Modeling and Hemofiltration Treatment of Acute Inflammation
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 clinical...
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doaj-5082bcbf07664ca1a2a27325dbf253432020-11-25T01:32:38ZengMDPI AGProcesses2227-97172016-10-01443810.3390/pr4040038pr4040038Modeling and Hemofiltration Treatment of Acute InflammationRobert S. Parker0Justin S. Hogg1Anirban Roy2John A. Kellum3Thomas Rimmelé4Silvia Daun-Gruhn5Morgan V. Fedorchak6Isabella E. Valenti7William J. Federspiel8Jonathan Rubin9Yoram Vodovotz10Claudio Lagoa11Gilles Clermont12Department of Chemical and Petroleum Engineering; Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USACarnegie Mellon–University of Pittsburgh Ph.D. Program in Computational Biology, 3501 Fifth Ave, 3064 BST3, Pittsburgh, PA 15260, USADepartment of Chemical and Petroleum Engineering; Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Critical Care Medicine, University of Pittsburgh Medical Center, 3550 Terrace St, Pittsburgh, PA 15213, USADepartment of Critical Care Medicine, University of Pittsburgh Medical Center, 3550 Terrace St, Pittsburgh, PA 15213, USADepartment of Critical Care Medicine, University of Pittsburgh Medical Center, 3550 Terrace St, Pittsburgh, PA 15213, USADepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Mathematics, University of Pittsburgh, 301 Thackeray Hall, Pittsburgh, PA 15261, USAMcGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, 450 Technology Dr, Suite 300, Pittsburgh, PA 15219, USADepartment of Surgery, University of Pittsburgh Medical Center, W944 Biomedical Sciences Tower, Pittsburgh, PA 15213, USADepartment of Chemical and Petroleum Engineering; Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USAThe 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.http://www.mdpi.com/2227-9717/4/4/38mathematical modelinflammationcytokinessepsisendotoxemiahemoadsorptionnonlinear MPCparticle filterstate estimation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Robert S. Parker Justin S. Hogg Anirban Roy John A. Kellum Thomas Rimmelé Silvia Daun-Gruhn Morgan V. Fedorchak Isabella E. Valenti William J. Federspiel Jonathan Rubin Yoram Vodovotz Claudio Lagoa Gilles Clermont |
spellingShingle |
Robert S. Parker Justin S. Hogg Anirban Roy John A. Kellum Thomas Rimmelé Silvia Daun-Gruhn Morgan V. Fedorchak Isabella E. Valenti William J. Federspiel Jonathan Rubin Yoram Vodovotz Claudio Lagoa Gilles Clermont Modeling and Hemofiltration Treatment of Acute Inflammation Processes mathematical model inflammation cytokines sepsis endotoxemia hemoadsorption nonlinear MPC particle filter state estimation |
author_facet |
Robert S. Parker Justin S. Hogg Anirban Roy John A. Kellum Thomas Rimmelé Silvia Daun-Gruhn Morgan V. Fedorchak Isabella E. Valenti William J. Federspiel Jonathan Rubin Yoram Vodovotz Claudio Lagoa Gilles Clermont |
author_sort |
Robert S. Parker |
title |
Modeling and Hemofiltration Treatment of Acute Inflammation |
title_short |
Modeling and Hemofiltration Treatment of Acute Inflammation |
title_full |
Modeling and Hemofiltration Treatment of Acute Inflammation |
title_fullStr |
Modeling and Hemofiltration Treatment of Acute Inflammation |
title_full_unstemmed |
Modeling and Hemofiltration Treatment of Acute Inflammation |
title_sort |
modeling and hemofiltration treatment of acute inflammation |
publisher |
MDPI AG |
series |
Processes |
issn |
2227-9717 |
publishDate |
2016-10-01 |
description |
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. |
topic |
mathematical model inflammation cytokines sepsis endotoxemia hemoadsorption nonlinear MPC particle filter state estimation |
url |
http://www.mdpi.com/2227-9717/4/4/38 |
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