Objective: To develop in genetically engineered mice an alternative screening method for evaluation of P-glycoprotein substrate toxicosis in ivermectin-sensitive Collies. Animals: 14 wild-type C57BL/6J mice (controls) and 21 genetically engineered mice in which the abcb1a and abcb1b genes were disrupted and the mutated canine ABCB1 gene was inserted. Procedures: Mice were allocated to receive 10 mg of ivermectin/kg via SC injection (n = 30) or a vehicle-only formulation of propylene glycol and glycerol formal (5). Each was observed for clinical signs of toxic effects from 0 to 7 hours following drug administration. Results: After ivermectin administration, considerable differences were observed in drug sensitivity between the 2 types of mice. The genetically engineered mice with the mutated canine ABCB1 gene had signs of severe sensitivity to ivermectin, characterized by progressive lethargy, ataxia, and tremors, whereas the wild-type control mice developed no remarkable effects related to the ivermectin. Conclusions and Clinical Relevance: The ivermectin sensitivity modeled in the transgenic mice closely resembled the lethargy, stupor, disorientation, and loss of coordination observed in ivermectin-sensitive Collies with the ABCB1–1Δ mutation. As such, the model has the potential to facilitate toxicity assessments of certain drugs for dogs that are P-glycoprotein substrates, and it may serve to reduce the use of dogs in avermectin derivative safety studies that are part of the new animal drug approval process.

Objective: To compare anesthetic, analgesic, and cardiorespiratory effects in dogs after IM administration of dexmedetomidine (7.5 μg/kg)–butorphanol (0.15 mg/kg)–tiletamine-zolazepam (3.0 mg/kg; DBTZ) or dexmedetomidine (15.0 μg/kg)-tramadol (3.0 mg/kg)-ketamine (3.0 mg/kg; DTrK) combinations. Animals: 6 healthy adult mixed-breed dogs. Procedures: Each dog received DBTZ and DTrK in a randomized, crossover-design study with a 5-day interval between treatments. Cardiorespiratory variables and duration and quality of sedation-anesthesia (assessed via auditory stimulation and sedation-anesthesia scoring) and analgesia (assessed via algometry and electrical nerve stimulation) were evaluated at predetermined intervals. Results: DBTZ or DTrK induced general anesthesia sufficient for endotracheal intubation ≤ 7 minutes after injection. Anesthetic quality and time from drug administration to standing recovery (131.5 vs 109.5 minutes after injection of DBTZ and DTrK, respectively) were similar between treatments. Duration of analgesia was significantly longer with DBTZ treatment, compared with DTrK treatment. Analgesic effects were significantly greater with DBTZ treatment than with DTrK treatment at several time points. Transient hypertension (mean arterial blood pressure > 135 mm Hg), bradycardia (heart rate < 60 beats/min), and hypoxemia (oxygen saturation < 90% via pulse oximetry) were detected during both treatments. Tidal volume decreased significantly from baseline with both treatments and was significantly lower after DBTZ administration, compared with DTrK, at several time points. Conclusions and Clinical Relevance: DBTZ or DTrK rapidly induced short-term anesthesia and analgesia in healthy dogs. Further research is needed to assess efficacy of these drug combinations for surgical anesthesia. Supplemental 100% oxygen should be provided when DBTZ or DTrK are used.

Objective: To determine intraocular pressure (IOP) in healthy Hermann's tortoises (Testudo hermanni). Animals: 26 outdoor-housed Hermann's tortoises (13 males and 13 females); body weight ranged from 255 to 2,310 g, and age ranged from 4 to > 50 years. Procedures: After a preliminary ophthalmic evaluation was performed, IOP was measured by means of a rebound tonometer in both eyes of each tortoise. Three measurements were obtained for each eye; successive measurements were obtained from alternate eyes. Each measurement was based on the mean of 6 values automatically provided by the rebound tonometer. Statistical analysis was used to evaluate correlations between variables and to identify sex- or size-related IOP variations, and changes in IOP over multiple measurements. Results: Mean ± SEM IOP of the 52 eyes was 15.74 ± 0.20 mm Hg (range, 9 to 22 mm Hg). Results for t tests did not reveal significant differences in IOP between the right and left eyes or between males and females. A significant moderate negative correlation (r = −0.41; r2 = 0.169) between IOP and body weight was detected. Results of repeated-measures ANOVA revealed a significant increase in IOP over multiple measurements. Conclusions and Clinical Relevance: Rebound tonometry was a practical and rapid means of determining IOP in small- to medium-sized tortoises that required minimal manual restraint of the animals. Establishing IOP values in healthy Hermann's tortoises will provide a reference frame for use during complete ophthalmic examinations, thus allowing clinicians to diagnose a broader spectrum of ocular pathological conditions in tortoises.

