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Query: UMLS:C0243026 (sepsis)
 52,417 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

Eighteen white rabbits were subjected to a 30 per cent TBSA full thickness burn. Wound infection was found 9-13 days after injury and became severe a week or so later. ATPase activities, antioxidation ability, the proteins of erythrocyte membranes, and the Na+ contents of erythrocytes and serum were determined. The Ca++-ATPase activity was elevated during the first 17 days postburn, but showed a decline at the time of severe wound infection; the Na+,K+-ATPase activity showed peaks on postburn days 2 and 6, and then fluctuated above the preburn level. The change in Mg++-ATPase activity was similar to Na+,K+-ATPase. The erythrocyte Na+ content was increased, and the level of serum Na+ was decreased up to postburn day 6. Subsequently the erythrocyte Na+ was reduced and the serum Na+ increased up to day 17 postburn. The percentage of erythrocyte haemolysis in H2O2 was increased after the burn and became markedly so during wound infection, indicating that the antioxidation ability of burned rabbit erythrocytes was markedly impaired. During the period of wound infection, Coomassie blue-stained protein bands in SDS-polyacrylamide gel showed some changes in size and proportion in burned rabbits. For example, the second band was wider, the band 2 to band 1 ratio increased, and band 5 was smaller than before injury. These results seem to show that burn injury, especially when associated with sepsis, may affect both the structure and function of biological membranes.
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PMID:Changes in erythrocyte membranes in burned rabbits. 285 50

Myocardial sarcoplasmic reticulum (SR) plays a critical role in the regulation of the cytosolic calcium fluctuations that occur during the cardiac cycle. One function of the SR is to lower the calcium concentration so that myocardial relaxation and thus ventricular filling can occur. The aim of the present study was to determine if hyperdynamic sepsis induced a decrease in the capacity of SR to take up calcium. This defect would result in decreased ventricular filling and thus decreased cardiac output, as has previously been shown in isolated perfused working hearts removed from septic rats. Therefore, rats were anesthetized with ether, and sepsis was induced by the injection of an aliquot of a fecal homogenate into the peritoneal cavity. Control animals either underwent surgery and received an aliquot of sterilized fecal inoculum (sham) or were untreated (no surgery). On day 2 after surgery, animals were anesthetized with pentobarbital, and hearts were removed, weighted, and SR isolated. The rate of uptake of 45Ca2+ by SR from septic rats was not depressed compared to controls but in fact was elevated. Maximum 45Ca2+ accumulated by the SR and Ca2+-stimulated ATPase activity were similar in SR from control and septic hearts. These results suggest that the contractile dysfunction noted in the myocardium in early sepsis is probably not due to inadequate SR removal of Ca2+ during diastole.
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PMID:Calcium uptake by sarcoplasmic reticulum isolated from hearts of septic rats. 297 70

Na+-K+-ATPase, Ca2+-ATPase and Mg2+-ATPase activities of erythrocyte membrane, microsomal fractions of rectus muscle, and liver were measured colorimetrically in the biopsy specimens of 14 control, 7 uncomplicated trauma (group 2), and 14 severe trauma or septic patients (groups 3-A and 3-B). In erythrocytes, these three ATPase activities in group 2 were not significantly changed but sepsis of both the acute (group 3-A) and ongoing type (group 3-B) decreased all of the ATPase activities. In muscle, there was a significant loss of three ATPase activities in the acute insult of severe trauma or sepsis (group 3-A), while Na+-K+-ATPase and Mg2+-ATPase activities were not significantly changed in ongoing, severe trauma (group 3-B). In the liver, a tendency for all three ATPase activities to decrease is noted in the severe traumatic group. However, a statistical difference between the control and severe traumatic group showed only for Na+-K+ ATPase and Mg2+-ATPase in group 3-A and Ca2+-ATPase in group 3-B. Correlation coefficients between erythrocyte, muscle, and liver for three ATPase activities are between 0.4 and 0.5. The mechanism which alters ATPase activity remains unknown in this study, but it may account for the variation in traumatic insult, in hemodynamic and hormone changes, and in tissue energy stores.
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PMID:Alterations of Na+-K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase activities in erythrocyte, muscle, and liver of traumatic and septic patients. 304 Feb 90

