Demonstration of thiopurine methyltransferase activity in the erythrocytes of cats

Azathioprine is a purine analogue used as an immunosuppressive and immunomodulator agent in various mammals, including cats. Several adverse reactions have been reported and have limited the use of the drug in the cat. Adverse reactions to azathioprine in humans have been correlated with reduced activity of thiopurine methyltransferase (TPMT) in erythrocytes. The purpose of this preliminary study was to determine if cats have TPMT activity in their erythrocytes and to compare the values obtained with the normal range for humans and the normal range for dogs in a preliminary report. Activity of the enzyme was measured in blood samples drawn from 41 cats. Blood also was taken from 5 dogs. The mean erythrocyte TPMT activity in the cats was 2.4 +/- 0.4 nmol (range, 1.2-3.9 nmol) per hour per milliliter of red blood cells (U/mL RBC) or 2-8 nmol per hour per gram of hemoglobin (U/g Hb). This range was far lower than the normal human range (8-15 U/mL RBC; 16-33 U/g Hb) and was of monopolar distribution. This observation apparently precludes any diagnostic purpose in assaying erythrocyte TPMT in this species. Erythrocyte TPMT activity in the 5 dogs ranged from 5.5 to 13.1 U/mL RBC (11-27 U/g Hb), which was comparable with normal and carrier ranges for humans, but proof of TPMT genetic polymorphism in either species will require genotyping studies.     

Thiopurine methyltransferase activity in red blood cells of dogs

Thiopurine methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurine medications such as azathioprine. In humans, activity varies widely among individuals, primarily because of genetic polymorphisms. Low TPMT activity increases the risk of myelosuppression from azathioprine and 6-mercaptopurine, whereas high TPMT activity is associated with poor drug efficacy. The purpose of this study was to determine whether dogs also show a wide range of TPMT activity. Heparinized blood samples were obtained from 177 dogs associated with a veterinary teaching hospital. Red blood cell (RBC) TPMT activity was measured by means of a modification of a radiochemical method as established for use in people. TPMT activity varied across a 9-fold range (7.9-71.8 U of RBC per milliliter; median, 21.7). Variation in TPMT activity was not associated with age, sex, or neutering status. Giant Schnauzers had much lower TPMT activity (7.9-20 U of RBC per milliliter; median, 13.1; P < .001) than did other breeds, and Alaskan Malamutes had much higher TPMT activity (22.7-71.8 U of RBC per milliliter; median, 36.0; P < .001) than did other breeds. Such variations in TPMT activity in the canine population and within groups of related dogs could affect thiopurine drug toxicity and efficacy in canine patients.     

Relationship between red blood cell thiopurine methyltransferase activity and myelotoxicity in dogs receiving azathioprine

Thiopurine methyltransferase (TPMT) produces inactive metabolites of azathioprine and, in humans, has a variable amount of activity. Humans with low TPMT activity commonly develop myelotoxicity when receiving azathioprine. Our study sought to characterize the distribution of TPMT activity in a population of dogs and to determine whether the pretreatment knowledge of red blood cell (RBC) TPMT activity could predict myelotoxicity in dogs receiving azathioprine. RBC TPMT activity was measured in 299 healthy dogs, and 9 dogs that represented a wide range of enzyme activity received azathioprine at a standard therapeutic dose for 30 days. TPMT activity in healthy dogs was log normally distributed and varied over an approximately 7-fold range. Geometric mean, minimum, and maximum RBC TPMT activities were 37.1, 16.3, and 115 nmol per gram of hemoglobin (gHb) per hour, respectively. TPMT deficiency was not identified. Two populations of TPMT activity in dogs were detected by statistical modeling (commingling analysis). Dogs with intermediate TPMT activity (14-38 nmol/gHb/h) receiving azathioprine had significantly lower neutrophil counts during week 4 than during weeks 0-3, whereas those with high activity (>39 nmol/gHb/h) did not have a significant change in neutrophil count. An analysis of TPMT activity in 6 dogs with a history of azathioprine-associated myelotoxicity in a clinical setting revealed either intermediate or high TPMT enzyme activity in all dogs, suggesting that TPMT activity, as measured in RBCs, is not the sole cause of severe azathioprine-associated myelosuppression in dogs.     

