key parameters associated with the ventricular and circulation models. Pressure measurements taken at several anatomical locations in the circulation during open-chest experiments on dogs are used as data in the identification process. The complete circulatory model, including septal and pericardial coupling, serves as a virtual testbed for assessing the global affects of localized mechanical or hemodynamic alterations. Studies of both direct and series ventricular interaction, as well as the effect of the pericardium on cardiac performance, are accomplished with this model. Alterations in model parameter values are used to predict the impact of disease and/or clinical interventions on steady-state hemodynamic performance. Additionally, a software package titled CardioPV has been developed to integrate the complete model with data acquisition tools and a sophisticated graphical user interface. The complete software package enables users to collect experimental data, use the data to estimate model parameters, and view the model outputs in an online setting. PMID:10944405

Olansen, J B; Clark, J W; Khoury, D; Ghorbel, F; Bidani, A




Microsoft Academic Search

In this paper we discuss a model of the human cardiovas- cular-respiratory control system. The mechanisms which control the ventilation rate _ VA are fairly well understood and mathematical equa- tions have been devised to describe this control. The cardiovascular control system, on the other hand, involves a complex set of interrela- tionships between heart rate, blood pressure, cardiac output,

Susanne Timischl-Teschl; Jerry J. Batzel; Franz Kappel


Cardiovascular Magnetic Resonance Imaging in Experimental Models  

PubMed Central

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.

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



The Application of Genetic Mouse Models to Elucidate a Role for Fibroblast Growth Factor2 in the Mammalian Cardiovascular System  

Microsoft Academic Search

\\u000a Fibroblast growth factor (FGF)-2 is a polypeptide growth factor which plays multiple roles in the mammalian cardiovascular\\u000a system, having direct proliferative, migratory and differentiation effects on cardiac myocytes, fibroblasts, smooth muscle\\u000a and endothelial cells. To date, a number of genetic approaches in mice have been used to further our understanding of these\\u000a roles and effects. The three main approaches used

Karen A. Detillieux; Sarah K. Jimenez; David P. Sontag; Elissavet Kardami; Peter W. Nickerson; Peter A. Cattini


Alcohol and the Cardiovascular System.  

National Technical Information Service (NTIS)

Numerous studies have concluded that moderate drinking is associated with improved cardiovascular health. As a result, there is considerable government, industry, and public debate as to whether this knowledge should serve as the basis for health recommen...

M. Wassef S. Zakhari



Effects of cardiovascular parameter changes on heart rate variability: analysis by a mathematical model of short-term cardiovascular regulation  

Microsoft Academic Search

A mathematical model of short-term cardiovascular regulation is used to investigate how heart period power spectrum reflects alterations in cardiovascular parameters. The model includes the pulsating heart, the systemic and pulmonary circulation, the mechanical effects of respiration on hemodynamics, two groups of receptors (arterial baroreceptors and lung-stretch receptors), the sympathetic and vagal efferent branches, several distinct effectors, and a very

E. Magosso; M. Ursino



Estrogen signaling in the cardiovascular system  

PubMed Central

Estrogen exerts complex biological effects through the two isoforms of estrogen receptors (ERs): ER? and ER?. Whether through alteration of gene expression or rapid, plasma membrane-localized signaling to non-transcriptional actions, estrogen-activated ERs have significant implications in cardiovascular physiology. 17-?-estradiol (E2) generally has a protective property on the vasculature. Estrogen treatment is anti-atherogenic, protecting injured endothelial surfaces and lowering LDL oxidation in animal models. Increased NO production stimulated by E2 results in vasodilation of the coronary vascular bed, and involves rapid activation of phosphotidylinositol-3 kinase (PI3K)/Akt signaling to eNOS in carotid and femoral arteries. Both isoforms of ERs impact various vascular functions, modulating ion channel integrity, mitigating the response to arterial injury, inducing vasodilation, and preventing development of hypertension in animal models. In addition to reducing afterload by vasodilation, ERs have a direct antihypertrophic effect on the myocardium. E2-activated ERs (E2/ER) antagonize the hypertrophic pathway induced by vasoactive peptides such as angiotensin II by activating PI3K, subsequent MICIP gene expression, leading to the inhibition of calcineurin activity and the induction of hypertrophic genes. In models of ischemia-reperfusion, E2/ER is antiapoptotic for cardiomyocytes, exerting the protective actions via PI3K and p38 MAP kinases and suppressing the generation of reactive oxygen species. In sum, E2-activated ERs consistently and positively modulate multiple aspects of the cardiovascular system.

Kim, Jin Kyung; Levin, Ellis R.



Acromegaly and the Cardiovascular System  

Microsoft Academic Search

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



User's Instructions for the Cardiovascular Walters Model.  

National Technical Information Service (NTIS)

The model is a combined, steady-state cardiovascular and thermal model. It was originally developed for interactive use, but was converted to batch mode simulation for the Sigma 3 computer. The model has the purpose to compute steady-state circulatory and...

R. C. Croston



Cardiovascular magnetic resonance in systemic hypertension  

PubMed Central

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.



Exercise and the Cardiovascular System  

PubMed Central

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.

Golbidi, Saeid; Laher, Ismail



Cortical modulation of the cardiovascular system.  


Cortical modulation of central cardiovascular control mechanisms has been recognized for many decades. However, it is only recently that the mechanisms underlying cortical influences on circulatory function have been systematically examined. This review considers the view that certain regions of the cerebral cortex, including the medial prefrontal cortex (MPFC) and insular cortex (IC), participate in specific aspects of central circulatory control. Anatomical investigations indicate that these cortical areas are connected with hypothalamic, midbrain, pontine and medullary brain regions involved in cardiovascular control. Lesions of the MPFC and IC have demonstrated modulation of the activity of cardiovascular reflexes such as the baroreceptor heart rate reflex and involvement in conditioned cardiovascular responses. Electrophysiological studies have provided evidence that cortical regions are able to influence premotor sympathoexcitatory vasomotor neurons within the rostral ventrolateral medulla and subsequently alter sympathetic vasomotor tone. Cortical regions such as the IC receive visceral sensory information arising from baroreceptors and chemoreceptors within the cardiovascular system. In contrast, the MPFC receives afferents predominantly from limbic sources, although its outputs include structures associated with central sympathetic vasomotor control. Cortical modulation of circulatory function has been demonstrated in man and may underlie the cardiovascular components of a number of conditions. It is suggested that cortical areas involved in visceral sensory or visceral motor processes associated with circulatory function may be involved in generation of patterns of cardiovascular responses specific for certain behaviours. PMID:9481796

Verberne, A J; Owens, N C



Thyrotoxicosis and the cardiovascular system.  


Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism. Palpitations, caused by sinus tachycardia and occasionally by atrial fibrillation, are the most frequent cardiovascular symptom. As atrial fibrillation may be the only manifestation of thyrotoxicosis, thyroid hormone excess should routinely be excluded in patients with this rhythm disturbance. Heart failure occurs mostly in the presence of underlying heart disease or tachycardia-induced cardiomyopathy in patients with long-standing atrial fibrillation. On occasion, long-standing hyperthyroidism may lead to heart failure even in the absence of concomitant cardiac conditions. Beta-blockers offer symptomatic relief and at the same time slow the ventricular response in patients with atrial fibrillation. Amiodarone, and occasionally iodinated contrast agents, may cause iodine-induced thyrotoxicosis. Clinical suspicion is essential in the diagnosis of amiodarone-induced thyrotoxicosis (AIT), because the antiadrenergic effect of the drug may conceal symptoms. AIT should be considered in any patient on amiodarone in the presence of new-onset or recurrent atrial arrhythmias or unexplained weight loss. Beyond discontinuation of amiodarone, treatment options include propylthiouracil or methimazole, potassium perchlorate, steroids, lithium and, if pharmacological treatment fails, surgery. Amiodarone may potentially be used less frequently in the future since recent studies have shown that this drug is inferior to implantable cardioverter defibrillators in prevention of sudden cardiac death in patients with severe heart failure. In addition, non-iodinated amiodarone analogues are currently in advanced phase of clinical testing. PMID:15988401

Roffi, M; Cattaneo, F; Brandle, M



Multifractal heart rate dynamics in human cardiovascular model  

NASA Astrophysics Data System (ADS)

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



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


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



Acute pneumonia and the cardiovascular system.  


Although traditionally regarded as a disease confined to the lungs, acute pneumonia has important effects on the cardiovascular system at all severities of infection. Pneumonia tends to affect individuals who are also at high cardiovascular risk. Results of recent studies show that about a quarter of adults admitted to hospital with pneumonia develop a major acute cardiac complication during their hospital stay, which is associated with a 60% increase in short-term mortality. These findings suggest that outcomes of patients with pneumonia can be improved by prevention of the development and progression of associated cardiac complications. Before this hypothesis can be tested, however, an adequate mechanistic understanding of the cardiovascular changes that occur during pneumonia, and their role in the trigger of various cardiac complications, is needed. In this Review, we summarise knowledge about the burden of cardiac complications in adults with acute pneumonia, the cardiovascular response to this infection, the potential effects of commonly used cardiovascular and anti-infective drugs on these associations, and possible directions for future research. PMID:23332146

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



[Rheumatoid arthritis. Systemic inflammation and cardiovascular morbidity].  


In recent years it could be shown that systemic inflammation, which typically occurs in chronic inflammatory rheumatic diseases, significantly contributes to cardiovascular morbidity and mortality. All rheumatic diseases inherit this enhanced risk for cardiovascular complications with rheumatoid arthritis being one of the most prominent. As the underlying pathophysiological mechanisms are very similar with respect to endothelial damage all rheumatic diseases and specifically rheumatoid arthritis should be monitored and treated with disease-modifying drugs and biological agents as consistently as possible to be able to improve the long-term outcome of affected patients as much as possible. PMID:23463461

Decker, E; Müller-Ladner, U



The cardiovascular system in the ageing patient  

PubMed Central

The ageing process is associated with important changes in the responses of the cardiovascular system to pharmacological stimuli. They are not limited to the arterial system, involved in the modulation of cardiac afterload and vascular resistance, but they also involve the low-resistance capacitance venous system and the heart. The main changes include loss of large artery compliance, dysfunction of some of the systems modulating resistance vessel tone, increased activity of the sympathetic nervous system, and reduced haemodynamic responses to inotropic agents. This review focuses on the effects of ageing on arterial and venous reactivity to drugs and hormones, the autonomic nervous system, and the cardiovascular responses to inotropic agents. Some of the age-related changes might be at least partially reversible. This may have important therapeutic implications.

Moore, A; Mangoni, A A; Lyons, D; Jackson, S H D



Effect of Photochemotherapy on the Cardiovascular System  

Microsoft Academic Search

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

E. P. Prens; G. Smeenk



Evaluation of the cardiovascular system using NMR.  


The current status and suggestions of the future potential for nuclear magnetic resonance imaging of the cardiovascular system are described. With many of the potential applications, there is overlap with existing methods. For example, imaging of the left ventricle can be accomplished with either echocardiography or radionuclide techniques with adequate evaluation of the left ventricular function. At current costs these conventional techniques may provide a more cost-effective approach for morphologic and functional assessment of the cardiovascular system. For this type of imaging, the advantages of NMR include its excellent resolution, the inherent tissue contrast, the sensitivity to blood motion, the 3-dimensional measure, and the lack of ionizing radiation. Because of these, NMR could provide an important adjunct for evaluation of the cardiovascular system. However for NMR to achieve its full promise as a cardiovascular imaging technique, some of its unique potentials need to be developed. These include: the ability to reliably image at least the proximal coronary arteries, the ability to delineate regional myocardial blood flow distribution, the ability to evaluate regional metabolic activity such as high-energy phosphate metabolites, and the ability to characterize myocardial disease using proton T1 and T2 alterations. PMID:2424388

Reeves, R C; Evanochko, W T; Pohost, G M



Estimation of cardiac output and systemic vascular resistance using a multivariate regression model with features selected from the finger photoplethysmogram and routine cardiovascular measurements  

PubMed Central

Background Cardiac output (CO) and systemic vascular resistance (SVR) are two important parameters of the cardiovascular system. The ability to measure these parameters continuously and noninvasively may assist in diagnosing and monitoring patients with suspected cardiovascular diseases, or other critical illnesses. In this study, a method is proposed to estimate both the CO and SVR of a heterogeneous cohort of intensive care unit patients (N=48). Methods Spectral and morphological features were extracted from the finger photoplethysmogram, and added to heart rate and mean arterial pressure as input features to a multivariate regression model to estimate CO and SVR. A stepwise feature search algorithm was employed to select statistically significant features. Leave-one-out cross validation was used to assess the generalized model performance. The degree of agreement between the estimation method and the gold standard was assessed using Bland-Altman analysis. Results The Bland-Altman bias ±precision (1.96 times standard deviation) for CO was -0.01 ±2.70 L min-1 when only photoplethysmogram (PPG) features were used, and for SVR was -0.87 ±412 when only one PPG variability feature was used. Conclusions These promising results indicate the feasibility of using the method described as a non-invasive preliminary diagnostic tool in supervised or unsupervised clinical settings.



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

PubMed Central

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

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



Mathematical biomarkers for the autonomic regulation of cardiovascular system  

PubMed Central

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.

Campos, Luciana A.; Pereira, Valter L.; Muralikrishna, Amita; Albarwani, Sulayma; Bras, Susana; Gouveia, Sonia



Effect of photochemotherapy on the cardiovascular system.  


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



Models of Cheyne-Stokes respiration with cardiovascular pathologies  

Microsoft Academic Search

Cheyne-Stokes respiration (CSR) is a periodic breathing pattern, characterized by short intervals of very little or no breathing\\u000a (apnea), each followed by an interval of very heavy breathing (hyperpnea). This work presents a new compartmental model of\\u000a the human cardio-respiratory system, simulating the factors that determine the concentrations of carbon dioxide in the compartments\\u000a of the cardiovascular system and the

Fang Dong; William F. Langford



A clinical decision support system prototype for cardiovascular intensive care  

Microsoft Academic Search

This paper describes the development and validation of a decision-support system prototype that can help manage hypovolemic\\u000a hypotension in the Cardiovascular Intensive Care Unit (CVICU). The prototype uses physiologic pattern-matching, therapeutic\\u000a protocols, computational drug-dosage response modeling and expert reasoning heuristics in its selection of intervention strategies\\u000a and choices. As part of model testing, the prototype simulated real-time operation by processing

Francis Lau



Subject-specific cardiovascular system model-based identification and diagnosis of septic shock with a minimally invasive data set: animal experiments and proof of concept.  


A cardiovascular system (CVS) model and parameter identification method have previously been validated for identifying different cardiac and circulatory dysfunctions in simulation and using porcine models of pulmonary embolism, hypovolemia with PEEP titrations and induced endotoxic shock. However, these studies required both left and right heart catheters to collect the data required for subject-specific monitoring and diagnosis-a maximally invasive data set in a critical care setting although it does occur in practice. Hence, use of this model-based diagnostic would require significant additional invasive sensors for some subjects, which is unacceptable in some, if not all, cases. The main goal of this study is to prove the concept of using only measurements from one side of the heart (right) in a 'minimal' data set to identify an effective patient-specific model that can capture key clinical trends in endotoxic shock. This research extends existing methods to a reduced and minimal data set requiring only a single catheter and reducing the risk of infection and other complications-a very common, typical situation in critical care patients, particularly after cardiac surgery. The extended methods and assumptions that found it are developed and presented in a case study for the patient-specific parameter identification of pig-specific parameters in an animal model of induced endotoxic shock. This case study is used to define the impact of this minimal data set on the quality and accuracy of the model application for monitoring, detecting and diagnosing septic shock. Six anesthetized healthy pigs weighing 20-30 kg received a 0.5 mg kg(-1) endotoxin infusion over a period of 30 min from T0 to T30. For this research, only right heart measurements were obtained. Errors for the identified model are within 8% when the model is identified from data, re-simulated and then compared to the experimentally measured data, including measurements not used in the identification process for validation. Importantly, all identified parameter trends match physiologically and clinically and experimentally expected changes, indicating that no diagnostic power is lost. This work represents a further with human subjects validation for this model-based approach to cardiovascular diagnosis and therapy guidance in monitoring endotoxic disease states. The results and methods obtained can be readily extended from this case study to the other animal model results presented previously. Overall, these results provide further support for prospective, proof of concept clinical testing with humans. PMID:21098941

Chase, J Geoffrey; Lambermont, Bernard; Starfinger, Christina; Hann, Christopher E; Shaw, Geoffrey M; Ghuysen, Alexandre; Kolh, Philippe; Dauby, Pierre C; Desaive, Thomas



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

ERIC Educational Resources Information Center

|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




PubMed Central

The mammalian Natriuretic Peptide (NP) system consists of neuro-hormones, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), c-type natriuretic peptide (CNP), and the N-Terminal fragment of BNP (NT-pro-BNP). In response to some cardiovascular derangement the heart (acting as an endocrine organ), brain and other structures secretes natriuretic peptides in an attempt to restore normal circulatory conditions. Their actions are modulated through membrane-bound guanylyl cyclased (GC) receptors. They induce diuresis, natriuresis and vasodilation in the presence of congestive heart failure. These neuro-hormones also play a role in the suppression of neointimal formation after vascular injury. In addition, they act as antifibrotic and antihypertrophic agents preventing cardiac remodeling after myocardial infarction. Further, NP have diagnostic and prognostic role in heart failure, vasoconstriction, left ventricular late remodeling after MI and others. At present, some drugs such as Nesiritide, NEP inhibitors and vasopeptidase inhibitors were synthetized from NP, to antagonize these cardiovascular derengements. In future, it will be possibile to elaborate some drugs similar to petidase inhibitors and some CNP-like drugs able to reduce many symptoms of cardiovascular derangements without significant side effects.

Federico, Cacciapuoti



Cardiovascular system of anomuran crabs, genus Lopholithodes.  


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



Corticosteroids: do they damage the cardiovascular system?  

PubMed Central

Since their introduction for the treatment of rheumatoid arthritis, corticosteroids have become widely used as effective agents in the control of inflammatory diseases. Although there have been undoubted benefits upon mortality in diseases such as systemic lupus erythematosus, many patients survive only to suffer a high incidence of premature atherosclerosis. There is also evidence of increased rates of vascular mortality in other corticosteroid-treated diseases, such as rheumatoid arthritis, reversible airways obstruction and transplant recipients. Possible mechanisms of damage include elevated blood pressure, impaired glucose tolerance, dyslipidaemia, and imbalances in thrombosis and fibrinolysis. This paper reviews the clinical evidence supporting the contention that there is an excess cardiovascular mortality in steroid-treated patients and the underlying mechanisms, and points to further areas of research.

Maxwell, S. R.; Moots, R. J.; Kendall, M. J.



The Ubiquitin-Proteasome System and Cardiovascular Disease  

PubMed Central

Over the past decade, the role of the ubiquitin–proteasome system (UPS) has been the subject of numerous studies to elucidate its role in cardiovascular physiology and pathophysiology. There have been many advances in this field including the use of proteomics to achieve a better understanding of how the cardiac proteasome is regulated. Moreover, improved methods for the assessment of UPS function and the development of genetic models to study the role of the UPS have led to the realization that often the function of this system deviates from the norm in many cardiovascular pathologies. Hence, dysfunction has been described in atherosclerosis, familial cardiac proteinopathies, idiopathic dilated cardiomyopathies, and myocardial ischemia. This has led to numerous studies of the ubiquitin protein (E3) ligases and their roles in cardiac physiology and pathophysiology. This has also led to the controversial proposition of treating atherosclerosis, cardiac hypertrophy, and myocardial ischemia with proteasome inhibitors. Furthering our knowledge of this system may help in the development of new UPS-based therapeutic modalities for mitigation of cardiovascular disease.

Powell, Saul R.; Herrmann, Joerg; Lerman, Amir; Patterson, Cam; Wang, Xuejun



The reactivity of the cardiovascular system in experimental noninfectious peritonitis  

Microsoft Academic Search

The author studied the reactivity of the cardiovascular system of the rabbit to adrenalin and caffeine in experimental noninfectious peritonitis. On intravenous injection of these drugs against the background of peritonitis, the cardiovascular system responded by a more intense pressor and depressor effect. The latter, however, was more pronounced, which may point to the higher tone of the cholinergic nerves

P. P. Gusach



Systems-based approaches to cardiovascular disease  

Microsoft Academic Search

Common cardiovascular diseases, such as atherosclerosis and congestive heart failure, are exceptionally complex, involving a multitude of environmental and genetic factors that often show nonlinear interactions as well as being highly dependent on sex, age, and even the maternal environment. Although focused, reductionistic approaches have led to progress in elucidating the pathophysiology of cardiovascular diseases, such approaches are poorly powered

W. Robb MacLellan; Yibin Wang; Aldons J. Lusis



Weightlessness - a model to understand how gravity modulates cardiovascular function  

Microsoft Academic Search

Gravity stresses the cardiovascular system in humans by decreasing the blood supply to the heart. As a consequence of this, reflexes are constantly activated to increase heart rate, constrict the blood vessels and diminish the renal output of fluid. To explore how gravity modulates cardiovascular function, longterm weightlessness in space is a useful tool. Therefore, we have participated in space

Peter Norsk


Local Renin Angiotensin Systems in the Cardiovascular System  

Microsoft Academic Search

\\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


Effects of Thyroid Hormone on the Cardiovascular System  

Microsoft Academic Search

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




Computational models of cardiovascular function for analysis of post-flight orthostatic intolerance.  


The work presented in this paper is part of an ongoing effort to use mathematical models to investigate the effects of microgravity on the cardiovascular system. In particular, a thirteen compartment lumped parameter representation of the cardiovascular system is used to simulate some of the current hypotheses concerning the mechanism of post-flight orthostatic intolerance. Simulations are compared to astronaut stand test data pre - and post-flight in an effort to quantitatively evaluate alternative hypotheses. PMID:11795340

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



Mechanisms of lipotoxicity in the cardiovascular system.  


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

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



The paleopathology of the cardiovascular system.  

PubMed Central

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

Zimmerman, M R



Angiotensin II-Forming Systems in Cardiovascular Diseases  

Microsoft Academic Search

Both the systemic and the tissue renin–angiotensin system (RAS)-are heavily involved in cardiovascular homeostasis, but their excess activation seems to be associated with increased morbidity and mortality in various stages of cardiovascular diseases, since angiotensin-converting enzyme (ACE) inhibitors have been shown to improve hypertension, congestive heart failure, and acute myocardial infarction. A clinical megastudy (ELITE) of elderly patients has recently

Hidenori Urata; Kikuo Arakawa



Sex steroids and the cardiovascular system  

Microsoft Academic Search

Summary HRT decreases significantly the risk of cardiovascular disease in postmenopausal women. More and more data indicate that this is true not only for unopposed oestrogen but also for combined oestrogen\\/progestin therapy. The latter point is of utmost importance since the global treatment strategy for women with an intact uterus includes a progestin.

C. Christiansen



Is the cardiovascular system a therapeutic target for cannabidiol?  


Cannabidiol (CBD) has beneficial effects in disorders as wide ranging as diabetes, Huntington's disease, cancer and colitis. Accumulating evidence now also suggests that CBD is beneficial in the cardiovascular system. CBD has direct actions on isolated arteries, causing both acute and time-dependent vasorelaxation. In vitro incubation with CBD enhances the vasorelaxant responses in animal models of impaired endothelium-dependent vasorelaxation. CBD protects against the vascular damage caused by a high glucose environment, inflammation or the induction of type 2 diabetes in animal models and reduces the vascular hyperpermeability associated with such environments. A common theme throughout these studies is the anti-inflammatory and anti-oxidant effect of CBD. In the heart, in vivo CBD treatment protects against ischaemia-reperfusion damage and against cardiomyopathy associated with diabetes. Similarly, in a different model of ischaemia-reperfusion, CBD has been shown to reduce infarct size and increase blood flow in animal models of stroke, sensitive to 5HT(1A) receptor antagonism. Although acute or chronic CBD treatment seems to have little effect on haemodynamics, CBD reduces the cardiovascular response to models of stress, applied either systemically or intracranially, inhibited by a 5HT(1A) receptor antagonist. In blood, CBD influences the survival and death of white blood cells, white blood cell migration and platelet aggregation. Taken together, these preclinical data appear to support a positive role for CBD treatment in the heart, and in peripheral and cerebral vasculature. However, further work is required to strengthen this hypothesis, establish mechanisms of action and whether similar responses to CBD would be observed in humans. PMID:22670794

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



BP fluctuations in the normotensive versus the hypertensive cardiovascular system: simulation and experiment  

Microsoft Academic Search

A computerised model has been designed in order to simulate blood pressure (BP) control and mean BP (MBP) fluctuations in the normal and the hypertensive cardiovascular system. The purpose of this model is to compare between the two systems by allowing their control limbs to function naturally, hoping to obtain the BP fluctuations as experimentally observed in the two strains.

S. Akselrod; G. Wasserman; O. Oz; S. Cohen; S. Eliash



Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism  

Microsoft Academic Search

In this review, we examine cardiovascular metabo- lism from three different, but highly complementary, perspectives. First, from the abstract perspective of a me- tabolite network, composed of nodes and links. We present fundamental concepts in network theory, including emer- gence, to illustrate how nature has designed metabolism with a hierarchal modular scale-free topology to provide a robust system of energy

James N. Weiss; Ling Yang; Zhilin Qu



Renin Angiotensin Aldosterone System and Cardiovascular Disease  

Microsoft Academic Search

\\u000a Aldosterone, aldo, is a rather minor component of the adrenal gland production with complex activity. Aldo and glucocorticoid\\u000a are in competition and the specificity of aldo action is due to a cellular component the 11-HSD2. Aldo at high concentrations\\u000a has pronounced and deleterious cardiovascular effects and causes pro-inflammatory reaction followed by myocardial and vascular\\u000a fibrosis. Fibrosis modifies cardiac performances and

Swynghedauw Bernard; Milliez Paul; Messaoudi Smail; Benard Ludovic; Samuel Jane-Lise; Delcayre Claude


A behavioral link between the oculomotor and cardiovascular systems  

Microsoft Academic Search

Although the eyes and the heart serve very different purposes, each receives autonomic innervation. Capitalizing on recent\\u000a theoretical and technological innovations in the understanding and assessment of oculomotor and cardiovascular behavior, three\\u000a experiments measured behavioral covariation between the oculomotor and cardiovascular systems. Measures of dark focus and\\u000a dark vergence indexed oculomotor tone, and the spectral decomposition of variations in heart

Richard A. Tyrrell; Julian F. Thayer; Bruce H. Friedman; Herschel W. Leibowitz; Ellie L. Francis



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


This review focuses on the role of adipokines in the maintenance of a healthy cardiovascular system, and the mechanisms by which these factors mediate the development of cardiovascular disease in obesity. Adipocytes are the major cell type comprising the adipose tissue. These cells secrete numerous factors, termed adipokines, into the blood, including adiponectin, leptin, resistin, chemerin, omentin, vaspin, and visfatin. Adipose tissue is a highly vascularised endocrine organ, and different adipose depots have distinct adipokine secretion profiles, which are altered with obesity. The ability of many adipokines to stimulate angiogenesis is crucial for adipose tissue expansion; however, excessive blood vessel growth is deleterious. As well, some adipokines induce inflammation, which promotes cardiovascular disease progression. We discuss how these 7 aforementioned adipokines act upon the various cardiovascular cell types (endothelial progenitor cells, endothelial cells, vascular smooth muscle cells, pericytes, cardiomyocytes, and cardiac fibroblasts), the direct effects of these actions, and their overall impact on the cardiovascular system. These were chosen, as these adipokines are secreted predominantly from adipocytes and have known effects on cardiovascular cells. PMID:22646022

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



Reactive oxygen species and the cardiovascular system.  


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



Cardiovascular Changes in Animal Models of Metabolic Syndrome  

PubMed Central

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.

Lehnen, Alexandre M.; Rodrigues, Bruno; Irigoyen, Maria Claudia; De Angelis, Katia; Schaan, Beatriz D'Agord



Remodeling and reparation of the cardiovascular system.  


Growth or altered metabolism of nonmyocyte cells (cardiac fibroblasts, vascular smooth muscle and endothelial cells) alters myocardial and vascular structure (remodeling) and function. However, the precise roles of circulating and locally generated factors such as angiotensin II, aldosterone and endothelin that regulate growth and metabolism of nonmyocyte cells have yet to be fully elucidated. Trials of pharmacologic therapy aimed at preventing structural remodeling and repairing altered myocardial structure to or toward normal in the setting of hypertension, heart failure and diabetes are reviewed. It is proposed that these are therapeutic goals that may reduce cardiovascular morbidity and mortality. Although this hypothesis remains unproved the primary goal of therapy should be to preserve or restore tissue structure and function. PMID:1318886

Weber, K T; Anversa, P; Armstrong, P W; Brilla, C G; Burnett, J C; Cruickshank, J M; Devereux, R B; Giles, T D; Korsgaard, N; Leier, C V



Verification of a one-dimensional finite element method for modeling blood flow in the cardiovascular system incorporating a viscoelastic wall model  

Microsoft Academic Search

In this study we present the implementation and verification of a space–time finite element method for solving the nonlinear one-dimensional (1-D) equations of blood flow incorporating a viscoelastic arterial wall model. The viscoelastic model used is based on the generalized Maxwell model and thin-walled tube theory assumptions. Verification of the implementation was conducted using two different methods: (1) the analytic

R. Raghu; C. A. Taylor



Technological innovations in the development of cardiovascular clinical information systems.  


Recent studies have shown that computerized clinical case management and decision support systems can be used to assist surgeons in the diagnosis of disease, optimize surgical operation, aid in drug therapy and decrease the cost of medical treatment. Therefore, medical informatics has become an extensive field of research and many of these approaches have demonstrated potential value for improving medical quality. The aim of this study was to develop a web-based cardiovascular clinical information system (CIS) based on innovative techniques, such as electronic medical records, electronic registries and automatic feature surveillance schemes, to provide effective tools and support for clinical care, decision-making, biomedical research and training activities. The CIS developed for this study contained monitoring, surveillance and model construction functions. The monitoring layer function provided a visual user interface. At the surveillance and model construction layers, we explored the application of model construction and intelligent prognosis to aid in making preoperative and postoperative predictions. With the use of the CIS, surgeons can provide reasonable conclusions and explanations in uncertain environments. PMID:20703637

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



Clinical Application of Stem Cells in the Cardiovascular System  

NASA Astrophysics Data System (ADS)

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


The Representative Porcine Model for Human Cardiovascular Disease  

PubMed Central

To improve human health, scientific discoveries must be translated into practical applications. Inherent in the development of these technologies is the role of preclinical testing using animal models. Although significant insight into the molecular and cellular basis has come from small animal models, significant differences exist with regard to cardiovascular characteristics between these models and humans. Therefore, large animal models are essential to develop the discoveries from murine models into clinical therapies and interventions. This paper will provide an overview of the more frequently used large animal models, especially porcine models for preclinical studies.

Suzuki, Yoriyasu; Yeung, Alan C.; Ikeno, Fumiaki



Effects of red wine polyphenolic compounds on the cardiovascular system  

Microsoft Academic Search

Phenolic phytochemicals are widely distributed in the plant kingdom. Regarding the protective effects on organisms, the polyphenol group is the most important. In different experiments, it has been shown that selected polyphenols, mainly flavonoids, possess protective effects on the cardiovascular system, as well as anticancer, antiviral and antiallergic properties. In coronary heart disease, the protective effects include mainly antithrombic, antioxidant,

Zenebe W; Pechanova O


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

PubMed Central

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

Cohen, Michael A; Taylor, J Andrew



Patient-specific modeling of cardiovascular and respiratory dynamics during hypercapnia.  


This study develops a lumped cardiovascular-respiratory system-level model that incorporates patient-specific data to predict cardiorespiratory response to hypercapnia (increased CO(2) partial pressure) for a patient with congestive heart failure (CHF). In particular, the study focuses on predicting cerebral CO(2) reactivity, which can be defined as the ability of vessels in the cerebral vasculature to expand or contract in response CO(2) induced challenges. It is difficult to characterize cerebral CO(2) 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 CO(2) 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 (CO(2) and O(2)) 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 CO(2) partial pressure. During eucapnia, seven cardiovascular parameters and four 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



Method of propulsion of a ferromagnetic core in the cardiovascular system through magnetic gradients generated by an MRI system  

Microsoft Academic Search

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



Potential approaches to evaluating the cardiovascular system using NMR.  


The current status and some of the future possibilities for nuclear magnetic resonance imaging of the cardiovascular system have been described. With many of these possibilities there is overlap with existing techniques. For example, functional analysis of the left ventricle can be obtained using either echocardiography or radionuclide techniques. With current instrumentation and current costs, these conventional techniques could frequently provide a more cost-effective approach for morphologic and functional assessment of the cardiovascular system. Nevertheless, because of the excellent resolution, the inherent contrast, the sensitivity to blood motion, the three-dimensional nature, and the lack of ionizing radiation, the cardiovascular morphologic imaging capabilities of NMR may provide justification for such applications. However, for NMR to achieve its most important status as a cardiovascular imaging technique, some of its unique possibilities will need to be developed. These include the ability to reproducibly depict the proximal coronary arteries, to define regional myocardial blood flow distribution, to evaluate regional high energy phosphate or other metabolic activity; and to characterize myocardial disease using proton T1 and T2 alterations. PMID:3523618

Reeves, R C; Evanochko, W T; Pohost, G M


Autonomic nervous system mediated effects of food intake : Interaction between gastrointestinal and cardiovascular systems  

Microsoft Academic Search

The studies presented in this thesis focused on the autonomic nervous system mediated interactions between the gastrointestinal and cardiovascular systems in response to food intake and on potential consequences of failure of these interactions. The effects of food intake on cardiovascular parameters, including muscle sympathetic nerve activity, were studied in healthy young and healthy elderly individuals, in patients who were

N. P. van Orshoven



Cardiovascular parasympathetic nervous system dysfunction in female rheumatoid arthritis patients.  


The autonomic dysfunction has been reported in patients with (rheumatoid arthritis) RA and systemic lupus erythematosus (SLE) like connective tissue disorders and it may be due to the vasculitis of vasa nervorum and secondary amyloidosis. The pathogenesis may also have an immune component that affects autonomic functions. In the present study, three standard cardiovascular parasympathetic function tests were performed in 207 RA patients and in 106 healthy controls. 14.45% patients were presented with symptoms related to cardiovascular autonomic dysfunction. Heart rate variation to deep breathing (DBD), standing (30:15 ratio), Valsalva ratio (VR) were found to be significantly reduced in RA patients and was weakly associated with female RA patients (r = 0.165, p = 0.018) and was not correlated to disease duration, RF positivity & severity of the disease. In conclusion, this study has confirmed the presence of significant subclinical cardiovascular parasympathetic nervous dysfunction in RA patients and its positive association with female gender. Hence, inclusion of cardiovascular autonomic function tests in the routine clinical examination may be helpful in the early detection of autonomic dysfunction in RA. PMID:24020095

Saraswathi, P V; Neelambikai, N; Mahesh, Arjun; Govindarajan, K


CaMKII in the Cardiovascular System: Sensing Redox States  

PubMed Central

The multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease. CaMKII is a multimeric serine-threonine kinase that is initially activated by binding calcified calmodulin (Ca2+/CaM). Under conditions of sustained exposure to elevated Ca2+/CaM CaMKII transitions into a Ca2+/CaM-autonomous enzyme by two distinct but parallel processes. Autophosphorylation of threonine 287 in the CaMKII regulatory domain ‘traps’ CaMKII into an open configuration even after Ca2+/CaM unbinding. More recently, our group identified a pair of methionines (281/282) in the CaMKII regulatory domain that undergo a partially reversible oxidation which, like autophosphorylation, prevents CaMKII from inactivating after Ca2+/CaM unbinding. Here we review roles of CaMKII in cardiovascular disease with an eye to understanding how CaMKII may act as a transduction signal to connect pro-oxidant conditions into specific downstream pathological effects that are relevant to rare and common forms of cardiovascular disease.