Mechanisms of subcellular dysfunction of the liver in sepsis are still obscure. The present study investigates changes in oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following live Escherichia coli injection (E coli, Serotype: 0--18. A 1.25--1.5 X 10(9)/100 gm body wt inoculum of E coli bacteria was injected via the tail vein, causing a 100% mortality rate within 24 hours after injection. In order to determine alteration of liver mitochondrial membrane permeability, serum ornithine carbamoyltransferase activity was measured following E coli injection. This activity increased ten to 100-fold over that of controls with time following injection. However, the yield of liver mitochondria from treated rats, estimated by the amount of collected mitochondrial protein and the recovery rate of succinate dehydrogenase activity in the final mitochondrial suspensions, was not significantly different from that of controls. Mitochondrial oxidative phosphorylative activity measured using glutamate as a substrate was enhanced throughout all period to death (P less than 0.01 at three and six hours, P less than 0.05 in the fatal stage) and was associated with concomitant increases in respiratory control ratios. Similar results were obtained using beta-hydroxybutyrate as a substrate. This enhancement was accompanied by an increase in 2-4-dinitrophenol-stimulated ATPase activity (160% at three hours and 130% in the fatal stage). Calcium-induced stimulation of mitochondrial respiration as well as initial calcium uptake rate linked to respiration, using glutamate as a substrate, were higher in liver mitochondria from rats with E coli treatment than in those of controls throughout all periods (P less than 0.01 or less). These results suggest the coexistence of hyperfunctioning as well as deteriorated mitochondria following lethal treatment with E coli.
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PMID:A study of oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following living Escherichia coli injection. 675 40

The underlying mechanism of Ca2+ uptake function of cardiac sarcoplasmic reticulum (SR) was investigated in the rat septic shock model produced by cecal ligation and puncture (CLP). The results are as follows. During the early phase of sepsis, the initial rate of ATP-dependent Ca2+ uptake by SR was decreased, while both the capacity of Ca2+ uptake and the activity of Ca(2+)-ATPase were unaffected. In the late sepsis, the impairment in SR function was even greater as the initial rate and the capacity of Ca2+ uptake by SR were significantly decreased, and this was paralleled by a reduction in Ca(2+)-ATPase activity. Although Ca2+ affinity (Km value) to calcium pump and the A0.5 values for Mg2+ and ATP activation on the Ca2+ uptake rate were unchanged, during sepsis the phosphorylation of SR vesicles by adding of catalytic subunit of the cAMP-dependent protein kinase (PKA), calmodulin, or the fragment of PKC into Ca2+ uptake buffer, failed to stimulate Ca2+ uptake activities of SR isolated from early or late septic rats. These data suggest that depression of cardiac SR function is aggravated as sepsis develops, the impairment of SR Ca2+ uptake is possibly based on a mechanism of defective phosphorylation of SR rather than the ionic and energic regulatory actions of Ca2+, Mg2+, ATP on cardiac SR.
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PMID:[Impaired calcium uptake by cardiac sarcoplasmic reticulum and its underlying mechanism during rat septic shock]. 748 74

The examination of septic children has revealed characteristics of iron and red cell metabolism: deep and persistent hypotransferrinemia, normo- or hypersideremia, normal ferritin levels. Red cells of septic children contain low concentrations of ATPase, histidine, lipoproteins, there is compensatory enhancement of 2,3-DPG, G-6-PD SH-group activity. In terminal sepsis the activity of the above parameters drastically falls entailing hemolysis, anemia and severe hypoxia.
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PMID:[The metabolic activity of the erythrocytes and the characteristics of ferrokinetics in children with sepsis]. 802 Jul 13