Glutathione peroxidase activity in whole blood and plasma of horses of different ages, sexes and different use]

GSH-Px activity in blood and plasma of 269 horses was determined and interrelated to age, sex, and type of use or breed. Furthermore values in blood were related to hematocrit and hemoglobin contents. Trotters and riding horses had higher GSH-Px activities in plasma as well as in blood (0.83 +/- 0.22 and 0.79 +/- 0.23 U/ml plasma or 27.2 +/- 4.3 and 24.0 +/- 7.0 U/ml blood) than Thoroughbreds in training and yearlings (0.61 +/- 0.,14 and 0.56 +/- 0.16 U/ml plasma or 20.6 2 +/- 6.9 and 24.6 +/- 4.3 U/ml blood). 3 to 6 years old Thoroughbreds had higher GSH-Px-activities than 1 to 2 years old ones. Colts and fillies did not have differing values.     

Pharmacokinetics of selamectin following intravenous,oral and topical administration in cats and dogs

The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.     

Reference values for cortisol, T4 and T-uptake in different horse groups using the fluorescence polarization immunoassay (FPIA)

Reference values for Cortisol, T4 and T-Uptake, determined with the Fluorescence-Polarization-Immunoassays (FPIAs) in blood-plasma of different horse groups were established. The highest Cortisol values were measured in blood samples from thoroughbred racehorses and riding horses taken between 7 and 8 a.m. (181 +/- 37 and 268 +/- 43 nmol/l), the lowest gained between 5 and 6 p.m. (69 +/- 45 and 85 +/- 32 nmol/l respectively). Peak values for T4 in riding horses were found in blood samples collected between 1 and 2 p.m. (28.2 +/- 5.7 nmol/l) followed by the samples taken at 5-6 p.m. and 7-8 a.m. T-Uptake values did not show a diurnal variation. Values of thoroughbred racehorses were much lower than in thoroughbred broodmares and riding horses (0.11 +/- 0.03, 0.18 +/- 0.03 and 0.24 +/- 0.05 units). The blood samples collected on 5 successive days showed significant variations for Cortisol. T4-values were stable whilst T-Uptake had small variations.     

New techniques to measure blood cholinesterase activity in domesticated animals.

A macromethod and a semimicromethod were developed to measure erythrocyte acetylcholinesterase activity in cattle, sheep, goats, horses, dogs, and swine, and to measure plasma cholinesterase activity in horses, dogs, and swine. Comparison of the 2 methods with erythrocytes of sheep, cattle, goats, and horses indicated both methods gave similar results. They can be done in a shorter time and are more sensitive than Michel's method. Normal deltapH values per minutes, with standard deviations for blood cholinesterase activity of animals of different ages, sexes, breeds, and species, were: 0.76 +/- 0.12/30; 0.65 +/- 0.10/15; 0.69 +/- 0.19/45; 0.78 +/- 0.11/45; 0.63 +/- 0.11/45; and 0.71 +/- 0.06/25 for sheep, cattle, goats, horses, dogs, and swine erythrocyte acetylcholinesterase, respectively; and 0.66 +/- 0.18/20; 0.67 +/- 0.20/30, and 0.46 +/- 0.05/60 for horses, dogs, and swine plasma cholinesterase, respectively. It was shown that either the chloride or the iodide salt of acetylcholine can be used as the enzyme substrate. tin blood samples stored at 5 C for 24 hours, there was no significant change of the enzymatic activity.     

Comparative pharmacokinetics of yohimbine in steers, horses and dogs.

