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Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans.

Berg RM, Taudorf S, Bailey DM, Lundby C, Larsen FS, Pedersen BK, Møller K - Crit Care (2010)

Bottom Line: Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy.We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human experimental model of systemic inflammation.Systemic inflammation may affect brain function by reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. ronan@dadlnet.dk

ABSTRACT

Introduction: Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human experimental model of systemic inflammation.

Methods: The BCAA/AAA ratio, the cerebral delivery, and net exchange of LNAAs and ammonia were measured before and 1 hour after a 4-hour intravenous infusion of Escherichia coli lipopolysaccharide (LPS) in 12 healthy young men.

Results: LPS induced systemic inflammation, reduced the BCAA/AAA ratio, increased the cerebral delivery and unidirectional influx of phenylalanine, and abolished the net cerebral influx of the BCAAs leucine and isoleucine. Furthermore, a net cerebral efflux of glutamine, which was independent of the cerebral net exchange of ammonia, was present after LPS infusion.

Conclusions: Systemic inflammation may affect brain function by reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

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Related in: MedlinePlus

Unidirectional cerebral influx of phenylalanine (Jin, Phe) after lipopolysaccharide (LPS) infusion in healthy humans. Triangles indicate means. **Different from baseline, P < 0.01.
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Figure 2: Unidirectional cerebral influx of phenylalanine (Jin, Phe) after lipopolysaccharide (LPS) infusion in healthy humans. Triangles indicate means. **Different from baseline, P < 0.01.

Mentions: LPS infusion increased plasma phenylalanine and decreased the concentration of all other LNAAs except isoleucine (Table 1), with a concurrent reduction in the BCAA/AAA ratio (baseline, 5.2 (4.7-5.7); LPS, 4.9 (4.4-5.3); Figure 1). Both the cerebral delivery (Table 2) and the unidirectional cerebral influx of phenylalanine increased (baseline, 8.3 (6.7-9.9) nmol/g/min; LPS, 9.2 (8.9-10.4) nmol/g/min; Figure 2), whereas its cerebral net exchange was unchanged (Table 3). Furthermore, a net cerebral influx observed at baseline for leucine and isoleucine was abolished after LPS infusion (Table 3). At baseline, a net cerebral influx of methionine was present; this was converted to a net cerebral efflux after LPS infusion (Table 3). Furthermore, a net cerebral efflux of glutamine that was not observed at baseline was present after LPS infusion (Table 3). There was no effect of LPS infusion on the arterial whole-blood concentration of ammonia (baseline, 78 (72-84] μmol/L; LPS, 69 (61-76) μmol/L; NS). The cerebral net exchange of ammonia did not differ from 0 at any time and was unaffected by LPS infusion (baseline, 139 ([-70] - 348) nmol/100 g/min; LPS, -98 ([-618] - 422) nmol/100 g/min; NS).


Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans.

Berg RM, Taudorf S, Bailey DM, Lundby C, Larsen FS, Pedersen BK, Møller K - Crit Care (2010)

Unidirectional cerebral influx of phenylalanine (Jin, Phe) after lipopolysaccharide (LPS) infusion in healthy humans. Triangles indicate means. **Different from baseline, P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875531&req=5

Figure 2: Unidirectional cerebral influx of phenylalanine (Jin, Phe) after lipopolysaccharide (LPS) infusion in healthy humans. Triangles indicate means. **Different from baseline, P < 0.01.
Mentions: LPS infusion increased plasma phenylalanine and decreased the concentration of all other LNAAs except isoleucine (Table 1), with a concurrent reduction in the BCAA/AAA ratio (baseline, 5.2 (4.7-5.7); LPS, 4.9 (4.4-5.3); Figure 1). Both the cerebral delivery (Table 2) and the unidirectional cerebral influx of phenylalanine increased (baseline, 8.3 (6.7-9.9) nmol/g/min; LPS, 9.2 (8.9-10.4) nmol/g/min; Figure 2), whereas its cerebral net exchange was unchanged (Table 3). Furthermore, a net cerebral influx observed at baseline for leucine and isoleucine was abolished after LPS infusion (Table 3). At baseline, a net cerebral influx of methionine was present; this was converted to a net cerebral efflux after LPS infusion (Table 3). Furthermore, a net cerebral efflux of glutamine that was not observed at baseline was present after LPS infusion (Table 3). There was no effect of LPS infusion on the arterial whole-blood concentration of ammonia (baseline, 78 (72-84] μmol/L; LPS, 69 (61-76) μmol/L; NS). The cerebral net exchange of ammonia did not differ from 0 at any time and was unaffected by LPS infusion (baseline, 139 ([-70] - 348) nmol/100 g/min; LPS, -98 ([-618] - 422) nmol/100 g/min; NS).

Bottom Line: Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy.We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human experimental model of systemic inflammation.Systemic inflammation may affect brain function by reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. ronan@dadlnet.dk

ABSTRACT

Introduction: Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human experimental model of systemic inflammation.

Methods: The BCAA/AAA ratio, the cerebral delivery, and net exchange of LNAAs and ammonia were measured before and 1 hour after a 4-hour intravenous infusion of Escherichia coli lipopolysaccharide (LPS) in 12 healthy young men.

Results: LPS induced systemic inflammation, reduced the BCAA/AAA ratio, increased the cerebral delivery and unidirectional influx of phenylalanine, and abolished the net cerebral influx of the BCAAs leucine and isoleucine. Furthermore, a net cerebral efflux of glutamine, which was independent of the cerebral net exchange of ammonia, was present after LPS infusion.

Conclusions: Systemic inflammation may affect brain function by reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

Show MeSH
Related in: MedlinePlus