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

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

Various metabolic, cellular, and subcellular alterations in cell function and morphology occur during shock or low-flow conditions. In attempting to find treatment programs that would be beneficial following shock, various substrates have been used. Infusion of hypertonic glucose during shock has been shown to improve survival; however, it is unlikely that the effect of glucose is by provision of energy until the circulation is restored. Infusion of glucose--insulin--potassium during shock has also been reported to be beneficial in certain clinical situations. Controversies exist concerning the efficacy of infusions of cyclic AMP, nicotinamide, and Krebs cycle intermediates during shock. Pretreatment of kidneys with inosine or raising glycogen stores of the myocardium have been shown to have protective effects of kidneys and myocardium during ischemia and these procedures may be suitable for organ preservation. Pretreatment with allopurinol has been shown to be beneficial in shock; however, it is unlikely that allopurinol by itself if given following shock would have any salutary effects. Treatment with ATP-MgCl2 has been shown to be beneficial following hemorrhagic shock, sepsis, endotoxin shock, burns, postischemic hepatic failure, and postischemic renal failure. Thus, provision of energy directly in the form of ATP during adverse circulatory conditions appears to be the most advantageous and direct method for the treatment of shock.
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PMID:The use of substrates and energy in the treatment of shock. 627 59

Studies in rats with a clinically relevant form of peritonitis indicate that tissue adenine nucleotide levels do not decrease in the early stages of sepsis. In contrast, hepatocellular active transport appears to be depressed even in the very early stages of sepsis. In late sepsis, however, tissue adenine nucleotide levels decrease significantly because of inadequate perfusion associated with peritonitis. Reticuloendothelial function (RES) is also significantly depressed at the late stages of sepsis. Administration of saline, glucose, or ATP-MgCl2 alone following sepsis does not produce any beneficial effects on survival. However, administration of high concentrations of ATP-MgCl2 together with hypertonic glucose results in a significant improvement in the survival of animals. This treatment regimen restores cellular ATP levels and also restores the depressed RES function to normal within three hours. Thus, extirpation of the lesion producing the septic process, combined with metabolic support, proves helpful without antibiotic treatment.
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PMID:Cellular energetics and ATP-MgCl2 therapy in sepsis. 639 98

Gluconeogenic and oxidative capabilities with lactate as a substrate were studied in perfused livers isolated from rats in late sepsis. Glucose release in the presence of 5 mM lactate was significantly depressed in livers from septic rats. When gluconeogenesis was stimulated by phenylephrine, livers from septic rats exhibited both a decreased sensitivity and lower maximal rate of glucose release when compared with livers from sham-operated rats. Oxygen consumption (VO2) by perfused livers from septic rats was also depressed under the above conditions. The addition of lysine in concentrations greater than 0.5 mM restored glucose production in livers from septic rats to a rate not different from sham-operated controls but did not restore VO2. However, inclusion of lysine (5 mM) in the perfusate was not able to restore sensitivity to stimulation by phenylephrine in livers from septic rats. Although hepatic ATP levels were depressed in sepsis, the decrease was not sufficient to explain the decreased rates of glucose production. We conclude from these results that primary cellular defects in gluconeogenic and oxidative capabilities occur during sepsis that are independent of inadequate perfusion.
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PMID:Regulation of glucose production from lactate in experimental sepsis. 640 37

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

Previous investigations have demonstrated impairment of hepatic gluconeogenic activity during both hypovolemia and sepsis, but the mechanisms responsible remain unclear. The present study was designed to determine the influence of lack of oxygen on gluconeogenesis independent of humoral factors, products of ischemic peripheral tissues or pH changes. Livers obtained from Sprague-Dawley rats fasted 24 hours were perfused with Krebs-Henseleit buffer containing 5 mM lactate for 30 minutes. In the control group (n = 8) perfusion was continued; in others, anoxia was induced by perfusing with buffer equilibrated with 95% N2 and 5% CO2 for periods of 15, 30, or 60 minutes (n = 4, 5, and 5, respectively). The initial conditions were then reinstituted for an additional 45 minutes. Anoxia caused hepatic release of K+, indicative of disordered hepatic cellular ionic gradients and an abrupt cessation of gluconeogenesis. Reoxygenation partially reversed these alterations but some impairment of gluconeogenesis persisted and the degree of uptake of K+ from the perfusion media was decreased as the duration of anoxia increased. The degree of restoration of gluconeogenesis after a period of anoxia was closely associated with restoration of cellular uptake of K+. By comparison, livers taken from hypovolemic animals maintained at a mean arterial blood pressure of 40 mm Hg until the beginning of the decompensatory stage of shock exhibited a gluconeogenic capacity of only 41% of control animals and was comparable to the compromise induced by between 30 and 60 minutes of anoxia. These results suggest that the abilities to restore hepatic electrolyte balance and gluconeogenesis after oxygen deprivation are affected in parallel and may reflect a common dependence on the restoration of ATP stores after the insult.
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PMID:Effect of hemorrhage and anoxia on hepatic gluconeogenesis and potassium balance in the rat. 684 34

This is a very brief, superficial and biased discussion of the pathophysiologic changes in shock. It was designed to provide some insight into the very complex changes that occur, with particular attention to a few examples of the impaired cell metabolism, including changes in ATP, cAMP, and calcium. Although inadequate tissue perfusion through nutrietn capillaries is the main etiologic factor in most types of shock, it is not the primary problem in many patients, particularly those with early or hyperdynamic sepsis. The importantance of oxygen consumption and the possible benefits of higher hemoglobin levels are discussed to some extent because of their possible clinical application.
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PMID:The pathophysiology of shock. 736 11

The initiating factor in ARDS is a matter of controversy. Some investigators relate ARDS development to diffuse pulmonary microemboli after stress ranging from sepsis to non-thoracic and thoracic trauma. Others indicate hyperoxic exposure as the causative agent. This investigation looked for a common factor in ischemia and hyperoxic exposure in lung which could cause the genesis of ARDS. Studies of oxidative phosphorylation, succinate dehydrogenase activity and ATP level were performed on ischemic and 100% O2 exposed lung. Results in both showed decreased respiration rate below the basal rate, decreased SDH activity, followed by marked decrease in ATP levels in pulmonary tissue. Decrease in respiration (ATP production) capacity and ATP levels in ischemic lung were such that normal cell functions could not be sustained if returned to normal circulation. Hyperbaric O2 therapy would subsequently decrease energy metabolism in regions of normal circulation and in previously ischemic regions.
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PMID:A common denominator in the etiology of adult respiratory distress syndrome. 743 54

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

Saturated Ca2+ extrusion rate through the Ca2+ pump of erythrocytes was determined by the cobalt-exposure method in normal subjects and septic patients. From 48 normal subjects, the value of Vmax of erythrocyte Ca2+ pump was 14.83 +/- 0.49 mmol/L cells/hr; from 29 sepsis patients, it was 9.49 +/- 0.59 mmol/L cels/hr, significantly (P < 0.001) lower than that from the erythrocytes of normal subjects. When the severity of sepsis was evaluated by the septic severity score (SSS), a significant correlation (P < 0.0001) was observed between the Vmax of Ca2+ pump and the patient's SSS, indicating that the inhibition of Ca2+ pump depended on the degree of the pathological development of sepsis. Since the ATP-dependent Ca2+ transport in rat liver plasma membrane is also reduced during the late stage of sepsis [Lau et al., Circ Shock 38:238-244, 1992], impairment of the activity of Ca2+ pump appears to have a general pathophysiological significance in the development of severe sepsis.
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PMID:Erythrocyte Ca2+ pump is defective during sepsis. 760 Jun 35


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