Effects of histidine load on ammonia, amino acid, and adenine nucleotide concentrations in rats
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The unique capability of proton buffering is the rationale for using histidine (HIS) as a component of solutions for induction of cardiac arrest and myocardial protection in cardiac surgery. In humans, infusion of cardioplegic solution may increase blood plasma HIS from ~ 70 to ~ 21,000 µM. We examined the effects of a large intravenous dose of HIS on ammonia and amino acid concentrations and energy status of the body. Rats received 198 mM HIS intravenously (20 ml/kg) or vehicle. Samples of blood plasma, urine, liver, and soleus (SOL) and extensor digitorum longus (EDL) muscles were analysed at 2 or 24 h after treatment. At 2 h after HIS load, we found higher HIS concentration in all examined tissues, higher urea and ammonia concentrations in blood and urine, lower ATP content and higher AMP/ATP ratio in the liver and muscles, higher concentrations of almost all examined amino acids in urine, and lower glycine concentration in blood plasma, liver, and muscles when compared with controls. Changes in other amino acids were tissue dependent, markedly increased alanine and glutamate in the blood and the liver. At 24 h, the main findings were lower ATP concentrations in muscles, lower concentrations of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in blood plasma and muscles, and higher carnosine content in SOL when compared with controls. It is concluded that a load of large HIS dose results in increased ammonia levels and marked alterations in amino acid and energy metabolism. Pathogenesis is discussed in the article.
KeywordsHTK solution Myocardial protection Tetrahydrofolate Glycine ATP depletion Branched-chain amino acids Ammonia Glutamine Ketoglutarate
Branched-chain amino acids (valine, leucine, and isoleucine)
Extensor digitorum longus muscle
High-performance liquid chromatography
- TCA cycle
Tricarboxylic acid cycle
This work was supported by PROGRES Q40/02 program. The authors wish to thank R. Fingrova, D. Jezkova, and K. Sildbergerova for their technical assistance.
MH outlined the experiments, performed the statistical analysis, interpreted the experimental results, and prepared the manuscript. MV was involved in the data acquisition and the data interpretation. Both authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
The Animal Care and Use Committee of Charles University, Faculty of Medicine in Hradec Kralove (licence no. 144879/2011-MZE-17214) approved this study on November 1, 2016 (identification code MSMT-33747/2016-4).
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