Integration of detailed modules in a core model of body fluid homeostasis and blood pressure regulation

Hernández, Alfredo; Rolle, Virginie Le; Ojeda, David; Baconnier, Pierre; Fontecave-Jallon, Julie; Guillaud, François; Grosse, Thibault; Moss, Robert; Hannaert, Patrick; Thomas, Sophie

doi:10.1016/j.pbiomolbio.2011.06.008

Cited by 22 publications

(14 citation statements)

References 40 publications

(64 reference statements)

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“…With this sensitivity index, which has been widely used in other modeling applications [25], [26], parameters with high sensitivity or strong interactions will have a high S ij . In this paper, the analysis of S ij will be used to evaluate the relative sensitivity of the collateral vessel parameters with respect to the other parameters of the model, and for the most important output variables.…”

Section: Sensitivity Analysismentioning

confidence: 99%

Sensitivity Analysis and Parameter Estimation of a Coronary Circulation Model for Triple-Vessel Disease

Ojeda

Rolle

Harmouche

et al. 2014

IEEE Trans. Biomed. Eng.

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Abstract-Mathematical models of the coronary circulation have been shown to provide useful information for the analysis of intra-coronary blood flow and pressure measurements acquired during coronary artery bypass graft (CABG) surgery. Although some efforts towards the patient-specific estimation of model parameters have been presented in this context, they are based on simplifying hypotheses about the collateral circulation and do not take advantage of the whole set of data acquired during CABG. In order to overcome these limitations, this paper presents an exhaustive parameter sensitivity analysis and a multiobjective patient-specific parameter estimation method, applied to a model of the coronary circulation of patients with triple vessel disease. The results of the sensitivity analysis highlighted the importance of capillary and collateral development. On the other hand, the estimation method was applied to intraoperative clinical data from ten patients obtained during CABG, which permitted to assess patient-specific collateral vessel situations. These approaches provide new insights regarding the heterogeneous configuration of the collateral circulation.

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Section: Sensitivity Analysismentioning

confidence: 99%

Sensitivity Analysis and Parameter Estimation of a Coronary Circulation Model for Triple-Vessel Disease

Ojeda

Rolle

Harmouche

et al. 2014

IEEE Trans. Biomed. Eng.

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“…Recently, attempts have been made to more accurately model the RAAS (14,29,52) and its effects on the cardiovascular system (20). Here we describe how the Guyton/Karaaslan model has been extended to incorporate a more detailed model of the RAAS pathway (29), allowing simulation of the blood pressure response to different classes of RAAS-targeting therapies.…”

mentioning

confidence: 99%

A model-based approach to investigating the pathophysiological mechanisms of hypertension and response to antihypertensive therapies: extending the Guyton model

Hallow

Lo²,

Beh³

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

125

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Reproducibly differential responses to different classes of antihypertensive agents are observed among hypertensive patients and may be due to interindividual differences in hypertension pathology. Computational models provide a tool for investigating the impact of underlying disease mechanisms on the response to antihypertensive therapies with different mechanisms of action. We present the development, calibration, validation, and application of an extension of the Guyton/Karaaslan model of blood pressure regulation. The model incorporates a detailed submodel of the renin-angiotensin-aldosterone system (RAAS), allowing therapies that target different parts of this pathway to be distinguished. Literature data on RAAS biomarker and blood pressure responses to different classes of therapies were used to refine the physiological actions of ANG II and aldosterone on renin secretion, renal vascular resistance, and sodium reabsorption. The calibrated model was able to accurately reproduce the RAAS biomarker and blood pressure responses to combinations of dual-RAAS agents, as well as RAAS therapies in combination with diuretics or calcium channel blockers. The final model was used to explore the impact of underlying mechanisms of hypertension on the blood pressure response to different classes of antihypertensive agents. Simulations indicate that the underlying etiology of hypertension can impact the magnitude of response to a given class of therapy, making a patient more sensitive to one class and less sensitive others. Given that hypertension is usually the result of multiple mechanisms, rather than a single factor, these findings yield insight into why combination therapy is often required to adequately control blood pressure.

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“…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].…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models.

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Integration of detailed modules in a core model of body fluid homeostasis and blood pressure regulation

Cited by 22 publications

References 40 publications

Sensitivity Analysis and Parameter Estimation of a Coronary Circulation Model for Triple-Vessel Disease

Sensitivity Analysis and Parameter Estimation of a Coronary Circulation Model for Triple-Vessel Disease

A model-based approach to investigating the pathophysiological mechanisms of hypertension and response to antihypertensive therapies: extending the Guyton model

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

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