Oral amino acid load mimicking hemoglobin results in reduced regional cerebral perfusion and deterioration in memory tests in patients with cirrhosis of the liver.
This study tests the hypothesis that administration of an oral amino acid load mimicking hemoglobin in patients with cirrhosis of the liver causes deterioration in neuropsychological function and a reduction in regional cerebral perfusion. Eight overnight fasted, metabolically stable cirrhotic patients with no evidence of overt hepatic encephalopathy were studied prior to and 4 h after simulating an upper gastrointestinal bleed by oral administration of 75 g of a solution mimicking the amino acid composition of hemoglobin. Neuropsychological function was measured using a test battery. Peripheral venous blood was collected for the measurement of ammonia and amino acid concentrations. Regional cerebral perfusion was measured using a head SPECT scanner following intravenous administration of technetium-99m hexamethyl propylamineoxime. The amino acid solution resulted in significant deterioration in the immediate and delayed story recall tests. Ammonia concentration increased from a median of 87 (range 67-94) micromol/L to 105 (98-112) micromol/L at 4 h after the simulated bleed (p < 0.01). The concentration of almost all amino acids increased; only isoleucine levels decreased following the upper gastrointestinal bleed. SPECT analysis showed a significant reduction in cerebral perfusion after the simulated bleed in both temporal lobes, left superior frontal gyrus, and right parietal and cingulate gyrus. An oral amino acid load mimicking hemoglobin in cirrhotic patients produces hyperammonemia and hypoisoleucinemia and causes a significant deterioration in memory tests, probably due to a reduction in regional cerebral perfusion. The model of simulating the metabolic effects of an upper gastrointestinal bleed in patients with cirrhosis of the liver seems to be useful in studying the metabolism of hepatic encephalopathy.
Jalan
Rajiv
R
Liver Failure Group, Institute of Hepatology, University College London Medical School, London, United Kingdom. r.jalan@ucl.ac.uk
Olde Damink
Steven W M
SW
Lui
Hock F
HF
Glabus
Mike
M
Deutz
Nicolaas E P
NE
Hayes
Peter C
PC
Ebmeier
Klaus
K
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage*; D001921:Brain / Q000000981:diagnostic imaging; D002545:Brain Ischemia / Q000209:etiology*; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000523:psychology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008875:Middle Aged; D015899:Tomography, Emission-Computed, Single-Photon
D000596:Amino Acids; D006454:Hemoglobins