Influence of Medetomidine on Acid-base Balance and Urine Excretion in Goats

Raekallio M., M. Hackzell and L. Eriksson: Influence of medetomidine on acid-base balance and urine excretion in goats. Acta vet. scand. 1994,35,283-288.– Seven goats were given medetomidine 5 μg/kg as an iv bolus injection. Venous blood samples were taken repeatedly and urine was collected continuously via a catheter up to 7h after the injection.Medetomidine caused deep clinical sedation. Base excess, pH and PCO₂ in venous blood rose after medetomidine administration. There were no significant changes in plasma concentrations of sodium, calcium, magnesium, creatinine or osmolality, whereas potassium and bicarbonate concentrations increased, and phosphate and chloride decreased. Medetomidine increased plasma glucose concentration, and in 4 of 7 goats glucose could also be detected in urine. Medetomidine did not influence urine flow rate, free water clearance, bicarbonate and phosphate excretion or pH, but renal chloride, sodium, potassium, calcium, magnesium and creatinine excretion were reduced.The results suggest that the metabolic alkalosis recorded after medetomidine administration is not caused by increased renal acid excretion.     

Effects of supplemental recombinant bovine somatotropin and mist-fan cooling on the renal tubular handling of sodium in different stages of lactation in crossbred Holstein cattle

The effect of supplementary administration of recombinant bovine somatotrophin (rbST) on the renal tubular handling of sodium in crossbred 87.5% Holstein cattle housed in normal shade (NS) or mist-fan cooled (MF) barns was evaluated. The cows were injected with 500 mg rbST at three different stages of lactation. The MF barn housed cows showed a slightly decreased ambient temperature and temperature humidity index, but an increased relative humidity. Rectal temperature and respiration rates were significantly lower in cooled cows. The rbST treated cows, housed in NS or MF barns, showed markedly increased milk yields, total body water, extracellular fluid and plasma volume levels, along with a reduced rate of urine flow and urinary excretion of sodium, potassium and chloride ions and osmolar clearance, in all three stages of lactation. Renal tubular sodium and water reabsorption were increased after rbST administration without any alteration in the renal hemodynamics. Lithium clearance data suggested that the site of response is in the proximal nephron segment, which may be mediated via increases in the plasma levels of aldosterone and IGF-1, but not vasopressin, during rbST administration.     

The effect of an angiotensin-converting enzyme inhibitor on water and electrolyte balance in water-restricted sheep

The importance of angiotensin II in the regulation of water and electrolyte balance in sheep is questionable. In this trial the effects of an angiotensin-converting enzyme (ACE) inhibitor were quantified in sheep on restricted water intake. Comparing the phase of water restriction only with that of water restriction plus ACE inhibition, significant increases were observed during the latter phase in urine volume, sodium and potassium excretion via the urine, sodium concentration in the plasma and osmolar clearance. Urine osmolarity decreased with inhibition of angiotensin II formation while variables such as water, sodium and potassium loss via the faeces were unaffected. Most of the renal effects of ACE inhibition, except the increase in urinary potassium excretion, were explicable in terms of the established functions of angiotensin II. Furthermore, results of this trial indicate that angiotensin II has no significant effect on the intestine in regulating water and electrolyte excretion via the faeces.     

Attenuation by phenylbutazone of the renal effects and excretion of frusemide in horses.

The objectives of this study were to determine the effect of phenylbutazone premedication on the pharmacokinetics and urinary excretion of frusemide in horses; and on frusemide-induced changes in urinary electrolyte excretion. Six Standardbred mares were used in a 3-way crossover design. The pharmacokinetics and renal effects of frusemide (1 mg/kg bwt i.v.) were studied with and without phenylbutazone premedication (8.8 mg/kg bwt per os 24 h before, followed by 4.4 mg/kg bwt i.v. 30 min before frusemide administration). A control (saline) treatment was also studied. Administration of frusemide without phenylbutazone led to diuresis, natriuresis, kaliuresis and chloruresis, and altered the ratio of sodium:chloride excretion from 0.4 to 1.0 in the first hour of diuresis. When frusemide and phenylbutazone were administered, sodium and chloride excretion in the first hour were significantly (P<0.05) reduced by 40 and 32%, respectively, when compared to frusemide administrationwithout phenylbutazone. The fractional clearance of sodium and chloride was also significantly reduced. Potassium excretion, potassium fractional clearance and the ratio of sodium to chloride excretion were not affected by administration of phenylbutazone. During peak diuresis, phenylbutazone did not affect the efficiency of frusemide with respect to electrolyte excretion. The plasma disposition of frusemide was not affected by phenylbutazone. However, the renal excretion of frusemide decreased by approximately 25%. We conclude that the decreased urinary excretion of frusemide by phenylbutazone led to an attenuation of frusemide-induced increases in urinary excretion of sodium and chloride. Since the efficiency of frusemide was not affected by phenylbutazone, we conclude that phenylbutazone attenuates the renal excretion of frusemide without inhibiting the intrarenal activity of frusemide in horses.     

