OBJECTIVE To investigate the pharmacokinetics of metformin hydrochloride in healthy dogs after IV and oral bolus administrations and determine the oral dose of metformin that yields serum concentrations equivalent to those thought to be effective in humans. ANIMALS 7 healthy adult mixed-breed dogs. PROCEDURES Each dog was given a single dose of metformin IV (mean ± SD dose, 24.77 ± 0.60 mg/kg) or PO (mean dose, 19.14 ± 2.78 mg/kg) with a 1-week washout period between treatments. For each treatment, blood samples were collected before and at intervals up to 72 hours after metformin administration. Seventy-two hours after the crossover study, each dog was administered metformin (mean dose, 13.57 ± 0.55 mg/kg), PO, twice daily for 7 days. Blood samples were taken before treatment initiation on day 0 and immediately before the morning drug administration on days 2, 4, 6, and 7. Serum metformin concentrations were determined by means of a validated flow injection analysis–tandem mass spectrometry method. RESULTS After IV or oral administration to the 7 dogs, there was high interindividual variability in mean serum metformin concentrations over time. Mean ± SD half-life of metformin following IV administration was 20.4 ± 4.1 hours. The mean time to maximum serum concentration was 2.5 ± 0.4 hours. Mean systemic clearance and volume of distribution were 24.1 ± 7.8 mL/min/kg and 44.8 ± 23.5 L/kg, respectively. The mean oral bioavailability was 31%. CONCLUSIONS AND CLINICAL RELEVANCE The study data indicated that the general disposition pattern and bioavailability of metformin in dogs are similar to those reported for cats and humans

OBJECTIVE To determine accuracy for a technique of needle redirection at a single craniolateral site for injection of 3 compartments of the equine stifle joint, describe the external needle position, and identify the location of the needle tip within each joint compartment. SAMPLE 24 equine cadaver stifle joints. PROCEDURES Stifle joints were placed in a customized stand. After the needle was placed, external needle position was measured and recorded. Each joint compartment (medial and lateral compartments of the femorotibial joint and the femoropatellar joint) was injected with a solution containing iodinated contrast medium, water, and dye. Radiography, assessment of intra-articular location of the needle tip, and gross dissection were performed to determine success of entering each joint compartment. Student t tests and an ANOVA were used to compare mean values. RESULTS Overall accuracy was 19 of 24 (79.1%), and accuracy for individual joint compartments was at least 21 of 24 (87.5%). Mean depth of needle insertion to access each compartment of the stifle joint was 5.71 cm. Mean angle of insertion (relative to the long axis of the tibia) was 82.1°, 80.3°, and 18.5° for the medial compartment of the femorotibial joint, lateral compartment of the femorotibial joint, and femoropatellar joint, respectively, and 28° medial, 7.3° lateral, and 1.3° lateral for the medial compartment of the femorotibial joint, lateral compartment of the femorotibial joint, and femoropatellar joint, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that this was an accurate technique for successful injection of the 3 equine stifle joint compartments.

OBJECTIVE To evaluate dynamic movement of the diaphragm of clinically normal dogs by use of fluoroscopy and to obtain quantitative data of diaphragmatic excursion during spontaneous breathing. ANIMALS 8 healthy male Beagles with no history of respiratory tract disease. PROCEDURES Fluoroscopy was performed during stabilized respiratory conditions. The beam center was located at the level of the diaphragm, and diaphragmatic motion was recorded during 3 respiratory cycles in dogs positioned in left lateral, right lateral, and dorsal recumbency. Extent of excursion of the diaphragmatic cupula and both crura, difference in excursion between the left and right crura, and ratios of the excursions of the diaphragmatic cupula and left and right crura to the length of the eighth thoracic vertebra were determined. RESULTS Diaphragmatic crural excursion was symmetric for dogs in right lateral recumbency, and the crural excursion was approximately three-quarters of the vertebral length; however, crural excursion appeared to be asymmetric for dogs in left lateral recumbency. Mean ± SD difference in excursion between the right and left crura was 22.68 ± 8.68% for left lateral recumbency, 16.63 ± 9.22% for right lateral recumbency, and 18.11 ± 12.96% for dorsal recumbency. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the fluoroscopic view of a dog positioned in right lateral recumbency may allow better evaluation of the symmetry of diaphragmatic excursion, compared with results for other recumbency positions. This study provided quantitative data on the excursion of diaphragmatic movement observed by use of fluoroscopy in clinically normal Beagles.

