Effect of age on myocardial function assessed by two-dimensional speckle-tracking echocardiography in healthy beagle dogs

ObjectivesThe objective of this study was to evaluate the effect of age on myocardial function assessed by two-dimensional speckle-tracking echocardiography (2D-STE) in healthy dogs.AnimalsThirty-two healthy Beagles were used.MethodsMyocardial function was assessed in each dog by using 2D-STE, and the results were compared between young and old dogs.ResultsThe myocardial deformations in systole, besides the apical rotation rate, were not significantly different between young and old dogs. In contrast, the early diastolic circumferential strain rate, basal rotation rate, and torsion rate were significantly lower in old dogs than in young dogs (P = 0.03, P = 0.033, and P = 0.015, respectively). Late diastolic longitudinal and radial strain rates were significantly higher in old dogs than in young dogs (P = 0.002 and P = 0.018, respectively).ConclusionsYoung and old dogs showed similar systolic myocardial deformations, but significant differences in the values of some diastolic deformation variables were found between young and old dogs, highlighting the need for using age-matched control subjects in studies of diastolic function.     

Plasma lactate measurements in healthy beagle dogs

Plasma lactate concentrations were determined in venous blood samples collected from 60 healthy Beagles aged 5 to 9 months. The range of values (0.42 to 3.58 mmol/L) obtained with an enzymatic method in the present study was similar to values reported in smaller studies with the colorimetric procedures.     

Intradermal and serological testing for mites in healthy beagle dogs

Background – Intradermal testing (IDT) is widely used in veterinary medicine to select allergens for immunotherapy. The recommended concentration for mites is 250 protein nitrogen units (PNU)/mL. It is not known whether healthy dogs responding to this concentration have asymptomatic sensitization or irritation. Furthermore, interbatch and intersupplier variability of allergens has not been fully addressed. Hypothesis/Objectives – The incidence of positive IDTs in healthy beagles was recorded and the value of combining these results with serology to differentiate between asymptomatic sensitization and irritancy evaluated. Additionally, the interbatch and intersupplier variability of allergens was assessed. Animals – Seventeen healthy laboratory beagles with no history or clinical signs of canine atopic dermatitis were used. Methods – Intradermal tests were performed with four mite allergens from two suppliers (varying batches). An initial IDT at 250 PNU/mL was used to determine whether decreasing or increasing test concentrations were used in the subsequent titration IDTs. Additionally, two IgE ELISA tests from different manufacturers were performed. Results – Seven of 17 dogs showed IDT reactions at 250 PNU/mL. There were highly significant allergen interbatch and significant intersupplier correlations and agreement. The associations between the IDT reactions and the IgE serologies statistically identified two groups of dogs: one with positive serology and IDT reactions at 250 PNU/mL; and another with negative serology and IDT reactions. Conclusions and clinical importance – Our results suggest that dogs that have IDT reactions and positive serology are asymptomatically sensitized, while dogs that react at higher allergen concentrations, but have negative serology, do so as a result of irritant reactions.     

Influence of age and body size on intestinal permeability and absorption in healthy dogs

OBJECTIVE: To evaluate effects of age and body size of dogs on intestinal permeability (unmediated diffusion) as measured by the ratio of urinary lactulose to L-rhamnose (L:R) and absorption (carrier-mediated transport) as measured by the ratio of urinary D-xylose to 3-O-methyl-D-glucose (X:MG) and to determine whether these variables correlated with fecal quality. ANIMALS: 6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE: A solution that contained lactulose and rhamnose or xylose and 3-O-methyl-D-glucose was administered orally to dogs that were 12, 22, 36, and 60 weeks old. Urine was collected 6 hours later, and urinary L:R and X:MG were calculated. Fecal moisture and scoring were recorded during the same periods. RESULTS: Age and breed did not affect intestinal absorption, and we did not detect a relationship between X:MG and fecal variables. In contrast, we detected significant effects of age and body size on intestinal permeability. Puppies (12 weeks old) and large dogs had higher intestinal permeability than adult (60 weeks old) and small dogs. The increased intestinal permeability in large dogs was associated with lower fecal quality as indicated by the significant positive correlations between L:R and fecal moisture (r, 0.61) and L:R and fecal scores (r, 0.86) in adult dogs. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that age and body size should be considered when assessing intestinal permeability by use of the L:R urinary excretion test in dogs. High intestinal permeability could be a possible cause of poor fecal quality in large dogs.     

