Objective: To evaluate intraday and interday variations in glucose concentrations in cats and to test the utility of a continuous glucose monitoring system (CGMS). Animals: 6 lean and 8 long-term (> 5 years) obese cats. Procedures: Blood glucose concentrations were measured during the course of 156 hours by use of a laboratory hexokinase-based reference method and a handheld glucometer. Interstitial glucose concentrations were evaluated with a CGMS. Results: Paired measures of glucose concentrations obtained with the CGMS typically were marginally higher than concentrations for the reference method and less biased than concentrations obtained with the glucometer. This was partially confirmed by the concordance correlation coefficients of the concentration for the CGMS or glucometer versus the concentration for the reference method, although the correlation coefficients were not significantly different. Mean ± SD area under the curve for the glucose concentration (AUCG) did not differ significantly between lean (14.0 ± 0.5 g/dL•h) and obese (15.2 + 0.5 g/dL•h) cats during the 156-hour period, but one of the obese cats had a much higher AUCG. Within-day glucose variability was small in both lean and obese cats. Conclusions and Clinical Relevance: Glucose homeostasis was maintained, even in long-term obese cats, and intraday glucose fluctuations were small. One obese cat might have been classified as prediabetic on the basis of the AUCG, which was approximately 25% higher than that of the other obese and lean cats. The CGMS can be useful in the evaluation of long-term effects of drugs or diet on glucose homeostasis in cats.

Objective: To compare the ability of 2 partial IV anesthesia (PIVA) techniques to maintain anesthesia, compared with isoflurane alone, in horses. Animals: 45 horses. Procedures: Client-owned horses requiring general anesthesia for a variety of procedures of at least 1 hour's duration were randomly allocated to 3 groups (n = 15/group) that differed for the maintenance protocol. Anesthesia was maintained with isoflurane with a starting end-tidal isoflurane concentration of 1.3% (isoflurane group) or a concentration of 1% supplemented with an adjustable continuous infusion of guaifenesin-ketamine (IGK group) or romifidine-ketamine (IRK group). A predefined scoring system was used to assess anesthetic depth and to adjust anesthetic delivery. The need for rescue anesthetics and recovery quality were compared. Results: A mean ± SD end-tidal isoflurane concentration of 1.36 ± 0.16% was necessary to maintain a surgical plane of anesthesia in the isoflurane group. Mean infusion rates of 5.0 ± 1.3 μL/kg/min and 5.1 ± 0.8 μL/kg/min were necessary to maintain a surgical plane of anesthesia in the IRK and IGK groups, respectively. A lower need for ketamine as a rescue anesthetic was observed in the IGK group, compared with the isoflurane group. Higher blood pressure and lower heart rates were found at selected time points for the IRK group, compared with the IGK and isoflurane groups. Conclusions and Clinical Relevance: Both PIVA protocols were satisfactory to maintain smooth and stable surgical anesthesia in horses. The present study supports previous findings in which PIVA has isoflurane-sparing effects. Furthermore, PIVA did not impair recovery quality.

Objective: To determine expression of microRNA (miRNA) in urinary bladder samples obtained from dogs with grossly normal urinary bladders, inflammatory bladder disease, or transitional cell carcinoma (TCC) and in cells of established canine TCC cell lines. Sample: Samples of grossly normal bladders (n = 4) and bladders from dogs with inflammatory bladder disease (13) or TCC (18), and cells of 5 established canine TCC cell lines. Procedures: Expression of 5 miRNAs (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) that target p53, Rb, or Bcl-2 protein pathways was determined for bladder samples and cells via quantitative real-time PCR assay. Effects of cisplatin (5μM) on proliferation and miRNA expression of cells were determined. Results: Expression of miR-34a and miR-106b was significantly higher in TCC samples than it was in samples of grossly normal bladders. Expression of miR-34a, miR-16, miR-103b, and miR-106b was higher in TCC samples than it was in bladder samples from dogs with inflammatory bladder disease. Cells of established canine TCC cell lines that had the lowest growth after cisplatin treatment had increased miR-34a expression after such treatment. Conclusions and Clinical Relevance: Findings of this study indicated results of miRNA expression assays can be used to distinguish between samples of grossly normal bladders and bladders of dogs with inflammatory bladder disease or TCC. This finding may have clinical relevance because currently available diagnostic tests cannot be used to differentiate these tissues, and inflammatory bladder disease and TCC are both prevalent in dogs. Validation of miRNA expression assays as diagnostic tests may be warranted.

