Abstract

The overall aim of this research is to investigate a spontaneously occurring animal model of airway obstruction and hyperreactivity two feature of human asthma. Horses and ponies develop recurrent airway obstruction and hyperreactivity to antigens, aerosol and intravenous histamine. This proposal will investigate autonomic mechanism and changes in the permeability of airway epithelium as potential mechanisms of the airway obstruction and hyperreactivity observed in ponies. Reactivity will be measured be determining changes in pulmonary resistance and dynamic compliance induced by increading doses of either histamine, citric acid, or methacholine. The role of the parasympathetic nervous system will be investigated by determining lung function and reactivity before an after muscarinic blockade with atropine. Beta adrenergic mechanisms will be determined by measuring lung function and reactivity before and after both beta blockade and beta agonist. Alpha-adrenergic involvement will be evaluated by determining dose response of airways to an alpha adrenergic agonist before and after muscarinic and beta-adrenergic blockade and by use of specific alpha1 and alpha2 antagonists. Airway epithelial permeability will be investigated using intratracheal injections of mannitol. All studies will be conducted during acute airway obstruction and during clinical remission.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL027619-05
Application #
3339238
Study Section
Pathology A Study Section (PTHA)
Project Start
1981-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Michigan State University
Department
Type
Schools of Veterinary Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824

  Publications

Sonea, I M; Bowker, R M; Robinson, N E et al. (1993) Distribution of dopamine beta-hydroxylase and neuropeptide Y-immunoreactive nerves in healthy equine lungs. Am J Vet Res 54:507-13
Sonea, I M; Bowker, R M; Broadstone, R V et al. (1993) Adrenergic and peptidergic innervation of the trachealis muscle in the normal horse: a preliminary report. Res Vet Sci 54:335-9
Scott, J S; Berney, C E; Derksen, F J et al. (1991) Beta-adrenergic receptor activity in ponies with recurrent obstructive pulmonary disease. Am J Vet Res 52:1416-22
LeBlanc, P H; Broadstone, R V; Derksen, F J et al. (1991) In vitro responses of distal airways in horses with recurrent airway obstruction. Am J Vet Res 52:999-1003
McKiernan, B C; Koritz, G D; Scott, J S et al. (1990) Plasma theophylline concentration and lung function in ponies with recurrent obstructive lung disease. Equine Vet J 22:194-7
Gray, P R; Derksen, F J; Robinson, N E et al. (1989) The role of cyclooxygenase products in the acute airway obstruction and airway hyperreactivity of ponies with heaves. Am Rev Respir Dis 140:154-60
Scott, J S; Garon, H; Broadstone, R V et al. (1988) Alpha 1-adrenergic-induced airway obstruction in ponies with recurrent pulmonary disease. J Appl Physiol 65:687-92
Scott, J S; Broadstone, R V; Derksen, F J et al. (1988) Beta-adrenergic blockade in ponies with recurrent obstructive pulmonary disease. J Appl Physiol 64:2324-8
Derksen, F J; Robinson, N E; Scott, J S et al. (1988) Aerosolized Micropolyspora faeni antigen as a cause of pulmonary dysfunction in ponies with recurrent airway obstruction (heaves). Am J Vet Res 49:933-8
Derksen, F J; Scott, J S; Slocombe, R F et al. (1987) Micropolyspora faeni causes airway inflammation but not hyperresponsiveness in sensitized ponies. J Appl Physiol 62:1398-404

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