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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of sepsis on skeletal muscle energetics and membrane function are poorly understood, and the time course of changes in energy metabolism are unclear. To clarify these relationships, high energy phosphate ratios, intracellular pH, and phosphocreatine breakdown rates were measured in vivo in the gastrocnemius muscle of adult male Wistar rats after cecal ligation and puncture or sham operation with 31P magnetic resonance spectroscopy. Adenosine triphosphate (ATP) concentration and Na(+)-K+ ATPase and creatine kinase activities were determined in vitro. Within 24 hours, Na(+)-K+ ATPase activity increased by 60% in rats with cecal ligation and puncture, all of which had positive bacterial cultures, as compared to none of the sham-operated controls. Phosphocreatine/ATP ratios decreased by 20% in association with a quantitatively similar increase in phosphocreatine breakdown (9.7 +/- 0.5 vs 11.9 +/- 0.5 mumoles/gm wet wt/sec; p = 0.01). ATP concentrations were maintained, and intracellular pH did not change significantly. In this model, changes in phosphocreatine breakdown were not related to total creatine kinase activity, which did not change significantly, or increases in adenosine 5'-diphosphate (ADP) concentration (62 +/- 8 vs 92 +/- 8 mumols/L; p = 0.02). Thus, in early sepsis before a measurable decrease in pH occurs, ATP is utilized at an increased rate to help maintain ionic balance and/or to support other metabolic processes. Phosphocreatine stores are used to buffer ATP concentrations.
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PMID:Sepsis alters skeletal muscle energetics and membrane function. 165 38

The effect of sepsis on energy and metabolite levels in the white, fast-twitch extensor digitorum longus (EDL) and the red, slow-twitch soleus (SOL) muscles was studied in rats. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. Sixteen hours later, metabolite levels in muscle tissue were determined. Adenosine triphosphate (ATP) levels and energy charge were reduced during sepsis in SOL, but were unchanged in EDL muscles. In contrast, phosphocreatine (PCr) concentration was reduced during sepsis in EDL, but not in SOL. Tissue glycogen levels were reduced and lactate concentrations were increased in both muscles during sepsis. Results suggest that sepsis affects energy metabolism differently in different types of skeletal muscle. Tissue lactate accumulation may be consistent with muscle hypoperfusion following CLP, although other mechanisms may also be involved.
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PMID:Tissue metabolite levels in different types of skeletal muscle during sepsis. 194 43

Neurological symptoms including lethargy, obtundation, and confusion are early and common findings in patients with sepsis. The etiology of the mental status changes that occur during severe infection is not known. We investigated the effects of sepsis on the levels of high-energy phosphates to determine whether decreased energy metabolism was a factor in the depressed neurological state. The time course of changes in brain pH and brain high-energy phosphate metabolites during an Escherichia coli infusion was determined from sequential phosphorus-31 nuclear magnetic resonance (31P-NMR) spectra of ketamine-xylazine-anesthetized rats. A second group of rats received 0.9% saline infusion and served as a control group. Despite severe obtundation and near loss of righting reflex, the rats in the septic group had no significant differences in the brain pH, the ratio of phosphocreatine (PCr) to beta-adenosine 5'-triphosphate (beta-ATP), or in the ratio of PCr to Pi. The only significant decrease in brain high-energy phosphates or pH occurred terminally in the septic rat group and corresponded with a rapidly falling arterial blood pressure. We conclude that the severe neurological depression that is characteristic of sepsis is not due to decreased levels of brain high-energy phosphates or brain acidosis.
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PMID:An in vivo examination of rat brain during sepsis with 31P-NMR spectroscopy. 261 Feb 45

High-energy phosphate metabolism in skeletal muscle is altered during sepsis, although the chronology of events is uncertain. Phosphorus 31 magnetic resonance spectroscopy was used to measure changes in muscle energy stores of the left hind limb musculature of adult male rats during sepsis. Following control scans, cecal ligation and puncture were performed and scanning was repeated 6, 24, and 48 hours after surgery. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), a measure of energy stores, and adenosine triphosphate (ATP) to Pi ratio, a measure of the energy available for immediate use, were determined from peak heights. Intracellular pH was calculated using the distance between Pi and PCr peaks. In surviving animals, a 40% decrease in PCr/Pi ratio (+/- SEM) was observed by 24 hours (22.3 +/- 3.0 at time 0 vs 13.3 +/- 2.8 at 24 hours), whereas energy availability (beta-ATP/Pi) was statistically unchanged (18.2 +/- 2.2 at time 0 vs 15.2 +/- 1.2 at 48 hours). Intracellular pH did not change. Both PCr/Pi and ATP/Pi ratios were inversely correlated with time. In this model of documented peritonitis, skeletal muscle energy metabolism is rapidly altered following severe infection, and these changes can be detected using 31P magnetic resonance spectroscopy.
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PMID:In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis. 317 91

Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr stores in skeletal muscle. To determine if systemic infection impairs mitochondrial function, in vivo 13P magnetic resonance spectroscopy (31P MRS) studies of the gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr after cecal ligation and 18-gauge needle single puncture (24 degrees CLP, n = 16; 48 degrees CLP, n = 15) or sham operation (24 degrees SHAM, n = 18; 48 degrees SHAM, n = 13). Physiologic saline (6 ml/100 g body wt) was injected intraperitoneally for fluid resuscitation. Water but no food was allowed in all animals. High resolution (8.45 Tesla) 31P MRS spectra, obtained at rest and during exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP, PCr/P(i) ratios, and intracellular pH. Steady-state muscle exercise was induced by supramaximal sciatic nerve stimulation at 10 Hz for 10 min. Recovery of PCr/(PCr + P(i)) ratios after exercise was fitted to a monoexponential curve. The resultant function was used to calculate the half time for PCr recovery, the initial PCr resynthesis rate, and the maximal oxidative ATP synthesis rate, which reflect the rephosphorylation of ADP and are therefore measures of mitochondrial oxidative capacity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after CLP, respectively. The PCr/P(i) ratios decreased incrementally (7% in 24 degrees CLP vs 23% in 48 degrees CLP animals). Twenty-four hours after operation the half time for PCr recovery was shortened while the initial PCr resynthesis rate and maximal oxidative ATP synthesis rate were accelerated in CLP animals compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The duration of infection modifies mitochondrial oxidative capacity in rat skeletal muscle. 763 Jan 22

The mechanism responsible for sepsis-induced myocardial depression is not known. To determine if sepsis-induced myocardial depression is caused by inadequate free energy available for work, we studied myocardial energy metabolism in a canine model of sepsis. Escherichia coli-infected (n = 18) or sterile (n = 16) fibrin clots were implanted intraperitoneally into beagles. Myocardial function and structure was assessed using radionuclide ventriculograms, echocardiograms, and light and electron microscopy. The adequacy of energy metabolism was evaluated by comparing catecholamine-induced work increases [myocardial O2 consumption (MVO2) and rate pressure product (RPP)] with a simultaneously obtained estimate of intracellular free energy [phosphocreatine-to-adenosine triphosphate ratio (PCr:ATP)] determined by 31P-magnetic resonance spectroscopy. When compared with control animals, septic animals had a decrease in left ventricular ejection fraction (EF, P < 0.0001) on day 1 and fractional shortening (FS, P < 0.0003) on day 2 after clot implantation. On day 2, neither septic nor control animals had statistically significant decreases in PCr:ATP, despite catecholamine-induced increases in MVO2 and RPP (mean maximal increases in septic animals 135 +/- 31 and 51 +/- 10%, respectively). Light and electron microscopic findings showed that hearts of septic animals, compared with control animals, had a greater degree of morphological abnormalities. Thus, in a canine model of sepsis with alterations in myocyte ultrastructure and documented myocardial depression (decreased EF and FS), intracellular free energy levels (PCr:ATP) were maintained despite catecholamine-induced increases in myocardial work (increased MVO2 and RPP), suggesting high-energy synthetic capabilities are not limiting cardiac function.
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PMID:Myocardial energy metabolism and morphology in a canine model of sepsis. 814 77

There is accumulating evidence that inflammatory cytokines are involved in the pathophysiology of cardiac dysfunction found in sepsis, myocardial infarction and acute rejection after heart transplantation. Although there are some previous reports on cytokines and myocardial depression, myocardial energy metabolism caused by cytokines have not been established yet. The purpose of the present study is to determine if the IL-2 effect on contractile function is related to impaired energy production. In isolated perfused rabbit hearts (n = 6), we measured developed pressure, ATP and phosphocreatine by 31P-NMR spectroscopy during and after a 5 minute infusion of IL-2 (200 U/ml/min). Although there was slightly increased inorganic phosphate which might be affect on myocardial contractility reduced, high energy phosphate and intracellular pH did not change by IL-2 infusion, suggesting another mechanism for myocardial depression caused by inflammatory cytokine, IL-2.
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PMID:[Cardiac disfunction and myocardial energy metabolism caused by interleukin-2 (IL-2)]. 872 57

