Three pH-buffering systems are primarily involved in the mammalian (human) body:
- pCO2 / HCO3- ion balance
- protein ‘zwitterion’ system, which is mutually dependent on the pCO2 /HCO3- ion balance and includes contributions made by the dissociation of the amphoteric, imidazole and histidine components of plasma proteins and haemoglobin
- ‘phosphate buffer’ (PO4-/PO3-) system
Of these three chemical systems, the ‘phosphate buffer’ system is the least effective, primarily because this pH buffering system is inefficient as a buffer above pH 7.2, and also because excessive phosphate ions cause undesirable side effects, e.g. alteration of calcium and magnesium ion levels through precipitation of their insoluble phosphates.
AQIX® RS-I contains a BES-Hydrogen Carbonate pH buffering system.
BES, N,N-bis (2-hydroxyethyl)-2-amino-ethanesulfonic acid
BES, a N-substituted organic acid derived from 2–aminoethanesulfonic acid (taurine) and one of the zwitterionic Good’s buffer.
It is used as a component of the pH buffering system in AQIX® RS-I as:
- It can substitute for the absence of the pH buffering (pKa) naturally afforded by the α-imidazole group of histidine of haemoglobin of human blood.
- It has a dissociation constant pKa (7.15) and -∆pK/ºC of 0.016@20ºC which equates closely to that of human haemoglobin (pH 7.30), maintains the pH of AQIX® RS-I solution between 7.18-7.45@10-37 ºC.
- It demonstrates negligible binding of both calcium and magnesium ions, thereby not interfering with a range of cellular processes. e.g. membrane receptor sensitivity
- Shown to be nontoxic in cell development and maintenance of mammalian tissues and human organs.
It is imperative that optimised serum levels of bicarbonate ions are achieved during the intravenous infusion of physiological fluids to ensure maintenance of the anion gap (3-11 mmoles/L), intracellular potassium ion levels, Gibbs-Donnan equilibria and ultimately, the integrity of cell membranes. While maintaining serum bicarbonate ion levels between 23-28 mmoles/L is paramount to the pH buffering capacity of haemoglobin as pCO2 levels will naturally vary during respiration.
One consequence of low bicarbonate ion levels is the gradual leakage of intracellular potassium ions (K+) into the surrounding medium which, over time, will have adverse effects on the permeability of cell membranes in terms of ionic balance, fluidity, receptor sensitivity, osmoregulation, and autolysis of essential metabolic components.
AQIX® RS-I contains 25 mmoles/L of hydrogen carbonate to match the normal plasma bicarbonate level.
Stability of pH buffer capacity of AQIX® RS-I solution over 120 hours has been observed when isolated perfused rat heart-lung, kidney, and liver organ preparations were perfused normothermically with AQIX® RS-I.
In a preclinical studies, the daily intravenous infusion of 1L AQIX® RS-I for three days did not compromise the normal haemodynamics, acid-base balance or serum potassium ion levels over a post-operative seven day period follow-up.