OBJECTIVE To determine repeatability of gait variables measured by use of extremity-mounted inertial measurement units (IMUs) in nonlame horses during trotting under controlled conditions of treadmill exercise. ANIMALS 10 horses. PROCEDURES Six IMUs were strapped to the metacarpal, metatarsal, and distal tibial regions of each horse. Data were collected in a standardized manner (3 measurements/d on 3 d/wk over a 3-week period) while each horse was trotted on a treadmill. Every measurement consisted of a minimum of 20 strides from which a minimum of 10 strides was selected for analysis. Spatial and temporal variables were derived from the IMUs. Repeatability coefficients based on the within-subject SD were computed for each gait analysis variable at each week. RESULTS Most of the temporal and spatial variables had high repeatability (repeatability coefficients < 10), and the repeatability coefficients were consistent among the 3 weeks of data collection. Some spatial variables, specifically the symmetry variables (which were calculated from other variables), had somewhat higher repeatability coefficients (ie, lower repeatability) only in the last week. CONCLUSIONS AND CLINICAL RELEVANCE With the exceptions of some symmetry variables, which may reflect individual variations during movement, the extremity-mounted IMUs provided data with high repeatability for nonlame horses trotting under controlled conditions of treadmill exercise. Repeatability was achieved for each instrumented limb segment with regard to the spatial relationship between 2 adjacent segments (joint angles) and the temporal relationship among all segments (limb phasing). Extremity-mounted IMUs could have the potential to become a method for gait analysis in horses.

The objective of this study was to test the hypothesis that porcine circovirus type-2 (PCV2) vaccination is efficacious when administered in the first week of life. Three groups of pigs were vaccinated with Circumvent either early (at the end of week 1), late (at the end of week 4), or not at all. All 3 groups were later challenged intranasally with PCV2 (at the end of week 5). Two other groups were immunized with keyhole limpet hemocyanin (KLH) as a novel antigen at the end of either week 1 or week 4. Weight, PCV2 genome copy number in serum and saliva, anti-KLH antibody titer, and serum PCV2-neutralizing antibodies were measured weekly. Early PCV2 vaccination or KLH antigen exposure resulted in earlier humoral responses that were slower to develop than in older piglets, yet converged with the responses to later vaccination within 5 wk. Both groups of vaccinated piglets had periods of higher PCV2-neutralizing antibody titers and lower viral levels shortly after weaning and PCV2 challenge, thus supporting the recent labelling of 1 Canadian PCV2 vaccine for use in week 1 and suggesting that early PCV2 vaccination can reduce piglet handling without compromising vaccine efficacy.

Myocardial dysfunction occurs in cats with hypertrophic cardiomyopathy (HCM), but little is known about the early stages of the disease. Strain imaging echocardiography is a method that enables the quantitative assessment of myocardial function and deformity, allowing the characterization of systolic dysfunction. The objective of this study was to assess systolic function using strain imaging echocardiography in Maine coon cats genetically tested for the A31P mutation in the MYBPC3 gene, with and without ventricular hypertrophy. For this purpose, 57 Maine coon cats of both genders, with an unknown status regarding the mutation at inclusion, were included prospectively and evaluated by conventional and strain imaging echocardiography. Comparisons were made among cats without hypertrophy (n = 45), suspect cats (n = 7), and cats with hypertrophic cardiomyopathy (n = 5), and also between the heterozygous for the mutation group (n = 26) and the negative for the mutation group (n = 28). Finally, in the group of phenotypically normal cats, heterozygous cats carrying the mutation were compared to cats without the mutation. Strain values were compared among the groups (blinded prospective study). While echocardiography demonstrated normal contractility, strain values (middle of the septum) were lower in HCM cats. Strain values (base of anterior wall of the left ventricle) were lower in heterozygous than in negative cats, even before hypertrophy. Negative correlation was observed between some values of myocardial strain and thickness. While strain imaging echocardiography was able to detect systolic abnormalities, despite apparent normality on conventional echocardiography, it was not able to identify cats that carry the A31P mutation in the MYBPC3 gene. Strain imaging echocardiography could be a useful tool, however, for detecting systolic alterations in HCM cats with an apparently normal systolic function or for detecting alterations in normal carriers of the MYBPC3 gene mutation.

