Objective: To determine the isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection. Animals: 13 purpose-bred adult cats. Procedures: Cats were infected with 100 third-stage larvae or received a sham inoculation, and the left caudal lung lobe was collected 278 to 299 days after infection. Isometric responses of intrapulmonary bronchiolar rings were studied by use of a wire myograph. Three cycles of contractions induced by administration of 10μM acetylcholine were followed by administration of the contractile agonists acetylcholine, histamine, and 5-hydroxy-tryptamine. To evaluate relaxation, intrapulmonary bronchiolar rings were constricted by administration of 10μM 5-hydroxytryptamine, and concentration-response curves were generated from administration of sodium nitroprusside, isoproterenol, and substance P. Results: Compared with tissues from control cats, contractile responses to acetylcholine and 5-hydroxytryptamine were reduced in tissues from heartworm-infected cats. Relaxation to isoproterenol was significantly reduced in tissues from heartworm-infected cats. Relaxation to substance P was increased in tissues from heartworm-infected cats, but relaxation to sodium nitroprusside was unchanged. Conclusions and Clinical Relevance: Results suggested that despite increased bronchiolar wall thickness in heartworm-infected cats, a hyperreactive response of the bronchiolar smooth muscle is not the primary mechanism of respiratory tract clinical signs. Reduced response of the airway to isoproterenol may indicate refractoriness to bronchiolar relaxation in heartworm-infected cats.

Objective: To evaluate the effects of the pacemaker funny current (If) inhibitor ivabradine on heart rate (HR), left ventricular (LV) systolic and diastolic function, and left atrial performance in healthy cats and cats with hypertrophic cardiomyopathy (HCM). Animals: 6 healthy cats and 6 cats with subclinical HCM. Procedures: Anesthetized cats underwent cardiac catheterization and were studied over a range of hemodynamic states induced by treatment with esmolol (200 to 400 μg/kg/min, IV), esmolol and dobutamine (5 μg/kg/min, IV), ivabradine (0.3 mg/kg, IV), and ivabradine and dobutamine. Left ventricular systolic and diastolic function, cardiac output, and left atrial function were studied via catheter-based methods and echocardiography. Results: Treatment with ivabradine resulted in a significant reduction of HR, rate-pressure product, and LV contractile function and a significant increase in LV end-diastolic pressure, LV end-diastolic wall stress, and LV relaxation time constant (tau) in cats with HCM. Concurrent administration of ivabradine and dobutamine resulted in a significant increase of LV contractility and lusitropy, with blunted chronotropic effects of the catecholamine. Left atrial performance was not significantly altered by ivabradine in cats with HCM. Regression analysis revealed an association between maximum rate of LV pressure rise and tau in cats with HCM. Conclusions and Clinical Relevance: Ivabradine had significant effects on several cardiovascular variables in anesthetized cats with HCM. Studies in awake cats with HCM are needed to clinically validate these findings.

Objective: To determine whether an interferon (IFN)-γ response sufficient to categorize cattle as positive for tuberculosis can be detected in blood collected at commencement of exsanguination at slaughter. Animals: 15 Holstein cows. Procedures: 12 cows were experimentally sensitized by SC injection with inactivated Mycobacterium bovis in mineral oil, which induced an immune response that mimicked natural infection with M bovis. Three nonsensitized control cows were injected SC with mineral oil alone. By 5 weeks after injection, only the 12 sensitized cows had positive results for tuberculosis with whole blood IFN-γ assay. At that time, all 15 cows were sent to slaughter and samples of blood were collected from each cow immediately before stunning and at commencement of exsanguination (within 90 seconds after stunning). A whole blood IFN-γ assay was performed on the samples. Conditional probability and paired t tests were used to analyze changes in the categorical test interpretation and qualitative IFN-γ production, respectively. Results: All 12 sensitized cows had positive results for tuberculosis in samples obtained immediately before stunning, and 9 retained positive results for samples obtained at commencement of exsanguination. There was a significant decrease in the mean background-corrected IFN-γ ELISA optical density values for samples obtained at commencement of exsanguination. Conclusions and Clinical Relevance: IFN-γ response sufficient to classify cattle as positive for tuberculosis could be detected in blood collected at commencement of exsanguination. These findings support further development and use of the IFN-γ assay on blood samples collected at exsanguination as part of a bovine tuberculosis surveillance program.

