OBJECTIVE To determine whether isoflurane-anesthetized cats with demonstrated resistance to the immobilizing effects of fentanyl would exhibit naltrexone-reversible sparing of the minimum alveolar concentration (MAC) of isoflurane when fentanyl was coadministered with the centrally acting catecholamine receptor antagonist acepromazine. ANIMALS 5 healthy male purpose-bred cats. PROCEDURES Anesthesia was induced and maintained with isoflurane in oxygen. Baseline isoflurane MAC was measured by use of a standard tail clamp stimulus and bracketing study design. Afterward, fentanyl was administered IV to achieve a plasma concentration of 100 ng/mL by means of target-controlled infusion, and isoflurane MAC was remeasured. Next, acepromazine maleate (0.1 mg/kg) was administered IV, and isoflurane MAC was remeasured. Finally, isoflurane concentration was equilibrated at 70% of the baseline MAC. Movement of cats in response to tail clamping was tested before and after IV bolus administration of naltrexone. Physiologic responses were compared among treatment conditions. RESULTS Isoflurane MAC did not differ significantly between baseline and fentanyl infusion (mean ± SD, 1.944 ± 0.111% and 1.982 ± 0.126%, respectively). Acepromazine with fentanyl significantly decreased isoflurane MAC to 1.002 ± 0.056% of 1 atm pressure. When isoflurane was increased to 70% of the baseline MAC, no cats moved in response to tail clamping before naltrexone administration, but all cats moved after naltrexone administration. CONCLUSIONS AND CLINICAL RELEVANCE Acepromazine caused fentanyl to decrease the isoflurane MAC in cats that otherwise did not exhibit altered isoflurane requirements with fentanyl alone. Results suggested that opioid-mediated increases in brain catecholamine concentrations in cats counteract the opioid MAC-sparing effect.

OBJECTIVE To determine the dose of coenzyme Q10 (CoQ10) needed to achieve at least a 3-fold increase in plasma CoQ10 concentration in dogs with myxomatous mitral valve disease (MMVD) and congestive heart failure (CHF). ANIMALS 18 dogs with CHF due to MMVD and 12 healthy dogs. PROCEDURES In a randomized, double-blinded, controlled trial, dogs with MMVD were given 50 or 100 mg of water-soluble CoQ10 (ubiquinone; total daily dose, 100 mg [n = 5] or 200 mg [6]) or a placebo (7), PO, twice a day for 2 weeks in addition to regular cardiac treatment. Plasma CoQ10 concentration was measured in dogs with MMVD before (baseline) and at various time points after supplementation began and in healthy dogs once. Concentrations were compared among and within groups. RESULTS No significant difference in median baseline plasma CoQ10 concentration was detected between healthy dogs and dogs with MMVD. Fold increases in plasma CoQ10 concentrations ranged from 1.7 to 4.7 and 3.2 to 6.8 for individual dogs in the 100-mg and 200-mg groups, respectively. The change in plasma CoQ10 concentration after supplementation began was significantly higher than in the placebo group at 4 hours and 1 and 2 weeks for dogs in the 200-mg group and at 1 and 2 weeks for dogs in the 100-mg group. CONCLUSIONS AND CLINICAL RELEVANCE A daily CoQ10 dose of 200 mg was sufficient to achieve at least a 3-fold increase in plasma CoQ10 concentration and may be used in CoQ10 supplementation studies involving dogs with CHF due to MMVD.

Chronic cholangiohepatitis (CCH) is a common pathological condition in cats with a guarded prognosis and unknown etiology. Recently, in human medicine, there has been increased interest in enhancing liver defense mechanisms as an effective treatment strategy to control liver diseases that have a poor prognosis. Metallothionein (MT) is a ubiquitous protein, which has been widely researched for its role in liver defense through heavy metal detoxification, neutralization of reactive oxygen species, and liver regeneration. In this study, immunohistochemistry was used to evaluate the role of MT in CCH and hepatocellular regeneration in 34 cats histologically diagnosed with this condition by assessing the correlation between hepatocellular MT and Ki-67 (marker for cellular proliferation) expression with histological parameters of CCH, such as inflammation, fibrosis, and bile duct proliferation. Statistical analysis was performed using the Spearman-rank correlation test. A significant positive correlation was observed between inflammation and the number of MT-positive hepatocytes (r = 0.36, P = 0.03) and MT labelling intensity (r = 0.37, P = 0.03). In 16 of 34 cases (47%) MT labelling intensity was noted to be pronounced towards the centrilobular zone and very weak or absent towards the portal zone. The results suggest that MT is induced in the liver during chronic inflammatory conditions, which could be speculated as a host defensive mechanism to protect the liver from inflammation-mediated liver injury. Therapeutic interventions utilizing MT, therefore, may have a positive effect on cats with chronic cholangiohepatitis.