Alterations of fluid and electrolyte balance in thoroughbred racehorses following strenuous exercise during training.

Alterations of acid-base status, and fluid and electrolyte balance subsequent to exercise in Thoroughbred racehorses in North America have not been well-characterized. Des-cribed here are the results of an observational study conducted to characterize changes in fluid and electrolytes following strenuous exercise of 16 Thoroughbreds under routine training conditions. Changes following strenuous exercise were determined for the following variables: serum concentrations of sodium (Na), potassium (K), chloride (Cl) and protein; pH of blood; osmolality of plasma and urine; body weight; and, fractional urinary excretion (FE) of Na, K and Cl. The following changes occurred during exercise: increased concentration of Na in blood; increased FE of Na; decreased concentration of Cl in blood; decreased FE of Cl; increased urinary and plasmal osmolality; weight-loss; decreased pH of blood; and, increased concentration of lactic acid. The concurrent decreased concentration of chloride in plasma and acidemia in these horses differed from the hypochloremic, metabolic alkalosis previously described among endurance horses. Acidemia was attributed to production of lactic acid by anaerobic glycolysis.     

Comparison of fractional excretion and 24-hour urinary excretion of sodium and potassium in clinically normal cats and cats with induced chronic renal failure.

The influence of induced chronic renal failure on 24-hour urinary excretion and fractional excretion of sodium and potassium was studied in cats. Induction of chronic renal failure significantly increased fractional excretion of potassium (P less than 0.0001) and sodium (P less than 0.05); however, 24-hour urinary excretion of sodium and potassium decreased slightly following induction of chronic renal failure. Fractional excretion and 24-hour urinary excretion of sodium and potassium were compared by linear regression in clinically normal cats, cats with chronic renal failure, and clinically normal and affected cats combined. In clinically normal cats, linear regression revealed only moderate correlation between fractional excretion and 24-hour urinary excretion for sodium and potassium. Linear regression of these same relationships in cats with chronic renal failure, and in clinically normal cats and cats with chronic renal failure combined, indicated low correlation. Fractional excretions of sodium and potassium were not reliable indicators of 24-hour urinary excretion of these electrolytes in cats with chronic renal failure or unknown glomerular filtration rate. Fractional excretion of potassium and sodium correlated only moderately with 24-hour urinary excretion in clinically normal cats.     

Urinary excretion of purine derivatives and plasma allantoin level in sheep and goats during fasting

The relationship between blood plasma level and urinary excretion of allantoin (AN) was examined in sheep and goats during fasting to investigate the possible use of purine derivatives (PD) in urine and/or plasma for estimating the microbial protein production in the rumen, and the further digestion in the lower guts of ruminants. Urinary AN excretion decreased markedly during fasting (0.13 mmol/kgW^0.75 per day), although urinary levels of other PD, hypoxanthine + xanthine and uric acid did not differ irrespective of the feeding condition, that is, feeding, fasting and refeeding in both species. The AN concentration in blood plasma also decreased drastically in the starvation period, and was suddenly increased on refeeding in sheep and goats, and these phenomena were very similar to those of urinary AN excretion. Therefore, there was a high positive correlation between plasma AN level and urinary AN excretion, and the coefficient of correlation was statistically significant (P < 0.01). These results clearly indicate that changes in urinary AN reflect change in plasma AN, which is induced by the catabolism of purine base in the body.     

