The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.

Sepsis, a life-threatening organ dysfunction, results from dysregulated host responses to infection and still has a high incidence and mortality. Although administration of vasopressors to treat septic shock is standard of care, the benefits are not well established. We evaluated the effect of conti...

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Main Authors: Tetsushi Yamashita, Jonathan M Street, Brianna C Halasa, Yoshitaka Naito, Takayuki Tsuji, Naoko Tsuji, Naoki Hayase, Peter S T Yuen, Robert A Star
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0271667
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author Tetsushi Yamashita
Jonathan M Street
Brianna C Halasa
Yoshitaka Naito
Takayuki Tsuji
Naoko Tsuji
Naoki Hayase
Peter S T Yuen
Robert A Star
author_facet Tetsushi Yamashita
Jonathan M Street
Brianna C Halasa
Yoshitaka Naito
Takayuki Tsuji
Naoko Tsuji
Naoki Hayase
Peter S T Yuen
Robert A Star
author_sort Tetsushi Yamashita
collection DOAJ
description Sepsis, a life-threatening organ dysfunction, results from dysregulated host responses to infection and still has a high incidence and mortality. Although administration of vasopressors to treat septic shock is standard of care, the benefits are not well established. We evaluated the effect of continuous intravenous norepinephrine infusion in a septic cecal ligation and puncture (CLP) mouse model, evaluating systemic hemodynamics and body temperature post-hoc. CLP surgery significantly decreased mean arterial blood pressure (MAP), heart rate, and body temperature within six hours. Continuous norepinephrine infusion (NE+, n = 12) started at the time of CLP surgery significantly increased MAP at 24 and 30 hours and heart rate at 6, 18, 24, and 30 hours after CLP vs CLP alone (NE-, n = 12). However, addition of norepinephrine did not improve survival rate (NE+ n = 34, NE- n = 31). Early (6 hours or earlier, when the animal became visibly sick) MAP did not predict 7-day mortality. However, heart rates at 3 and at 6 hours after CLP/norepinephrine (NE+) were highly predictive of mortality, as also been found in one clinical study. We conclude that limited hemodynamic support can be provided in a mouse sepsis model. We propose that heart rate can be used to stratify severity of illness in rodent preclinical studies of sepsis therapeutics.
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spelling doaj.art-b4d40688bd954ab489d12e49c24aa2832022-12-22T03:08:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01178e027166710.1371/journal.pone.0271667The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.Tetsushi YamashitaJonathan M StreetBrianna C HalasaYoshitaka NaitoTakayuki TsujiNaoko TsujiNaoki HayasePeter S T YuenRobert A StarSepsis, a life-threatening organ dysfunction, results from dysregulated host responses to infection and still has a high incidence and mortality. Although administration of vasopressors to treat septic shock is standard of care, the benefits are not well established. We evaluated the effect of continuous intravenous norepinephrine infusion in a septic cecal ligation and puncture (CLP) mouse model, evaluating systemic hemodynamics and body temperature post-hoc. CLP surgery significantly decreased mean arterial blood pressure (MAP), heart rate, and body temperature within six hours. Continuous norepinephrine infusion (NE+, n = 12) started at the time of CLP surgery significantly increased MAP at 24 and 30 hours and heart rate at 6, 18, 24, and 30 hours after CLP vs CLP alone (NE-, n = 12). However, addition of norepinephrine did not improve survival rate (NE+ n = 34, NE- n = 31). Early (6 hours or earlier, when the animal became visibly sick) MAP did not predict 7-day mortality. However, heart rates at 3 and at 6 hours after CLP/norepinephrine (NE+) were highly predictive of mortality, as also been found in one clinical study. We conclude that limited hemodynamic support can be provided in a mouse sepsis model. We propose that heart rate can be used to stratify severity of illness in rodent preclinical studies of sepsis therapeutics.https://doi.org/10.1371/journal.pone.0271667
spellingShingle Tetsushi Yamashita
Jonathan M Street
Brianna C Halasa
Yoshitaka Naito
Takayuki Tsuji
Naoko Tsuji
Naoki Hayase
Peter S T Yuen
Robert A Star
The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.
PLoS ONE
title The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.
title_full The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.
title_fullStr The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.
title_full_unstemmed The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.
title_short The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.
title_sort effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically monitored mouse model of sepsis
url https://doi.org/10.1371/journal.pone.0271667
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