Abstract
The unique capability of proton buffering is the rationale to use histidine (HIS) as a component of solutions for induction of cardiac arrest and myocardial protection in cardiac surgery. Their administration increases blood plasma HIS from ~70 µM 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. The overnight fasted rats received intravenously 198 mM HIS (20 ml/kg body weight) or vehicle.
The animals were euthanized at 2 and 24 hours after treatment. Samples of blood plasma, urine, the liver, and soleus (SOL) and extensor digitorum longus (EDL) muscles were analysed.
At 2 hours 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 concentration of almost all examined amino acids in urine, and lower glycine concentration in blood plasma, liver, and muscles when compared with controls. Changes in concentrations of other amino acids were tissue dependent.
At 24 hours the most of alterations observed at 2 hours returned to normal. The main findings were higher ammonia and 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 therapeutic strategy is needed to avoid adverse effects of a load of large HIS dose on ammonia formation and altered metabolism of tetrahydrofolate, glycine, BCAA, and adenine nucleotides.