The role of plasma protein binding on the metabolism and renal excretion of sulphadimethoxine and its metabolite N4-acetylsulphadimethoxine in pigs

The effects of plasma protein binding on the elimination of sulphadimethoxine (SDM) were examined after intravenous administration of 6.25, 12.5, 25, 50, 100 and 150 mg/kg to pigs. At an early stage of the experiment, the animals were anaesthetised by inhalation of enflurane to obtain a more exact relationship between plasma concentration and the renal excretion. SDM and its acetylated conjugate, N4-acetylsulphadimethoxine (N4-SDM) were detected in plasma and urine of all animals, and the recovery of the doses was almost complete in two animals with negligible renal excretion of SDM. The percentages of plasma protein binding of SDM and N4-SDM were almost similar, and ranged from 30 to 95%, depending on the plasma concentration. The metabolic clearance of SDM by acetylation increased when the plasma protein binding decreased. These results suggested that the main elimination route of SDM in pigs is acetylation, and that the plasma protein binding can have a large effect on the elimination of SDM in pigs. The effect of plasma protein binding on the renal clearance of SDM was not so evident, because urine pH had a much greater effect on it. The deacetylation of N4-SDM was detected after 25 mg/kg intravenous administration of N4-SDM, which suggests that the metabolic clearance of SDM is part of an acetylation-deacetylation equilibrium. Saturation of the active tubular reabsorption of SDM and of the active tubular secretion of N4-SDM was also suggested after higher doses of SDM.     

The effect of ethacrynic acid, bumetanide, frusemide, spironolactone and ADH on electrolyte excretion in ponies

The effect of ethacrynic acid, bumetanide, frusemide, spironolactone and antidiuretic hormone (ADH) on the urinary and faecal excretion of water and electrolytes by ponies was studied. Ethacrynic acid, bumetanide, and frusemide given intravenously, increased urinary sodium excretion, and, excepting frusemide, decreased faecal sodium excretion. Given by stomach tube ethacrynic acid reduced urinary and faecal sodium. Bumetanide, given intravenously, spironolactone, frusemide and ADH increased urinary sodium and all except frusemide intravenously decreased faecal sodium regardless of route of administration. Ethacrynic acid and bumetanide, given by stomach tube or intravenously decreased urinary and faecal potassium excretion, as did spironolactone and frusemide given orally. Ethacrynic acid and bumetanide given orally or intravenously, frusemide given orally and ADH intranasally reduced urinary chloride excretion; these same drugs by the same routes also reduced faecal chloride excretion. Excepting frusemide given intravenously, and ethacrynic acid orally, the effect of the drugs studied was not the same on urinary sodium excretion as on faecal sodium excretion. This suggested that different mechanisms were involved in the control of sodium excretion by the kidney and in the gut. There were similarities in the treatment of potassium and chloride by these organs.     

Effect of bile acid on hepatic excretion and storage of bilirubin in ponies.

Endogenous bilirubin uptake from plasma and biliary bilirubin excretion were determined in ponies with chronic biliary T-tube fistulas. Excreted bile was quantitatively recovered. Uptake was calculated from the plasma disappearance of 14C-labeled bilirubin. Biliary bilirubin excretion was determined directly in excreted bile. When bile acid excretion was low (during continuous drainage without bile acid replacment), bilirubin excretion was 37% less than uptake. Uptake and excretion were essentially identical when taurocholic acid was infused to replace bile acids. After depletion of the bile acid pool, replacement of bile acids (by taurocholic acid infusion) greatly increased both bilirubin excretion and its biliary concentration for approximately 1 hour. After this initial increase, bilirubin excretion was maintained at a rate approximately 30% greater than the preinfusion rate. Bile acid excretion was found to be essential for normal, endogenous bilirubin excretion.     

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.     

Metabolism and renal handling of sodium arsenate in dogs

Renal handling of sodium arsenate was studied in 5 dogs. Using a low dose (0.73 mg/kg of body weight) of sodium arsenate given IV, variable arsenite concentrations were detected in plasma and urine. Using a medium dose (7.33 mg/kg), the renal tubule cells were determined to be the probable sites of reabsorption of arsenate, reduction of arsenate to arsenite, and secretion or diffusion of the latter into urine. However, using a high dose (14.66 mg/kg), despite a similar pattern of reduction of arsenate to arsenite, marked reabsorption of arsenite into plasma took place instead of secretion or diffusion into urine. Because of reabsorption, the amount of arsenite in plasma (18.4 +/- 3.5% of the total As) was about 3 times higher than that measured during the medium dose experiment (6.0 +/- 1.0%). During the clearance experiments which lasted 110 minutes, only 40% to 45% of the arsenate infused was excreted in urine, and a minimal amount of dimethylarsinic acid (DMAA) was detected. In contrast, by the next day, DMAA was the major metabolite excreted in urine. This excretion of As as DMAA was partly due to delayed excretion of 55% to 60% As that was stored in the body and was subsequently metabolized.     

