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PubMed2003

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

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.

Animals↗

PubMed2003

Blood pressure lowering and life expectancy based on a Markov model of cardiovascular events.

The life expectancy benefits of antihypertensive treatment, based on both systolic and diastolic blood pressure reduction, was estimated with a cardiovascular disease event Markov model with prospective data from 57 573 men and women. Seven patient states were defined, including (1) no cardiovascular disease, (2) stroke, (3) myocardial infarction, (4) revascularization, (5) history of cardiovascular disease, (6) noncardiovascular disease death, and (7) cardiovascular death. Risk functions were developed from gender-specific multivariate Cox proportional hazards models for primary events and age-, smoking-, and diabetes-adjusted models for secondary events. At baseline we assumed (1) hypothetical pretreatment blood pressures of 160/95 or 150/90 mm Hg; (2) strategies A and B lower blood pressure by 20/13 and 13/8 mm Hg, respectively; and (3) baseline age of 35 years. For subjects initially at 160/95 mm Hg, those with antihypertensive treatment, antihypertensive treatment and diabetes, or antihypertensive treatment, diabetes, and currently smoking had corresponding gains in life expectancy of 2.43, 2.80, and 2.43 years for Strategy A. An initial blood pressure of 150/90 mm Hg resulted in similar gains. Compared with Strategy B, with blood pressure reductions of 13/8 mm Hg, Strategy A provided additional gains in life expectancy of 0.84, 0.99, and 0.87 years for those with antihypertensive treatment, antihypertensive treatment and diabetes, or antihypertensive treatment, diabetes, and currently smoking. The initial blood pressure level did not affect the magnitude of life expectancy gains for equivalent blood pressure reductions. Greater gains in life expectancy among hypertensive and diabetic women suggest that blood pressure lowering may yield greater benefits in selected subgroups.

Adult↗

PubMed2006

Vascular anatomy of the developing medaka, Oryzias latipes: a complementary fish model for cardiovascular research on vertebrates.

The zebrafish has become a very useful vertebrate model for cardiovascular research, but detailed morphogenetic studies have revealed that it differs from mammals in certain aspects of the primary circulatory system, in particular, the early vitelline circulation. We searched for another teleost species that might serve as a complementary model for the formation of these early primary vessels. Here (and online at http://www.shigen.nig.ac.jp/medaka/atlas/), we present a detailed characterization of the vascular anatomy of the developing medaka embryo from the stage 24 (1 day 20 hr) through stage 30 (3 days 10 hr). Three-dimensional images using confocal microangiography show that the medaka, Oryzias latipes, follows the common embryonic circulatory pattern consisting of ventral aorta, aortic arches, dorsal aorta, transverse vessels, vitelline capillary plexus, and marginal veins. The medaka, thus, may serve as a valuable model system for genetic analysis of the primary vasculature of vertebrates.

Animals↗

PubMed2004

Mathematical modeling of cardiovascular system dynamics using a lumped parameter method.

This work reviews the main aspects of cardiovascular system dynamics with an emphasis on modeling hemodynamic characteristics by the use of a lumped parameter approach. The methodological and physiological aspects of the circulation dynamics are summarized with the help of existing mathematical models. The main characteristics of the hemodynamic elements, such as the heart and arterial and venous systems, are first described. Distributed models of an arterial network are introduced, and their characteristics are compared with those of lumped parameter models. We also discuss the nonlinear characteristics of the pressure-volume relationship in veins. Then the control pathways that participate in feedback mechanisms (baroreceptors and cardiopulmonary receptors) are described to explain the interaction between hemodynamics and autonomic nerve control in the circulation. Based on a set-point model, the computational aspects of reflex control are explained.

Animals↗

PubMed2003

Invited review: Identifying new mouse models of cardiovascular disease: a review of high-throughput screens of mutagenized and inbred strains.

