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.     

Production and clearance of plasma triacylglycerols in ponies fed diets containing either medium-chain triacylglycerols or soya bean oil

The hypothesis was tested that feeding ponies a diet containing medium-chain triacylglcyerols (MCT) instead of soya bean oil causes an increase in the production of plasma triacylglycerols, which, under steady-state conditions, is associated with an increased clearance of triacylglycerols. Six ponies were fed rations containing either MCT or an isoenergetic amount of soya bean oil according to a cross-over design. The concentration of MCT in the total dietary dry matter was about 13%. When the ponies were fed the diets for 3 weeks, plasma triacylglycerol concentrations were 0.42 +/- 0.09 and 0.17 +/- 0.03 mmol/l (mean +/- SE, n = 6; p < 0.05) for the MCT and soya bean-oil treatment, respectively. Plasma triacylglycerol production was assessed using the Triton method and clearance with the use of Intralipid(R) infusion. Plasma triacylglycerol production was 2.91 +/- 0.88 and 0.50 +/- 0.14 micromol/l.min (means +/- SE, n = 4; p < 0.05) for the diets containing MCT and soya bean oil, respectively. It is suggested that the calculated rates of triacylglycerol production are underestimated, the deviation being greatest when the ponies were fed the ration of soya bean oil. Triacylglycerol clearance rates were calculated on the basis of group mean values for both the fractional clearance rate and the baseline levels of plasma triacylglycerols; the values were 4.28 and 3.52 micromol/l.min for MCT and soya bean oil feeding, respectively. The mean, absolute clearance rates as based on those found in individual ponies did not show an increase when the diet with MCT was fed. Nevertheless, it is concluded that the data obtained support our hypothesis.     

Effect of Food Availability on the Physiological Responses to Water Deprivation in Ponies

Six ponies were deprived of drinking water and food and compared over 24 hours with nondeprived ponies, ponies deprived of water but with food available, and ponies deprived of food but with water available. When food was eaten during water deprivation, plasma osmolality rose 4% from 284 mOsm/kg to 295 mOsm/kg. During water and food deprivation, plasma osmolality failed to rise, even over 24 hours, and usually fell. Packed cell volume was higher when food but not water was available. Food and/or water deprivation had no significant effect on plasma protein concentration. When food was available, the ponies drank three times more water (13.1 ± 2.1 kg) than when water but not food was available (3.5 ± 1.4 kg). Blood volume changes were calculated from packed cell volume and plasma protein data, and it was found that blood volume did not change significantly with deprivation. Urine volume did not vary with deprivation, but free water clearance changed significantly, falling when food but not water was available. Under these conditions, blood volume is maintained, but the mechanisms are not clear. When deprived of both drinking water and food, ponies failed to develop the hyperosmolality expected under these conditions. Water deprivation while food is available is a more powerful challenge to water and electrolyte homeostasis than deprivation of both food and water.     

Cardiovascular, acid-base, electrolyte, and plasma volume changes in ponies developing alimentary laminitis.

Twelve Shetland ponies were fed a high-starch ration. Seven ponies which had a transitory metabolic acidosis developed laminitis 56 hours (+/- 3.5, SEM) after overfeeding. These ponies also developed persistent hypokalemia, hyperthermia, and increased heart rate 24 hours before the onset of lameness. Serum sodium, serum chloride, hematocrit, plasma volume, and blood volume were unchanged. At the onset of clinical signs of laminitis, cardiac output and blood pressure increased, but total peripheral resistance was unchanged. None of the measured or calculated values predicted the onset of laminitis. Hypertension appeared to be a response to, rather than a cause of, lameness. Three of the remaining ponies apparently died of shock 29.3 +/- 2.7 hours after overfeeding. All 3 had severe metabolic acidosis; decreased cardiac output, systemic arterial pressure, and plasma volume; and increased hematocrit, total peripheral resistance, and pulmonary vascular resistance. The 11th pony was unaffected and the 12th pony was euthanatized.     

