Cardiac modeling

Cardiac models are amongst the most advanced in silico tools for bio-med-icine, and the above scenario is bound to become reality rather sooner than later. Both cellular and whole organ models have aheady matured to a level where they have started to possess predictive power. We will now address some aspects of single cell model development (the cars ), and then look at how virtual cells interact to simulate the spreading wave of electrical excitation in anatomically representative, virtual hearts (the traffic ). 

Garny, A., Noble, D., and Kohl, P, Dimensionality in cardiac modelling, Prog. Biophys. Mol. 

Some physiological aspects in the development of cardiac models... 

A cardiac model convenient for vascular load coupling... 

It is known and widely applied a method, when the spatial model of object is formed by a set of plane sections or tomographic slices. An experienced sample, created in Californian University and reffered to as Dynamic Cardiac 3D densitometer, is constructed by this principle [2]. The serial model of this tomograph of the company Imatron Associates appeared on the market in the end 1983r.[13]. On this basis a line of computer tomographs has been created. 

Weiner and Rosenbluth had used a discrete diffusion model with excitable kinetics to study phenomenologically observed spatial phenomena in cardiac muscle tissue. 

Physiologically Based Phamiacokinetic (PBPK) Model—Comprised of a series of compartments representing organs or tissue groups with realistic weights and blood flows. These models require a variety of physiological information tissue volumes, blood flow rates to tissues, cardiac output, alveolar ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called biologically based tissue dosimetry models. 

Wexler MR, Halon DA, Teitelbaum A, et al (1984) The prevention of cardiac arrhythmias produced in an animal model by topical application of a phenol preparation in common use for face peeling. Plast Recontsr Surg 73 595-598... 

Marshal G, Grover FL, Henderson WG, Hammermeister KE. Assessment of predictive models for binary outcomes an empirical approach using operative death from cardiac surgery. Stat Med 1994 13 1501-11. 

The reasons for this are diverse and include the fact that models of cardiac cellular activity were among the first cell models ever developed. Analytical descriptions of virtually all cardiac cell types are now available. Also, the large-scale integration of cardiac organ activity is helped immensely by the high degree of spatial and temporal regularity of functionally relevant events and structures, as cells in the heart beat synchronously. 

This approach is, at the same time, the great advantage and a major limitation of membrane potential models. As they are rather compact, models of this type were the first to be used in investigations of the spread of excitation in multi-dimensional tissue representations consisting of relatively large numbers of interconnected excitable elements their role in assessing biophysical behaviour like cardiac impulse propagation is undiminished. 

The major drawback of these models, however, is their lack of a clear reference between model components and constituent parts of the biological system (e.g. structures like ion channels, transporter proteins, receptors, etc.). These models, therefore, do not permit the simulation of patho-physiological detail, such as the series of events that follows a reduction in oxygen supply to the cardiac muscle and, ultimately, causes serious disturbances in heart rhythm. 

In contrast to the pre-existing models that merely portrayed membrane potentials, the new generation of models calculated the ion fluxes that give rise to the changes in cell electrical potential. Thus, the new models provided the core foundation for a mechanistic description of cell function. Their concept was applied to cardiac cells by Denis Noble in 1960. 

These detailed cell models can be used to study the development in time of processes like myocardial ischaemia (a reduction in coronary blood flow that causes under-supply of oxygen to the cardiac muscle), or effects of genetic mutations on cellular electrophysiology. They allow to predict the outcome of changes in the cell s environment, and may even be used to assess drug actions. 

These may be produced by grouping together multiple cell models to form virtual tissue segments, or even the whole organ. The validity of such multi-cellular constructs crucially depends on whether or not they take into account the heart s fine architecture, as cardiac structure and function are tightly interrelated. 

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