Role of skeletal muscle Na+–K+ ATPase activity in increased lactate production in sub–acute sepsis

McCarter, Freda D; Nierman, S.Renee; James, J. Howard; Wang, Li; King, Jy-Kung; Friend, Lou Ann; Fischer, Josef E.

doi:10.1016/s0024-3205(02)01475-3

Cited by 40 publications

(19 citation statements)

References 29 publications

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“…Although the mechanism of the acute response observed in our initial experiment is not known at present, it is possible that dexamethasone-induced changes in Na ϩ transport and concentrations and in Na ϩ /Ca 2ϩ exchange were involved (55). In a previous study, Na ϩ transport was altered in catabolic muscle from rats with sepsis (47), lending support to the concept that changes in calcium and sodium homeostasis may be connected in muscle wasting. Regardless of the mechanism involved, the present observations are important because they suggest that glucocorticoids can increase muscle calcium uptake through different mechanisms.…”

Section: Discussionsupporting

confidence: 71%

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism

Itagaki

Menconi

Antoniu

et al. 2010

American Journal of Physiology-Cell Physiology

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Hasselgren PO. Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A 2-dependent mechanism. Am J Physiol Cell Physiol 298: C1127-C1139, 2010. First published January 27, 2010; doi:10.1152/ajpcell.00309.2009.-Muscle wasting in various catabolic conditions is at least in part regulated by glucocorticoids. Increased calcium levels have been reported in atrophying muscle. Mechanisms regulating calcium homeostasis in muscle wasting, in particular the role of glucocorticoids, are poorly understood. Here we tested the hypothesis that glucocorticoids increase intracellular calcium concentrations in skeletal muscle and stimulate storeoperated calcium entry (SOCE) and that these effects of glucocorticoids may at least in part be responsible for glucocorticoid-induced protein degradation. Treatment of cultured myotubes with dexamethasone, a frequently used in vitro model of muscle wasting, resulted in increased intracellular calcium concentrations determined by fura-2 AM fluorescence measurements. When SOCE was measured by using calcium "add-back" to muscle cells after depletion of intracellular calcium stores, results showed that SOCE was increased 15-25% by dexamethasone and that this response to dexamethasone was inhibited by the store-operated calcium channel blocker BTP2. Dexamethasone treatment stimulated the activity of calcium-independent phospholipase A 2 (iPLA2), and dexamethasone-induced increase in SOCE was reduced by the iPLA 2 inhibitor bromoenol lactone (BEL). In additional experiments, treatment of myotubes with the store-operated calcium channel inhibitor gadolinium ion or BEL reduced dexamethasone-induced increase in protein degradation. Taken together, the results suggest that glucocorticoids increase calcium concentrations in myocytes and stimulate iPLA 2-dependent SOCE and that glucocorticoid-induced muscle protein degradation may at least in part be regulated by increased iPLA 2 activity, SOCE, and cellular calcium levels. glucocorticoids; muscle; wasting MUSCLE WASTING, mainly reflecting stimulated degradation of myofibrillar proteins, is commonly seen in patients with sepsis, severe injury, and cancer (24, 52). Loss of muscle mass also occurs in patients with muscular dystrophy (30, 31). In previous studies, we found evidence (4, 15, 79) that sepsis-induced muscle proteolysis was associated with increased uptake and tissue levels of calcium in skeletal muscle. Additional reports suggest that muscle atrophy caused by other catabolic conditions, including denervation, burn injury, and muscular dystrophy, is also associated with increased tissue concentrations of calcium (2,3,10,17,64,73). These observations are significant because calcium is an important regulator of muscle protein balance and may link systemic catabolic responses to stimulated protein breakdown in skeletal muscle (16,34,50). The mechanisms regulating calcium entry and cellular levels of calcium in muscle-wasting conditions are not known.Glucocorticoids are prom...

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Section: Discussionsupporting

confidence: 71%

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism

Itagaki

Menconi

Antoniu

et al. 2010

American Journal of Physiology-Cell Physiology

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“…Epinephrine exerts direct metabolic effects that increase blood lactate concentrations without reducing tissue perfusion. 20,21 We found a strong positive correlation between serum lactate concentrations at 10 min and the bolus dose of epinephrine administered. The highest doses of epinephrine reliably produced the worst metabolic profiles.…”

