In Phase I of this award I will obtain a Ph.D. in physiology investigating autonomic regulation of horse airways. Our laboratory is presently studying airway reactivity in a group of ponies with spontaneously occurring airway disease and in a group of normal ponies. Studies of mechanisms of disease are hampered by lack of knowledge of autonomic innervation and function of the tracheobronchial smooth muscle. Autonomic function will be studied in vivo and in vitro. In vivo pulmonary resistance dynamic and static compliance will be measured during vagal stimulation at a range of frequencies and voltages after adrenergic blockade. Sympathetic stimulation will be achieved with dimethylphenylpiperazinium (DMPP) after cholinergic blockade. Adrenalectomy and use of DMPP will allow determination of adrenergic receptors stimulated by circulating catecholamines and those stimulated by sympathetic nerves. In vitro, trachealis muscle strips and bronchial rings from three generations of bronchi will be suspended in organ baths. Response to field electrical stimulation in the presence of appropriate blockers will determine the presence and function of sympathetic and parasympathetic innervation at differing levels of the tracheobronchia tree. Responses to electrical stimulation will be compared to responses to adrenergic and cholinergic agonists to compare receptors accessible to nerve stimulation and those accessible to circulating agonists. These two series of experiments will determine autonomic distribution in pony airways. Phase II experiments will investigate interactions of airay epithelium with bronchial smooth muscle. Responses to field electrical stimulation and autonomic agonists will be compared in adjacent muscle strips and bronchial rings with and without epithelium. These experiments will be conducted in airways from normal ponies and those with chronic airway disease. By use of """"""""epithelial sandwiches"""""""" I will determine if factors produced by normal and diseased epithelium modulate smooth muscle function. Crossover experiments will apply """"""""diseased"""""""" epithelium to """"""""normal"""""""" muscle and """"""""normal"""""""" epithelium to """"""""diseased"""""""" muscle.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Physician Scientist Award (K11)
Project #
5K11HL001742-03
Application #
3087336
Study Section
(SRC)
Project Start
1986-08-01
Project End
1991-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Michigan State University
Department
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Broadstone, R V; LeBlanc, P H; Derksen, F J et al. (1991) In vitro responses of airway smooth muscle from horses with recurrent airway obstruction. Pulm Pharmacol 4:191-202
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
Zeintl, H; Sack, F U; Intaglietta, M et al. (1989) Computer assisted leukocyte adhesion measurement in intravital microscopy. Int J Microcirc Clin Exp 8:293-302
Broadstone, R V; Scott, J S; Derksen, F J et al. (1988) Effects of atropine in ponies with recurrent airway obstruction. J Appl Physiol 65:2720-5