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

The effect of chronic sepsis on the concentration of active pyruvate dehydrogenase complex has been investigated in liver and skeletal muscle of normal, sterile inflammatory, and chronic septic (small and large abscess) animals. Hyperdynamic sepsis was induced by the intraperitoneal introduction of a rat fecal-agar pellet of known size and bacterial composition (Escherichia coli + Bacteroides fragilis). Total pyruvate dehydrogenase complex activity was not altered in either liver or skeletal muscle in any of the conditions studied. In hepatic tissue, sterile inflammation increased the proportion of active complex 2.5-fold compared with control. The same increase in the concentration of active complex was observed in animals with a small abscess. When the abscess size was increased (large abscess), the concentration of active complex was decreased relative to sterile inflammatory or small abscess septic animals. In contrast to liver, sterile inflammation did not alter the proportion of active complex in skeletal muscle. Sepsis (either small or large septic abscess) resulted in threefold decrease in the concentration of active complex relative to control or sterile inflammatory animals. Changes in the concentration of active complex did not appear to be dependent on the ATP/ADP concentration ratio or tissue pyruvate levels but were consistent with changes in the acetyl-coenzyme A-to-coenzyme A concentration ratio. The mechanism responsible for altered concentration of active complex may be mediated through changes in the activity of the pyruvate dehydrogenase kinase, secondary to alterations in the effector concentration ratios.
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PMID:Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. 352 10

The concept of early selective mitochondrial injury has been proposed to explain the global metabolic dysfunction observed in the septic state. A two phase study was undertaken to test the validity of this hypothesis. In the initial phase, an endotoxin shock model was employed in the rat to delineate the function of skeletal muscle mitochondria. Mitochondrial function was determined polarimetrically, comparing state three and state four rates, respiratory control index (RCI) and ADP:O ratios. No significant alteration in these parameters was observed in the endotoxic state. Phase II of the study was designed to investigate mitochondrial function in a bacterial peritonitis rat model. Both liver and skeletal muscle mitochondrial function were determined to control for possible alterations in liver metabolism. Neither muscle nor liver mitochondria exhibited functional impairment during sepsis. We conclude from this study that neither endotoxemia nor peritonitis selectively "kills" mitochondria as previously suggested.
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PMID:Mitochondrial death in sepsis: a failed concept. 352 91

In the present study protein synthesis and energy level in liver tissue were studied in bacteremic rats following intravenous infusion of 8 +/- 4 X 10(9) live E. coli bacteria and in control animals receiving a corresponding infusion of sterile saline. For the study of protein synthesis, liver slices were incubated in a medium containing 14C-leucine and incorporation rate of amino acid into protein was determined. Hepatic concentrations of ATP, ADP, and AMP were measured and energy charge (EC) was calculated. Twenty-four hours after infusion of E. coli, hepatic protein synthesis rate was 55% higher than in control animals. Liver weight and hepatic protein content were also increased in bacteremic animals. There were no significant differences in adenine nucleotide levels or EC in liver tissue between control and bacteremic animals. Since impairment of various other liver functions has been reported during sepsis, the present results suggest that hepatic protein synthesis has high priority in this condition.
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PMID:Protein and energy metabolism in liver tissue following intravenous infusion of live E. coli bacteria in rats. 354 30

Energy-consuming, ATP-dependent step of transmembrane transmission of the signal for chemotaxis was studied at the pathway between receptors of formylpeptide and membrane kinase of polymorphonuclears leukocytes. Some peptides, particularly formylmethionyl leucylphenylalanine (FMLP), were demonstrated to have a property of chemostimulation, i.e. they had an ability to stimulate phagocytosis in human and animal neutrophils due to presence of specific receptors on the cell surface. Isolation, identification and use of the membrane ATP, synthesized in presence of the chemotactic peptide FMLP, is described. The ATP was produced within 1 min on the surface of polymorphonuclear leukocytes during aerobic phosphorylation from ADP and inorganic phosphate, coupled with transmission of electrons and protons. The ATP-producing activity of polymorphonuclear leukocytes, stimulated by the formylpeptide, was distinctly decreased in the patients with various forms of purulent surgical infections--sepsis, pyo-resorptive fever. The ATP, synthesized in plasmatic membranes of polymorphonuclear leukocytes, appears to serve as a translator of the chemotactic, energy-consuming signal.
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PMID:[Formation of signal ATP in plasma membranes of polymorphonuclear leukocytes activated by formyl-methionyl-leucyl-phenylalanine]. 377 22

