Objective: To compare the cardiorespiratory, gastrointestinal, analgesic, and behavioral effects between IV and IM administration of morphine in conscious horses with no signs of pain. Animals: 6 healthy adult horses. Procedures: Horses received saline (0.9% NaCl) solution (IM or IV) or morphine sulfate (0.05 and 0.1 mg/kg, IM or IV) in a randomized, masked crossover study design. The following variables were measured before and for 360 minutes after drug administration: heart and respiratory rates; systolic, diastolic, and mean arterial blood pressures; rectal temperature; arterial pH and blood gas variables; intestinal motility; and response to thermal and electrical noxious stimuli. Adverse effects and horse behavior were also recorded. Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were measured via liquid chromatography–mass spectrometry. Results: No significant differences in any variable were evident after saline solution administration. Intravenous and IM administration of morphine resulted in minimal and short-term cardiorespiratory, intestinal motility, and behavioral changes. A decrease in gastrointestinal motility was detected 1 to 2 hours after IM administration of morphine at doses of 0.05 and 0.1 mg/kg and after IV administration of morphine at a dose of 0.1 mg/kg. Morphine administration yielded no change in any horse's response to noxious stimuli. Both morphine-3-glucuronide and morphine-6-glucuronide were detected in plasma after IV and IM administration of morphine. Conclusions and Clinical Relevance: Clinically relevant doses of morphine sulfate yielded minimal and short-term behavioral and intestinal motility effects in healthy horses with no signs of pain. Neither dose of morphine affected their response to a noxious stimulus.

The effects of 2 different continuous rate infusions (CRIs) of medetomidine over an 8-hour period on sedation score, selected cardiopulmonary parameters, and serum levels of medetomidine were evaluated in 6 healthy, conscious dogs using a crossover study design. The treatment groups were: CONTROL = saline bolus followed by saline CRI; MED1 = 2 μg/kg body weight (BW) medetomidine loading dose followed by 1 μg/kg BW per hour CRI; and MED2 = 4 μg/kg BW medetomidine loading dose followed by 2 μg/kg BW per hour CRI. Sedation score (SS), heart rate (HR), respiratory rate (RR), temperature (TEMP), systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP), arterial and mixed venous blood gas analyses, lactate, and plasma levels of medetomidine were evaluated at baseline, at various intervals during the infusion, and 2 h after terminating the infusion. Statistical analysis involved a repeated measures linear model. Both infusion rates of medetomidine-induced dose-dependent increases in SS and dose-dependent decreases in HR, SAP, MAP, and DAP were measured. Respiratory rate (RR), TEMP, central venous pH, central venous oxygen tension, and oxygen extraction ratio also decreased significantly in the MED2 group at certain time points. Arterial oxygen and carbon dioxide tensions were not significantly affected by either infusion rate. In healthy dogs, both infusion rates of medetomidine-induced clinically relevant sedative effects, accompanied by typical alpha2 agonist-induced hemodynamic effects, which plateaued during the infusion and subsequently returned to baseline. While additional studies in unhealthy animals are required, the results presented here suggest that medetomidine infusions at the doses studied may be useful in canine patients requiring sedation for extended periods.

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 evaluate the expression of Ki67 and epidermal growth factor receptor (EGFR), mitotic index (MI), and microvascular density (MVD) in feline oral squamous cell carcinoma (SCC) via immunohistochemical staining on archival tumor tissues and to seek a correlation between these markers and clinical variables. Sample: 22 archived tumor samples of feline oral SCC. Procedures: Immunohistochemical staining for Ki67, MVD, and EGFR was performed and scored. Patient survival information was obtained from the medical records. These molecular markers as well as MI were correlated with tumor locations and patient survival time. Results: The 22 tumors had wide variation in Ki67 expression, MI, MVD, and EGFR expression. Tongue SCC had higher MVD than did mandibular and maxillary SCC. Tumor expression of EGFR was inversely proportional to survival time. Conclusions and Clinical Relevance: Results suggested that EGFR expression might be a valuable prognostic factor for treatment outcome in feline oral SCC. It also identified higher angiogenesis in tongue SCC, compared with mandibular and maxillary SCC, which may account for a different clinical outcome. Further prospective characterization of feline oral SCC may provide a better understanding of the underlying molecular factors that drive its behavior and offer the possibility for future patient-specific treatment plans.

Objective: To determine the distribution of cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) in skin (including hair follicles and sweat and sebaceous glands) of clinically normal dogs and dogs with atopic dermatitis (AD) and to compare results with those for positive control samples for CB1 (hippocampus) and CB2 (lymph nodes). Sample: Skin samples from 5 healthy dogs and 5 dogs with AD and popliteal lymph node and hippocampus samples from 5 cadavers of dogs. Procedures: CB1 and CB2 were immunohistochemically localized in formalin-fixed, paraffin-embedded sections of tissue samples. Results: In skin samples of healthy dogs, CB1 and CB2 immunoreactivity was detected in various types of cells in the epidermis and in cells in the dermis, including perivascular cells with mast cell morphology, fibroblasts, and endothelial cells. In skin samples of dogs with AD, CB1 and CB2 immunoreactivity was stronger than it was in skin samples of healthy dogs. In positive control tissue samples, CB1 immunoreactivity was detected in all areas of the hippocampus, and CB2 immunoreactivity was detected in B-cell zones of lymphoid follicles. Conclusions and Clinical Relevance: The endocannabinoid system and cannabimimetic compounds protect against effects of allergic inflammatory disorders in various species of mammals. Results of the present study contributed to knowledge of the endocannabinoid system and indicated this system may be a target for treatment of immune-mediated and inflammatory disorders such as allergic skin diseases in dogs.

