Objective: To investigate the effects of the concurrent administration of 70% N2O on the minimum alveolar concentration (MAC) for sevoflurane in dogs, the MAC derivative that blocks motor movement (MAC(NM)), and the MAC derivative that blocks autonomic responses (MAC(BAR)). Animals: 7 adult sexually intact male mixed-breed dogs. Procedures: For each dog, anesthesia was induced with sevoflurane delivered via a face mask. Initially, the baseline MAC, MAC(NM), and MAC(BAR) for sevoflurane were determined by use of a noxious stimulus (50 V, 50 Hz, and 10 milliseconds) applied subcutaneously over a midulnar region. Nitrous oxide (70%) was added to the breathing circuit, and MAC, MAC(NM), and MAC(BAR) were determined again. Percentage changes from the respective baseline concentrations for MAC, MAC(NM)’ and MAC(BAR) were calculated after the administration of N2O. Results: Baseline median values for the MAC, MAC(NM), and MAC(BAR) for sevoflurane were 1.75%, 2.00%, and 2.50%, respectively. Addition of 70% N2O significantly decreased MAC, MAC(NM), and MAC(BAR) by 24.4%, 25.0%, and 35.2%, respectively, and these values did not differ significantly from each other. Conclusions and Clinical Relevance: Supplementation with 70% N2O caused a clinically important and significant decrease in the MAC, MAC(NM)’ and MAC(BAR) for sevoflurane in dogs.

Objective: To determine associations between serum concentrations of omega-3 polyunsaturated fatty acids or body condition and serum concentrations of adiponectin, leptin, insulin, glucose, or triglyceride in healthy dogs. Animals: 62 healthy adult client-owned dogs. Procedures: Body condition score and percentage of body fat were determined. Blood samples were collected after food was withheld for 12 hours. Serum was harvested for total lipid determination, fatty acid analysis, and measurement of serum concentrations of adiponectin, leptin, insulin, glucose, and triglyceride. Associations between the outcome variables (adiponectin, leptin, insulin, glucose, and triglyceride concentrations) and each of several variables (age, sex, percentage of body fat, and concentrations of total lipid, α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) were determined. Results: Serum concentrations of docosapentaenoic acid were significantly positively associated with concentrations of adiponectin and leptin and negatively associated with concentrations of triglyceride. Serum concentrations of α-linolenic acid were significantly positively associated with concentrations of triglyceride. No significant associations were detected between serum concentrations of eicosapentaenoic acid or docosahexaenoic acid and any of the outcome variables. Percentage of body fat was significantly positively associated with concentrations of leptin, insulin, and triglyceride but was not significantly associated with adiponectin concentration. Age was positively associated with concentrations of leptin, insulin, and triglyceride and negatively associated with concentrations of adiponectin. Sex did not significantly affect serum concentrations for any of the outcome variables. Conclusions and Clinical Relevance: Docosapentaenoic acid may increase serum concentrations of adiponectin and leptin and decrease serum triglyceride concentration in healthy dogs.

Objective: To assess joint kinematics in dogs with osteoarthritis of the hip joints during walking up an incline or down a decline and over low obstacles and to compare findings with data for nonlame dogs. Animals: 10 dogs with osteoarthritis of the hip joints (mean ± SD age, 6.95 ± 3.17 years; mean body weight, 34.33 ± 13.58 kg) and 8 nonlame dogs (3.4 ± 2.0 years; 23.6 ± 4.6 kg). Procedures: Reflective markers located on the limbs and high-speed cameras were used to record joint kinematics during walking up an incline or down a decline and over low obstacles. Maximal flexion, extension, and range of motion of the hip joints were calculated. Results: Osteoarthritis of the hip joints reduced extension of both hip joints and flexion of the contralateral hind limb, compared with flexion of the lame hind limb, during walking down a decline. Walking up an incline resulted in decreased extension of the stifle joint in both hind limbs of osteoarthritic dogs; extension was significantly decreased for the lame hind limb. During walking over low obstacles, maximal flexion of the stifle joint was increased significantly for the contralateral hind limb. Maximal flexion was increased in both tarsal joints. Conclusions and Clinical Relevance: Osteoarthritis of the hip joints led to complex changes in the gait of dogs, which involved more joints than the affected hip joint alone. Each exercise had specific effects on joint kinematics that must be considered when planning a rehabilitation program.

