Muscle weakness in a sepsis mouse model.

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 sepsis could serve as a model for ICU-AW.

METHODS

A total of 24 C57BL/6J mice were infected intranasally with viable . 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, 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 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 inoculation.

CONCLUSIONS

diaphragm weakness, but no limb weakness was found in the 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.