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Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis

Sepsis and sepsis-associated multiorgan failure represent the major cause of mortality in intensive care units worldwide. Cardiovascular dysfunction, a key component of sepsis pathogenesis, has received much research interest, although research translatability remains severely limited. There is a cr...

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Autores principales: Sand, Claire A., Starr, Anna, Wilder, Catherine D. E., Rudyk, Olena, Spina, Domenico, Thiemermann, Christoph, Treacher, David F., Nandi, Manasi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Physiological Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312846/
https://www.ncbi.nlm.nih.gov/pubmed/25477352
http://dx.doi.org/10.1152/japplphysiol.00793.2014
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author Sand, Claire A.
Starr, Anna
Wilder, Catherine D. E.
Rudyk, Olena
Spina, Domenico
Thiemermann, Christoph
Treacher, David F.
Nandi, Manasi
author_facet Sand, Claire A.
Starr, Anna
Wilder, Catherine D. E.
Rudyk, Olena
Spina, Domenico
Thiemermann, Christoph
Treacher, David F.
Nandi, Manasi
author_sort Sand, Claire A.
collection PubMed
description Sepsis and sepsis-associated multiorgan failure represent the major cause of mortality in intensive care units worldwide. Cardiovascular dysfunction, a key component of sepsis pathogenesis, has received much research interest, although research translatability remains severely limited. There is a critical need for more comprehensive preclinical sepsis models, with more clinically relevant end points, such as microvascular perfusion. The purpose of this study was to compare microcirculatory blood flow measurements, using a novel application of laser speckle contrast imaging technology, with more traditional hemodynamic end points, as part of a multiparameter monitoring system in preclinical models of sepsis. Our aim, in measuring mesenteric blood flow, was to increase the prognostic sensitivity of preclinical studies. In two commonly used sepsis models (cecal ligation and puncture, and lipopolysaccharide), we demonstrate that blood pressure and cardiac output are compromised postsepsis, but subsequently stabilize over the 24-h recording period. In contrast, mesenteric blood flow continuously declines in a time-dependent manner and in parallel with the development of metabolic acidosis and organ dysfunction. Importantly, these microcirculatory perturbations are reversed by fluid resuscitation, a mainstay intervention associated with improved outcome in patients. These data suggest that global hemodynamics are maintained at the expense of the microcirculation and are, therefore, not sufficiently predictive of outcome. We demonstrate that microcirculatory blood flow is a more sensitive biomarker of sepsis syndrome progression and believe that incorporation of this biomarker into preclinical models will facilitate sophisticated proof-of-concept studies for novel sepsis interventions, providing more robust data on which to base future clinical trials.
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spelling pubmed-43128462015-02-10 Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis Sand, Claire A. Starr, Anna Wilder, Catherine D. E. Rudyk, Olena Spina, Domenico Thiemermann, Christoph Treacher, David F. Nandi, Manasi J Appl Physiol (1985) Articles Sepsis and sepsis-associated multiorgan failure represent the major cause of mortality in intensive care units worldwide. Cardiovascular dysfunction, a key component of sepsis pathogenesis, has received much research interest, although research translatability remains severely limited. There is a critical need for more comprehensive preclinical sepsis models, with more clinically relevant end points, such as microvascular perfusion. The purpose of this study was to compare microcirculatory blood flow measurements, using a novel application of laser speckle contrast imaging technology, with more traditional hemodynamic end points, as part of a multiparameter monitoring system in preclinical models of sepsis. Our aim, in measuring mesenteric blood flow, was to increase the prognostic sensitivity of preclinical studies. In two commonly used sepsis models (cecal ligation and puncture, and lipopolysaccharide), we demonstrate that blood pressure and cardiac output are compromised postsepsis, but subsequently stabilize over the 24-h recording period. In contrast, mesenteric blood flow continuously declines in a time-dependent manner and in parallel with the development of metabolic acidosis and organ dysfunction. Importantly, these microcirculatory perturbations are reversed by fluid resuscitation, a mainstay intervention associated with improved outcome in patients. These data suggest that global hemodynamics are maintained at the expense of the microcirculation and are, therefore, not sufficiently predictive of outcome. We demonstrate that microcirculatory blood flow is a more sensitive biomarker of sepsis syndrome progression and believe that incorporation of this biomarker into preclinical models will facilitate sophisticated proof-of-concept studies for novel sepsis interventions, providing more robust data on which to base future clinical trials. American Physiological Society 2014-12-04 2015-02-01 /pmc/articles/PMC4312846/ /pubmed/25477352 http://dx.doi.org/10.1152/japplphysiol.00793.2014 Text en Copyright © 2015 the American Physiological Society Licensed under Creative Commons Attribution CC-BY 3.0 (http://creativecommons.org/licenses/by/3.0/deed.en_US) : © the American Physiological Society.
spellingShingle Articles
Sand, Claire A.
Starr, Anna
Wilder, Catherine D. E.
Rudyk, Olena
Spina, Domenico
Thiemermann, Christoph
Treacher, David F.
Nandi, Manasi
Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis
title Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis
title_full Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis
title_fullStr Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis
title_full_unstemmed Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis
title_short Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis
title_sort quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312846/
https://www.ncbi.nlm.nih.gov/pubmed/25477352
http://dx.doi.org/10.1152/japplphysiol.00793.2014
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