Objective: To determine the influence of intensified training and subsequent reduced training on glucose metabolism rate and peripheral insulin sensitivity in horses and identify potential markers indicative of early overtraining. Animals: 12 Standardbred geldings. Procedures: Horses underwent 4 phases of treadmill-based training. In phase 1, horses were habituated to the treadmill. In phase 2, endurance training was alternated with high-intensity exercise training. In phase 3, horses were divided into control and intensified training groups. In the intensified training group, training intensity, duration, and frequency were further increased via a protocol to induce overtraining; in the control group, these factors remained unaltered. In phase 4, training intensity was reduced. Standardized exercise tests were performed after each phase and hyperinsulinemic euglycemic clamp (HEC) tests were performed after phases 2, 3, and 4. Results: 10 of 12 horses completed the study. Dissociation between mean glucose metabolism rate and mean glucose metabolism rate-to-plasma insulin concentration ratio (M:I) was evident in the intensified training group during steady state of HEC testing after phases 3 and 4. After phase 4, mean glucose metabolism rate was significantly decreased (from 31.1 ± 6.8 μmol/kg/min to 18.1 ± 3.4 μmol/kg/min), as was M:I (from 1.05 ± 0.31 to 0.62 ± 0.17) during steady state in the intensified training group, compared with phase 3 values for the same horses. Conclusions and Clinical Relevance: Dissociation between the glucose metabolism rate and M:I in horses that underwent intensified training may reflect non-insulin–dependent increases in glucose metabolism.

Objective: To evaluate the effects of oral administration of diphenhydramine on pupil diameter, intraocular pressure (IOP), tear production, tear film quality, corneal sensitivity, and conjunctival goblet cell density (GCD) in clinically normal adult dogs. Animals: 12 healthy adult dogs. Procedures: All dogs received diphenhydramine (2.2 mg/kg, PO, q 12 h) for 21 days. Conjunctival biopsy samples were obtained immediately before (day 1) and after (day 21) treatment with diphenhydramine and conjunctival GCDs were determined. Gross ophthalmic examinations and fluorescein staining of corneas were performed, and pupil diameter, corneal sensitivity, IOP, tear production, and tear film breakup time were determined prior to administration of diphenhydramine on days 1 through 5 and on day 21; pupil diameter and IOP measurements were repeated on each of those days at 20 and 40 minutes and 1, 3, 6, and 8 hours after administration of diphenhydramine. Data were analyzed to detect differences among values for dogs. Results: Clinically important increases in pupil diameter were not detected after administration of diphenhydramine to dogs. Day 1 corneal sensitivity and tear film breakup time for dogs were significantly higher than day 21 values for those variables. Conclusions and Clinical Relevance: Results of this study suggested that oral administration of diphenhydramine to healthy adult dogs was not likely to acutely induce glaucoma or keratoconjunctivitis sicca. However, effects of diphenhydramine in dogs with keratoconjunctivitis sicca or primary glaucoma or dogs genetically predisposed to development of those conditions were not determined. Administration of diphenhydramine to dogs decreased corneal sensitivity and tear film breakup time, although these effects were not clinically important.