In steers, horses and dogs, the comparative pharmacokinetics of yohimbine were determined using model-independent analysis. The intravenous dose of yohimbine was 0.25 mg/kg of body weight in steers, 0.075 or 0.15 mg/kg in horses, and 0.4 mg/kg in dogs. The mean residence time (+/- SD) of yohimbine was 86.7 +/- 46.2 min in steers, 106.2 +/- 72.1 to 118.7 +/- 35.0 min in horses, and 163.6 +/- 49.7 min in dogs. The mean apparent volume of distribution of yohimbine at steady state was 4.9 +/- 1.4 L/kg for steers, 2.7 +/- 1.0 to 4.6 +/- 1.9 L/kg for horses, and 4.5 +/- 1.8 L/kg for dogs. The total body clearance of yohimbine was 69.6 +/- 35.1 mL/min/kg for steers, 34.0 +/- 19.4 to 39.6 +/- 16.6 mL/min/kg for horses, and 29.6 +/- 14.7 mL/min/kg for dogs. Between-species comparisons indicated that the mean area under the serum concentration versus time curve was significantly greater (P less than 0.05) in dogs than in horses. There were no significant differences (P greater than 0.05) between the means for the apparent volume of distribution, clearance, mean residence time, terminal rate constant, and area under the curve between horses given the two doses of yohimbine. The harmonic mean effective half-life (+/- pseudo standard deviation) of yohimbine was 46.7 +/- 24.4 min in steers, 52.8 +/- 27.8 to 76.1 +/- 23.1 min in horses, and 104.1 +/- 32.1 min in dogs. The data may explain why steers, horses, and dogs given certain sedatives and anesthetics do not relapse when aroused by an intravenous injection of yohimbine hydrochloride.     

N3 potentials in response to high intensity auditory stimuli in animals with suspected cochleo-saccular deafness

We describe a previously un-reported vertex-negative potential evoked by high intensity click auditory stimuli in some dogs and cats with suspected cochleo-saccular deafness. Brainstem auditory evoked potential tracings from 24 unilaterally or bilaterally deaf animals, 22 dogs and 2 cats, among which 21 belonged to breeds with high prevalence of suspected or histologically confirmed cochleo-saccular deafness, were studied retrospectively. Values for latency, amplitude and threshold of this potential in dogs were 2.15+/-0.23 ms, 0.49+/-0.25 microV, and 91.9+/-4.7 dB NHL, respectively (mean+/-SD). Latency and threshold values in cats were in the mean+/-2 SD range of the dog values. Sensitivity to click stimulus polarity and to click stimulus delivery rate pointed towards a neural potential instead of a receptor potential. The vertex-negative wave observed in these animals shares all characteristics with the N3 potential described in some deaf humans with cochlear deafness, where it is presumed to arise from saccular stimulation. The combined degeneration of cochlea and sacculus usually reported in deaf white dogs and cats suggest that N3 may have a different origin in these species.     

Mammalian erythrocyte glutathione reductase: kinetic constants and saturation with cofactor.

Glutathione reductase (GR) was studied in erythrocytes of horses, cats, dogs, and man. Glutathione reductase activity was measured in hemolysates with and without preincubation of hemolysates with flavinadenine dinucleotide. The percentage saturation of GR apoenzyme with cofactor (flavin-adenine dinucleotide) was lower in cats and dogs than in horses or man. The greatest amount of inactive apoenzyme was in feline erythrocytes. Total GR activity listed in order by species is cat greater than man greater than dog greater than horse. Kinetic constants for oxidized glutathione and reduced nicotinamide-adenine dinucleotide phosphate were determined in each species. Although kinetic constant (reduced nicotinamide-adenine dinucleotide phosphate) values for GR were similar, considerable species variation was observed in the kinetic constant (oxidized glutathione) for GR. The kinetic constant (oxidized glutathione) for equine GR was approximately 3 times that for human GR, with intermediate values determined for feline and canine GR.     