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



CaMKII in the cardiovascular system: sensing redox states.  


The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease. CaMKII is a multimeric serine-threonine kinase that is initially activated by binding calcified calmodulin (Ca(2+)/CaM). Under conditions of sustained exposure to elevated Ca(2+)/CaM, CaMKII transitions into a Ca(2+)/CaM-autonomous enzyme by two distinct but parallel processes. Autophosphorylation of threonine-287 in the CaMKII regulatory domain "traps" CaMKII into an open configuration even after Ca(2+)/CaM unbinding. More recently, our group identified a pair of methionines (281/282) in the CaMKII regulatory domain that undergo a partially reversible oxidation which, like autophosphorylation, prevents CaMKII from inactivating after Ca(2+)/CaM unbinding. Here we review roles of CaMKII in cardiovascular disease with an eye to understanding how CaMKII may act as a transduction signal to connect pro-oxidant conditions into specific downstream pathological effects that are relevant to rare and common forms of cardiovascular disease. PMID:21742790

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



Cardiovascular disease in systemic sclerosis - an emerging association?  

PubMed Central

Microvascular disease is a prominent feature of systemic sclerosis (SSc) and leads to Raynaud's phenomenon, pulmonary arterial hypertension, and scleroderma renal crisis. The presence of macrovascular disease is less well established, and, in particular, it is not known whether the prevalence of coronary heart disease in SSc is increased. Furthermore, in terms of cardiac involvement in SSc, there remains conjecture about the relative contributions of atherosclerotic macrovascular disease and myocardial microvascular disease. In this review, we summarize the literature describing cardiovascular disease in SSc, discuss the pathophysiological mechanisms common to SSc and atherosclerosis, and review the surrogate markers of cardiovascular disease which have been examined in SSc. Proposed mediators of the vasculopathy of SSc which have also been implicated in atherosclerosis include endothelial dysfunction, a reduced number of circulating endothelial progenitor cells, and an increased number of microparticles. Excess cardiovascular risk in SSc is suggested by increased arterial stiffness and carotid intima thickening and reduced flow-mediated dilatation. Cohort studies of adequate size are required to resolve whether this translates into an increased incidence of cardiovascular events in patients with SSc.



5Hydroxytryptamine receptors in the human cardiovascular system  

Microsoft Academic Search

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



Therapy Insight: cardiovascular disease in pediatric systemic lupus erythematosus  

Microsoft Academic Search

In 15–20% of cases, systemic lupus erythematosus (SLE) presents before the age of 18 years, and such early-onset SLE seems to be particularly severe. SLE is an independent risk factor for premature atherosclerosis and death in young, premenopausal women with SLE, even after controlling for traditional cardiovascular risk factors. Children and adolescents with SLE are particularly susceptible to this long-term

Stacy P Ardoin; Laura Schanberg; Christy Sandborg



Clinical Application of Stem Cells in the Cardiovascular System  

Microsoft Academic Search

\\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



Controlled-release drug delivery systems in cardiovascular medicine  

Microsoft Academic Search

Controlled-release drug delivery technology has had a significant effect on the pharmacotherapy of cardiovascular diseases. Oral and transcutaneous controlled-release systems allow relatively short-acting drugs to be administered once or twice daily with comparable therapeutic efficacy and fewer adverse reactions compared with standard formulations. They can provide decreased fluctuations in drug concentrations in plasma while possibly reducing the total amount of

Baruch Katz; Andrew Rosenberg; William H. Frishman



Redox modification of cell signaling in the cardiovascular system  

PubMed Central

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

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



Congenital Heart Disease: An Ontology-Based Approach for the Examination of the Cardiovascular System  

Microsoft Academic Search

Congenital Heart Disease (CHD) represents the most common group of congenital malformations of the heart and of its blood\\u000a vessels. In this paper, we present an ontology-based approach to detect abnormalities and malformations due to CHD. In particular,\\u000a we propose a formal and well-defined model to represent the anatomy of the cardiovascular system, based on the SNOMED vocabulary.\\u000a The model

M. Esposito



Mental stress and the cardiovascular system part II: Acute mental stress and cardiovascular disease  

Microsoft Academic Search

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



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

Microsoft Academic Search

BACKGROUND: Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus

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



Cardiovascular defects in a mouse model of HOXA1 syndrome  

PubMed Central

Congenital heart disease is one of the most common human birth defects, yet many genes and pathways regulating heart development remain unknown. A recent study in humans revealed that mutations in a single Hox gene, HOXA1 (Athabascan Brainstem Dysgenesis Syndrome, Bosley-Salih-Alorainy Syndrome), can cause severe cardiovascular malformations, some of which are lethal without surgical intervention. Since the discovery of the human syndromes, there have been no reports of any Hox mouse mutants with cardiac defects, hampering studies to explore the developmental causes of the human disease. In this study, we identify severe cardiovascular malformations in a Hox mouse model, which mimic the congenital heart defects in HOXA1 syndrome patients. Hoxa1 null mice show defects such as interrupted aortic arch, aberrant subclavian artery and Tetralogy of Fallot, demonstrating that Hoxa1 is required for patterning of the great arteries and outflow tract of the heart. We show that during early embryogenesis, Hoxa1 is expressed in precursors of cardiac neural crest cells (NCCs), which populate the heart. We further demonstrate that Hoxa1 acts upstream of several genes, important for neural crest specification. Thus, our data allow us to suggest a model in which Hoxa1 regulates heart development through its influence on cardiac NCCs, providing insight into the mechanisms underlying the human disease.

Makki, Nadja; Capecchi, Mario R.



Cardiovascular defects in a mouse model of HOXA1 syndrome.  


Congenital heart disease is one of the most common human birth defects, yet many genes and pathways regulating heart development remain unknown. A recent study in humans revealed that mutations in a single Hox gene, HOXA1 (Athabascan Brainstem Dysgenesis Syndrome, Bosley-Salih-Alorainy Syndrome), can cause severe cardiovascular malformations, some of which are lethal without surgical intervention. Since the discovery of the human syndromes, there have been no reports of any Hox mouse mutants with cardiac defects, hampering studies to explore the developmental causes of the human disease. In this study, we identify severe cardiovascular malformations in a Hox mouse model, which mimic the congenital heart defects in HOXA1 syndrome patients. Hoxa1 null mice show defects such as interrupted aortic arch, aberrant subclavian artery and Tetralogy of Fallot, demonstrating that Hoxa1 is required for patterning of the great arteries and outflow tract of the heart. We show that during early embryogenesis, Hoxa1 is expressed in precursors of cardiac neural crest cells (NCCs), which populate the heart. We further demonstrate that Hoxa1 acts upstream of several genes, important for neural crest specification. Thus, our data allow us to suggest a model in which Hoxa1 regulates heart development through its influence on cardiac NCCs, providing insight into the mechanisms underlying the human disease. PMID:21940751

Makki, Nadja; Capecchi, Mario R



Endocannabinoid system in cardiovascular disorders - new pharmacotherapeutic opportunities  

PubMed Central

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

Cunha, Pedro; Romao, Ana M.; Mascarenhas-Melo, Filipa; Teixeira, Helena M.; Reis, Flavio



Cardiovascular function in patients with progressive systemic sclerosis (scleroderma).  


Sixteen patients with progressive systemic sclerosis (PSS), including 3 with the "CREST" (calcinosis, Raynaud's, esophageal dysfunction, sclerodactyly, and/or telangiectasias) variant, were evaluated with resting M-mode echocardiography and noninvasive measurements of cardiac output at rest and during submaximal exercise to determine the nature and extent of any cardiovascular impairment. No patient had arterial hypertension, significant renal impairment, clinical evidence of large vessel coronary artery disease, or severe pulmonary dysfunction. The duration of disease was 1 to 12 years (9 to 30 for patients with the CREST variant). Echocardiographic abnormalities included increased right ventricular dimension (3 patients), reduced left ventricular ejection fraction (3 patients), and pericardial effusion (3 patients). Cardiac index (CI) and stroke volume index (SVI) at rest were similar for patients and controls. Patients and controls were exercised to similar heart rates (130 +/- 3 vs 124 +/- 4; p, NS). Total peripheral resistance (TPR) was higher for patients (1123 +/- 81 vs 810 +/- 44 dyn X s X cm-5) and their mean SVI failed to increase significantly compared with sitting rest values (30 +/- 2 vs 35 +/- 3 ml/m2). The control subjects had the expected increase in SVI (36 +/- 2 vs 51 +/- 5; p less than 0.01). Ten patients with an abnormal hemodynamic response to exercise had a normal echocardiographic circumferential fiber shortening (VCF) or ejection fraction (EF) at rest. The data indicate that PSS patients have a greater degree of cardiovascular dysfunction than would be predicted from clinical data and laboratory evaluation of cardiovascular and pulmonary function at rest. Multiple mechanisms, including right and left ventricular dysfunction and abnormal vasoconstrictor activity, are likely to contribute to the reduction in exercise capacity seen in patients with PSS. PMID:6217013

Gaffney, F A; Anderson, R J; Nixon, J V; Blomqvist, C G



Noisy fluctuation of heart rate indicates cardiovascular system instability.  


Heart rate spontaneously fluctuates despite homeostatic regulatory mechanisms to stabilize it. Harmonic and fractal fluctuations have been described. Non-harmonic non-fractal fluctuation has not been studied because it is usually thought that it is caused by apparatus noise. We hypothesized that this fluctuation looking like apparatus noise (that we call "noisy fluctuation") is linked to challenged blood pressure stabilization and not to apparatus noise. We assessed noisy fluctuation by quantifying the small and fastest beat-to-beat fluctuation of RR-interval by means of spectral analysis (Nyquist power of heart rate variability: nyHRV) after filtering out its fractal component. We observed nyHRV in healthy supine subjects and in patients with vasovagal symptoms. We challenged stabilization of blood pressure by upright posture (by means of a head-up tilt table test). Head-up position on the tilt table dramatically decreased nyHRV (0.128 ± 0.063 vs. 0.004 ± 0.002, p < 0.01) in healthy subjects (n = 12). Head-up position also decreased nyHRV in patients without vasovagal symptoms (n = 24; 0.220 ± 0.058 vs. 0.034 ± 0.015, p < 0.05), but not in patients with vasovagal symptoms during a head-up tilt table test (age and sex paired, 0.103 ± 0.041 vs. 0.122 ± 0.069, not significant). Heart rate variability includes a physiological non-harmonic non-fractal noisy fluctuation. This noisy fluctuation indicates low engagement of regulatory mechanisms because it disappears when the cardiovascular system is challenged (upright posture). It also indicates cardiovascular instability because it does not disappear in upright patients before vasovagal syncope, a transient failure of cardiovascular regulation. PMID:23652709

Fortrat, Jacques-Olivier; Baum, Charlotte; Jeanguillaume, Christian; Custaud, Marc-Antoine



Real-time gating system for mouse cardiovascular MR imaging.  


Mouse cardiac MR gating using ECG is affected by the hostile MR environment. It requires appropriate signal processing and correct QRS detection, but gating software methods are currently limited. In this study we sought to demonstrate the feasibility of digital real-time automatically updated gating methods, based on optimizing a signal-processing technique for different mouse strains. High-resolution MR images of mouse hearts and aortic arches were acquired using a chain consisting of ECG signal detection, digital signal processing, and gating signal generation modeled using Simulink (The MathWorks, Inc., Natick, MA, USA). The signal-processing algorithms used were respectively low-pass filtering, nonlinear passband, and wavelet decomposition. Both updated and nonupdated gating signal generation methods were tested. Noise reduction was assessed by comparison of the ECG signal-to-noise ratio (SNR) before and after each processing step. Gating performance was assessed by measuring QRS detection accuracy before and after online trigger-level adjustments. Low-pass filtering with trigger-level adjustment gave the best performance for mouse cardiovascular imaging using gradient-echo (GE), spin-echo (SE), and fast SE (FSE) sequences with minimum induced delay and maximum gating efficiency (99% sensitivity and R-peak detection). This simple digital gating interface will allow various gating strategies to be optimized for cardiovascular MR explorations in mice. PMID:17152077

Sabbah, Maher; Alsaid, Hasan; Fakri-Bouchet, Latifa; Pasquier, Cédric; Briguet, André; Canet-Soulas, Emmanuelle; Fokapu, Odette



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

PubMed Central

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.

Roytvarf, Alexander; Shusterman, Vladimir



Contemporary model for cardiovascular risk prediction in people with type 2 diabetes  

Microsoft Academic Search

Background: Existing cardiovascular risk prediction equations perform non-optimally in different populations with diabetes. Thus, there is a continuing need to develop new equations that will reliably estimate cardiovascular disease (CVD) risk and offer flexibility for adaptation in various settings. This report presents a contemporary model for predicting cardiovascular risk in people with type 2 diabetes mellitus.Design and methods: A 4.5-year

Andre Pascal Kengne; Anushka Patel; Michel Marre; Florence Travert; Michel Lievre; Sophia Zoungas; John Chalmers; Stephen Colagiuri; Diederick E Grobbee; Pavel Hamet; Simon Heller; Bruce Neal; Mark Woodward



Mental stress and the cardiovascular system part V. Chrome mental stress and cardiovascular disease: Job stress  

Microsoft Academic Search

Parameters of job stress include degree of job control and magnitude of psychological stress. These occupational characteristics may be multiplicative when low job control coexists with high psychological stress. Cardiovascular entities adversely affected by these two occupational characteristics (either alone or in combination) include hypertension, diastolic blood pressure, and coronary artery disease. Some studies challenge these hypotheses. Organism behavior may

W. Victor R. Vieweg; Robin Tucker; Nelson L. Bernardo; Linda M. Dougherty



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

PubMed Central

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

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



Comprehensive quality assurance phantom for cardiovascular imaging systems  

NASA Astrophysics Data System (ADS)

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.





The renin/angiotensin system (RAS) is a tonic anti-drop regulator of arterial blood pressure in many teleosts. In trout, angiotensin II (ANG II) has no direct constrictor effect on large arteries or veins and the identity of specific cardiovascular pressor effectors is unknown. Potential targets of angiotensin activation were examined in the present experiments using perfused organs and isolated tissues from the rainbow trout Oncorhynchus mykiss. Perfused gill (arches 2 and 3), perfused skeletal muscle-kidney (via the dorsal aorta; PDA) and perfused splanchnic (via the celiacomesenteric; PCM) circulations vasoconstrict in response to salmonid ANG II in a dose-dependent manner. ANG II was significantly (P¾0.05) more potent in the PCM than in the PDA, and both preparations were more responsive than the gills: pD2=8.0±0.20 (10) for PCM; pD2=7.5±0.07 (13) for PDA; pD2=6.9 ±0.21 (8) for gill arch 3; pD2=6.7±0.23 (8) for gill arch 2; mean ± s.e.m. (N), respectively. Salmonid angiotensin I (ANG I) also produced a dose-dependent constriction of the PDA and PCM. Angiotensin converting enzyme (ACE) activated nearly 100 % of ANG I to ANG II in a single pass through the PDA, whereas PCM conversion was estimated to be less than 10 %. Inhibitors of adrenergic constriction partially prevented ANG II responses in the PDA but did not affect PCM responses. ANG II did not affect paced rings of ventricular muscle in the presence of high or low [Ca2+] or epinephrine concentrations, nor did it have any inotropic or chronotropic effects in the in situ perfused heart. Red blood cell swelling was unaffected by ANG II. Similarly, the effects of ANG II on gut, urinary bladder and gall bladder smooth muscle were negligible or non-existent; thus, an increase in splanchnic resistance due to extravascular compression can be discounted. These results indicate that, in trout, the systemic microcirculation is the major cardiovascular effector of angiotensin-mediated pressor responses. In addition, the RAS has little direct effect on non-vascular smooth muscle or the heart. From an evolutionary perspective, the initial site of direct systemic RAS action appears to be the vascular microcirculation. PMID:9317454

Olson; Chavez; Conklin; Cousins; Farrell; Ferlic; Keen; Kne; Kowalski; Veldman



Theory and Developments in an Unobtrusive Cardiovascular System Representation: Ballistocardiography  

PubMed Central

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

Pinheiro, Eduardo; Postolache, Octavian; Girao, Pedro



Exploratory and Developmental Studies Leading Toward Optimization of Accoustical Holography Imaging of Cardiovascular System.  

National Technical Information Service (NTIS)

The general objective of this program was to apply liquid surface acoustical holography to image the cardiovascular system. Feedback from clinical studies using normal and diseased patients contributed to engineering revisions in the system to obtain bett...

B. B. Brenden J. L. Diechman W. W. Taylor



Systems biology approaches and pathway tools for investigating cardiovascular disease.  


Systems biology aims to understand the nonlinear interactions of multiple biomolecular components that characterize a living organism. One important aspect of systems biology approaches is to identify the biological pathways or networks that connect the differing elements of a system, and examine how they evolve with temporal and environmental changes. The utility of this method becomes clear when applied to multifactorial diseases with complex etiologies, such as inflammatory-related diseases, herein exemplified by atherosclerosis. In this paper, the initial studies in this discipline are reviewed and examined within the context of the development of the field. In addition, several different software tools are briefly described and a novel application for the KEGG database suite called KegArray is presented. This tool is designed for mapping the results of high-throughput omics studies, including transcriptomics, proteomics and metabolomics data, onto interactive KEGG metabolic pathways. The utility of KegArray is demonstrated using a combined transcriptomics and lipidomics dataset from a published study designed to examine the potential of cholesterol in the diet to influence the inflammatory component in the development of atherosclerosis. These data were mapped onto the KEGG PATHWAY database, with a low cholesterol diet affecting 60 distinct biochemical pathways and a high cholesterol exposure affecting 76 biochemical pathways. A total of 77 pathways were differentially affected between low and high cholesterol diets. The KEGG pathways "Biosynthesis of unsaturated fatty acids" and "Sphingolipid metabolism" evidenced multiple changes in gene/lipid levels between low and high cholesterol treatment, and are discussed in detail. Taken together, this paper provides a brief introduction to systems biology and the applications of pathway mapping to the study of cardiovascular disease, as well as a summary of available tools. Current limitations and future visions of this emerging field are discussed, with the conclusion that combining knowledge from biological pathways and high-throughput omics data will move clinical medicine one step further to individualize medical diagnosis and treatment. PMID:19462016

Wheelock, Craig E; Wheelock, Asa M; Kawashima, Shuichi; Diez, Diego; Kanehisa, Minoru; van Erk, Marjan; Kleemann, Robert; Haeggström, Jesper Z; Goto, Susumu



Systemic Lupus Erythematosus and the Risk of Cardiovascular Disease: Results From the Nurses' Health Study  

Microsoft Academic Search

Objective. Systemic lupus erythematosus (SLE) has been associated with an increased risk of cardiovascular disease. However, prospective population-based data addressing this association have been lacking. Methods. We conducted a prospective cohort study among 119,332 women participating in the Nurses' Health Study who were free of cardiovascular disease and SLE at baseline in 1976. Incident SLE was confirmed by medical record

A. Elisabeth Hak; Elizabeth W. Karlson; Diane Feskanich; Meir J. Stampfer; Karen H. Costenbader



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


A cardiovascular system model and parameter identification method have previously been validated for porcine experiments of induced pulmonary embolism and positive end-expiratory pressure (PEEP) titrations, accurately tracking all the main hemodynamic trends. In this research, the model and parameter identification process are further validated by predicting the effect of intervention. An overall population-specific rule linking specific model parameters to increases in PEEP is formulated to predict the hemodynamic effects on arterial pressure, pulmonary artery pressure and stroke volume. Hemodynamic changes are predicted for an increase from 0 to 10 cm H(2)O with median absolute percentage errors less than 7% (systolic pressures) and 13% (stroke volume). For an increase from 10 to 20 cm H(2)O median absolute percentage errors are less than 11% (systolic pressures) and 17% (stroke volume). These results validate the general applicability of such a rule, which is not pig-specific, but holds over for all analyzed pigs. This rule enables physiological simulation and prediction of patient response. Overall, the prediction accuracy achieved represents a further clinical validation of these models, methods and overall approach to cardiovascular diagnosis and therapy guidance. PMID:18472180

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



Cysteine oxidative posttranslational modifications: emerging regulation in the cardiovascular system.  


In the cardiovascular system, changes in oxidative balance can affect many aspects of cellular physiology through redox-signaling. Depending on the magnitude, fluctuations in the cell's production of reactive oxygen and nitrogen species can regulate normal metabolic processes, activate protective mechanisms, or be cytotoxic. Reactive oxygen and nitrogen species can have many effects including the posttranslational modification of proteins at critical cysteine thiols. A subset can act as redox-switches, which elicit functional effects in response to changes in oxidative state. Although the general concepts of redox-signaling have been established, the identity and function of many regulatory switches remains unclear. Characterizing the effects of individual modifications is the key to understand how the cell interprets oxidative signals under physiological and pathological conditions. Here, we review the various cysteine oxidative posttranslational modifications and their ability to function as redox-switches that regulate the cell's response to oxidative stimuli. In addition, we discuss how these modifications have the potential to influence other posttranslational modifications' signaling pathways though cross-talk. Finally, we review the increasing number of tools being developed to identify and quantify the various cysteine oxidative posttranslational modifications and how this will advance our understanding of redox-regulation. PMID:23329793

Chung, Heaseung S; Wang, Sheng-Bing; Venkatraman, Vidya; Murray, Christopher I; Van Eyk, Jennifer E



Gravity, the hydrostatic indifference concept and the cardiovascular system.  


Gravity, like any acceleration, causes a hydrostatic pressure gradient in fluid-filled bodily compartments. At a force of 1G, this pressure gradient amounts to 10 kPa/m. Postural changes alter the distribution of hydrostatic pressure patterns according to the body's alignment to the acceleration field. At a certain location--referred to as hydrostatically indifferent--within any given fluid compartment, pressure remains constant during a given change of position relative to the acceleration force acting upon the body. At this specific location, there is probably little change in vessel volume, wall tension, and the balance of Starling forces after a positional manoeuvre. In terms of cardiac function, this is important because arterial and venous hydrostatic indifference locations determine postural cardiac preload and afterload changes. Baroreceptors pick up pressure signals that depend on their respective distance to hydrostatic indifference locations with any change of body position. Vascular shape, filling volume, and compliance, as well as temperature, nervous and endocrine factors, drugs, and time all influence hydrostatic indifference locations. This paper reviews the physiology of pressure gradients in the cardiovascular system that are operational in a gravitational/acceleration field, offers a broadened hydrostatic indifference concept, and discusses implications that are relevant in physiological and clinical terms. PMID:20857139

Hinghofer-Szalkay, Helmut



Vasopressin and Oxytocin in Control of the Cardiovascular System  

PubMed Central

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.

Japundzic-Zigon, Nina



Peroxisome proliferator-activated receptors in the cardiovascular system  

PubMed Central

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.

Bishop-Bailey, David



Metal ions affecting the pulmonary and cardiovascular systems.  


Some metals, such as copper and manganese, are essential to life and play irreplaceable roles in, e.g., the functioning of important enzyme systems. Other metals are xenobiotics, i.e., they have no useful role in human physiology and, even worse, as in the case of lead, may be toxic even at trace levels of exposure. Even those metals that are essential, however, have the potential to turn harmful at very high levels of exposure, a reflection of a very basic tenet of toxicology--"the dose makes the poison." Toxic metal exposure may lead to serious risks to human health. As a result of the extensive use of toxic metals and their compounds in industry and consumer products, these agents have been widely disseminated in the environment. Because metals are not biodegradable, they can persist in the environment and produce a variety of adverse effects. Exposure to metals can lead to damage in a variety of organ systems and, in some cases, metals also have the potential to be carcinogenic. Even though the importance of metals as environmental health hazards is now widely appreciated, the specific mechanisms by which metals produce their adverse effects have yet to be fully elucidated. The unifying factor in determining toxicity and carcinogenicity for most metals is the generation of reactive oxygen and nitrogen species. Metal-mediated formation of free radicals causes various modifications to nucleic acids, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Whilst copper, chromium, and cobalt undergo redox-cycling reactions, for metals such as cadmium and nickel the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. This chapter attempts to show that the toxic effects of different metallic compounds may be manifested in the pulmonary and cardiovascular systems. The knowledge of health effects due to metal exposure is necessary for practising physicians, and should be assessed by inquiring about present and past occupational history and environmental exposure. PMID:21473377

Corradi, Massimo; Mutti, Antonio



[Psychosocial factors as predictors of atherosclerosis and cardiovascular events: contribution from animal models].  


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



FoxO proteins: cunning concepts and considerations for the cardiovascular system  

PubMed Central

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

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



Effectiveness of three models for comprehensive cardiovascular disease risk reduction  

Microsoft Academic Search

Cost and accessibility contribute to low participation rates in phase 2 cardiac rehabilitation programs in the United States. In this study, we compared the clinical effectiveness of 2 less costly and potentially more accessible approaches to cardiovascular risk reduction with that of a contemporary phase 2 cardiac rehabilitation program. Low- or moderate-risk patients (n = 155) with coronary artery disease

Neil F. Gordon; Carla D. English; Aashish S. Contractor; Richard D. Salmon; Richard F. Leighton; Barry A. Franklin; William L. Haskell



P2 receptor subtypes in the cardiovascular system.  

PubMed Central

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.

Kunapuli, S P; Daniel, J L



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

PubMed Central

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

Lassegue, Bernard; San Martin, Alejandra; Griendling, Kathy K.



The cardiovascular and autonomic properties of N-phenylpiperazine (NPP) in several animal models.  


A number of isolated tissue and intact animal models were utilized to investigate in more detail the cardiovascular actions of N-phenylpiperazine (NPP), a known compound having adrenergic blocking properties. In isolated tissues its autonomic profile is characterized by alpha and beta adrenergic blocking activity. Compared to other beta receptor antagonists, NPP displays moderate in vitro beta-1 blockade in guinea-pig atria. Cumulative administration of NPP (0.1--0.3 mg/kg i.v.) in the intact dog also produces dose-dependent inhibition of myocardial contractility following isoproterenol administration. The oral antihypertensive potency of NPP in the deoxycorticosterone acetate hypertensive rat is compared with phenoxybenzamine and labetalol. Its profile is similar to labetalol but differs from phenoxybenzamine, causing a fall in blood pressure and a decrease in heart rate. Hemodynamic data obtained with NPP in the anesthetized animal reveal a complex cardiovascular profile involving the interactions of the sympathetic nervous system. Canine hind limb perfusion studies using cumulative doses (0.1--0.3 mg/kg i.v.) appear to preclude a direct vasodilator mechanism in the reserpinized-pretreated animal. In other studies, nonselective vasoconstrictor responses induced by exogenous administration of norepinephrine and lumbar sympathetic nerve stimulation are inhibited to the same degree by NPP (0.1--10 mg/kg i.v.) autonomic interactions with NPP in the nictitating membrane provide evidence for inhibition of neuronal catecholamine uptake and catecholamine release. From the data obtained in the present study, it is suggested that NPP has a predominant influence on the response of the sympathetic nervous system to provide a unique cardiovascular profile. The manner in which blood pressure is regulated by either direct or nonselective mechanisms will be discussed. PMID:6126578

Cohen, M R; Hinsch, E; Palkoski, Z; Vergona, R; Urbano, S; Sztokalo, J



[The adaptive capacities of the cardiovascular system in miners exposed to vibration].  


Diagnostics criteria for work-related adaptation disorders in respect of cardiovascular system factors have been developed; the stages of disadaptation have been characterized through the example of vibration exposed miners working under the conditions of cool microclimate. PMID:23785816

Konevskikh, L A; Oranski?, I E; Makogon, I S



Regulation of NAD(P)H oxidases by AMPK in cardiovascular systems  

PubMed Central

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are ubiquitously produced in cardiovascular systems. Under physiological conditions, ROS/RNS function as signaling molecules that are essential in maintaining cardiovascular function. Aberrant concentrations of ROS/RNS have been demonstrated in cardiovascular diseases due to increased production or decreased scavenging, which have been considered as common pathways for the initiation and progression of cardiovascular diseases such as atherosclerosis, hypertension, (re)stenosis, and congestive heart failure. NAD(P)H oxidases are primary sources of ROS and can be induced or activated by all known cardiovascular risk factors. Stresses, hormones, vasoactive agents, and cytokines via different signaling cascades control the expression and activity of these enzymes and of their regulatory subunits. But the molecular mechanisms by which NAD(P)H oxidase is regulated in cardiovascular systems remain poorly characterized. Investigations by us and others suggest that adenosine monophosphate-activated protein kinase (AMPK), as an energy sensor and modulator, is highly sensitive to ROS/RNS. We have also obtained convincing evidence that AMPK is a physiological suppressor of NAD(P)H oxidase in multiple cardiovascular cell systems. In this review, we summarize our current understanding of how AMPK functions as a physiological repressor of NAD(P)H oxidase.

Song, Ping; Zou, Ming-Hui



Thioredoxin in the Cardiovascular System—Towards a Thioredoxin-Based Antioxidative Therapy  

Microsoft Academic Search

\\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


[The functional state of the cardiovascular and central nervous system in patients with occupational deafness].  


The workers of the Orenburg gas-processing plant have been found to be at high risk for concomitant diseases of the cardiovascular, central nervous, and other systems in the presence of occupational sensorineural deafness. Among the comorbidities in deaf patients, cardiovascular disease heads the list (63%), of them autonomic vascular dystonia is most common (22%); diseases of the central nervous system and lung rank second (13%) and third (11%), respectively. PMID:19802944

Tin'kov, A N; Ra?tselis, I V


[The cardiovascular system during adaptation of students residing in a South-Siberian region].  


The trend in adaptation processes was studied by the parameters of the cardiovascular system in Tuvian and Russian students during their study at a higher educational establishment. Not only the age- and sex-related features, but also ethnical features of students living under extreme climatic and geographic conditions were shown to affect education adaptation processes. Junior students of natural ethnicity had lower indices of cardiovascular system function than those of Russian ethnicity and a more adequate adaptive response to study. PMID:20376941

Buduk-ool, L K; A?zman, R I


Ocular and cardiovascular effects of local and systemic pindolol  

Microsoft Academic Search

Ocular and cardiovascular effects of topical and intravenous pindolol have been studied in a balanced cross-0ver double-blind trial in 6 healthy volunteers. When applied to 1 eye pindolol lowered intraocular pressure in both the treated and untreated eyes with only minimal reduction in resting pupil diameter and light reflex response. The concentration in plasma was much lower and inhibiton of

S E Smith; S A Smith; F Reynolds; V B Whitmarsh



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

Microsoft Academic Search

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



Long-lasting adverse effects of prenatal hypoxia on developing autonomic nervous system and cardiovascular parameters in rats  

Microsoft Academic Search

To determine whether prenatal hypoxia increases the risk of developing cardiovascular disorders as an adult and, if so, the identity of the cell mechanisms involved in such dysfunction, we evaluated the sympathoadrenal system and central areas related to cardiovascular events during development and the cardiovascular parameters in adults. Pregnant rats were exposed to hypoxia (10% oxygen) from embryonic day (E)

Julie Peyronnet; Yvette Dalmaz; Marcus Ehrström; Julie Mamet; Jean-Christophe Roux; Jean-Marc Pequignot; Peter H. Thorén; Hugo Lagercrantz



C-type natriuretic peptide effects on cardiovascular nitric oxide system in spontaneously hypertensive rats.  


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 (NO(x)) were determined. Catalytic NO synthase (NOS) activity and endothelial (eNOS), neuronal (nNOS) and inducible NOS (iNOS) were measured in the heart and aorta artery. NOS activity induced by CNP was determined in presence of: iNOS or nNOS inhibitors, NPR-A/B natriuretic peptide receptors blocker and Gi protein and calmodulin inhibitors. CNP diminished MAP and increased NO(x) in both groups. Cardiovascular NOS activity was higher in SHR than in WKY. CNP increased NOS activity, but this activation was lower in SHR. CNP had no effect on NOS isoforms expression. iNOS and nNOS inhibitors did not modify CNP-induced NOS activity. NPR-A/B blockade induced no changes in NOS stimulation via CNP in both tissues. Cardiovascular NOS response to CNP was reduced by Gi protein and calmodulin inhibitors in both groups. CNP interacts with NPR-C receptors, activating Ca-calmodulin eNOS via Gi protein. NOS response to CNP is impaired in the heart and aorta of SHR. Alterations in the interaction between CNP and NO would be involved in the maintenance of high blood pressure in this model of hypertension. PMID:20363270

Caniffi, Carolina; Elesgaray, Rosana; Gironacci, Mariela; Arranz, Cristina; Costa, María Angeles



Autonomic Nervous System Dysfunction and Inflammation Contribute to the Increased Cardiovascular Mortality Risk Associated With Depression  

PubMed Central

Objective To investigate prospectively whether autonomic nervous system (ANS) dysfunction and inflammation play a role in the increased cardiovascular disease (CVD)-related mortality risk associated with depression. Methods Participants in the Cardiovascular Health Study (n = 907; mean age, 71.3 ± 4.6 years; 59.1% women) were evaluated for ANS indices derived from heart rate variability (HRV) analysis (frequency and time domain HRV, and nonlinear indices, including detrended fluctuation analysis (DFA1) and heart rate turbulence). Inflammation markers included C-reactive protein, interleukin-6, fibrinogen, and white blood cell count). Depressive symptoms were assessed, using the 10-item Centers for Epidemiological Studies Depression scale. Cox proportional hazards models were used to investigate the mortality risk associated with depression, ANS, and inflammation markers, adjusting for demographic and clinical covariates. Results Depression was associated with ANS dysfunction (DFA1, p = .018), and increased inflammation markers (white blood cell count, p = .012, fibrinogen p = .043) adjusting for covariates. CVD-related mortality occurred in 121 participants during a median follow-up of 13.3 years. Depression was associated with an increased CVD mortality risk (hazard ratio, 1.88; 95% confidence interval, 1.23–2.86). Multivariable analyses showed that depression was an independent predictor of CVD mortality (hazard ratio, 1.72; 95% confidence interval, 1.05–2.83) when adjusting for independent HRV and inflammation predictors (DFA1, heart rate turbulence, interleukin-6), attenuating the depression-CVD mortality association by 12.7% (p < .001). Conclusion Autonomic dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression, but a large portion of the predictive value of depression remains unexplained by these neuroimmunological measures.

Kop, Willem J.; Stein, Phyllis K.; Tracy, Russell P.; Barzilay, Joshua I.; Schulz, Richard; Gottdiener, John S.



Circadian Rhythm in the Cardiovascular System: Considerations in Non-Invasive Electrophysiology  

Microsoft Academic Search

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



Nprl3 is required for normal development of the cardiovascular system.  


C16orf35 is a conserved and widely expressed gene lying adjacent to the human ?-globin cluster in all vertebrate species. In-depth sequence analysis shows that C16orf35 (now called NPRL3) is an orthologue of the yeast gene Npr3 (nitrogen permease regulator 3) and, furthermore, is a paralogue of its protein partner Npr2. The yeast Npr2/3 dimeric protein complex senses amino acid starvation and appropriately adjusts cell metabolism via the TOR pathway. Here we have analysed a mouse model in which expression of Nprl3 has been abolished using homologous recombination. The predominant effect on RNA expression appears to involve genes that regulate protein synthesis and cell cycle, consistent with perturbation of the mTOR pathway. Embryos homozygous for this mutation die towards the end of gestation with a range of cardiovascular defects, including outflow tract abnormalities and ventriculoseptal defects consistent with previous observations, showing that perturbation of the mTOR pathway may affect development of the myocardium. NPRL3 is a candidate gene for harbouring mutations in individuals with developmental abnormalities of the cardiovascular system. PMID:22538705

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



High-Resolution Cardiovascular MRI by Integrating Parallel Imaging with Low-Rank and Sparse Modeling.  


