Neurokinin-1 antagonism as a novel treatment for feline asthma : investigation of the role of substance p in airflow limitation and airway inflammation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Feline asthma, a chronic respiratory condition, results cough and/or episodic respiratory distress induced by airway hyperresponsiveness (AHR), airway eosinophilia, and airway remodeling. Homeostasis in the lung is partially maintained by the neuroimmune axis, where cross-talk between these systems is mediated via cytokines, neuropeptides and their receptors. The studies described herein evaluate tachykinins and their receptors as diagnostic tools and/or interventions using an experimental model of feline asthma. The first phase of this project evaluated capsaicin, a transient receptor potential cation channel subfamily V member 1 (TRPV1) agonist, as an indirect bronchoprovocant in experimentally asthmatic cats. Five cats induced to have asthma using Bermuda grass allergen (BGA) were studied. Twenty-four hours after aerosol challenge of BGA, cats were anesthetized and aerosols of saline followed by 10 fold increasing concentrations of capsaicin (0.4 to 4000 [mu]M) were nebulized. This was followed by ventilator acquired pulmonary mechanics. No significant alteration was seen in either SPO2 or airway resistance (EC200raw) indicating that capsaicin is not an effective bronchoprovocant in a feline asthma model. The second phase of the study examined acute and chronic administration of maropitant citrate, a NK1 receptor antagonist, on clinical signs, airway hyperresponsiveness, and airway eosinophilia when given immediately following allergen challenge and in a chronic setting. To study efficacy in acute asthmatic crises, 7 cats received subcutaneous maropitant (2mg/kg) or placebo (PBS) 10 minutes after BGA challenge; after a 2 week washout, alternate treatment was given. To study efficacy for chronic airway damage, six cats received maropitant (2mg/kg) in a food treat or a food treat alone every 48 hrs for 4 weeks; after a 2 week washout, alternate treatment was given. Study endpoints included a subjective scoring system with visual analogue scale (VAS), ventilator-acquired pulmonary mechanics to assess AHR after bronchoprovocation with methacholine, and airway eosinophilia. Mann-Whitney Rank Sum Tests were used with P<0.05 considered significant. A single injection of maropitant failed to diminish VAS scoring (P= 0.710), AHR (P=0.456) or airway eosinophilia (P= 0.165) versus placebo. Chronic administration of maropitant failed to diminish VAS scoring (P=0.589), AHR (P=0.818), or airway eosinophilia (P = 0.699) versus placebo. Maropitant failed to improve any measured parameter of feline asthma in either an acute crisis or with chronic ongoing inflammation and cannot be recommended as a treatment.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Veterinary biomedical sciences (MU)

Grantor dc:publisher

University of Missouri--Columbia

Year dc:date.issued

2018

Author dc:creator

• Grobman, Megan Elizabeth

Advisor dc:contributor.advisor

• Reinero, Carol R.

Statement dc:rights

• Access to files is limited to the campuses of the University of Missouri with SSO login.

Language dc:language.iso

eng, English

DOI

https://doi.org/10.32469/10355/67735

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/67735