OBJECTIVE To investigate the effects of orally administered trazodone on intraocular pressure (IOP), pupil diameter measured in the vertical plane (ie, vertical pupil diameter [VPD]), selected physical examination variables, and sedation level in healthy equids. ANIMALS 7 horses and 1 pony. PROCEDURES Food was withheld for 12 hours prior to drug administration. After baseline (time 0) sedation scoring, physical examination, and measurement of IOP and VPD, equids received 1 dose (approx 6 mg/kg) of trazodone orally. Examination and measurement procedures were repeated 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Blood samples were collected at each time point for analysis of plasma trazodone concentrations. Repeated-measures analysis was used to compare examination results between downstream time points and baseline. RESULTS 7 of 8 equids had mild sedation from 0.5 to 8 hours after treatment; compared with baseline values, mean IOP was significantly lower from 0.5 hours to 8 hours, mean VPD was significantly smaller at 0.5 hours, and mean rectal temperature was significantly lower from 1 to 8 hours after drug administration. Adverse effects (signs of excitement in 1 equid and sweating in 4) were self-limiting and considered minor. Mean maximum plasma concentration of trazodone was 1,493 ng/mL 0.75 hours after administration, and terminal half-life of the drug was 9.96 hours. CONCLUSIONS AND CLINICAL RELEVANCE The described oral dose of trazadone elicited sedation with a few self-limiting adverse effects in the study sample. Drug effects on IOP and VPD may alter ocular examination findings. Further investigation is warranted prior to use of trazodone for sedation in equids, particularly those with ophthalmic conditions.

The purpose of this study was to analyze the morpho-functional features of the ovaries and uterus of sows with different genotypes for the estrogen receptor (ESR), prolactin receptor (PRLR), and follicle-stimulating hormone subunit beta (FSHβ) genes associated with reproductive traits. Healthy Large White sows were studied. The genotypic status of the ESR, PRLR, and FSHβ genes was detected by polymerase chain reaction-restriction fragment length polymorphism. The structure of the ovaries and uterus was studied using quantitative assessment of organs and histological research. Sows with the ESR BB genotype significantly exceeded animals with the ESR AA genotype in milk yield (by 0.3 kg) and in the number of piglets at birth (by 0.9 animals) and at weaning (by 0.7 animals). Sows with the ESR AB genotype were midway between those with ESR BB and ESR AA genotypes in terms of these reproductive traits. Animals with the PRLR AA genotype significantly exceeded those with the PRLR BB genotype in the number of piglets born (P < 0.05); the differences in litter weight at birth were not significant. Compared to other genotypes, sows with genotypes ESR BB (P < 0.05) and PRLR AA (AB) (P < 0.05) had larger uteruses and more yellow bodies, tertiary follicles, and primordial follicles in their ovaries. Animals with the FSHβ BB genotype significantly exceeded animals with the FSHβ AB genotype in the length of uterus by 21 cm (P < 0.05).

OBJECTIVE To evaluate whether mesenchymal stem cells (MSCs) can be safely administered IV to dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD) to improve cardiac function and prolong survival time. ANIMALS 10 client-owned dogs with CHF secondary to MMVD. PROCEDURES Dogs with an initial episode of CHF secondary to MMVD were enrolled in a double-blind, placebo-controlled clinical trial. Five dogs in the MSC group received allogeneic Wharton jelly-derived MSCs (2 × 106 cells/kg, IV), and 5 dogs in the placebo group received a 1% solution of autologous serum (IV) for 3 injections 3 weeks apart. Cell-release criteria included trilineage differentiation, expression of CD44 and CD90 and not CD34 and major histocompatability complex class II, normal karyotype, and absence of contamination by pathogenic microorganisms. Patients were followed for 6 months or until death or euthanasia. Echocardiographic data, ECG findings, serum cardiac biomarker concentrations, CBC, and serum biochemical analysis results were obtained prior to and 4 hours after the first injection and every 3 months after the final injection. RESULTS Lymphocyte and eosinophil counts decreased significantly 4 hours after injection, and monocytes decreased significantly only in dogs that received an MSC injection. No significant differences were seen in the echocardiographic variables, ECG results, serum cardiac biomarker concentrations, survival time, and time to first diuretic drug dosage escalation between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE This study showed that MSCs can be easily collected from canine Wharton jelly as an allogeneic source of MSCs and can be safely delivered IV to dogs with CHF secondary to MMVD.