Magnetic resonance imaging (MRI) has long been recognized as a powerful tool for cardiovascular imaging because of its unique potential to measure blood flow, cardiac wall motion and tissue properties jointly. However, many clinical applications of cardiac MRI have been limited by low imaging speed. In this paper, we present a novel method to accelerate cardiovascular MRI through the integration of parallel imaging, low-rank modeling, and sparse modeling. This method consists of a novel image model and specialized data acquisition. Of particular novelty is the proposed low-rank model component, which is specially adapted to the particular low-rank structure of cardiovascular signals. Simulations and in vivo experiments were performed to evaluate the method, as well as an analysis of the low-rank structure of a numerical cardiovascular phantom. Cardiac imaging experiments were carried out on both human and rat subjects without the use of ECG or respiratory gating and without breath holds. The proposed method reconstructed 2D human cardiac images up to 22 fps and 1.0 mm × 1.0 mm spatial resolution and 3D rat cardiac images at 67 fps and 0.65 mm × 0.65 mm × 0.31 mm spatial resolution. These capabilities will enhance the practical utility of cardiovascular MRI. PMID:23744657

Christodoulou, Anthony; Zhang, Haosen; Zhao, Bo; Hitchens, T; Ho, Chien; Liang, Zhi-Pei



Gender, sex hormones and autonomic nervous control of the cardiovascular system  

Microsoft Academic Search

Differences in the autonomic system may be due to differences in afferent receptor stimulation, in central The autonomic nervous system is of importance in the reflex transmission, in the efferent nervous system and in natural history and treatment of a number of post synaptic signaling. At each of these potential sites of pathophysiological states involving the cardiovascular difference, there may

Anthony M. Dart; Xiao-Jun Du; Bronwyn A. Kingwell


Cardiovascular deconditioning: From autonomic nervous system to microvascular dysfunctions.  


Weightlessness induces an acute syndrome called the cardiovascular deconditioning, associating orthostatic intolerance with syncope, increase in resting heart rate and decrease in physical capability. Orthostatic intolerance occurs after short term and long term head down bed rest and after long term space flight. Both head down bed rest and space flight induce a significant decrease of the spontaneous baroreflex sensitivity. However, spontaneous baroreflex sensitivity only characterizes the cardiac baroreflex loop. To go further with the analysis of cardiovascular deconditioning we were interested in the microcirculation. As the endothelium plays a crucial role in the regulation of vascular homeostasis and local blood flow, we hypothesized that endothelial dysfunction is associated with bed rest induced changes. We investigated endothelial properties before and after 56 days of bed rest in 8 women of control group and in 8 women who regularly performed physical exercise as countermeasure. Our study shows that prolonged bed rest causes impairment of endothelium-dependent functions at the microcirculation level, along with an increase in circulating endothelial cells. Endothelium should be a target for countermeasures during periods of prolonged bed rest or exposure to weightlessness. PMID:19379845

Coupé, M; Fortrat, J O; Larina, I; Gauquelin-Koch, G; Gharib, C; Custaud, M A



Measurement Error Case Series Models with Application to Infection-Cardiovascular Risk in OlderPatients on Dialysis.  


Infection and cardiovascular disease are leading causes of hospitalization and death in older patients on dialysis. Our recent work found an increase in the relative incidence of cardiovascular outcomes during the ~ 30 days after infection-related hospitalizations using the case series model, which adjusts for measured and unmeasured baseline confounders. However, a major challenge in modeling/assessing the infection-cardiovascular risk hypothesis is that the exact time of infection, or more generally "exposure," onsets cannot be ascertained based on hospitalization data. Only imprecise markers of the timing of infection onsets are available. Although there is a large literature on measurement error in the predictors in regression modeling, to date there is no work on measurement error on the timing of a time-varying exposure to our knowledge. Thus, we propose a new method, the measurement error case series (MECS) models, to account for measurement error in time-varying exposure onsets. We characterized the general nature of bias resulting from estimation that ignores measurement error and proposed a bias-corrected estimation for the MECS models. We examined in detail the accuracy of the proposed method to estimate the relative incidence. Hospitalization data from United States Renal Data System, which captures nearly all (> 99%) patients with end-stage renal disease in the U.S. over time, is used to illustrate the proposed method. The results suggest that the estimate of the cardiovascular incidence following the 30 days after infections, a period where acute effects of infection on vascular endothelium may be most pronounced, is substantially attenuated in the presence of infection onset measurement error. PMID:23650442

Mohammed, Sandra M; Sentürk, Damla; Dalrymple, Lorien S; Nguyen, Danh V



Measurement Error Case Series Models with Application to Infection-Cardiovascular Risk in OlderPatients on Dialysis  

PubMed Central

Infection and cardiovascular disease are leading causes of hospitalization and death in older patients on dialysis. Our recent work found an increase in the relative incidence of cardiovascular outcomes during the ~ 30 days after infection-related hospitalizations using the case series model, which adjusts for measured and unmeasured baseline confounders. However, a major challenge in modeling/assessing the infection-cardiovascular risk hypothesis is that the exact time of infection, or more generally “exposure,” onsets cannot be ascertained based on hospitalization data. Only imprecise markers of the timing of infection onsets are available. Although there is a large literature on measurement error in the predictors in regression modeling, to date there is no work on measurement error on the timing of a time-varying exposure to our knowledge. Thus, we propose a new method, the measurement error case series (MECS) models, to account for measurement error in time-varying exposure onsets. We characterized the general nature of bias resulting from estimation that ignores measurement error and proposed a bias-corrected estimation for the MECS models. We examined in detail the accuracy of the proposed method to estimate the relative incidence. Hospitalization data from United States Renal Data System, which captures nearly all (> 99%) patients with end-stage renal disease in the U.S. over time, is used to illustrate the proposed method. The results suggest that the estimate of the cardiovascular incidence following the 30 days after infections, a period where acute effects of infection on vascular endothelium may be most pronounced, is substantially attenuated in the presence of infection onset measurement error.

Mohammed, Sandra M.; Senturk, Damla; Dalrymple, Lorien S.; Nguyen, Danh V.



Effectiveness and cost effectiveness of cardiovascular disease prevention in whole populations: modelling study  

PubMed Central

Objective To estimate the potential cost effectiveness of a population-wide risk factor reduction programme aimed at preventing cardiovascular disease. Design Economic modelling analysis. Setting England and Wales. Population Entire population. Model Spreadsheet model to quantify the reduction in cardiovascular disease over a decade, assuming the benefits apply consistently for men and women across age and risk groups. Main outcome measures Cardiovascular events avoided, quality adjusted life years gained, and savings in healthcare costs for a given effectiveness; estimates of how much it would be worth spending to achieve a specific outcome. Results A programme across the entire population of England and Wales (about 50 million people) that reduced cardiovascular events by just 1% would result in savings to the health service worth at least £30m (€34m; $48m) a year compared with no additional intervention. Reducing mean cholesterol concentrations or blood pressure levels in the population by 5% (as already achieved by similar interventions in some other countries) would result in annual savings worth at least £80m to £100m. Legislation or other measures to reduce dietary salt intake by 3 g/day (current mean intake approximately 8.5 g/day) would prevent approximately 30?000 cardiovascular events, with savings worth at least £40m a year. Legislation to reduce intake of industrial trans fatty acid by approximately 0.5% of total energy content might gain around 570?000 life years and generate NHS savings worth at least £230m a year. Conclusions Any intervention that achieved even a modest population-wide reduction in any major cardiovascular risk factor would produce a net cost saving to the NHS, as well as improving health. Given the conservative assumptions used in this model, the true benefits would probably be greater.



A multilevel model for cardiovascular disease prevalence in the US and its application to micro area prevalence estimates  

PubMed Central

Background Estimates of disease prevalence for small areas are increasingly required for the allocation of health funds according to local need. Both individual level and geographic risk factors are likely to be relevant to explaining prevalence variations, and in turn relevant to the procedure for small area prevalence estimation. Prevalence estimates are of particular importance for major chronic illnesses such as cardiovascular disease. Methods A multilevel prevalence model for cardiovascular outcomes is proposed that incorporates both survey information on patient risk factors and the effects of geographic location. The model is applied to derive micro area prevalence estimates, specifically estimates of cardiovascular disease for Zip Code Tabulation Areas in the USA. The model incorporates prevalence differentials by age, sex, ethnicity and educational attainment from the 2005 Behavioral Risk Factor Surveillance System survey. Influences of geographic context are modelled at both county and state level, with the county effects relating to poverty and urbanity. State level influences are modelled using a random effects approach that allows both for spatial correlation and spatial isolates. Results To assess the importance of geographic variables, three types of model are compared: a model with person level variables only; a model with geographic effects that do not interact with person attributes; and a full model, allowing for state level random effects that differ by ethnicity. There is clear evidence that geographic effects improve statistical fit. Conclusion Geographic variations in disease prevalence partly reflect the demographic composition of area populations. However, prevalence variations may also show distinct geographic 'contextual' effects. The present study demonstrates by formal modelling methods that improved explanation is obtained by allowing for distinct geographic effects (for counties and states) and for interaction between geographic and person variables. Thus an appropriate methodology to estimate prevalence at small area level should include geographic effects as well as person level demographic variables.

Congdon, Peter



Cardiovascular simulation toolbox.  


A toolbox for Matlab Simulink (trademark of Mathworks corp. etc.) was developed to simulate various models of flow in the cardiovascular system and study effects of different pathological conditions. The toolbox was based on well-known analog lumped models of blood flow in vessels, the varying elastance heart model, blood flow through vessels, shunts, and valves as well as models of oxygen exchange at lungs and tissue. The toolbox is modular providing the basic building blocks of the cardiovascular system. Parameters for the individual components may be set by the user to adapt the component to the simulated system. Several examples are shown. This modeling system is described and is also available for downloading as an open source for free use. The authors see this as the basis for wide collaboration and standardization in modeling. A web site will be available for accepting contributions from other researchers and to create a free exchange. PMID:17570062

Sheffer, Liron; Santamore, William P; Barnea, Ofer



Evolutionary hypernetwork models for aptamer-based cardiovascular disease diagnosis  

Microsoft Academic Search

We present a biology-inspired probabilistic graphical model, called the hypernetwork model, and its application to medical diagnosis of disease. The hypernetwork models are a way of simulated DNA computing. They have a set of hyperedges repre- senting a subset of features in the training data. These characteris- tics allow the hypernetwork models to work similarly to associa- tive memories and

Jung-Woo Ha; Jae-hong Eom; Sung-chun Kim; Byoung-tak Zhang



Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system  

PubMed Central

Prostacyclin is an antithrombotic hormone produced by the endothelium, whose production is dependent on cyclooxygenase (COX) enzymes of which two isoforms exist. It is widely believed that COX-2 drives prostacyclin production and that this explains the cardiovascular toxicity associated with COX-2 inhibition, yet the evidence for this relies on indirect evidence from urinary metabolites. Here we have used a range of experimental approaches to explore which isoform drives the production of prostacyclin in vitro and in vivo. Our data show unequivocally that under physiological conditions it is COX-1 and not COX-2 that drives prostacyclin production in the cardiovascular system, and that urinary metabolites do not reflect prostacyclin production in the systemic circulation. With the idea that COX-2 in endothelium drives prostacyclin production in healthy individuals removed, we must seek new answers to why COX-2 inhibitors increase the risk of cardiovascular events to move forward with drug discovery and to enable more informed prescribing advice.

Kirkby, Nicholas S.; Lundberg, Martina H.; Harrington, Louise S.; Leadbeater, Philip D. M.; Milne, Ginger L.; Potter, Claire M. F.; Al-Yamani, Malak; Adeyemi, Oladipupo; Warner, Timothy D.; Mitchell, Jane A.



Swine Models of Type 2 Diabetes Mellitus: Insulin Resistance, Glucose Tolerance, and Cardiovascular Complications  

Microsoft Academic Search

In humans, diabetes mellitus (DM) is considered a hetero- geneous metabolic disorder. Swine have been used as a model for many human conditions including type 1 (insulin- deficient) and type 2 (insulin-resistant) DM research be- cause of their phenotypic similarities to humans including: cardiovascular anatomy and function, metabolism, lipopro- tein profile, size, tendency to obesity, and omnivorous hab- its. There

Dwight A. Bellinger; Elizabeth P. Merricks; Timothy C. Nichols



Cardiovascular parameters in anaesthetized guinea pigs: A safety pharmacology screening model  

Microsoft Academic Search

IntroductionAssessment of cardiovascular functions in vivo is part of the core battery of guideline ICH S7A and is thereby required by regulatory authorities. The haemodynamic effects of repeated intravenous administrations of reference compounds were analyzed in order to validate the guinea pig model for safety pharmacology studies under GLP conditions.

Daniela S. Hauser; Matthias Stade; Angela Schmidt; Guido Hanauer



Salud Para Su Corazón: A Community-Based Latino Cardiovascular Disease Prevention and Outreach Model  

Microsoft Academic Search

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



The relationship between subtypes of depression and cardiovascular disease: a systematic review of biological models  

PubMed Central

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.

Baune, B T; Stuart, M; Gilmour, A; Wersching, H; Heindel, W; Arolt, V; Berger, K



Leptin and cardiovascular diseases.  


1. Leptin is a 16-kDa hormone, synthesized primarily by adipocyte, which acts as a key factor for maintenance of energy homeostasis in central and peripheral tissues. In most obese individuals, serum leptin levels are increased and correlate with the individual's body mass index. 2. Abundant investigations ranging from clinical and animal model studies to in vitro analyses show that leptin plays a pivotal role in obesity-related cardiovascular diseases (CVD). Hyperleptinaemia has been confirmed to be a predictor of acute cardiovascular events. However, some studies have shown that leptin has a cardioprotective effect in leptin-deficient models. These data suggest the influences of leptin on the pathophysiology of cardiovascular diseases are complex and not completely understood. 3. In the present review, we summarize the major leptin signalling pathways, including Janus-activated kinase/signal transducers and activators of transcription (Jak/STAT), mitogen-activated protein kinases (MAPK), and phosphatidylinositol 3-kinase (PI-3K) signalling pathways, and analyse the probable mechanisms of selective leptin resistance. We then provide a detailed review of the effects of leptin on the cardiovascular system, including sympathoactivation, oxidative stress, vascular inflammation, endothelial dysfunction, vascular cell proliferation, cardiomyocytes hypertrophy, as well as fatty acid metabolism, all of which contribute to the pathogenesis of cardiovascular diseases (e.g. ischaemic heart disease). The central premise of this review is to elucidate the mechanisms by which leptin affects the cardiovascular function and provide insight into obesity-related CVD. PMID:21957899

Hou, Ning; Luo, Jian-Dong



[Implementing cardiovascular prevention in the real world: presentation of an integrated hospital-field model].  


Numerous studies have documented that cardiovascular prevention in subjects at high risk has a large impact on the clinical outcomes. Data also show the efficacy of an early, intensive, well-structured, professionally expert, multidisciplinary intervention, making use of adequate behavioural and pharmacologic instruments, on the global risk. Such intervention is, however, available at present for very few healthcare users, while the majority, above all in primary prevention, receive a programme of low impact, with poor feedback between the hospital specialist and general practitioner (GP), and often limited to the simple prescription of treatment or to specialist check-ups and/or general advice on lifestyle. The project of implementation takes as its starting point this analysis and the premise that for an intervention of cardiovascular prevention to be effective, particularly in the long term, and really applicable to the broad population, it must be governed primarily by the GP--providing that s/he be adequately trained, utilize new and more dynamic caring modes, and be able to count concretely both on integration with the specialist and on the support of a multidisciplinary team for specific interventions. The paper presents the various stages of the project: from definition of the resources available (health district, GPs, hospital specialists) to the need for GP training, to the modes of operation: instruments for risk calculation, procedures followed, model of integration between GP and specialist, identification of the goals and indicators. This is a low cost project in terms of both the human and structural resources employed, utilizing what is already available in the healthcare system of our country. One of its most original aspects is the medical visit jointly conducted by the GP and hospital specialist, which realizes in concrete terms the integration of the skills: GPs can finally confront in the field the specialist of referral, acquire new skills, improve their daily mode of operating, while they will be gratified by a work more in line with their professional image, and become promoters of health. Finally, this project highlights the propositive and operative role assumed by cardiac rehabilitation and prevention, which, after developing over the years a specific know-how on the subject, now transmits these skills to other healthcare resources and creates a link with the local territory, so providing an appropriate response to the need to put into practice primary and secondary cardiovascular prevention. PMID:12918169

Griffo, Raffaele; Blondett, Massimo; Stellini, Fabio; Camerini, Alberto; Picciotto, Rinaldo



Health system challenges of cardiovascular disease and diabetes in four Eastern Mediterranean countries.  


This paper presents evidence from research into health system challenges of cardiovascular disease (CVD) and diabetes in four Eastern Mediterranean countries: the occupied Palestinian territory, Syria, Tunisia and Turkey. We address two questions. How has the health system in each country been conceptualised and organised to manage the provision of care for those with CVD or diabetes? And what were key concerns about the institutional ability to address this challenge? Research took place from 2009 to 2010, shortly before the political upheavals in the region, and notably in Syria and Tunisia. Data collection involved a review of key documents, interviews with key informants and brief data collection in clinics. In analysing the data, we adopted the analytical schema proposed by Walt and Gilson, distinguishing content, actors, context and process. Key findings from each country highlighted concerns about fragmented provision and a lack of coordination. Specific concerns included: the lack of patient referral pathways, functioning health information systems and investment in staff. Regarding issues underlying these 'visible' problems in managing these diseases, we highlight implications of the wider systemic pressure for reform of health-sector finance in each country, based on neoliberal models. PMID:24004405

Phillimore, Peter; Zaman, Shahaduz; Ahmad, Balsam; Shoaibi, Azza; Khatib, Rasha; Khatib, Rana; Husseini, Abdullatif; Fouad, Fouad; Elias, Madonna; Maziak, Wasim; Tlili, Faten; Tinsa, Francine; Ben Romdhane, Habiba; K?l?ç, Bülent; Kalaça, Sibel; Unal, Belgin; Critchley, Julia



Cardiovascular Risk Associated with Interactions among Polymorphisms in Genes from the Renin-Angiotensin, Bradykinin, and Fibrinolytic Systems  

PubMed Central

Background Vascular fibrinolytic balance is maintained primarily by interplay of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1). Previous research has shown that polymorphisms in genes from the renin-angiotensin (RA), bradykinin, and fibrinolytic systems affect plasma concentrations of both t-PA and PAI-1 through a set of gene-gene interactions. In the present study, we extend this finding by exploring the effects of polymorphisms in genes from these systems on incident cardiovascular disease, explicitly examining two-way interactions in a large population-based study. Methodology/Principal Findings Data from the population-based PREVEND study in Groningen, The Netherlands (n?=?8,138) were analyzed. The effects of the polymorphisms and their interactions on cardiovascular events were analyzed via Cox proportional hazards models. There was no association between five of the six polymorphisms singly and risk of cardiovascular disease. There was a significant main effect for the ACE I/D polymorphism for both dominant and additive coding schemes. There were significant interactions between the following polymorphism pairs even after adjustment for known risk factors: ACE I/D & PAI-1 4G/5G (p?=?0.012), BDKRB2 C181T & ACE I/D (p?=?0.016), BDKRB2 C58T & ACE I/D (p?=?0.025), BDKRB2 exon 1 I/D & AT1R A1166C (p?=?0.017), and BDKRB2 C58T & AT1R A1166C (p?=?0.015). Conclusions/Significance This study suggests possible interactions between genes from the RA, bradykinin, and fibrinolytic systems on the risk of cardiovascular disease, extending previous research that has demonstrated that interactions among genes from these systems influence plasma concentrations of both t-PA and PAI-1. Further explorations of these interactions are needed.

Bentley, John P.; Asselbergs, Folkert W.; Coffey, Christopher S.; Hebert, Patricia R.; Moore, Jason H.; Hillege, Hans L.; van Gilst, Wiek H.



A Follow-Up Study of Medical Students' Biomedical Understanding and Clinical Reasoning Concerning the Cardiovascular System  

ERIC Educational Resources Information Center

|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



The cardiovascular and central nervous system effects in the human of U-62066E  

Microsoft Academic Search

The cardiovascular and central nervous system effects of the kappa opioid receptor agonist U-62066E were investigated in ten normal male subjects who received U-62066E or placebo with low or high dose naloxone in a randomized, double blind study.

G. H. Rimoy; D. M. Wright; N. K. Bhaskar; P. C. Rubin



C-type natriuretic peptide effects on cardiovascular nitric oxide system in spontaneously hypertensive rats  

Microsoft Academic Search

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 role of the renin-angiotensin system in the development of cardiovascular disease  

Microsoft Academic Search

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

Thomas Unger



Experimental Models of Oxidative Stress Related to Cardiovascular Diseases and Diabetes  

Microsoft Academic Search

\\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


A computational model of the cardiovascular system coupled with an upper-arm oscillometric cuff and its application to studying the suprasystolic cuff oscillation wave, concerning its value in assessing arterial stiffness  

Microsoft Academic Search

A variety of methods have been proposed to noninvasively assess arterial stiffness using single or multiple oscillometric cuffs. A common pitfall of most of such methods is that the individual-specific accuracy of assessment is not clearly known due to an insufficient understanding of the relationships between the characteristics of cuff oscillometry and cardiovascular properties. To provide a tool for quantitatively

Fuyou Liang; Shu Takagi; Ryutaro Himeno; Hao Liu



Driving forces behind increasing cardiovascular drug utilization: a dynamic pharmacoepidemiological model  

PubMed Central

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTSeveral studies indicate that switch to more expensive drugs and increasing treatment intensity, rather than population ageing have been responsible for rising drug expenditures during the 1990s.Little is known about the driving forces behind the increasing treatment intensity with cardiovascular drugs. WHAT THIS STUDY ADDSThis study provides a new pharmacoepidemiological method to analyse drug utilization trends, applying dispensing data at the individual level.The suggested semi-Markov model allows for quantification of the influence of changing incidence, discontinuation and user mortality on rising treatment prevalence.Increasing treatment incidence was the main driver behind rising treatment prevalence for most cardiovascular drug categories.Whereas declining discontinuation drove some of the growth, declining mortality among drug users had little influence. AIMS To investigate the driving forces behind increasing utilization of cardiovascular drugs. METHODS Using register data, all Danish residents as of 1 January 1996 were followed until 2006. Cohort members were censored at death or emigration. Cardiovascular drug utilization on the individual level was traced, applying registered out-of-hospital dispensing. The impact of population ageing on cardiovascular drug utilization was investigated using standardized intensities and prevalences. Based on a three-state (untreated, treated and dead) semi-Markov model, we explored to what extent increasing treatment prevalence was driven by changing incidence, discontinuation and mortality. Expected treatment prevalences were modelled, applying stratum-specific cohort prevalence in 1996 along with incidence, discontinuation and drug user mortality either throughout 1996–2004 or at fixed 1996 levels. RESULTS Treatment prevalence (ages ?20 years) with cardiovascular drugs increased by 39% during 1996–2005 from 192.4 to 256.9 per 1000 inhabitants (95% confidence interval 256.5, 257.3). Treatment intensity grew by 109% from 272 to 569 defined daily doses 1000?1 day?1. Population ‘middle-ageing’ accounted for 11.5 and 20.3%, respectively. Increasing treatment incidence was the main driver of the rising treatment prevalence in most drug categories. Declining discontinuation drove some of the growth, declining drug user mortality less. Even with fixed incidence in the model, treatment prevalence continued to increase. CONCLUSIONS Age-related increases in treatment intensity and prevalence, rather than population ageing, drove the increasing treatment intensity with cardiovascular drugs. Increasing treatment prevalence in subgroups was primarily caused by increasing incidence. Due to pharmacoepidemiological disequilibrium, treatment prevalence will continue to grow even with unchanged incidence.

Kildemoes, Helle Wallach; St?vring, Henrik; Andersen, Morten



Cardiovascular risk with SCORE system in patients with different degree of renal function impairment.  


A risk prediction system, Systematic Coronary Risk Evaluation, that is based on European studies has been developed and recommended to define absolute 10-year risk of a fatal cardiovascular event and mortality. The aim of the study was to compare cardiovascular risk calculated with SCORE system at patients with different degree of renal impairment. The study included 90 patients divided in 4 groups: 1st group=30 patients without renal failure, 2nd group=25 patients with CRF in predialysis stage, 3rd group=19 hemodialysis non-diabetic patients and 4th group=16 hemodialysis diabetics patients. SCORE was calculated from age, sex, systolic blood pressure, smoking and cholesterol levels. There were no significant differences in age and blood pressure in four examined groups. The incidence of smokers and cholesterol level were higher in predialysis patients. The highest SCORE was calculated in predialysis patients: 1st group: 2.5+/-1.8; 2nd group: 5.3+/-4.3, 3rd group: 3.7+/-1.1 and 4th group: 4.06+/-4. We supposed that traditional risk factors from SCORE risk system are suitable to explain the cardiovascular risk and mortality in all population but underestimates cardiovascular risk of high-risk groups like patients with chronic renal disease. PMID:18928168

Deliyska, Boriana; Shurliev, Ventzislav; Nenchev, Nencho; Krivoshiev, Stefan; Strashimirova, Violeta



A plausible radiobiological model of cardiovascular disease at low or fractionated doses  

NASA Astrophysics Data System (ADS)

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


Subclinical Cardiovascular System Changes in Obese Patients with Juvenile Idiopathic Arthritis  

PubMed Central

Objective. We aimed to determine the prevalence of excess body mass in juvenile idiopathic arthritis (JIA) children and to investigate the influence of obesity into the early, subclinical changes in cardiovascular system in these patients. Methods. Fifty-eight JIA patients, aged median 13 years, were compared to 36 healthy controls. Traditional cardiovascular risk factors and inflammatory markers (hsCRP, IL-6, TNF?, adiponectin) were studied together with IMT (intima-media thickness), FMD (flow mediated dilation), and LVMi (left ventricle mass index) as surrogate markers of subclinical atherosclerosis. Results. Thirteen JIA children (22%) were obese and had increased systolic blood pressure, cholesterol, triglycerides, insulin, HOMA, hsCRP, and IL-6 compared to nonobese JIA and controls. FMD was decreased compared to nonobese JIA and controls, whereas IMT and LVMi were increased. In multivariate regression analysis, TNF?, SDS-BMI, and systolic blood pressure were independent predictors of early CV changes in JIA. Conclusions. Coincident obesity is common in JIA children and is associated with insulin resistance, dyslipidemia, and increased levels of inflammatory markers leading to early changes in cardiovascular system. Thus, medical care of children with JIA should include strategies preventing cardiovascular disease by maintenance of adequate body weight.

Glowinska-Olszewska, Barbara; Bossowski, Artur; Dobrenko, Elzbieta; Hryniewicz, Andrzej; Konstantynowicz, Jerzy; Milewski, Robert; Luczynski, Wlodzimierz; Piotrowska-Jastrzebska, Janina; Kowal-Bielecka, Otylia



Cardiovascular Development and Survival During Gestation in the TS65DN Mouse Model for Down Syndrome  

PubMed Central

The Ts65Dn mouse model for Down syndrome (DS) exhibits many phenotypes seen in human DS. Previous research has revealed a reduced rate of transmission of the T65Dn marker chromosome in neonates. To analyze potential fetal loss, litters from trisomic females at 10.5dpc through 14.5dpc were genotyped. No significant differences from the expected Mendelian ratio were found in transmission of T65Dn at any stage. Cardiovascular defects found in trisomic neonates are associated with formation of pharyngeal arch arteries. Vessel tracing was used to identify anomalies in 10.5dpc, 11.5dpc, and 13.5dpc embryos. Comparison of trisomic versus euploid embryos injected with India ink revealed delay and abnormality in cardiovascular development in trisomic embryos at each stage. Through the analysis of transmission rate and cardiovascular development in embryonic mice, we learn more about prenatal mortality and the origins of cardiac abnormality in the Ts65Dn mice to assist in understanding cardiovascular malformation associated with DS.

Lorandeau, Candice G.; Hakkinen, Lauren A.; Moore, Clara S.



Method of propulsion of a ferromagnetic core in the cardiovascular system through magnetic gradients generated by an MRI system.  


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



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


It is now well established that the developing embryo is very sensitive to oxidative stress, which is a contributing factor to pregnancy-related disorders. However, little is known about the effects of reactive oxygen species (ROS) on the embryonic cardiovascular system due to a lack of appropriate ROS control method in the placenta. In this study, a small molecule called 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH), a free radicals generator, was used to study the effects of oxidative stress on the cardiovascular system during chick embryo development. When nine-day-old (stage HH 35) chick embryos were treated with different concentrations of AAPH inside the air chamber, it was established that the LD50 value for AAPH was 10 µmol/egg. At this concentration, AAPH was found to significantly reduce the density of blood vessel plexus that was developed in the chorioallantoic membrane (CAM) of HH 35 chick embryos. Impacts of AAPH on younger embryos were also examined and discovered that it inhibited the development of vascular plexus on yolk sac in HH 18 embryos. AAPH also dramatically repressed the development of blood islands in HH 3+ embryos. These results implied that AAPH-induced oxidative stress could impair the whole developmental processes associated with vasculogenesis and angiogenesis. Furthermore, we observed heart enlargement in the HH 40 embryo following AAPH treatment, where the left ventricle and interventricular septum were found to be thickened in a dose-dependent manner due to myocardiac cell hypertrophy. In conclusion, oxidative stress, induced by AAPH, could lead to damage of the cardiovascular system in the developing chick embryo. The current study also provided a new developmental model, as an alternative for animal and cell models, for testing small molecules and drugs that have anti-oxidative activities. PMID:23469224

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



Instantaneous nonlinear assessment of complex cardiovascular dynamics by laguerre-volterra point process models.  


We report an exemplary study of instantaneous assessment of cardiovascular dynamics performed using point-process nonlinear models based on Laguerre expansion of the linear and nonlinear Wiener-Volterra kernels. As quantifiers, instantaneous measures such as high order spectral features and Lyapunov exponents can be estimated from a quadratic and cubic autoregressive formulation of the model first order moment, respectively. Here, these measures are evaluated on heartbeat series coming from 16 healthy subjects and 14 patients with Congestive Hearth Failure (CHF). Data were gathered from the on-line repository PhysioBank, which has been taken as landmark for testing nonlinear indices. Results show that the proposed nonlinear Laguerre-Volterra point-process methods are able to track the nonlinear and complex cardiovascular dynamics, distinguishing significantly between CHF and healthy heartbeat series. PMID:24111139

Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo



Prototype for an organ system (liver) localization cardiovascular catheter  

NASA Astrophysics Data System (ADS)

This study describes the function and potential clinical utility of a sensor which can serve as a guidance mechanism allowing for the selective cannulation of the hepatic venous system without the need for additional imaging technology. The sensor is based upon a homogeneous affinity fluorescence assay system utilizing the lectin Ricinus cummunis agglutinin I and covalently linked to the fluorophol Alexa 488 and its conjugate polydextran labeled with rhodamine and lactose. The affinity between these two macromolecules is sensitive to ambient galactose concentration which exists as a steep gradient at the hepatic venous/vena caval junction allowing this anatomic region to be discriminated from irrelevant regions. This sensor system permits venous access for additional monitoring approaches such as venous oximetry.

Ballerstadt, Ralph; Dahn, Michael S.; Lange, M. Patricia; Schultz, Jerome S.



Naturally Occurring and Iatrogenic Animal Models of Valvular, Infectious, and Arrhythmic Cardiovascular Disease  

Microsoft Academic Search

Most naturally occurring congenital cardiovascular entities found in humans have been identified in one or more species of\\u000a animals but the utility of these naturally occurring models as research subjects is not well established. Many of the congenital\\u000a diseases are associated with noncardiovascular defects and some of these may result in infertility, impotence, and other reproductive\\u000a problems that preclude the

David R. Gross


Computer diagnostic of cardiovascular system development experience and prospects  

Microsoft Academic Search

The paper addresses a number of problems solved in the design of computer systems for functional diagnostics, in particular - the synthesis and restoration of electrocardiographic leads, fetal electrocardiogram separation and analysis during abdominal cardiography, the development of telemedicine and personal diagnostic devices.

A. Zelensky; V. Sharonov; V. Shulgin



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

PubMed Central

The posttranslational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide ?-N-acetylglucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification. Protein O-GlcNAcylation is rapidly emerging as a key regulator of critical biological processes including nuclear transport, translation and transcription, signal transduction, cytoskeletal reorganization, proteasomal degradation, and apoptosis. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are both major hallmarks of diabetes mellitus and diabetes-related cardiovascular complications. Conversely, there is a growing body of data demonstrating that the acute activation of O-GlcNAc levels is an endogenous stress response designed to enhance cell survival. Reports on the effect of altered O-GlcNAc levels on the heart and cardiovascular system have been growing rapidly over the past few years and have implicated a role for O-GlcNAc in contributing to the adverse effects of diabetes on cardiovascular function as well as mediating the response to ischemic injury. Here, we summarize our present understanding of protein O-GlcNAcylation and its effect on the regulation of cardiovascular function. We examine the pathways regulating protein O-GlcNAcylation and discuss, in more detail, our understanding of the role of O-GlcNAc in both mediating the adverse effects of diabetes as well as its role in mediating cellular protective mechanisms in the cardiovascular system. In addition, we also explore the parallels between O-GlcNAc signaling and redox signaling, as an alternative paradigm for understanding the role of O-GlcNAcylation in regulating cell function.

Laczy, Boglarka; Hill, Bradford G.; Wang, Kai; Paterson, Andrew J.; White, C. Roger; Xing, Dongqi; Chen, Yiu-Fai; Darley-Usmar, Victor; Oparil, Suzanne; Chatham, John C.



Improving Cardiovascular Care Through Outpatient Cardiac Rehabilitation: An Analysis of Payment Models That Would Improve Quality and Promote Use.  


BACKGROUND:: Much attention has been paid to improving the care of patients with cardiovascular disease by focusing attention on delivery system redesign and payment reforms that encompass the healthcare spectrum, from an acute episode to maintenance of care. However, 1 area of cardiovascular disease care that has received little attention in the advancement of quality is cardiac rehabilitation (CR), a comprehensive secondary prevention program that is significantly underused despite evidence-based guidelines that recommending its use. PURPOSE:: The purpose of this article was to analyze the applicability of 2 payment and reimbursement models-pay-for-performance and bundled payments for episodes of care - that can promote the use of CR. CONCLUSIONS:: We conclude that a payment model combining elements of both pay-for-performance and episodes of care would increase the use of CR, which would both improve quality and increase efficiency in cardiac care. Specific elements would need to be clearly defined, however, including: (a) how an episode is defined, (b) how to hold providers accountable for the care they provider, (c) how to encourage participation among CR providers, and (d) how to determine an equitable distribution of payment. CLINICAL IMPLICATIONS:: Demonstrations testing new payment models must be implemented to generate empirical evidence that a melded pay-for-performance and episode-based care payment model will improve quality and efficiency. PMID:23416941

Mead, Holly; Grantham, Sarah; Siegel, Bruce



The relationship between subtypes of depression and cardiovascular disease: a systematic review of biological models  

Microsoft Academic Search

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

B T Baune; M Stuart; A Gilmour; H Wersching; W Heindel; V Arolt; K Berger



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

PubMed Central

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

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



Air pollution and its impact on the cardiovascular system Poluição atmosférica e seu impacto no sistema cardiovascular  

Microsoft Academic Search

Despite the great medical advances, cardiovascular disease remains one of the major causes of mortality worldwide, especially in industrialized countries. It develops as a result of countless complex interactions between genetic factors such as those related to age, sex, family history, weight, and post-menopausal status in women; and to environment-related factors such as cigarette smoking, alcohol use, eating habits, physical

Marjorie Paris Colombini


Toxic effects of mercury on the cardiovascular and central nervous systems.  


Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton



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

PubMed Central

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

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



Effects of zinc-deficient diets on the cardiovascular system in rabbits  

Microsoft Academic Search

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

J. W. Carter; S. I. Koo



Have the Renin-Angiotensin-Aldosterone System Perturbations in Cardiovascular Disease Been Exhausted?  