Changes in muscle high-energy phosphates in varying degrees of resting hypermetabolism were studied. Eleven patients were investigated before and 4 days after total hip replacement. The postoperative results were compared with those seen in major traumas and sepsis. High-energy phosphates were not significantly changed in muscle after total hip replacement or moderate injury; muscle lactate and pyruvate increased. Increased degrees of hypermetabolism such as severe trauma and sepsis were associated with reduction of muscle ATP and PC; AMP, free CR, lactate, and pyruvate rose. Simultaneously determined levels of high-energy phosphates in red blood cells did not reflect muscle changes, confirming the need for continued direct tissue measurements. Alterations in the ATP--ADP--AMP system in the muscle cell suggest a low-energy charge following severe trauma especially if accompanied by sepsis. This would indicate a decreased capcity for biosynthetic reactions and production of storage compounds. Tissue high-energy phosphates and cellular energy levels thus may be the cellular expression of the catabolic state.
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PMID:Effect of injury and sepsis on high-energy phosphates in muscle and red cells. 644

This brief review summarizes recent observations about leukocyte and platelet involvements during sepsis and septic shock. Endotoxins are known to exert significant effects on leukocytes and platelets as well as monocytes, macrophages, endothelial, and mast cells. The presence of endotoxin itself is reported to enhance the phagocytic and killing capacity of neutrophils. Transfusion of additional white blood cells has been shown to increase the probability of recovery from sepsis. Defects in neutrophil function, impaired opsonization, sequestration of neutrophils in pulmonary capillaries, and depressed metabolic states adversely affecting neutrophils may significantly contribute to the lethal outcome of septic shock. Platelet responses in septic shock are reported to include aggregation accompanied by release of several agents, including vasoactive amines, ADP, and platelet factor 3. In summary, leukocytes and platelets are known to perform significant roles in sepsis and septic shock although the precise mechanisms of their involvement remain to be clearly defined.
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PMID:Hematologic disturbances during sepsis: platelets and leukocytes. 675 24

Previous studies have yielded contradictory results about interrelations between endotoxin and endothelium-derived relaxing factor (EDRF). We tested the hypothesis that in vivo endotoxemia inhibits basal and/or agonist-mediated release of EDRF and nitric oxide (NO). EDRF bioactivity, NO production, and NO synthase (NOS) activity were measured in aorta from guinea pigs following 16 h of Escherichia coli endotoxemia (4 mg/kg endotoxin i.p.). Endothelium-dependent relaxation of aortic rings was studied under standard isometric conditions. Endotoxemia resulted in an 89% reduction in basal EDRF bioactivity and a 62% reduction in basal NO production in perfused aorta. EDRF bioactivity and NO production in response to the receptor-dependent agonists acetylcholine and ADP were significantly reduced in perfused aorta from endotoxemic animals. In contrast, endotoxin did not significantly inhibit EDRF bioactivity and NO production by the receptor-independent agonist A-23187. Aortic rings from endotoxemic animals likewise showed decreased vasodilator responses to acetylcholine and ADP but not to A-23187. Inducible (Ca2+ independent) NOS activity was not significantly different in control and endotoxin-treated animals. These findings indicate that prolonged endotoxemia resulted in diminution of release of EDRF, consistent with the interpretation that endotoxemia decreases basal and agonist-stimulated EDRF bioactivity and NO production with loss of endothelium-dependent vasodilator reserves during gram-negative sepsis.
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PMID:Release of EDRF and NO in ex vivo perfused aorta: inhibition by in vivo E. coli endotoxemia. 753 9

