%0 Journal Article
%A Parker, Robert
%A Hogg, Justin
%A Roy, Anirban
%A Kellum, John
%A Rimmelé, Thomas
%A Daun-Gruhn, Silvia
%A Fedorchak, Morgan
%A Valenti, Isabella
%A Federspiel, William
%A Rubin, Jonathan
%A Vodovotz, Yoram
%A Lagoa, Claudio
%A Clermont, Gilles
%T Modeling and Hemofiltration Treatment of Acute Inflammation
%J Processes
%V 4
%N 4
%@ 2227-9717
%C Basel
%I MDPI
%M FZJ-2017-00246
%P 38 -
%D 2016
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000391592700005
%R 10.3390/pr4040038
%U https://juser.fz-juelich.de/record/825974