Objective: To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy. Sample: Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy). Procedures: Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs. Results: Activity of complex I and complex IV was significantly decreased in anesthetized dogs, compared with activities in the control dogs and dogs with juvenile-onset or adult-onset dilated cardiomyopathy. Conclusions and Clinical Relevance: Inhalation anesthesia disrupted the electron transport chain in the dogs, which potentially led to an outburst of reactive oxygen species that caused mitochondrial dysfunction. Inhalation anesthesia depressed mitochondrial function in dogs, similar to results reported in other species. This effect is important to consider when anesthetizing animals with myocardial disease and suggested that antioxidant treatments may be beneficial in some animals. Additionally, this effect should be considered when designing studies in which mitochondrial enzyme activity will be measured. Additional studies that include a larger number of animals are warranted.

This study investigated if parenteral administration of a prototype adjuvanted vaccine against porcine circovirus type 2 (PCV2) could override maternally derived antibodies and induce acquired immunity in young piglets. Piglets with high levels of maternal PCV2 antibodies at 1 wk of age were randomly grouped into vaccinates and controls on the basis of body weight and inoculated with the vaccine or a control preparation twice, with an interval of 3 wk. Both groups were challenged 3 wk after the booster vaccination and euthanized 3 wk after challenge. The pigs were evaluated for clinical disease, histologic lesions in sections of gastric and left inguinal lymph nodes stained with hematoxylin and eosin, and the amount of PCV2 antigen in the lymph nodes by immunohistochemical study. The PCV2 antibody titers were monitored by competitive enzyme-linked immunosorbent assay throughout the experiment. The vaccinates showed significantly less decline (P < 0.05) in PCV2 antibody titers after the booster vaccination. Clinical disease did not develop in any of the piglets. The vaccinates and controls did not differ in either histologic lesions or amount of PCV2 antigen in the lymph nodes. This study demonstrated some evidence of priming of young piglets in the presence of maternal antibodies. Further studies are recommended to determine the optimum concentration of PCV2 antigen and a suitable adjuvant for the vaccine to achieve the full potential of the strategy of inducing acquired immunity in young piglets that have maternally derived antibodies.

Objective-To evaluate respiratory mechanical function and bronchoalveolar lavage (BAL) cytologic results in healthy alpacas. Animals-16 client-owned adult alpacas. Procedures-Measurements of pulmonary function were performed, including functional residual capacity (FRC) via helium dilution, respiratory system resistance via forced oscillatory technique (FOT), and assessment of breathing pattern by use of respiratory inductive plethysmography (RIP) in standing and sternally recumbent alpacas. Bronchoalveolar lavage was performed orotracheally during short-term anesthesia. Results-Mean +/- SD measurements of respiratory function were obtained in standing alpacas for FRC (3.19 +/- 0.53 L), tidal volume (0.8 +/- 0.13 L), and respiratory system resistance at 1 Hz (2.70 +/- 0.88 cm H2O/L/s), 2 Hz (2.98 +/- 0.70 cm H2O/L/s), 3 Hz (3.14 +/- 0.77 cm H2O/L/s), 5 Hz (3.45 +/- 0.91 cm H2O/L/s), and 7 Hz (3.84 +/- 0.93 cm H2O/L/s). Mean phase angle, as a measurement of thoracoabdominal asynchrony, was 19.59 +/- 10.06°, and mean difference between nasal and plethysmographic flow measurements was 0.18 +/- 0.07 L/s. Tidal volume, peak inspiratory flow, and peak expiratory flow were significantly higher in sternally recumbent alpacas than in standing alpacas. Cytologic examination of BAL fluid revealed 58.52 +/- 12.36% alveolar macrophages, 30.53 +/- 13.78% lymphocytes, 10.95 +/- 9.29% neutrophils, 0% mast cells, and several ciliated epithelial cells. Conclusions and Clinical Relevance-Pulmonary function testing was tolerated well in nonsedated untrained alpacas. Bronchoalveolar lavage in alpacas yielded samples with adequate cellularity that had a greater abundance of neutrophils than has been reported in horses.