The purpose of this retrospective analysis was to determine if fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) could potentially be an accurate staging tool for detecting metastatic lymph nodes in dogs with appendicular osteosarcoma based on the quantitative measurement of the maximum standard uptake value (SUVmax) of lymph nodes. A total of 53 dogs were identified that presented for staging via 18F-FDG PET/CT for primary appendicular osteosarcoma. Patients were categorized according to lymph node status of having either metastatic or non-metastatic nodes based on cytological or histological analysis. Maximum standard uptake (SUVmax) values of the sampled lymph node(s) were recorded and 3/77 (3.9%) of sampled lymph nodes were confirmed metastatic. A Mann-Whitney test revealed a statistical difference in the SUVmax of the metastatic versus non-metastatic lymph nodes [median: 6.6 to 95% confidence interval (CI): 2.56 to 14.37 versus 2.18 95% CI: 2.32 to 3.17, respectively, P-value = 0.05]. This retrospective analysis revealed a significant difference in the SUVmax as measured on 18F-FDG PET/CT between metastatic lymph nodes and non-metastatic lymph nodes in canine patients afflicted with appendicular osteosarcoma, in spite of the small numbers analyzed. While these results are promising, they should be interpreted with caution and further studies are justified.

In humans and other mammals, general anesthesia impairs thermoregulation, leading to warm core blood redistributing to the periphery. This redistribution is an important contributor to hypothermia that can be reduced with pre-warming before anesthesia. Additionally, sedation following premedication has been associated with hypothermia in dogs. In a prospective, randomized, cross-over study, 8 adult male and female rats (weighing 388 to 755 g) were sedated with intramuscular ketamine-midazolam-hydromorphone, then placed in an unwarmed cage or warmed box for 14 minutes, followed by 30 minutes of isoflurane anesthesia with active warming. Core body temperature was monitored throughout. After sedation, warmed rats gained 0.28°C ± 0.13°C and unwarmed rats lost 0.19°C ± 0.43°C, a significant difference between groups (P = 0.004). After anesthesia, warmed rats maintained higher core temperatures (P < 0.0001) with 2/8 and 6/8 of warmed and unwarmed rats becoming hypothermic, respectively. Pre-warming during sedation and active warming during general anesthesia is effective in minimizing hypothermia.

From 50 to 60% of companion animals in the United States are overweight or obese and this obesity rate is rising. As obesity is associated with a number of health problems, an agent that can help weight loss in pets and assist in clinically managing obesity through veterinary prescription foods and medication would be beneficial. Many studies have shown that celastrol, a phytochemical compound found in Celastrus orbiculatus extract (COE), has anti-obesity and anti-inflammatory effects, although these effects have not yet been determined in canine or canine-derived cells. The objective of this study was to investigate the effects of celastrol on the adipogenic differentiation and lipolysis of canine adipocytes. Primary preadipocytes were isolated from the gluteal region of a beagle dog and the primary adipocytes were differentiated into mature adipocytes by adipocyte differentiation media containing isobutylmethylxanthine, dexamethasone, and insulin. In a water-soluble tetrazolium (WST) assay, the cell viability of mature adipocytes was decreased after treatment with COE (0, 0.93, 2.32, and 4.64 nM celastrol) in a concentration-dependent manner, although preadipocytes were not affected. Oil Red O (ORO) staining revealed that COE inhibited the differentiation into mature adipocytes and lipid accumulation in adipocytes. In addition, treatment with COE significantly reduced triglyceride content and increased lipolytic activities by 1.5-fold in canine adipocytes. Overall, it was concluded that COE may enhance anti-obesity activity in canine adipocytes by inhibiting lipid accumulation and increasing lipolytic activity.

OBJECTIVE To compare pregnancy-associated glycoprotein 1 (PAG1) concentrations in maternal (jugular vein) and fetal (uterine vein) circulations and amniotic fluid samples between pregnant ewes that were and were not experimentally infected with bovine viral diarrhea virus (BVDV). ANIMALS 11 healthy pregnant yearling ewes. PROCEDURES Before study initiation, all ewes were naïve to BVDV and confirmed pregnant by transabdominal ultrasonography at approximately 60 days of gestation. At 65 days of gestation, ewes were intranasally inoculated with a noncytopathic BVDV type 1b strain (concentration, 107 TCID50/mL; 2 mL/nostril; n = 6) or an equal volume of BVDV-free viral culture medium (control; 5). A blood sample was collected for measurement of PAG1 concentration before inoculation. At 80 days of gestation, each ewe was anesthetized and underwent an ovariohysterectomy. While sheep were anesthetized, blood samples from the jugular and uterine veins and an amniotic fluid sample were collected for measurement of PAG1 concentration. Fetal tissues underwent real-time PCR analysis for BVDV RNA, and placental specimens underwent histologic evaluation and immunohistochemical staining for BVDV antigen. RESULTS At 80 days of gestation, BVDV RNA in fetal tissues and mild placentitis were detected in 5 of 6 BVDV-inoculated ewes. Mean PAG1 concentrations in the maternal and fetal circulations of BVDV-inoculated ewes were significantly less than those in control ewes. Mean amniotic fluid PAG1 concentration did not differ significantly between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Concentration of PAG1 in the maternal circulation may be a useful biomarker for determining placental health in sheep after viral infection of the reproductive tract.