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 complex disorders. There remains a need for new animal models that closely represent human disease. To expedite their development, we have established the Center for New Mouse Models of Heart, Lung, Blood, and Sleep Disorders at The Jackson Laboratory. We are using a phenotype-driven approach to identify mutations leading to atherosclerosis, hypertension, obesity, blood disorders, lung dysfunction, thrombosis, and disordered sleep. Our high-throughput, comprehensive phenotyping draws from two sources for new models: 1) the natural variation among over 40 inbred mouse strains and 2) chemically induced, whole-genome mutagenized mice. Here, we review our cardiovascular screens and present some hypertensive, obese, and cardiovascular models identified with this approach.

Animals↗

PubMed2004

Dynamic three-dimensional reconstruction and modeling of cardiovascular anatomy in children with congenital heart disease using biplane angiography.

Modeling and simulation of cardiovascular biomechanics and fluid dynamics from patient-specific data is a continuing topic of research investigation. Several methodologies utilizing CT, MRI and ultrasound to re-create the three-dimensional anatomy of the cardiovascular system have been examined. Adaptation of these models to pediatric applications has not been studied as extensively. There is significant need for such techniques in pediatric congenital heart disease since local anatomy may exhibit highly unusual geometry, and three-dimensional information would be of significant use for surgical and interventional planning, biomechanical and fluid dynamic simulation, and patient counseling. We report here on the adaptation and application of a three-dimensional reconstruction technique that utilizes bi-plane angiographic images as the base data sets. The method has been validated in a variety of adult imaging situations including coronary artery imaging and intervention. The method uses a skeletonization approach whereby local centerline, diameter, branching and tortuosity of the vasculature are obtained to create the three-dimensional model. Ten patients with a variety of etiology were imaged and 3D reconstructions were obtained. Excellent images were obtained of complex anatomy including the highly branched pulmonary vasculature and Fontan surgical connections. The data were then translated into solid and surface models to facilitate viewing, export into computational fluid dynamic grids, and into files suitable for stereo lithography fabrication (STL). This method appears promising for the dynamic study of complex cardiovascular anatomy found in congenital heart disease. Optimization of the method to facilitate on-line reconstruction and simulation are currently ongoing.

Algorithms↗

PubMed1991

A model of cardiovascular activation components for studies using autonomic receptor antagonists.

Alpha-adrenergic, beta-adrenergic, and cholinergic responses are often considered important activation components when conceptual and empirical analyses are made of single physiological variables and of patterns of cardiovascular reactivity; these autonomic distinctions are also of particular significance in autonomic blockade studies. A Model of Cardiovascular Activation Components is introduced that relates these components to both the measured cardiovascular variables and the protocol of autonomic blockade studies. It is pointed out that a restricted form of the complete model is often implicitly used in cardiovascular psychophysiology. The differential consequences of an erroneous employment of the restricted model are discussed for single and dual blockade protocols. Critical evaluations of autonomic blockade as a tool in cardiovascular psychophysiology are examined and are proposed to be often the consequence of the restricted model assumptions. Lastly, the utility of the Activation Components Model for a componential description of tasks and for componential intertask relationships is illustrated with data from the literature.

Arousal↗

PubMed1999

Construction of a model demonstrating cardiovascular principles.

We developed a laboratory exercise that involves the construction and subsequent manipulation of a model of the cardiovascular system. The laboratory was designed to engage students in interactive, inquiry-based learning and to stimulate interest for future science study. The model presents a concrete means by which cardiovascular mechanics can be understood as well as a focal point for student interaction and discussion of cardiovascular principles. The laboratory contains directions for the construction of an inexpensive, easy-to-build model as well as an experimental protocol. From this experience students may gain an appreciation fo science that cannot be obtained by reading a book or interacting with a computer. Students not only learn the significant physiological concepts but also appreciate the importance of laboratory experimentation for understanding complex concepts. Model construction provides a hands-on experience that may substantially improve performance in science processes. We believe that model construction is an appropriate method for teaching advanced concepts.

Cardiovascular Physiological Phenomena↗

PubMed2001

Manipulating the contractile apparatus: genetically defined animal models of cardiovascular disease.