Evaluation of a rebound tonometer for measuring intraocular pressure in dogs and horses

OBJECTIVE: To compare intraocular pressure (IOP) measurements obtained with a rebound tonometer in dogs and horses with values obtained by means of applanation tonometry and direct manometry. DESIGN: Prospective study. ANIMALS: 100 dogs and 35 horses with clinically normal eyes, 10 enucleated eyes from 5 dogs, and 6 enucleated eyes from 3 horses. PROCEDURES: In the enucleated eyes, IOP measured by means of direct manometry was sequentially increased from 5 to 80 mm Hg, and IOP was measured with the rebound tonometer. In the dogs and horses, results of rebound tonometry were compared with results of applanation tonometry. RESULTS: For the enucleated dog and horse eyes, there was a strong (r2 = 0.99) linear relationship between pressures obtained by means of direct manometry and those obtained by means of rebound tonometry. Mean +/- SD IOPs obtained with the rebound tonometer were 10.8 +/- 3.1 mm Hg (range, 5 to 17 mm Hg) and 22.1 +/- 5.9 mm Hg (range, 10 to 34 mm Hg) for the dogs and horses, respectively. Mean IOPs obtained with the applanation tonometer were 12.9 +/- 2.7 mm Hg (range, 8 to 18 mm Hg) and 21.0 +/- 5.9 mm Hg (range, 9 to 33 mm Hg), respectively. Values obtained with the rebound tonometer were, on average, 2 mm Hg lower in the dogs and 1 mm Hg higher in the horses, compared with values obtained with the applanation tonometer. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the rebound tonometer provides accurate estimates of IOP in clinically normal eyes in dogs and horses.     

Blood vitamin and choline concentrations in healthy domestic cats, dogs, and horses

Blood concentrations of thiamin, biotin, nicotinates, pantothenates, folates, riboflavin, vitamins A, B6, B12, C, E, beta-carotene and choline were analyzed in healthy animals (23 horses, 25 dogs, and 29 cats). B-Complex vitamins and choline also were analyzed in the liver of the dogs and cats. Vitamin concentrations in the blood and livers of dogs were similar; however, blood vitamin A and beta-carotene concentrations were lower in the cat than in the dog. Horses had a higher B12 blood concentration than did the dogs and cats. These data can be useful for detecting overt and hidden vitamin deficits in these species due to various conditions.     

Comparison of pyrimidine 5'nucleotidase activity in erythrocytes of sheep, dogs, cats, horses, calves, and Mongolian gerbils

Pyrimidine 5'nucleotidase (P5N) activities of erythrocytes for Mongolian gerbils, cats, dogs, sheep, horses, and calves were measured, using a radiometric technique with [14C]cytidine monophosphate as the substrate. Erythrocytes of gerbils had the highest activity [1,177.1 +/- 133.6 mU/g of hemoglobin (Hb)]. Feline erythrocytes had 327.4 +/- 204.4 mU/g of Hb. Canine erythrocytes had 148.0 +/- 19.8 mU/g of Hb. Ovine erythrocytes (44.3 +/- 20.9 mU/g of Hb), equine erythrocytes (30.0 +/- 15.9 mU/g of Hb), and bovine erythrocytes (14.1 +/- 6.9) had relatively low P5N activity. The P5N activity was approximately proportional to the reticulocyte percentage of and inversely proportional to the mean erythrocyte life span in these species.     

Effects of plasma sample storage on blood ammonia, bilirubin, and urea nitrogen concentrations: cats and horses

