Heart simulation

Molecular Dynamics and Monte Carlo Simulations. At the heart of the method of molecular dynamics is a simulation model consisting of potential energy functions, or force fields. Molecular dynamics calculations represent a deterministic method, ie, one based on the assumption that atoms move according to laws of Newtonian mechanics. Molecular dynamics simulations can be performed for short time-periods, eg, 50—100 picoseconds, to examine localized very high frequency motions, such as bond length distortions, or, over much longer periods of time, eg, 500—2000 ps, in order to derive equiUbrium properties. It is worthwhile to summarize what properties researchers can expect to evaluate by performing molecular simulations ... 

Combined Quantum and Molecular Mechanical Simulations. A recentiy developed technique is one wherein a molecular dynamics simulation includes the treatment of some part of the system with a quantum mechanical technique. This approach, QM/MM, is similar to the coupled quantum and molecular mechanical methods introduced by Warshel and Karplus (45) and at the heart of the MMI, MMP2, and MM3 programs by AUinger (60). These latter programs use quantum mechanical methods to treat the TT-systems of the stmctures in question separately from the sigma framework. 

This makes choline an important nutritional substance. It is also of great physiological interest because one of its esters, acetylcholine [51-84-3] appears to be responsible for the mediation of parasympathetic nerve impulses and has been postulated to be essential to the transmission of all nerve impulses. Acetylcholine and other more stable compounds that simulate its action are pharmacologically important because of their powerful effect on the heart and on smooth muscle. Choline is used clinically in Hver disorders and as a constituent in animal feeds. 

They point out that at the heart of technical simulation there must be unreality otherwise, there would not be need for simulation. The essence of the subject linder study may be represented by a model of it that serves a certain purpose, e.g., the use of a wind tunnel to simulate conditions to which an aircraft may be subjected. One uses the Monte Carlo method to study an artificial stochastic model of a physical or mathematical process, e.g., evaluating a definite integral by probability methods (using random numbers) using the graph of the function as an aid. 

The mark of a good simulation is that it separates the essential from the incidental, cutting through what is deemed irrelevant detail to get at the heart of the problem. 

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 ). 

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. 

The same applies to pathologically-disturbed function. A simulated reduction in coronary blood flow (heart attack) would lead to reduced oxygen supply to the cells in the virtual heart, which would reduce efficiency of cardiac contraction and possibly give rise to heart rhythm disturbances. Ventricular pressure development would be compromised, as would the blood supply to all organs of the body, including the heart. All these implications can be studied in a virtual heart. 

Thus, the virtual heart may be used to simulate cardiac pathologies, their effect on the ECG, and the consequences of drug administration. It can be seen that drug discovery and assessment will be among the first fields where in silico technologies could reform research and development in a whole industry. 

Analytical models of the heart are a reality. They are based on detailed descriptions of cardiac tissue architecture and anatomy, including the coronary vasculature. In sihco cardiac tissues possess realistic passive mechanical properties, and both electrical and mechanical activity can be simulated with high accuracy. Descriptions of key components of cellular metabolism have been introduced, as have models of drug-receptor interactions. 

The individual modules of the in situ heart can be coupled together to compute a whole sequence from ventricular pressure development, coronary perfusion, tissue supply of metabolites, cell energy consumption, and electrophysiology, to contractile activity and ventricular pressure development in the subsequent beat. The starting point (here chosen as ventricular pressure development) can be freely selected, and drug effects on the system can be simulated. Inserted into a virtual torso, these models allow one to compute the spread of excitation, its cellular basis, and the consequences for an ECG under normal and pathological conditions. 

Whilst finite-element modelling of gap junctions occurs at a sub-cellular level, these models do not consider the operation of intact organs. Conversely, in models of the complete heart the discretisation is usually on a milhmetre scale. However, the cochlea (see Figure 9.3) is already being simulated on a 0.01 mm, or cellular, scale. Although cochlear malfunction is not hfe threatening, damage to it does adversely affect the ability of almost 1000000000 people to communicate. 

Daidone, I., Amadei, A., Roccatano, D., Nola, A. D., Molecular dynamics simulation of protein folding by essential dynamics sampling folding landscape of horse heart cytochrome c, Biophys. J. 2003, 85, 2865-2871... 

M. J. Achs and D. Garfinkel, Computer simulation of energy metabolism in anoxic perfused rat heart. Am. J. Physiol. Regul. Integr. Comp. Physiol. 232, R164 R174 (1977). 

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