Microsoft Academic Search

The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure control and volume homeostasis.\\u000a Inappropriate activation of the RAAS has been implicated in the pathogenesis of hypertension and related cardiovascular disease.\\u000a Several classes of agents that block RAAS signaling have been shown to be effective antihypertensives and to have cardioprotective\\u000a and renoprotective properties. Because blockade of the RAAS is

Sulaf J. Mansur; Fadi G. Hage; Suzanne Oparil



Is an Intracrine Renin-Angiotensin System Involved in the Control of Cardiovascular Function?  

Microsoft Academic Search

\\u000a We review the evidence that there is an intracrine renin angiotensin system in the heart and vessels which contributes to\\u000a the regulation of cardiovascular function. Angiotensin II, like a variety of other peptide hormones, has been shown to bind\\u000a to intracellular receptors after either internalization or intracellular synthesis. The evidence of an intracrine action of\\u000a Ang II on regulation of

Walmor C. De Mello; Richard N. Re


Attenuated Cardiovascular Response to Sympathetic System Activation during Exercise in Patients with Dialysis-Induced Hypotension  

Microsoft Academic Search

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



OCT imaging of the musculoskeletal and cardiovascular systems  

NASA Astrophysics Data System (ADS)

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.



Physiology and pharmacology of the cardiovascular adrenergic system  

PubMed Central

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.

Lymperopoulos, Anastasios



Chronic contamination of rats with 137 cesium radionuclide: impact on the cardiovascular system.  


Cardiovascular system impairment has been observed in children and in liquidators exposed to the Chernobyl nuclear power plant accident. No experimental studies of animals have analyzed whether these disorders might be attributed to chronic ingestion of low levels of cesium 137 ((137)Cs). Biochemical, physiological, and molecular markers of the cardiovascular system were analyzed in rats exposed through drinking water to (137)Cs at a dose of 500 Bq kg(-1) (6500 Bq l(-1)). Plasma concentrations of CK and CK-MB were higher (+52%, P < 0.05) in contaminated rats. No histological alteration of the heart was observed, but gene expression was modified in the atria. Specifically, levels of ACE (angiotensin converting enzyme) and BNP (brain natriuretic peptide) gene expression increased significantly (P < 0.05). ECG analysis did not disclose any arrhythmia except ST- and RT-segment shortening (-9% and -11%, respectively, P < 0.05) in rats exposed to (137)Cs. Mean blood pressure decreased (-10%, P < 0.05), and its circadian rhythm disappeared. Overall, chronic contamination by an extreme environmental dose of (137)Cs for 3 months did not result in cardiac morphological changes, but the cardiovascular system impairments we observed could develop into more significant changes in sensitive animals or after longer contamination. PMID:18327657

Guéguen, Yann; Lestaevel, Philippe; Grandcolas, Line; Baudelin, Cédric; Grison, Stéphane; Jourdain, Jean-René; Gourmelon, Patrick; Souidi, Maâmar



[Relationship between spinal PCP receptor on cardiovascular effect and noradrenergic system].  


By using receptor blockade, HPLC, destroying catecholaminergic nerve terminals by 6-OHDA, autoradiography, and other techniques, the relationship between effects of the spinal PCP receptor on cardiovascular function and noradrenergic system was studied. The main results were as following. Hypotension and bradycardia induced by ith PCP were significantly antagonized by prazosin and yohimbine; the MHPG levels in spinal CSF were significantly increased during the ith PCP induced hypotension and bradycardia; pretreatment with 6-OHDA to destroy NA terminals in the spinal cord significantly decreased the ith PCP induced hypotension and bradycardia, and the density of PCP receptors in the spinal cord. The results suggest that there are PCP receptors on the NA terminals in the spinal cord, which promoted the release of NA and/or inhibited the reuptake of NA. This may be a possible mechanism underlying the influence of spinal PCP receptors on cardiovascular function. PMID:2175945

Yu, C X; Wang, Q P; Xia, Y; Xu, S F



Protective effects of red wine polyphenolic compounds on the cardiovascular system  

PubMed Central

Phenolic phytochemicals are widely distributed in the plant kingdom. In terms of protective effects on organisms, the group of polyphenols is the most important. In various experiments, it has been shown that selected polyphenols, mainly flavonoids, confer protective effects on the cardiovascular system and have anti-cancer, antiviral and antiallergic properties. In coronary artery disease, the protective effects are due mainly to antithrombic, antioxidant, anti-ischemic and vasorelaxant properties of flavonoids. Flavonoids are low molecular weight compounds composed of a three-ring structure with various substitutions, which appear to be responsible for the antioxidant and antiproliferative properties. It has been hypothesized that the low incidence of coronary artery disease in the French population may be partially related to the pharmacological properties of polyphenolic compounds present in red wine. Many epidemiological studies have shown that regular flavonoid intake is associated with reduced risk of cardiovascular diseases.

Zenebe, Woineshet; Pechanova, Olga; Bernatova, Iveta



Physical activity ameliorates cardiovascular health in elderly subjects: the functional role of the ? adrenergic system  

PubMed Central

Aging is a complex process characterized by a gradual decline in organ functional reserves, which eventually reduces the ability to maintain homeostasis. An exquisite feature of elderly subjects, which constitute a growing proportion of the world population, is the high prevalence of cardiovascular disorders, which negatively affect both the quality of life and the life expectancy. It is widely acknowledged that physical activity represents one of the foremost interventions capable in reducing the health burden of cardiovascular disease. Interestingly, the benefits of moderate-intensity physical activity have been established both in young and elderly subjects. Herein we provide a systematic and updated appraisal of the literature exploring the pathophysiological mechanisms evoked by physical activity in the elderly, focusing on the functional role of the ? adrenergic system.

Santulli, Gaetano; Ciccarelli, Michele; Trimarco, Bruno; Iaccarino, Guido



Effects of cyclooxygenase inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia  

PubMed Central

The cardiovascular effects of cyclooxygenase (COX) inhibition remain controversial, especially in the setting of cardiovascular comorbidities. We examined the effects of nonselective and selective COX inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. Twenty-four intact male Yorkshire swine underwent left circumflex ameroid constrictor placement and were subsequently given either no drug (HCC; n = 8), a nonselective COX inhibitor (440 mg/day naproxen; HCNS; n = 8), or a selective COX-2 inhibitor (200 mg/day celecoxib; HCCX; n = 8). After 7 wk, myocardial functional was measured and myocardium from the nonischemic ventricle and ischemic area-at-risk (AAR) were analyzed. Regional function as measured by segmental shortening was improved in the AAR of HCCX compared with HCC. There was no significant difference in perfusion to the nonischemic ventricle between groups, but myocardial perfusion in the AAR was significantly improved in the HCCX group compared with controls at rest and during pacing. Endothelium-dependent microvessel relaxation was diminished by ischemia in HCC animals, but both naproxen and celecoxib improved vessel relaxation in the AAR compared with controls, and also decreased the vasoconstrictive response to serotonin. Thromboxane levels in the AAR were decreased in both HCNS and HCCX compared with HCC, whereas prostacyclin levels were decreased only in HCNS, corresponding to a decrease in prostacyclin synthase expression. Chronic ischemia increased apoptosis in Troponin T negative cells and intramyocardial fibrosis, both of which were reduced by celecoxib administration in the AAR. Capillary density was decreased in both the HCNS and HCCX groups. Protein oxidative stress was decreased in both HCNS and HCCX, whereas lipid oxidative stress was decreased only in the HCCX group. Thus nonselective and especially selective COX inhibition may have beneficial myocardial effects in the setting of hypercholesterolemia and chronic ischemia. Whether these effects modulate cardiovascular risk in patients taking these drugs remains to be seen, but evidence to date suggests that they do not.

Chu, Louis M.; Robich, Michael P.; Bianchi, Cesario; Feng, Jun; Liu, Yuhong; Xu, Shu-Hua; Burgess, Thomas



Investigating Properties of the Cardiovascular System Using Innovative Analysis Algorithms Based on Ensemble Empirical Mode Decomposition  

PubMed Central

Cardiovascular system is known to be nonlinear and nonstationary. Traditional linear assessments algorithms of arterial stiffness and systemic resistance of cardiac system accompany the problem of nonstationary or inconvenience in practical applications. In this pilot study, two new assessment methods were developed: the first is ensemble empirical mode decomposition based reflection index (EEMD-RI) while the second is based on the phase shift between ECG and BP on cardiac oscillation. Both methods utilise the EEMD algorithm which is suitable for nonlinear and nonstationary systems. These methods were used to investigate the properties of arterial stiffness and systemic resistance for a pig's cardiovascular system via ECG and blood pressure (BP). This experiment simulated a sequence of continuous changes of blood pressure arising from steady condition to high blood pressure by clamping the artery and an inverse by relaxing the artery. As a hypothesis, the arterial stiffness and systemic resistance should vary with the blood pressure due to clamping and relaxing the artery. The results show statistically significant correlations between BP, EEMD-based RI, and the phase shift between ECG and BP on cardiac oscillation. The two assessments results demonstrate the merits of the EEMD for signal analysis.

Yeh, Jia-Rong; Lin, Tzu-Yu; Chen, Yun; Sun, Wei-Zen; Abbod, Maysam F.; Shieh, Jiann-Shing



Investigating properties of the cardiovascular system using innovative analysis algorithms based on ensemble empirical mode decomposition.  


Cardiovascular system is known to be nonlinear and nonstationary. Traditional linear assessments algorithms of arterial stiffness and systemic resistance of cardiac system accompany the problem of nonstationary or inconvenience in practical applications. In this pilot study, two new assessment methods were developed: the first is ensemble empirical mode decomposition based reflection index (EEMD-RI) while the second is based on the phase shift between ECG and BP on cardiac oscillation. Both methods utilise the EEMD algorithm which is suitable for nonlinear and nonstationary systems. These methods were used to investigate the properties of arterial stiffness and systemic resistance for a pig's cardiovascular system via ECG and blood pressure (BP). This experiment simulated a sequence of continuous changes of blood pressure arising from steady condition to high blood pressure by clamping the artery and an inverse by relaxing the artery. As a hypothesis, the arterial stiffness and systemic resistance should vary with the blood pressure due to clamping and relaxing the artery. The results show statistically significant correlations between BP, EEMD-based RI, and the phase shift between ECG and BP on cardiac oscillation. The two assessments results demonstrate the merits of the EEMD for signal analysis. PMID:22919434

Yeh, Jia-Rong; Lin, Tzu-Yu; Chen, Yun; Sun, Wei-Zen; Abbod, Maysam F; Shieh, Jiann-Shing



Introducing a baroreflex model for studying cardiovascular effects of mental workload.  


A quantitative baroreflex control model is presented aimed at estimating differences in autonomic activation due to mental task performance. The model, which builds on earlier work of Wesseling and colleagues, is strongly supported by well-established knowledge of physiological control processes. Spectral measures of heart rate and blood pressure variability provide the information to estimate autonomic gain and tone parameters. The article gives a detailed model description as well as an evaluation in terms of spectral variability distributions, respiratory sinus arrhythmia, and vagal control mechanisms. The estimation procedure is outlined while presenting two studies that describe the effects of mental workload and vagal blockade, respectively. It is concluded that, using the model approach, cardiovascular effects of mental task performance can be interpreted in terms of specific changes in autonomic state. The model is implemented in a Matlab/Simulink environment and is available for other researchers in the field. PMID:15563349

Van Roon, Arie M; Mulder, Lambertus J M; Althaus, Monika; Mulder, Gijsbertus



Cardiovascular phantom  

SciTech Connect

A cardiovascular phantom is described for providing the proper indexing of a cine camera for X-Ray cineangiography consisting of: a plastic boardlike substrate; a metallic X-Ray absorptive material configured with the arborescent outline of a system of coronary arteries on the plastic boardlike substrate for absorbing X-Rays; and a covering material for the board.

Ridge, W.B.



[Non-medicamentous correction of changes in the cardiovascular and respiratory systems in subjects exposed to chrysolite asbestos dust].  


Two physiotherapeutic complexes are proposed for the improvement of functional characteristics of the respiratory and cardiovascular systems that can be used for the non-medicamentous treatment of patients with cardiovascular diseases or concurrent broncho-pulmonary and cardiovascular pathologies. One complex is designed for the treatment of patients with asbestosis including that complicated by chronic obstructive bronchitis in the phase of remission with the well-apparent signs of myocardial electric instability. The use of the other complex is indicated to patients with chronic obstructive bronchitis in the phase of exacerbation and the signs of chronic pulmonary heart associated with cardiac dysrhythmia. PMID:19284111

Obukhova, T Iu; Bugaeva, I V; Karpova, E A; Tereshina, L G; Budkar', L N


Methods for establishing a surveillance system for cardiovascular diseases in Indian industrial populations.  

PubMed Central

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.

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.



Air pollution and autonomic and vascular dysfunction in patients with cardiovascular disease: interactions of systemic inflammation, overweight, and gender.  


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



Air Pollution and Autonomic and Vascular Dysfunction in Patients With Cardiovascular Disease: Interactions of Systemic Inflammation, Overweight, and Gender  

PubMed Central

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 (PM2.5), black carbon, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide were measured continuously, with validation of concurrent real-time measurements of personal exposure to PM2.5 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/m3, 2.02 µg/m3, and 13.7 ppb in prior 4-hour exposure to PM2.5, 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.

Huang, Wei; Zhu, Tong; Pan, Xiaochuan; Hu, Min; Lu, Shou-En; Lin, Yong; Wang, Tong; Zhang, Yuanhang; Tang, Xiaoyan



Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health.  


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



Hypertensive Cardiovascular and Renal Disease and Target Organ Damage: Lessons from Animal Models  

PubMed Central

This brief review discusses some aspects of hypertensive damage to the kidneys and cardiovascular system. A comparison of renal and cardiac manifestations of hypertensive disease between results of clinical and experimental studies was made, with a major focus on the possible role of salt and the renin-angiotensin system (RAS) in inducing target organ damage. Thus, some degree of renal impairment is often present in patients with essential hypertension, varying from microalbuminuria to end-stage renal disease, whereas in rats with spontaneous hypertension only slight renal damage is seen in old rats with little evidence of renal failure. Since renal damage in hypertensive rats is induced when they are exposed to increased salt intake, we suggested that salt may also account for kidney injury in hypertensive patients. Similarly, cardiac damage is aggravated in hypertensive human beings and rats when given salt excess. We further presented evidence that the RAS may mediate adverse cardiac and renal effects of excessive salt intake. Finally, we also discussed some aspects of the cardiovascular physiology in the giraffe, the only mammal that in comparison with the human being has extremely high pressure at the level of the heart and kidneys but no target organ damage.

Susic, Dinko; Frohlich, Edward D.



Qualitative-fuzzy decision support system for monitoring patients with cardiovascular risk  

Microsoft Academic Search

Cardiovascular diseases are increasingly common in many countries. Cardiovascular risk (CVR) patients can continue their daily activities, but they must be monitored continuously in order to detect and respond to cardiovascular emergencies in the shortest possible time. Monitoring provides information to the medical personnel, which helps them make a diagnosis and decide upon a tailored treatment. This paper proposes a

Cesar Uribe; Claudia Isaza; Jose F. Florez-Arango



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


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



Milan PM1 Induces Adverse Effects on Mice Lungs and Cardiovascular System  

PubMed Central

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

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



Sent to Destroy: The Ubiquitin Proteasome System Regulates Cell Signaling and Protein Quality Control in Cardiovascular Development and Disease  

PubMed Central

The ubiquitin proteasome system (UPS) plays a crucial role in biological processes integral to the development of the cardiovascular system and cardiovascular diseases. The UPS prototypically recognizes specific protein substrates and places polyubiquitin chains on them for subsequent destruction by the proteasome. This system is in place to degrade not only misfolded and damaged proteins, but is essential also in regulating a host of cell signaling pathways involved in proliferation, adaptation to stress, regulation of cell size, and cell death. During the development of the cardiovascular system, the UPS regulates cell signaling by modifying transcription factors, receptors, and structural proteins. Later, in the event of cardiovascular diseases as diverse as atherosclerosis, cardiac hypertrophy, and ischemia reperfusion injury, ubiquitin ligases and the proteasome are implicated in protecting and exacerbating clinical outcomes. However, when misfolded and damaged proteins are ubiquitinated by the UPS, their destruction by the proteasome is not always possible due to their aggregated confirmations. Recent studies have discovered how these ubiquitinated misfolded proteins can be destroyed by alternative “specific” mechanisms. The cytosolic receptors p62, NBR, and HDAC6 recognize aggregated ubiquitinated proteins and target them for autophagy in the process of “selective autophagy”. Even the ubiquitination of multiple proteins within whole organelles that drive the more general macro-autophagy may be due, in part, to similar ubiquitin-driven mechanisms. In summary, the cross-talk between the UPS and autophagy highlight the pivotal and diverse roles the UPS plays in maintaining protein quality control and regulating cardiovascular development and disease.

Willis, Monte S.; Townley-Tilson, W.H. Davin; Kang, Eunice Y.; Homeister, Jonathon W.; Patterson, Cam



Nuclear magnetic resonance imaging of the cardiovascular system: normal and pathologic findings  

SciTech Connect

Whole body nuclear magnetic resonance (NMR) imaging of the cardiovascular system was carried out in early clinical trials in 244 volunteers and patients using a 3.5 KGauss (0.35 T) unit. The spin echo technique with multiple imaging parameters was used. Blood vessels were clearly discriminated from solid organs and lesions because little or no intraluminal signal is seen with laminar blood flow at normal velocities, whereas a more intense image is generated by solid organs. Characteristic flow signals were observed in normal patients and were accentuated by varying the imaging parameters. Cardiac chambers were well delineated in some patients on nongated images. In one case, internal topography of the ventricles was exquisitely displayed on a gated image. Intraluminal pathology, such as dissection of the aorta, aneurysms of the aorta and left ventricle, and aortic atheroma, was clearly demonstrated. Patency of coronary arterial bypass grafts was shown. Abnormal flow patterns due to slow or turbulent flow were accentuated on images using the second spin echo. The preliminary experience indicated the considerable potential of NMR imaging in the evaluation of cardiovascular disease.

Herfkens, R.J.; Higgins, C.B.; Hricak, H.; Lipton, M.J.; Crooks, L.E.; Lanzer, P.; Botvinick, E.; Brundage, B.; Sheldon, P.E.; Kaufman, L.



Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system  

PubMed Central

Peroxisome-proliferator-activated receptors (PPARs) comprise three subtypes (PPAR?, ? and ?) to form a nuclear receptor superfamily. PPARs act as key transcriptional regulators of lipid metabolism, mitochondrial biogenesis, and anti-oxidant defense. While their roles in regulating lipid metabolism have been well established, the role of PPARs in regulating redox activity remains incompletely understood. Since redox activity is an integral part of oxidative metabolism, it is not surprising that changes in PPAR signaling in a specific cell or tissue will lead to alteration of redox state. The effects of PPAR signaling are directly related to PPAR expression, protein activities and PPAR interactions with their coregulators. The three subtypes of PPARs regulate cellular lipid and energy metabolism in most tissues in the body with overlapping and preferential effects on different metabolic steps depending on a specific tissue. Adding to the complexity, specific ligands of each PPAR subtype may also display different potencies and specificities of their role on regulating the redox pathways. Moreover, the intensity and extension of redox regulation by each PPAR subtype are varied depending on different tissues and cell types. Both beneficial and adverse effects of PPAR ligands against cardiovascular disorders have been extensively studied by many groups. The purpose of the review is to summarize the effects of each PPAR on regulating redox and the underlying mechanisms, as well as to discuss the implications in the cardiovascular system.

Kim, Teayoun; Yang, Qinglin



Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status  

PubMed Central

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.

Ma, Terry KW; Kam, Kevin KH; Yan, Bryan P; Lam, Yat-Yin



Autonomic nervous system-dependent and -independent cardiovascular effects of exendin-4 infusion in conscious rats  

PubMed Central

Background and purpose: Glucagon-like peptide-1 (GLP) receptor agonists are promising therapeutic agents for the treatment of type II diabetes, but effects other than those on glucoregulation need assessing. Cardiovascular actions of bolus doses of the GLP receptor agonist exendin-4 have been reported, but to date the effects of continuous infusions have not been described. Experimental approach: The regional haemodynamic effects and possible underlying mechanisms of 6?h infusions of exendin-4 were measured in conscious, chronically instrumented rats. Key results: A 6?h infusion of exendin-4 (up to 6?pmol?kg?1?min?1) only modestly influenced blood pressure, but caused substantial, opposing, regionally selective vascular effects and tachycardia. A major involvement of ?-adrenoceptors in the vasodilator and cardiac effects was identified, with little or no direct contribution from ?-adrenoceptors to the vasoconstriction seen. Under conditions where ?- and ?-adrenoceptors were antagonized, or when ganglionic transmission was blocked, a marked vasoconstrictor effect of exendin-4 was revealed in the mesenteric and hindquarters vascular beds (about 50% fall in vascular conductances). No role for endogenous angiotensin II, vasopressin, endothelin, neuropeptide Y or prostanoids could be shown in these vasoconstrictor actions of exendin-4. Conclusions and implications: The results show not only an important involvement of the autonomic nervous system in the cardiovascular actions of exendin-4 infusion but also an underlying non-autonomically mediated vasoconstrictor action, the mechanism of which remains to be identified.

Gardiner, S M; March, J E; Kemp, P A; Bennett, T



Markers of Systemic Bacterial Exposure in Periodontal Disease and Cardiovascular Disease Risk: A Systematic Review and Meta-Analysis  

Microsoft Academic Search

Background: Recent meta-analyses reported a weak associ- ation between periodontal disease (PD) on clinical examination and cardiovascular disease (CVD). Systemic bacterial expo- sure from periodontitis, which correlates poorly with the clinical examination, has been proposed as the more biologically perti- nent risk factor. The purpose of this study was to review and analyze the association between PD with elevated systemic

Indra Z. Mustapha; Sarah Debrey; Michael Oladubu; Richard Ugarte



Cardiovascular parameters and scoring systems in the evaluation of response to therapy in sepsis and septic shock  

Microsoft Academic Search

Summary In 47 medical and postoperative ICU patients with 57 episodes of sepsis and septic shock, cardiovascular parameters including systemic vascular resistance (SVR), cardiac index (CI), stroke volume index (SVI), left ventricular stroke work index (LVSWI) as well as six scoring systems (APACHE II, Elebute, Goris, HIS, SAPS and SSS) were studied regarding their usefulness in the assessment of disease

G. Pilz; K. Werdan



A Computational Cardiovascular Model for Characterizing Arterial pulses under Various Physiopathological Conditions  

Microsoft Academic Search

\\u000a Arterial pulse is one of the most important biosignals monitored in clinics for diagnosing cardiovascular disease. Despite\\u000a the many past efforts attempted to correlate characteristics of arterial pulse with cardiovascular diseases, the precise characteristics\\u000a of arterial pulse that best predict the risk of cardiovascular disease yet remain a subject of considerable debate. This is\\u000a due to the fact that arterial

Fuyou Liang; Shu Takagi; Ryutaro Himeno; Hao Liu


System for clinical research and clinical management of cardiovascular risk using ambulatory blood pressure monitoring and actigraphy  

US Patent & Trademark Office Database

Disclosed embodiments include a web-enabled system especially adapted for clinical research and clinical management of cardiovascular risk using ambulatory blood pressure monitoring (ABPM) data, actigraphy data, and clinical data. According to a disclosed embodiment the web-enabled system comprises (a) a web-enabled graphical user interface to enable a user to securely authenticate, securely upload clinical data, and navigate through a plurality of software modules; (b) a database to store user profiles, protocols, clinical data, ambulatory blood pressure monitoring (ABPM) recordings, actigraphy recordings, research data, and study results; and (c) a plurality of statistical methods and analysis techniques especially designed to automatically analyze the clinical cardiovascular risk data, and create customized reports of the results designed to assess cardiovascular risk based on ABPM and actigraphy.

Mojon Ojea; Artemio (Vigo, ES); Hermida Dominguez; Ramon (Vigo, ES); Fernandez Bernardez; Jose Ramon (Vigo, ES)



Relative activities of atenolol and metoprolol on the cardiovascular system of man.  


The effects or oral atenolol (100 mg once/day) and metoprolol (100 mg once/day, 100 mg twice/day and 300 mg once/day) have been compared with placebo on the heart rate and systolic blood pressure responses to exercise in 5 healthy volunteers. The drugs were given for 5 days in a double blind randomised fashion with each volunteer receiving each dose of drug. Measurements were made after the first dose on day 1 and after 5 days of dosing. The results on both heart rate and systolic blood pressure showed that overall (over a 24 h period) after acute (day 1) or after chronic (5 days) dosing, atenolol 100 mg once/day, metoprolol 100 mg twice/day and 300 mg once/day, were equivalent as beta-adrenoceptor blocking doses. Thus milligram for milligram atenolol and metoprolol do not produce equivalent blockade on the cardiovascular system of man. PMID:7308277

Harry, J D; Cruickshank, J M; Young, J; Barker, N



Pharmacological Studies on Myrica rubra Sieb et zucc. Effects on the Cardiovascular System and Platelets.  


The effects of 50% Drink of Myrica rubra (MRD) on the cardiovascular system of the rat and on the platelets aggregation of rats and guinea pigs were studied.Different groups of male Wistar rats were treated either with 50% Myrica rubra drink as drinking vehicle (4 weeks) or water. The animals were then prepared for the measurement of arterial blood pressure and heart rate, ECG, sensitivity of the baroreceptors, platelets' aggregation, blood clotting time and cardiac parasympathetic ganglia. The mechanism of action of any induced effect was elucidated using different receptor blockers.Treatment induced a significant decrease in the arterial blood pressure and heart rate on Wistar rats, but no significant changes in the ECG were observed. Pretreatment of rats with MRD 10 or 20 ml/kg (i. p.) significantly suppressed vagal electrical stimulation to the heart and nicotine-induced bradycardia, via decreasing phenylephrine-induced rise in the arterial blood pressure and the reflexly-induced bradycardia. It significantly suppressed the Baroreceptor Sensitivity Index (BSI). The treatment also significantly suppressed ADP-induced platelets aggregation in rats and arachidonic acid-induced aggregation in guinea pigs.All these actions seemed to be mediated by the MRD constituents such as proanthocyanidins, polyphenols and flavonoids. The decreases in the heart rate and BSI were probably caused by an inherent ability to block the parasympathetic ganglia.The results of this study regarding the effects of MRD actions on the cardiovascular system and platelets qualify the drink to be classified as a functional food. PMID:23804250

Alajmi, M F; Al-Hadiya, B M; El Tahir, K E H



Cardiovascular effect of peripheral injected melittin in normotensive conscious rats: Mediation of the central cholinergic system.  


Recently we demonstrated that centrally administrated melittin, a phospholipase A(2) (PLA(2)) activator, caused the pressor effect in normotensive, conscious rats. In the present study, we aimed to determine the cardiovascular effect of peripherally injected melittin and the involvement of the central cholinergic system on these effects in the normotensive conscious rats. For this reason, 250, 500 or 1000microg/kg doses of melittin were injected intraperitoneally to normotensive male Sprague Dawley rats. Melittin produced dose- and time-dependent increases in mean arterial pressure (MAP) and heart rate (HR). Both peripheral (5mg/kg; i.p.) and central (500microg; i.c.v.) pretreatment with indomethacin, nonselective inhibitor of cyclooxygenase (COX) 1 and 2, totally abolished cardiovascular effect of melittin. Intraperitoneal (i.p.) pretreatment with propranolol, a nonselective beta-adrenergic receptor blocker, completely abolished the tachycardic response to melittin. Also, the pressor effect of melittin was partially attenuated in these rats. In order to test the mediation of the central cholinergic system on the pressor and tachycardic effects of melittin, the rats were pretreated with atropine sulfate (10microg; i.c.v.), a cholinergic nonselective muscarinic receptor antagonist, mecamylamine (50microg; i.c.v.), a cholinergic nonselective nicotinic receptor antagonist, methyllycaconitine (10microg; i.c.v.) or alpha-bungarotoxin (10microg; i.c.v.), selective antagonists of alpha7 subtype nicotinic acetylcholine receptors (alpha7nAChRs) 15min prior to melittin (500microg/kg; i.p.) injection. Pretreatment with mecamylamine, methyllycaconitine or alpha-bungarotoxin partially diminished the pressor and tachycardic response to melittin in the normotensive conscious rats whereas pretreatment with atropine sulfate had no effect. In conclusion, our data demonstrate that peripherally administered melittin exerts a clear pressor and tachycardic effect by activating COX pathway. The activation of central cholinergic nicotinic receptors, predominantly alpha7nAChRs, appears to be involved in the pressor and tachycardic effects of the drug. PMID:19910175

Yalcin, Murat; Aydin, Cenk; Savci, Vahide



Transgenic animals in cardiovascular disease research.  


Worldwide, the highest morbidity and mortality results from such cardiovascular diseases as hypertension, myocardial infarction, cardiac and renal failure, as well as stroke. Since the cardiovascular system and its regulation is quite complex, study of these disorders has been grossly limited to whole organism models. As a result, in recent years, transgenic technology has played a significant role in the discovery of specific gene products for cardiovascular regulation and disease aetiology. Genetic manipulation in rats and mice has altered the expression of numerous genes. In this review, some of the important new genetically modified animals (i.e. transgenic models) with alterations in hormone and second messenger systems involved in cardiovascular regulation are summarized. PMID:11187966

Bader, M; Bohnemeier, H; Zollmann, F S; Lockley-Jones, O E; Ganten, D



Cardiovascular microbubble transport in vessel bifurcations with pulsatile flow: experimental model and theory  

NASA Astrophysics Data System (ADS)

The behavior of long gas bubbles suspended in liquid flowing through successive bifurcations was investigated experimentally and theoretically as a model of cardiovascular bubble transport in gas embolotherapy. In this developmental cancer therapy, perflurocarbon droplets are vaporized in the vasculature and travel through a bifurcating network of vessels before lodging. The homogeneity of tumor necrosis is directly correlated with the transport and lodging of the emboli. An experimental model was used to explore the effects of flow pulsatility, frequency, gravity, and bifurcation roll angle on bubble splitting and lodging. At a bifurcation roll angle of 45-degrees, the most distinct difference in splitting ratios between three physiologic frequencies (1, 1.5, 2 Hz) was observed. As roll angle increased, lodged bubble volume in the first generation channel increased while bubble volume beyond the second bifurcation proportionately decreased. A corresponding time-dependent one-dimensional theoretical model was also developed. The results elucidate the effects of pulsatile flow and suggest the potential of gas embolotherapy to occlude blood flow to tumors.

Valassis, Doug; Dodde, Robert; Eshpuniyani, Brijesh; Fowlkes, J. Brian; Bull, Joseph



A Double-Edged Sword Role for Ubiquitin-Proteasome System in Brain Stem Cardiovascular Regulation During Experimental Brain Death  

PubMed Central

Background Brain stem cardiovascular regulatory dysfunction during brain death is underpinned by an upregulation of nitric oxide synthase II (NOS II) in rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from blood pressure of comatose patients that disappears before brain death ensues. Furthermore, the ubiquitin-proteasome system (UPS) may be involved in the synthesis and degradation of NOS II. We assessed the hypothesis that the UPS participates in brain stem cardiovascular regulation during brain death by engaging in both synthesis and degradation of NOS II in RVLM. Methodology/Principal Findings In a clinically relevant experimental model of brain death using Sprague-Dawley rats, pretreatment by microinjection into the bilateral RVLM of proteasome inhibitors (lactacystin or proteasome inhibitor II) antagonized the hypotension and reduction in the life-and-death signal elicited by intravenous administration of Escherichia coli lipopolysaccharide (LPS). On the other hand, pretreatment with an inhibitor of ubiquitin-recycling (ubiquitin aldehyde) or ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1) potentiated the elicited hypotension and blunted the prevalence of the life-and-death signal. Real-time polymerase chain reaction, Western blot, electrophoresis mobility shift assay, chromatin immunoprecipitation and co-immunoprecipitation experiments further showed that the proteasome inhibitors antagonized the augmented nuclear presence of NF-?B or binding between NF-?B and nos II promoter and blunted the reduced cytosolic presence of phosphorylated I?B. The already impeded NOS II protein expression by proteasome inhibitor II was further reduced after gene-knockdown of NF-?B in RVLM. In animals pretreated with UCH-L1 inhibitor and died before significant increase in nos II mRNA occurred, NOS II protein expression in RVLM was considerably elevated. Conclusions/Significance We conclude that UPS participates in the defunct and maintained brain stem cardiovascular regulation during experimental brain death by engaging in both synthesis and degradation of NOS II at RVLM. Our results provide information on new therapeutic initiatives against this fatal eventuality.

Wu, Carol H. Y.; Chan, Julie Y. H.; Chan, Samuel H. H.; Chang, Alice Y. W.



General pharmacology of IY-80843, a new H 2 -receptor antagonist: Effects on the central nervous and cardiovascular systems  

Microsoft Academic Search

IY-80843, N-[2-(2-Methoxyphenyl)ethyl]-N?-[4-(Imidazole-4-yl) phenyl] formamidine, is a new potent H2-receptor antagonist. The potential secondary pharmacologic effects of this agent, on the central nervous and cardiovascular\\u000a systems were studied. IY-80843 caused ptosis, suppression of locomotion, hypothermia, prolongation of sleeping time and hypotensive\\u000a effects in mice, rats and dogs. These results suggest that IY-80843 affects the function of the central nervous and cardiovascular

Eun Joo Kim; Hwa Sup Shin; Shi Yong Ryu; Byung Ho Lee; Soon Hyun Cho



Modeling AGV systems  

Microsoft Academic Search

Computer simulation is often used as an analysis tool during the design of Automated Guided Vehicle (AGV) systems. However, because of the complexities inherent in automated material handling systems, general-purpose simulation languages must be used creatively to capture the desired detail in the model. This paper presents some general concepts which can be used to model AGV systems. Also, some

Deborah A. Davis; Calder Sq



External System Modeling  

Microsoft Academic Search

In this thesis a novel design strategy is presented. The key elements of the design strategy comprise the modeling of the physical sources, the separation of the system into the design component and the external system, the characterization of the external system as a complex source, and finally the use of the complex source\\/design component model to optimize the performance

Bryce Kevin Gardner



Autonomic Nervous System Activity and Decline as Prognostic Indicators of Cardiovascular and Cerebrovascular Events: The ‘PROOF’ Study  

Microsoft Academic Search

Background: Transversal studies have underlined the association between the decline in autonomic nervous system (ANS) activity and all-cause mortality. However, the predictive value of ANS has never been prospectively assessed in a general population-based cohort. Method: The PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events) cohort study was designed to prospectively assess the predictive value of ANS activity level in

Jean-Claude Barthélémy; Vincent Pichot; Virginie Dauphinot; Sébastien Celle; Bernard Laurent; Arnauld Garcin; Delphine Maudoux; Judith Kerleroux; Jean-René Lacour; Michel Kossovsky; Jean-Michel Gaspoz; Frédéric Roche



First-Year Medical Students' Conceptual Understanding of and Resistance to Conceptual Change Concerning the Central Cardiovascular System  

ERIC Educational Resources Information Center

|Medical students often have initial understanding concerning medical domains, such as the central cardiovascular system (CCVS), when they enter the study programme. These notions may to some extent be in conflict with scientific understanding, which can be seen as a challenge for medical teaching. Hence, the purpose of this study was to analyse…

Mikkila-Erdmann, Mirjamaija; Sodervik, Ilona; Vilppu, Henna; Kaapa, Pekka; Olkinuora, Erkki



The role of endothelin system in cardiovascular disease and the potential therapeutic perspectives of its inhibition.  


