Journal
SHOCK
Volume 15, Issue 3, Pages 200-207Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00024382-200115030-00007
Keywords
proteolysis; cachexia; myofibrillar proteins; catabolic; atrophy; muscle; sepsis
Funding
- NIDDK NIH HHS [DK37908] Funding Source: Medline
- NIGMS NIH HHS [T32GM08478-07] Funding Source: Medline
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The effects of dantrolene on serum TNF alpha and corticosterone levels and on muscle calcium. calpain gene expression, and protein breakdown were studied in rats with abdominal sepsis induced by cecal ligation and puncture. Treatment of rats with 10 mg/kg of dantrolene 2 h before and 8 h after induction of sepsis reduced serum TNF alpha and corticosterone, muscle calcium levels, mRNA levels for m- and mu -calpain, and the muscle specific calpain p94, as well as total and myofibrillar protein breakdown rates, determined as release of tyrosine and 3-methylhistidine, respectively. from incubated extensor digitorum longus muscles. The results support the concept that increased calcium concentrations may be an important mechanism of sepsis-induced muscle protein breakdown. The data also indicate that other mechanisms, in addition to reduced muscle calcium concentrations such as decreased levels of TNF alpha and glucocorticoids, may contribute to the anti-catabolic effects of dantrolene during sepsis. The observations are important from a clinical standpoint because they suggest that the catabolic response in skeletal muscle during sepsis may be prevented by treatment with a calcium antagonist.
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