Within the last 10 years via gene targeting and transgenesis, numerous models of cardiovascular disease have been established and used to determine if a protein's presence or absence causes cardiovascular disease. By affecting the heart's protein complement in a defined manner, the function of the different mutated proteins or protein isoforms present in the contractile apparatus can be determined and pathogenic mechanism(s) explored. We can now remodel the cardiac protein profile and effect replacement of even the most abundant contractile proteins. Precise genetic manipulation allows exploration of the structure-function relationships which underlie cardiac function, and the consequences of defined mutations at the molecular, biochemical, cytological and physiologic levels can be determined.

Animals↗

PubMed2006

Shifts in the myosin heavy chain isozymes in the mouse heart result in increased energy efficiency.

Cardiac-specific transgenesis in the mouse is widely used to study the basic biology and chemistry of the heart and to model human cardiovascular disease. A fundamental difference between mouse and human hearts is the background motor protein: mouse hearts contain predominantly the alphaalpha-myosin heavy chain (MyHC) isozyme while human hearts contain predominantly the betabeta-MyHC isozyme. Although the intrinsic differences in mechanical and enzymatic properties of the alphaalpha- and betabeta-MyHC molecules are well known, the consequences of isozyme shifts on energetics of the intact beating heart remain unknown. Therefore, we compared the free energy of ATP hydrolysis (|DeltaG( approximately ATP)|) determined by (31)P-NMR spectroscopy in isolated perfused littermate mouse hearts containing the same amount of myosin comprised of either >95% alphaalpha-MyHC or approximately 83% betabeta-MyHC. |DeltaG( approximately ATP)| was approximately 2 kJ mol(-1) higher in the betabeta-MyHC hearts at all workloads. Furthermore, upon inotropic challenge, hearts containing predominantly betabeta-MyHC hearts increased developed pressure more than alphaalpha-MyHC hearts whereas heart rate increased more in alphaalpha-MyHC hearts. Thus, hearts containing predominantly the betabeta-MyHC isozyme are more energy efficient than alphaalpha-MyHC hearts. We suggest that these fundamental differences in the motor protein energy efficiency at the whole heart level should be considered when interpreting results using mouse-based cardiovascular modeling of normal and diseased human hearts.

Adenosine Triphosphate↗

PubMed2003

The influence of inflow boundary conditions on intra left ventricle flow predictions.

The combination of computational fluid dynamics (CFD) and magnetic resonance imaging (MRI) offers a promising tool that enables the prediction of blood flow patterns in subject-specific cardiovascular models. The influence of the model geometry on the accuracy of the simulation is well recognized. This paper addresses the impact of different boundary conditions on subject-specific simulations of left ventricular (LV) flow. A novel hybrid method for prescribing effective inflow boundary conditions in the mitral valve plane has been developed. The detailed quantitative results highlight the strengths as well as the potential pitfalls of the approach.

Blood Flow Velocity↗

PubMed1995

Respiratory sinus arrhythmia: time domain characterization using autoregressive moving average analysis.

Fourier-based techniques are mathematically noncausal and are therefore limited in their application to feedback-containing systems, such as the cardiovascular system. In this study, a mathematically causal time domain technique, autoregressive moving average (ARMA) analysis, was used to parameterize the relations of respiration and arterial blood pressure to heart rate in eight humans before and during total cardiac autonomic blockade. Impulse-response curves thus generated showed the relation of respiration to heart rate to be characterized by an immediate increase in heart rate of 9.1 +/- 1.8 beats.min-1.l-1, followed by a transient mild decrease in heart rate to -1.2 +/- 0.5 beats.min-1.l-1 below baseline. The relation of blood pressure to heart rate was characterized by a slower decrease in heart rate of -0.5 +/- 0.1 beats.min-1.mmHg-1, followed by a gradual return to baseline. Both of these relations nearly disappeared after autonomic blockade, indicating autonomic mediation. Maximum values obtained from the respiration to heart rate impulse responses were also well correlated with frequency domain measures of high-frequency "vagal" heart rate control (r = 0.88). ARMA analysis may be useful as a time domain representation of autonomic heart rate control for cardiovascular modeling.

