Establishment of a murine, lipopolysaccharide-induced sepsis model for testing anaerobic exercise thresholds and early mobilization

Yujiro Matsuishi, Nobutake Shimojo, Haruhiko Hoshino, Yuki Enomoto, Bryan J. Mathis, Sechang Oh, Satoru Kawano, Kanae Myoenzono, Seiji Maeda, Junichi Shoda, Shigeaki Inoue, Yoshiaki Inoue*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Several methods have been proposed to prevent post intensive care syndrome after sepsis, including early mobilization, but controversy remains in mechanisms and outcomes. Therefore, the aim of this study is to establish a septic mouse model and classify exercise intensities during the acute phase of sepsis to generate a murine sepsis rehabilitation model. Methods: Adult, male C57/B6 mice received lipopolysaccharide (LPS) injections (20 mg/kg). We recorded survival rates and metabolic changes, such as resting energy expenditure (REE), compared with controls up to 72 h after LPS administration. We also observed vital signs (rectal temperature and weight change), inflammation (TNF-α and IL-6), and exercise intensity via metabolic monitoring treadmill. We analyzed the anaerobic threshold (AT) by the V-Slope method. Result: Around 30% of the mice survived 72 h after LPS induction with the lowest REE at around 22–24 h later (REE at 22 h: 2.26 ± 0.34 kcal/day p < 0.05 vs. baseline). Blood concentrations of TNF-α were highest at the 12 h timepoint (41.23 ± 24.39 pg/mL, p < 0.05 vs. baseline) and IL-6 was highest at 24 h after LPS induction (1476.5 ± 274.7 pg/mL, p < 0.05 vs. baseline). With V-Slope, we observed the AT at each timepoint (6 h:14 m/min,12 h: 9 m/min, 24 h:4 m/min,36 h:10 m/min, 48 h:16 m/min, 60 h:20 m/min, 72 h:22 m/min) and classified these into very low intensity exercise training, low intensity exercise training, or moderate intensity exercise training at each timepoint. Conclusion: We classified exercise intensities out to 72 h after sepsis recovery using a mouse model. These data may serve as a bridge to clinical studies to fill gaps in best practice for sepsis rehabilitation.

Original languageEnglish
Article number100074
JournalMedicine in Drug Discovery
Publication statusPublished - 2021 Mar
Externally publishedYes


  • Early mobilization
  • Sepsis
  • Translational study

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)


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