Section: Discussionmentioning

confidence: 59%

Epinephrine Induces Rapid Deterioration in Pulmonary Oxygen Exchange in Intact, Anesthetized Rats

et al. 2012

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Background Previous studies indicate epinephrine adversely affects arterial oxygenation when administered in a rat model of local anesthetic overdose. The authors tested whether epinephrine alone exerts similar effects in the intact animal. Methods Anesthetized rats received a single intravenous injection of epinephrine (25, 50, or 100 mcg/kg); matched cohorts were pretreated with phentolamine (100 mcg/kg); n = 5 for each of the six treatment groups. Arterial pressure and blood gases were measured at baseline, 1 and 10 min after epinephrine administration. Pulmonary capillary pressures during epinephrine infusion with normal and increased flows were measured in an isolated lung preparation. Results Epinephrine injection in the intact animal caused hypoxemia, hypercapnia, and acidosis at all doses. Arterial oxygen tension was reduced within 1 min of injection. Hyperlactatemia occurred by 10 min after 50 and 100 mcg/kg. Rate pressure product was decreased by 10 min after 100 mcg/kg epinephrine. Pretreatment with phentolamine attenuated these effects except at 100 mcg/kg epinephrine. In the isolated lung preparation, epinephrine in combination with increased pulmonary flow increased pulmonary capillary pressure and lung water. Conclusions Bolus injection of epinephrine in the intact, anesthetized rat impairs pulmonary oxygen exchange within 1 min of treatment. Effects were blunted by a-adrenergic receptor blockade. Edema occurred in the isolated lung above a threshold pulmonary capillary pressure when epinephrine treatment was coupled with an increase in pulmonary flow. These results potentially argue against using traditional doses of epinephrine for resuscitation, particularly in the anesthetized patient.

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“…It was an additional aim to evaluate the effects of FO on plasma lactic acid concentrations and skeletal muscle lacticogenesis in critically ill patients. Since several experimental works supported the hypothesis that increased lactate production may be related to a stimulation of Na-K ATPase in sepsis (McCarter et al, 2002;Bundgaard et al, 2003;Hsieh et al, 2003), we attempted to specifically assess the effects of FO on Na-K ATPase-dependent lactic acid formation. The study finally aimed at testing the safety and the clinical impact of FO containing PN after this type of surgery.…”

Section: Introductionmentioning

confidence: 99%

Fish oil after abdominal aorta aneurysm surgery

et al. 2007

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Objective: Fish oil (FO) may attenuate the inflammatory response after major surgery such as abdominal aortic aneurysm (AAA) surgery. We aimed at evaluating the clinical impact and safety aspects of a FO containing parenteral nutrition (PN) after AAA surgery. Methods: Intervention consisted in 4 days of either standard (STD: Lipofundin medium-chain triglyceride (MCT): long-chain triglyceride (LCT)50%-MCT50%) or FO containing PN (FO: Lipoplus: LCT40%-MCT50%-FO10%). Energy target were set at 1.3 times the preoperative resting energy expenditure by indirect calorimetry. Blood sampling on days 0, 2, 3 and 4. Glucose turnover by the 2 H 2 -glucose method. Muscle microdialysis. Clinical data: maximal daily T1, intensive care unit (ICU) and hospital stay. Results: Both solutions were clinically well tolerated, without any differences in laboratory safety parameters, inflammatory, metabolic data, or in organ failures. Plasma tocopherol increased similarly; with FO, docosahexaenoic and eicosapentaenoic acid increased significantly by day 4 versus baseline or STD. To increased postoperatively, with a trend to lower values in FO group (P ¼ 0.09). After FO, a trend toward shorter ICU stay (1.670.4 versus 2.370.4), and hospital stay (9.972.4 versus 11.372.7 days: P ¼ 0.19) was observed. Conclusions: Both lipid emulsions were well tolerated. FO-PN enhanced the plasma n-3 polyunsaturated fatty acid content, and was associated with trends to lower body temperature and shorter length of stay.

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Role of skeletal muscle Na+–K+ ATPase activity in increased lactate production in sub–acute sepsis

Cited by 40 publications

References 29 publications

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism

Epinephrine Induces Rapid Deterioration in Pulmonary Oxygen Exchange in Intact, Anesthetized Rats

Fish oil after abdominal aorta aneurysm surgery

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Role of skeletal muscle Na+–K+ ATPase activity in increased lactate production in sub–acute sepsis

Cited by 40 publications

References 29 publications

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A2-dependent mechanism

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A2-dependent mechanism

Epinephrine Induces Rapid Deterioration in Pulmonary Oxygen Exchange in Intact, Anesthetized Rats

Fish oil after abdominal aorta aneurysm surgery

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Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism