Histidine and other amino acids in blood and urine after administration of Bretschneider solution (HTK) for cardioplegic arrest in patients: effects on N-metabolism

Abstract

Bretschneider (histidine-tryptophan-ketoglutarate, HTK) solution employed for induction of cardioplegic arrest possesses a high histidine concentration (198 mM). Due to the large volume administered, massive amounts of histidine are incorporated. The aim of the study was to evaluate alterations in amino acid and nitrogen metabolism originating from histidine degradation. Between 07/2014 and 10/2014, a total of 29 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass (CPB) were enrolled in this prospective observational study. The patients received 1.6 L cardioplegic Bretschneider solution on average. Blood gas and urine samples obtained were analyzed for amino acid as well as urea and ammonium concentrations. After CPB initiation, plasma histidine concentration greatly increased to 21,000 µM to reach 8000 µM at the end. Within the operative period, plasma concentrations of aspartate, glutamate, asparagine, alanine, and glutamine increased variable in magnitude. During the same time, urinary analysis revealed histidine excretion of 19,500 µmol in total and marked elevations in glutamate and glutamine excretion. The absolute amounts of urea and ammonium excreted additionally were 3 mmol and 8 mmol, respectively. Already during CPB, distinct amounts of the histidine administered are metabolized, mainly to other amino acids, but only small amounts to urea and ammonia. Thus, the impact of the histidine incorporated on acid–base status in the intraoperative phase is minor. On the other hand, intraoperative provision of several amino acids arising from histidine metabolism might mitigate postaggression syndrome.

Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement

“…Third, several studies have shown that HIS administration may lead to marked alterations in aminoacidaemia, which may impair signs of hepatic encephalopathy. Increases in glutamate, alanine, and glutamine concentrations and decreases in glycine and branched-chain amino acid (BCAA; valine, leucine, and isoleucine) concentrations in blood plasma have been reported frequently [39,59,[140][141][142][143].…”

Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Blood Electrolytes and Metabolites—A Randomized Controlled Trial

“…In an experimental rat model of ex vivo lung perfusion, it was found that HTK solution attenuated pulmonary edema until 12 h post-perfusion compared to both saline and low-potassium dextran solution, another extracellular based preservation solution [ 42 , 43 ]. We have recently shown that lung ischemia-reperfusion injury during CPB is characterized by augmented inflammation, metabolic acidosis, protease activity, and oxidative stress and that patients receiving lung protection with HTK solution seemed better protected against severe acidosis, excessive fatty acid oxidation, and inflammation compared to pulmonary artery perfusion with normothermic oxygenated blood or no pulmonary perfusion during CPB [ 44 ].…”

Postoperative Compensatory Ammonium Excretion Subsequent to Systemic Acidosis in Cardiac Patients

“…During the operation as well as in the postoperative phase, patients received different fluids intravenously (Table 1), according to those values published previously [4, 16]. …”