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Modeling obstetric cardiovascular physiology on a full-scale patient simulator.

To our knowledge, this is the first attempt at adapting an existing cardiovascular model to simulate the hemodynamics of a particular patient population. Despite attempts to define the physiologic alterations in advance, we discovered there were critical parameters not completely defined in the literature. These were discovered through the iterative process of testing, comparing resulting vital signs with targets, and literature review. A list of the parameters that should be sought for future modeling efforts is provided (Table 3), but this list is by no means exhaustive. As further work is performed in this area, additional independent and essential parameters will be identified (pressure characteristics of valvular anomalies, for example). To define a physiology that is less well described in the literature, empirical alterations and best-guess estimates of parameter changes will be required with significantly more iterations. Finally, we have described only modeling of cardiovascular physiology, modeling the respiratory system will require a similar process.

Computer Simulation↗

Sheep, pig, and human platelet-material interactions with model cardiovascular biomaterials.

The relationship between cardiovascular device performance in animals and humans is not straightforward. As the principal formed element in a thrombus, platelets play a major role in determining the hemocompatibility of mechanical heart valves and other high-shear-rate cardiovascular devices. Since larger animals are required to test many such devices, sheep and porcine platelet responses were compared to humans. Adhesion, spreading, and the formation of thrombilike structures were examined in vitro on pyrolytic carbon mechanical heart valve leaflets, National Institutes of Health-reference polyethylene and silicone rubber, and Formvar. Principal findings were that platelet responses are strongly dependent upon the biomaterial and the species: Porcine and human platelets spread extensively on pyrolytic carbon, formed thrombuslike structures on Formvar, and were least active on silicone rubber. Human and porcine platelets responded differently to polyethylene: Human platelets spread extensively, while porcine platelets remained pseudopodial. In contrast, sheep platelets attached much less, never reached fully spread shapes, and were far less active overall. Since porcine responses were generally similar to humans, pigs may be a useful predictor of in vivo platelet-biomaterial interaction in humans. Conversely, as ovine platelets were much less active, this must be accounted for in the evaluation of cardiovascular devices tested in sheep.

Adult↗

Multi-formalism modelling and simulation: application to cardiac modelling.

Cardiovascular modelling has been a major research subject for the last decade. Different cardiac models have been developed at a cellular level as well as at the whole organ level. Most of these models are defined by a comprehensive cellular modelling using continuous formalisms or by a tissue-level modelling often based on discrete formalisms. Nevertheless, both views still suffer from difficulties that reduce their clinical applications: the first approach requires heavy computational resources while the second one is not able to reproduce certain pathologies. This paper presents an original methodology trying to gather advantages from both approaches, by means of a hybrid model mixing discrete and continuous formalisms. This method has been applied to define a hybrid model of cardiac action potential propagation on a 2D grid of endocardial cells, combining cellular automata and a set of cells defined by the Beeler-Reuter model. For simulations under physiological and ischemic conditions, results show that the action potential propagation as well as electrogram reconstructions are consistent with clinical diagnosis. Finally, the advantage of the proposed approach is discussed within the frame of cardiac modelling and simulation.

Action Potentials↗

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.

Adolescent↗

Animal models in cardiovascular diseases: new insights from conditional models.

Conditional systems have proven to be efficient and powerful to delineate several aspects of cardiac pathophysiology and diseases. The possibility of addressing a particular time point in animal life is certainly an important breakthrough allowed by conditional strategies with temporal control of either transgene expression or gene modifications. The purpose of this review is to present various mouse models for cardiovascular diseases based on conditional approaches.

Animals↗

Using models in cardiovascular research: report on the satellite meeting to the International Congress of Physiological Sciences, Models in Cardiovascular Research.

Humans have used animals for centuries to understand their own biology. From September 2-4, 2001, scientists from around the world converged on Brisbane, in Australia, to discuss the use of animal models in cardiovascular research at a satellite meeting to the 34th International Congress of Physiological Sciences (August 26-September 1, 2001, Christchurch, New Zealand). The appropriateness of each model to the human disease was a major consideration. Other themes were the use of models to understand pathological processes, and to determine potential new targets for pharmacological intervention.

Animals↗

Modeling preclinical cardiovascular risk for use in epidemiologic studies: Miami community health study.

