OBJECTIVE To determine the pharmacokinetics of cefovecin sodium after SC administration of a single dose to African lions (Panthera leo). ANIMALS 3 adult (9 to 10 years old; 1 male and 2 females) and 3 juvenile (2 years old; 1 male and 2 females) African lions. PROCEDURES A crossover study was conducted. A single dose of cefovecin was administered SC at 4 mg/kg (half dose) and 8 mg/kg (full dose) to African lions. Blood samples were collected daily for 14 days after cefovecin injection. Plasma drug concentrations were determined by use of high-performance liquid chromatography with UV detection. RESULTS Cefovecin had first-order elimination kinetics for doses of 4 and 8 mg/kg. Mean ± SD maximum plasma concentration was 9.73 ± 1.01 μg/mL and 18.35 ± 0.94 μg/mL after doses of 4 and 8 mg/kg, respectively. Time to maximum plasma concentration was approximately 4 hours for both doses. Mean elimination half-life was approximately 111 and 115 hours after doses of 4 and 8 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Cefovecin was detected in lion plasma for 336 hours after administration at both 4 and 8 mg/kg at concentrations greater than the reported minimum inhibitory concentration (0.06 μg/mL) for common bacterial organisms in domestic cats. These results indicated that cefovecin administered at 4 mg/kg SC reached therapeutic concentrations for an extended period in African lions.

Assays were done to assess the ability of 5 methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates from difference sources to adhere to canine and human corneocytes. Cell wall-associated (CWA) protein gene profiles were examined to look for associations with adherence. Five MRSP strains were studied: 3 with the same CWA protein gene profile (14 genes) and belonging to sequence type (ST) 45 were isolated from a dog, a human, and the environment. The other 2 were an environmental isolate belonging to ST433 that had the lowest number of CWA protein genes (12) and a canine clinical isolate belonging to ST733 that had the greatest number of CWA protein genes (18). The 3 isolates of MRSP ST45, a major clone in Thailand, had the greatest ability to adhere to canine and human corneocytes. Nevertheless, MRSP adherence ability could not be predicted from the profile of genes encoding CWA proteins.

The objective of this study was to assess whether concentrations of epidermal growth factor (EGF), fibronectin, and alpha(α)-2-macroglobulin in canine serum remain stable under different storage conditions. Serum was obtained from 10 adult dogs and stored for 7 d at room temperature (RT) and at 4°C and for 1, 3, and 6 mo at -20°C. Bacterial cultures of serum were carried out after 7 d at 4°C and at RT. For each dog and time point, EGF, fibronectin, and α-2-macroglobulin were quantified in duplicate by enzyme-linked immunosorbent assay (ELISA). Mean concentrations of each factor at each time point were used for statistical analysis. No bacterial growth was observed in any samples. Compared to baseline (232.24 ± 49.47 pg/mL), EGF concentration was significantly lower after 1 wk of storage at 4°C (135.39 ± 27.12 pg/mL, P = 0.006), but not at RT (315.85 ± 79 pg/mL, P = 0.6) or after 1, 3, or 6 mo of storage at -20°C (220.84 ± 41.07 pg/mL, P = 0.7; 220.98 ± 78.26 pg/mL, P = 0.8; 266.06 ± 20.39 pg/mL, P = 0.4, respectively). Compared to baseline, concentrations of fibronectin after 1 wk of storage at 4°C or at RT and 1, 3, or 6 mo of storage at -20°C were not statistically different. Compared to baseline (186.67 ± 45.20 mg/dL), the concentration of α-2-macroglobulin after 1 wk of storage at 4°C was significantly increased (244.61 ± 58.27 mg/dL, P = 0.002), but not at RT (177.09 ± 26.99 mg/dL, P = 0.2). The differences in concentration after 3 and 6 mo of storage at -20°C were significant compared to baseline (243.32 ± 42.64 mg/dL, P = 0.005 and 56.39 ± 21.78 mg/dL, P < 0.0001, respectively), but not after 1 mo of storage at -20°C (136.79 ± 25.61 mg/dL, P = 0.1). One week of storage at RT has little effect on the stability of EGF, fibronectin, and α-2-macroglobulin in canine serum. Measured factors remain stable for 3 mo of storage at -20°C.

The use of dietary supplements as an alternative treatment for joint-related pathologies such as osteoarthritis (OA) is increasing. However, there is little scientific evidence to support the intended use. The aim of this study was to evaluate the anti-inflammatory effects of creatine- and amino acid-based supplements in primary cultured canine chondrocytes (CnCs) as an in-vitro model of OA and compare the effects to more commonly used agents, such as the non-steroidal anti-inflammatory drug (NSAID), carprofen, and the joint supplement, glucosamine (GS). CnCs were stimulated with interleukin-1β (IL-1β) and the subsequent release of prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNFα) was measured using an enzyme-linked immunosorbent assay (ELISA). Changes in oxylipins were also assessed using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). All compounds examined were able to significantly reduce the release of PGE2 and TNFα and were associated with reductions in cyclooxygenase-2 (COX-2) expression and nuclear factor-kappaB (NF-κB) phosphorylation. The creatine- and amino acids-based supplements also altered the profile of oxylipins produced. All compounds examined were less effective at reducing the release of PGE2 than carprofen. Carprofen significantly increased release of TNFα from CnCs, however, while the other agents reduced TNFα release. This study suggests that creatine- and amino acid-based supplements may have a beneficial role in preventing inflammation within the joint and that further studies are warranted.