Ten horses, a pony, and 13 cats were used to evaluate base-line blood ammonia, bilirubin, and urea nitrogen concentrations and to determine The effects of prolonged cold storage (-20 degrees C) before assay. Base-line plasma ammonia concentrations in cats (0.992 +/- 0.083 [SE] micrograms/ml) did not change significantly after 48 hours of storage (0.871 +/- 0.073 micrograms/ml); however, they were increased 4.2- and 13-fold after 168 and 216 hours of storage, respectively. In contrast to base-line plasma-ammonia values in cats, those of horses were significantly (0.265 +/- 0.044 micrograms/ml) lower, and significantly increased from base-line values after 48 hours of storage (0.861 +/- 0.094 micrograms/ml) and continued to increase 25.6-fold at 168 hours and 18.4-fold at 216 hours. Plasma urea nitrogen concentrations in cats (25.8 +/- 1.06 mg/dl) and horses (11.2 +/- 0.749 mg/dl) did not change significantly during 168 hours of storage. Total plasma bilirubin values from both cats (0.19 +/- 0.049 mg/dl) and horses (0.75 +/- 0.064 mg/dl) also did not change significantly during storage. These results indicate that feline plasma samples for ammonia determinations may be stored at -20 degrees C for up to 48 hours, whereas equine plasma ammonia values tend to increase during that time. The reason for the increase remains unexplained. Both feline and equine plasma urea nitrogen and total bilirubin are stable for at least 168 hours of storage at -20 degrees C.     

Comparative pharmacokinetics of meloxicam in clinically normal horses and donkeys

OBJECTIVE: To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species. ANIMALS: 5 clinically normal horses and 5 clinically normal donkeys. PROCEDURES: Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables. RESULTS: In horses and donkeys, mean +/- SD area under the curve was 18.8 +/- 7.31 microg/mL/h and 4.6 +/- 2.55 microg/mL/h, respectively; mean residence time (MRT) was 9.6 +/- 9.24 hours and 0.6 +/- 0.36 hours, respectively. Total body clearance (CL(T)) was 34.7 +/- 9.21 mL/kg/h in horses and 187.9 +/- 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VD(SS)) was 270 +/- 160.5 mL/kg in horses and 93.2 +/- 33.74 mL/kg in donkeys. All values, except VD(SS), were significantly different between donkeys and horses. CONCLUSIONS AND CLINICAL RELEVANCE: The small VD(SS) of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CL(T) for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CL(T) of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.     

In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats.

OBJECTIVE: To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats. SAMPLE POPULATION: Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats. PROCEDURE: Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in whole blood with and without the addition of various concentrations of phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, carprofen, 5-bromo-2[4-fluorophenyl]-3-14-methylsulfonylphenyl]-thiophene (DuP 697), 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furan one (DFU), 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone (MF-tricyclic), and celecoxib. Potency of each test compound was determined by calculating the concentration that resulted in inhibition of 50% of COX activity (IC50). Selectivity was determined by calculating the ratio of IC50 for COX-1 to IC50 for COX-2 (COX-1/COX-2 ratio). RESULTS: The novel compound DFU was the most selective COX-2 inhibitor in equine, canine, and feline blood; COX-1/COX-2 ratios were 775, 74, and 69, respectively. Carprofen was the weakest inhibitor of COX-2, compared with the other COX-2 selective inhibitors, and did not inhibit COX-2 activity in equine blood. In contrast, NSAID such as phenylbutazone and flunixin meglumine were more potent inhibitors of COX-1 than COX-2 in canine and equine blood. CONCLUSIONS AND CLINICAL RELEVANCE: The novel COX-2 inhibitor DFU was more potent and selective in canine, equine, and feline blood, compared with phenylbutazone, flunixin meglumine, and carprofen. Compounds that specifically inhibit COX-2 may result in a lower incidence of adverse effects, compared with NSAID, when administered at therapeutic dosages to horses, dogs, and cats.     