Purpose. The purpose of this study was to investigate the relationship between hepatic energy status and liver injury during sepsis, using transgenic mice which express creatine kinase in the liver catalyzing the phosphocreatine/creatine system. Methods. Creatine kinase transgenic mice were fed with normal rodent chow or chow containing 10% creatine for 5 days. Lipopolysaccharide (0.2 mg/kg) combined with d-galactosamine (600 mg/kg) was administered intraperitoneally. Results. Eighty percent of the creatine-fed transgenic mice had survived at 48 h post-d-galactosamine and lipopolysaccharide administration, compared with none of the normally fed transgenic mice. Hepatic phosphocreatine and ATP levels in the normally fed transgenic mice were significantly lower than those in the creatine-fed transgenic mice before and after lipopolysaccharide combined with d-galactosamine was administered. Massive hepatic hemorrhagic necrosis with apoptosis was seen in response to d-galactosamine and lipopolysaccharide in normally fed transgenic mice. These results are consistent with a significant increase in serum aminotransferase at 8 h. In contrast, there were faint necrotic changes in the liver with minimal cellular infiltration in creatine-fed transgenic mice. Conclusions. Maintenance of hepatic ATP levels protects from sepsis-induced liver injury and mortality.
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PMID:The beneficial effect of phosphocreatine accumulation in the creatine kinase transgenic mouse liver in endotoxin-induced hepatic cell death. 987 18

The present study was designed to test the hypothesis that induction of chronic peritoneal sepsis in rats would produce a more severe calcium paradox-mediated myocardial injury in isolated heart preparation than is seen in normal hearts, and that this would be inhibited by sucrose as in normal hearts. Male Sprague-Dawley rats were made septic using 200 mg of cecal material (obtained from a donor rat) suspended in 5 mL of 5% dextrose in sterile water D5 W/kg. In septic animals, the cecal material was injected in the peritoneum, while sham-septic animals received only D5 W/kg (5 mL/kg). A third group consisting of normal rats (no surgery) group was also included. Hearts were harvested from all three groups and were subjected to a calcium paradox-mediated injury in an isolated heart preparation. Hearts were perfused with Krebs-Henseleit (KH) medium and were allowed to stabilize, followed by a perfusion with Ca2+-free KH for 10 min. After this 10-min Ca2+-free KH perfusion, rats were reperfused with KH medium for 60 min. Ca2+-free KH medium was used in control experiments, while sucrose experiments were conducted with the same medium except that 150 mM sucrose replaced 75 mM NaCl. A marked decrease in ATP and phosphocreatine occurred during Ca2+ reperfusion in all hearts in absence of sucrose. In the presence of the disaccharide, no change in high-energy phosphate (HEP) levels was observed in normal hearts, while lower ATP concentrations were seen in sham and septic hearts. Thus, sucrose did not inhibit cellular injury in sham and septic hearts as it did in normal hearts, and this might be due to a smaller HEP availability. Control studies with normal, sham, and septic hearts exhibited cessation of contractions in the absence of Ca2+, and appearance of large amounts of cytosolic protein in the effluent perfusate during Ca2+ reperfusion. With normal hearts, perfusion with sucrose caused a 96% inhibition of the total creatine kinase (CK) release observed in control experiments. With sham hearts, 32% of CK release was inhibited by sucrose, while 68% of the CK release was attributed to stress associated with surgery performed in the sham-septic group. In septic hearts, only 8% of the CK release was inhibited by sucrose, suggesting that more severe myocardial injury occurs when septic hearts are subjected to a calcium paradox as compared to other groups. It is evident that sucrose can inhibit a small fraction of the CK release from septic hearts during the calcium paradox as compared to the large CK loss associated with sham sepsis. We have concluded that induction of sepsis made the heart more susceptible to a calcium paradox-mediated myocardial injury.
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PMID:Induction of peritoneal sepsis increases the susceptibility of isolated hearts to a calcium paradox-mediated injury. 1190 Mar 37

Bacterial sepsis is frequently accompanied by increased blood concentration of lactic acid, which traditionally is attributed to poor tissue perfusion, hypoxia and anaerobic glycolysis. Therapy aimed at improving oxygen delivery to tissues often does not correct the hyperlactatemia, suggesting that high blood lactate in sepsis is not due to hypoxia. Various tissues, including skeletal muscle, demonstrate increased lactate production under well-oxygenated conditions when the activity of the Na+-K+ ATPase is stimulated. Although both muscle Na+-K+ ATPase activity and muscle plasma membrane content of Na+, K+-ATPase subunits are increased in sepsis, no studies in vivo have demonstrated correlation between lactate production and changes in intracellular Na+ and K+ resulting from increased Na+-K+ pump activity in sepsis. Plasma concentrations of lactate and epinephrine, a known stimulator of the Na+-K+ pump, were increased in rats made septic by E. coli injection. Muscle lactate content was significantly increased in septic rats, although muscle ATP and phosphocreatine remained normal, suggesting oxygen delivery remained adequate for mitochondrial energy metabolism. In septic rats, muscle intracellular ratio of Na+:K+ was significantly reduced, indicating increased Na+-K+ pump activity. These data thus demonstrate that increased muscle lactate during sepsis correlates with evidence of elevated muscle Na+-K+ ATPase activity, but not with evidence of impaired oxidative metabolism. This study also further supports a role for epinephrine in this process.
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PMID:Role of skeletal muscle Na+-K+ ATPase activity in increased lactate production in sub-acute sepsis. 1200 73


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