Format

Send to

Choose Destination
Crit Care. 2017 Aug 8;21(1):210. doi: 10.1186/s13054-017-1783-1.

Voluntary running exercise protects against sepsis-induced early inflammatory and pro-coagulant responses in aged mice.

Tyml K1,2, Swarbreck S1, Pape C1,3, Secor D1, Koropatnick J4,5,6,7, Feng Q1,5, Veldhuizen RAW1,8,3,5, Gill SE9,10,11,12.

Author information

1
Centre for Critical Illness Research, London, Ontario, Canada.
2
Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
3
Department of Medicine, University of Western Ontario, London, Ontario, Canada.
4
Cancer Research Program, Lawson Health Research Institute, London, Ontario, Canada.
5
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
6
Department of Oncology, University of Western Ontario, London, Ontario, Canada.
7
Department of Pathology, University of Western Ontario, London, Ontario, Canada.
8
Division of Respirology, University of Western Ontario, London, Ontario, Canada.
9
Centre for Critical Illness Research, London, Ontario, Canada. sgill8@uwo.ca.
10
Division of Respirology, University of Western Ontario, London, Ontario, Canada. sgill8@uwo.ca.
11
Department of Medicine, University of Western Ontario, London, Ontario, Canada. sgill8@uwo.ca.
12
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada. sgill8@uwo.ca.

Abstract

BACKGROUND:

Despite many animal studies and clinical trials, mortality in sepsis remains high. This may be due to the fact that most experimental studies of sepsis employ young animals, whereas the majority of septic patients are elderly (60 - 70 years). The objective of the present study was to examine the sepsis-induced inflammatory and pro-coagulant responses in aged mice. Since running exercise protects against a variety of diseases, we also examined the effect of voluntary running on septic responses in aged mice.

METHODS:

Male C57BL/6 mice were housed in our institute from 2-3 to 22 months (an age mimicking that of the elderly). Mice were prevented from becoming obese by food restriction (given 70-90% of ad libitum consumption amount). Between 20 and 22 months, a subgroup of mice ran voluntarily on wheels, alternating 1-3 days of running with 1-2 days of rest. At 22 months, mice were intraperitoneally injected with sterile saline (control) or 3.75 g/kg fecal slurry (septic). At 7 h post injection, we examined (1) neutrophil influx in the lung and liver by measuring myeloperoxidase and/or neutrophil elastase in the tissue homogenates by spectrophotometry, (2) interleukin 6 (IL6) and KC in the lung lavage by ELISA, (3) pulmonary surfactant function by measuring percentage of large aggregates, (4) capillary plugging (pro-coagulant response) in skeletal muscle by intravital microscopy, (5) endothelial nitric oxide synthase (eNOS) protein in skeletal muscle (eNOS-derived NO is putative inhibitor of capillary plugging) by immunoblotting, and (6) systemic blood platelet counts by hemocytometry.

RESULTS:

Sepsis caused high levels of pulmonary myeloperoxidase, elastase, IL6, KC, liver myeloperoxidase, and capillary plugging. Sepsis also caused low levels of surfactant function and platelet counts. Running exercise increased eNOS protein and attenuated the septic responses.

CONCLUSIONS:

Voluntary running protects against exacerbated sepsis-induced inflammatory and pro-coagulant responses in aged mice. Protection against pro-coagulant responses may involve eNOS upregulation. The present discovery in aged mice calls for clinical investigation into potential beneficial effects of exercise on septic outcomes in the elderly.

KEYWORDS:

Aging; Capillary plugging; Pulmonary inflammation; Voluntary running; sepsis

PMID:
28789683
PMCID:
PMC5549433
DOI:
10.1186/s13054-017-1783-1
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center