The degree of analgesia provided by blind techniques for brachial plexus blocks (BPBs) has not been compared in clinical cases undergoing surgery of the thoracic limb. The objective of this study was to evaluate the anesthetic conditions and postoperative analgesia resulting from 3 different BPB local anesthetic techniques in canine patients undergoing such surgery. Twenty-four client-owned dogs received a standardized premedication/induction protocol (hydromorphone and acepromazine/propofol), maintained with isoflurane in oxygen using mechanical ventilation, in a prospective, randomized, blinded clinical trial. Before surgery, dogs received 1 of 3 anatomical BPB techniques: traditional, perpendicular, or axillary, with 0.2 mL/kg body weight (BW) of bupivacaine 0.5%. Cardiorespiratory variables and isoflurane end-tidal concentrations were recorded throughout anesthesia. Scores for anesthetic maintenance (0-best to 4-responsive), recovery quality (0-not responsive to 3-responsive), and Glasgow pain scale were recorded for up to 24 h postoperatively. All dogs recovered uneventfully from anesthesia and no differences in the measured variables or scores were noted among groups, during and after anesthesia. When thoracic limb amputations in each of the 3 groups (n = 9; 4 in traditional, 3 in perpendicular, 2 in axillary) were compared to the other surgical procedures (n = 15); however, scores for anesthetic maintenance were higher [0 (0 to 1) versus 0 (0 to 0); median (interquartile range)], recovery [1 (0 to 2) versus 0 (0 to 0)], and pain [2.4 (2.4 to 3.0) versus 1.6 (1.4 to 2.2)] in the first 3 h post-extubation. Surgery times were also longer with amputations [115 min (100 to 138 min) versus 50 min (41 to 90 min)]. The 3 BPB techniques provided similar anesthesia and postoperative pain scores. Despite higher pain scores in thoracic limb amputations than in less invasive surgeries, the BPB appeared to provide significant comfort.

OBJECTIVE To determine variability of global longitudinal strain (GLS) and strain rate (SR) measurements in dogs with and without cardiac disease derived from 2-D speckle tracking echocardiography (STE) by use of various software. ANIMALS 2 cohorts comprising 44 dogs (23 cardiovascularly healthy and 21 with cardiac disease) and 40 dogs (18 cardiovascularly healthy and 22 with cardiac disease). PROCEDURES Transthoracic echocardiographic images in each cohort were analyzed with vendor-independent software and vendor-specific 2-D STE software for each of 2 vendors. Values for GLS and SR obtained from the same left parasternal apical views with various software were compared. Intraobserver and interobserver variability was determined, and agreement among results for the various software was assessed. RESULTS Strain analysis was not feasible with vendor-independent software for 20% of images obtained with the ultrasonography system of vendor 1. Intraobserver and interobserver coefficient of variation was < 10% for GLS values, whereas SR measurements had higher variance. There was a significant difference in GLS and SR obtained for each cohort with different software. Evaluation of Bland-Altman plots revealed wide limits of agreement, with variance for GLS of up to 6.3 units in a single dog. CONCLUSIONS AND CLINICAL RELEVANCE Results of longitudinal strain analysis were not uniform among software, and GLS was the most reproducible measurement. Significant variability in results among software warrants caution when referring to reference ranges or comparing serial measurements in the same patient because changes of < 6.5% in GLS might be within measurement error for different postprocessing software.

OBJECTIVE To describe a technique for endoscopic evaluation of the coelomic viscera of koi (Cyprinus carpio) and to evaluate the ability to visually examine coelomic structures by use of an approach cranial or caudal to the pelvic girdle. ANIMALS 16 subadult koi. PROCEDURES Koi were anesthetized with buffered tricaine methanesulfonate. Coelioscopic examination was performed via a ventral midline incisional approach cranial or caudal to the pelvic girdle. A 2.7-mm × 18-cm 30° oblique endoscope within a 4.8-mm operating sheath and infusion of saline (0.9% NaCl) solution was used. Ease of entry into the coelomic cavity and visual examination of structures were scored for each fish. Fish were euthanized 2 or 8 weeks after the procedure, and necropsy was performed. RESULTS The coelioscopic procedure was tolerated well, and all koi recovered uneventfully. For all fish, ease of entry and visual examination scores of the liver, intestines, gonads, heart, and anterior kidney were satisfactory to excellent. Visual examination of the posterior kidney and swim bladder was satisfactory to difficult, whereas the spleen and gallbladder were not visually identified. No significant differences were noted in entry or visual examination scores between the cranial and caudal approaches or between sexes. Minor complications included mild hemorrhage, rupture of the gonadal capsule, formation of adhesions between the viscera and incision site, and delayed healing of the incision. CONCLUSIONS AND CLINICAL RELEVANCE Diagnostic coelioscopy of koi appeared to be safe and effective. This procedure could have potential for use in examination of coelomic structures and disease diagnosis.

