Personalized mathematical model of endotoxin-induced inflammatory responses in young men and associated changes in heart rate variability

Renee Brady, Dennis Frank-Ito, Hien Tran, Susanne Janum, Kirsten Møller, Susanne Brix, Johnny T. Ottesen, Jesper Mehlsen, Mette Olufsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The objective of this study is to develop a personalized inflammatory model and
estimate subject-specific parameters that can be related to changes in heart rate
variability (HRV), a measure that can be obtained non-invasively in real time. An
inflammatory model is developed and calibrated to measurements of interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), interleukin-8 (IL-8) and interleukin-10 (IL-10) over 8 hours in 20 subjects administered a low dose of lipopolysaccharide. For this model, we estimated 11 subject-specific parameters for all 20 subjects. Estimated parameters were correlated with changes in HRV, computed from ECG Measurements using a built-in HRV module available in Labchart. Results revealed that patients could be separated into two groups expressing normal and abnormal responses to endotoxin. Abnormal responders exhibited increased HRV, most likely as a result of increased vagal firing. The observed correlation between the inflammatory response and HRV brings us a step further towards understanding if HRV predictions can be used as a marker for inflammation. Analyzing HRV parameters provides an easy, noninvasively
obtained measure that can be used to asses the state of the subject,
potentially translating to identifying a non-invasive marker that can be used to detect the onset of sepsis.
OriginalsprogEngelsk
Artikelnummer42
TidsskriftMathematical Modelling of Natural Phenomena
Vol/bind13
Udgave nummer5
Antal sider20
ISSN0973-5348
DOI
StatusUdgivet - 2018

Citer dette

Brady, Renee ; Frank-Ito, Dennis ; Tran, Hien ; Janum, Susanne ; Møller, Kirsten ; Brix, Susanne ; Ottesen, Johnny T. ; Mehlsen, Jesper ; Olufsen, Mette. / Personalized mathematical model of endotoxin-induced inflammatory responses in young men and associated changes in heart rate variability. I: Mathematical Modelling of Natural Phenomena. 2018 ; Bind 13, Nr. 5.
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title = "Personalized mathematical model of endotoxin-induced inflammatory responses in young men and associated changes in heart rate variability",
abstract = "The objective of this study is to develop a personalized inflammatory model andestimate subject-specific parameters that can be related to changes in heart ratevariability (HRV), a measure that can be obtained non-invasively in real time. Aninflammatory model is developed and calibrated to measurements of interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), interleukin-8 (IL-8) and interleukin-10 (IL-10) over 8 hours in 20 subjects administered a low dose of lipopolysaccharide. For this model, we estimated 11 subject-specific parameters for all 20 subjects. Estimated parameters were correlated with changes in HRV, computed from ECG measurements using a built-in HRV module available in Labchart. Results revealed that patients could be separated into two groups expressing normal and abnormal responses to endotoxin. Abnormal responders exhibited increased HRV, most likely as a result of increased vagal firing. The observed correlation between the inflammatory response and HRV brings us a step further towards understanding if HRV predictions can be used as a marker for inflammation. Analyzing HRV parameters provides an easy, noninvasivelyobtained measure that can be used to asses the state of the subject, potentially translating to identifying a non-invasive marker that can be used to detectthe onset of sepsis.",
keywords = "Acute inflammation, mathematical modeling, heart rate variability, Parameter estimation",
author = "Renee Brady and Dennis Frank-Ito and Hien Tran and Susanne Janum and Kirsten M{\o}ller and Susanne Brix and Ottesen, {Johnny T.} and Jesper Mehlsen and Mette Olufsen",
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Personalized mathematical model of endotoxin-induced inflammatory responses in young men and associated changes in heart rate variability. / Brady, Renee; Frank-Ito, Dennis; Tran, Hien; Janum, Susanne; Møller, Kirsten; Brix, Susanne; Ottesen, Johnny T.; Mehlsen, Jesper; Olufsen, Mette.

I: Mathematical Modelling of Natural Phenomena, Bind 13, Nr. 5, 42, 2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Personalized mathematical model of endotoxin-induced inflammatory responses in young men and associated changes in heart rate variability

AU - Brady, Renee

AU - Frank-Ito, Dennis

AU - Tran, Hien

AU - Janum, Susanne

AU - Møller, Kirsten

AU - Brix, Susanne

AU - Ottesen, Johnny T.

AU - Mehlsen, Jesper

AU - Olufsen, Mette

PY - 2018

Y1 - 2018

N2 - The objective of this study is to develop a personalized inflammatory model andestimate subject-specific parameters that can be related to changes in heart ratevariability (HRV), a measure that can be obtained non-invasively in real time. Aninflammatory model is developed and calibrated to measurements of interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), interleukin-8 (IL-8) and interleukin-10 (IL-10) over 8 hours in 20 subjects administered a low dose of lipopolysaccharide. For this model, we estimated 11 subject-specific parameters for all 20 subjects. Estimated parameters were correlated with changes in HRV, computed from ECG measurements using a built-in HRV module available in Labchart. Results revealed that patients could be separated into two groups expressing normal and abnormal responses to endotoxin. Abnormal responders exhibited increased HRV, most likely as a result of increased vagal firing. The observed correlation between the inflammatory response and HRV brings us a step further towards understanding if HRV predictions can be used as a marker for inflammation. Analyzing HRV parameters provides an easy, noninvasivelyobtained measure that can be used to asses the state of the subject, potentially translating to identifying a non-invasive marker that can be used to detectthe onset of sepsis.

AB - The objective of this study is to develop a personalized inflammatory model andestimate subject-specific parameters that can be related to changes in heart ratevariability (HRV), a measure that can be obtained non-invasively in real time. Aninflammatory model is developed and calibrated to measurements of interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), interleukin-8 (IL-8) and interleukin-10 (IL-10) over 8 hours in 20 subjects administered a low dose of lipopolysaccharide. For this model, we estimated 11 subject-specific parameters for all 20 subjects. Estimated parameters were correlated with changes in HRV, computed from ECG measurements using a built-in HRV module available in Labchart. Results revealed that patients could be separated into two groups expressing normal and abnormal responses to endotoxin. Abnormal responders exhibited increased HRV, most likely as a result of increased vagal firing. The observed correlation between the inflammatory response and HRV brings us a step further towards understanding if HRV predictions can be used as a marker for inflammation. Analyzing HRV parameters provides an easy, noninvasivelyobtained measure that can be used to asses the state of the subject, potentially translating to identifying a non-invasive marker that can be used to detectthe onset of sepsis.

KW - Acute inflammation

KW - mathematical modeling

KW - heart rate variability

KW - Parameter estimation

U2 - 10.1051/mmnp/2018031

DO - 10.1051/mmnp/2018031

M3 - Journal article

VL - 13

JO - Mathematical Modelling of Natural Phenomena

JF - Mathematical Modelling of Natural Phenomena

SN - 0973-5348

IS - 5

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ER -