The role of cyclooxygenase products in the acute airway obstruction and airway hyperreactivity of ponies with heaves.
Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. To document the role of cyclooxygenase products of arachidonic acid metabolism in the pathogenesis of heaves, we measured plasma and bronchoalveolar lavage (BAL) fluid concentrations of metabolites of thromboxane (TX)A2 and prostaglandins (PG) I2 and D2 in five affected ponies and their age- and gender-matched controls prior to and during acute airway obstruction precipitated by housing the ponies in a barn and exposing them to hay dust. Pulmonary resistance increased significantly and dynamic compliance and arterial oxygen tension decreased significantly in affected ponies that were placed in the barn. At this time, histamine aerosol challenge demonstrated the presence of airway hyperresponsiveness in the affected ponies. Plasma TXB2 was the only metabolite that increased significantly during the acute disease state. In a subsequent experiment, the ponies were treated with flunixin meglumine, a cyclooxygenase inhibitor, to determine if this would alter the onset or development of clinical disease. At a dose of 1.1 mg/kg intramuscularly, 3 times daily, flunixin meglumine inhibited TXB2 production but did not alter the degree of airway obstruction or airway hyperreactivity measured at pasture and in the barn. We conclude that cyclooxygenase products of arachidonic acid metabolism are altered but do not play a role in the airway obstruction and hyperreactivity observed in ponies with heaves.
Gray
P R
PR
Pulmonary Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing 48824-1314.
Derksen
F J
FJ
Robinson
N E
NE
Carpenter-Deyo
L J
LJ
Johnson
H G
HG
Roth
R A
RA
D000403:Airway Resistance; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D011464:Epoprostenol / Q000378:metabolism*; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses; D015230:Prostaglandin D2 / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000378:metabolism / Q000662:veterinary*; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2