Since its identification in 1988 and the recognition of its primary role as a potent vasoconstrictor, endothelin has been extensively studied and is now considered as a ubiquitous protein, involved in important aspects of human homeostasis as well as in several pathophysiological pathways, mostly associated with cardiovascular disease. From an evolutionary point of view, endothelin consists a primitive molecule with the rare characteristic of being exactly the same in all mammals, thus permitting scientists to perform experiments in animals and doing predictions for humans. The understanding of its contribution to the genesis, evolution and maintenance of disease through activation of special receptor subtypes has led to the development of both selective and unselective receptor antagonists. Despite the disappointing results of these antagonists in the field of heart failure, almost from the initial animal trials of bosentan, a dual endothelin receptor antagonist, in pulmonary arterial hypertension, it has been demonstrated that the drug leads at least to hemodynamic and clinical improvement of the patients, thus receiving official approval for the management of this rare but eventually lethal disease. Resistant hypertension is another area where endothelin receptor blockers might potentially play a role, while the pathophysiological role of endothelin in atherosclerotic coronary artery disease is well-established and the relative research goes on. The main goal of this review is to describe the endothelin system and mostly to enlighten its role in pathophysiologic pathways, as well to state the relative research in the various fields of cardiovascular disease and also highlight its prognostic significance wherever there exists one. PMID:23470073

Kaoukis, Andreas; Deftereos, Spyridon; Raisakis, Konstantinos; Giannopoulos, Georgios; Bouras, Georgios; Panagopoulou, Vasiliki; Papoutsidakis, Nikolaos; Cleman, Michael W; Stefanadis, Christodoulos



O-GlcNAcylation and oxidation of proteins: is signalling in the cardiovascular system becoming sweeter?  


O-GlcNAcylation is an unusual form of protein glycosylation, where a single-sugar [GlcNAc (N-acetylglucosamine)] is added (via ?-attachment) to the hydroxyl moiety of serine and threonine residues of nuclear and cytoplasmic proteins. A complex and extensive interplay exists between O-GlcNAcylation and phosphorylation. Many phosphorylation sites are also known glycosylation sites, and this reciprocal occupancy may produce different activities or alter the stability in a target protein. The interplay between these two post-translational modifications is not always reciprocal, as some proteins can be concomitantly phosphorylated and O-GlcNAcylated, and the adjacent phosphorylation or O-GlcNAcylation can regulate the addition of either moiety. Increased cardiovascular production of ROS (reactive oxygen species), termed oxidative stress, has been consistently reported in various chronic diseases and in conditions where O-GlcNAcylation has been implicated as a contributing mechanism for the associated organ injury/protection (for example, diabetes, Alzheimer's disease, arterial hypertension, aging and ischaemia). In the present review, we will briefly comment on general aspects of O-GlcNAcylation and provide an overview of what has been reported for this post-translational modification in the cardiovascular system. We will then specifically address whether signalling molecules involved in redox signalling can be modified by O-GlcNAc (O-linked GlcNAc) and will discuss the critical interplay between O-GlcNAcylation and ROS generation. Experimental evidence indicates that the interactions between O-GlcNAcylation and oxidation of proteins are important not only for cell regulation in physiological conditions, but also under pathological states where the interplay may become dysfunctional and thereby exacerbate cellular injury. PMID:22757958

Lima, Victor V; Spitler, Kathryn; Choi, Hyehun; Webb, R Clinton; Tostes, Rita C



Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome?  

Microsoft Academic Search

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



Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems  

Microsoft Academic Search

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



[Biomarkers and risk factors of cardiovascular system disease in diabetics type 2].  


The content of glycated hemoglobin, a biomarker of diabetes in patients with type 2 diabetes correlates with risk factors for cardiovascular disease: hypertension, BMI and ratio of total cholesterol to HDL cholesterol. Therefore, increase in glycosylated hemoglobin should be considered a predictor of cardiovascular disease in patients with type 2 diabetes. PMID:23951913


A simulation model to investigate the impact of cardiovascular risk in renal transplantation.  


Premature cardiovascular (CV) disease is the leading cause of death following renal transplantation and, as a consequence of death with a functioning graft, it is a major cause of graft loss. Renal transplant recipients have a high prevalence of CV risk factors that influence both patient and graft survival. We used data on the relationship between CV risk factors and graft and patient survivals to develop a discrete event simulation model to study the possible impact of CV risk factor reduction on transplant outcome. The simulation was based on a renal unit in a population that has the risk factor profile of patients from the West of Scotland. We studied the dynamic between patient numbers on the waiting list compared to the transplanted list. After establishing results pertinent to the renal unit, we investigated in what way potential changes to transplant policy affected patient numbers. These perturbations included changing the number of transplants performed, changing the incidence of acute rejection, and interventional policies where patients on the waiting list were selectively transplanted taking into account their CV risk factor profiles. Overall, the model predicts that reducing CV risk in the population with end-stage renal failure awaiting kidney transplantation will have comparable benefits to foreseeable developments in immunosuppression or attainable increases in transplant numbers. Moreover, addressing CV risk has benefits for all patients regardless of whether or not they ultimately receive a kidney transplant. PMID:15964361

McLean, D R; Jardine, A G



Exposure Analysis Modeling System  

EPA Science Inventory

The Exposure Analysis Modeling System (EXAMS) is an interactive software application for formulating aquatic ecosystem models and evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals including pesticides, industrial materials, and leachates f...


Cardiovascular health promotion for children: a model for a Parish (County)-wide program (implementation and preliminary results).  


Cardiovascular (CV) risk factors in childhood result in a lifetime burden on the CV system. The Bogalusa Heart Study, a prevention program for children, addresses behaviors and lifestyles associated with CV risk. This prevention program utilizes the substructure of a Parish (County) that can be a model for other areas. All aspects in educating school children-the classroom, physical activity, cafeteria, teachers, and parents with community involvement-are included. The program requires cooperation of parents, schools, physicians, and political and business personnel. Their collaboration helps implement and sustain the program. Understanding the origin of coronary artery disease, hypertension, diabetes, and now the obesity epidemic shows the need to develop a framework for improving lifestyles and behaviors beginning in childhood. In addition to nutrition and exercise, the program addresses tobacco, alcohol, and drug use, and societal problems such as dropping out of school, violent behavior, and teenage pregnancy. An initial accomplishment is the entry into all elementary schools, representing approximately 7000 children. Early results show reduction in obesity, increased physical activity, improved decision making, and healthy attitudes. This public health model is inexpensive by utilizing prior research findings and integrating into community resources. Health education of children is an important aspect of preventive cardiology with a need for pediatric and adult cardiologists' involvement. PMID:20021623

Berenson, Gerald S



The role of adenosine in the respiratory and cardiovascular response to systemic hypoxia in the rat.  

PubMed Central

1. In rats anaesthetized with Saffan we have studied the effects of the adenosine receptor antagonists, theophylline and 8-phenyltheophylline, upon the respiratory and cardiovascular responses evoked by 5 min periods of systemic hypoxia. 2. In the group of animals that were to receive theophylline (15 mg kg-1 i.v.), arterial O2 pressure (Pa,O2) fell from 83 +/- 2 mmHg during air breathing to 38 +/- 3 or 34 +/- 3 mmHg during the 5th minute of two different control periods of hypoxia, while in the group that were to receive 8-phenyltheophylline (10 mg kg-1 i.v.), Pa,O2 fell from 83 +/- 1 to 53 +/- 2 mmHg. Neither drug significantly altered the levels of Pa,O2 reached during hypoxia. 3. During the control periods of hypoxia respiration increased, but the increase evoked at the 5th minute was significantly less than that evoked at the 2nd minute of hypoxia. This secondary waning of the hyperventilation was abolished by both drugs. 4. Similarly, both drugs attenuated the tendency for the hypoxia-induced tachycardia to wane between the 2nd and 5th minute. 5. Further, both drugs substantially reduced both the hypoxia-induced fall in arterial pressure and the increases in vascular conductance in hindlimb muscle, carotid vasculature and kidney. 6. Thus, we propose that in the rat the release of adenosine by hypoxic tissues makes a major contribution to the secondary decrease in respiration and heart rate that occurs during systemic hypoxia and to the accompanying vasodilatation in muscle and fall in arterial pressure. The effects of the adenosine antagonists on the carotid and renal vasculature are more equivocal and may be partly explained as a smaller autoregulatory dilatation to a smaller fall in systemic arterial pressure. 7. These results and proposals are discussed in relation to the conditions that are known to cause release of adenosine and in relation to its known effects upon the respiratory and cardiovascular systems.

Neylon, M; Marshall, J M



Salud para su Corazón: a community-based Latino cardiovascular disease prevention and outreach model.  


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: (1) to design an intervention model appropriate to Latino populations; (2) to pilot test the model in a specific community with the objectives of increasing awareness about heart disease, raising knowledge about CVD prevention, and promoting heart-healthy lifestyles; and (3) to disseminate the model and the materials developed to other communities with similar needs. An agency-community partnership, under the leadership of the Community Alliance for Heart Health, guided all stages of the community intervention project. The multimedia bilingual community intervention included television telenovela format public service announcements (PSAs), radio programs, brochures, recipe booklets, charlas, a promotores training manual, and motivational videos. An evaluation survey assessed the impact of the intervention. A pre-post intervention survey was conducted with more than 300 participants, and results showed that the respondents were substantially more aware of risk factors for CVD, and had greatly increased their knowledge of ways to prevent heart disease. Dissemination efforts have resulted in numerous requests by health organizations, universities, and health maintenance organizations (HMOs) for educational materials and communication strategies produced by Salud para su Corazón. In addition, Univision, the largest Spanish-language broadcast television network, is airing the initiative's PSAs. Also, training seminars for promotores are being conducted in different regions of the United States, and several locations are planning to replicate this study. PMID:10555925

Alcalay, R; Alvarado, M; Balcazar, H; Newman, E; Huerta, E



Genetic Models in Applied Physiology: Invited Review: Identifying new mouse models of cardiovascular disease: a review of high-throughput screens of mutagenized and inbred strains  

Microsoft Academic Search

The mouse is a proven model for studying human disease. Many strains exist that exhibit either natural or engineered genetic variation and thereby enable the elucidation of pathways involved in the development of cardiovascular disease. Although those mouse models have been fundamental to advancing our knowledge base, we are still at an early stage in understanding how genes contribute to

K L Svenson; M A Bogue; L L Peters




EPA Science Inventory

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 ...


Strategic integration of in vivo cardiovascular models during lead optimization: predictive value of 4 models independent of species, route of administration, and influence of anesthesia.  


The strategic integration of in vivo cardiovascular models is important during lead optimization to enable a wide therapeutic index for cardiovascular safety. However, under what conditions (eg, species, route of administration, anesthesia) studies should be performed to drive go/no-go is open to interpretation. Two compounds, torcetrapib and a novel steroid hormone mimetic (SHM-1121X), both with off-target cardiovascular liabilities, were profiled in 4 in vivo cardiovascular models. Overlapping plasma concentrations of torcetrapib were achieved in all models tested; values ranged from therapeutic to supratherapeutic. In anesthetized rats, intravenous torcetrapib elicited dose-dependent increases in mean arterial pressure (MAP; 2-18 mm Hg above vehicle during the low- and high-dose infusion), and in anesthetized dogs, torcetrapib increased MAP from 4 to 22 mm Hg. In conscious rats, a single oral dose of torcetrapib increased MAP from 10 to 18 mm Hg in the low-dose and high-dose groups, respectively, whereas in conscious dogs, MAP increased from 3 to 12 mm Hg. SHM-1121X produced marked hypotension in the same models. Pharmacokinetic-pharmacodynamic analysis demonstrated strong correlation across the models tested for both compounds. Results suggest that equivalency across models allows for flexibility to address key issues and enable go/no-go during lead optimization without concern for discordant results. The predictive value of each model was validated with torcetrapib and, when put into practice, led to a decisive no-go for SHM-1121X. PMID:22179024

Fryer, Ryan M; Harrison, Paul C; Muthukumarana, Akalushi; Nodop Mazurek, Suzanne G; Ng, Khing Jow; Chen, Rong Rhonda; Harrington, Kyle E; Dinallo, Roger M; Chi, Liguo; Reinhart, Glenn A



A Model of Cardiovascular Disease Giving a Plausible Mechanism for the Effect of Fractionated Low-Dose Ionizing Radiation Exposure  

PubMed Central

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.

Little, Mark P.; Gola, Anna; Tzoulaki, Ioanna



Cardiovascular Surgery. Guideline Series.  

National Technical Information Service (NTIS)

Guidelines adopted by the Health Systems Agency of Southwestern Pennsylvania to facilitate the development of a community-oriented system of quality cardiovascular surgery are presented. Using the guidelines, subarea planning councils, in collaboration wi...



Virtual clay modeling system  

Microsoft Academic Search

This paper describes a CAD system in which a user can directly manipulate the shape of a virtual object like a clay model and can produce its solid model data. The key component of its hardware is a special input device with a 3D position tracker and a tactile sensor. In this system, the movement of a virtual object is

Ken-ichi Kameyama



Polyphenols: benefits to the cardiovascular system in health and in aging.  


Numerous studies have demonstrated the importance of naturally occurring dietary polyphenols in promoting cardiovascular health and emphasized the significant role these compounds play in limiting the effects of cellular aging. Polyphenols such as resveratrol, epigallocatechin gallate (EGCG), and curcumin have been acknowledged for having beneficial effects on cardiovascular health, while some have also been shown to be protective in aging. This review highlights the literature surrounding this topic on the prominently studied and documented polyphenols as pertaining to cardiovascular health and aging. PMID:24077237

Khurana, Sandhya; Venkataraman, Krishnan; Hollingsworth, Amanda; Piche, Matthew; Tai, T C



Erythropoietin Promotes Deleterious Cardiovascular Effects and Mortality Risk in a Rat Model of Chronic Sports Doping  

Microsoft Academic Search

Athletes who abuse recombinant human erythropoietin (rhEPO) consider only the benefit to performance and usually ignore the\\u000a potential short and long-term liabilities. Elevated haematocrit and dehydratation associated with intense exercise may reveal\\u000a undetected cardiovascular risk, but the mechanisms underlying it remain to be fully explained. This study aimed to evaluate\\u000a the cardiovascular effects of rhEPO in rats under chronic aerobic

Nuno Piloto; Helena M. Teixeira; Edite Teixeira-Lemos; Belmiro Parada; Patrícia Garrido; José Sereno; Rui Pinto; Lina Carvalho; Elísio Costa; Luís Belo; Alice Santos-Silva; Frederico Teixeira; Flávio Reis



Using a Telemedicine System to Decrease Cardiovascular Disease Risk in an Underserved Population: Design, Use, and Interim Results  

Microsoft Academic Search

Cardiovascular disease is the leading cause of morbidity and mortality in the USA. Disease management programs, while successful, are intensive and expensive. Follow-up is often inadequate, incomplete, and inconsistent. To address these problems, we developed an Internet- Telemedicine system. Patients send\\/receive data to\\/from their care provider via the Internet. The system optimizes function and minimizes cost (all hardware is off

William P. Santamore; Carol J. Homko; Abul Kashem; Timothy R. McConnell; A. A. Bove



Construction of a three-dimensional model of cardiovascular disease and deployment of a new method of fostering patient adherence to instruction  

PubMed Central

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.

Nakano, Masuyo; Shirotake, Shoichi



Share and enjoy: anatomical models database-generating and sharing cardiovascular model data using web services.  


Sharing data between scientists and with clinicians in cardiac research has been facilitated significantly by the use of web technologies. The potential of this technology has meant that information sharing has been routinely promoted through databases that have encouraged stakeholder participation in communities around these services. In this paper we discuss the Anatomical Model Database (AMDB) (Gianni et al. Functional imaging and modeling of the heart. Springer, Heidelberg, 2009; Gianni et al. Phil Trans Ser A Math Phys Eng Sci 368:3039-3056, 2010) which both facilitate a database-centric approach to collaboration, and also extends this framework with new capabilities for creating new mesh data. AMDB currently stores cardiac geometric models described in Gianni et al. (Functional imaging and modelling of the heart. Springer, Heidelberg, 2009), a number of additional cardiac models describing geometry and functional properties, and most recently models generated using a web service. The functional models represent data from simulations in geometric form, such as electrophysiology or mechanics, many of which are present in AMDB as part of a benchmark study. Finally, the heartgen service has been added for producing left or bi-ventricle models derived from binary image data using the methods described in Lamata et al. (Med Image Anal 15:801-813, 2011). The results can optionally be hosted on AMDB alongside other community-provided anatomical models. AMDB is, therefore, a unique database storing geometric data (rather than abstract models or image data) combined with a powerful web service for generating new geometric models. PMID:23436208

Kerfoot, Eric; Lamata, Pablo; Niederer, Steve; Hose, Rod; Spaan, Jos; Smith, Nic



Mathematical model of cardiovascular mechanics for diagnostic analysis and treatment of heart failure: Part 2. Analysis of vasodilator therapy and planning of optimal drug therapy.  


Using a mathematical model of cardiovascular mechanics, various complicated responses to vasodilator therapy for heart failure have been well accounted for through common logic: (i) the differential effects of various vasodilators on cardiac output; (ii) the opposite response of cardiac output to sodium nitroprusside in a normal state and heart failure state; (iii) the different responses of cardiac index, arterial pressure and left ventricular end-diastolic pressure to hydralazine in different types of heart failure. The response to combined vasodilator-inotropic agent therapy was simulated well by the model. The optimal therapeutic regimen was then formulated to simultaneously control the cardiac output, systemic and pulmonary arterial and venous pressures, and the degree of coronary ischaemia by multiple drug delivery, and the problem was solved using the model. We conclude that the model provides a useful basis for obtaining a guidance for more appropriate therapeutic regimen in heart failure. PMID:8182956

Tsuruta, H; Sato, T; Ikeda, N



Testing a model of physical activity and obesity tracking from youth to adulthood: the cardiovascular risk in young Finns study  

Microsoft Academic Search

Objective:To test a potential model of the relationship between physical activity and obesity from youth to adulthood.Design:Longitudinal study data from the cardiovascular risk in young Finns study.Subjects:A total of 1319 boys (n=626) and girls (n=693) aged 9, 12, 15 and 18 years were randomly selected from five university towns and their rural surroundings in 1980. They were followed up for

X Yang; R Telama; E Leskinen; K Mansikkaniemi; J Viikari; O T Raitakari



Arsenic-Induced Oxidative Stress: Evidence on In Vitro Models of Cardiovascular, Diabetes Mellitus Type 2 and Neurodegenerative Disorders  

Microsoft Academic Search

\\u000a This chapter provides an overview of the evidence of oxidative stress and compensatory responses in response to arsenic exposure\\u000a in diverse in vitro models of cardiovascular diseases, type 2 diabetes mellitus and neurodegenerative disorders. The studies\\u000a described here are recent approaches related to (1) the presence of oxidative and nitrosative damage; (2) the activation of\\u000a novel and sensitive oxidative stress

Rubén Ruíz-Ramos; Patricia Ostrosky-Wegman; Mariano E. Cebrián


Spectrofluorimetric methods of stability-indicating assay of certain drugs affecting the cardiovascular system  

NASA Astrophysics Data System (ADS)

Two stability-indicating spectrofluorimetric methods have been developed for the determination of ezetimibe and olmesartan medoxomil, drugs affecting the cardiovascular system, and validated in the presence of their degradation products. The first method, for ezetimibe, is based on an oxidative coupling reaction of ezetimibe with 3-methylbenzothiazolin-2-one hydrazone hydrochloride in the presence of cerium (IV) ammonium sulfate in an acidic medium. The quenching effect of ezetimibe on the fluorescence of excess cerous ions is measured at the emission wavelength, ?em, of 345 nm with the excitation wavelength, ?ex, of 296 nm. Factors affecting the reaction were carefully studied and optimized. The second method, for olmesartan medoxomil, is based on measuring the native fluorescence intensity of olmesartan medoxomil in methanol at ?em = 360 nm with ?ex = 286 nm. Regression plots revealed good linear relationships in the assay limits of 10-120 and 8-112 g/ml for ezetimibe and olmesartan medoxomil, respectively. The validity of the methods was assessed according to the United States Pharmacopeya guidelines. Statistical analysis of the results exposed good Student's t-test and F-ratio values. The introduced methods were successfully applied to the analysis of ezetimibe and olmesartan medoxomil in drug substances and drug products as well as in the presence of their degradation products.

Moussa, B. A.; Mohamed, M. F.; Youssef, N. F.



Increased proteoglycan synthesis by the cardiovascular system of coarctation hypertensive rats  

SciTech Connect

Proteoglycan (PG) synthesis in the cardiovascular system of coarctation hypertensive rats was examined by in vivo and in vitro labeling of glycosaminoglycans with 35SO4 in rats made hypertensive for short (4 days) and longer (14 days) durations. With in vivo labeling, only tissues directly exposed to elevated pressure (left ventricle, LV and aorta above the clip, AOR increases) exhibited elevated PG synthesis after 4 days of hypertension. By 14 days, tissues both exposed to (LV and AOR increases) and protected from elevated pressure (right ventricle and kidney) exhibited elevated PG synthetic rates. Slight elevations in the proportion of galactosaminoglycans were observed with a concurrent proportional decrease in heparan sulfate PGs. Using the in vitro labeling procedure, no significant increases in PG synthesis were observed in any tissue at either 4 days or 14 days of hypertension. These data indicate that: (1) coarctation hypertension stimulates PG production that is dependent initially on increased pressure and later, on additional non-pressure related factors, (2) these other factors are responsible for enhanced PG production in tissues not directly exposed to pressure overload, (3) pressure and/or these other factors are essential for enhanced PG production in coarctation hypertension, and (4) synthesis of all GAG types appears to be affected.

Lipke, D.W.; Couchman, J.R. (Hypertension Program, University of Alabama, Birmingham (USA))



Effect of Intermittent Versus Continuous Parathyroid Hormone in the Cardiovascular System of Rats  

PubMed Central

Objective: PTH increases ionic calcium concentration in the serum, acting primarily on bone and kidney cells through the type 1 PTH receptor. Interestingly, PTH stimulates bone formation when administrated intermittently but causes severe bone loss with continuous administration. Daily injections of PTH are used as the most promising anabolic agent in the treatment of severe osteoporosis. Elevated PTH is reported an independent risk factor for left ventricle hypertrophy. Design: in rats we investigated the effect of intermittent and continuous administration of PTH on blood pressure, heart rate and development of cardiac hypertrophy and fibrosis. Results: We did not find PTH to induce heart hypertrophy. In contrast, continuous administration of PTH the mRNA level of a hypertrophic marker gene, atrial natriuretic peptide. When comparing the effect of continuously versus injected PTH collagen 1 mRNA was significantly higher in continuously treated animals. Conclusion: our data demonstrated a decrease in heart rate upon continuous administration of PTH in rats. No changes in blood pressure were observed. Moreover, neither intermittent nor continuous administration of PTH induced ventricular hypertrophy. But continuous PTH induced a marker of collagen 1. Thus, these data did not reveal any negative effects of the injection of PTH on the cardiovascular system.

Smajilovic, Sanela; Schaal-Jensen, Rasmus; Jabbari, Reza; Smajilovic, Una; Haunso, Stig; Tfelt-Hansen, Jacob



Circulating Endotoxemia: A Novel Factor in Systemic Inflammation and Cardiovascular Disease in Chronic Kidney Disease  

PubMed Central

Summary Background and objectives Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD). Design, setting, participants, & measurements Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival. Results Circulating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality. Conclusions CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients.

Harrison, Laura E.A.; Eldehni, M. Tarek; Jefferies, Helen J.; Szeto, Cheuk-Chun; John, Stephen G.; Sigrist, Mhairi K.; Burton, James O.; Hothi, Daljit; Korsheed, Shvan; Owen, Paul J.; Lai, Ka-Bik; Li, Philip K.T.



Effects of simulated microgravity on closed-loop cardiovascular regulation and orthostatic intolerance: analysis by means of system identification.  


Microgravity-induced orthostatic intolerance (OI) continues to be a primary concern for the human space program. To test the hypothesis that exposure to simulated microgravity significantly alters autonomic nervous control and, thus, contributes to increased incidence of OI, we employed the cardiovascular system identification (CSI) technique to evaluate quantitatively parasympathetic and sympathetic regulation of heart rate (HR). The CSI method analyzes second-to-second fluctuations in noninvasively measured HR, arterial blood pressure, and instantaneous lung volume. The coupling mechanisms between these signals are characterized by using a closed-loop model. Parameters reflecting parasympathetic and sympathetic responsiveness with regard to HR regulation can be extracted from the identified coupling mechanisms. We analyzed data collected from 29 human subjects before and after 16 days of head-down-tilt bed rest (simulated microgravity). Statistical analyses showed that parasympathetic and sympathetic responsiveness was impaired by bed rest. A lower sympathetic responsiveness and a higher parasympathetic responsiveness measured before bed rest identified individuals at greater risk of OI before and after bed rest. We propose an algorithm to predict OI after bed rest from measures obtained before bed rest. PMID:14514703

Xiao, Xinshu; Mukkamala, Ramakrishna; Sheynberg, Natalie; Grenon, S Marlene; Ehrman, Michael D; Mullen, Thomas J; Ramsdell, Craig D; Williams, Gordon H; Cohen, Richard J



Primary Human Cardiomyocyte Culture: A Model for Assessment of Cardiovascular Disorders  

Microsoft Academic Search

Background: Animal model systems have long been used to simulate and study human cardiac physiology and pathophysiology. However, application from the laboratory setting to human clinical studies has proven to be difficult to replicate. The purpose of this research is to establish an in vitro cardiac system using primary human cardiomyocyte cultures. We hypothesized that the neurotransmitter, norepinephrine (NE), and

Jessica Scott



Application of leukocyte transcriptomes to assess systemic consequences of risk factors for cardiovascular disease.  


Prevention of cardiovascular disease (CVD) remains a major health issue in the Western world. The diagnostic and therapeutic approach is currently based on risk factor assessment and treatment, which adequately predicts CVD at population level, but not at the level of a single individual. This may arise from the fact that the stage and activity of complex disease states are not likely to be captured by a single parameter or a small set of markers and thus may need a more complex representation. The aim of this review is to explore the possibility of pursuing the use of high-throughput gene expression profiling as a way to improve diagnosis, prognosis and monitoring of the disease. Novel chip-based techniques such as oligo- and cDNA microarrays can measure the abundance of thousands of mRNA transcripts in parallel and thus provide a comprehensive picture of the cell phenotype. Circulating white blood cells (WBCs), which are exposed to the systemic environment (including the risk factors) and are directly involved in the low-grade chronic inflammation related to CVD, have the potential to be used in this context to improve phenotyping of the patient. The paper reviews conceptual limitations in the use of risk factors and biomarkers, and shows the rationale beyond the possible use of circulating WBCs or subpopulations as representative cells to monitor systemic consequences of CVD. Methodological issues in performing microarray analysis of WBCs are also addressed, including controversies related to the choice of adequate cell populations and reference samples. Reproducibility and challenges occurring in the definition of a disease-specific gene panel are also discussed. The available proofs of principle from the literature presented in the last section of the review further support exploration of the application of circulating cell transcriptomics in CVD. PMID:17635069

Ardigo, Diego; Gaillard, Carlo A J M; Braam, Branko



A biochemical rationale for the discrete behavior of nitroxyl and nitric oxide in the cardiovascular system  

PubMed Central

The redox siblings nitroxyl (HNO) and nitric oxide (NO) have often been assumed to undergo casual redox reactions in biological systems. However, several recent studies have demonstrated distinct pharmacological effects for donors of these two species. Here, infusion of the HNO donor Angeli's salt into normal dogs resulted in elevated plasma levels of calcitonin gene-related peptide, whereas neither the NO donor diethylamine/NONOate nor the nitrovasodilator nitroglycerin had an appreciable effect on basal levels. Conversely, plasma cGMP was increased by infusion of diethylamine/NONOate or nitroglycerin but was unaffected by Angeli's salt. These results suggest the existence of two mutually exclusive response pathways that involve stimulated release of discrete signaling agents from HNO and NO. In light of both the observed dichotomy of HNO and NO and the recent determination that, in contrast to the O2/\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\pagestyle{empty} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{-}\\end{equation*}\\end{document} couple, HNO is a weak reductant, the relative reactivity of HNO with common biomolecules was determined. This analysis suggests that under biological conditions, the lifetime of HNO with respect to oxidation to NO, dimerization, or reaction with O2 is much longer than previously assumed. Rather, HNO is predicted to principally undergo addition reactions with thiols and ferric proteins. Calcitonin gene-related peptide release is suggested to occur via altered calcium channel function through binding of HNO to a ferric or thiol site. The orthogonality of HNO and NO may be due to differential reactivity toward metals and thiols and in the cardiovascular system, may ultimately be driven by respective alteration of cAMP and cGMP levels.

Miranda, Katrina M.; Paolocci, Nazareno; Katori, Tatsuo; Thomas, Douglas D.; Ford, Eleonora; Bartberger, Michael D.; Espey, Michael G.; Kass, David A.; Feelisch, Martin; Fukuto, Jon M.; Wink, David A.



A biochemical rationale for the discrete behavior of nitroxyl and nitric oxide in the cardiovascular system.  


The redox siblings nitroxyl (HNO) and nitric oxide (NO) have often been assumed to undergo casual redox reactions in biological systems. However, several recent studies have demonstrated distinct pharmacological effects for donors of these two species. Here, infusion of the HNO donor Angeli's salt into normal dogs resulted in elevated plasma levels of calcitonin gene-related peptide, whereas neither the NO donor diethylamine/NONOate nor the nitrovasodilator nitroglycerin had an appreciable effect on basal levels. Conversely, plasma cGMP was increased by infusion of diethylamine/NONOate or nitroglycerin but was unaffected by Angeli's salt. These results suggest the existence of two mutually exclusive response pathways that involve stimulated release of discrete signaling agents from HNO and NO. In light of both the observed dichotomy of HNO and NO and the recent determination that, in contrast to the O2/O2- couple, HNO is a weak reductant, the relative reactivity of HNO with common biomolecules was determined. This analysis suggests that under biological conditions, the lifetime of HNO with respect to oxidation to NO, dimerization, or reaction with O2 is much longer than previously assumed. Rather, HNO is predicted to principally undergo addition reactions with thiols and ferric proteins. Calcitonin gene-related peptide release is suggested to occur via altered calcium channel function through binding of HNO to a ferric or thiol site. The orthogonality of HNO and NO may be due to differential reactivity toward metals and thiols and in the cardiovascular system, may ultimately be driven by respective alteration of cAMP and cGMP levels. PMID:12865500

Miranda, Katrina M; Paolocci, Nazareno; Katori, Tatsuo; Thomas, Douglas D; Ford, Eleonora; Bartberger, Michael D; Espey, Michael G; Kass, David A; Feelisch, Martin; Fukuto, Jon M; Wink, David A



Rethinking the renin-angiotensin system and its role in cardiovascular regulation.  


Angiotensin-converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (RAS) and ACE-inhibitors are widely used in several clinical conditions, including hypertension and heart failure. Recently, a homologue of ACE, ACE(2) has been discovered. Both ACE and ACE(2) are emerging as key enzymes of the RAS, where ACE(2) may play a role as negative regulator of ACE. Moreover, ACE(2) appears to be an important enzyme outside the classical RAS, as it hydrolyzes apelins, dynorphin A 1-13, des-Arg-bradykinin and other peptide substrates. The precise interplay between tissue ACE, ACE(2), and their substrates and by-products are presently still unclear.ACE-inhibitors reduce angiotensin II formation and bradykinin degradation, but do not inhibit ACE(2) activity. Moreover, ACE-inhibitors differ in their affinity for tissue ACE, and it has been suggested that tissue ACE affinity might be responsible for some of the beneficial properties of these drugs. ACE-inhibitors also increase nitric oxide availability, and activate several kinases that may regulate protein synthesis by interacting with the nucleus of the cells (outside-in signaling). The outside-in signaling may also be activated by bradykinin itself. Although, the precise significance of the outside-in signaling is still unclear, this new role of ACE-inhibitors may represent a discriminant factor versus angiotensin II receptors antagonists. This mini review will summarize some new aspects concerning the recently discovered biological functions of RAS and in particular of ACE, ACE(2) and ACE-inhibitors in cardiovascular system. PMID:15883759

Pagliaro, Pasquale; Penna, Claudia



System Effectiveness Model Formulation  

SciTech Connect

Evaluation of system effectiveness has numerous pitfalls. System objectives may be poorly defined, may shift during the system life or may be hard to quantify. Further, individual perceptions of the quantifications may differ. Whatever the cause, system effectiveness has been an elusive term to quantitatively define. The proposed model presents a quantitative system effectiveness model and establishes a utilitarian approach for its use with the illustrative application to a nuclear safeguards system. The model uses the Type I and Type II statistical error rates as input to the component or subsystem effectiveness calculation which, when combined using a utilitarian methodology, quantify the overall system effectiveness. The methodology will use a survey of expert judgment to determine the relative importance of the individual subsystems through a statistically designed web survey. The web based survey will be available to nuclear material protection, control, and accounting experts attending the 2008 INMM conference. This model and methodology will provide a repeatable quantifiable measure for any system but in this case a simple safeguards system is used as an example.

Coates, Cameron W [ORNL; Jackson, Denise F [ORNL



Multiscale cloud system modeling  

NASA Astrophysics Data System (ADS)

The central theme of this paper is to describe how cloud system resolving models (CRMs) of grid spacing ˜1 km have been applied to various important problems in atmospheric science across a wide range of spatial and temporal scales and how these applications relate to other modeling approaches. A long-standing problem concerns the representation of organized precipitating convective cloud systems in weather and climate models. Since CRMs resolve the mesoscale to large scales of motion (i.e., 10 km to global) they explicitly address the cloud system problem. By explicitly representing organized convection, CRMs bypass restrictive assumptions associated with convective parameterization such as the scale gap between cumulus and large-scale motion. Dynamical models provide insight into the physical mechanisms involved with scale interaction and convective organization. Multiscale CRMs simulate convective cloud systems in computational domains up to global and have been applied in place of contemporary convective parameterizations in global models. Multiscale CRMs pose a new challenge for model validation, which is met in an integrated approach involving CRMs, operational prediction systems, observational measurements, and dynamical models in a new international project: the Year of Tropical Convection, which has an emphasis on organized tropical convection and its global effects.

Tao, Wei-Kuo; Moncrieff, Mitchell W.



A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model.  


Hutchinson-Gilford progeria syndrome (HGPS) is the most dramatic form of human premature aging. Death occurs at a mean age of 13 years, usually from heart attack or stroke. Almost all cases of HGPS are caused by a de novo point mutation in the lamin A (LMNA) gene that results in production of a mutant lamin A protein termed progerin. This protein is permanently modified by a lipid farnesyl group, and acts as a dominant negative, disrupting nuclear structure. Treatment with farnesyltransferase inhibitors (FTIs) has been shown to prevent and even reverse this nuclear abnormality in cultured HGPS fibroblasts. We have previously created a mouse model of HGPS that shows progressive loss of vascular smooth muscle cells in the media of the large arteries, in a pattern that is strikingly similar to the cardiovascular disease seen in patients with HGPS. Here we show that the dose-dependent administration of the FTI tipifarnib (R115777, Zarnestra) to this HGPS mouse model can significantly prevent both the onset of the cardiovascular phenotype as well as the late progression of existing cardiovascular disease. These observations provide encouraging evidence for the current clinical trial of FTIs for this rare and devastating disease. PMID:18838683

Capell, Brian C; Olive, Michelle; Erdos, Michael R; Cao, Kan; Faddah, Dina A; Tavarez, Urraca L; Conneely, Karen N; Qu, Xuan; San, Hong; Ganesh, Santhi K; Chen, Xiaoyan; Avallone, Hedwig; Kolodgie, Frank D; Virmani, Renu; Nabel, Elizabeth G; Collins, Francis S



Systems model for learning  

Microsoft Academic Search

Develops a model of learning that differs greatly from traditional or intuitive models. This hard system is specifically designed for the context of problem-solving\\/higher-order thinking, rather than automatic learning. Research in educational psychology and cognitive science provides the basis for the model. Learning is the integration of new knowledge\\/behaviors into a framework, and subsequently recalling what is relevant in the

Philip Buriak; Brian McNurlen; Joe Harper



Optical Detection System Model.  