Pharmacokinetics of low‐dose methotrexate in healthy beagle dogs

Methotrexate may be an alternative to ciclosporin in the treatment of canine atopic dermatitis (cAD) as suggested by recent data. The aim of the study was to investigate both the tolerance and the pharmacokinetic behavior of methotrexate (MTX) in plasma, following intravenous (i.v.), subcutaneous (s.c.) or oral (OR) administration over several weeks. Six healthy dogs were given oral MTX once a week, respectively, per dog at 2.5 mg/1 week, 5 mg/4 weeks, 7.5 mg/3 weeks, 10 mg/6 weeks and 12.5 mg/5 weeks. No clinically relevant abnormalities of laboratory parameters were noticed. A high inter‐individual variation of MTX plasma concentration was observed with a suspicion of saturation phenomenon in absorption. To compare with other routes of administration, six healthy beagle dogs followed a crossover design study at 7.5 mg per dog MTX. The absolute bioavailability was 93% for SC injection and 30% for the oral route. The inter‐individual variability was quite low following SC administration compared to oral route. Just as in human, given the substantial variability of oral absorption, clinicians cannot assume consistent oral bioavailability of MTX. Therefore, they may consider switching dogs to the SC route in case of absence of clinical response with a weekly oral dose.     

Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant‐bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 μg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady‐state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half‐life (T_1/2) in dogs with IHD decreased compared with those without IHD, and the reduction in T_1/2 was greater in renal failure patients than in normal patients. Sixty‐nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.     

Influence of age on myelogram in dogs

The influence of age on the myelogram and on the different indices (ratios) was studied on bone marrow aspirates of 131 healthy dogs which were divided into different age groups (A [4-6 months] to G [> 8 years]). Myelograms were obtained by performing a differential count on 1000 cells. Age dependent differences were particularly seen in the 4 to 6 month old dogs. These dogs had significantly higher percentages of immature erythroid cells (p < 0.01) than dogs of the other age groups and, consequently, the lowest proportion of myeloid cells. This fact was also reflected by a lower quotient of number of myeloid cells/number of erythroid cells (M:E-ratio) and increased erythroid maturation index (I:ME-ratio). In addition, the proportions of monocytes and lymphocytes were increased and the number of plasma cells was decreased in juvenile dogs. The results in young dogs which were different from the values of adult animals reflect the increased requirements of red cell mass during the time of growth and ontogenesis of the immune system. These findings have to be considered in the interpretation of bone marrow films of young dogs.     

Effects of long-term oral administration of ketoprofen in clinically healthy beagle dogs

To investigate the adverse effects of long-term administration of ketoprofen in dogs, ketoprofen (1 mg/kg) was administered to five clinically healthy beagle dogs (ketoprofen group) and gelatin capsules (control group) were administered to four clinically healthy beagle dogs for 30 days. We monitored the dogs through periodic physical examination, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests, urinalysis, urinary enzyme indices and cuticle bleeding time analysis. The lesions in the stomach, especially in the pyloric antrum, and fecal occult blood progressively worsened in the ketoprofen group. However, the differences between the ketoprofen group and the control group were not statistically significant. One dog in the ketoprofen group temporarily exhibited a decrease in renal plasma flow and two dogs exhibited enzymuria. However, these changes did not persist and the other examinations showed no significant difference between premedication and postmedication in the ketoprofen group. Therefore, the adverse effects of long-term administration of ketoprofen observed in this study were not clinically important in healthy dogs. Nevertheless, further investigation of adverse renal effects from long-term administration of ketoprofen is necessary in the dogs with subclinical renal disease.     

Influence of parity and litter size on gestation length in beagle dogs

This study was conducted to investigate the effects of parity and litter size on gestation length in beagle bitches. The mean duration of the initial elevation (>2 ng/mL) in progesterone concentrations after the onset of proestrus was shorter (P < 0.05) in bitches without (nulliparous) whelping experience than in bitches with (multiparous) whelping experience (6.9 d versus 8.0 d). When calculated as the interval between the day of initial elevation in progesterone concentrations and the day of whelping, the gestation length in the nulliparous bitches was noted to be similar to that in the multiparous bitches (64.3 d versus 64.2 d). No significant correlation between gestation length and litter size was observed in any of the bitches. Our results indicate that the gestation length in beagle bitches is not affected by parity or litter size.     

Impact of the advances in age on the gastrointestinal microflora of beagle dogs.

The gastrointestinal microflora of male beagle dogs in two different age groups; I) less than month 12 of age, and II) more than year 11 of age, was compared. No detectable difference occurred on the microflora of stomach, duodenum, jejunum, and ileum in both dogs. Large bowel (cecum, colon and rectum) microflora in both dogs yielded the different microbial populations. In all regions of large bowel, the levels of bacteroides, eubacteria, peptostreptococci, bifidobacteria, lactobacilli, and staphylococci in the elderly dogs were lower than those in the younger animals, whereas the numbers of Clostridium perfringens and streptococci in the elderly animals were higher than those in the youngers. The high incidence of lecithinase-negative clostridia was observed with advances in age, but not that of spiral shaped rods. The result of this study shows that the advances in age of beagle dogs yield some changes in the microbial population of large bowel in the animals.     

