Muscle weakness in a S. pneumoniae sepsis mouse model.

Autor:	Witteveen E; Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands.; Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, Amsterdam, The Netherlands.; Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands., Wieske L; Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands.; Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, Amsterdam, The Netherlands.; Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands., Manders E; Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands., Verhamme C; Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands., Ottenheijm CAC; Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands., Schultz MJ; Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands.; Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, Amsterdam, The Netherlands., van Schaik IN; Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands., Horn J; Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands.; Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Annals of translational medicine [Ann Transl Med] 2019 Jan; Vol. 7 (1), pp. 9.
DOI:	10.21037/atm.2018.12.45
Abstrakt:	Background: The pathophysiology of intensive care unit-acquired weakness (ICU-AW), which affects peripheral nerves, limb muscles and respiratory muscles, is complex and incompletely understood. This illustrates the need for an ICU-AW animal model. However, a translatable and easily applicable ICU-AW animal model does not exist. The objective of this study was to investigate whether induction of a S. pneumoniae sepsis could serve as a model for ICU-AW. Methods: A total of 24 C57BL/6J mice were infected intranasally with viable S. pneumoniae . Control mice (n=8) received intranasal saline and mice of the blank group (n=4) were not inoculated. Ceftriaxone was administered at 24 h (n=8) or at 48h after inoculation (n=8), or as soon as mice lost 10% of their body weight (n=8). The primary endpoint, in vivo grip strength, was measured daily. At the end of the experiment, at 120 h after inoculation, electrophysiological recordings were performed and diaphragm muscle was excised to determine ex vivo muscle fiber strength and myosin/action ratio. Results: Grip strength over time was similar between experimental and control groups and electrophysiological recordings did not show signs of ICU-AW. Diaphragm fiber contractility measurements showed reduced strength in the group that received ceftriaxone at 48 h after S. pneumoniae inoculation. Conclusions: Ex vivo diaphragm weakness, but no in vivo limb weakness was found in the S. pneumoniae mouse model in which severe illness was induced. This does not reflect the full clinical picture of ICU-AW as seen in humans and as such this model did not fulfill our predefined requirements. However, this model may be used to study inflammation induced diaphragmatic weakness. Competing Interests: Conflicts of Interest: Prof. IN van Schaik received departmental honoraria for serving on scientific advisory boards and a steering committee for CSL-Behring. The other authors have no conflicts of interest to declare.
Databáze:	MEDLINE
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