phosphocreatine and Hepatic-Encephalopathy

MR spectroscopy in a patient with hyponatremic encephalopathy due to the syndrome of inappropriate secretion of antidiuretic hormone revealed decreased N-acetyl-aspartate, creatine plus phosphocreatine, choline-containing compounds, and myo-inositol, with normal glutamate and increased glutamine, which normalized after Na normalization. The decreased concentrations of creatine plus phosphocreatine, choline-containing compounds and myo-inositol are explained by their release as osmolytes from brain cells to adapt to hypo-osmolality induced cerebral edema. Increased glutamine, which not only acts as an osmolyte but also protects neurons under excitotoxic conditions, may suggest that a disrupted glutamate-glutamine cycle may play an important role in the pathogenesis of hyponatremic encephalopathy.

Topics: Aspartic Acid; Child; Creatine; Glutamic Acid; Glutamine; Hepatic Encephalopathy; Humans; Hyponatremia; Inositol; Magnetic Resonance Spectroscopy; Male; Neurochemistry; Phosphocreatine; Sodium

The brain energy metabolism of rats affected by chronic hepatic encephalopathy due to portacaval shunting was monitored by in vivo 31P-nuclear magnetic resonance spectroscopy before and after ammonium acetate administration. With respect to healthy unoperated and to sham operated controls, portacaval shunting decreased the levels of the nuclear magnetic resonance (NMR) visible brain phosphocreatine and nucleoside phosphates, and the intracellular [free Mg(2+)]. Ammonium acetate induced a further decrease of the levels of the NMR detectable phosphocreatine and nucleoside triphosphates and of the [free Mg(2+)], while the PMR spectra of the brain of non-shunted rats did not show any significant change even after treatment with ammonium acetate.

Topics: Ammonia; Animals; Brain; Chronic Disease; Energy Metabolism; Hepatic Encephalopathy; Magnetic Resonance Spectroscopy; Male; Nucleotides; Phosphates; Phosphocreatine; Rats; Rats, Sprague-Dawley

Hyperammonemia is a consistent finding in many metabolic disorders. The excess ammonia (NH4Cl) interferes with brain energy metabolism possibly in part by inhibiting the tricarboxylic acid (TCA) cycle. Inhibition of the TCA cycle may result in depletion of ATP in the brain cells. In this study, the acute and chronic effect of NH4Cl (7.5 mM and 15 mM) on the metabolism of isolated neurons and neuroblastoma cells was examined. These cells were treated with NH4Cl for 15 minutes and 24 hours. Morphologic and metabolic toxicity were greater in neuroblastoma cells than in primary neurons. Following 15 minutes treatment, concentration of lactate increased significantly in neuroblastoma cells but, the concentration of other metabolites did not change significantly in neuroblastoma cells and in primary neurons. Following 24 hours treatment, the glucose utilization increased in both cell types. This high utilization of glucose in neuroblastoma cells was in concert with an increase in lactate and decrease in glutamate and ATP. In primary neurons, following 24 hours treatment, the glucose utilization significantly increased, but the concentration of the other metabolites did not change significantly. Neuroblastoma cells consumed more glucose than primary neurons in absence of NH4Cl, but generated the same amount of lactate as neurons.

Topics: Adenosine Triphosphate; Ammonium Chloride; Animals; Brain; Cell Death; Energy Metabolism; Female; Fetus; Glucose; Glutamic Acid; Hepatic Encephalopathy; Hyperammonemia; Lactic Acid; Neuroblastoma; Neurons; Phosphocreatine; Pregnancy; Rats; Rats, Sprague-Dawley; Tumor Cells, Cultured

Quantitative proton and quantitative proton-decoupled 31P magnetic resonance spectroscopy (MRS) of the brain was performed in 16 patients with liver disease (10 with and six without chronic hepatic encephalopathy) and four patients with hyponatremia, as well as 20 age-matched normal subjects. Patients with hepatic encephalopathy were distinguished from controls by significant reduction in levels of cerebral nucleoside triphosphate (2.45 +/- 0.20 vs. 2.91 +/- 0.21 mmol/kg of brain; p < 0.0003), inorganic phosphate (p < 0.03), and phosphocreatine (p < 0.04). In addition of increased levels of cerebral glutamate plus glutamine and decreased concentrations of myo-inositol, patients with hepatic encephalopathy showed a reduction of total visible choline and of glycerophosphorylcholine (0.67 +/- 0.13 vs. 0.92 +/- 0.20 mmol/kg of brain in controls; p < 0.005) in 1H MRS, and of glycerophosphorylethanolamine (0.40 +/- 0.12 vs. 0.68 +/- 0.12 mmol/kg of brain in controls; p < 0.0003) in proton-decoupled 31P MRS. Of the reduction of "total choline," 61% was accounted for by glycerophosphorylcholine, a cerebral osmolyte. Similar metabolic abnormalities were seen in hyponatremic patients. The results are consistent with disturbances of cerebral osmoregulation and energy metabolism in patients with chronic hepatic encephalopathy.

