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Modeling and Hemofiltration Treatment of Acute Inflammation

Parker, Robert and Hogg, Justin and Roy, Anirban and Kellum, John and Rimmelé, Thomas and Daun-Gruhn, Silvia and Fedorchak, Morgan and Valenti, Isabella and Federspiel, William and Rubin, Jonathan and Vodovotz, Yoram and Lagoa, Claudio and Clermont, Gilles (2016) Modeling and Hemofiltration Treatment of Acute Inflammation. Processes, 4 (4). ISSN 2227-9717

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The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin) and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D) differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL)-6, tumor necrosis factor (TNF), and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC) algorithm was synthesized to control a hemoadsorption (HA) device, a blood purification treatment for acute inflammation. A particle filter (PF) algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i) the apparent primary mechanism of HA efficacy is white blood cell (WBC) capture, with cytokine capture a secondary benefit; and (ii) differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Parker, RobertGradAD_ssoe@pitt.eduGradAD_ssoe
Hogg, Justin
Roy, Anirban
Kellum, Johnkellum@pitt.edukellum
Rimmelé, Thomas
Daun-Gruhn, Silvia
Fedorchak, Morganfedorchak@pitt.edufedorchak
Valenti, Isabella
Federspiel, William
Rubin, Jonathanjonrubin@pitt.edujonrubin
Vodovotz, Yoramvodovotz@pitt.eduvodovotz
Lagoa, Claudio
Clermont, Gillescler@pitt.educler
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Date: 18 October 2016
Date Type: Publication
Journal or Publication Title: Processes
Volume: 4
Number: 4
Publisher: MDPI AG
DOI or Unique Handle: 10.3390/pr4040038
Schools and Programs: Swanson School of Engineering > Chemical and Petroleum Engineering
Refereed: Yes
Uncontrolled Keywords: mathematical model, inflammation, cytokines, sepsis, endotoxemia, hemoadsorption, nonlinear MPC, particle filter, state estimation
ISSN: 2227-9717
Official URL:
Funders: NIH
Article Type: Research Article
Date Deposited: 04 Feb 2021 18:07
Last Modified: 04 Feb 2021 18:07


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