Efficacy of the oral supplement, Equine Omega Complete, for the prevention of gastric ulcers and alpha-tocopherol supplementation in horses.

BACKGROUND: Omega-3 fatty acid and alpha-tocopherol supplementation reduces gastric ulcer formation in humans and rodents; however, efficacy of prevention in horses is unknown. Equine Omega Complete (EOC) is an oral supplement containing omega-3 fatty acids and alpha-tocopherol. HYPOTHESIS/OBJECTIVE: Determine if EOC supplementation prevents gastric ulcers and increases serum alpha-tocopherol concentrations in healthy horses. ANIMALS: Nine thoroughbred geldings; 5-13 years old. METHODS: Prospective randomized block design, repeated in crossover model. Horses were administered EOC, omeprazole, or water PO for 28 days. Horses underwent an established gastric ulcer induction protocol from days 21-28 via intermittent feed deprivation. Gastroscopies were performed on days 0, 21, and 28. Serum alpha-tocopherol concentrations were measured on days 0 and 28. The effects of treatment and time on ulcer grades were assessed with ordinal logistic regression, with significance at P-value <.05. RESULTS: Ulcer grades increased during ulcer induction in control and EOC but not omeprazole groups (P = .02). Grades increased in EOC-treated horses after ulcer induction from a median of 1 [95% confidence interval 0-2.5] (day 0) to 2.5 [1.5-3.5] (day 28) and were similar to the control group (P = .54). Serum alpha-tocopherol increased in EOC-treated horses from day 0 to day 28 (mean 2.2 ± 0.43 µg/mL to 2.96 ± 0.89 µg/mL; P < .001) with high individual variation; this increase was not different from omeprazole or control groups. CONCLUSION AND CLINICAL IMPORTANCE: Supplementation with EOC for 28 days did not prevent gastric ulcer formation nor increase alpha-tocopherol concentrations relative to the control group.

Changes in Heart Rate Variability with Induction of Gastric Ulcers in Adult Horses.

Gastric ulceration can be induced by athletic training and is a significant welfare concern. The objective of this study was to evaluate the effect of gastric ulcer induction on heart rate variability (HRV) in the horse. We hypothesized that induction of gastric ulcers would decrease HRV and increase low frequency fluctuations, consistent with increased sympathetic tone. A convenience sample of 8 horses in a larger study were enrolled. Horses were randomly assigned to receive water or 2 mg/kg omeprazole orally once daily for 28 days. Gastric ulcers were induced through intermittent feed withholding on days 21 to 28. Gastroscopy was performed and gastric ulcers were graded (0-IV) by three blinded reviewers on days 21 and 28. Continuous electrocardiograms were obtained for one hour at the start and end of ulcer induction. HRV was assessed in 1-hour recordings for time domain variables and 5 minute sections for frequency domain analysis. HRV and ulcer grade across treatments were compared by a mixed effect model, with treatment and time as fixed effects and horse as a random effect. Gastric ulcer grade increased with induction protocol (P < .0001) and decreased with omeprazole treatment (P = .0007). Omeprazole treatment increased R-R intervals (P = .01) and decreased ratio of low frequency/high frequency signal (P = .008) as compared to horses receiving water. This was attributable to decreasing low frequency fluctuations (P = .05). While limited by the small sample size (four horses/treatment), this study suggests that omeprazole treatment decreases heart rate, and LF/HF ratio during ulcer induction, consistent with a decrease in sympathetic tone.

Validation and method comparison for a point-of-care lateral flow assay measuring equine whole blood insulin concentrations.

The Wellness Ready Test (WRT) is a lateral flow, stall-side assay that measures equine insulin in whole blood and requires validation before recommending clinical use. We evaluated intra- and inter-assay precision and linearity and compared the WRT with a radioimmunoassay (RIA). Tested concentrations ranged from <139 to >695 pmol/L (<20 to >100 µIU/mL). For 20 replicates at each insulin level, intra-assay CVs of the WRT for insulin were 13.3%, 12.9%, and 15.3% at low (139-278 pmol/L; 20-40 µIU/mL), intermediate (278-417 pmol/L; 40-60 µIU/mL), and high (>417 pmol/L; >60 µIU/mL) concentrations, respectively. For 10 replicates at each level (3 assay lots), inter-assay CVs were 15.9%, 11.0%, and 11.7%, respectively. In the weighted linear regression of 5 measured insulin concentrations against expected concentrations, R2 = 0.98, slope = 1.02, and y-intercept = 14.4 pmol/L (2.08 µIU/mL). The Spearman correlation coefficient (rs) was 0.90 (95% CI: 0.85-0.94) between the WRT and RIA; the WRT = f(RIA) Passing-Bablok regression yielded the fit, y = 1.005x + 24.3 pmol/L (3.50 µIU/mL). The WRT result averaged 10.4% higher than the RIA result, with targeted bias of 25.9, 26.1, and 26.7 pmol/L (3.74, 3.76, and 3.84 µIU/mL) for cutoffs used to diagnose insulin dysregulation of 312, 347, and 451 pmol/L (45, 50, and 65 µIU/mL). Assay clinical sensitivities, specificities, and accuracies determined at the 3 selected clinical cutoffs and using the RIA as gold standard were 87-95%, 92-96%, and 91-95%, respectively (n = 99 samples). Observed total error was 28.4-30.4%. The WRT had acceptable precision, excellent linearity, and good association with the RIA.

Association of globulin concentrations with prognosis in horses with lymphoma.

