UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Sand, CA; Starr, A; Wilder, CDE; Rudyk, O; Spina, D; Thiemermann, C; Treacher, DF; (2015) Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis. Journal of Applied Physiology , 118 (3) pp. 344-354. 10.1152/japplphysiol.00793.2014. Green open access

[img]
Preview
Text
Wilder,_japplphysiol.00793.2014.pdf - Published version

Download (1MB) | Preview

Abstract

Sand CA, Starr A, Wilder CD, Rudyk O, Spina D, Thiemermann C, Treacher DF, Nandi M. Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis. J Appl Physiol 118: 344–354, 2015. First published December 4, 2014; doi:10.1152/japplphysiol.00793.2014.—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.

Type: Article
Title: Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1152/japplphysiol.00793.2014
Publisher version: http://doi.org/10.1152/japplphysiol.00793.2014
Language: English
Additional information: Copyright & Permissions: Copyright © 2015 the American Physiological Society Licensed under Creative Commons Attribution CC-BY 3.0: © the American Physiological Society.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/10024955
Downloads since deposit
57Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item