β-Hydroxy-β-methylbutyrate (HMB) prevents sepsis-induced diaphragm dysfunction in mice

Gerald S. Supinski, Leigh A. Callahan

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Infections induce severe respiratory muscle weakness. Currently there are no treatments for this important clinical problem. We tested the hypothesis that β-hydroxy-β-methylbutyrate (HMB) would prevent sepsis-induced diaphragm weakness. Four groups of adult male mice were studied: controls (saline-injected), sepsis (intraperitoneal lipopolysaccharide), sepsis. +. HMB (injected intravenously), and HMB. Diaphragm force generation and indices of caspase 3, calpain, 20S proteasomal subunit, and double-stranded RNA-dependent protein kinase (PKR) activation were assessed after 24. h. Sepsis elicited large reductions in diaphragm specific force generation at all stimulation frequencies. Endotoxin also activated caspase 3, calpain, the 20S proteasomal subunit and PKR in the diaphragm. HMB blocked sepsis-induced caspase 3, 20S proteasomal and PKR activation, but did not prevent calpain activation. Most importantly, HMB administration significantly attenuated sepsis-induced diaphragm weakness, preserving muscle force generation at all stimulation frequencies ( p<. 0.01). We speculate that HMB may prove to be an important therapy in infected patients, with the potential to increase diaphragm strength, to reduce the duration of mechanical ventilation and to decrease mortality in this patient population.

Original languageEnglish
Pages (from-to)63-68
Number of pages6
JournalRespiratory Physiology and Neurobiology
Volume196
Issue number1
DOIs
StatePublished - Jun 1 2014

Bibliographical note

Funding Information:
This work was supported by the following grants from the National Institutes of Health : HL080429 , HL081525 , and HL112085 .

Keywords

  • Caspase 3
  • Diaphragm
  • PKR
  • Proteolysis
  • Sepsis
  • β-Hydroxy-β-methylbutyrate (HMB)

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology
  • Pulmonary and Respiratory Medicine

Fingerprint

Dive into the research topics of 'β-Hydroxy-β-methylbutyrate (HMB) prevents sepsis-induced diaphragm dysfunction in mice'. Together they form a unique fingerprint.

Cite this