Objective: To evaluate the pharmacokinetics and pharmacodynamics of zolpidem after oral administration of a single dose (0.15 or 0.50 mg/kg) and assess any associated antianxiety and sedative effects in dogs. Animals: 8 clinically normal sexually intact male dogs of various breeds. Procedures: Dogs were assigned to 2 groups (4 dogs/group) and administered zolpidem orally once at a dose of 0.15 or 0.50 mg/kg in a crossover study; each dog received the other treatment once after an interval of 1 week. Blood samples were collected before and at intervals during the 24-hour period following dose administration. For each time point, plasma zolpidem concentration was evaluated via a validated method of high-performance liquid chromatography coupled with fluorescence detection, and pharmacodynamics were assessed via subjective assessments of sedation and level of agitation and selected clinical variables. Results: The pharmacokinetic profile of zolpidem in dogs was dose dependent, and the plasma drug concentrations attained were lower than those for humans administered equivalent doses. The lower dose did not result in any clinical or adverse effects, but the higher dose generated paradoxical CNS stimulation of approximately 1 hour's duration and a subsequent short phase of mild sedation. This sedation phase was not considered to be of clinical relevance. The desired clinical effects were not evident at plasma zolpidem concentrations ≤ 30 ng/mL, and the minimal plasma concentration that induced adverse effects was 60 ng/mL. Conclusions and Clinical Relevance: Results indicated that zolpidem is not a suitable drug for inducing sedation in dogs.

Objective: To compare effects of sterilization with hydrogen peroxide gas plasma (HPGP), ethylene oxide, and steam on bioadhesive properties of nylon and polyethylene lines used for stabilization of canine stifle joints. Sample: Samples of a 36.3-kg test nylon leader line, 57.8-kg test nylon fishing line, and 2-mm ultrahigh–molecular weight polyethylene (UHMWPE) were used. Procedures: In this in vitro study, samples of nylon leader line, fishing line, and UHMWPE sterilized by use of HPGP, ethylene oxide, and steam or unsterilized samples were used. Bacterial adherence on unsterilized and sterilized samples was tested with Staphylococcus epidermidis and Escherichia coli. Five samples were examined for each line type and sterilization condition, and final colony counts were obtained. Results: Bacterial adherence was significantly affected by method of sterilization for all 3 line types. For most of the samples, bacterial adherence was similar or lower when HPGP sterilization was used, compared with results for sterilization via ethylene oxide and steam, respectively. Bacterial adherence was significantly higher for UHMWPE, compared with adherence for the nylon line, regardless of the sterilization method used. Bacterial adherence was higher for nylon fishing line than for nylon leader line for S epidermidis after ethylene oxide sterilization and for E coli after HPGP and ethylene oxide sterilization. Conclusions and Clinical Relevance: Effects of HPGP sterilization on bioadhesive properties of nylon and polyethylene lines compared favorably with those for ethylene oxide and steam sterilization. Also, nylon line may be a more suitable material than UHMWPE for suture prostheses on the basis of bacterial adherence properties.

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.

Objective: To characterize mucosal gene expression in dogs with chronic enteropathy (CE). Animals: 18 dogs with CE and 6 healthy control dogs. Procedures: Small intestinal mucosal biopsy specimens were endoscopically obtained from dogs. Disease severity in dogs with CE was determined via inflammatory bowel index scores and histologic grading of biopsy specimens. Total RNA was extracted from biopsy specimens and microchip array analysis (approx 43,000 probe sets) and quantitative reverse transcriptase PCR assays were performed. Results: 1,875 genes were differentially expressed between dogs with CE and healthy control dogs; 1,582 (85%) genes were downregulated in dogs with CE, including neurotensin, fatty acid–binding protein 6, fatty acid synthase, aldehyde dehydrogenase 1 family member B1, metallothionein, and claudin 8, whereas few genes were upregulated in dogs with CE, including genes encoding products involved in extracellular matrix degradation (matrix metallopeptidases 1, 3, and 13), inflammation (tumor necrosis factor, interleukin-8, peroxisome proliferator–activated receptor γ, and S100 calcium-binding protein G), iron transport (solute carrier family 40 member 1), and immunity (CD96 and carcinoembryonic antigen–related cell adhesion molecule [CEACAM] 18). Dogs with CE and protein-losing enteropathy had the greatest number of differentially expressed genes. Results of quantitative reverse transcriptase PCR assay for select genes were similar to those for microchip array analysis. Conclusions and Clinical Relevance: Expression of genes encoding products regulating mucosal inflammation was altered in dogs with CE and varied with disease severity. Impact for Human Medicine: Molecular pathogenesis of CE in dogs may be similar to that in humans with inflammatory bowel disease.