Adult↗

PubMed1997

[Simulation study on the blood volume feedback control].

To describe the relationship between blood volume and the cardiac function mathematically, a computer cardiovascular model, was developed including a systemic circulation, a heart and a pulmonary model and a blood volume feedback control. Simulation results indicate that the chronic heart failure could be compensated by increasing the blood volume to maintain the proper arterial pressure. Deterioration in heart failure causes an increase in blood volume, as well as increases in heart volume and cardiac energy consumption. These results are in agreement with the clinical data and results reported in the literature. The simulation also shows that for a predetermined ventricular contractility, an adequate increase in blood volume will increase the heart volume but decrease the cardiac energy consumption and lead the heart to work in an optimum condition.

Aerospace Medicine↗

PubMed2001

Relationship between systolic and diastolic function with improvements in forward stroke volume following reduction in mitral regurgitation.

Efforts to improve mitral regurgitation (MR) are often performed in conjunction with coronary revascularization. However, the independent effects of a reduced MR area (MRa) are difficult to quantify. Using a previously developed cardiovascular model, ventricular contractility (elastance 1-8 mmHg/ml) and relaxation (tau: 40-150 msec) were independently adjusted for four grades of MR orifice areas (0.0 to 0.8 cm2). Improvements in forward stroke volume (fSV) were determined for the permutations of reduced MRa. For all conditions, LV end-diastolic pressure and volumes ranged from 7.3-24.2 mmHg and 64.8-174.3 ml, respectively. Overall, fSV ranged from 36.0-89.4 (mean: 64.2 +/- 12.8) ml, improved between 6.4 and 35.3% (mean: 15.6 +/- 8.1%), and was best predicted by (r=0.97, p<0.01) %delta(fSV)[correction of fVS]=34[MRa initial] - 46[MRa final] -0.5[elastance]. Reduced MRa, independent of relaxation and minimally influence by contractility, yield improved fSVs.

Blood Pressure↗

PubMed1992

A modular mock circulation for hydromechanical studies on valves, stenoses, vascular grafts and cardiac assist devices.

P6vices for hydrodynamic simulation are required in a variety of studies such as device evaluation, cardiovascular modeling and for student training. Most studies today use different, incompatible circuits, which must be redesigned for every new application. To obtain a universal apparatus, a unitized system with standard connectors was developed. Three types of connectors were selected: 1" flange connectors, 1/2" tubing connectors and Luer-connectors with a 2 mm lumen. The complete system consists of reservoirs, throttles, valve holders, adapters for Doppler ultrasound probes, and converters to link these basic diameters. The apparatus can be driven by membrane, centrifugal and geared pumps. The system has successfully been used in echocardiographic studies of stenosis and valvular insufficiency, for pulse propagation in vascular grafts, and to test the hydraulic performance of cardiac assist devices. Flow rates between 0.1 and 30 l/min and pressure gradients up to 250 mmHg were achieved. In practical use, the system can be adapted to suit various investigations, with minimal expense. Standardization of the parts and connectors results in simple documentation and good reproducibility.

Blood Circulation↗

PubMed2004

Modelling the cardiovascular effects of ephedrine.

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

Administration, Oral↗

PubMedDate not supplied

[Mathematical modeling of cardiovascular system in patients with hemorrhage and hypothermia].

Mathematical modeling is the most expedient method for studying the response of human cardiovascular system to a combined effect of several external factors, in particular, hemorrhage and hypothermia. A complex mathematical model integrating models of the functional systems of human body and the physiological effects of disturbing factors can be used to study the combined effect of external factors. It allows the response of human body to various combinations of external effects of different intensities to be assessed with high accuracy. In addition, the model makes it possible to prognosticate the dynamics of changes in the cardiovascular system parameters from their initial variation. This facilitates prediction of the development of patient's state.

Cardiovascular System↗

PubMed1994

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.

Cardiotonic Agents↗