OBJECTIVE To evaluate and quantify the kinematic behavior of canine mandibles before and after bilateral rostral or unilateral segmental mandibulectomy as well as after mandibular reconstruction with a locking reconstruction plate in ex vivo conditions. SAMPLE Head specimens from cadavers of 16 dogs (range in body weight, 30 to 35 kg). PROCEDURE Specimens were assigned to undergo unilateral segmental (n = 8) or bilateral rostral (8) mandibulectomy and then mandibular reconstruction by internal fixation with locking plates. Kinematic markers were attached to each specimen in a custom-built load frame. Markers were tracked in 3-D space during standardized loading conditions, and mandibular motions were quantified. Differences in mandibular range of motion among 3 experimental conditions (before mandibulectomy [ie, with mandibles intact], after mandibulectomy, and after reconstruction) were assessed by means of repeated-measures ANOVA. RESULTS Both unilateral segmental and bilateral rostral mandibulectomy resulted in significantly greater mandibular motion and instability, compared with results for intact mandibles. No significant differences in motion were detected between mandibles reconstructed after unilateral segmental mandibulectomy and intact mandibles. Similarly, the motion of mandibles reconstructed after rostral mandibulectomy was no different from that of intact mandibles, except in the lateral direction. CONCLUSIONS AND CLINICAL RELEVANCE Mandibular kinematics in head specimens from canine cadavers were significantly altered after unilateral segmental and bilateral rostral mandibulectomy. These alterations were corrected after mandibular reconstruction with locking reconstruction plates. Findings reinforced the clinical observations of the beneficial effect of reconstruction on mandibular function and the need for reconstructive surgery after mandibulectomy in dogs.

The proposed advantages of intra-arterial chemotherapy (IAC) are based on the premises of local dose escalation to the tumor and reduced availability of systemic drugs. There is a lack of objective pharmacokinetic data to confirm the advantage of IAC in dogs with naturally occurring urogenital tumors. The objective of this study was to determine if IAC administration in urogenital tumors would result in decreased systemic drug exposure when compared to intravenous routes. Twenty-two dogs with naturally occurring urogenital tumors were enrolled in this prospective case-controlled study. Mitoxantrone, doxorubicin, or carboplatin were administered by IAC and intravenous routes [intravenous awake (intravenous chemotherapy - IVC) and under general anesthesia (IVGAC)] 3 weeks apart. Serum assays were used to determine the extent of systemic drug exposure. Dose-normalized peak systemic serum concentration (Cmax) and area under the serum drug concentration-time curve (AUC) were used to quantify systemic exposure. A total of 26 mitoxantrone treatments were administered to 10 dogs. While there was no significant difference in Cmax, the AUC was significantly lower after IAC compared with IVGAC. Ten doxorubicin treatments were administered to 5 dogs. There were no significant differences in Cmax or AUC. A total of 14 carboplatin treatments were administered to 7 dogs. The Cmax was significantly lower for IAC compared to IVC, while the AUC values were equivocal. This study demonstrates certain lower serum values may be achieved after IAC delivery of carboplatin and mitoxantrone. These chemotherapy agents may have a preferred pharmacological profile for regional chemotherapy delivery in dogs with urogenital tumors.

OBJECTIVE To characterize the pharmacokinetics of a clinically relevant dose of misoprostol administered PO or per rectum (PR) to horses. ANIMALS 8 healthy adult horses. PROCEDURES In a randomized 3-way crossover design, horses received a single dose of misoprostol (5 μg/kg) administered PO (with horses fed and unfed) and PR, with a minimum 3-week washout period separating the experimental conditions. Blood samples were obtained before and at various points after drug administration (total, 24 hours), and plasma concentrations of misoprostol free acid were measured. RESULTS Mean maximum plasma concentration of misoprostol was significantly higher in the PR condition (mean ± SD, 967 ± 492 pg/mL) and unfed PO condition (655 ± 259 pg/mL) than in the fed PO condition (352 ± 109 pg/mL). Mean area under the concentration-versus-time curve was significantly lower in the PR condition (219 ± 131 pg•h/mL) than in the unfed (1,072 ± 360 pg•h/mL) and fed (518 ± 301 pg•h/mL) PO conditions. Mean time to maximum concentration was ≤ 30 minutes for all conditions. Mean disappearance half-life was shortest in the PR condition (21 ± 29 minutes), compared with values for the unfed (170 ± 129 minutes) and fed (119 ± 51 minutes) PO conditions. No adverse effects were noted. CONCLUSIONS AND CLINICAL RELEVANCE Misoprostol was rapidly absorbed and eliminated regardless of whether administered PO or PR to horses. Rectal administration may be a viable alternative for horses that cannot receive misoprostol PO, but this route may require more frequent administration to maintain therapeutic drug concentrations.