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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Format: | Article |
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Public Library of Science (PLoS)
2022-01-01
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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. |
first_indexed | 2024-04-13T01:46:45Z |
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id | doaj.art-b4d40688bd954ab489d12e49c24aa283 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-13T01:46:45Z |
publishDate | 2022-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
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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