Changes in the distribution of (Na+ + K+)-ATPase in two subcellular fractions, the sarcolemma and the light vesicle, of rat heart during sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). The alpha-subunit of (Na+ + K+)-ATPase was photoaffinity labeled with [alpha-32P]8-N3ATP. The results show that septic rat heart exhibits hyperdynamic (hypermetabolic) phase during early (9 hr post-CLP), followed by hypodynamic (hypometabolic) phase during late (18 hr post-CLP) sepsis. Marker enzyme and beta-adrenergic receptor assays depict that the light vesicle fraction is the intracellular site of surface receptor. The incorporation of the photolabel into the alpha-subunit (M(r) = 98,000) of the (Na+ + K+)-ATPase in sarcolemmal fraction was increased by 60% (P < 0.01) during early sepsis, but was decreased by 63% (P < 0.01) during late sepsis. In contrast, the binding of 98,000-M(r) peptide in light vesicles was decreased by 40% (P < 0.01) in early sepsis, but was increased by 102% (P < 0.01) during late sepsis. The ouabain-sensitive (Na+ + K+)-ATPase activity was increased by 31% (P < 0.05) during the early sepsis, but was decreased by 32% (P < 0.01) during late sepsis in the sarcolemmal fraction; while in the light vesicle fraction, the (Na+ + K+)-ATPase activity was decreased by 21% (P < 0.01) during early sepsis, but was increased by 47% (P < 0.01) during the late phase of sepsis. The yield of membrane proteins for each specific fraction remained unchanged for control, early sepsis, and late sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Externalization and internalization of (Na+ + K+)-ATPase in rat heart during different phases of sepsis. 840 43

The muscarinic receptor changes in two subcellular fractions of rat myocardium during sepsis, the sarcolemma (SL) and light vesicles (LV), were studied. [3H]-quinuclidinyl benzilate ([3H]-QNB) was used as a radioligand. Sepsis was induced by cecal ligation and puncture (CLP). The septic rats had higher pulse rates and slightly higher blood glucose levels than control rats. The marker enzyme assays revealed that the SL fraction was enriched with 5'-nucleotidase and the Na(+)-K(+)-ATPase activity increased over 20-fold, while the LV fraction showed very little enrichment when compared with the homogenate. [3H]-QNB binding studies showed that Bmax increased by 58.8% in SL with no changes in LV during early sepsis (9 h post-CLP), but there was no significant change in the Kd value. These data indicate that muscarinic cholinergic receptors in rat heart SL increase during early sepsis. Since the muscarinic cholinergic receptors mediate parasympathetic modulation of myocardial contractility, changes in the number of muscarinic receptors in the cardiac SL may have a pathophysiologic significance in the development of hemodynamic changes during sepsis.
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PMID:Density of muscarinic receptors in rat myocardium during early sepsis. 852 71

Endotoxins (lipopolysaccharides; LPS) are known to cause multiple organ failure, including renal dysfunction. The present report elucidates LPS distribution and effect on renal proximal tubules in an attempt to gain a better understanding of the cellular mechanism underlying the pathogenesis of renal dysfunction in endotoxemia and sepsis. Rats were intravenously treated with biotin-linked or regular Escherichia coli (0111:B4) LPS (3 mg/kg) and sacrificed at different times. Kidneys were retrieved and examined for LPS localization, tubular permeability, ultracytochemical alterations, leukocyte sequestration, and ICAM-1 expression. The functional impact of endotoxemia was also assessed by monitoring the changes in urine levels of glucose in timed collections up to 6 h. LPS was localized on the plasma membranes of the apical microvilli, the labyrinth of the lateral intercellular spaces, in various organelles of epithelial cells, and in the endothelial cells of the peritubular capillaries. LPS caused structural damage and calcium accumulation in the mitochondria, leakage of tight junctions, widening of the basolateral intercellular spaces, intracellular and extracellular edema, leukocyte margination and accumulation, vascular expression of ICAM-1, and decrease of plasma membrane and mitochondrial Ca2(+)-ATPase. Physiological study showed that both urine volume and glucose were greatly increased after LPS infusion. The pathological alterations in the proximal tubules may directly contribute to the reduction in the reabsorption ability of the proximal tubules.
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PMID:Distribution and role of lipopolysaccharide in the pathogenesis of acute renal proximal tubule injury. 860 2


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