National Technical Information Service (NTIS)

An Optical Detection System (ODS) computer code has been developed for the simulation of an electro-optical sensor. The primary emphasis has been devoted to modeling the temporal response of the system to an arbitrary time varying input signal. Input sign...

E. S. Fishburne J. V. Kuhlman F. J. Brickle M. P. Cundiff



Evaluating the evidence for models of life course socioeconomic factors and cardiovascular outcomes: a systematic review  

Microsoft Academic Search

BACKGROUND: A relatively consistent body of research supports an inverse graded relationship between socioeconomic status (SES) and cardiovascular disease (CVD). More recently, researchers have proposed various life course SES hypotheses, which posit that the combination, accumulation, and\\/or interactions of different environments and experiences throughout life can affect adult risk of CVD. Different life course designs have been utilized to examine

Ricardo A Pollitt; Kathryn M Rose; Jay S Kaufman



Computational Prediction Models for Early Detection of Risk of Cardiovascular Events Using Mass Spectrometry Data  

Microsoft Academic Search

Early prediction of the risk of cardiovascular events in patients with chest pain is critical in order to provide appropriate medical care for those with positive diagnosis. This paper introduces a computational methodology for predicting such events in the context of robust computerized classification using mass spectrometry data of blood samples collected from patients in emergency departments. We applied the

Tuan D. Pham; Honghui Wang; Xiaobo Zhou; Dominik Beck; Miriam Brandl; Gerard Hoehn; Joseph Azok; Marie-luise Brennan; Stanley L. Hazen; King Li; Stephen T. C. Wong



Modeling of dynamic cardiovascular responses during G-transition-induced orthostatic stress in pitch and roll rotations.  


Dynamic and fuzzy models for a typical subject's cardiovascular response to the orthostatic stress have been developed based on experimental data. In our original study (Cheung et al., 1999), arterial blood pressure (BP) time-series data were obtained using a man-rated tilt table that applies gigahertz-acceleration transitions from +0.861 Gz [head-up (HU)] to -0.707 G [head-down (HD)] and back to +0.861 Gz (HU) using either pitch or roll rotations (Cheung et al., 1999). G transitions of different duration and onset rates are common in fighter maneuvers. Based on these data, two types of predictive models have been developed in this paper: 1) second-order discrete-time models that predict BP dynamics during pitch and roll rotations and 2) fuzzy logic models that predict important variations in a subject's cardiovascular dynamics induced by HU-to-HD and HD-to-HU transitions. These two types of models assist in providing an operationally important predictive view on the characteristics of BP responses to orthostatic stress induced by pitch and roll rotations of a fighter jet pilot. The new models are being currently utilized in the design of operational recommendations for more G-tolerant operational flight regimes (e.g., split-S tactical maneuver) than the ones currently in use for modern combat aircraft. PMID:12549730

Melek, William W; Lu, Ziren; Kapps, Alex; Cheung, Bob



The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model  

PubMed Central

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.



Distributed fuzzy system modeling  

SciTech Connect

The paper introduces and studies an idea of distributed modeling treating it as a new paradigm of fuzzy system modeling and analysis. This form of modeling is oriented towards developing individual (local) fuzzy models for specific modeling landmarks (expressed as fuzzy sets) and determining the essential logical relationships between these local models. The models themselves are implemented in the form of logic processors being regarded as specialized fuzzy neural networks. The interaction between the processors is developed either in an inhibitory or excitatory way. In more descriptive way, the distributed model can be sought as a collection of fuzzy finite state machines with their individual local first or higher order memories. It is also clarified how the concept of distributed modeling narrows down a gap between purely numerical (quantitative) models and the qualitative ones originated within the realm of Artificial Intelligence. The overall architecture of distributed modeling is discussed along with the detailed learning schemes. The results of extensive simulation experiments are provided as well. 17 refs.

Pedrycz, W.; Chi Fung Lam, P.; Rocha, A.F. [Univ. of Manitoba, Winnipeg, Manitoba (Canada)



Study of the Effects of Drugs upon the Cardiovascular and Respiratory Systems.  

National Technical Information Service (NTIS)

A comparison was made of a variety of cardiovascular and pulmonary effects of WR-6026.2HCl and primaquine diphosphate in anesthetized dogs utilizing dose rates which were either only minimally effective in producing changes or those producing marked effec...

R. W. Caldwell C. B. Nash



Methods for establishing a surveillance system for cardiovascular diseases in Indian industrial populations  

Microsoft Academic Search

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

K S Reddy; Thankappan KR; Ahmed FU



Effects of calcium intake on the cardiovascular system in postmenopausal women.  


The use of calcium supplements for the prevention of complications of osteoporosis has significantly increased during the last years. The effects of calcium intake in postmenopausal women on cardiovascular parameters such as blood pressure, serum lipids and cardiovascular events are controversial. Even though transient beneficial effects of calcium supplementation have been reported, especially in women with low dietary calcium intake, their long-term outcomes are inconclusive. Only a very few studies investigating serum lipids in postmenopausal women have been described and these showed significant increases in high-density lipoprotein and high-density lipoprotein to low-density lipoprotein ratio. With regards to cardiovascular events in this population group adverse effects have been reported on the rates of myocardial infarction and stroke with increased calcium intake by some authors, however, others described no effects or even beneficial outcomes. We present a review of the current literature which provides a balanced summary of the possible beneficial and adverse effects of calcium intake in postmenopausal women on cardiovascular parameters. Taking into account the modest effect of calcium supplementation in reducing fracture rates, a reassessment of the role, benefits and adverse effects of calcium supplements should be conducted in postmenopausal women. PMID:24125401

Challoumas, D; Cobbold, C; Dimitrakakis, G



Cardiovascular Responses with TLSS, ATAGS, and Eagle Life Support Systems During Rapid Decompression.  

National Technical Information Service (NTIS)

This study compared the cardiovascular responses and degree of oxygen saturation of subjects exposed to 60,000 and 72,000 ft. rapid decompressions while wearing the U.S. Navy Enhanced Anti-G Lower Ensemble (EAGLE) and the U.S. Air Force Advanced Tactical ...

W. D. Fraser K. N. Ackles



How the Health Care System Can Influence Cardiovascular Disease Risk Factors  

Microsoft Academic Search

Only a small fraction of the health-care dollar is directed toward lifestyle changes that would reduce the social burden from cardiovascular diseases (CVD). Here we discuss the challenge, opportunity, methods, and potential for managed care to implement risk reduction strategies and preventive care. A systematic team approach involving nurses, nutritionists, exercise physiologists, and behavioral experts has been shown to be

Sidney C. Smith



Cardiovascular health among adults in Syria: a model from developing countries  

PubMed Central

Background Despite the considerable mortality and morbidity associated with cardiovascular disease (CVD) many developing countries lack reliable surveillance of these ailments and their risk factors to guide intervention. This study aims to provide the first population-based estimates of CVD morbidity and mortality among adults in Aleppo-Syria and the distribution of their risk factors. Methods A cross-sectional survey of adults 18-65 years old residing in Aleppo-Syria was carried out in 2004 involving 2038 household representatives (45.2% men, mean age 35.3 years, response rate 86%). Main outcomes of interest were physician-diagnosed CVD (infarction, angina, failure, stroke) among survey participants, and past 5 year mortality due to CVD among their household members > 20 years of age (n=6252, 49.5% men). Measurement of blood pressure (BP), height and weight, and smoking history were obtained as well. Findings Prevalence of CVD was 4.8% for heart disease and 1.0% for stroke. CVD was responsible for 45.0% of overall mortality reported in the past 5 years, whereby 49% of CVD deaths occurred before the age of 65 year. Mean age of death was 62.6 years (63.6 years for HD and 61.4 years for stroke). Annual crude death rate due to CVD was 314 per 100,000 (95%CI: 215-414), of these 179 were due to heart disease, and 135 due to stroke. More men died from heart disease than women, while the opposite was true for stroke. Hypertension was detected in 40.6% (47.7% men, 34.9%women), obesity in 38.2% (28.8% men, 46.4% women), and smoking (cigarettes or waterpipe) in 38.7% (63.6% men, 19.2% women) of participants. Of those surveyed, 39.3% had 1 CVD risk factor, 27.4% had 2 risk factors, and 8.3% had 3 risk factors. Main predictors of clustering of risk factors were older age, male gender, and low education. Conclusions Syria is currently undergoing a stage, where morbidity and mortality from CVD are high but likely to increase based on the population's risk profile. CVD risk distribution in the Syrian society highlights the non-generalizability of CVD models from developed societies, and calls for local studies to inform effective interventions and policies.

Maziak, Wasim; Rastam, Samer; Mzayek, Fawaz; Ward, Kenneth D; Eissenberg, Thomas; Keil, Ulrich



Kisspeptins: a multifunctional peptide system with a role in reproduction, cancer and the cardiovascular system  

PubMed Central

The pairing of the kisspeptins (KP) with the KISS1 (GPR54) receptor has received growing attention since the description of the receptor as a molecular switch for puberty. The role of KP and its receptor, GPR54, in puberty is the most exciting finding made in the field of reproductive biology since the discovery of Gonadotropin Releasing Hormone (GnRH) in 1970s. A significant body of evidence across several species now suggests that KISS1 (GPR54) activation is a critical point in the commencement of puberty, although further investigation is required to characterize the interaction between KP and GnRH cascade. Given such pivotal roles of kisspeptins and GPR54 as gatekeepers of reproductive function, and the proven ability of sex steroids to physiologically regulate this system, it is plausible that environmental compounds with ability to interfere oestrogen and/or androgen signaling (agonists or antagonists) may target the hypothalamic kiss-1/GPR54 system, thereby inducing functional alterations of the hypothalamic-pituitary-gonadal axis. Synthetic agonists targeting KISS1 (GPR54) may represent novel therapeutic agents for the treatment of hypogonadotrophic hypogonadism in some affected individuals. The diverse multifunctional nature of the KP is beginning to unravel. The unexpected role of these peptides in puberty has raised a number of important questions that remain to be answered.

Votsi, E; Roussos, D; Katsikis, I; Karkanaki, A; Kita, M; Panidis, D



Climate system modeling program  

SciTech Connect

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.




Modeling the earth system  

SciTech Connect

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.



Introducing a model of cardiovascular prevention in Nairobi's slums by integrating a public health and private-sector approach: the SCALE-UP study  

PubMed Central

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.

van de Vijver, Steven; Oti, Samuel; Tervaert, Thijs Cohen; Hankins, Catherine; Kyobutungi, Catherine; Gomez, Gabriela B.; Brewster, Lizzy; Agyemang, Charles; Lange, Joep



Fishing for the genetic basis of cardiovascular disease  

PubMed Central

Cardiovascular disease (CVD) has recently overtaken infectious disease to become the biggest global killer. Genetic factors have emerged as being of major importance in the pathogenesis of CVD. Owing to disease heterogeneity, variable penetrance and high mortality, human genetic studies alone are not sufficient to elucidate the genetic basis of CVD. Animal models are needed to identify novel genes that are involved in cardiovascular pathology and to verify the effect of suspected disease genes on cardiovascular function. An intriguing model organism is the zebrafish danio rerio. Several features of the zebrafish, such as a closed cardiovascular system, transparency at embryonal stages, rapid and external development, and easily tractable genetics make it ideal for cardiovascular research. Moreover, zebrafish are suitable for forward genetics approaches, which allow the unbiased identification of novel and unanticipated cardiovascular genes. Zebrafish mutants with various cardiovascular phenotypes that closely correlate with human disease, such as congenital heart disease, cardiomyopathies and arrhythmias, have been isolated. The pool of zebrafish mutants, for which the causal gene mutation has been identified, is constantly growing. The human orthologues of several of these zebrafish genes have been shown to be involved in the pathogenesis of human CVD. Cardiovascular zebrafish models also provide the opportunity to develop and test novel therapeutic strategies, using innovative technologies such as high throughput in vivo small molecule screens.

Dahme, Tillman; Katus, Hugo A.; Rottbauer, Wolfgang



Security system throughput modeling  

Microsoft Academic Search

One of the keys to integrating 100% checked bag screening into airports is identifying realistic throughput rates of various explosive detection system (EDS) machines available to Transportation Security Administration (TSA) planners. This study discusses some of the issues associated with the implementation of EDS equipment and performs an analysis on the throughput of the equipment using modeling and discrete event

K. Leone




EPA Science Inventory

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...



Technology Transfer Automated Retrieval System (TEKTRAN)

The goal of this paper is to provide a brief review of how mathematical models may be used in planning agricultural production systems. The processes involved in producing palatable and nutritious food for people from livestock and poultry are numerous, complex, and interactive. Traditional experi...


Emerging anti-cancer therapeutic targets and the cardiovascular system: Is there cause for concern?  

PubMed Central

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.

Peng, Xuyang; Pentassuglia, Laura; Sawyer, Douglas B.



Modelling resonant planetary systems  

NASA Astrophysics Data System (ADS)

Many discovered multi-planet systems are in meanmotion resonances. The aim of this work is to study dynamical processes leading to the formation of resonant configurations on the basis of a unified model described earlier [1]. The model includes gravitational interactions of planets and migration of planets due to the presence of a gas disc. For the observed systems 24 Sex, HD 37124, HD 73526, HD 82943, HD 128311, HD 160691, Kepler 9, NN Ser with planets moving in the 2:1 resonance, it is shown that the capture in this resonance occurs at very wide ranges of parameters of both type I and type II migration. Conditions of migration leading to the formation of the resonant systems HD 45364 ? HD 200964 (3:2 and 4:3, respectively) are obtained. Formation scenarios are studied for the systems HD 102272, HD 108874, HD 181433, HD 202206 with planets in high order resonances. We discuss also how gravitational interactions of planets and planetesimal discs lead to the breakup of resonant configurations and the formation of systems similar to the 47 UMa system.

Emel'yanenko, V.



Genetics and cardiovascular system: influence of human genetic variants on vascular function  

Microsoft Academic Search

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



The endocannabinoid system and its role in the pathogenesis and treatment of cardiovascular disturbances in cirrhosis.  


It has been known for over half a century that liver cirrhosis is associated with abnormal cardiovascular function. Although the mechanisms underlying the association of portal hypertension and hyperdynamic circulation have been intensively investigated during the past decades, the results are still inconclusive. This review focuses on the role that the endocannabinoids and their receptors could play in the pathogenesis of the cirrhotic cardiomyopathy, as well as on the treatment options that they offer. PMID:23898556

Manitiu, M?ries L



Cardiovascular Disease: Application of a Composite Risk Index from the Telehealth System in a District Community  

Microsoft Academic Search

Assessing a combination of cardiovascular disease (CVD)-risk factors may be a practical tool for risk assessment and for finding the high-risk group among local community members. This study examines the association between the num- ber of CVD-risk factors, regardless of any specific combination with the CVD ambit, using data from 1,570 residents in Tsing Yi community (Hong Kong) who registered

Y. B. Yip; Thomas K. S. Wong; Joanne W. Y. Chung; Stanley K. K. Ko; Janet W. H. Sit; Tony M. F. Chan



From form to function: the role of Nox4 in the cardiovascular system.  


The NADPH oxidase (Nox) family of proteins is comprised of seven members, including Noxes1-5 and the Duoxes 1 and 2. Nox4 is readily distinguished from the other Nox isoforms by its high level of expression in cardiovascular tissues and unique enzymatic properties. Nox4 is constitutively active and the amount of reactive oxygen species (ROS) contributed by Nox4 is primarily regulated at the transcriptional level although there is recent evidence for post-translational control. Nox4 emits a different pattern of ROS and its subcellular localizations, tissue distribution and influence over signaling pathways is different from the other Nox enzymes. Previous investigations have revealed that Nox4 is involved in oxygen sensing, vasomotor control, cellular proliferation, differentiation, migration, apoptosis, senescence, fibrosis, and angiogenesis. Elevated expression of Nox4 has been reported in a number of cardiovascular diseases, including atherosclerosis, pulmonary fibrosis, and hypertension, cardiac failure and ischemic stroke. However, many important questions remain regarding the functional significance of Nox4 in health and disease, including the role of Nox4 subcellular localization and its downstream targets. The goal of this review is to summarize the recent literature on the genetic and enzymatic regulation, subcellular localization, signaling pathways, and the role of Nox4 in cardiovascular disease states. PMID:23125837

Chen, Feng; Haigh, Stephen; Barman, Scott; Fulton, David J R



Kepler System Model  

NSDL National Science Digital Library

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.

Timberlake, Todd



Individualized patient-centered lifestyle recommendations: an expert system for communicating patient specific cardiovascular risk information and prioritizing lifestyle options.  


We propose a proof-of-concept machine-learning expert system that learned knowledge of lifestyle and the associated 10-year cardiovascular disease (CVD) risks from individual-level data (i.e., Atherosclerosis Risk in Communities Study, ARIC). The expert system prioritizes lifestyle options and identifies the one that maximally reduce an individual's 10-year CVD risk by (1) using the knowledge learned from the ARIC data and (2) communicating for patient-specific cardiovascular risk information and personal limitations and preferences (as defined by variables used in this study). As a result, the optimal lifestyle is not only prioritized based on an individual's characteristics but is also relevant to personal circumstances. We also explored probable uses and tested the system in several examples using real-world scenarios and patient preferences. For example, the system identifies the most effective lifestyle activities as the starting point for an individual's behavior change, shows different levels of BMI changes and the associated CVD risk reductions to encourage weight loss, identifies whether weight loss or smoking cessation is the most urgent change for a diabetes patient, etc. Answers to the questions noted above vary based on an individual's characteristics. Our validation results from clinical trial simulations, which compared original with the optimal lifestyle using an independent dataset, show that the optimal individualized patient-centered lifestyle consistently reduced 10-year CVD risks. PMID:22903051

Chi, Chih-Lin; Nick Street, W; Robinson, Jennifer G; Crawford, Matthew A



Effects of Mono and Dual Blockade of the Renin-Angiotensin System on Markers of Cardiovascular Status in Hypertensive Patients with Mild and Moderate Renal Failure  

Microsoft Academic Search

Background\\/Aims: Dual renin-angiotensin system (RAS) blockade has no more efficiency to decrease cardiovascular mortality than mono-blockade. Our goal was to explore differences between other cardiovascular markers in patients with RAS blockade. Methods: We analyzed two groups of patients treated with a long-term ACE inhibitor (MONO-group, n = 20) and an ACE inhibitor and angiotensin II receptor blocker (DUAL-group, n =

Gábor Nagy; István A. Szijártó; Balázs Gaszner; Éva Lányi; Lajos Markó; Ákos Mérei; Gergo? A. Molnár; Kinga Németh; József Betlehem; István Wittmann



Model performance evaluation (validation and calibration) in model-based studies of therapeutic interventions for cardiovascular diseases : a review and suggested reporting framework.  


Decision analytic models play an increasingly important role in the economic evaluation of health technologies. Given uncertainties around the assumptions used to develop such models, several guidelines have been published to identify and assess 'best practice' in the model development process, including general modelling approach (e.g., time horizon), model structure, input data and model performance evaluation. This paper focuses on model performance evaluation. In the absence of a sufficient level of detail around model performance evaluation, concerns regarding the accuracy of model outputs, and hence the credibility of such models, are frequently raised. Following presentation of its components, a review of the application and reporting of model performance evaluation is presented. Taking cardiovascular disease as an illustrative example, the review investigates the use of face validity, internal validity, external validity, and cross model validity. As a part of the performance evaluation process, model calibration is also discussed and its use in applied studies investigated. The review found that the application and reporting of model performance evaluation across 81 studies of treatment for cardiovascular disease was variable. Cross-model validation was reported in 55 % of the reviewed studies, though the level of detail provided varied considerably. We found that very few studies documented other types of validity, and only 6 % of the reviewed articles reported a calibration process. Considering the above findings, we propose a comprehensive model performance evaluation framework (checklist), informed by a review of best-practice guidelines. This framework provides a basis for more accurate and consistent documentation of model performance evaluation. This will improve the peer review process and the comparability of modelling studies. Recognising the fundamental role of decision analytic models in informing public funding decisions, the proposed framework should usefully inform guidelines for preparing submissions to reimbursement bodies. PMID:23456647

Haji Ali Afzali, Hossein; Gray, Jodi; Karnon, Jonathan



Laser Doppler flowmetry signals to quantify effects of isoflurane on the peripheral cardiovascular system of healthy rats  

NASA Astrophysics Data System (ADS)

The optical Doppler effect resulting from interactions between laser light photons and red blood cells of the microcirculation is used to characterize the influence of isoflurane, an halogenated volatile anesthetic, on the peripheral cardiovascular system. After having recorded laser Doppler flowmetry blood perfusion signals on isoflurane-induced anesthetized healthy rats, wavelet analyses show a significant decrease of the myogenic and neurogenic activities when isoflurane dose increases from 1.5% to 3%. Moreover, the approximate entropy shows a weak decrease of signal irregularity when dose of isoflurane increases. These findings demonstrate the usefulness of the optical Doppler effect in physiological and pharmacological applications.

Humeau, Anne; Fizanne, Lionel; Roux, Jérôme; Asfar, Pierre; Cales, Paul; Rousseau, David; Chapeau-Blondeau, François



Statistical validation of system models.  

National Technical Information Service (NTIS)

It is common practice in system analysis to develop mathematical models for system behavior. Frequently, the actual system being modeled is also available for testing and observation, and sometimes the test data are used to help identify the parameters of...

P. Barney C. Ferregut L. E. Perez N. F. Hunter T. L. Paez



Amelioration of central cardiovascular regulatory dysfunction by tropomyocin receptor kinase B in a mevinphos intoxication model of brain stem death  

PubMed Central

BACKGROUND AND PURPOSE Little information exists on the mechanisms that precipitate brain stem death, the legal definition of death in many developed countries. We investigated the role of tropomyocin receptor kinase B (TrkB) and its downstream signalling pathways in the rostral ventrolateral medulla (RVLM) during experimental brain stem death. EXPERIMENTAL APPROACH An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos bilaterally into the RVLM of Sprague–Dawley rats was used, in conjunction with cardiovascular, pharmacological and biochemical evaluations. KEY RESULTS A significant increase in TrkB protein, phosphorylation of TrkB at Tyr516 (pTrkBY516), Shc at Tyr317 (pShcY317) or ERK at Thr202/Tyr204, or Ras activity in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Microinjection bilaterally into RVLM of a specific TrkB inhibitor, K252a, antagonized those increases. Pretreatment with anti-pShcY317 antiserum, Src homology 3 binding peptide (Grb2/SOS inhibitor), farnesylthioacetic acid (Ras inhibitor), manumycin A (Ras inhibitor) or GW5074 (Raf-1 inhibitor) blunted the preferential augmentation of Ras activity or ERK phosphorylation in RVLM and blocked the up-regulated NOS I/protein kinase G (PKG) signalling, the pro-life cascade that sustains central cardiovascular regulation during experimental brain stem death. CONCLUSIONS AND IMPLICATIONS Activation of TrkB, followed by recruitment of Shc/Grb2/SOS adaptor proteins, leading to activation of Ras/Raf-1/ERK signalling pathway plays a crucial role in ameliorating central cardiovascular regulatory dysfunction via up-regulation of NOS I/PKG signalling cascade in the RVLM in brain stem death. These findings provide novel information for developing therapeutic strategies against this fatal eventuality.

Chan, SHH; Chan, JYH; Hsu, KS; Li, FCH; Sun, EYH; Chen, WL; Chang, AYW



Cardiovascular performance with E. coli challenges in a canine model of human sepsis  

SciTech Connect

The authors investigated cardiovascular dysfunction by injecting lethal and nonlethal bacterial challenges into conscious dogs. E coli bacteria of varying numbers were placed in a peritoneal clot. Cardiovascular function was studied with simultaneous radionuclide scans and thermodilution cardiac outputs. In surviving animals, the number of bacteria in the clot increased as the corresponding systolic cardiac function decreased. Cardiac function was measured by left ventricular (LV) ejection fraction (EF) and LV function curves. Furthermore, the diastolic volume-pressure relationship of survivors shifted progressively to the right. This increase in LV size was associated with maintenance of measures of cardiac performance at similar levels. Death occurred only in the group with the highest bacterial dose. Compared with survivors receiving the same number of bacterial, nonsurvivors had a decrease in LV size, a leftward shift in LV diastolic volume-pressure relationship, and a decrease in both LVSWI and SVI. Data from survivors suggest that increasing the number of bacteria produces changes in myocardial compliance and contractility. These changes increase LV size (preload), a major determinant of cardiac performance that possibility enhances survival.

Natanson, C.; Danner, R.L.; Fink, M.P.; MacVittie, T.J.; Walker, R.I.; Conklin, J.J.; Parrillo, J.E. (National Institutes of Health, Bethesda, MD (USA) Naval Medical Research Institute and Armed Forces Radiobiology Research Institute, Bethesda, MD (USA) Univ. of Massachusetts Medical Center, Worcester (USA))



Evidence-based diuretic therapy for improving cardiovascular prognosis in systemic hypertension.  


Diuretics are among the most commonly prescribed cardiovascular (CV) medications. The strength of evidence supporting the effectiveness of diuretics in lowering blood pressure and for preventing major adverse CV events in patients with hypertension varies considerably among diuretic classes and even among agents within the same class. Unfortunately, common prescribing habits among American physicians, including specialists in CV diseases, are not in line with the existing evidence regarding diuretic therapy for improving CV prognosis. In conclusion, although hydrochlorothiazide is the standard diuretic used for hypertension, the outcomes data suggest that chlorthalidone, indapamide, and possibly even the aldosterone receptor blockers (spironolactone and eplerenone) may be superior agents. PMID:21316640

Al Badarin, Firas J; Abuannadi, Mohammad A; Lavie, Carl J; O'Keefe, James H



Cardiovascular disease: the other face of diabetes.  


Despite glycemic control, evidence suggests that mortality and morbidity remain high in diabetes. Regulatory agencies deem, therefore, additional safety trials necessary for the approval of new antidiabetic drugs. Nevertheless, markers of cardiovascular risk, which can be used as response predictors, are not available. In contrast with current efforts on further understanding of glucose-insulin homeostasis, a model-based approach is required to assess the correlation between hyperglycemia and cardiometabolic phenotypes, enabling prediction of the underlying cardiovascular risk.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e81; doi:10.1038/psp.2013.57; advance online publication 23 October 2013. PMID:24153424

Vlasakakis, G; Pasqua, O Della



System of systems modeling and analysis.  

SciTech Connect

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.



Contaminación atmosférica y daño cardiovascular  

Microsoft Academic Search

The damaging effect of atmospheric pollution with particulate matter and toxic gases on the respiratory system and its effect in the incidence and severity of respiratory diseases, is well known. A similar effect on the cardiovascular system is currently under investigation. Epidemiological studies have demonstrated that the inhalation of particu- late matter can increase cardiovascular disease incidence and mortality, specially

Oscar Román A; María José Prieto; Pedro Mancilla



Effects of thyroid hormone on. beta. -adrenergic responsiveness of aging cardiovascular systems  

SciTech Connect

The authors have compared the effects of ..beta..-adrenergic stimulation on the heart and peripheral vasculature of young (2-mo-old) and older (12-mo-old) rats both in the presence and absence of triiodothyronine (T/sub 3/)-induced hyperthyroidism. The hemodynamic consequences of T/sub 3/ treatment were less prominent in the aged hyperthyroid rats compared with young hyperthyroid rats (both in intact and pithed rats). There was a decrease in sensitivity of chronotropic responsiveness to isoproterenol in older pithed rats, which was apparently reversed by T/sub 3/ treatment. The number and affinity of myocardial ..beta..-adrenergic receptor sites measured by (/sup 125/I)cyanopindolol were not significantly different in young and older control rats; also, ..beta..-receptor density increased to a similar extent in both young and older T/sub 3/-treated rats. The ability of isoproterenol to relax mesenteric arterial rings, markedly blunted in older rats, was partially restored by T/sub 3/ treatment without their being any change in isoproterenol-mediated relaxation in the arterial preparation from young rats. The number and affinity of the ..beta..-adrenergic receptors measured in the mesenteric arteries was unaffected by either aging or T/sub 3/ treatment. The data suggest that effects of thyroid hormone and age-related alterations of cardiovascular responsiveness to ..beta..-adrenergic stimulation are interrelated in a complex fashion with a net result that the hyperkinetic cardiovascular manifestations in hyperthyroidism are attenuated in the older animals.

Tsujimoto, G.; Hashimoto, K.; Hoffman, B.B.



User Models in Dialog Systems  

Microsoft Academic Search

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




EPA Science Inventory

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-...


Sodium heat transfer system modeling  

NASA Astrophysics Data System (ADS)

The sodium heat transfer system of the international energy agency (IEA) small solar power systems (SSPS) central receiver system (CRS), which includes the heliostat field, receiver, hot and cold storage vessels, and sodium/water steam generator was modeled. The computer code SOLTES (simulator of large thermal energy systems), was used to model this system. The results from SOLTES are compared to measured data.

Baker, A. F.; Fewell, M. E.



Regulation of Cell Physiology and Pathology by Protein S-Glutathionylation: Lessons Learned from the Cardiovascular System  

PubMed Central

Abstract Significance: Reactive oxygen and nitrogen species contributing to homeostatic regulation and the pathogenesis of various cardiovascular diseases, including atherosclerosis, hypertension, endothelial dysfunction, and cardiac hypertrophy, is well established. The ability of oxidant species to mediate such effects is in part dependent on their ability to induce specific modifications on particular amino acids, which alter protein function leading to changes in cell signaling and function. The thiol containing amino acids, methionine and cysteine, are the only oxidized amino acids that undergo reduction by cellular enzymes and are, therefore, prime candidates in regulating physiological signaling. Various reports illustrate the significance of reversible oxidative modifications on cysteine thiols and their importance in modulating cardiovascular function and physiology. Recent Advances: The use of mass spectrometry, novel labeling techniques, and live cell imaging illustrate the emerging importance of reversible thiol modifications in cellular redox signaling and have advanced our analytical abilities. Critical Issues: Distinguishing redox signaling from oxidative stress remains unclear. S-nitrosylation as a precursor of S-glutathionylation is controversial and needs further clarification. Subcellular distribution of glutathione (GSH) may play an important role in local regulation, and targeted tools need to be developed. Furthermore, cellular redundancies of thiol metabolism complicate analysis and interpretation. Future Directions: The development of novel pharmacological analogs that specifically target subcellular compartments of GSH to promote or prevent local protein S-glutathionylation as well as the establishment of conditional gene ablation and transgenic animal models are needed. Antioxid. Redox Signal. 16, 524–542.

Pimentel, David; Haeussler, Dagmar Johanna; Matsui, Reiko; Burgoyne, Joseph Robert; Cohen, Richard Alan



Sleep and Cardiovascular Disease  

Microsoft Academic Search

Sleep is an important modulator of cardiovascular function, both in physiological conditions and in disease states. In individuals without a primary sleep disorder, sleep may exert significant effects on the autonomic nervous system, systemic hemodynamics, cardiac function, endothelial function, and coagulation. Some of these influences can be directly linked to specific modulatory effects of sleep stages per se; others result

Robert Wolk; Apoor S. Gami; Arturo Garcia-Touchard; Virend K. Somers



Cardiovascular Side Effects of Atomoxetine and Its Interactions with Inhibitors of the Cytochrome P450 System  

PubMed Central

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders of childhood and adolescence. Classically, stimulants have been used in the treatment of this condition. Atomoxetine (Strattera; Eli Lilly and Company) is a selective norepinephrine reuptake inhibitor (SNRI), one of the first medications in the nonstimulant class of medications that has been approved by the FDA for the treatment of ADHD. Atomoxetine is a phenoxypropylamine derivative and is structurally related to the antidepressant fluoxetine. The common side effects reported with the use of atomoxetine include mainly GI disturbances. Cardiovascular side effects are less commonly reported. The increase in the noradrenergic tone may explain some of the side effects noted with the use of this medication. Here, we present a case of a patient who presented with syncope, orthostatic hypotension, and tachycardia and discuss the various clinical implications based on the pharmacokinetics and pharmacodynamics of the drug.

Kasi, Pashtoon Murtaza; Mounzer, Rawad; Gleeson, George H.



MicroRNAs and Cardiovascular Diseases  

PubMed Central

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have gained status as important regulators of gene expression. Recent studies have demonstrated that miRNAs are aberrantly expressed in the cardiovascular system under some pathological conditions. Gain- and loss-of-function studies using in vitro and in vivo models have revealed distinct roles for specific miRNAs in cardiovascular development and physiological function. The implications of miRNAs in cardiovascular disease have recently been recognized, representing the most rapidly evolving research field. In the present article, the currently relevant findings on the role of miRNAs in cardiac diseases will be updated and the target genes of these miRNAs are summarized.

Ono, Koh; Kuwabara, Yasuhide; Han, Jiahuai



Automated evaluation of electronic discharge notes to assess quality of care for cardiovascular diseases using Medical Language Extraction and Encoding System (MedLEE)  

Microsoft Academic Search

The objective of this study was to develop and validate an automated acquisition system to assess quality of care (QC) measures for cardiovascular diseases. This system combining searching and retrieval algorithms was designed to extract QC measures from electronic discharge notes and to estimate the attainment rates to the current standards of care. It was developed on the patients with

Jung-Hsien Chiang; Jou-Wei Lin; Chen-Wei Yang



Effects of spinal manipulative therapy on autonomic activity and the cardiovascular system: A case study using the electrocardiogram and arterial tonometry  

Microsoft Academic Search

Objective: To determine if there is alteration in the autonomic nervous and cardiovascular systems after chiropractic manipulative therapy (CMT). A novel approach was used to quantitatively probe for changes in the activity of the autonomic nervous system, in blood pressure, and in pressure pulse transmission time. This approach uses the electrocardiogram and arterial tonometry equipment. Design: This case study involves

M. Darcy Driscoll; Marty J. Hall



Dissection of cardiovascular development and disease pathways in zebrafish.  


The use of animal models in medicine has contributed significantly to the development of drug treatments and surgical procedures for the last century, in particular for cardiovascular disease. In order to model human disease in an animal, an appreciation of the strengths and limitations of the system are required to interpret results and design the logical sequence of steps toward clinical translation. As the world's population ages, cardiovascular disease will become even more prominent and further progress will be essential to stave off what seems destined to become a massive public health issue. Future treatments will require the imaginative application of current models as well as the generation of new ones. In this review, we discuss the resources available for modeling cardiovascular disease in zebrafish and the varied attributes of this system. We then discuss current zebrafish disease models and their potential that has yet to be exploited. PMID:21377626

Chan, Joanne; Mably, John D



Cardiovascular Pharmacology of Cannabinoids  

PubMed Central

Cannabinoids and their synthetic and endogenous analogs affect a broad range of physiological functions, including cardiovascular variables, the most important component of their effect being profound hypotension. The mechanisms of the cardiovascular effects of cannabinoids in vivo are complex and may involve modulation of autonomic outflow in both the central and peripheral nervous systems as well as direct effects on the myocardium and vasculature. Although several lines of evidence indicate that the cardiovascular depressive effects of cannabinoids are mediated by peripherally localized CB1 receptors, recent studies provide strong support for the existence of as-yet-undefined endothelial and cardiac receptor(s) that mediate certain endocannabinoid-induced cardiovascular effects. The endogenous cannabinoid system has been recently implicated in the mechanism of hypotension associated with hemorrhagic, endotoxic, and cardiogenic shock, and advanced liver cirrhosis. Furthermore, cannabinoids have been considered as novel antihypertensive agents. A protective role of endocannabinoids in myocardial ischemia has also been documented. In this chapter, we summarize current information on the cardiovascular effects of cannabinoids and highlight the importance of these effects in a variety of pathophysiological conditions.

Pacher, P.; Batkai, S.; Kunos, G.



