Effects of simulated upper gastrointestinal hemorrhage on ammonia and related amino acids in blood and brain of chronic portacaval-shunted rats.
Gastrointestinal (GI) hemorrhage during compromised liver function is known to precipitate portal-systemic encephalopathy (PSE). Hypothetically, the induced hyperammonemia depletes cerebral glutamate pools. To investigate this hypothesis, rats were studied 14 days after portacaval shunt (PCS) or sham surgery (SHAM). Rats received 3 mL bovine erythrocytes or saline at t = 0, 1, 2, and 3h via a previously placed gastrostomy catheter. At t = 0, 2, 4, 6 and 8h arterial blood and at t = 8h cerebral cortex were sampled for determination of ammonia and amino acids. Control rats (NORM) were sampled without previous surgery. Repeated intragastric blood administration increased the already elevated arterial ammonia levels in PCS rats further. This resulted in higher cerebral cortex ammonia and glutamine levels after blood administration. Despite the accumulation of ammonia and glutamine, cerebral cortex glutamate concentrations remained unaltered. Yet, PCS rats became more encephalopathic after blood gavages, suggesting that there is not a clear-cut relation between cerebral cortex glutamate concentrations and degree of PSE. Interestingly, cerebral cortex concentrations of GABA, tyrosine and phenylalanine were markedly increased. Whether these observations are pathogenetically related to PSE remains to be established. The present model of simulated GI hemorrhage in PCS rats seems to be a suitable, clinically valid model for future research regarding hepatic encephalopathy.
Olde Damink
S W
SW
Department of Surgery, Maastricht University, The Netherlands.
Dejong
C H
CH
Deutz
N E
NE
Soeters
P B
PB
D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D000641:Ammonia / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001834:Body Water / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004435:Eating / Q000502:physiology; D006471:Gastrointestinal Hemorrhage / Q000378:metabolism*; D008297:Male; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D001798:Blood Proteins; D000641:Ammonia