Studies on the effects of total nephrectomy in sheep.

Effects of total nephrectomy were studied in six sheep. There was no marked deterioration in the clinical condition of the animals except anorexia and reduced water intake. Three sheep survived the period of observation of 120 hours when they were euthanized. One animal suddenly died at each of 76, 80 and 100 hours. Progressive increase of blood urea nitrogen concentration was accompanied by severe metabolic acidosis in the later stages. Plasma creatinine rose significantly but the change was not marked. Plasma inorganic phosphorous and calcium decreased significantly. Unaffected plasma sodium levels were accompanied by hyperkalemia and hypochloremia. Plasma total proteins and albumin decreased significantly in the later stages. Results showed markedly different responses to total nephrectomy in sheep as compared to changes reported in cattle and nonruminants.     

Preliminary investigations into factors that affect plasma aldosterone concentrations in horses

The effect of feeding diets with low, adequate and high sodium contents on plasma aldosterone concentrations in horses and ponies was evaluated using human immunoassay kits. The effect of moderate to high intensity exercise of up to six minutes duration on plasma aldosterone concentrations in three thoroughbred- horses was also investigated. On an adequate sodium diet plasma aldosterone concentrations increased to a peak around four hours after feeding. Little daily variation was found in the pre-feeding aldosterone concentrations over three days. Feeding additional salt resulted initially in no increase in plasma aldosterone concentrations in three out of four animals. After five days all four animals had lower pre-feeding concentrations, an increase in the magnitude of the response to feeding but a decreased rise in absolute concentration. Feeding a diet with a decreased sodium content for several months did not result in a consistent change in the pre-feeding aldosterone concentrations although there were times when all three animals showed an increase in the magnitude of the aldosterone response to feeding. No correlation between changes in the fractional electrolyte excretion values determined and alterations in aldosterone response was found. Exercise resulted in a marked increase in aldosterone concentrations. The expected biological response to feeding and exercise was demonstrated with an acceptable level of reproducibility and repeatability. Samples had similar values when assayed by either of the kits evaluated.     

Pathophysiologic response of the juxtaglomerular apparatus to dietary sodium restriction in the dog.

Pathophysiologic changes in the juxtaglomerular apparatus (JGA) of the dog were induced by 10 days of dietary sodium restriction (less than 1 mEq of Na+/day). Plasma renin activity increased 12-fold and plasma aldosterone values increased 60-fold, whereas urinary sodium excretion decreased precipitously. Urinary potassium excretion remained within normal values throughout the period of sodium restriction. The JGA cell counts, determined by light microscopy, were significantly (P = less than 0.05) increased after 2 days of sodium restriction and remained increased through day 10. Adrenal gland weights and the cross-sectional width of the zona glomerulosa were not altered. Ultrastructurally, JGA cells showed progressive hypertrophy and hyperplasia. The Golgi apparatus became more prominent. The endoplasmic reticulum increased, as did the number of ribosomes. Cytoplasmic secretory granules increased in number and size from day 2 through day 6. On days 8 and 10, fewer and smaller secretory granules were encountered, even though plasma renin and aldosterone values continued to increase. In the dog maintained in a balanced sodium state, little renin is stored in cytoplasmic granules of the juxtaglomerular cells. Short-term stimulation results in increased plasma renin values and increased production and storage of renin in JGA cells. Continued stimulation results in depletion of cytoplasmic stores, although plasma renin content continues to rise, suggesting that renin is produced and secreted directly during more prolonged stimulation.     

Canine cystine urolithiasis

Cystine uroliths form as a result of a complex metabolic disturbance in amino acid metabolism and transport. The inheritance of this disease is obscure because it does not follow a standard mendelian pattern. Uroliths are a vexing clinical problem because the recurrence rate is high. Accurate diagnosis of uroliths requires use of crystallographic methods. The renal defect leading to excessive excretion of cystine is variable. The only effective method of prevention of recurrence is use of D-penicillamine, which is poorly tolerated by some dogs.     