Objective: To determine the effects of intratumoral injection of a hyaluronan-cisplatin nanoconjugate on local and systemic platinum concentrations and systemic toxicosis. Animals: 5 dogs with spontaneous soft tissue sarcomas (STSs). Procedures: For each dog, approximately 1.5 mL of hyaluronan nanocarrier conjugated with 20 mg of cisplatin was injected into an external STS. Blood samples were collected immediately before (0 hours) and at 0.5, 1, 2, 3, 4, 24, and 96 hours after hyaluronan-cisplatin injection for pharmacokinetic analyses. Urine samples were obtained at 0 and at 96 hours after hyaluronan-cisplatin injection for urinalysis. Each treated STS and its sentinel lymph nodes were surgically removed 96 hours after the hyaluronan-cisplatin injection. Inductively coupled plasma mass spectrometry was used to measure platinum concentrations in blood samples, tumors, and lymph nodes. Results: No tissue reactions were detected 96 hours after hyaluronan-cisplatin injection. Mean ± SD area under the curve, peak concentration, and terminal half-life for unbound (plasma) and total (serum) platinum were 774.6 ± 221.1 ng•h/mL and 3,562.1 ± 2,031.1 ng•h/mL, 56.5 ± 20.9 ng/mL and 81.6 ± 40.4 ng/mL, and 33.6 ± 16.1 hours and 51.2 ± 29.1 hours, respectively. Platinum concentrations ranged from 3,325 to 8,229 ng/g in STSs and 130 to 6,066 ng/g in STS-associated lymph nodes. Conclusions and Clinical Relevance: Intratumoral injection of the hyaluronan-cisplatin nanoconjugate was well tolerated in treated dogs. Following intratumoral hyaluronan-cisplatin injection, platinum concentration was 1,000-fold and 100-fold greater within treated tumors and tumor-draining lymphatics, respectively, compared with that in plasma.

Objective: To investigate the influence of oxidative stress in terms of antioxidant capacity and lipid peroxidation on the probability of motor neuron disease (MND) in horses. Animals: 88 horses with MND (cases) and 49 controls. Procedures: Blood samples were collected from all horses enrolled, and RBCs and plasma were harvested. Activity of the enzyme erythrocytic superoxide dismutase 1 (SOD1) was determined in the RBCs. Plasma concentrations of α-tocopherols and β-carotenes and activity of glutathione peroxidase were also evaluated. Degree of lipid peroxidation was measured by determining plasma concentrations of lipid hydroperoxides. Differences were evaluated between horse groups. Results: Cases had lower erythrocyte SOD1 activity than did controls, but the difference was not significant. On the other hand, plasma vitamin E concentrations differed significantly between groups, with the cases having lower concentrations. Neither plasma vitamin A concentration nor glutathione peroxidase activity differed between groups; however, cases had significantly higher concentrations of lipid hydroperoxides (18.53μM) than did controls (12.35μM). Conclusions and Clinical Relevance: Horses with MND differed from those without MND by having a lower plasma concentration of vitamin E and higher concentrations of lipid hydroperoxides. Results parallel the findings in humans with sporadic amyotrophic sclerosis and provide evidence supporting the involvement of oxidative stress in the 2 conditions.

Objective: To describe the effect of systemically administered oxytetracycline on the viscoelastic properties of rat tail tendon fascicles (TTfs) to provide a mechanistic rationale for pharmacological treatment of flexural limb deformities in foals. Sample: TTfs from ten 1-month-old and ten 6-month-old male Sprague-Dawley rats. Procedures: 5 rats in each age group were administered oxytetracycline (50 mg/kg, IP, q 24 h) for 4 days. The remaining 5 rats in each age group served as untreated controls. Five days after initiation of oxytetracycline treatment, TTfs were collected and their viscoelastic properties were evaluated via a stress-relaxation protocol. Maximum modulus and equilibrium modulus were compared via a 2-way ANOVA. Collagen fibril size, density, and orientation in TTfs were compared between treated and control rats. Results: Viscoelastic properties were significantly decreased in TTfs from 1-month-old oxytetracycline-treated rats, compared with those in TTfs from 1-month-old control rats. Oxytetracycline had no effect on the viscoelastic properties of TTfs from 6-month-old rats. Collagen fibril size, density, and orientation in TTfs from 1-month-old rats did not differ between oxytetracycline-treated and control rats. Conclusions and Clinical Relevance: Results confirmed that systemically administered oxytetracycline decreased the viscoelastic properties of TTfs from 1-month-old rats but not those of TTfs from 6-month-old rats. The decrease in viscoelastic properties associated with oxytetracycline treatment does not appear to be caused by altered collagen fibril diameter or organization. The age-dependent effect of oxytetracycline on the viscoelastic properties of tendons may be related to its effect on the maturation of the extracellular matrix of developing tendons.