Effects of phenobarbital treatment on 3-methylindole toxicosis in ponies

To study the role of cytochrome P-450-dependent mixed function oxidase reactions in equine 3-methylindole (3MI) toxicosis, ponies were given 20 mg of phenobarbital/kg of body weight at 72, 60, 48, 36, and 24 hours before 100 mg of oral 3MI/kg to induce cytochrome P-450 or no treatment (controls). Maximal 3MI plasma concentration was decreased and clearance was faster in phenobarbital-treated ponies. Plasma 3MI was still detectable 12 and 36 hours after dosing in phenobarbital-treated and control ponies, respectively. Phenobarbital treatment induced a distribution phase with transition from a 1-compartment to a 2-compartment extravascular model. Bronchiolitis occurred in all ponies 72 hours after 3MI, but was more severe in those treated with phenobarbital. Appearance of a distribution phase, increased total body clearance, and more severe bronchiolitis in phenobarbital-treated ponies indicated that mixed function oxidases are involved in metabolism and conversion of 3MI to a toxic metabolite.     

Pharmacokinetics of phenolsulfonphthalein in horse and pony mares

Pharmacokinetics of phenolsulfonphthalein (PSP) in horse and pony mares was determined after injection of 1 mg/kg of body weight, IV. A plasma PSP concentration vs time curve was described adequately in horses and ponies by an open, 2-compartment model. There were significant differences in the elimination phase parameters, apparent volume of distribution at steady state, and apparent volume of distribution of horses and ponies. The harmonic mean elimination half-life of PSP in horses was significantly longer (P less than 0.001) than that in the ponies (16.4 and 10.0 minutes, respectively). The mean plasma clearance of PSP in horses was significantly (P less than 0.05) less than that in ponies (0.00554 and 0.00701 L/min/kg, respectively). There was no difference between horses and ponies in the metabolic clearance of PSP. The fraction of the administered dose of PSP excreted in the urine in the first 15 minutes was not significantly different between horses and ponies.     

Indwelling Cecal Catheters for Fluid Administration in Ponies

Two different fluid solutions were infused through percutaneous cecal catheters in 6 healthy ponies to determine the effects on body weight; CBC; packed cell volume (PCV); total plasma protein concentration; plasma fibrinogen concentration; abdominal fluid analysis; concentrations of blood urea nitrogen (BUN), serum creatinine, Ca, total CO₂ (TCO₂), Na, CI, K, and P; and fractional clearance (FC) of Na, CI, K, and P. During intracecal administration of solution 1, FC_Na and FC_CI were significantly increased, whereas FC_K and BUN were significantly decreased. During administration of solution 2, FC_Na and serum P were significantly increased, while PCV was significantly decreased. All ponies developed peritonitis during the study. Complications included catheter-related problems, diarrhea, laminitis, and hypocalcemia. We concluded that hydration and electrolyte balance could be maintained by administration of crystalloid solutions intracecally, but that complications were associated with the procedure.     

Hepatobiliary transport of indocyanine green and sulfobromophthalein in fed and fasted horses

Fasting is associated with unconjugated hyperbilirubinemia in several species, including the horse. Studies in ponies showed that a 3-day fast decreased plasma clearance of bilirubin, cholic acid, and sulfobromophthalein (BSP). Since these organic anions are conjugated with different substrates, it is possible that observed differences in plasma clearance result from a general decrease in hepatic conjugating capacity during the animals' fasting. To test this hypothesis, the effects of a 3-day fast on plasma clearance of IV injected BSP (4.4 to 5.1 mg/kg), which is conjugated to glutathione, and indocyanine green (ICG; 0.8 to 1.1 mg/kg), which is not conjugated, were studied in 10 healthy horses and 2 ponies with diverted enterohepatic circulations (indwelling T tubes). Blood samples were obtained for 30 minutes after injection, and bile samples from ponies were obtained for 3 hours. Fasting increased plasma bilirubin concentration in all animals studied (from 1.03 +/- 0.337 mg/dl in control animals to 3.49 +/- 1.01 mg/dl in fasted animals). Kinetic values of ICG disappearance were determined from single exponential functions, and those for BSP were determined from both single and curvilinear (2-exponential) functions. Plasma clearance of BSP in fed horses (8.65 +/- 1.02 ml X min-1 X kg-1) was greater than clearance of ICG (3.54 +/- 0.67 ml X min-1 X kg-1), results similar to those reported in dogs, cats, rats, and persons. Fasting significantly decreased fractional plasma disappearance rate of both BSP (-36%) and ICG (-58%) and similarly reduced plasma clearance (BSP,-48%; ICG,-55%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Additive effects of a sodium chloride restricted diet and furosemide administration in healthy dogs.