To test the hypothesis that release of endothelium-derived relaxing factor/nitric oxide is inhibited by Gram-negative lipopolysaccharide (LPS; endotoxin), we examined endothelium-independent and endothelium-dependent vasodilator agents in aortic vascular smooth muscle isolated from guinea pigs 4 h after injection of saline (controls) or induction of Escherichia coli endotoxemia. LPS significantly inhibited vasodilator responses to the endothelium-dependent agonists acetylcholine (ACh; 10(-10)-10(-5) M) and ADP (10(-8)-10(-5) M). However, LPS did not affect vasodilator responses to the endothelium-independent agonist nitroprusside (10(-10)-10(-4) M). The nitric oxide synthase (NOS) inhibitor N gamma-nitro-L-arginine methyl ester (L-NAME) inhibited the vasodilator response to ACh; whereas, the cyclooxygenase inhibitor indomethacin (INDO) did not reduce vasodilator effects of ACh. Neither L-NAME nor INDO affected the vasodilator effects of nitroprusside in LPS or control vessels. In contrast, L-NAME converted the vasodilator action of ADP to a vasoconstrictor response that was blocked individually by INDO and the thromboxane synthase inhibitor dazoxiben, suggesting that ADP releases NO and also the vasoconstrictor and platelet aggregating eicosanoid thromboxane A2. These findings suggest that acute (4 h) endotoxemia inhibits function of the constitutive isoform of NOS in vascular endothelial cells. Since L-NAME unmasked a vasoconstrictor action of the endogenous purinoceptor agonist ADP, pharmacologic agents that inhibit NOS may exacerbate LPS-induced inhibition of endothelial NOS; this series of events could lead to diminution of vasodilator reserves and perhaps to augmentation of platelet aggregation during Gram-negative sepsis.
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PMID:Inhibition of endothelium-dependent vasodilation by Escherichia coli endotoxemia. 753 38

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

Increased release of endothelium-derived relaxing factor/nitric oxide has been proposed as the final common pathway for vasodilator responses to gram-negative lipopolysaccharide (endotoxin). To test this hypothesis, we examined endothelium-dependent and endothelium-independent vasodilator agents in vascular smooth muscle isolated from guinea pigs 16 hours after injection of saline (control group) or induction of Escherichia coli endotoxemia; aortic rings (approximately 1 mm in diameter) were studied with standard isometric tension techniques. Endotoxemia resulted in a significant loss of vasodilator responses to the endothelium-dependent receptor agonists acetylcholine (10(-10)-10(-5) M) and ADP (10(-8)-10(-5) M). In contrast, endotoxemia did not affect vasodilator responses to either the endothelium-dependent receptor agonist substance P (10(-11)-10(-7) M), the endothelium-dependent and receptor-independent agonist A23187 (10(-9)-10(-6) M), or the endothelium-independent agonist nitroprusside (10(-10)-10(-4) M). The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) inhibited the vasodilator response to acetylcholine more in vessels from lipopolysaccharide-injected than control guinea pigs. Unexpectedly, L-NAME converted the endothelium-dependent vasodilator action of ADP to an endothelium-dependent vasoconstrictor response that was blocked individually by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor dazoxiben, and the thromboxane A2 receptor antagonist SQ29548. We conclude that in vivo endotoxemia inhibits the constitutive isoform of nitric oxide synthase in endothelial cells by selectively disrupting receptor-coupled activation mechanisms shared by acetylcholine and ADP. Furthermore, since L-NAME unmasks a thromboxane A2-mediated vasoconstrictor action of the endogenous purinoceptor agonist ADP, drugs that inhibit nitric oxide synthase could exacerbate sepsis-induced vasoconstriction and ischemia by synergizing with lipopolysaccharide-induced inhibition of endothelial nitric oxide synthase.
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PMID:Selective inhibition of endothelium-dependent vasodilator capacity by Escherichia coli endotoxemia. 767 34


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