Objective: To determine the accuracy of 3-D and 2-D ultrasonography for quantification of tumor volume in dogs with transitional cell carcinoma (TCC) of the urinary bladder. Animals: 10 dogs with biopsy-confirmed TCC. Procedures: The urinary bladder of each dog was distended with saline (0.9% NaCl) solution (5.0 mL/kg), and masses were measured via 3-D and 2-D ultrasonography. Masses were also measured via 3-D ultrasonography after bladders were distended with 2.5 and 1.0 mL of saline solution/kg. Subsequently, the bladder was deflated and distended with CO2 (5.0 mL/kg); CT was performed after IV contrast medium administration. Tumor volumes were calculated via 3-D ultrasonography, 2-D ultrasonography, and CT (reference method) and compared via ANOVA, Deming regression, and Bland-Altman plots. Repeated-measures ANOVA was used to assess effects of bladder distension on 3-D tumor volume measurements. Repeatability of measurements was estimated via the coefficient of variation for each method. Results: Repeatability was considered good for all 3 methods. There was no significant difference in tumor volume measurements obtained via 3-D ultrasonography at different degrees of urinary bladder distension. Results of Deming regression and Bland-Altman plots indicated excellent agreement between tumor volume measurement with 3-D ultrasonography and CT, but not between 2-D ultrasonography and CT. Conclusions and Clinical Relevance: Tumor volume in dogs with TCC of the urinary bladder was accurately measured via 3-D ultrasonography. Use of 3-D ultrasonography can provide a less expensive and more practical method for monitoring response to treatment than CT and was more accurate than 2-D ultrasonography.

Objective: To determine cardiopulmonary effects of incremental doses of dopamine and phenylephrine during isoflurane-induced hypotension in cats with hypertrophic cardiomyopathy (HCM). Animals: 6 adult cats with severe naturally occurring HCM. Procedures: Each cat was anesthetized twice (once for dopamine treatment and once for phenylephrine treatment; treatment order was randomized). Hypotension was induced by increasing isoflurane concentration. Cardiopulmonary data, including measurement of plasma concentration of cardiac troponin I (cTnI), were obtained before anesthesia, 20 minutes after onset of hypotension, and 20 minutes after each incremental infusion of dopamine (2.5, 5, and 10 μg/kg/min) or phenylephrine (0.25, 0.5, and 1 μg/kg/min). Results: Mean ± SD end-tidal isoflurane concentration for dopamine and phenylephrine was 2.44 ± 0.05% and 2.48 ± 0.04%, respectively. Cardiac index and tissue oxygen delivery were significantly increased after administration of dopamine, compared with results after administration of phenylephrine. Systemic vascular resistance index was significantly increased after administration of phenylephrine, compared with results after administration of dopamine. Oxygen consumption remained unchanged for both treatments. Systemic and pulmonary arterial blood pressures were increased after administration of both dopamine and phenylephrine. Acid-base status and blood lactate concentration did not change and were not different between treatments. The cTnI concentration increased during anesthesia and infusion of dopamine and phenylephrine but did not differ significantly between treatments. Conclusions and Clinical Relevance: Dopamine and phenylephrine induced dose-dependent increases in systemic and pulmonary blood pressure, but only dopamine resulted in increased cardiac output. Hypotension and infusions of dopamine and phenylephrine caused significant increases in cTnI concentrations.