Virtual heart

As a coen2yme component in tissue oxidation—reduction and respiration, riboflavin is distributed in some degree in virtually aU naturally occurring foods. Liver, heart, kidney, milk, eggs, lean meats, malted barley, and fresh leafy vegetables are particularly good sources of riboflavin (see Table 1). It does not seem to have long stabiUty in food products (8). 

The reaetor-generator (Figure 4-45) is die heart of die FCC proeess. In a modern eat eraeker, virtually all of die reaetions oeeur in die riser over a short period 2-4 see before die eatalyst and die produets are separated in die reaetor. However, some diermal and nonseleetive eatalytie eraeking reaetions eontinue to oeeur in die reaetor housing. A number of refineries are modifying die riser termination deviees to eliminate diis problem. 

The reactor-regenerator is the heart of the FCC process. In a modem cat cracker, virtually all the reactions occur in 1.5 to 3.0 seconds before the catalyst and the products are separated in the reactor. 

Na+/Ca2+ exchanger activity is present in virtually evety cell type examined. The NCX1 gene is expressed in several tissues, including brain, heart, skeletal... 

Anaphylaxis is the most dramatic and potentially catastrophic manifestation of allergic disorders. It can affect virtually any organ including the cardiovascular system. Cardiovascular collapse and hypotensive shock in anaphylaxis have been attributed to peripheral vasodilation, enhanced vascular permeability and plasma leakage, rather than any direct effect on the myocardium. However, there is increasing experimental and clinical evidence that the human heart is a site and target of anaphylaxis. 

In order to understand the dimensions of the making of the virtual heart - let s stand back, for a minute, and consider the difficulties of studying and describing any unknown complex system. 

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. 

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 ). 

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. 

Modern representations of the virtual heart, therefore, describe structural aspects like fibre orientation in cardiac muscle, together with the distribution of various cell types, active and passive electrical and mechanical properties, as well as the coupling between cells. This then allows accurate reproduction of the spread of the electrical wave, subsequent contraction of the heart, and effects on blood pressure, coronary perfusion, etc. It is important to point out, here, that all these parameters are closely interrelated, and changes in any one of them influence the behaviour of all others. This makes for an exceedingly complex system. 

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. 

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. 

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