Influence of age and body size on gastrointestinal transit time of radiopaque markers in healthy dogs

OBJECTIVE: To compare gastric emptying time, small-intestinal transit time (SITT), and orocecal transit time (OCTT) of radiopaque markers in dogs varying in age and body size and to determine whether fecal variables (ie, consistency and moisture content) are related to gastrointestinal tract transit times in dogs. ANIMALS: 24 eight-week-old female puppies, including 6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE: Gastrointestinal tract transit time experiments were performed at 12, 22, 36, and 60 weeks of age. Dogs were fed 30 small radiopaque markers mixed with a meal. Abdominal radiographs were taken. The time at which 50% of the markers had left the stomach (T50) and the time at which the first marker reached the colon were calculated. Fecal moisture content and scoring on the basis of fecal consistency were recorded during the same periods. RESULTS: Puppies had a shorter mean T50 than adults, and mean OCTT decreased significantly only during growth of large-breed dogs. However mean fecal moisture content significantly increased with age, except in Giant Schnauzers. No effect of body size on T50 was found regardless of age, and no difference was observed between OCTT of small- and large-breed adult dogs. The effect of age on the mean SITT was not significant for any breed. However, a strong positive correlation was recorded between body size and fecal moisture content (r2 = 0.77) or fecal scores (r2 = 0.69) in adult dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Age affects T50 in small- and large-breed dogs and OCTT in large-breed dogs. However, body size does not affect T50 or OCTT. A relationship does not exist between gastrointestinal tract transit time and fecal variables in healthy dogs.     

Effect of repetitive bronchoalveolar lavage on cytologic findings in healthy dogs

OBJECTIVE: To determine reference values for cytologic examination results of bronchoalveolar lavage fluid (BALF) and to investigate effects of repeated lavages on pulmonary health and on results of cytologic examination of BALF in dogs. ANIMALS: 16 healthy adult Beagles. PROCEDURE: All dogs underwent pulmonary lavage to obtain BALF. Eleven dogs were repeatedly lavaged 6 times at 5- to 7-week intervals. Analyses for total and differential cell counts and for viability of cells before and after cell processing were performed. Arterial blood gas analysis before and after bronchoalveolar lavage was used to study the safety of the lavage procedure. Histologic and radiologic examinations were used to study effects of repeated lavages on pulmonary health. RESULTS: Mean (+/- SD) cell count was 104 +/- 69 cells/microl, comprising 75 +/- 7% alveolar macrophages, 13 +/- 6% lymphocytes, 5 +/- 4% neutrophils, 4 +/- 5% eosinophils, 2 +/- 2% mast cells, 0.6 +/- 0.7% epithelial cells, and 0.3 +/- 0.4% plasma cells. Centrifugation of samples and washing of cells caused significant cell loss (59 +/- 13%). Repeated lavages did not cause significant variations in cell counts of BALF or results of arterial blood gas analysis, thoracic radiography, or histologic examination of pulmonary specimens. Only a moderate, although significant, decrease in arterial oxygen content was observed after bronchoalveolar lavage. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis indicated that several lavages performed at 5- to 7-week intervals can safely and reliably be used to study the kinetics of pathologic processes in pulmonary tissues or for evaluation of therapeutic efficacy.     

Immunohistochemical localization of fibroblast growth factor 18 in hair follicles of healthy beagle dogs

Increasing emphasis is being placed on the role of fibroblast growth factors (FGFs) in hair follicle cycling. In mice, expression of FGF18 mRNA peaks during the late telogen phase, leading to the hypothesis that FGF plays a role in anagen induction. There are no data on the presence of FGF18 in dogs. The main objective of this study was to identify and locate FGF18 in the canine hair follicle. The second objective was to assess potential differences in FGF18 concentration between biopsies taken in winter and summer, shoulder and flank regions, and between different sexes. Skin tissue from 10 healthy beagle dogs (three intact females, three spayed females and four intact males) was collected from the shoulder and flank. The biopsies were collected in February and August on day 0, after which the dogs were clipped and biopsies collected again from the shoulder and flank on days 1, 3, 7 and 17. Paraffin sections (4 μm thick) of the biopsies were stained with an anti-FGF18 antibody. The FGF18-positive cells were counted in the hair follicle epithelium from seven follicular units of each biopsy. Fibroblast growth factor 18 was detected as granular cytoplasmatic staining in follicles at the level of the inner root sheath, and rarely in the outer root sheath and dermal papilla. It was also detected in the apocrine glands, in arrector pili muscles and in vascular endothelial cells. There was no statistical difference in the number of FGF18-positive cells or follicles between sexes, different anatomical locations, seasons or the consecutive days of sampling.     

