SAPHIR: a physiome core model of body fluid homeostasis and blood pressure regulation

Abstract

We present the current state of the development of the SAPHIR project (a Systems Approach for PHysiological Integration of Renal, cardiac and respiratory function). The aim is to provide an open-source multi-resolution modelling environment that will permit, at a practical level, a plug-and-play construction of integrated systems models using lumped-parameter components at the organ/tissue level while also allowing focus on cellular-or molecular-level detailed sub-models embedded in the larger core model. Thus, an in silico exploration of gene-to-organ-to-organism scenarios will be possible, while keeping computation time manageable. As a first prototype implementation in this environment, we describe a core model of human physiology targeting the short-and long-term regulation of blood pressure, body fluids and homeostasis of the major solutes. In tandem with the development of the core models, the project involves database implementation and ontology development.

Graphical simulation environments for modelling and simulation of integrative physiology

“…The Simulink implementation of Guyton's model under the SAPHIR project [52] differs significantly from the model presented here. Thomas et al [52] specified the model in discrete-time, using discrete-time integration blocks and a forward Euler method.…”

“…A variety of simulation environments have been examined in this paper with a view to the mathematical modelling of large-scale physiological systems; however not many environments allow the desired visual diagrammatic representation and speed of implementation. Some computer implementations of the original 1972 Guyton model exist [52,51], as well as an implementation of a 1986 version of the model [51]; however the Simulink model presented in this paper is the first implementation of the most recent 1992 version of the model. If a core model is to be created and made available for extension/improvement, it should be the most up to date model recognised by the research and teaching community.…”

“…The 1972 published version of Guyton's model has been implemented by a number of researchers ( [51,52]) in the Simulink format suggested in this study. A 1986 version of Guyton's model, which was not published, has also been implemented by Kofranek et al [51].…”

“…A sample 'reference' experiment, similar to those described in [1,52], was simulated by reducing kidney mass to 30% of normal and increasing salt intake to 9 times normal at the start of the experiment. The responses of the MODSIM implementation and our Simulink version of the model are shown in Fig.…”

“…Thomas et al [52] specified the model in discrete-time, using discrete-time integration blocks and a forward Euler method. In addition, all subsystems were treated as 'atomic subunits', thus all computations within a subsystem were executed before moving to the next subsystem.…”