Previously we described the development of an attenuated Pasteurella multocida mutant that expresses only the N-terminal truncated fragment of P. multocida toxin (N-PMT) and its protective effects in a mouse model. This paper details our evaluation of the vaccine potential of this mutant strain in pigs. Pigs vaccinated with the mutant showed significantly higher rates of antibody induction and lower nasal conchal (turbinate) scores for atrophic rhinitis than controls, which suggests that this mutant strain may be a good candidate for a live attenuated vaccine.

This cross-sectional clinical study compared inflammation, including expression of the chemokine interleukin (IL)-8 and intercellular cell adhesion molecule-1 (ICAM-1), in the stifle joints of 4 control dogs and 23 dogs with cranial cruciate ligament rupture (CCLR). The CCL, synovial membrane, meniscus, cartilage, and synovial fluid from the affected stifle joints of all the dogs were examined. Inflammatory cell counts were performed on the synovial fluid, and the tissues were processed for histologic study and immunohistochemical detection of IL-8 and ICAM-1. The synovial fluid from the stifle joints of the dogs with CCLR had an increased percentage of neutrophils (P = 0.054) and a decreased percentage of lymphocytes (P = 0.004) but not macrophages compared with the fluid from the control dogs. There was accumulation of inflammatory cells and increased expression of IL-8 and ICAM-1 in the vascular endothelium of the synovial membrane and the CCL of the dogs with CCLR. The increase in inflammatory cells in the stifle joints of dogs with CCLR may therefore be due to increased expression of IL-8 and ICAM-1 in the synovial membrane and the CCL after the injury. These data may help in understanding the mechanisms of inflammation associated with CCLR.

The objective of this study was to determine whether post-vaccination antibody titers vary according to body weight in adult dogs. Antibody titers against canine parvovirus type 2 (CPV-2), canine distemper virus (CDV), and canine adenovirus type 1 (CAdV-1) were measured for 978 domestic adult dogs from 2 to 6 y of age. The dogs had been vaccinated approximately 12 mo earlier with a commercial combination vaccine. The dogs were divided into groups according to their weight. It was found that mean antibody titers in all weight groups were sufficient to prevent infection. Intergroup comparison, however, revealed that CPV-2 antibody titers were significantly higher in the Super Light (< 5 kg) group than in the Medium (10 to 19.9 kg) and Heavy (> 20 kg) groups and were also significantly higher in the Light (5 to 9.9 kg) group than in the Heavy group. Antibody titers against CDV were significantly higher in the Super Light, Light, and Medium groups than in the Heavy group. There were no significant differences among the groups for the CAdV-1 antibody titers.

Objective: To identify gait characteristics during trotting on a treadmill in nonlame Labrador Retrievers presumed predisposed or not predisposed to cranial cruciate ligament disease (CCLD). Animals: Clinically normal Labrador Retrievers presumed predisposed (n = 10) or not predisposed (7) to CCLD. Procedures: The right hind limb of each dog was classified by use of a predictive score equation that combined tibial plateau angle and femoral anteversion angle as presumed predisposed (high score [> −1.5]) or not predisposed (low score [≤ −1.5]) to CCLD. Tarsal joint, stifle joint, and hip joint kinematics, net moments, and powers were computed. Results: The stifle joint was held at a greater degree of flexion in limbs presumed predisposed to CCLD (130.9° vs 139.3°). More power was generated by muscles acting on the stifle joint in the early stance phase of limbs presumed to be predisposed to CCLD (2.93 vs 1.64 W/kg). The tarsal joint did not reach the same degree of extension in limbs presumed predisposed to CCLD, compared with that in limbs presumed not predisposed to CCLD (179.0° vs 161.0°). Velocity, stance time, vertical and craniocaudal forces, angular velocities, and net joint muscle moments did not differ between groups. Conclusions and Clinical Relevance: Gait mechanics of dogs with high (> −1.5) and low (≤ −1.5) tibial plateau angle and femoral anteversion angle scores were characterized on a treadmill, which may help in the identification of dogs predisposed to CCLD.