OBJECTIVE: To determine the effects of a low or high sodium (Na) diet with or without furosemide administration on plasma electrolyte concentrations and the renin-angiotensin-aldosterone system in healthy dogs. ANIMALS: 20 healthy adult dogs. PROCEDURE: Dogs were randomly allotted to 4 groups of 5 dogs each as follows: dogs fed a low Na diet (0.08% Na and 0.8% chloride [CI] on a dry matter [DM] basis); dogs fed a low Na diet with added NaCl (1.0% Na and 2.2% Cl on a DM basis); dogs fed a low Na diet and treated with furosemide (2 mg/kg of body weight, PO, q 12 h); and dogs fed a low Na diet with added NaCl and treated with furosemide. Plasma electrolyte concentrations were measured on days 0, 21, and 35. Plasma renin activity and aldosterone concentration were analyzed by use of radioimmunoassays on days 0, 21, 35, and 53. RESULTS: Furosemide treatment significantly decreased plasma Cl concentration and significantly increased plasma renin activity and aldosterone concentration. Dogs fed a low Na diet had significantly higher plasma renin activities and plasma aldosterone concentrations. A significant interaction between a low Na diet and furosemide administration resulted in the lowest plasma Cl concentrations, highest plasma renin activities, and highest plasma aldosterone concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, feeding a low Na diet and administering furosemide resulted in an additive effect on plasma Cl concentration, renin activity, and aldosterone concentration, which may be an important consideration for treating dogs with cardiac disease.     

Effect of dietary fructans and dexamethasone administration on the insulin response of ponies predisposed to laminitis

OBJECTIVE: To determine whether pasture, and specifically the addition of fructan carbohydrate to the diet, induces exaggerated changes in serum insulin concentration in laminitispredisposed (LP) ponies, compared with ponies with no history of the condition, and also to determine insulin responses to the dexamethasone suppression test. DESIGN: Prospective study. ANIMALS: 10 LP and 11 control adult nonobese mixed-breed ponies. PROCEDURES: Insulin-modified IV glucose tolerance tests were performed (5 ponies/group). In diet studies, ponies were kept on pasture and then changed to a hay diet (10 ponies/group). Second, ponies were maintained on a basal hay diet (4 weeks) before being fed a hay diet supplemented with inulin (3 g/kg/d [1.4 g/lb/d]). Serum insulin and plasma glucose concentrations were analyzed before and after dietary changes. Serum cortisol and insulin concentrations were also measured in a standard dexamethasone suppression test. RESULTS: The LP ponies were insulin resistant (median insulin sensitivity of 0.27 x 10(4) L min(-1) mU(-1) in LP ponies, compared with 0.64 x 10(4) L min(-1) mU(-1) in control ponies). Median insulin concentration in LP ponies was significantly greater than that in control ponies at pasture, decreased in response to feeding hay, and was markedly increased (5.5-fold) following the feeding of inulin with hay. The LP ponies had a greater increase in serum insulin concentration at 19 hours after dexamethasone administration (median, 222.9 mU/L), compared with control ponies (45.6 mU/L). CONCLUSIONS AND CLINICAL RELEVANCE: Nonobese ponies predisposed to develop laminitis had compensated insulin resistance, and this phenotype was revealed by feeding plant fructan carbohydrate or by dexamethasone administration.     

Effect of Concentrate form on blood and gastric fluid variables in ponies

Eight ponies were used in a two-period, crossover design experiment to determine if the physical form of a concentrate feed affected selected gastric fluid and blood variables. Each pony had been surgically fitted with a gastric cannula 2 years prior to the study. In each 29-day period, four ponies received hay and a pelleted concentrate and four ponies received hay and a textured (sweet feed) concentrate. The concentrate portions of the diets were identical except for physical form and contained 57.5% corn, 25% oat, 8.5% soybean meal, 7% molasses and 2% minerals and vitamins. On day 15 of each period, the ponies received a concentrate meal (.4% of body weight) and blood and gastric fluid samples were obtained for 9 h after feeding.Feeding a concentrate meal resulted in increased plasma glucose, serum insulin, gastric fluid glucose and gastric fluid L-lactate concentrations. The pH of gastric fluids before feeding ranged from 1.4 to 8.36, but gastric fluid pH was at least 5.0 within 30 min of eating in all ponies. Few effects of concentrate form were observed, but plasma glucose concentrations at 150 and 180 min after feeding were higher (P < .05) when the ponies received the pelleted feed than when they received the textured feed. One objective of the study was to evaluate rate of gastric emptying by making total gastric collections at 2, 4, 6 and 8 h after feeding on days 22 and 29 of each period. Unfortunately, the gastric cannulae did not prove suitable for making total gastric collections, thus no con- clusions regarding the effect of concentrate form on rate of digesta passage from the stomach could be made.     

