Minimal-invasive approach to study pulmonary, metabolic and renal responses to alimentary acid-base changes in conscious rabbits.

Abstract

Systemic acid-base balance is maintained by the complex interplay of renal and pulmonary control functions and metabolic adaptations, whereby intake and mineral composition of feed are important factors. It was intended to explore the role of alimentary acid-base load and carbonic anhydrase activity for regulatory responses of renal, pulmonary or metabolic origin in rabbits as typical herbivores. Sixty-eight conscious male rabbits (about 3.5 kg) were kept in a metabolic cage, to determine daily water intake, urine excretion and food consumption. Different groups were fed either alkali-rich rabbit standard pellets, or modified rabbit chow with low Ca++-content, or a special diet with very low alkali content, or standard food together with a low oral dose (about 20 mg x kg(-1) x d(-1)) acetazolamide. Samples from the central ear artery were analyzed for blood gases (PaO2, PaCO2), pHa, base excess (BE) and actual bicarbonate (HCO3a-). The metabolic CO2 production (VCO2 STPD) was determined, to calculate alveolar ventilation (VA BTPS). Anaerobically collected urine was analyzed for pHu and for concentrations of bicarbonate/carbonate (HCO3-/CO3--), ammonium (NH4+), and phosphate. 1) Systemic BE was not affected by alimentary alkali load, either varied spontaneously by standard food intake or by the low-Ca++ diet, and decreased only slightly on the low-alkali diet, but distinctly upon carbonic anhydrase inhibition. 2) Under all conditions of alimentation, PaCO2 was closely correlated with BE without a detectable set-point, the normal-range variability of BE being sufficient to elicit corresponding changes in VA. In contrast, acetazolamide led to much lower values of PaCO2 than predicted by the reference PCO2/BE relationship, being primarily caused by significant reductions in VCO2 (> 20%). 3) Prior to other systems, renal base excretion, normally being high on species-adapted standard chow, closely followed any variation of alimentary alkali load and approached zero upon the low-alkali diet. It was, however, not significantly influenced by carbonic anhydrase (CA) inhibition on alkalirich alimentation. Blood acid-base balance in rabbits is maintained over a wide range of alimentary alkali load by effective adaptation of renal base excretion, independent of CA activity. Ventilatory pH control is perpetuated even in the normal range of BE, provided metabolic rate is not impaired, e. g., by CA inhibition. These results may help one understand the different manifestations of acid-base disorders in body fluids under clinical conditions.