To develop a method for assessing preclinical cardiovascular disease risk, models of resting cardiovascular regulation and of insulin metabolic syndrome were derived from information collected from 1991 to 1996 in a culturally heterogeneous sample of 319 healthy men and women (aged 25-44 years) from Miami-Dade County, Florida. The model of resting cardiovascular regulation used 8 noninvasive measures of autonomic and cardiovascular function. Three factors were derived: 1) parasympathetic, 2) inotropy, and 3) systemic vascular resistance. The model of insulin metabolic syndrome used 12 measures assessing body mass, insulin, glucose, and lipid metabolism. Four factors were derived: 1) body mass and fat distribution, 2) glucose level and regulation, 3) insulin level and regulation, and 4) plasma lipid levels. Analyses of the association of the two models revealed that subjects with lower cardiac contractility had greater body mass, higher fasting and postload insulin and glucose levels, and lower insulin sensitivity. Subjects with greater vascular resistance had greater body mass, higher total cholesterol and triglyceride levels, and lower high density lipoprotein cholesterol levels. These findings indicate that preclinical cardiovascular disease risk may involve pathophysiologic processes in which cardiac inotropic and vasodilatory functions are linked to specific aspects of insulin metabolic syndrome.

Adult↗

Methodologic issues in policy modeling for cardiovascular disease.

Clinical decision models are intended to guide the choices of individual clinicians; policy models are intended to guide the choices of persons and organizations that affect the aggregate allocations of resources to health care problems. Although it is difficult to identify any single policymaker in the United States who can alter the aggregate effect of the millions (or billions) of individual clinical decisions, there are many potential users of policy models: payers, providers, state and local health departments, the National Institutes of Health, professional organizations, hospitals and producers of medical devices, among others. Policy models deal with populations of individuals, may be static or dynamic and may be descriptive or prescriptive. Two types of policy models that have been applied to cardiovascular disease with a focus on coronary artery bypass surgery are discussed: 1) economic evaluation models, specifically cost-effectiveness, cost utility and cost-benefit analyses; and 2) population simulation models. Cost-effectiveness models are preferable for reasons that are discussed.

Adult↗

Simulating transient ventricular interaction using a minimal cardiovascular system model.

A minimal closed-loop cardiovascular system (CVS) model has been developed that can simulate ventricular interaction due to both direct interaction through the septum and series interaction through the circulation system. The model is used to simulate canine experiments carried out to study the transient response of the left ventricle due to changes in right ventricle pressures and volumes. The model-simulated trends in left and right ventricle pressures and volumes, septum deflection and arterial flow rates are compared with the experimental results. In spite of the limited physiological data available describing the animals, the model is shown to capture all the transient trends in the experimental data. This is the first known example of a physiological model that can capture all these trends. The model is then used to illustrate the separate effects of direct and series interactions independently. This study proves the value of this modelling method to be used in conjunction with experimental data for delineating and understanding the factors that contribute to ventricular dynamics.

Animals↗

A model for educational simulation of infant cardiovascular physiology.

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

Aging↗

Hidden Markov models based on symbolic dynamics for statistical modeling of cardiovascular control in hypertensive pregnancy disorders.

Discrete hidden Markov models (HMMs) were applied to classify pregnancy disorders. The observation sequence was generated by transforming RR and systolic blood pressure time series using symbolic dynamics. Time series were recorded from 15 women with pregnancy-induced hypertension, 34 with preeclampsia and 41 controls beyond 30th gestational week. HMMs with five to ten hidden states were found to be sufficient to characterize different blood pressure variability, whereas significant classification in RR-based HMMs was found using fifteen hidden states. Pregnancy disorders preeclampsia and pregnancy induced hypertension revealed different patho-physiological autonomous regulation supposing different etiology of both disorders.

Algorithms↗

Mathematical model of cardiovascular mechanics for diagnostic analysis and treatment of heart failure: Part 1. Model description and theoretical analysis.

