phosphocreatine and Escherichia-coli-Infections

Experiments on 55 male chinchilla rabbits with model widespread purulent peritonitis have been performed for determinig structural changes in adrenal glands with the aid of optical microscopy. The introduction of aerobic-anaerobic culture of E. Coli and B. Fragilis into the abdominal cavity causes expressed structural changes in parenchyma of adrenal glands within 6 hours. It is established for the first time that the administration of metabolic drugs citoflavin (containing succinic acid) and neoton (containing creatine phosphate) prevents the development of pathological structural changes in adrenal glands under conditions of experimental widespread purulent peritonitis.

Topics: Adrenal Glands; Animals; Bacteroides fragilis; Bacteroides Infections; Escherichia coli; Escherichia coli Infections; Injections, Intravenous; Male; Microscopy; Microtomy; Paraffin Embedding; Peritonitis; Phosphocreatine; Rabbits; Succinic Acid; Suppuration

The mechanisms responsible for acute renal failure in sepsis are not understood. Measurement of tissue ATP might help to understand this process but, in the large animal, it is hampered by major technical difficulties.. To develop a technique to monitor ATP in the kidney of a large mammal during the induction of septic shock and then circulatory arrest.. Implantation of a custom-made phosphorus coil around the left kidney. Induction of septic shock by intravenous E. coli administration. Acquisition of 31 P magnetic resonance (MR) spectroscopic data at 3-tesla before and during septic shock over several hours. Induction of euthanasia and measurement of the same 31 P signal immediately and thirty minutes after circulatory arrest.. Clear reproducible 31 P MR spectra were obtained before and after the induction of septic shock and euthanasia. They indicated limited changes in ATP during septic shock. An expected rapid and dramatic decrease in ATP occurred with euthanasia.. It is possible to sequentially monitor renal bioenergetics in a large mammal during septic shock using an implanted custom-made phosphorus coil and 3-tesla MR technology. This technique offers a novel approach to the investigation of septic renal failure.

Topics: Acute Kidney Injury; Adenosine Triphosphate; Animals; Bacteremia; Disease Models, Animal; Escherichia coli Infections; Female; Kidney; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus Isotopes; Sheep; Shock; Shock, Septic; Thionucleotides

To determine whether epinephrine increases lactate concentration in sepsis through hypoxia or through a particular thermogenic or metabolic pathway.. Prospective, controlled experimental study in rats.. Experimental laboratory in a university teaching hospital.. Three groups of anesthetized, mechanically ventilated male Wistar rats received an intravenous infusion of 15 mg/kg Escherichia coli O127:B8 endotoxin. Rats were treated after 90 min by epinephrine ( n=14), norepinephrine ( n=14), or hydroxyethyl starch ( n=14). Three groups of six rats served as time-matched control groups and received saline, epinephrine, or norepinephrine from 90 to 180 degrees min. Mean arterial pressure, aortic, renal, mesenteric and femoral blood flow, arterial blood gases, lactate, pyruvate, and nitrate were measured at baseline and 90 and 180 min after endotoxin challenge. At the end of experiments biopsy samples were taken from the liver, heart, muscle, kidney, and small intestine for tissue adenine nucleotide and lactate/pyruvate measurements.. Endotoxin induced a decrease in mean arterial pressure and in aortic, mesenteric, and renal blood flow. Plasmatic and tissue lactate increased with a high lactate/pyruvate (L/P) ratio. ATP decreased in liver, kidney, and heart. The ATP/ADP ratio did not change, and phosphocreatinine decreased in all organs. Epinephrine and norepinephrine increased mean arterial pressure to baseline values. Epinephrine increased aortic blood flow while renal blood low decreased with both drugs. Plasmatic lactate increased with a stable L/P ratio with epinephrine and did not change with norepinephrine compared to endotoxin values. Nevertheless epinephrine and norepinephrine when compared to endotoxin values did not change tissue L/P ratios or ATP concentration in muscle, heart, gut, or liver. In kidney both drugs decreased ATP concentration.. Our data demonstrate in a rat model of endotoxemia that epinephrine-induced hyperlactatemia is not related to cellular hypoxia.