OBJECTIVE To predict histologic grade of meningiomas in dogs via texture analysis (TA) of MRI scans of the brain and spinal cord. SAMPLE 58 sets of MRI scans of the brain and spinal cord of dogs with histologically diagnosed meningioma. PROCEDURES MRI sequences were divided into a training set and a test set, and results of histologic assessment were obtained. Tumors were histologically grouped as benign (stage I) or atypical-anaplastic (stage II or III). Texture analysis was performed by use of specialized software on T2-weighted (T2W) and pre- and postcontrast T1-weighted (T1W) images. A set of 30 texture features that provided the highest discriminating power between the 2 histologic classes in the training set was automatically selected by the TA software. Linear discriminant analysis was performed, and the most discriminant factor (MDF) was calculated. The previously selected texture features were then used for linear discriminant analysis of the test set data, and the MDF was calculated. RESULTS For the training set, TA of precontrast T1W images provided the best diagnostic accuracy; a cutoff MDF of < 0.0057 resulted in a sensitivity of 97.4% and specificity of 95.0% for discriminating benign from atypical-anaplastic meningiomas. Use of postcontrast T1W and T2W images yielded poorer diagnostic performances. Application of the MDF cutoff calculated with the training set to the MDF calculated with the test set provided a correct classification rate of 96.8% for precontrast T1W images, 92.0% for postcontrast T1W images, and 78.9% for T2W images. CONCLUSIONS AND CLINICAL RELEVANCE Findings supported the potential clinical usefulness of TA of MRI scans for the grading of meningiomas in dogs.

OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

OBJECTIVE To evaluate the effect of bilateral ventriculocordectomy via ventral laryngotomy on laryngeal airway resistance (LAR) in canine cadaver larynges. SAMPLE 6 clinically normal canine cadaver larynges. PROCEDURES LAR was determined for each specimen before (baseline) and after bilateral ventriculocordectomy with the epiglottis open and closed. After ventral laryngotomy was performed, the vocal cords were sharply excised, and the incised mucosal edges were apposed with 4-0 glycomer 631 suture in a simple continuous pattern. The thyroid cartilage was apposed with 3-0 polypropylene suture in a simple continuous pattern. RESULTS With the epiglottis closed, baseline median LAR was 27.6 cm H2O/L/s (range, 21.2 to 30.6 cm H2O/L/s), which did not differ significantly from the median LAR after bilateral ventriculocordectomy (24.7 cm H2O/L/s [range, 20.6 to 27.7 cm H2O/L/s]). With the epiglottis open, baseline median LAR was 7.3 cm H2O/L/s (range, 5.4 to 7.8 cm H2O/L/s), which did not differ significantly from the median LAR after bilateral ventriculocordectomy (7.2 cm H2O/L/s [range, 6.6 to 7.6 cm H2O/L/s]). CONCLUSIONS AND CLINICAL RELEVANCE Bilateral ventriculocordectomy did not affect LAR with an open epiglottis in canine cadaver larynges. Therefore, it may not be an effective treatment for laryngeal paralysis. It also did not affect LAR with a closed epiglottis, which may indicate protection against aspiration pneumonia.

OBJECTIVE To investigate the effects of meloxicam administration before long-distance transport on inflammatory mediators and leukocyte function of cattle at feedlot arrival. ANIMALS 60 healthy yearling beef steers. PROCEDURES Single-source steers were assigned to a transported (n = 40) or nontransported (20) group. Then, half of the steers within each group were assigned to receive meloxicam (1 mg/kg, PO) or a lactose placebo (1 bolus/steer, PO). All steers were transported approximately 1,300 km overnight to a feedlot; however, the nontransported group was moved before treatment (meloxicam or placebo) administration and allowed a 17-day acclimation period, whereas the transported group was moved immediately after treatment administration on day −1. Blood samples for measurement of inflammatory mediators and leukocyte function were collected from all steers on days −1, 0, and 3. RESULTS For steers that received meloxicam, mean plasma meloxicam concentration for the transported group was significantly greater than that for the nontransported group on day 0. For steers that received the placebo, mean haptoglobin-matrix metalloproteinase-9 complex for the transported group was significantly greater than that for the nontransported group on day 0. Mean haptoglobin concentration, neutrophil L-selectin intensity, and polymorphonuclear leukocyte count for the transported group were significantly greater than those for the nontransported group. Mean substance P concentration for nontransported steers that received meloxicam was significantly lower than that for the other 3 treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated meloxicam administration to healthy steers immediately before long-distance transport did not significantly mitigate the effects of transport-induced stress on leukocyte function or inflammatory markers.