The planning of drug therapy for heart failure should involve both the diagnostic analysis of the patient's defective state and a prediction of the drug effects on the identified state. We have devised a mathematical model of cardiovascular system mechanics, on which both quantitative diagnosis and evaluation of drug effects can be made. The model was composed of systemic and pulmonary circulatory networks including the dynamics of the left and right ventricles. The model of the ventricles can represent both systolic and diastolic problems in heart failure through the parameters of ventricular contractility and diastolic stiffness. Each vascular network was composed of arterial and venous resistances and total vascular capacitance. Patient's ventricular and vascular parameters were estimated simultaneously from the clinically measurable haemodynamic variables based on the model. Despite the simplicity of the model, the results showed good agreement with clinical and experimental data. The clinically significant haemodynamic classification of heart failure by Forrester et al. (Forrester et al., 1977) was simulated well by the model. This model provides a useful basis for analysing pathophysiological states in heart failure and evaluating drug effects on the disease.

Heart↗

Modelling of cardiovascular system: development of a hybrid (numerical-physical) model.

Physical models of the circulation are used for research, training and for testing of implantable active and passive circulatory prosthetic and assistance devices. However, in comparison with numerical models, they are rigid and expensive. To overcome these limitations, we have developed a model of the circulation based on the merging of a lumped parameter physical model into a numerical one (producing therefore a hybrid). The physical model is limited to the barest essentials and, in this application, developed to test the principle, it is a windkessel representing the systemic arterial tree. The lumped parameters numerical model was developed in LabVIEW environment and represents pulmonary and systemic circulation (except the systemic arterial tree). Based on the equivalence between hydraulic and electrical circuits, this prototype was developed connecting the numerical model to an electrical circuit--the physical model. This specific solution is valid mainly educationally but permits the development of software and the verification of preliminary results without using cumbersome hydraulic circuits. The interfaces between numerical and electrical circuits are set up by a voltage controlled current generator and a voltage controlled voltage generator. The behavior of the model is analyzed based on the ventricular pressure-volume loops and on the time course of arterial and ventricular pressures and flow in different circulatory conditions. The model can represent hemodynamic relationships in different ventricular and circulatory conditions.

Coronary Circulation↗

Intestinal vascular obstruction in the cat. Right heart function in a shock model.

Cardiovascular function was studied in a model of intestinal vascular obstruction in cats. To measure right ventricular end diastolic pressure and maximal dP/dt, a tip transducer catheter was placed into the right ventricle. The intestinal vascular obstruction resulted in shock with decreases of blood pressure, cardiac output, and external cardiac work. Small intestinal mucosal lesions were found in all shocked cats. At an increased preload to the heart, right ventricular function was depressed in shocked cats. The model corresponds to one used earlier in the rat, where cardioinhibitory activity in venous blood was found in vitro. In this corresponding model of intestinal shock in the cat a depressed function of the right ventricle of the heart was found in vivo.

Animals↗

Toward a causal model of cardiovascular responses to stress and the development of cardiovascular disease.

OBJECTIVE: Cardiovascular reactivity is hypothesized to mediate the relationship between stress and cardiovascular disease. We describe three considerations that are crucial for a causal model of cardiovascular responses to stress: the need for laboratory-life generalizability, the role of interactions between environmental exposures and individual response predispositions, and the importance of the duration of both stressor exposure and cardiovascular responding. METHODS: We illustrate current understanding of stress-cardiovascular disease relationships with examples from the human and animal psychophysiology, epidemiology, and genetics literature. RESULTS: In a causal model of reactivity, the usefulness of laboratory assessment rests on the assumption that laboratory-based cardiovascular reactivity predicts responses in the natural environment. We find only limited generalizability and suggest that cardiovascular responses to stress can be better understood when examined in the natural environment. The interaction of individual response predispositions and stressor exposures contributes to the development and progression of cardiovascular disease; stress-disease relationships could therefore be better understood if predispositions and exposures were assessed simultaneously in interactive models. Cardiovascular responses to stress are likely to be most deleterious when responses are prolonged. Responses may vary in their magnitude, frequency, and duration; however, reactivity captures only response magnitude. The assessment of anticipatory and recovery measures, with response magnitude, may therefore lead to a more useful model of the stress-disease relationship. CONCLUSIONS: A causal model of cardiovascular responses to stress should generalize to the real world, assess interactions between individual predispositions and environmental exposures, and focus on sustained pathogenic exposures and responses.

Adolescent↗

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

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

Algorithms↗