Effects of acute hyperammonemia on cerebral amino acid metabolism and pHi in vivo, measured by 1H and 31P nuclear magnetic resonance.
The effects of an acute intravenous infusion of ammonium acetate on rat cerebral glutamate and glutamine concentrations, energy metabolism, and intracellular pH were measured in vivo with 1H and 31P nuclear magnetic resonance (NMR). The level of blood ammonia maintained by the infusion protocol used in this study (approximately 500 microM, arterial blood) did not cause significant changes in arterial PCO2, PO2, or pH. Cerebral glutamate levels fell to at least 80% of the preinfusion value, whereas glutamine concentrations increased 170% relative to the preinfusion controls. The fall in brain glutamate concentrations followed a time course similar to that of the rise of brain glutamine. There were no detectable changes in the content of phosphocreatine (PCr) or nucleoside triphosphates (NTP), within the brain regions contributing to the sensitive volume of the surface coil, during the ammonia infusion. Intracellular pH, estimated from the chemical shift of the inorganic phosphate resonance relative to the resonance of PCr in the 31P spectrum, was also unchanged during the period of hyperammonemia. 1H spectra, specifically edited to allow quantitation of the brain lactate content, indicated that lactate rose steadily during the ammonia infusion. Detectable increases in brain lactate levels were observed approximately 10 min after the start of the ammonia infusion and by 50 min of infusion had more than doubled. Spectra acquired from rats that received a control infusion of sodium acetate were not different from the spectra acquired prior to the infusion of either ammonium or sodium acetate.(ABSTRACT TRUNCATED AT 250 WORDS)
Fitzpatrick
S M
SM
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.
Hetherington
H P
HP
Behar
K L
KL
Shulman
R G
RG
D000085:Acetates / Q000494:pharmacology; D000641:Ammonia / Q000097:blood*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009711:Nucleotides / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D005971:Glutamates; D007773:Lactates; D009711:Nucleotides; D011522:Protons; D010725:Phosphocreatine; D005973:Glutamine; D010758:Phosphorus; D019344:Lactic Acid; D018698:Glutamic Acid; D000641:Ammonia; C018824:ammonium acetate