Increasing plasma methadone concentrations are associated with decreased leukocyte oxidative burst without affecting cytokine production or phagocytosis in healthy dogs.
Lauren Chittick, Jared A Jaffey, Charles A Veltri, Charlotte Bolch, Imani Carswell, Heather Perkins, Anderson da Cunha
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引用次数: 0
Abstract
Objective: To determine whether methadone administration affects leukocyte phagocytic function, oxidative burst, and cytokine production and if immune function is associated with plasma methadone concentrations in dogs.
Methods: This was a prospective, randomized, placebo-controlled, nonblinded crossover study. Ten client-owned healthy dogs were included in the study. Dogs were randomized to receive either methadone (0.3 mg/kg, IV) or placebo (0.9% NaCl, IV) once every 6 hours for 24 hours. Dogs were crossed over to the alternative treatment following a 7-day interval period. Blood was collected at baseline (ie, before treatment administration) and then 10 minutes, 6 hours, and 24 hours after the first treatment administration. Immune function tests and plasma methadone concentrations were measured at all time points (before treatment administration and 10 minutes, 6 hours, and 24 hours after the first treatment administration). Plasma methadone concentrations were measured with liquid chromatography quadrupole time-of-flight mass spectrometry. Whole blood cultures were performed with exposure to PBS, lipopolysaccharide, and lipoteichoic acid. Canine-specific multiplex assay was used to measure tumor necrosis factor-α, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor concentrations in the supernatant. Granulocytic and monocytic phagocytosis and oxidative burst were evaluated via flow cytometry.
Results: There was a moderate inverse association between the percentage of granulocytes and monocytes undergoing oxidative burst and plasma methadone concentrations (r = -0.88, r2 = 0.77, P < .001). Oxidative burst percentage increased over time regardless of treatment (F[1,67] = 7.758; P < .007). No other between treatment or time differences were identified.
Conclusions: Increasing methadone concentrations is associated with decreased leukocyte oxidative burst in healthy dogs.
Clinical relevance: Methadone may have immunologic effects in dogs but requires additional investigation.
期刊介绍：
The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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