Systemic arterial baroreceptors in ducks and the consequences of their denervation on some cardiovascular responses to diving  

PubMed Central

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

Jones, D. R.



A Functional Melanocortin System May Be Required for Chronic CNS-Mediated Antidiabetic and Cardiovascular Actions of Leptin  

PubMed Central

OBJECTIVE We recently showed that leptin has powerful central nervous system (CNS)-mediated antidiabetic and cardiovascular actions. This study tested whether the CNS melanocortin system mediates these actions of leptin in diabetic rats. RESEARCH DESIGN AND METHODS A cannula was placed in the lateral ventricle of Sprague-Dawley rats for intracerebroventricular infusions, and arterial and venous catheters were implanted to measure mean arterial pressure (MAP) and heart rate 24 h/day and for intravenous infusions. After recovery from surgery for 8 days, rats were injected with streptozotocin (STZ), and 5 days later, either saline or the melanocortin 3 and 4 receptor (MC3/4R) antagonist SHU-9119 (1 nmol/h) was infused intracerebroventricularly for 17 days. Seven days after starting the antagonist, leptin (0.62 ?g/h) was added to the intracerebroventricular infusion for 10 days. Another group of diabetic rats was infused with the MC3/4R agonist MTII (10 ng/h i.c.v.) for 12 days, followed by 7 days at 50 ng/h. RESULTS Induction of diabetes caused hyperphagia, hyperglycemia, and decreases in heart rate (?76 bpm) and MAP (?7 mmHg). Leptin restored appetite, blood glucose, heart rate, and MAP back to pre-diabetic values in vehicle-treated rats, whereas it had no effect in SHU-9119–treated rats. MTII infusions transiently reduced blood glucose and raised heart rate and MAP, which returned to diabetic values 5–7 days after starting the infusion. CONCLUSIONS Although a functional melanocortin system is necessary for the CNS-mediated antidiabetic and cardiovascular actions of leptin, chronic MC3/4R activation is apparently not sufficient to mimic these actions of leptin that may involve interactions of multiple pathways.

da Silva, Alexandre A.; do Carmo, Jussara M.; Freeman, J. Nathan; Tallam, Lakshmi S.; Hall, John E.



Relationship between renal and cardiovascular changes in a murine model of glucose intolerance.  


Nutrition is an important variable which may affect the risk for renal disease. We previously showed that a high fructose diet in mice produced hypertension and sympathetic activation [8]. The purpose of this study was to determine if a fructose diet altered renal function. A high fructose diet for 12 weeks impaired glucose tolerance, but caused no change in body weight, blood glucose or plasma insulin. Impairment in renal function was documented by the almost two fold increase in urinary protein excretion (Control: 6.6+/-0.6 vs. Fructose: 15.0+/-0.7 mmol protein/mmol creatinine; p<0.05) which was also accompanied by increases in urinary volume. The diet produced little change in renal histology, kidney weight or kidney weight/body weight ratio. Urinary excretion of angiotensin II/creatinine (Control: 78.9+/-16.6 vs. Fructose: 80.5+/-14.2 pg/mmol) and renal angiotensin converting enzyme activity (Control: 9.2+/-1.6 vs. Fructose: 7.6+/-1.0 ACE units) were not different between groups. There was a positive correlation between mean arterial pressure (r=0.7, p=0.01), blood pressure variability (BPV) (r=0.7, p=0.02), low frequency BPV component (r=0.677, p=0.03) and urinary protein excretion. Results show that consumption of a high fructose diet in mice had deleterious effects on renal function, which were correlated with cardiovascular changes. PMID:17207869

Cunha, Tatiana S; Farah, Vera; Paulini, Janaina; Pazzine, Mariana; Elased, Khalid M; Marcondes, Fernanda K; Cláudia Irigoyen, Maria; De Angelis, Kátia; Mirkin, L David; Morris, Mariana



A Novel Closed-Chest Porcine Model of Chronic Ischemic Heart Failure Suitable for Experimental Research in Cardiovascular Disease  

PubMed Central

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.

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



Body mass index trajectories and predictors among 3rd to 12th graders using growth curve mixture modeling the Child and Adolescent Trial for Cardiovascular Health (CATCH) study  

Microsoft Academic Search

This dissertation examined body mass index (BMI) growth trajectories and the effects of gender, ethnicity, dietary intake, and physical activity (PA) on BMI growth trajectories among 3rd to 12th graders (9-18 years of age). Growth curve model analysis was performed using data from The Child and Adolescent Trial for Cardiovascular Health (CATCH) study. The study population included 2909 students who

Hao T Duong



FNMOC Model Verification System.  

National Technical Information Service (NTIS)

Fleet Numerical Meteorology and Oceanography Center (FNMOC) forecasts the atmospheric environment and weather using several meteorological and oceanographic models. These models' forecasting abilities are verified by comparing the model forecast against t...

K. P. Pace



User Modeling in Dialog Systems  

Microsoft Academic Search

In this paper the definitions of and approaches to user modeling in natural language dialog systems have been reviewed. The contents of user models are discussed; how user modeling in different research areas relates to user modeling are reviewed; examples of some techniques for building user models through natural language interaction and observed behavior in other media channels are given.

Pontus Johansson



Cardiovascular effects of leptin  

Microsoft Academic Search

A wealth of investigations, ranging from clinical and animal model studies to in vitro analyses, have generated great interest in the cardiovascular effects of leptin. Accordingly, many studies have examined the contribution of leptin to cardiac remodeling in heart failure and whether the effects of leptin on metabolism, apoptosis, extracellular matrix remodeling, and hypertrophy could explain the so-called obesity paradox.

Gary Sweeney



Patient interaction in homecare systems to treat cardiovascular diseases in the long term.  


The rapid aging of the population worldwide will dramatically increase the number of people affected by chronic diseases in the next years. This social situation makes it necessary a paradigm shift from reactive care to preventive care. New technological paradigms, like Ambient Intelligence and Ubiquitous Computing, allow the development of Personal Health Systems (PHS) that guarantee the continuity of care and a better use of health resources. Therefore, patients should become the centre of the health care process, and PHS should be designed to fulfill the patient's goals and needs. User-centred methodologies provide a good framework for designing general use applications, but they do not usually take into account factors like the context where the interaction is taking place or the medical, social and business contexts that surround the patient. This paper presents a model for designing user's interaction in medical applications. The final goal is to develop highly usable user interfaces and to improve the user experience, aiming to guarantee the patient's adherence to the medical protocols and recommendations. PMID:19964214

Peinado, Ignacio; Arredondo, Maria Teresa; Villalba, Elena; Salvi, Dario; Ottaviano, Manuel



Cardiovascular risk and sildenafil  

Microsoft Academic Search

Sildenafil citrate is the first oral agent approved for the treatment of erectile dysfunction (ED); other oral agents are in the process of development. Because the mechanism of action of many of these agents involves vasodilation, there is a potential for interaction with the cardiovascular system. Sildenafil inhibits phosphodiesterase-5 (PDE-5) which is found in the corpus cavernosum and in the

Robert A Kloner



Stress in cardiovascular diseases  

Microsoft Academic Search

Results: Stress plays a major role in various (patho)physiological processes associated with the circula- tory system. Thereby, it potentially has ameliorating or detrimental capacities. However, with regard to cardiovascular diseases, stress most often is related to deleterious results. The specif- ic outcome depends on multiple variables (amount of stress, duration of its influence, patient's history\\/predisposition, genetic components - as they

Tobias Esch; George B. Stefano; Gregory L. Fricchione; Herbert Benson



A Model of Cardiovascular Disease Giving a Plausible Mechanism for the Effect of Fractionated Low-Dose Ionizing Radiation Exposure  

Microsoft Academic Search

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

Mark P. Little; Anna Gola; Ioanna Tzoulaki



Requirements for Complex Systems Modeling  

Microsoft Academic Search

Function modeling (FM) is the name given to the activity of developing models of devices\\/products\\/objects\\/processes based on their functionalities. Problems still exist in the design processes of complex systems which FM claims to address. Fundamental to these problems is the lack of system overview models. FM theories address issues including knowledge representation problems in product development, overall description and better

T. Tomiyama


Wavelet transform coherence based investigation of existence of relationship between the cardiovascular and postural control systems during orthostatic challenge.  


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



The Effects of Chronic Exposure to Low Levels of Carbon Monoxide on the Cardiovascular System of Dogs. II. Exposure to 50 and 150 PPM Carbon Monoxide.  

National Technical Information Service (NTIS)

A study of the effects due to chronic exposure to low levels of carbon monoxide on the cardiovascular and hematologic systems of dogs continued for the second year. In the previous report, the data were derived from animals exposed to 100 ppm carbon monox...

D. A. DeBias N. C. Birkhead C. M. Banerjee M. H. F. Friedman



Cardiovascular Proteomics  

Microsoft Academic Search

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


Advanced Restraint System Modeling.  

National Technical Information Service (NTIS)

The Articulated Total Body (ATB) model is currently being used by the AFAMRL to study the biomechanics of the pilot-seat ejection from an aircraft. The new ATB-II model presented in this report incorporates features developed since the original ATB model ...

F. E. Butler J. T. Fleck



Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system  

Microsoft Academic Search

Notch signaling is required for multiple aspects of cardiovascular development, including arterial-venous differentiation, septation and cushion formation. Despite recognition of the importance of the Notch pathway in normal cardiovascular development, the proximate downstream effectors are not yet known. Likely candidate effectors are members of the hairy and enhancer of split related (hesr) family of bHLH transcription factors. However, mutational analysis

Hiroki Kokubo; Sachiko Miyagawa-Tomita; Makoto Nakazawa; Yumiko Saga; Randy L. Johnson



[Cardiovascular system reaction to periodic head-to-tail G-force effects on a short-radius centrifuge].  


As a result of 370 experiments in a 2 m-arm centrifuge, high human tolerance to acceleration of +0.8, 1.2 and 1.6 Gz (at the level of feet) was demonstrated. Cardiovascular reactions depended on the value, duration and frequency of acceleration exposures. Cardiovascular responses included, primarily, changes in regional circulation of the legs. PMID:7359868

Vil'-Vil'iams, I F; Shul'zhenko, E B


Interactive Communication Systems Modeling Study.  

National Technical Information Service (NTIS)

This report deals with an effort to develop an interactive computer model for analysis and design of digital communications systems. In this report concepts are formulated and described for a Model for Interactive design and Analysis of Communication Syst...

R. W. Moss R. W. Rice D. R. Sentz



Interactive Communication Systems Modeling Study.  

National Technical Information Service (NTIS)

This interim report deals with the initial activities under an effort to develop an interactive computer model for analysis and design of digital communications systems. In this report concepts are formulated and described for a model for Interactive Desi...

R. W. Moss J. L. Hammond E. E. Donaldson




EPA Science Inventory

The Exposure Analysis Modeling System (EXAMS), first published in 1982 (EPA-600/3-82-023), provides interactive computer software for formulating aquatic ecosystem models and rapidly evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals--pesti...


Experimental study and constitutive modelling of the passive mechanical properties of the porcine carotid artery and its relation to histological analysis: Implications in animal cardiovascular device trials.  


The present study focusses on the determination, comparison and constitutive modelling of the passive mechanical properties of the swine carotid artery over very long stretches in both proximal and distal regions. Special attention is paid to the histological and mechanical variations of these properties depending on the proximity to the heart. The results can have clinical relevance, especially in the research field of intravascular device design. Before the final clinical trials on humans, research in the vascular area is conducted on animal models, swine being the most common due to the similarities between the human and swine cardiovascular systems as well as the fact that the swine size is suitable for testing devices, in this case endovascular carotid systems. The design of devices usually involves numerical techniques, and an important feature is the appropriate modelling of the mechanical properties of the vessel. Fourteen carotid swine arteries were harvested just after sacrifice and cyclic uniaxial tension tests in longitudinal and circumferential directions were performed for distal and proximal samples. The stress-stretch curves obtained were fitted with a hyperelastic anisotropic model. Stress-free configuration states were also analyzed. Finally, human and swine samples were processed in a histological laboratory and images were used to quantify their microconstituents. The statistical analysis revealed significant differences between the mechanical behavior of proximal and distal locations in the circumferential but not in the longitudinal direction. Circumferential direction samples show clear differences both in residual stretches and tensile curves between the two locations, while the features of longitudinal specimens are independent of the axial position. The statistical analysis provides significant evidence of changes depending on the position of the sample, mainly in elastin and SMC quantification. PMID:21371929

García, A; Peña, E; Laborda, A; Lostalé, F; De Gregorio, M A; Doblaré, M; Martínez, M A



Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: Insights from basic science and clinical studies.  


Recent publications describing the results of the Women's Health Initiative (WHI) and other studies reporting the impact of hormone therapy on aging women have spurred reexamination of the broad use of estrogens and progestins during the postmenopausal years. Here, we review the complex pharmacology of these hormones, the diverse and sometimes opposite effects that result from the use of different estrogenic and progestinic compounds, given via different delivery routes in different concentrations and treatment sequence, and to women of different ages and health status. We examine our new and growing appreciation of the role of estrogens in the immune system and the inflammatory response, and we pose the concept that estrogen's interface with this system may be at the core of some of the effects on multiple physiological systems, such as the adipose/metabolic system, the cardiovascular system, and the central nervous system. We compare and contrast clinical and basic science studies as we focus on the actions of estrogens in these systems because the untoward effects of hormone therapy reported in the WHI were not expected. The broad interpretation and publicity of the results of the WHI have resulted in a general condemnation of all hormone replacement in postmenopausal women. In fact, careful review of the extensive literature suggests that data resulting from the WHI and other recent studies should be interpreted within the narrow context of the study design. We argue that these results should encourage us to perform new studies that take advantage of a dialogue between basic scientists and clinician scientists to ensure appropriate design, incorporation of current knowledge, and proper interpretation of results. Only then will we have a better understanding of what hormonal compounds should be used in which populations of women and at what stages of menopausal/postmenopausal life. PMID:16763155

Turgeon, Judith L; Carr, Molly C; Maki, Pauline M; Mendelsohn, Michael E; Wise, Phyllis M



Computer analysis of cardiovascular parameters.  


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



Systemic vasculopathy with altered vasoreactivity in a transgenic mouse model of scleroderma  

Microsoft Academic Search

INTRODUCTION: Vasculopathy, including altered vasoreactivity and abnormal large vessel biomechanics, is a hallmark of systemic sclerosis (SSc). However, the pathogenic link with other aspects of the disease is less clear. To assess the potential role of transforming growth factor beta (TGF-?) overactivity in driving these cardiovascular abnormalities, we studied a novel transgenic mouse model characterized by ligand-dependent activation of TGF-?

Emma C Derrett-Smith; Audrey Dooley; Korsa Khan; Xu Shi-wen; David J Abraham; Christopher P Denton



Game Models for Open Systems.  

National Technical Information Service (NTIS)

An open system is a system whose behavior is jointly determined by its internal structure and by the input it receives from the environment. To solve control and verification problem open systems have often been modeled as games between the System and the...

L. de Alfaro



Modeling formalisms in Systems Biology  

PubMed Central

Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future.



Physical system modeling with Modelica  

Microsoft Academic Search

A new language, called ModelicaTM, for the modeling of physical systems has been developed in an international effort. The main objective was to make it easy to exchange models and model libraries. The design approach builds on non-causal modeling with true ordinary differential and algebraic equations and the use of object-oriented constructs to facilitate the reuse of modeling knowledge. There

Sven Erik Mattsson; Hilding Elmqvist; Martin Otter



Developmental plasticity in the cardiovascular system of fish, with special reference to the zebrafish  

Microsoft Academic Search

During development the circulatory system of vertebrates typically starts operating earlier than any other organ. In these early stages, however, blood flow is not yet linked to metabolic requirements of tissues, as is well established for adults. While the autonomic nervous system becomes functional only quite late during development, in the early stages control of blood flow appears to be

Bernd Pelster



The adrenergic regulation of the cardiovascular system in the South American rattlesnake, Crotalus durissus.  


The present study investigates adrenergic regulation of the systemic and pulmonary circulations of the anaesthetised South American rattlesnake, Crotalus durissus. Haemodynamic measurements were made following bolus injections of adrenaline and adrenergic antagonists administered through a systemic arterial catheter. Adrenaline caused a marked systemic vasoconstriction that was abolished by phentolamine, indicating this response was mediated through alpha-adrenergic receptors. Injection of phentolamine gave rise to a pronounced vasodilatation (systemic conductance (G(sys)) more than doubled), while injection of propranolol caused a systemic vasoconstriction, pointing to a potent alpha-adrenergic, and a weaker beta-adrenergic tone in the systemic vasculature of Crotalus. Overall, the pulmonary vasculature was far less responsive to adrenergic stimulation than the systemic circulation. Adrenaline caused a small but non-significant pulmonary vasodilatation and there was tendency of reducing this dilatation after either phentolamine or propranolol. Injection of phentolamine increased pulmonary conductance (G(pul)), while injection of propranolol produced a small pulmonary constriction, indicating that alpha-adrenergic and beta-adrenergic receptors contribute to a basal regulation of the pulmonary vasculature. Our results suggest adrenergic regulation of the systemic vasculature, rather than the pulmonary, may be an important factor in the development of intracardiac shunts. PMID:17669676

Galli, Gina L J; Skovgaard, Nini; Abe, Augusto S; Taylor, Edwin W; Wang, Tobias



Parametric conditional frailty models for recurrent cardiovascular events in the lipid study  

Microsoft Academic Search

Background Analysis of recurrent event data is frequently needed in clinical and epidemiological studies. An important issue in such analysis is how to account for the dependence of the events in an individual and any unobserved heterogeneity of the event propensity across individuals.Methods We applied a number of conditional frailty and nonfrailty models in an analysis involving recurrent myocardial infarction

Jisheng Cui; Andrew Forbes; Adrienne Kirby; Ian Marschner; John Simes; Malcolm West; Andrew Tonkin



Semiparametric risk prediction models for recurrent cardiovascular events in the LIPID study  

Microsoft Academic Search

BACKGROUND: Traditional methods for analyzing clinical and epidemiological cohort study data have been focused on the first occurrence of a health outcome. However, in many situations, recurrent event data are frequently observed. It is inefficient to use methods for the analysis of first events to analyse recurrent event data. METHODS: We applied several semi-parametric proportional hazards models to analyze the

Jisheng Cui; Andrew Forbes; Adrienne Kirby; Ian Marschner; John Simes; David Hunt; Malcolm West; Andrew Tonkin



Noise, sleep and poor health: Modeling the relationship between road traffic noise and cardiovascular problems  

Microsoft Academic Search

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



Large scale expansion of human umbilical cord cells in a rotating bed system bioreactor for cardiovascular tissue engineering applications.  


Widespread use of human umbilical cord cells for cardiovascular tissue engineering requires production of large numbers of well-characterized cells under controlled conditions. In current research projects, the expansion of cells to be used to create a tissue construct is usually performed in static cell culture systems which are, however, often not satisfactory due to limitations in nutrient and oxygen supply. To overcome these limitations dynamic cell expansion in bioreactor systems under controllable conditions could be an important tool providing continuous perfusion for the generation of large numbers of viable pre-conditioned cells in a short time period. For this purpose cells derived from human umbilical cord arteries were expanded in a rotating bed system bioreactor for up to 9 days. For a comparative study, cells were cultivated under static conditions in standard culture devices. Our results demonstrated that the microenvironment in the perfusion bioreactor was more favorable than that of the standard cell culture flasks. Data suggested that cells in the bioreactor expanded 39 fold (38.7 ± 6.1 fold) in comparison to statically cultured cells (31.8 ± 3.0 fold). Large-scale production of cells in the bioreactor resulted in more than 3 x 10(8) cells from a single umbilical cord fragment within 9 days. Furthermore cell doubling time was lower in the bioreactor system and production of extracellular matrix components was higher. With this study, we present an appropriate method to expand human umbilical cord artery derived cells with high cellular proliferation rates in a well-defined bioreactor system under GMP conditions. PMID:23847691

Reichardt, Anne; Polchow, Bianca; Shakibaei, Mehdi; Henrich, Wolfgang; Hetzer, Roland; Lueders, Cora



Space: Modeling the Solar System  

NSDL National Science Digital Library

In this activity, students compare and contrast the diameters of the other planets in the solar system to that of the Earth, create a scale factor based on a reasonable size for the Earth's model and build a scale model of the solar system.



SP-100 control system modeling  

NASA Astrophysics Data System (ADS)

SP-100 Control Systems modeling was done using a thermal hydraulic transient analysis model called ARIES-S. The ARIES-S Computer Simulation provides a basis for design, integration and analysis of the reactor including the control and protection systems. It is a modular digital computer simulation written in FORTRAN that operates interactively in real time on a VAX minicomputer.

Meyer, R. A.; Halfen, F. J.; Alley, A. D.


Nurse-based models for cardiovascular disease prevention From research to clinical practice  

Microsoft Academic Search

The worldwide personal and societal costs related to diseases of the vascular system are enormous. International research efforts have focused on discovering ways to implement prevention strategies shown to be both effective and cost-efficient. Teams comprising health care professionals with expertise in nursing, dietetics, physical activity, and behavioral skills have shown high levels of success in preventive efforts, particularly in

Kathy Berra; Nancy Houston Miller; Catriona Jennings



The Effects of Chronic Exposure to Carbon Monoxide (100 PPM) on the Cardiovascular System of Monkeys.  

National Technical Information Service (NTIS)

The purpose of the study was to obtain quantitative correlations between chronic exposure to 100 ppm carbon monoxide and physiologic parameters of the cardiovascule system and blood of normal monkeys, and monkeys with induced myocardial infarction. Pathol...

D. A. DeBias



Nonlinear Systems Dynamics in Cardiovascular Physiology: The Heart Rate Delay MAP and Lower Body Negative Pressure.  

National Technical Information Service (NTIS)

A preliminary study of the applicability of nonlinear dynamic systems analysis techniques to low body negative pressure (LBNP) studies. In particular, the applicability of the heart rate delay map is investigated. It is suggested that the heart rate delay...

J. C. Hooker



Induced Chromosome Deletion in a Williams-Beuren Syndrome Mouse Model Causes Cardiovascular Abnormalities  

Microsoft Academic Search

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 DSSAT cropping system model  

Microsoft Academic Search

The decision support system for agrotechnology transfer (DSSAT) has been in use for the last 15 years by researchers worldwide. This package incorporates models of 16 different crops with software that facilitates the evaluation and application of the crop models for different purposes. Over the last few years, it has become increasingly difficult to maintain the DSSAT crop models, partly

J. W. Jones; G. Hoogenboom; C. H. Porter; K. J. Boote; W. D. Batchelor; L. A. Hunt; P. W. Wilkens; U. Singh; A. J. Gijsman; J. T. Ritchie



Partial Restoration of Cardio-Vascular Defects in Rescued Severe Model of Spinal Muscular Atrophy  

PubMed Central

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.

Shababi, Monir; Habibi, Javad; Ma, Lixin; Glascock, Jacqueline; Sowers, James R.; Lorson, Christian L.



Dynamic System Modeling and Control  

NSDL National Science Digital Library

This web page, authored by Hugh Jack of Grand Valley State University, provides free links to the chapters of a text providing detailed systems analysis and modeling information. The author defines in depth different systems from mechanical to electrical to magnetics. Included is much mathematical technique analysis including laplace transforms and bode plots. Broadly covers analysis and the mathematical strategies for performing it. This text could be used as a stand-alone for systems modeling.

Jack, Hugh



Launch systems operations cost modeling  

NASA Astrophysics Data System (ADS)

This paper describes the launch systems operations modeling portion of a larger model development effort, NASA's Space Operations Cost Model (SOCM), led by NASA HQ. The SOCM study team, which includes cost and technical experts from each NASA Field Center and various contractors, has been tasked to model operations costs for all future NASA mission concepts including planetary and Earth orbiting science missions, space facilities, and launch systems. The launch systems operations modeling effort has near term significance for assessing affordability of our next generation launch vehicles and directing technology investments, although it provides only a part of the necessary inputs to assess life cycle costs for all elements that determine affordability for a launch system. Presented here is a methodology to estimate requirements associated with a launch facility infrastructure, or Spaceport, from start-up/initialization into steady-state operation. Included are descriptions of the reference data used, the unique estimating methodology that combines cost lookup tables, parametric relationships, and constructively-developed correlations of cost driver input values to collected reference data, and the output categories that can be used by economic and market models. Also, future plans to improve integration of launch vehicle development cost models, reliability and maintainability models, economic and market models, and this operations model to facilitate overall launch system life cycle performance simulations will be presented.

Jacobs, Mark K.



Cardiovascular Disease  

PubMed Central

Health Issue Cardiovascular disease (CVD) is the leading cause of death in Canadian women and men. In general, women present with a wider range of symptoms, are more likely to delay seeking medial care and are less likely to be investigated and treated with evidence-based medications, angioplasty or coronary artery bypass graft than men. Key Findings In 1998, 78,964 Canadians died from CVD, almost half (39,197) were women. Acute myocardial infarction, which increases significantly after menopause, was the leading cause of death among women. Cardiovascular disease accounted for 21% of all hospital admissions for Canadian women over age 50 in 1999. Admissions to hospital for ischemic heart disease were more frequent for men, but the mean length of hospital stay was longer for women. Mean blood pressure increases with age in both men and women. After age 65, however, high blood pressure is more common among Canadian women. More than one-third of postmenopausal Canadian women have hypertension. Diabetes increases the mortality and morbidity associated with CVD in women more than it does in men. Depression also contributes to the incidence and recovery from CVD, particularly for women who experience twice the rate of depression as men. Data Gaps and Recommendations CVD needs to be recognized as a woman's health issue given Canadian mortality projections (particularly heart failure). Health professionals should be trained to screen, track, and address CVD risk factors among women, including hypertension, elevated lipid levels, smoking, physical inactivity, depression, diabetes and low socio-economic status.

Grace, Sherry L; Fry, Rick; Cheung, Angela; Stewart, Donna E



Relationship of Paraoxonase 1 (PON1) Gene Polymorphisms and Functional Activity With Systemic Oxidative Stress and Cardiovascular Risk  

PubMed Central

Context Paraoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. The relationship between PON1 genotypes and functional activity with systemic measures of oxidative stress and cardiovascular disease (CVD) risk in humans has not been systematically investigated. Objective To investigate the relationship of genetic and biochemical determinants of PON1 activity with systemic measures of oxidative stress and CVD risk in humans. Design, Setting, and Participants The association between systemic PON1 activity measures and a functional polymorphism (Q192R) resulting in high PON1 activity with prevalent CVD and future major adverse cardiac events (myocardial infarction, stroke, or death) was evaluated in 1399 sequential consenting patients undergoing diagnostic coronary angiography between September 2002 and November 2003 at the Cleveland Clinic. Patients were followed up until December 2006. Systemic levels of multiple structurally defined fatty acid oxidation products were also measured by mass spectrometry in 150 age-, sex-, and race-matched patients and compared with regard to PON1 genotype and activity. Main Outcome Measures Relationship between a functional PON1 polymorphism and PON1 activity with global indices of systemic oxidative stress and risk of CVD. Results The PON1 genotype demonstrated significant dose-dependent associations (QQ192>QR192>RR192) with decreased levels of serum PON1 activity and with increased levels of systemic indices of oxidative stress. Compared with participants with either the PON1 RR192 or QR192 genotype, participants with the QQ192 genotype demonstrated an increased risk of all-cause mortality (43/681 deaths [6.75%] in RR192 and QR192 and 62/584 deaths [11.1%] in QQ192; adjusted hazard ratio, 2.05; 95% confidence interval [CI], 1.32–3.18) and of major adverse cardiac events (88/681 events [13.6%] in RR192 and QR192 and 102/584 events [18.0%] in QQ192; adjusted hazard ratio, 1.48; 95% CI, 1.09–2.03; P=.01). The incidence of major adverse cardiac events was significantly lower in participants in the highest PON1 activity quartile (23/315 [7.3%]) and 235/324 [7.7%] for paraoxonase and arylesterase, respectively) compared with those in the lowest activity quartile (78/311 [25.1%] and 75/319 [23.5%]; P<.001 for paraoxonase and arylesterase, respectively). The adjusted hazard ratios for major adverse cardiac events between the highest and lowest PON1 activity quartiles were, for paraoxonase, 3.4 (95% CI, 2.1–5.5; P<.001) and for arylesterase, 2.9 (95% CI, 1.8–4.7; P<.001) and remained independent in multivariate analysis. Conclusion This study provides direct evidence for a mechanistic link between genetic determinants and activity of PON1 with systemic oxidative stress and prospective cardiovascular risk, indicating a potential mechanism for the atheroprotective function of PON1.

Bhattacharya, Tamali; Nicholls, Stephen J.; Topol, Eric J.; Zhang, Renliang; Yang, Xia; Schmitt, David; Fu, Xiaoming; Shao, Mingyuan; Brennan, Danielle M.; Ellis, Stephen G.; Brennan, Marie-Luise; Allayee, Hooman; Lusis, Aldons J.; Hazen, Stanley L.



Sodium heat transfer system modeling  

SciTech Connect

The sodium heat transfer system of the International Energy Agency (IEA) Small Solar Power Systems (SSPS) Central Receiver System (CRS), which includes the heliostat field, receiver, hot and cold storage vessels, and sodium/water steam generator has been modeled. The computer code SOLTES (Simulator of Large Thermal Energy Systems), developed by Sandia National Laboratories, was used to model this system. Based on data provided to Sandia by the IEA-SSPS/CRS project, the results from SOLTES are compared to measured data. The comparison between measured data and predictions from SOLTES is very good for the day evaluated.

Baker, A.F.; Fewell, M.E.



[Cardiovascular disease and sexuality].  


Sexual activity corresponds to light to moderate physical exercise and entails no significant risk to the majority of patients with cardiovascular disease. In patients suffering from severe angina or chronic heart failure, however, sexual activity might trigger coital angina or cardiac decompensation necessitating hospitalization. Nevertheless, even for patients with coronary artery disease the absolute risk of having a heart attack or fatal event during sexual activity is extremely low. Due to systemic atherosclerosis and concomitant endothelial dysfunction the prevalence of sexual dysfunction is higher in patients with cardiovascular disease as compared to the general population. PDE-5 inhibitors can be safely used by many patients suffering from both, cardiovascular disease and sexual dysfunction as long as no concomitant medication with nitrates exists. The concomitant use of PDE-5 inhibitors and nitrates is strictly contraindicated because of the risk of life-threatening hypotension. It is therefore of utmost importance to ask patients presenting with coital angina about PDE-5 inhibitor intake before the administration of nitrate-based anti-ischemic therapies. The recommendations of the Princeton Consensus Conference provide a useful framework for risk stratification and counseling of patients with cardiovascular disease regarding sexual activity. PMID:20235042

Pfister, Otmar



The Intelligent System of Cardiovascular Disease Diagnosis Based on Extension Data Mining  

NASA Astrophysics Data System (ADS)

This thesis gives the general definition of the concepts of extension knowledge, extension data mining and extension data mining theorem in high dimension space, and also builds the IDSS integrated system by the rough set, expert system and neural network, develops the relevant computer software. From the diagnosis tests, according to the common diseases of myocardial infarctions, angina pectoris and hypertension, and made the test result with physicians, the results shows that the sensitivity, specific and accuracy diagnosis by the IDSS are all higher than the physicians. It can improve the rate of the accuracy diagnosis of physician with the auxiliary help of this system, which have the obvious meaning in low the mortality, disability rate and high the survival rate, and has strong practical values and further social benefits.

Sun, Baiqing; Li, Yange; Zhang, Lin


Modeling Towed Cable System Dynamics.  

National Technical Information Service (NTIS)

A method for modeling the dynamics of towed cable systems is described. The cable system is assumed to be a multiple branched system with towed bodies. These bodies may be spheres or more general vehicles having a single plane of symmetry. The motion of t...

J. W. Kamman T. C. Nguyen



Information Systems Outsourcing Relationship Model  

Microsoft Academic Search

Increasing attention is being paid to what determines the success of an information systems outsourcing arrangement. The current research aims to provide an improved understanding of the factors influencing the outcome of an information systems outsourcing relationship and to provide a preliminary validation of an extended outsourcing relationship model by interviews with information systems outsourcing professionals in both the client

Richard Flemming; Graham Low



Chemical compositions and properties of Schinus areira L. essential oil on airway inflammation and cardiovascular system of mice and rabbits.  


The main purpose was to investigate the effects of essential plant-oil of Schinus areira L. on hemodynamic functions in rabbits, as well as myocardial contractile strength and airways inflammation associated to bacterial endotoxin lipopolysaccharide (LPS) in mice. This study shows the important properties of the essential oil (EO) of S. areira studied and these actions on lung with significant inhibition associated to LPS, all of which was assessed in mice bronchoalveolar lavage fluid and evidenced by stability of the percentage of alveolar macrophages, infiltration of polymorphonuclear leukocytes and tumor necrosis factor-? concentration, and without pathway modifications in conjugated dienes activity. Clinical status (morbidity or mortality), macroscopic morphology and lung/body weight index were unaffected by the administration of the EO S. areira. Furthermore, the ex vivo analysis of isolated hearts demonstrated the negative inotropic action of the EO of S. areira in a mice model, and in rabbits changes in the hemodynamic parameters, such as a reduction of systolic blood pressure. We conclude that EO S. areira could be responsible for modifications on the cardiovascular and/or airway parameters. PMID:22546367

Bigliani, María C; Rossetti, Víctor; Grondona, Ezequiel; Lo Presti, Silvina; Paglini, Patricia M; Rivero, Virginia; Zunino, María P; Ponce, Andrés A



A biochemical rationale for the discrete behavior of nitroxyl and nitric oxide in the cardiovascular system  

Microsoft Academic Search

The redox siblings nitroxyl (HNO) and nitric oxide (NO) have often been assumed to undergo casual redox reactions in biological systems. However, several recent studies have demonstrated distinct pharmacological effects for donors of these two species. Here, infusion of the HNO donor Angeli's salt into normal dogs resulted in elevated plasma levels of calcitonin gene-related peptide, whereas neither the NO

Katrina M. Miranda; Nazareno Paolocci; Tatsuo Katori; Douglas D. Thomas; Eleonora Ford; Michael D. Bartberger; Michael G. Espey; David A. Kass; Martin Feelisch; Jon M. Fukuto; David A. Wink



Dual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials challenge existing evidence?  

PubMed Central

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.



Effect of vitamin E and C supplements on antioxidant defense system in cardiovascular disease patients in Zahedan, southeast Iran.  


Oxidative stress plays an important role in the pathogenesis of cardiovascular disease (CVD). Growing evidence suggest that antioxidant vitamins might reduce the risk of disease outcomes by their ability to scavenge free radicals. The aim of the present study was to evaluate the supplementation of vitamins E and C on oxidant and antioxidant status in CVD patients. We conducted a case-control study with vitamin E (400 IU/d) and vitamin C (500 mg/d) supplementation in 40 CVD patients for 2 mo. Antioxidant (enzymatic and non-enzymatic) and oxidant status were analyzed pre and post supplementation. In the initial stage the activity of both enzymatic and non-enzymatic antioxidants were lower, while the malondialdehyde (MDA) level was elevated (p<0.0001). After intervention, a significant increase in superoxide dismutase (SOD) activity (61.7%), glutathione peroxidase (GPx) activity (59.3%), the levels of vitamin E (83.7%), C (145.3%), total antioxidant capacity (TAC) (62.8%) and a significant decrease in MDA (40%) value were observed (p<0.0001). There was a significant negative correlation between MDA and TAC. The results suggest that supplementation with a combination of vitamins E and C reduced lipid peroxidation and strengthened the antioxidant defense system. Hence, there will be beneficial effects on the heart by reducing oxidative stress in CVD patients. PMID:21422713

Karajibani, Mansour; Hashemi, Mohammad; Montazerifar, Farzaneh; Dikshit, Madhurima



euHeart: personalized and integrated cardiac care using patient-specific cardiovascular modelling  

PubMed Central

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.