Effect of short-term treatment with meloxicam and pimobendan on the renal function in healthy beagle dogs

The aim of the study was to investigate the renal function in clinically normal dogs receiving meloxicam and pimobendan alone or in combination. Ten adult female beagle dogs were administered the treatment for 7 days in a randomized crossover trial (control/meloxicam/pimobendan/meloxicam and pimobendan). Renal function was assessed by blood urea, creatinine, sodium, potassium and chloride concentrations and by glomerular filtration rate, measured by means of renal scintigraphy [renal uptake of ^99mTc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of ^99mTc-DTPA. As compared with the control group, renal uptake and plasma clearance of ^99mTc-DTPA were not significantly modified after a 7-day period of treatment with meloxicam or pimobendan alone, or meloxicam and pimobendan in combination. Furthermore, urea, creatinine, sodium, potassium and chloride levels in the serum of the dogs during the 7-day period treatment were not significantly modified in relation to the treatments. It was therefore concluded that meloxicam and pimobendan alone or in combination did not alter renal function in healthy dogs.     

Electroretinography recordings using a light emitting diode active corneal electrode in healthy beagle dogs

Electroretinography (ERG) is a well-established diagnostic procedure for objectively evaluating retinal function. In this study, ERG in beagle dogs, which are a popular experimental animal, was performed to determine the normal range of ERG variables and assess differences between the left and right eyes. ERG findings including rod, combined rod-cone, single-flash cone, and 30-Hz flicker responses were recorded with an LED-electrode in 43 sedated beagle dogs. The subjects were divided into young (< 1 year old), adult (1~5 years old), and senile animals (≥ 6 years old). Normal ERG ranges were obtained. Significant differences in b-wave amplitude along with b/a ratio of the combined rod-cone response were found between the young and adult animals as well as young and senile dogs. No significant differences were observed between the left and right eyes. ERG variables in beagle dogs differed by age due to age-related retinal changes. Thus, we propose that normal ERG ranges should be determined according to age in each clinic and laboratory using its own equipment because each institution usually has different systems or protocols for ERG testing.     

Colonisation status of Malassezia pachydermatis on the hair and in the hair follicle of healthy beagle dogs

Hair and hair follicle carriage of Malassezia pachydermatis was studied in 12 healthy beagle dogs. The yeast was isolated from hair clipped from the lip region at 13 sites in nine dogs but was less frequently recovered from the interdigital spaces on the forefeet and from two sites on the trunk. Population sizes at the lip were significantly greater (P < 0.01) than those at other sites. Skin biopsy specimens were obtained from the same sites and epidermal and follicular tissues dissected following immersion in 1 M CaBr(2). Epidermal carriage of M. pachydermatis was identified in nine biopsy specimens taken from five dogs. Hair follicle carriage was identified in five skin specimens (four foot, one lip) from three dogs. This study indicates that M. pachydermatis is readily recovered from the distal hair in healthy dogs and that hair follicle carriage is infrequent or that populations are low at that site.     

Pharmacokinetics of tildipirosin in beagle dogs

The objective of this study was to investigate the pharmacokinetic profile of tildipirosin (TD) in 24 beagle dogs following intravenous (i.v.) and intramuscular (i.m.) administration, respectively, at 2, 4, and 6 mg/kg. Plasma samples at certain time points (0–14 days) were collected, and the concentrations of drug were quantified by UPLC‐MS/MS. Plasma concentration–time data and relevant parameters were described by noncompartmental through WinNonlin 6.4 software. After single i.m. injection at 2, 4, and 6 mg/kg body weight, mean maximum concentration (C_max) was 412.73 ± 76.01, 1,051 ± 323, and 1,061 ± 352 ng/ml, respectively. Mean time to reach C_max was 0.36 ± 0.2, 0.08 ± 0.00, and 0.13 ± 0.07 hr after i.m. injection at 2, 4, and 6 mg/kg, respectively. The mean value of T_1/2λz for i.m. administration at doses of 2, 4, and 6 mg/kg was 71.39 ± 28.42, 91 .33 ± 50.02, and 96.43 ± 45.02 hr, respectively. The mean residence times were 63.81 ± 10.96, 35.83 ± 15.13, and 38.18 ± 16.77 hr for doses of 2, 4, and 6 mg/kg, respectively. These pharmacokinetic characteristics after i.m. administration indicated that TD could be rapidly distributed into tissues on account of the high lipid solubility and then released into plasma. In addition, the absolute bioavailability of 2 mg/kg after i.m. injection was 112%. No adverse effects were observed after i.v. and i.m. administration.