Effects of a specific endothelin-1A antagonist on exercise-induced pulmonary haemorrhage (EIPH) in thoroughbred horses.
BACKGROUND
During high intensity exercise, the very high pulmonary artery pressure (Ppa) experienced by Thoroughbred horses is considered a major factor in the aetiology of exercise-induced pulmonary haemorrhage (EIPH). Recently, endothelin-1 (ET-1), a potent vasoconstrictive hormone, has been found to increase Ppa in horses at rest via binding to its ET-1A receptor subtype. In addition, plasma concentrations of ET-1 are increased in horses during and after high intensity exercise.


OBJECTIVE
If ET-1 increases Ppa during exercise in the horse, administration of a specific ET-1A antagonist would decrease Ppa and therefore EIPH.


METHODS
Saline (CON) or an ET-1A receptor antagonist, TBC3214 (3 mg/kg bwt i.v.; ANTAG) was administered to horses 1 h prior to maximal incremental exercise on a high-speed treadmill. Gas exchange measurements were made breath-by-breath and blood samples collected during each 1 min stage to determine blood gases, acid-base status and cardiac output. EIPH was determined via bronchoalveolar lavage (BAL) approximately 30 min after exercise.


RESULTS
The time to fatigue, gas exchange and cardiovascular responses were not different between groups (P>0.05). Resting and peak Ppa did not differ significantly between treatments. Most importantly, ANTAG did not decrease EIPH.


CONCLUSIONS
These results do not support a deterministic role for ET-1 in the increased Ppa and therefore EIPH, during maximal exercise in the equine athlete.


CONCLUSIONS
Treatment with an ET-1A receptor antagonist does not appear to be a viable therapeutic intervention in the prevention of EIPH.
Padilla
D J
DJ
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506, USA.
Epp
T S
TS
McDonough
P
P
Marlin
D J
DJ
Erickson
H H
HH
Poole
D C
DC
D000818:Animals; D001774:Blood Chemical Analysis / Q000662:veterinary; D001784:Blood Gas Analysis / Q000662:veterinary; D018592:Cross-Over Studies; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000097:blood*; D006470:Hemorrhage / Q000097:blood / Q000517:prevention & control / Q000662:veterinary*; D006734:Horse Diseases / Q000097:blood / Q000517:prevention & control*; D006736:Horses; D007555:Isoxazoles / Q000627:therapeutic use; D008171:Lung Diseases / Q000097:blood / Q000517:prevention & control / Q000662:veterinary*; D010101:Oxygen Consumption / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000009:adverse effects / Q000502:physiology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000627:therapeutic use
D019332:Endothelin-1; D007555:Isoxazoles; D013449:Sulfonamides; C424912:TBC 3214