Objective: To retrospectively assess the safety and efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) used as part of autologous bone marrow transplantation in dogs with lymphoma. Animals: 21 dogs with lymphoma at any disease stage. Procedures: Medical records of dogs with lymphoma that underwent intensified chemotherapy and received an autologous bone marrow transplant following owner administration of recombinant human G-CSF (5 μg/kg, SC, q 12 h) for 7 days between January 2007 and July 2009 were reviewed. Results of physical examinations and CBCs performed before and at intervals during a 24-month period after G-CSF treatment were assessed. The safety of recombinant human G-CSF administration was determined via assessment of both short-term (ie, during the 7-day G-CSF treatment period) and long-term adverse effects. Results: None of the dogs developed any adverse effect attributable to the administration of recombinant human G-CSF during G-CSF administration or during follow-up periods of 1 month to 2 years (median follow-up period, 4 months). Among the 18 dogs for which CBC results were available for analysis, mean circulating neutrophil count significantly increased after administration of recombinant human G-CSF, compared with value before treatment. Conclusions and Clinical Relevance: Results indicated that recombinant human G-CSF administered SC at a dosage of 5 μg/kg every 12 hours for 7 days appeared to be safe and effective when used in dogs with lymphoma that were undergoing autologous bone marrow transplant.

Objective: To determine alterations of serum biochemical variables in relation to changes of near- and far-field mean grayscale histogram (MGSH) and attenuation rates in liver ultrasonograms of periparturient cows. Animals: 67 Holstein cows. Procedures: Cows were allocated on the basis of body condition score into underconditioned (n = 21), moderately conditioned (23), and overconditioned (23) groups. Serum samples (obtained every 10 days from 30 days before to 30 days after calving) were analyzed for aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltransferase activities and BUN, albumin, calcium, and inorganic phosphorus concentrations along with digital estimation of near- and far-field MGSH values of liver ultrasonograms and deep attenuation. Values were compared among groups and within each group, and their correlations were determined in the pre- and postpartum periods. Results: Serum biochemical variables did not differ significantly among groups. Aspartate aminotransferase and γ-glutamyltransferase activities increased in the postpartum period. Fluctuations of alanine aminotransferase activity were not significant; BUN decreased significantly in the peripartum period. Albumin concentration decreased prior to parturition and remained low, but significantly increased after parturition. Calcium concentration decreased on day 10 but subsequently increased. Phosphorus concentration decreased stepwise until day 10 after calving. Postpartum biochemical variables had weak correlations with near- and far-field MGSH values in overconditioned cows. The highest levels of sound attenuation were found in overconditioned cows on calving day. Conclusions and Clinical Relevance: Liver ultrasonographic features were poorly correlated with changes of serum biochemical variables. This suggests that liver ultrasonography is not a good technique for estimating functional liver abnormalities in periparturient cows.

Objective: To evaluate the analgesic efficacy of ABT-116, a transient receptor potential cation channel vanilloid subfamily V member 1 antagonist, and compare it with that of buprenorphine by measurement of mechanical and thermal nociceptive thresholds in dogs. Animals: Six 7- to 8-month-old dogs (3 males and 3 females). Procedures: In a crossover study design, all dogs received ABT-116 (30 mg/kg, PO) and buprenorphine (0.03 mg/kg, orotransmucosally), with each treatment separated by 1 week. Physiologic variables were recorded prior to and 1, 6, and 24 hours after drug administration. Thermal (thoracic) and mechanical (dorsolateral aspect of the radius [proximal] and dorsopalmar aspect of the forefoot [distal]) nociceptive thresholds were assessed prior to (baseline) and 15 minutes and 1, 2, 4, 6, 12, 18, and 24 hours after treatment. Results: Buprenorphine administration resulted in higher overall thermal and proximal mechanical nociceptive thresholds, compared with ABT-116. Distal mechanical nociceptive thresholds after treatment were higher than baseline values for both treatments, but the magnitude of change was greater for buprenorphine at 1 hour after administration. Whereas HR and RR sporadically differed from baseline values after ABT-116 administration, rectal temperature increased from a baseline value of 39 ± 0.2°C (mean ± SD) to a peak of 40.6 ± 0.2°C at 6 hours. Conclusions and Clinical Relevance: In dogs without inflammation or nerve injury, PO administration of ABT-116 did not consistently result in an increase in nociceptive thresholds. However, clinically relevant increases in rectal temperature were identified after ABT-116 administration.

