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

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

Medicine in Drug Discovery (Mar 2021)

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

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

Affiliations

Yujiro Matsuishi, RN, MS: Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Pediatric Intensive Care Unit, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
Nobutake Shimojo, MD, PhD: Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Haruhiko Hoshino, RN, PhD: Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Pediatric Intensive Care Unit, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
Yuki Enomoto, MD: Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Pediatrics, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Bryan J. Mathis, PhD: Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Sechang Oh, PhD: Medical Sciences, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Satoru Kawano, MD, PhD: Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Kanae Myoenzono, PhD: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
Seiji Maeda, PhD: Faculty of Health and Sport Sciences, University of Tsukuba, Ibaraki, Japan
Junichi Shoda, MD, PhD: Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Shigeaki Inoue, MD, PhD: Department of Disaster and Emergency and Critical Care Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Yoshiaki Inoue, MD, PhD: Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Corresponding author at: Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

Journal volume & issue: Vol. 9
p. 100074

Abstract

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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.

Published in Medicine in Drug Discovery

ISSN: 2590-0986 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Pharmacy and materia medica
Website: https://www.journals.elsevier.com/medicine-in-drug-discovery

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