Diurnal variation in concentrations of various markers of bone metabolism in dogs.

OBJECTIVE: To evaluate diurnal variation in concentrations of selected markers of bone metabolism in dogs. ANIMALS: Ten 3- to 4-year-old ovariectomized Beagles. PROCEDURE: Blood and urine samples were obtained in the morning before dogs were fed (8 AM) and then at 2-hour intervals for 24 hours. This procedure was repeated 2 weeks later. Concentrations of osteocalcin (OC) and carboxy terminal telopeptide of type-I collagen (ICTP) were measured in serum, using a radioimmunoassay; concentrations of hydroxyproline (HYP), pyridinoline (PYD), and deoxypyridinoline (DPD) were analyzed in urine. Hydroxyproline concentration was measured by means of a colorimetric test, whereas PYD and DPD concentrations were quantified by use of high-performance liquid chromatography. RESULTS: In both parts of the study, HYP concentrations increased significantly, compared with values before feeding, until 8 hours after feeding; HYP concentrations then returned to prefeeding values. Concentrations of DPD and PYD decreased from before feeding until 2 PM and then increased until 8 PM. The ICTP concentrations slowly decreased until 4 PM but returned to prefeeding values thereafter. In both parts of the study, concentrations of OC decreased during the day and then increased to reach values similar to those obtained before feeding. CONCLUSIONS: Changes in the concentrations of bone markers were detected throughout the day in the dogs of this study. Increase in HYP concentration most likely was related to feeding. As documented for bone resorption and formation in other species, circadian rhythms were evident for concentrations of DPD, PYD, and OC. Investigators should consider the time of sample collection when measuring these markers.     

Effects of oral administration of furosemide and torsemide in healthy dogs

OBJECTIVE: To investigate the diuretic effects, tolerability, and adverse effects of furosemide and torsemide after short- and long-term administration in healthy dogs. ANIMALS: 8 mixed-breed dogs. PROCEDURES: In a crossover study, furosemide (2 mg/kg), torsemide (0.2 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally to each dog every 12 hours for 14 days. Blood and urine samples were collected before the study (baseline data) and at intervals on the 1st (short-term administration) and 14th day (long-term administration) of treatment for assessment of urine volume and specific gravity and selected clinicopathologic variables including BUN, creatinine, and aldosterone concentrations, and creatinine clearance. RESULTS: Compared with the baseline value, short-term administration of furosemide or torsemide immediately increased urine volume significantly; after long-term administration of either drug, urine specific gravity decreased significantly. Compared with the effect of placebo, the 24-hour urine volume was significantly increased after short-term administra-tion of furosemide or torsemide. In addition, it was significantly increased after long-term administration of torsemide, compared with that of short-term administration. Long-term administration of furosemide or torsemide increased the BUN and plasma creatinine con-centrations, compared with the baseline value. Compared with the baseline value, plasma aldosterone concentration was significantly increased after long-term administration of either drug and was significantly higher after torsemide treatment than after furosemide treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, diuretic resistance developed after 14 days of furosemide, but not torsemide, administration; however, both loop diuretics were associated with increased BUN and plasma creatinine concentrations, compared with values before treatment.     

Acute hemolytic anemia after oral administration of L-tryptophan in ponies

The hematologic and pathologic effects of orally administered L-tryptophan and indoleactic acid and of L-tryptophan administered IV were studied in ponies. Sixteen adult Shetland ponies were allotted into 4 experimental groups. Group 1 consisted of 5 ponies (1-5) given 0.6 g of tryptophan/kg of body weight in a water slurry via stomach tube. Group 2 included 4 ponies (6-9) given 0.35 g of tryptophan/kg orally. Group-3 ponies (10-13) were given 0.35 g of indoleacetic acid/kg orally. Group 4 consisted of 3 ponies (14-16) given a single 4-hour IV infusion of 0.1 g of tryptophan/kg. Restlessness, increased respiratory rate, hemolysis, and hemoglobinuria were detected in 4 of the 5 group-1 ponies. Only pony 7 in group 2 developed hemolysis, hemoglobinuria, and a significant increase in respiratory rate. Renal pathologic lesions, consistent with hemoglobinuric nephrosis, were seen in ponies 2, 4, 5, and 7. Bronchiolar degeneration was evident in 4 of 9 ponies given tryptophan orally. The importance of these respiratory lesions was unknown. Clinical or pathologic abnormalities were not noticed in the ponies of groups 3 and 4. Mean plasma tryptophan values increased significantly in groups 1 and 2 at 6 hours after dosing. A second peak of tryptophan was detected in both groups at 12 hours. Values returned to predose values by 48 hours. Plasma indole and 3-methylindole concentrations were detectable in only 2 ponies (4 and 7). In vitro incubations of cecal fluid from ponies 6, 8, and 9 yielded a percentage conversion of tryptophan to indole of 16.75%, 5.84%, and 7.96%, respectively. 3-Methylindole was not produced. These results suggested that indole was the major metabolite of orally administered tryptophan in these ponies.     