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



Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development  

PubMed Central

The growth factor family of neurotrophins has major roles both inside and outside the nervous system. Here, we report a detailed histological analysis of key phenotypes generated by the ablation of the Kinase D interacting substrate of 220?kDa/Ankyrin repeat-rich membrane spanning (Kidins220/ARMS) protein, a membrane-anchored scaffold for the neurotrophin receptors Trk and p75NTR. Kidins220 is important for heart development, as shown by the severe defects in the outflow tract and ventricle wall formation displayed by the Kidins220 mutant mice. Kidins220 is also important for peripheral nervous system development, as the loss of Kidins220 in vivo caused extensive apoptosis of DRGs and other sensory ganglia. Moreover, the neuronal-specific deletion of this protein leads to early postnatal death, showing that Kidins220 also has a critical function in the postnatal brain.

Cesca, F; Yabe, A; Spencer-Dene, B; Arrigoni, A; Al-Qatari, M; Henderson, D; Phillips, H; Koltzenburg, M; Benfenati, F; Schiavo, G



Neurohistochemical and electron microscopic investigations of pathological and age-related changes in the cardiovascular system.  


Neurohistochemical and electron microscopic investigations of the autonomic nervous system (ANS) of man and animals suggest that its ontogenesis can be divided into the premediatory, mediatory and postmediatory periods of development. The postmediatory period begins heterochronically in various ganglia of the ANS. A normal process of early cardiac desympathization usually occurs at the age of 35 to 60 years. Specific changes of preceding sudden cardiac death are elicited in different parts of the ANS and adrenal glands. This is accompanied by focal myocardial desympathization. Coronary vessels and conducting system which may influence myocardial hypersensitivity zones to catecholamines are involved in the process of destabilization of the cardiac function. Moreover, relationships are demonstrated which exist between the atherosclerotic lesions of the aortic wall and the status of its nerve plexuses. PMID:1584987

Shvalev, V N; Guski, H; Fernández-Britto, J E; Sosunov, A A; Pavlovich, E R; Anikin AYu; Zhuchkova, N I; Kargina-Terentyeva, R A



Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation  

Microsoft Academic Search

Angiotensin-converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (RAS) and ACE-inhibitors are widely used in several clinical conditions, including hypertension and heart failure. Recently, a homologue of ACE, ACE2 has been discovered. Both ACE and ACE2 are emerging as key enzymes of the RAS, where ACE2 may play a role as negative regulator of ACE. Moreover, ACE2

Pasquale Pagliaro; Claudia Penna



Absence of Chlamydia pneumoniae and Signs of Atherosclerotic Cardiovascular Disease in Adolescents with Systemic Lupus Erythematosus  

Microsoft Academic Search

Patients with systemic lupus erythematosus (SLE) have accelerated atherogenesis. A recent study suggested that Chlamydia pneumoniae infection might also be a contributing factor in the development of atherogenesis in patients with SLE. The objective of\\u000a this study was to investigate the possible association of C. pneumoniae infection with markers of atherosclerosis in adolescents with SLE compared with age-matched healthy controls.

Corinna S. Bowser; Swati Kumar; Louis Salciccioli; Andrei Kutlin; Jason Lazar; Imran Rahim; Amy Suss; Stephan Kohlhoff; Margaret R. Hammerschlag; Hamid Jack Moallem



Advances in a fully integrated intravascular OCT-ultrasound system for cardiovascular imaging  

NASA Astrophysics Data System (ADS)

Intracoronary optical coherence tomography (OCT) and intravascular ultrasound (IVUS) are two popular techniques for the detection and determination of atherosclerosis. IVUS allows visualization of plaques while also providing a large penetration depth to determine plaque volume. Intracoronary OCT provides the ability to capture microscopic features associated with high risk plaque. Traditionally to utilize the benefits of both modalities, separate probes and systems had to be used one at a time to image a vessel. We present work required to create a combined OCT IVUS system capable of simultaneous imaging to detect atherosclerotic plaques. A novel integrated probe of size 0.69 mm OD featuring sequential placement of components was created to acquire co-registered images within small coronary vessels. By utilizing commercial graphics processing units (GPUs) real time visualization of acquired data is possible up to a maximum 48 frames per second per channel. In vitro studies on human coronary artery samples as well as in vivo studies in rabbits and pigs show various plaque buildups in both OCT and IVUS images which match histology results, demonstrating the capabilities of the system.

Jing, Joe; Li, Jiawen; Li, Xiang; Yin, Jiechen; Zhang, Jun; Hoang, Khiet; Patel, Pranav; Zhou, Qifa; Chen, Zhongping



Pediatric cardiovascular drug development and research: integration of modeling and simulation as one future direction.  


The integration of the needs of children into the legal drug development process since 1997 in the United States and since 2007 in the European Union has improved health and stimulated innovative approaches in the design of clinical trials and will benefit both current and future populations. According to the US Food and Drug Administration, to date, 394 pediatric labels together with safer medicines and better dosing practices have provided a sound basis for the safer and more effective use of drugs in a pediatric population. This may be measurable with fewer medication errors and perhaps shorter hospital stays in the future. Although relevant data have been generated by clinical trials in pediatric populations, challenges, such as nonefficacy and safety issues, have arisen. Heterogeneity in the physiological maturation and growth processes and differences in the etiology and pathogenesis of disease in patients from birth to 18 years of age may explain these results. The use of cutting-edge technology, such as modeling and simulation of "in silico" pediatric populations, may allow the integration of data from previous trials and experiments into the design of future clinical trials and allow exploration in other areas that have the potential to enhance the outcome of clinical trials in children. PMID:21654330

Läer, Stephanie



Interventional Cardiovascular MRI  

Microsoft Academic Search

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


Biomechanics of the cardiovascular system: the aorta as an illustratory example  

PubMed Central

Biomechanics relates the function of a physiological system to its structure. The objective of biomechanics is to deduce the function of a system from its geometry, material properties and boundary conditions based on the balance laws of mechanics (e.g. conservation of mass, momentum and energy). In the present review, we shall outline the general approach of biomechanics. As this is an enormously broad field, we shall consider a detailed biomechanical analysis of the aorta as an illustration. Specifically, we will consider the geometry and material properties of the aorta in conjunction with appropriate boundary conditions to formulate and solve several well-posed boundary value problems. Among other issues, we shall consider the effect of longitudinal pre-stretch and surrounding tissue on the mechanical status of the vessel wall. The solutions of the boundary value problems predict the presence of mechanical homeostasis in the vessel wall. The implications of mechanical homeostasis on growth, remodelling and postnatal development of the aorta are considered.

Kassab, Ghassan S



Effect of decimeter waves on functional state of cardiovascular system, some biochemical and immunological parameters of patients recovering from myocardial infarction  

SciTech Connect

Optimum localization of decimeter wave (DMW) treatment and its intensity was determined to investigate the effect of DMW on functional state of the cardiovascular system, and clinical biochemical parameters of patients with myocardial infarction in the early posthospitalization period. It is assumed that the effect of DMW via the segmented autonomic system leads to marked changes in the systems. With delivery of treatment to the DI-DV region, the effect on the heart occurs first through the autonomic nervous system which is shown by its vagotropic effect.

Sorokina, Y.I.; Poshkus, N.B.; Tupitsina, Y.Y.; Volkova, L.P.; Shubina, A.V.; Krasnikov, V.Y.



[The functional state of the cardiovascular system and the level of physical performance in 7-8-year-old children under conditions of aerotechnogenic pollution].  


The aim of the study was to investigate the functional state of the cardiovascular system and the level of physical performance in 7-8-year-old children living in the urban area where air pollution caused by heavy vehicle traffic is high. The cardiovascular system and physical performance were evaluated using the conventional methods in 7-8-year-old 1097 children: a control group included 652 children (363 boys and 289 girls) and a comparison group consisted of 445 persons (239 boys and 206 girls). Under aerotechnogenic pollution, diastolic and mean blood pressures were found to be higher in both groups; the maximum oxygen consumption was lower in the boys and the girls had a decreased heart rate following 4-minute exercise. PMID:22834270

Tuliakova, O V


Exercise hemodynamics during extended continuous flow left ventricular assist device support: the response of systemic cardiovascular parameters and pump performance.  


Patients on continuous flow left ventricular assist devices (cf-LVADs) are able to return to an active lifestyle and perform all sorts of physical activities. This study aims to evaluate exercise hemodynamics in patients with a HeartMate II cf-LVAD (HM II). Thirty (30) patients underwent a bicycle exercise test. Along with exercise capacity, systemic cardiovascular responses and pump performance were evaluated at 6 and 12 months after HM II implantation. From rest to maximum exercise, heart rate increased from 87?±?14 to 140?±?32 beats/minute (bpm) (P?Systemic vascular resistance (SVR) decreased from 1776?±?750 to 1013?±?383 dynes.s/cm(5) (P?

Martina, Jerson; Jonge, Nicolaas; Rutten, Marcel; Kirkels, J Hans; Klöpping, Corinne; Rodermans, Ben; Sukkel, Eveline; Hulstein, Nelienke; Mol, Bas; Lahpor, Jaap



Nrf2 and Cardiovascular Defense  

PubMed Central

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.



Quantitative Coronary Angiographic and Intravascular Ultrasound Assessment of a New Nonarticulated Stent: Report From the Advanced Cardiovascular Systems MultiLink Stent Pilot Study  

Microsoft Academic Search

Objectives. The purpose of this study was to evaluate the safety, feasibility, optimal deployment technique and 1-year clinical outcome for the Advanced Cardiovascular Systems (ACS) MultiLink stent.Background. Optimal stent deployment assessed by quantitative coronary angiography and intravascular ultrasound (IVUS) is associated with improved clinical outcome.Methods. Forty-nine consecutive patients with a discrete stenosis in a native coronary artery 3 to 4

Joseph P. Carrozza; James B. Hermiller; Thomas J. Linnemeier; Jeffrey J. Popma; Paul G. Yock; Gary S. Roubin; Larry S. Dean; Richard E. Kuntz; Linda Robertson; Kalon K. L. Ho; Donald E. Cutlip; Donald S. Baim



Down-regulation of corticotropin-releasing hormone receptor type 2? mRNA expression in the rat cardiovascular system following food deprivation  

Microsoft Academic Search

The present study was conducted to assess the effect of nutritional stress induced by food deprivation on expression of messenger ribonucleic acid (mRNA) for corticotropin-releasing hormone receptor type 2? (CRH-R2?) in the rat cardiovascular system in the presence or absence of changes in circulating corticosterone. Food deprivation for 96 h caused a robust increase in plasma corticosterone levels and a

Hossein Pournajafi Nazarloo; Mitsuru Nishiyama; Yasushi Tanaka; Koichi Asaba; Kozo Hashimoto



Kidney modeling and systems physiology.  


We present an overview of currently available resources in renal systems physiology and indicate directions for development toward the renal physiome. After a brief resumé of objectives, we summarize legacy-modeling studies that can serve as the foundation for a more complete toolset. These include detailed models of practically all renal cell types and nephron segments and a variety of models of nephro-vascular exchanges in the medulla, of renal hemodynamics, and studies of tubuloglomerular feedback and autoregulation. Recent detailed anatomical reconstructions have brought surprising new results to bear on classic unsolved problems. In parallel with the modeling environment, progress has been made toward the quantitative database and model repository resources that must accompany the modeling environment in order to attain the goal of an open-ended, flexible, and collaborative infrastructure for renal systems biology, with an indication of prospects for integration with initiatives in the larger IUPS Physiome Project. PMID:20835990

Thomas, S Randall


Hemodynamic Energy Dissipation in the Cardiovascular System: Generalized Theoretical Analysis on Disease States  

PubMed Central

Background We present a fundamental theoretical framework for analysis of energy dissipation in any component of the circulatory system and formulate the full energy budget for both venous and arterial circulations. New indices allowing disease-specific subject-to-subject comparisons and disease-to-disease hemodynamic evaluation (quantifying the hemodynamic severity of one vascular disease type to the other) are presented based on this formalism. Methods and Results Dimensional analysis of energy dissipation rate with respect to the human circulation shows that the rate of energy dissipation is inversely proportional to the square of the patient body surface area and directly proportional to the cube of cardiac output. This result verified the established formulae for energy loss in aortic stenosis that was solely derived through empirical clinical experience. Three new indices are introduced to evaluate more complex disease states: (1) circulation energy dissipation index (CEDI), (2) aortic valve energy dissipation index (AV-EDI), and (3) total cavopulmonary connection energy dissipation index (TCPCEDI). CEDI is based on the full energy budget of the circulation and is the proper measure of the work performed by the ventricle relative to the net energy spent in overcoming frictional forces. It is shown to be 4.01 ± 0.16 for healthy individuals and above 7.0 for patients with severe aortic stenosis. Application of CEDI index on single-ventricle venous physiology reveals that the surgically created Fontan circulation, which is indeed palliative, progressively degrades in hemodynamic efficiency with growth (p <0.001), with the net dissipation in a typical Fontan patient (Body surface area = 1.0 m2) being equivalent to that of an average case of severe aortic stenosis. AV-EDI is shown to be the proper index to gauge the hemodynamic severity of stenosed aortic valves as it accurately reflects energy loss. It is about 0.28 ± 0.12 for healthy human valves. Moderate aortic stenosis has an AV-EDI one order of magnitude higher while clinically severe aortic stenosis cases always had magnitudes above 3.0. TCPC-EDI represents the efficiency of the TCPC connection and is shown to be negatively correlated to the size of a typical “bottle-neck” region (pulmonary artery) in the surgical TCPC pathway (p <0.05). Conclusions Energy dissipation in the human circulation has been analyzed theoretically to derive the proper scaling (indexing) factor. CEDI, AV-EDI, and TCPC-EDI are proper measures of the dissipative characteristics of the circulatory system, aortic valve, and the Fontan connection, respectively.

Dasi, Lakshmi P.; Pekkan, Kerem; de Zelicourt, Diane; Sundareswaran, Kartik S.; Krishnankutty, Resmi; Delnido, Pedro J.; Yoganathan, Ajit P.



Advising Models and Delivery Systems.  

ERIC Educational Resources Information Center

|Reviews factors influencing the organization and delivery of academic advising services. Discusses the strengths and weaknesses of seven two-year college organizational models, including faculty only, supplementary, split, dual, total intake, satellite, and self-contained models. Describes advising delivery systems using faculty advisors,…

King, Margaret C.



Enterprise Systems Analysis and Modelling  

Microsoft Academic Search

In ES implementations, process modelling is a critical and often overlooked activity. This paper proposes a framework for process modelling of ES. The four steps method involves: Current Situation Analysis, Business Process Improvements and Requirements, Gap Analysis, and To-be process to develop. Outputs of the methodology are an interdependent set of organizational and system proposed changes, and feedback loops to




Probabilistic Models of Computer Systems  

Microsoft Academic Search

In this paper we examine certain problems related to the use of diffusion approximations for the approximate modelling of computer systems. In particular we develop a model which allows us to handle waiting times and batch arrivals: these results are a new approach to the use of diffusion approximations. We also examine the effect of the distribution of holding times

Erol Gelenbe




EPA Science Inventory

This paper reviews the use of models for predicting water quality in distribution systems. esults of an extensive field study conducted by the USEPA and North Penn Mater Authority are examined. A case study of the model application to a waterborne disease outbreak in Cabool, Miss...


Respiratory and cardiovascular indicators of autonomic nervous system dysregulation in familial dysautonomia.  


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



Local and Systemic Cardiovascular Effects from Monochromatic Infrared Therapy in Patients with Knee Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Study  

PubMed Central

Infrared (IR) therapy is used for pain relief in patients with knee osteoarthritis (OA). However, IR's effects on the cardiovascular system remain uncertain. Therefore, we investigated the local and systemic cardiovascular effects of monochromatic IR therapy on patients with knee OA in a double-blind, randomized, placebo-controlled study. Seventy-one subjects with knee OA received one session of 40?min of active or placebo monochromatic IR treatment (with power output of 6.24?W, wavelength of 890?nm, power density of 34.7?mW/cm2 for 40?min, total energy of 41.6?J/cm2 per knee per session) over the knee joints. Heart rate, blood pressure, and knee arterial blood flow velocity were periodically assessed at the baseline, during, and after treatment. Data were analyzed by repeated-measure analysis of covariance. Compared to baseline, there were no statistically significant group x time interaction effects between the 2 groups for heart rate (P = 0.160), blood pressure (systolic blood pressure: P = 0.861; diastolic blood pressure: P = 0.757), or mean arterial blood flow velocity (P = 0.769) in follow-up assessments. The present study revealed that although there was no increase of knee arterial blood flow velocity, monochromatic IR therapy produced no detrimental systemic cardiovascular effects.

Hsieh, Ru-Lan; Liao, Wei-Cheng; Lee, Wen-Chung



Modelling of thermal plasma systems  

Microsoft Academic Search

Thermal plasma systems, comprising two different states of matter, plasma and particles, for thermal plasma processing were studied. The primary objective of is to develop computational models for thermal plasma systems and to extent the knowledge of thermal plasma processing through theoretical considerations. The thermal plasma is regarded as a continuum fluid, and the global governing equations can be derived

Yau-Pin Chyou



Pharmacogenomics and cardiovascular disease.  


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



EB 2010 Refresher Course - Cardiovascular Physiology  

NSDL National Science Digital Library

Cardiovascular physiology is one of the basics of a medical school course. This area is very complex is a basis for the first year physiology and the clinical medicine. The intent of this refresher course is to bring together a cadre of instructors with extensive knowledge and experience in teaching cardiovascular physiology. Not only will this benefit instructors assigned to teach cardiovascular physiology, but it can also benefit those interested in understanding the topic better. The most fundamental aspects of cardiovascular physiology will be covered in this refresher course, including: Cardiac Function, Local Control of Blood Flow, Neural Control of Circulation and the Integrative Cardiovascular Physiology. By establishing a solid grounding in cardiovascular physiology, one can only enhance the perspective of students as they examine specific processes relevant to cardiovascular physiology at a systems level.

PhD Donna H. Korzick (Pennsylvania State University Dept. of Physiology and Kinesiology); Philip Clifford (Medical College of Wisconsin); PhD Gail Thomas (Cedars-Sinai Medical Center); Michael J Joyner (Mayo Clinic Anesthesiology)



Cardiovascular risk in juvenile idiopathic arthritis.  


JIA is the most common chronic inflammatory arthritis in children and young people. More than one-third of individuals have persistent active disease into adulthood. In RA, there has been considerable interest in long-term cardiovascular outcomes. Increased cardiovascular mortality and morbidity have been observed and consensus guidelines recommend annual cardiovascular risk assessment for adults with RA. The increased risk is attributed to a higher prevalence of traditional cardiovascular risk factors and the role of systemic inflammation in the acceleration of atherosclerosis. The long-term risk of cardiovascular disease for individuals with JIA remains uncertain and guidance on risk assessment is not currently available. Given the potential for longer disease duration, it is possible that cardiovascular risk in this group surpasses that observed in adult-onset inflammatory arthritides. In this article, we consider the evidence for cardiovascular risk in JIA. PMID:23502074

Coulson, Elizabeth J; Ng, Wan-Fai; Goff, Iain; Foster, Helen E



Joint modeling and simulation system  

NASA Astrophysics Data System (ADS)

The defense budget is shrinking. Weapon systems are getting more complex. Test requirements are increasing. The training and war gaming scenarios are getting more demanding as fielded systems and training simulators are integrated to support combined arms training. To cope with these requirements and still stay within the budget, the Department of Defense is relying on modeling and simulation. The state of the modeling and simulation (M&S) art has advanced to the point where a user can now create incredibly realistic, extremely detailed models which can augment test and evaluation, support the acquisition process, enhance training and war gaming, facilitate intelligence gathering, and support detailed engineering.

Boyer, Richard T.; McQuay, William K.



Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study  

PubMed Central

Objectives To evaluate the cardiac safety of central nervous system stimulants in children and adolescents. Design Population based retrospective cohort study. Setting Automated healthcare claims data from 1?219?847 children and young people eligible for 28 state Medicaid programmes from 1999 to 2006 linked to the Social Security Death Master File and the National Death Index. Participants Children and young people age 3-18 entered the cohort at the first diagnosis of a mental health condition commonly treated with stimulants (such as attention-deficit/hyperactivity disorder) after a minimum period of six months’ eligibility and were followed until loss of eligibility, their 19th birthday, admission to hospital for longer than 30 days, or death. Exclusion criteria included transplant recipients, receipt of dialysis, or claims indicating substance misuse. We retained high risk groups with similar use of stimulants as low risk children (such as children with congenital heart disease). Sociodemographic characteristics, cardiac risk factors, and psychiatric diagnoses obtained from before the index period were summarised with a propensity score. We used discrete survival analysis to estimate the relative risk for periods of stimulant use and non-use, adjusted for propensity score and antipsychotic use for the full cohort and the high risk and low risk groups. Main outcome measures Composite endpoint of stroke, acute myocardial infarction, or sudden cardiac death; a secondary composite endpoint added ventricular arrhythmia Results A total of 66 (95 including ventricular arrhythmia) events occurred during 2?321?311 years of follow-up. The odds ratio adjusted for propensity score and antipsychotic use for current versus no stimulant use was 0.62 (95% confidence interval 0.27 to 1.44), with a corresponding adjusted incidence rate of 2.2 and 3.5 per 100?000 patient years for current stimulant and non-use, respectively. Twenty six events occurred in high risk patients (incidence rate 63 per 100?000 patient years) with an odds ratio of 1.02 (0.28 to 3.69). Odds ratios for the secondary endpoint were similar to those for the primary endpoint (0.74, 0.38 to 1.46). Conclusions Treatment of children with central nervous stimulants is not significantly associated with an increase in the short term risk of severe cardiac events. Analyses cannot be generalised to children with long term use of stimulants. Furthermore, long term effects of slight increases in heart rate or blood pressure are unknown.



A Computational Model of the Circulating Renin-Angiotensin System and Blood Pressure Regulation  

Microsoft Academic Search

The renin-angiotensin system (RAS) is critical in sodium and blood pressure (BP) regulation, and in cardiovascular-renal (CVR)\\u000a diseases and therapeutics. As a contribution to SAPHIR project, we present a realistic computer model of renin production\\u000a and circulating RAS, integrated into Guyton’s circulatory model (GCM). Juxtaglomerular apparatus, JGA, and Plasma modules were implemented in C ++\\/M2SL (Multi-formalism Multi-resolution Simulation Library) for fusion

François Guillaud; Patrick Hannaert




EPA Science Inventory

System biology models holistically describe, in a quantitative fashion, the relationships between different levels of a biologic system. Relationships between individual components of a system are delineated. System biology models describe how the components of the system inter...


Spectral analysis of systemic and cerebral cardiovascular variabilities in preterm infants: relationship with clinical risk index for babies (CRIB).  


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



Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system  

PubMed Central

There is growing recognition that the O-linked attachment of N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic post-translational modification that plays a key role in signal transduction pathways. Numerous proteins have been identified as targets of O-GlcNAc modifications including kinases, phosphatases, transcription factors, metabolic enzymes, chaperons and cytoskeletal proteins. Modulation of O-GlcNAc levels has been shown to modify DNA binding, enzyme activity, protein-protein interactions, half-life of proteins and subcellular localization. The level of O-GlcNAc is regulated in part by the metabolism of glucose via the hexosamine biosynthesis pathway (HBP) and the metabolic abnormalities associated with insulin resistance and diabetes, such as hyperglycemia, hyperlipidemia and hyperinsulinemia are all associated with increased flux through the HBP and elevated O-GlcNAc levels. Increased HBP flux and O-GlcNAc levels have been implicated in relaxation of isolated cardiomyocytes; blunted response to angiotensin II and phenylephrine; hyperglycemia-induced cardiomyocyte apoptosis and endothelial and vascular cell dysfunction. In contrast to these adverse effects, recent studies have also shown that O-GlcNAc levels increase in response to an acute stress and that this is associated with increased cell survival. Thus, while the relationship between O-GlcNAc levels and cellular function is complex and is not well understood, it is clear that these pathways play a critical role in the regulation of cell function and survival in the cardiovascular system and may be implicated in the adverse effects of metabolic disease on the heart.

Fulop, Norbert; Marchase, Richard B.; Chatham, John C.



[Effect of periodic "head-foot" G-forces in a short-radius centrifuge on human cardiovascular system responses].  


During 3- and 6-day immersion studies test subjects were two or three times a day (60 min each time) exposed to head-to-feet acceleration of 1-2 G in a 2 m arm centrifuge. In 297 runs cardiovascular reactions were compared with respect to their adaptation or cumulation. The results showed that the principle of periodic application of acceleration in a short-arm centrifuge as a countermeasure against cardiovascular deconditioning can be complemented by the principle of cyclic exposures. The study demonstrated that 3-day cycles including 60 min exposures to 1-2 Gz twice a day were most efficient. PMID:7421101

Vil'-Vil'iams, I F


Systems medicine and metabolic modelling.  


Several complex diseases are caused by the malfunction of human metabolism, and deciphering the underlying molecular mechanisms can elucidate their aetiology. Systems biology is an integrative approach combining experimental and computational biology to identify and describe the molecular mechanisms of complex biological systems. Systems medicine has the potential to elucidate the onset and progression of complex metabolic diseases through the use of computational approaches. Advances in biotechnology have resulted in the provision of high-throughput data, which provide information about different metabolic processes. The systems medicine approach can utilize such data to reconstruct genome-scale metabolic models that can be used to study the function of specific enzymes and pathways in the context of the complete metabolic network. In this review, we outline the importance of genome-scale models in systems medicine and discuss how they may contribute towards the development of personalized medicine. PMID:22142312

Mardinoglu, A; Nielsen, J



Kinetic Modeling of Biological Systems  

PubMed Central

The dynamics of how the constituent components of a natural system interact defines the spatio-temporal response of the system to stimuli. Modeling the kinetics of the processes that represent a biophysical system has long been pursued with the aim of improving our understanding of the studied system. Due to the unique properties of biological systems, in addition to the usual difficulties faced in modeling the dynamics of physical or chemical systems, biological simulations encounter difficulties that result from intrinsic multiscale and stochastic nature of the biological processes. This chapter discusses the implications for simulation of models involving interacting species with very low copy numbers, which often occur in biological systems and give rise to significant relative fluctuations. The conditions necessitating the use of stochastic kinetic simulation methods and the mathematical foundations of the stochastic simulation algorithms are presented. How the well-organized structural hierarchies often seen in biological systems can lead to multiscale problems, and possible ways to address the encountered computational difficulties are discussed. We present the details of the existing kinetic simulation methods, and discuss their strengths and shortcomings. A list of the publicly available kinetic simulation tools and our reflections for future prospects are also provided.

Petzold, Linda; Pettigrew, Michel F.



[Air pollution and cardiovascular disease].  


Cardiovascular atherothrombosis is the most common cause of death globally, with several well-known risk factors. Air pollution is a byproduct of fuel combustion by motor vehicles, power plants and industrial factories. It is composed of gases, fluids and particulate matter (PM) of different sizes, which include basic carbon, organic carbonic molecules and metals such as vanadium, nickel, zinc and iron. These particles are subdivided by their median size, a major contributing factor for their capability to enter the human body through the respiratory system. Most of the epidemiological studies have shown correlation between acute and long-term exposure to air pollution elements and cardiovascular morbidity in general, and angina pectoris and acute myocardial infarction specifically. Physiological studies have found different arrhythmias as the etiologic cause of cardiovascular morbidity and mortality following exposure to air pollution. A major finding was a decline in heart rate variability, a phenomenon known as endangering for cardiovascular morbidity and mortality, especially in patients after acute myocardial infarction. To date, several pathways have been proposed, including a hypercoagulable state following an inflammatory response, cardiac nervous autonomic disequilibrium, endothelial dysfunction with blood vessel contraction and direct toxic impact on cardiac muscle. Additional research is needed for clarifying the pathophysiological pathways by which air pollution affects the cardiovascular system. That might allow forthcoming with preventive measures and correct treatment, and hence a decrease in cardiovascular morbidity and mortality. Another important target is dose-outcome correlation curves for safety threshold calculation as a basis for air pollution regulations. PMID:17990383

Haber, Guy; Witberg, Guy; Danenberg, Haim



Multimodality Cardiovascular Molecular Imaging Technology  

PubMed Central

Cardiovascular molecular imaging is a new discipline that integrates scientific advances in both functional imaging and molecular probes to improve our understanding of the molecular basis of the cardiovascular system. These advances are driven by in vivo imaging of molecular processes in animals, usually small animals, and are rapidly moving toward clinical applications. Molecular imaging has the potential to revolutionize the diagnosis and treatment of cardiovascular disease. The 2 key components of all molecular imaging systems are the molecular contrast agents and the imaging system providing spatial and temporal localization of these agents within the body. They must deliver images with the appropriate sensitivity and specificity to drive clinical applications. As work in molecular contrast agents matures and highly sensitive and specific probes are developed, these systems will provide the imaging technologies required for translation into clinical tools. This is the promise of molecular medicine.

O'Donnell, Matthew; McVeigh, Elliot R.; Strauss, H. William; Tanaka, Atsushi; Bouma, Brett E.; Tearney, Guillermo J.; Guttman, Michael A.; Garcia, Ernest V.



Comparison of Different Electrocardiographic Scoring Systems for Detection of any Previous Myocardial Infarction as Assessed With Cardiovascular Magnetic Resonance Imaging.  


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



Disease severity and therapy as predictors of cardiovascular risk in psoriasis: a population-based cohort study  

PubMed Central

Background Previous studies suggest an increased risk of cardiovascular disease in psoriasis, but the relative contributions of traditional risk factors and markers of disease severity are unclear. We examined the effect of psoriasis disease characteristics on cardiovascular risk after adjusting for traditional cardiovascular risk factors. Methods Study populations included (a) case-cohort sample of 771 patients nested within a population-based psoriasis incidence cohort, and (b) cohort of 1905 patients with incident and prevalent psoriasis patients. Both cohorts were followed up to ascertain disease and treatment characteristics, traditional cardiovascular risk factors and cardiovascular outcomes. Cox proportional hazards regression models were used to identify predictors of cardiovascular outcomes. Results After adjusting for traditional risk factors, increasing number of psoriasis affected body sites at disease onset (HR 1.53 per additional site, 95% CI: 1.20, 1.95) was significantly associated with an increased risk of cardiovascular outcomes. Phototherapy (HR 3.76, 95% CI: 2.45, 5.77) and systemic therapy (HR 2.17, 95% CI: 1.50, 3.13) were associated with a higher risk of cardiovascular outcomes in univariate analyses, but these relatively strong associations disappeared after adjusting for cardiovascular risk factors. Conclusion Increasing number of psoriasis affected body sites may be a severity indicator in psoriasis and is associated with an increased cardiovascular risk. Due to low number of patients exposed to systemic therapy, this study had limited power to examine the effect of treatment on cardiovascular risk. Strong associations with phototherapy and systemic therapy suggest that the cardiovascular risk in psoriasis is confined to patients with severe disease.

Maradit-Kremers, Hilal; Icen, Murat; Ernste, Floranne C.; Dierkhising, Ross A.; McEvoy, Marian T.



Complex Systems: Control and Modeling Problems.  

National Technical Information Service (NTIS)

The Final Proceedings for Complex Systems: Control and Modeling Problems, 14 June 2004 - 19 June 2004 This is a computer science conference broadly covering topics related to modeling and control of complex systems and 'systems of systems'. Specific topic...

E. A. Fedosov N. A. Kuznetsov V. A. Vittikh



Short-Term Complexity of Cardiac Autonomic Control during Sleep: REM as a Potential Risk Factor for Cardiovascular System in Aging  

PubMed Central

Introduction Sleep is a complex phenomenon characterized by important modifications throughout life and by changes of autonomic cardiovascular control. Aging is associated with a reduction of the overall heart rate variability (HRV) and a decrease of complexity of autonomic cardiac regulation. The aim of our study was to evaluate the HRV complexity using two entropy-derived measures, Shannon Entropy (SE) and Corrected Conditional Entropy (CCE), during sleep in young and older subjects. Methods A polysomnographic study was performed in 12 healthy young (21.1±0.8 years) and 12 healthy older subjects (64.9±1.9 years). After the sleep scoring, heart period time series were divided into wake (W), Stage 1–2 (S1-2), Stage 3–4 (S3-4) and REM. Two complexity indexes were assessed: SE(3) measuring the complexity of a distribution of 3-beat patterns (SE(3) is higher when all the patterns are identically distributed and it is lower when some patterns are more likely) and CCEmin measuring the minimum amount of information that cannot be derived from the knowledge of previous values. Results Across the different sleep stages, young subjects had similar RR interval, total variance, SE(3) and CCEmin. In the older group, SE(3) and CCEmin were reduced during REM sleep compared to S1-2, S3-4 and W. Compared to young subjects, during W and sleep the older subjects showed a lower RR interval and reduced total variance as well as a significant reduction of SE(3) and CCEmin. This decrease of entropy measures was more evident during REM sleep. Conclusion Our study indicates that aging is characterized by a reduction of entropy indices of cardiovascular variability during wake/sleep cycle, more evident during REM sleep. We conclude that during aging REM sleep is associated with a simplification of cardiac control mechanisms that could lead to an impaired ability of the cardiovascular system to react to cardiovascular adverse events.

Chellappa, Sarah L.; Casali, Karina Rabello; Porta, Alberto; Montano, Nicola



Compositions and methods for the treatment and diagnosis of cardiovascular disease  

US Patent & Trademark Office Database

The present invention is based on the generation and phenotypic characterization of transgenic knockout homozygous rchd534 mutant mice which display characteristic cardiovascular disease symptoms. Such transgenic knockout homozygous rchd534 mutant mice are useful models for the analysis and characterization of rchd534 protein involvement in development and homeostasis of the cardiovascular system and tissue-specific regulation of the TGF-.beta. signaling pathways. Such transgenic mice may be used for screening compounds that may potentially useful for treating or preventing cardiovascular disease.



Airborne imaging system performance model  

NASA Astrophysics Data System (ADS)

This presentation describes a personal computer-based Pascal code which allows evaluation of airborne imaging system installation parameters by calculating the sensor imaging performance and comparing the sensor's laboratory resolution and its installed resolution, and by calculating the installed sensor's field of view obscuration or vignetting. A variation of this code has been used to characterize Stratospheric Observatory for Infrared Astronomy (SOFIA) and Advanced Tactical Airborne Reconnaissance System (ATARS) sensors. Flowcharts and applications of the airborne imaging system performance model are presented. Selected results from the use of similar codes also are shown.

Redus, Wesley D.



Modeling system performance in MMORPG  

Microsoft Academic Search

Massive multiplayer online games are becoming popular and prosperous rapidly. Although many papers have been published on system performance for online games in recent years, most of them are focusing on network perspective in first personal shooter (FPS) or strategy games. This paper describes a method to modeling network traffic and game server performance in a standard MMORPG (massive multiplayer

Gao Huang; Meng Ye; Long Cheng



Heating Systems Course Development Model  

NSDL National Science Digital Library

The Advanced Technology Environmental and Energy Center (ATEEC) has provided this course development model on heating systems, including gas, fuel oil, and electric furnaces, and heat pumps. Energy conservation, efficiency options and environmental impacts are also covered. Users must download this resource for viewing, which requires a free log-in. There is no cost to download the item.



Pharmacological studies of mabuterol, a new selective beta 2-stimulant. II: Effects on the cardiovascular system and smooth muscle organs.  


Effects of dl-1-(4-amino-3-chloro-5-trifluorome-thyl-phenyl)-2-tert.-bu tylamino-ethanol hydrochloride (mabuterol) on the cardiovascular system and smooth muscle organs were investigated in comparison with those of isoprenaline (isoproterenol), salbutamol and procaterol, and the following results were obtained. Mabuterol (i.v.) produced a dose-dependent decrease in the blood pressure at doses ranging from 0.3-1000 micrograms/kg, and the heart rate was slightly increased at 0.3-30 micrograms/kg but decreased at 100-