Susceptibility of bacteria from feline and canine urinary tract infections to doxycycline and tetracycline concentrations attained in urine four hours after oral dosage

OBJECTIVES: To measure urinary concentrations of doxycycline in cats and dogs and tetracycline in dogs 4 h after conventional oral dosing and determine whether these antibiotics were present in sufficient concentrations to be effective against common feline and canine urinary tract pathogens as assessed in vitro by Epsilometer and disc diffusion antimicrobial susceptibility methods. DESIGN: A prospective study involving oral administration to clinically normal cats and dogs of doxycycline or tetracycline (dogs only) and culture of bacteria from dogs and cats with urinary tract infections to determine their susceptibility to both doxycycline and tetracycline in vitro. PROCEDURE: In the first study, nine cats and eight dogs were administered doxycycline monohydrate (5 mg/kg every 12 h) and a further eight dogs were administered tetracycline hydrochloride (20 mg/kg every 8 h) for 72 h. Blood was collected at 2 and 4 h, and urine at 4 h, after the last dose. The concentration of each agent in serum and urine was determined by modified agar diffusion. In the second study, 45 urine samples from cats and dogs with urinary tract infections were cultured. Every bacterial isolate was tested in vitro using both Epsilometer (doxycycline and tetracycline) and disc diffusion (doxycycline, tetracycline or amoxycillin-clavulanate) tests. RESULTS: Serum doxycycline concentrations in sera of cats and dogs at 2 h were 4.2 +/- 1.0 mg/mL and 3.4 +/- 1.1 mg/mL, respectively. The corresponding concentrations at 4 h were 3.5 +/- 0.7 mg/mL and 2.8 +/- 0.6 mg/mL. Urinary doxycycline concentrations at 4 h (53.8 +/- 24.4 mg/mL for cats and 52.4 +/- 24.1 mg/mL for dogs) were substantially higher than corresponding serum values. Serum tetracycline concentrations in dogs at 2 and 4 h, and in urine at 4 h, were 6.8 +/- 2.8, 5.4 +/- 0.8, 144.8 +/- 39.4 mg/mL, respectively. Most of the urinary tract pathogens (35/45) were susceptible to urinary concentrations of doxycycline and 38/45 were susceptible to tetracycline. In contrast 41/45 of all isolates were susceptible to amoxycillin-clavulanate. CONCLUSION: This is the first report of urinary concentrations of doxycycline after conventional oral administration. Concentrations attained in the urine of normal cats and dogs were sufficient to inhibit the growth of a significant number of urinary tract pathogens and thus doxycycline may be a useful antimicrobial agent for some urinary tract infections.     

Evaluation of a continuous glucose monitoring system for use in dogs, cats, and horses

OBJECTIVE: To evaluate a continuous glucose monitoring system (CGMS) for use in dogs, cats, and horses. DESIGN: Prospective clinical study. Animals-7 horses, 3 cats, and 4 dogs that were clinically normal and 1 horse, 2 cats, and 3 dogs with diabetes mellitus. PROCEDURE: Interstitial glucose concentrations were monitored and recorded every 5 minutes by use of a CGMS. Interstitial glucose concentrations were compared with whole blood glucose concentrations as determined by a point-of-care glucose meter. Interstitial glucose concentrations were also monitored in 2 clinically normal horses after oral and i.v. administration of glucose. RESULTS: There was a positive correlation between interstitial and whole blood glucose concentrations for clinically normal dogs, cats, and horses and those with diabetes mellitus. Events such as feeding, glucose or insulin administration, restraint, and transport to the clinic were recorded by the owner or clinician and could be identified on the graph and associated with time of occurrence. CONCLUSIONS AND CLINICAL RELEVANCE: Our data indicate that use of CGMS is valid for dogs, cats, and horses. This system alleviated the need for multiple blood samples and the stress associated with obtaining those samples. Because hospitalization was not required, information obtained from the CGMS provided a more accurate assessment of the animal's glucose concentrations for an extended period, compared with measurement of blood glucose concentrations. Use of the CGMS will promote the diagnostic and research potential of serial glucose monitoring.     

