SAPHIR - a multi-scale, multi-resolution modeling environment targeting blood pressure regulation and fluid homeostasis

Abstract

Abstract-We present progress on a comprehensive, modular, interactive modeling environment centered on overall regulation of blood pressure and body fluid homeostasis. We call the project SAPHIR, for "a Systems Approach for PHysiological Integration of Renal, cardiac, and respiratory functions". The project uses state-of-the-art multi-scale simulation methods. The basic core model will give succinct input-output (reduced-dimension) descriptions of all relevant organ systems and regulatory processes, and it will be modular, multi-resolution, and extensible, in the sense that detailed submodules of any process(es) can be "plugged-in" to the basic model in order to explore, eg. system-level implications of local perturbations. The goal is to keep the basic core model compact enough to insure fast execution time (in view of eventual use in the clinic) and yet to allow elaborate detailed modules of target tissues or organs in order to focus on the problem area while maintaining the system-level regulatory compensations.

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

“…This would allow the model predictions to be directly compared to clinical studies such as INDANA [90]. To this end, refinements are being incorporated into the original Guyton model [32] as part of the SAPHIR project [13], such as a detailed model of the RAAS [34]. The culmination of these efforts will result in a richly-detailed and more accurate model of renal autoregulation being incorporated into the Guyton model, providing a platform for pharmacological predictions that may assist in the diagnosis and treatment of hypertension [77].…”

“…Furthermore, since one of the main limitations of the early Guyton models is the low-resolution description of most of their constituting modules, a framework was built to allow replacement of the original sub-modules by new versions at a higher temporal or spatial resolution [32]; e. g., a pulsatile heart was introduced to treat systolic and diastolic blood pressures instead of only mean blood pressure [33], and a detailed model of the renin-angiotensin-aldosterone system (RAAS) has also been integrated [34]. That work was also linked to efforts in the European VPH via two Exemplar Projects, one of which used our modular reimplementation of the Guyton model as the basic set of “bricks” for a collaborative core-modeling environment for multi-organ physiology modeling [13], [14], and the other uses the Guyton model as a demonstrator for the tagging of parameters and variables with a set of reference ontologies common to databases of high-throughput genomic and proteomic data [35]. Collaborators in the Physiome/VPH community have also carried out XML markup of the individual modules of the Guyton model in CellML (http://models.cellml.org/workspace/guyton_2008), thus providing precious documentation of its structure and content.…”

A Computational Model of the Circulating Renin-Angiotensin System and Blood Pressure Regulation

“…?/ M2SL (Multi-formalism Multi-resolution Simulation Library; Hernandez et al 2009), ultimately producing a validated C ? ?/M2SL version of GCM (Thomas et al 2007;Thomas et al 2008;Hernandez et al 2009). On the basis of a careful analysis of the relevant literature, we have constructed the present model of the RAS, keeping the description of aldosterone-related processes as in native GCM.…”

“…IUPS Physiome Project, QHP/QCP Quantitative Human/ Circulatory Physiology, european VPH Virtual Physiological Human). In this line of view, our collaborative initiative, SAPHIR project, develops an integrated and progressively refined description of the cardiovascular, renal and respiratory human physiology (Thomas et al 2007). In order to address blood pressure homeostasis and hypertensive pathology, we have based our model on the influential ''large circulatory model'' by Guyton and coworkers (Guyton et al 1972; see Abram et al 2007; Montani and Van Vliet 2009a, b;Osborn et al 2009a, b).…”

Systems biology of kidney diseases

“…The SAPHIR (a Systems Approach for Physiological Integration of Renal, Cardiac, and Respiratory function) is the best example of a multiorgan model. 78 This is a model of body fluid homeostasis and blood pressure regulation and has been reviewed by Thomas. 79 Karaaslan et al 80 developed an integrated cardiovascular/renal model with emphasis on the role of renal sympathetic nerve activity.…”