Pharmacokinetics of phenylbutazone in two age groups of ponies: a preliminary study

A clinical dose rate (4.4 mg/kg bodyweight) of phenylbutazone was administered intravenously and orally to six Welsh mountain ponies to provide data on the pharmacokinetics and bioavailability of the drug. In three, three-year-old ponies, clearance of the drug from plasma after intravenous administration was almost twice as rapid as in three ponies aged eight to 10 years. After oral administration, plasma phenylbutazone levels were greater in the older ponies, the area under the plasma concentration time curve being almost twice as high. This did not result from more efficient absorption but from slower plasma clearance. The fractional absorption of phenylbutazone was similar in young and older ponies, 0.78 and 0.75, respectively. The 24 hour urinary excretion of phenylbutazone and its hydroxylated metabolites, oxyphenbutazone and gamma-hydroxyphenylbutazone, accounted for approximately 25 per cent of the administered intravenous dose in both young and older ponies. The possible fate(s) of the remaining 75 per cent were considered.     

Cephalexin in ponies: a preliminary investigation

The administration of a single dose of the antibacterial agent cephalexin intramuscularly to six ponies at a dose rate of 7 mg/kg was well tolerated. No reactions at the injection site were apparent. It was absorbed rapidly and reached a mean peak plasma concentration of 6.77 micrograms/ml after a mean of 1.41 hours; plasma concentrations above 2.0 and 0.5 micrograms/ml were maintained for 3.8 and 9.8 hours, respectively.     

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)     

Assessing the efficiency of a pharmacokinetic-based algorithm for target-controlled infusion of ketamine in ponies

The objective of this study was to assess a pharmacokinetic algorithm to predict ketamine plasma concentration and drive a target-controlled infusion (TCI) in ponies.Firstly, the algorithm was used to simulate the course of ketamine enantiomers plasma concentrations after the administration of an intravenous bolus in six ponies based on individual pharmacokinetic parameters obtained from a previous experiment. Using the same pharmacokinetic parameters, a TCI of S-ketamine was then performed over 120 min to maintain a concentration of 1 μg/mL in plasma. The actual plasma concentrations of S-ketamine were measured from arterial samples using capillary electrophoresis.The performance of the simulation for the administration of a single bolus was very good. During the TCI, the S-ketamine plasma concentrations were maintained within the limit of acceptance (wobble and divergence <20%) at a median of 79% (IQR, 71–90) of the peak concentration reached after the initial bolus. However, in three ponies the steady concentrations were significantly higher than targeted.It is hypothesized that an inaccurate estimation of the volume of the central compartment is partly responsible for that difference. The algorithm allowed good predictions for the single bolus administration and an appropriate maintenance of constant plasma concentrations.     

Protein supplement resistant against ruminal degradation as a factor improving utilization of urea in ruminant feeding

The metabolic and productive effects of the blood meal and formaldehyde (FA) treated casein supplements (5-10% of crude protein content) given with urea concentrates in sheep and fattening bulls were investigated. The blood meal has a similar composition of essential amino acids (EAA) to casein. The mean solubility of the FA treated casein and the blood meal after 6 hours of incubation in the sterilized rumen contents amounted 10.5% and 8.5% respectively. The average rumen ammonia concentration and plasma urea level was the highest in bulls fed urea ration without protected protein supplement. The supplementation of this ration with blood meal diminished the large daily fluctuation of plasma AA level and increased plasma EAA/NEAA ratio. The blood meal supplement improved the nitrogen retention in sheep (14%) and body gains in bulls (9%) but did not influence digestible coefficients and rumen protein synthesis in sheep.