Background
The derangement in oxygen utilization occurring during sepsis is likely to be linked
to impaired mitochondrial functioning. Skeletal muscle comprises 50%–60% of body cell
mass and represents the largest organ potentially affected by systemic inflammation.
Thus, we investigated whether sepsis induced by cecal ligation and puncture (CLP)
modifies mitochondrial activity in respiratory and nonrespiratory skeletal muscle.
Materials and Methods
Wistar rats were subjected to CLP and at different times, diaphragm and quadriceps
were removed for the determination of electron transfer chain activities and mitochondrial
oxidative stress. In addition, we determined diaphragm contractile strength.
Results
In the quadriceps, 12 h after CLP we demonstrated a significant diminution on complex
II-III activity. At late times (48 h after CLP), we demonstrated a decrease in the
activity of all electron transfer chain complexes, which seemed to be secondary to
early oxidative stress and correlates with diaphragm contractile strength. Differently
from diaphragm, electron transfer chain was not decreased after sepsis and even oxidative
stress was not increased at all times tested.
Conclusion
Our results suggest that quadriceps mitochondria are more resistant to sepsis-induced
dysfunction.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Surgical ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Association between mitochondrial dysfunction and severity and outcome of septic shock.Lancet. 2002; 219: 223
- Free radicals alter maximal diaphragmatic oxygen consumption in endotoxin-induced sepsis.Free Radic Biol Med. 2001; 129: 138
- Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function.Crit. Care. 2006; : R118
- Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle.Crit Care Med. 2007; 2150: 2155
- Endogenous peroxynitrite mediates mitochondrial dysfunction in rat diaphragm during endotoxemia.FASEB J. 1999; 1637: 1647
- Ileal VO2-DO2 alterations induced by endotoxin correlate with severity of mitochondrial injury.Am J Respir Crit Care Med. 1999; 1347: 1353
- Different sensitivity of rabbit heart and skeletal muscle to endotoxin-induced impairment of mitochondrial function.Eur J Biochem. 2001; 1422: 1429
- Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure.Am J Physiol Regul Integr Comp Physiol. 2004; R491: R497
- Mitochondrial respiratory chain and creatine kinase activities in rat brain after sepsis induced by cecal ligation and perforation.Mitochondrion. 2008; 313: 318
- Antioxidant treatment reverses mitochondrial dysfunction in a sepsis animal model.Mitochondrion. 2008; 211: 218
- Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis.Arch Surg. 1998; 1316: 1321
- Sepsis and the systemic inflammatory response syndrome: Neuromuscular manifestations.Crit Care Med. 1996; 24: 1408
- Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: Mechanisms at the cellular and molecular levels.Crit Care Med. 2000; 34: 45
- Mitochondrial function in sepsis: Respiratory versus leg muscle.Crit Care Med. 2007; S449: S453
- Sepsis and septic shock—a review of laboratory models and a proposal.J Surg Res. 1980; 189: 199
- Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis.Crit Care Med. 2004; 32: 342
- Differential inhibitory cation of nitric oxide and peroxynitrite on mitochondrial electron transport.Arch Biochem Biophys. 1996; 358: 309
- Differential investigation of the capacity of succinate oxidation in human skeletal muscle.Clin Chim Acta. 1885; 23: 26
- Cytochrome c oxidase assay in minute amounts of human skeletal muscle using single wavelength spectrophotometers.J Neurosci Methods. 1998; 107: 111
- Protein measurement with the Folin phenol reagent.J Biol Chem. 1951; 265: 275
- Malondialdehyde determination as index of lipid peroxidation.Methods Enzymol. 1990; 421: 431
- Nitric oxide, superoxide, and hydrogen peroxide production in brain mitochondria after haloperidol treatment.Nitric Oxide. 1999; 235: 243
- Free radical-induced contractile protein dysfunction in endotoxin-induced sepsis.Am J Respir Cell Mol Biol. 2001; 24: 210
- Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure.Am J Physiol Endocrinol Metab. 2006; 291: E1044
- Endotoxin administration alters the force versus pCa relationship of skeletal muscle fibers.Am J Physiol Regul Integr Comp Physiol. 2000; 278: R891
- Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin.Am Rev Respir Dis. 1992; 1350: 1354
- Effect of free radical scavengers on diaphragmatic contractility in septic peritonitis.Am J Respir Crit Care Med. 2000; 2159: 2165
- Hemin prevents cardiac and diaphragm mitochondrial dysfunction in sepsis.Free Radic Biol Med. 2006; 127: 137
Article info
Publication history
Published online: January 27, 2011
Received:
August 2,
2010
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