Topics: Adenosine Triphosphate; Adult; Aged; Brain; Choline; Ethanolamine; Female; Hepatic Encephalopathy; Humans; Hyponatremia; Magnetic Resonance Imaging; Male; Middle Aged; Osmosis; Phosphates; Phosphocreatine; Phosphorus Isotopes; Phosphorylation; Protons; Water-Electrolyte Balance

Proton magnetic resonance (MR) spectroscopy of the brain was performed in 11 patients with chronic hepatic encephalopathy (CHE), and the results were compared with those of patients with liver disease but without CHE; clinical control subjects with diabetes, uremia, or cortical atrophy; and healthy subjects. The technique of water-suppressed stimulated-echo hydrogen-1 MR spectroscopy for detection of cerebral glutamate, glutamine, glucose, N-acetylaspartate, choline metabolites, (phospho)creatine, and myo-inositol is described. Specific changes in the brain of CHE patients included the anticipated elevation in cerebral glutamine levels (P less than or equal to .0001), a 23% reduction in choline metabolite levels (P less than or equal to .0001), and a more than 50% reduction in cerebral myo-inositol levels (P less than or equal to .0001). In four of the 15 patients with liver disease but without clinical CHE, a significant reduction in the myo-inositol level was detected, and in two of these patients an elevation in the glutamine concentration was also observed. These findings indicate a role for image-guided H-1 MR spectroscopy in the diagnosis and monitoring of both overt and preclinical CHE.

Topics: Aspartic Acid; Brain; Choline; Female; Glucose; Glutamates; Glutamic Acid; Glutamine; Hepatic Encephalopathy; Humans; Inositol; Liver Diseases; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Reproducibility of Results

During the development of acute hepatic encephalopathy, induced by acute liver ischemia, changes in brain 31P NMR spectra and EEG spectra were studied over 8:45 h in eight rats. At the end of this period the brain amino acid concentrations were determined. The results were compared with the same measurements in four normal and three portacaval shunted rats. Signs of acute HE, as judged by the EEG left index, started 5 h after the induction of acute liver ischemia. No accompanying significant changes in the cortical relative phosphocreatine and ATP concentration and intracellular pH were observed. The cortical relative Pi concentration had only slightly increased at t = 8 h. The concentrations of almost all measured brain amino acids, especially glutamine had increased at t = 8:45 h. At t = 8 h, rats with very severe HE had a small, but significant decrease of brain ATP concentrations. Their brain amino acid concentrations were more disturbed than in rats with less severe HE. It is concluded that a change in the cortical cerebral energy rich phosphate concentration is not an important pathophysiological mechanism during the development of acute HE. The observed changes in brain amino acids concentrations could be either part of a multifactorial pathogenesis or could be epiphenomena.

Topics: Adenosine Triphosphate; Amino Acids; Ammonia; Animals; Cerebral Cortex; Electroencephalography; Hepatic Encephalopathy; Ischemia; Liver Circulation; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Phosphorus; Rats; Rats, Inbred Strains; Reference Values

Brain energy reserve, tricarboxylic cycle intermediate and some putative neurotransmitters were measured in a devascularisation model with portacaval shunt and hepatic artery ligation done in two interventions. Conditions were standardized in that physiologic parameters, i.e. body temperature, systemic arterial pressure, PO2, PCO2 and pH, were kept constant and brain tissue was obtained with the "freeze-blowing" technique designed for deep freezing brain substance in less than one second. 1. Measured values indicative of the brain energy reserve (glucose, glycogen, ATP and phosphocreatin) were not found to differ from those of sham-operated animals. 2. Of the stimulating neurotransmitters, norepinephrine, dopamine, glutamic acid and aspartic acids were reduced with the exception of acetylcholine among the inhibitory neurotransmitters GABA and cAMP were unchanged, while all others including serotonin, octopamine, and phenylethanolamine were increased. 3. The results of these experiments suggest that an inbalance of amino acids with resultant changes in neurotransmitter profiles rather than an energy deficit constitutes the factor underlying hepatic coma.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Ammonia; Animals; Brain; Energy Metabolism; gamma-Aminobutyric Acid; Glucose; Glutarates; Glycogen; Hepatic Encephalopathy; Malates; Phosphocreatine; Rats

After controlling the physiological parameters during 6 hours of experimental hepatic coma in Sprague-Dawley rats the results show 1. No shortage of brain energy supply of the four main cerebral energy reserves, the brain glycogen is significantly elevated, and the phosphocreatine, ATP and glucose unaltered. 2. No alterations in intermediates of the glycolytic pathway and the tricarboxylic acid cycle in brain tissue. 3. A highly significant decrease in the brain content of the "excitatory" transmitter amino acids glutamate and aspartate. These findings do not support the well-known hypothesis of BESSMAN and BESSMANN and later authors on the role of ammonia in the pathogenesis of hepatic coma.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Female; Glucose; Glycogen; Hepatic Encephalopathy; Ketone Bodies; Lactates; Liver; Male; Neurotransmitter Agents; Phosphocreatine; Rats

Topics: Acid-Base Equilibrium; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Bicarbonates; Brain; Carbon Dioxide; Disease Models, Animal; Hemoglobins; Hepatectomy; Hepatic Encephalopathy; Hydrogen-Ion Concentration; Lactates; Male; NAD; Oxygen; Partial Pressure; Phosphocreatine; Pyruvates; Rats

Topics: Adenosine Triphosphate; Amino Acids; Ammonia; Animals; Brain; Electroencephalography; Fatty Acids; Glutamates; Glutamine; Hepatic Encephalopathy; Humans; Imines; Ketoglutaric Acids; Methionine; Oxygen Consumption; Phosphocreatine; Tryptophan