Objective: To determine various measurements of medial retropharyngeal lymph nodes (MRPLNs) in healthy cats via ultrasonography and CT. Animals: 45 cats (age range, 2 to 8 years). Procedures: Cats underwent CT of the head and ultrasonography of the cervical region. Various measurements of MRPLNs were obtained, and parenchymal heterogeneity, presence of a hilus, appearance of margins, and attenuation of MRPLNs were determined. Results: Data for 7 cats were excluded because they did not meet inclusion criteria; data for 38 cats were evaluated. Measurements of left and right MRPLNs were not significantly different. Mean length × rostral height × rostral width dimensions of MRPLNs were 20.7 × 12.4 × 3.7 mm and 20.7 × 13.1 × 4.7 mm in ultrasonographic and CT images, respectively. Maximum MRPLN dimensions were approximately 32 × 20 × 7 mm. Mean attenuation of MRPLNs was 40.2 Hounsfield units. Parenchyma of MRPLNs was mildly (via CT) to moderately (via ultrasonography) heterogeneous. A hilus was identified in 95% (via ultrasonography) and 24% or 92% (via CT [depending on criteria used to define a hilus]) of MPRLNs. Lymph node margins were smooth in CT images and mildly irregular in ultrasonographic images. A negative linear correlation was detected between age of cat and MRPLN volume. Conclusions and Clinical Relevance: MRPLNs in cats were easily imaged via ultrasonography and CT. Left and right MRPLNs were symmetric, and MRPLNs were larger in young adult cats versus old cats. Data were intended to serve as references for evaluation of MRPLNs in healthy cats.

During the last ten years, numerous species have been treated with deslorelin implants to induce contraception. The aims of the study were 1) to assess contraceptive efficacy of 4.7 mg subcutaneous deslorelin implants in rats, 2) to determine the latency of contraceptive effect, and 3) to determine potential side effects. Three experimental females were implanted and their estrous cycle was studied by vaginal smear. Two weeks after implantation, a male whose fertility was previously assessed with a control female, was introduced into their cage. No female conceived during the 4 mo following implantation. Additionally, 38 pet rats were recruited from clients in practice to test for potential side effects, including 6 males and 32 females with a mean age of 14 mo. Local reaction and transient weight gain during the first 2 wk, as well as behavioral changes were recorded. According to this pilot study, deslorelin implant could be used as a contraceptive method in female rats. The latency period is about 2 wk. Nevertheless, it might be possible to refine the treatment further using hormonal measurements. The duration of contraceptive effect is to be determined in an upcoming study.

Objective: To determine whether the reported drug-drug interaction between the flea medication spinosad and ivermectin is attributable to inhibition of P-glycoprotein by spinosad. Animals: 6 healthy adult dogs with the ABCB1 wildtype genotype. Procedures: The study was conducted as a prospective, masked, randomized crossover design. Six dogs were allocated to 2 groups; each dog served as its own control animal. Dogs in one of the groups received spinosad at the manufacturer's recommended dose; the other group received no treatment. Forty-eight hours later, scintigraphic imaging of the head and abdomen were performed with the radiolabeled P-glycoprotein substrate methoxy-isobutyl-isonitrile (sestamibi) in both groups of dogs. After a washout period of 60 days, the dogs in each group received the alternate treatment, and scintigraphic imaging again was performed 48 hours later. Gallbladder-to-liver and brain-to-neck musculature ratios of technetium Tc 99m sestamibi were calculated for each dog and compared between treatments. Results: No significant differences in gallbladder-to-liver or brain-to-neck musculature ratios were found between treatments. Conclusions and Clinical Relevance: Results provided evidence that spinosad did not inhibit P-glycoprotein function 48 hours after spinosad was administered at the manufacturer's recommended dose. Further investigations will be necessary to elucidate the mechanism of the reported toxic interaction between spinosad and ivermectin.

Objective: To determine whether vaccine virus can be detected by use of reverse transcriptase (RT)-PCR assays for pooled and individual skin samples obtained from cattle after vaccination with a commercially available modified-live bovine viral diarrhea virus (BVDV) vaccine. Animals: 12 BVDV-seropositive steer calves and 7 BVDV-seronegative (antibody titer < 1:4) heifers; all cattle were free of persistent infection with BVDV. Procedures: 2 experiments were conducted. Cattle were vaccinated on day 0 with a commercially available modified-live BVDV vaccine. Skin samples were collected on days 0, 3 to 14, 16, and 18 for virus detection by use of RT-PCR assay on individual and pooled samples. In addition, blood samples and nasal swab specimens were collected for virus isolation. Results: All cattle, regardless of serologic status, had negative results for BVDV as determined by use of RT-PCR assay of individual and pooled skin samples. Virus was detected via virus isolation in serum or the buffy coat in 5 of 7 heifers that were seronegative when vaccinated. Conclusions and Clinical Relevance: These findings indicated that it would be unlikely to detect BVDV vaccine virus in skin by use of RT-PCR assay of individual or pooled skin samples obtained from cattle after vaccination with a commercially available modified-live BVDV vaccine. Veterinarians and producers should be confident that positive test results for BVDV on skin samples would not likely be caused by the vaccination virus after administration of a modified-live virus vaccine.