Quantitative assessment of blood volume, blood flow, and permeability of the brain of clinically normal dogs by use of dynamic contrast-enhanced computed tomography

OBJECTIVE: To determine effects of regional variation, interobserver variability, and vessel selection on quantitative vascular variables derived by dynamic contrast-enhanced computed tomography (DCE-CT) of the brain of clinically normal dogs. ANIMALS: 14 adult dogs with no evidence of CNS dysfunction. PROCEDURES: Dogs were randomly assigned to 4 groups, and DCE-CT was performed at the level of the frontal lobe, rostral portion of the parietal-temporal lobes, caudal portions of the parietal-temporal lobes, or occipital lobe-cerebellum for groups 1 to 4, respectively. Cerebral blood flow (CBF), cerebral blood volume (CBV), and permeability in gray and white matter for both a large and small artery were calculated and compared. Values among 3 observers and 4 regions of the brain were calculated and compared. RESULTS: Significant interobserver variability was detected for CBF and permeability in white matter. Values calculated for large and small arteries were correlated for CBV and CBF but not for permeability. Overall mean +/- SD for CBF, CBV, and permeability in gray matter was 53.5 +/- 27.7 mL/min/100 g, 2.9 +/- 1.4 mL/100 g, and 1.4 +/- 2.2 mL/min/100 g, respectively. Mean for CBF, CBV, and permeability in white matter was 44.2 +/- 28.5 mL/min/100 g, 2.5 +/- 1.5 mL/100 g, and 0.9 +/- 0.7 mL/min/100 g, respectively. Values did not differ significantly among brain regions. CONCLUSIONS AND CLINICAL RELEVANCE: Significant regional variations were not detected for quantitative vascular variables in the brain of clinically normal dogs. However, interobserver variability and vessel selection have an important role in variable estimation.     

Pharmacokinetics and pharmacodynamics of a therapeutic dose of unfractionated heparin (200 U/kg) administered subcutaneously or intravenously to healthy dogs

BACKGROUND: Heparin treatment has been recommended for dogs in hypercoagulable states such as disseminated intravascular coagulation, however, potential benefits have to be balanced against the bleeding risk if overdosage occurs. A better understanding of the pharmacology of heparin and tests to monitor heparin therapy in dogs may help prevent therapeutic hazards. OBJECTIVES: The purpose of this study was to evaluate the effects of 200 U/kg of sodium unfractionated heparin (UFH) on coagulation times in dogs after intravenous (IV) and subcutaneous (SC) administration and to compare these effects with plasma heparin concentrations assessed by its antifactor Xa (aXa) activity. METHODS: 200 U/kg of UFH were administered IV and SC to 5 healthy adult Beagle dogs with a washout period of at least 3 days. Activated partial thromboplastin time (APTT), prothrombin time (PT), and plasma aXa activity were determined in serial blood samples. RESULTS: After IV injection, PT remained unchanged except for a slight increase in 1 dog; APTT was not measurable (>60 seconds) for 45-90 minutes, and then decreased gradually to baseline values between 150 and 240 minutes. High plasma heparin concentrations were observed (maximal concentration = 4.64 +/-1.4 aXa U/mL) and decreased according to a slightly concave-convex pattern on a semilogarithmic curve, but returned to baseline slightly more slowly (t240-t300 minutes) than did APTT. After SC administration, APTT was moderately prolonged (by a ratio of 1.55 +/-0.28 APTT t0, range 1.35-2.01) between 1 and 4 hours after administration. Plasma aXa activity reached a maximum of 0.56 +/-0.20 aXa U/mL (range 0.42-0.9 U/mL) after 132 +/-26.8 minutes; this lasted for 102 +/-26.8 minutes. Prolongation of APTTs of 120-160% corresponded to plasma heparin concentrations of 0.3-0.7 aXa U/mL. CONCLUSIONS: As in humans, the pharmacokinetics of UFH in dogs was nonlinear. Administration of 200 U/kg of UFH SC in healthy dogs resulted in sustained plasma heparin concentrations in accordance with human recommendations for thrombosis treatment or prevention, without excessively increased bleeding risks. In these conditions, APTT can be used as a surrogate to assess plasma heparin concentrations. These findings need to be confirmed in diseased animals.