Description of Guyton autonomics module

Model Status

This CellML model has not been validated. The equations in this file may contain errors and the output from the model may not conform to the results from the MODSIM program. Due to the differences between procedural code (in this case C-code) and declarative languages (CellML), some aspects of the original model were not able to be encapsulated by the CellML model (such as the damping of variables). Work is underway to fix these omissions and validate the CellML model. We also anticipate that many of these problems will be fixed when the CellML 1.0 models are combined in a CellML 1.1 format.

Model Structure

Arthur Guyton (1919-2003) was an American physiologist who became famous for his 1950s experiments in which he studied the physiology of cardiac output and its relationship with the peripheral circulation. The results of these experiments challenged the conventional wisdom that it was the heart itself that controlled cardiac output. Instead Guyton demonstrated that it was the need of the body tissues for oxygen which was the real regulator of cardiac output. The "Guyton Curves" describe the relationship between right atrial pressures and cardiac output, and they form a foundation for understanding the physiology of circulation.

The Guyton model of fluid, electrolyte, and circulatory regulation is an extensive mathematical model of human circulatory physiology, capable of simulating a variety of experimental conditions, and contains a number of linked subsystems relating to circulation and its neuroendocrine control.

This is a CellML translation of the Guyton model of the regulation of the circulatory system. The complete model consists of separate modules each of which characterise a separate physiological subsystems. The Circulation Dynamics is the primary system, to which other modules/blocks are connected. The other modules characterise the dynamics of the kidney, electrolytes and cell water, thirst and drinking, hormone regulation, autonomic regulation, cardiovascular system etc, and these feedback on the central circulation model. The CellML code in these modules is based on the C code from the programme C-MODSIM created by Dr Jean-Pierre Montani.

This particular CellML model describes the autonomic control of the circulation, which primarily operates through the sympathetic system, though also to a slight extent through parasympathetic signals to the heart. These have been lumped together, and there are basically three separate feedback mechanisms in this computational block. These are: (1) feedback from the baroreceptor control system; (2) feedback from the peripheral chemoreceptors in the carotid and aortic bodies,; and (3) feedback control of the circulatory system caused by central nervous system ischemia, that is, ischemia of the vasomotor center of the brainstem. Several other inputs that affect the autonomic nervous system are also included. These are: activation of the autonomic nervous system during exercise; baroreceptor feedback effects from pulmonary artery pressure (PPA), left atrial pressure (PLA), and an effect of low blood PO2 (PO2ART).

A systems analysis diagram for the full Guyton model describing circulation regulation.

A schematic diagram of the components and processes described in the current CellML model. Note: Not shown in the diagram is also a variable (STA) that is normally zero. When it is set to any level above zero, the value of the general autonomic multiplier (AU) becomes fixed to the value of STA.

There are several publications referring to the Guyton model. One of these papers is cited below:

Circulation: Overall Regulation, A.C. Guyton, T.G. Coleman, and H.J. Granger, 1972, Annual Review of Physiology , 34, 13-44. PubMed ID: 4334846