A decrease in plasma isoleucine levels after simulated upper digestive tract bleeding in human volunteers

Berio, C.L.H. van; Dejong, C.H.C.; Meyerink, W.J.H.J.; Meyenfeldt, M.F. von; Fick, T E; Deutz, N.E.P.; Soeters, P.B.

doi:10.1016/0261-5614(91)90176-d

Cited by 5 publications

(4 citation statements)

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“…In a similar experiment, we showed that a blood meal in healthy human volunteers induced a reduction in plasma isoleucine concentration to <50% of normal fasting values. Concomitantly, the concentration of all other amino acids increased 15 . In patients with normal and impaired liver function presenting with an UGI bleed, we have also demonstrated a reduction in isoleucine concentration by 60–70% 16 .…”

Section: Isoleucine Deficiency In the Haemoglobin Moleculesupporting

confidence: 56%

Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis

Damink

Dejong

Jalan

2009

Aliment Pharmacol Ther

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Summary Background Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of the liver induces hyperammonaemia and leads to a catabolic cascade that precipitates life‐threatening complications. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and contains high amounts of leucine and valine. UGI bleed therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce net catabolism. Aim To describe the hyperammonaemic and catabolic consequences of UGI bleeding in cirrhosis. Methods A semi‐structured literature search was performed using PubMed and article references. Results It has recently been proven that (‘simulation of ’) a UGI bleed in patients with cirrhosis leads to impaired protein synthesis that can be restored by intravenous infusion of isoleucine. This may have therapeutic implications for the function of rapidly dividing cells and short half‐life proteins such as clotting factors. Renal and small bowel ammoniagenesis were shown to be the most prominent causes for the hyperammonaemia that resulted from a UGI bleed. This provides an explanation for the therapeutic failure of the current clinical therapies that are aimed at large bowel‐derived ammonia production. Isoleucine infusion did not diminish renal ammoniagenesis. Conclusions New pharmacological therapies to diminish postbleeding hyperammonaemia should target the altered inter‐organ ammonia metabolism and promote ammonia excretion and/or increase the excretion of precursors of ammoniagenesis, e.g. l‐ornithine–phenylacetate.

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Section: Isoleucine Deficiency In the Haemoglobin Moleculesupporting

confidence: 56%

Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis

Damink

Dejong

Jalan

2009

Aliment Pharmacol Ther

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“…In a series of studies, isoleucine concentrations were shown to decrease markedly after an actual or a simulated upper GI bleed, whereas the concentration of most other amino acids increased [7][8][9][10][11]. Post-bleeding hypoisoleucinemia has been shown to occur in experimental animals [8,10], in healthy volunteers [8], and in patients with impaired and normal liver function [9,11].…”

Section: Introductionmentioning

confidence: 97%

“…Post-bleeding hypoisoleucinemia has been shown to occur in experimental animals [8,10], in healthy volunteers [8], and in patients with impaired and normal liver function [9,11]. We hypothesized that decreased plasma and tissue isoleucine concentrations could impair protein synthesis [5], and therefore influence the function of rapidly dividing cells (e.g.…”

Section: Introductionmentioning

confidence: 99%

Protein synthesis is severely diminished following a simulated upper GI bleed in patients with cirrhosis

Damink

Jalan

Deutz

et al. 2008

Journal of Hepatology

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“…[3][4][5] Within six hours after intragastric blood administration in healthy pigs as well as after a blood pudding meal in healthy volunteers, a more than 50%/ decrease in the plasma values of the essential branched chain amino acid isoleucine (ILE) was observed, while the concentration of the other two branched chain amino acids leucine (LEU) and valine (VAL) and most other amino acids reached extremely high concentrations.3-5 Simultaneously, arterial urea and ammonia values increased.3 Isonitrogenous control meals led to an increase of most amino acids, including ILE, and a less pronounced increase in arterial ammonia and urea. Analysis of the amino acid composition of blood protein (mainly haemoglobin) showed an almost complete absence of the essential amino acid ILE.3 As a consequence, blood protein has a low biological value.6…”

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confidence: 99%

Decreased plasma isoleucine concentrations after upper gastrointestinal haemorrhage in humans.

Dejong

Meijerink

Berlo

et al. 1996

Gut

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Background-A decrease in arterial isoleucine values after intragastric blood administration in pigs has been observed. This contrasted with increased values of most other amino acids, ammonia, and urea. After an isonitrogenous control meal in these pigs all amino acids including isoleucine increased, and urea increased to a lesser extent, suggesting a relation between the arterial isoleucine decrease and uraemia after gastrointestinal haemorrhage. Methods-To extend these findings to humans, plasma amino acids were determined after gastrointestinal haemorrhage in patients with peptic ulcers (n=9) or oesophageal varices induced by liver cirrhosis (n=4) and compared with preoperative patients (n= 106). Results-After gastrointestinal haemorrhage, isoleucine decreased in all patients by more than 60% and normalised within 48 hours. Most other amino acids increased and also normalised within 48 hours. Uraemia occurred in both groups, hyperammonaemia was seen in patients with liver cirrhosis. Conclusions-These results confirm previous findings in animals and healthy volunteers that plasma isoleucine decreases after simulated upper gastrointestinal haemorrhage. This supports the hypothesis that the absence of isoleucine in blood protein causes decreased plasma isoleucine values after gastrointestinal haemorrhage, and may be a contributory factor to uraemia and hyperammonaemia in patients with normal and impaired liver function, respectively. Intravenous isoleucine administration after gastrointestinal haemorrhage could be beneficial and will be the subject of further research.

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A decrease in plasma isoleucine levels after simulated upper digestive tract bleeding in human volunteers

Cited by 5 publications

References 0 publications

Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis

Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis

Protein synthesis is severely diminished following a simulated upper GI bleed in patients with cirrhosis

Decreased plasma isoleucine concentrations after upper gastrointestinal haemorrhage in humans.

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