Topics: Acidosis, Lactic; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Blood Gas Analysis; Disease Models, Animal; Drug Evaluation, Preclinical; Endotoxemia; Energy Metabolism; Epinephrine; Escherichia coli Infections; Glycolysis; Hemodynamics; Humans; Kidney; Lactic Acid; Liver; Myocardium; Nitrates; Norepinephrine; Phosphocreatine; Pyruvates; Rats; Rats, Wistar; Tissue Distribution

To study the influence of shock on muscle and plasma adenine nucleotide and creatine pools and their metabolites, and to identify early markers of cellular injury in shock.. Surgical research laboratory, Kuwait and UAE.. Experimental study.. 19 New Zealand rabbits.. 15 rabbits were injected with Escherichia coli endotoxin, and an additional 4 rabbits acted as controls.. Blood and muscle energy metabolites, platelet count, arterial blood gas tensions, and arterial pressure were followed until the animals died.. Five minutes after injection of endotoxin muscle ATP, creatine phosphate, and total adenine purine concentration decreased. This decrease was later reversed, but again decline to a critical level in the terminal phase. Loss of the muscle creatine pool indicated cellular damage after 3 hours. Plasma hypoxanthine, creatine, and lactate concentrations increased continuously throughout the study.. Hypoxanthine formation is a possible source of oxygen free radicals in shock. The rise of hypoxanthine, creatine, and lactate concentrations in plasma during septic shock may reflect early high energy nucleotide failure, membrane injury, and anaerobic metabolism, respectively.

Topics: Adenine; Adenine Nucleotides; Adenosine Triphosphate; Animals; Biomarkers; Blood Pressure; Carbon Dioxide; Creatine; Endotoxins; Energy Metabolism; Escherichia coli Infections; Free Radicals; Hypoxanthine; Hypoxanthines; Lactates; Lipopolysaccharides; Muscles; Oxygen; Phosphocreatine; Platelet Count; Rabbits; Reactive Oxygen Species; Shock, Septic

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.

Topics: Adenosine Triphosphate; Animals; Bacteremia; Disease Models, Animal; Dogs; Endothelium, Vascular; Energy Metabolism; Epinephrine; Escherichia coli Infections; Heart; Mitochondria, Heart; Mitochondrial Swelling; Myocardium; Myofibrils; Oxygen Consumption; Phenylephrine; Phosphocreatine; Reference Values; Time Factors; Ventricular Function, Left

Alterations in skeletal muscle cellular function during septic shock have been previously demonstrated. However, whether these alterations represent a specific response to the septic state or are simply a consequence of low flow is uncertain. The present study was designed to evaluate the cellular membrane response to the early bacteremic state, prior to the onset of hemodynamic compromise. A clinically relevant model of sepsis was achieved in six mongrel dogs by intraarterial infusion of live Escherichia coli organisms and concurrent volume loading with lactated Ringer's solution. Four sham-treated dogs served as controls. Forty-eight hours after induction of sepsis, resting transmembrane potential (Em) was measured in a hindlimb adductor muscle. Contemporaneous muscle biopsy was performed for determination of transmembrane water and electrolyte distribution. The bacteremic state was associated with depolarization of Em to -79.7 +/- 1.2 mV from a basal value of -89.3 +/- 0.2 mV (P less than 0.01), while Em in the sham-treated group remained unchanged over the same time course. In addition, there was a significant increase in the calculated intracellular Na+ and Cl- concentrations in the septic group (P less than 0.02), while intracellular K+ was unchanged. These data are consistent with a selective increase in cell membrane permeability to Na+ and indicate that cellular alterations in skeletal muscle occur early in the septic course, in the absence of hemodynamic compromise. This alteration in membrane permeability appears to be common to cells of disparate organ systems in response to sepsis, and may represent a protean manifestation of cellular injury.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Cardiac Output; Cell Membrane; Cell Membrane Permeability; Chlorides; Dogs; Escherichia coli Infections; Female; Heart Rate; Male; Membrane Potentials; Muscles; Phosphocreatine; Potassium; Pulmonary Wedge Pressure; Sepsis; Sodium; Vascular Resistance