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 the prevalence of selected virulence genes and the antimicrobial susceptibility of multidrug-resistant (MDR) Escherichia coli isolated from diarrheic neonatal calves. Sample: 97 E coli isolates from diarrheic neonatal calves. Procedures: E coli isolates were tested via PCR assay for 6 virulence genes and susceptibility to 17 drugs belonging to 9 classes. A 2-sample test of proportions was used to make comparisons between proportions of virulent and avirulent MDR isolates. Results: 23 of 97 (23.7%) isolates were virulent, and 74 (76.3%) were avirulent. Of the 23 virulent isolates, 15 (65.2%) were positive for K99, 14 (60.9%) for F41, 12 (52.2%) for STa, 9 (39.1%) for Stx1, 6 (26.1%) for intimin, and 0 (0%) for Stx2. Twenty of 23 (87.0%) virulent isolates expressed ≥ 2 virulence genes, and 3 of 23 (13.0%) were positive for 1 virulence factor. Eight of 23 (34.8%) virulent isolates expressed STa, K99, and F41, whereas 1 of 23 (4.4%) was positive for STa, F41, intimin, and Stx1. The second most frequent gene pattern was Stx1 and intimin. Twenty of 23 (87.0%) virulent isolates were MDR; the highest prevalence of resistance was recorded for the macrolide-lincosides, followed by the tetracyclines and penicillins. Also, 17 of 23 (74.0%) virulent isolates were resistant to sulfadimethoxine, and 10 of 23 (43.5%) were resistant to trimethoprim-sulfamethoxazole. Additionally, 60 of 74 (81.0%) avirulent isolates were MDR. Conclusions and Clinical Relevance: The prevalence of multidrug resistance was comparable for virulent and avirulent E coli isolated from diarrheic neonatal calves. Cephalosporins and aminoglycosides had reasonable susceptibility.

Objective: To perform repeated anterior chamber fluorophotometry on both eyes of ophthalmologically normal dogs to measure fluorescein concentrations over a 5-day period and identify any change in the degree of anterior chamber fluorescence over time or difference between eyes. Animals: 9 healthy adult dogs (18 eyes). Procedures: Each dog received an IV injection of 10% fluorescein solution, and anterior chamber fluorophotometry was performed 1 hour later on both eyes. This procedure was repeated at the same time each day for 5 consecutive days. Results: A significant increase in fluorescein concentration was evident in the anterior chamber on day 5 in the right eye and days 2, 3, 4, and 5 in the left eye. There was no significant difference in concentration between the left and the right eyes on any day. Conclusions and Clinical Relevance: The increase in ocular fluorescein concentration in the study dogs was unlikely to be of clinical importance and is only pertinent for subsequent research studies. This is a limitation that should be considered when reporting fluorophotometry data as fluorescein concentration or as change in fluorescein concentration from baseline.

Objective: To assess the status of antimicrobial resistance (AMR), identify extraintestinal virulence factors (VFs) and phylogenetic origins, and analyze relationships among these traits in extraintestinal pathogenic Escherichia coli (ExPEC) isolates from companion animals. Sample: 104 E coli isolates obtained from urine or genital swab samples collected between 2003 and 2010 from 85 dogs and 19 cats with urogenital infections in Japan. Procedures: Antimicrobial susceptibility of isolates was determined by use of the agar dilution method; a multiplex PCR assay was used for VF gene detection and phylogenetic group assessment. Genetic diversity was evaluated via randomly amplified polymorphic DNA analysis. Results: Of the 104 isolates, 45 (43.3%) were resistant to > 2 antimicrobials. Phylogenetically, 64 (61.5%), 22 (21.2%), 13 (12.5%), and 5 (4.8%) isolates belonged to groups B2, D, B1, and A, respectively. Compared with other groups, group B2 isolates were less resistant to all tested antimicrobials and carried the pap, hly, and cnf genes with higher frequency and the aer gene with lower frequency. The aer gene was directly associated and the pap, sfa, hly, and cnf genes were inversely associated with AMR. Randomly amplified polymorphic DNA analysis revealed 3 major clusters, comprised mainly of group B1, B2, and D isolates; 2 subclusters of group B2 isolates had different VF and AMR status. Conclusions and Clinical Relevance Prevalences of multidrug resistance and human-like phylogenetic origins among ExPEC isolates from companion animals in Japan were high. It is suggested that VFs, phylogenetic origins, and genetic diversity are significantly associated with AMR in ExPEC.