Effects of halothane anesthesia on equine liver function

Effects of halothane anesthesia were investigated in ponies prepared surgically with chronic external biliary fistulas (T tubes) to determine the effects on liver function and biliary excretion during 2 hours of anesthesia. Four studies were performed on 2 ponies, 2 to 6 months after surgery with the enterohepatic circulation held intact between studies. Intravenous bile acid infusion was used to maintain steady-state bile flow, bilirubin, and bile acid excretion during each study. Compared with the immediate 2-hour preanesthesia values (base line), halothane caused a 138% increase in bilirubin excretion, a 60% increase in biliary bilirubin concentration, and a 43% increase in PCV. Halothane anesthesia also caused a 16% reduction in plasma bilirubin, a 46% reduction in biliary bile acid concentration, and a 27% reduction in bile acid excretion. The bile acid independent fraction of bile flow appeared to increase. Plasma aspartate transaminase concentration did not change during anesthesia. The ratio of conjugated bilirubin fractions in bile [82% to 83% disconjugates of glucuronide and glucoside (2 forms) and 17% to 18% monoconjugates of glucoside, glucuronide, and xyloside] did not change during anesthesia and less than 1% was excreted unconjugated. Halothane anesthesia did not appear to affect adversely the activity of the transferase-conjugating enzymes in the presence of an increased bilirubin load. Seemingly, greatly increased conjugated bilirubin excretion observed during halothane anesthesia was most likely the result of a combination of increased hepatic clearance from plasma and increased hepatic bilirubin production from turnover of free hepatic heme or heme from the induced cytochrome P-450 system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uric acid and phosphorus excretion in dogs with lymphosarcoma

Serum uric acid and phosphorus concentrations were determined for 27 dogs with multicentric lymphosarcoma before and after chemotherapy. Mean serum uric acid values in dogs before treatment were significantly higher (P less than 0.05) than those of a control group of healthy dogs. Serum uric acid values did not change after treatment. Of the 27 dogs, 13 had 24-hour urine collections to determine endogenous creatinine clearance and quantitation of uric acid and phosphorus excretion before and after treatment for lymphosarcoma. Mean values for 24-hour creatinine clearance before and after treatment were statistically similar in dogs with lymphosarcoma, although the values were lower than those in a normal range. Total urinary phosphorus excretions were increased significantly (P less than 0.01) after treatment without change in fractional excretion. Chemotherapeutic agents used accounted for the significant (P less than 0.05) increase in urine volume after treatment and may have affected the excretion of uric acid and phosphorus. Seemingly, dogs with uncomplicated lymphosarcoma rarely have renal dysfunction or clinically important alterations in uric acid or phosphorus excretion secondary to rapid tumor lysis. However, preexisting renal disease or systemic complications, such as hypercalcemia, may be associated with increased risk of further renal impairment during treatment.     

Renal sodium and potassium excretion in sheep given amiloride.

When amiloride was given (IV) to unanesthetized ewes, potassium excretion decreased to one-third of baseline values, and sodium excretion increased 6- to 180-fold. Potassium excretion during amiloride administration was relatively invariant with respect to duration (0 to 270 minutes) or rate of amiloride administration (0.125 to 2.0 mg/minute), but sodium excretion clearly increased with both duration and dose rate in individual experiments. This increase was independent of the rate of concomitant saline administration. Thus, sheep fed a normal ration (about 600 mEq of potassium per day) respond to amiloride as do man, dogs, and rats. The relationship of sodium excretion to rate and duration of amiloride administration is not unique to sheep, but has not been stressed in previous studies on other species.     

Fanconi Syndrome in a Labrador Retriever

A 2-year-old male Labrador Retriever was presented to the University of Missouri Veterinary Teaching Hospital with the primary complaints of polydipsia, polyuria, and joint or muscle pain. Low blood urea nitrogen concentration, hyperchloremia, and marked proteinuria were the only abnormalities in a serum biochemical profile and urinalysis. Decreased creatinine clearance and increased renal fractional excretion of sodium, potassium, calcium, and phosphorus were detected by renal clearance studies. Increased excretion of most amino acids was found by amino acid analysis of urine, but not all amino acids were lost with equal magnitude. Amino acids with secondary amino groups or basic side chains were lost at increased rates, whereas those with acidic side chains were not. These differences could be related to defects in specific renal amino acid transport mechanisms. Identification of these transport mechanisms may allow for pharmacologic intervention at the point of renal loss to alleviate clinical signs of disease.