Infusion of an acidified ethanolic-dextrose solution enhances urinary ammonium excretion and increases acid resilience in non-mechanically ventilated acidotic rabbits.

Hitherto, the rabbit has long been known to have a very poor tolerance to non-volatile acid. In this study, we tested the hypothesis that acid resilience in the acidotic rabbit can be increased by enhancing the plasma availability of a naturally occurring volatile fatty acid, namely acetate. To ascertain the relative merits of the respiratory and renal systems in contributing to that resilience, we conducted our studies in non-ventilated and mechanically ventilated acidotic animals. Using ethanol as a feeder of acetate, and to counteract the antidiuretic effects of surgical interventions, we induced acidosis in anaesthetised rabbits, by intravenously infusing an acidified ethanolic dextrose solution. We observed very potent respiratory regulation of arterial blood pH coupled with a notable renal response by way of a 25-fold increase in urinary ammonium excretion in the non-ventilated group. In contrast, arterial blood pH plummeted much more rapidly in the mechanically-ventilated animals, but the compensated renal response was enormous, in the form of an 85 -fold increase in urinary ammonium output. Despite this significant adaptive renal response, the non -mechanically ventilated group of rabbits showed the greater acid resilience. This was attributed to an acetate stimulated flux through a series of metabolic pathways, generating supplementary buffer in the form of bicarbonate and ammonia, complemented by a robust respiratory response.

The kinetics of inorganic phosphate excretion in the acidotic rabbit during intravenous phosphate loading: a pseudo-ruminant model.

The rabbit is a much-used experimental animal in renal tubule physiology studies. Although a monogastric mammal, the rabbit is a known hindgut fermenter. That ruminant species excrete inorganic phosphate (Pi) mainly through the digestive system while non-ruminants eliminate surplus phosphate primarily through the renal system are acknowledged facts. To understand phosphate homeostasis in the acidotic rabbit, anaesthetized animals were infused with hydrochloric acid, after which they underwent intravenous phosphate loading. Biofluids were collected during the infusion process for analysis. Plasma Pi increased (7.9 ± 1.7 mmoles.Litre-1 (N = 5) vs 2.2 ± 0.4 mmoles.Litre-1 (N = 10) pre-infusion, (p < 0.001)), while urinary phosphate excretion was also enhanced (74.4 ± 15.3 from a control value of 4.7 ± 3 µmol.min-1 (N = 9), pre-infusion, p < 0.001)) over an 82.5 minute Pi loading period. However, the fractional excretion of Pi (FePi) only increased from 14.2 ± 5.4% to a maximum of 61.7 ± 19% (N = 5) over the infusion period. Furthermore, the renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmPi/GFR) computed to 3.5 mmol.L-1, while a reading of 23.2 µmol.min-1.Kg.0.75 was obtained for the transport maximum for Pi (TmPi). The high reabsorptivity of the rabbit nephrons coupled with possibly a high secretory capacity of the salivary glands for Pi, may constitute a unique physiological mechanism that ensures the rabbit hindgut receives adequate phosphate to regulate caecal pH in favour of the resident metabolically - active microbiota. The handling of Pi by the rabbit is in keeping with the description of this animal as a monogastric, pseudo-ruminant herbivore.

An appraisal of the in vivo role of phosphate as a modulator of urinary ammonium and titratable acid excretion in the acidotic rabbit.

Previous studies have shown that the intravenous infusion of inorganic phosphate increased urinary ammonium excretion 8- to 10-fold in the acidotic rabbit. This was considered to be a very important observation at the time and to be unique to the rabbit. While investigating this finding, we discovered that the formol titration procedure, used to measure urinary ammonium by this research group, is subject to interference by phosphate, casting doubt on the validity of the urinary ammonium excretion data reported by them in the literature. In order to re-assess the importance of phosphate as a potential modulator of urinary ammonium excretion in the acidotic rabbit, renal net acid excretion studies were carried out in phosphate-loaded acidotic animals. We observed that while urinary ammonium excretion increased significantly (p < 0.05) after 50 min of phosphate infusion, the maximum concentrations excreted were substantially less than previously reported in the literature. However, through its urinary buffering capacity, we observed that inorganic phosphate, via an experimentally induced phosphaturia, could substantially enhance titratable acid excretion. Contrary to earlier reports, we demonstrated that phosphate plays a relatively minor in vivo modulator role in enhancing renal net acid excretion through the vehicle of ammonium during acute metabolic acidosis in the hyperphosphataemic rabbit. The findings reported in this study constitute an important update on ammonia metabolism in the acidotic rabbit.

Collection of untainted urinary specimens from the bladder of an anesthetized rabbit.

It is difficult to collect untainted urine specimens over short intervals of time during renal studies with rabbits. This is because both the ureters and the bladder of this species are relatively friable and minor manipulation can easily cause intraluminal bleeding. We have developed and refined an effective technique and protocol for placing an indwelling urinary bladder catheter into an anesthetized rabbit. The procedure is easy to perform and completely effective and reliable, allowing high-quality urinary specimens to be collected at intervals of 15-20 min over a period of 3-4 hours during a study of acute metabolic acidosis.