Introduction: Lymphoma is the most common hemopoietic neoplasia in horses. Common clinicopathologic abnormalities in equine lymphoma include hyperglobulinemia, hypoalbuminemia, hyperfibrinogenemia, anemia, thrombocytopenia and lymphocytosis. Hypoglobulinemia has been reported in other species with lymphoma, however it has not been well-described in horses. The objectives of this study were to examine the prevalence of hypoglobulinemia in equine lymphoma, and to identify prognosis and clinicopathological abnormalities associated with serum globulin concentrations. Methods: Ninety-six horses with lymphoma were investigated in this retrospective study. Patients were allocated into groups based on serum globulin concentration. Survival analysis was performed to determine risk factors associated with globulin concentration and outcome. Results: Nineteen horses were hypoglobulinemic (≤2.1 g/dL), 63/98 were normoglobulinemic (2.2-4.3 g/dL), and 16/98 were hyperglobulinemic (≥4.4 g/dL). Hyperglobulinemia was associated with a higher anion gap (P = 0.0005), lower bicarbonate (P = 0.006), sodium (P = 0.03) and chloride concentrations (P = 0.002), and higher total protein than hypoglobulinemic horses (P < 0.0001). For location, 37% of horses with mucocutaneous lymphoma were hypoglobulinemic, compared to none in the hyperglobulinemic group (P = 0.02). Survival times were significantly different between low, normal and high globulin groups (P = 0.0002, median [range] survival times: 333 [1-3792], 43 [1-4,001] and 4 [1-129] days, respectively). Significant risk factors for shortened time to death were hyperglobulinemia (HR 2.4, P = 0.02), T cell lymphoma (HR 3.5, P < 0.0001), and multicentric (HR 3.1, P = 0.0008) and mediastinal (HR 6.4, P = 0.006) forms of lymphoma. Lack of chemotherapy was associated with shortened survival time (HR 4.5, P < 0.0001). B cell lymphomas (P < 0.0001) and mucocutaneous lymphoma location (P < 0.0001) were associated with longer survival times. Discussion: Serum globulin concentrations are associated with location of lymphoma, clinicopathologic abnormalities, and survival times in equine lymphoma.

Pharmacokinetics of maropitant citrate after oral administration of multiple doses in adult horses.

The neurokinin-1 (NK-1) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood in horses, and clinical use of NK-1 receptor antagonists has not been reported. This study aimed to determine the pharmacokinetics and safety of maropitant after administration of multiple doses. We hypothesized that maropitant concentrations would be similar at steady state to those reported in dogs, with minimal adverse effects. Maropitant was administered at 4 mg/kg orally, once daily for 5 days in seven adult horses. Serial plasma maropitant concentrations were measured by liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic parameters were determined. The maximum, minimum, and average concentrations of maropitant achieved at steady state were 375.5 ± 200, 16.8 ± 7.7, and 73.5 ± 45.1 ng/ml, respectively. The terminal elimination half-life was 11.6 ± 1.4 hr, and the accumulation index was 1.3 ± 0.07. Heart rate decreased between Day 1 and Day 5 (p = .005), with three horses having heart rates of 20 beats per minute and atrioventricular block on Day 5. Pharmacokinetics of repeated maropitant administration suggests the drug could be considered for use in healthy horses. Further investigation on the clinical relevancy of its cardiac effects is warranted.

Pharmacokinetics of single doses of maropitant citrate in adult horses.

The neurokinin-1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under-recognized in horses. Use of NK-1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC-MS/MS. Pharmacokinetic parameters were determined using noncompartmental analysis. The mean plasma maropitant concentration 3 min after IV administration was 800 ± 140 ng/ml, elimination half-life was 10.37 ± 2.07 h, and volume of distribution was 6.54 ± 1.84 L/kg. The maximum concentration following IG administration was 80 ± 40 ng/ml, and elimination half-life was 9.64 ± 1.27 hr. Oral bioavailability was variable at 13.3 ± 5.3%. Maropitant concentrations achieved after IG administration were comparable to those in small animals. Concentrations after IV administration were lower than in dogs and cats. Elimination half-life was longer than in dogs and shorter than in cats. This study is the basis for further investigations into using maropitant in horses.

Comparison of corneal degeneration and calcific band keratopathy from 2000 to 2013 in 69 horses.

OBJECTIVE: To compare signalment, presentation, treatment, and outcome in horses diagnosed with corneal degeneration (CD) or calcific band keratopathy (CBK) at a referral hospital. ANIMALS STUDIED: Sixty-nine horses (87 eyes) diagnosed with either CD or CBK. PROCEDURES: Medical records of horses diagnosed with CD or CBK at the University of California-Davis Veterinary Medical Teaching Hospital (UCD-VMTH) between 2000 and 2013 were reviewed. Signalment, concurrent ophthalmic diagnoses, previous therapies, diagnostic tests, systemic diagnoses, treatment, follow-up, and outcomes were compared between horses diagnosed with CD or CBK. Age, breed, and gender were compared between the CD/CBK and UCD-VMTH populations. RESULTS: Thirty-three horses (42 eyes) and 36 horses (45 eyes) were diagnosed with CD and CBK, respectively. Horses with CD or CBK were significantly older (P < 0.001) than the UCD-VMTH population with a median age of 16 or 18 years, respectively. Appaloosas were significantly overrepresented in the CD/CBK population (33%) in comparison with the UCD-VMTH population (1.8%, P < 0.001). Equine recurrent uveitis was concurrently diagnosed in 67% and 84% of horses with CD or CBK, respectively. Pituitary pars intermedia dysfunction (PPID) was diagnosed significantly less often in horses with CD vs. CBK (P = 0.03). Chemical chelation with ethylenediaminetetraacetic acid was performed significantly less frequently in horses diagnosed with CD (7.1%) vs. CBK (31.1% of eyes) (P = 0.012). CONCLUSIONS: Despite some differences, equine CD and CBK are relatively similar conditions and may represent a continuum of disease severity. Horses with PPID should be monitored closely for corneal disease including CBK.