Effects of a specific endothelin-1A antagonist on exercise-induced pulmonary haemorrhage (EIPH) in thoroughbred horses.
Abstract: 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.
Publication Date: 2007-04-04 PubMed ID: 17402418DOI: 10.1111/j.2042-3306.2006.tb05539.xGoogle Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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This study investigated whether a certain medication could reduce blood pressure in the lungs of racehorses during intense exercise, in order to prevent exercise-induced pulmonary hemorrhage (EIPH), a common health problem in these animals. However, the experiment did not find any beneficial effects of this medication.
Exercise-Induced Pulmonary Hemorrhage in Horses
- Thoroughbred horses often experience very high pulmonary artery pressure (Ppa), a condition known as exercise-induced pulmonary hemorrhage (EIPH), during high intensity exercise.
- This health problem can be serious and potentially limit a horse’s athletic performance.
The Role of Endothelin-1 Hormone
- Past research suggests that endothelin-1 (ET-1), a hormone known to constrict blood vessels, can increase Ppa in resting horses. This happens when ET-1 binds to its specific receptor subtype, ET-1A.
- Moreover, scientists have found that ET-1 blood levels rise in horses during and after intense exercise. Hence, they speculated that ET-1 might also be responsible for elevating Ppa during physical activity.
The Experimental Approach
- The researchers decided to test this theory by administering either saline (a control treatment) or TBC3214 (an antagonist of ET-1A) to horses before treadmill exercises. They hypothesized that if ET-1 was causing the increase in Ppa during exercise, blocking its receptor with TBC3214 would lower Ppa and thus, prevent EIPH.
- They carefully monitored the horses, taking measurements at each 1-minute stage of the exercise. They also carried out a bronchoalveolar lavage to detect any signs of EIPH about half an hour after the exercise session.
Results of the Study
- The researchers found that the control and treatment groups were not significantly different regarding time to fatigue, cardiovascular response, and gas exchange.
- Additionally, there was no significant difference between resting and peak Ppa in either group. Critically, the ET-1A antagonist didn’t appear to reduce EIPH in the horses.
Conclusion
- Due to these findings, the researchers concluded that ET-1 does not play a significant role in increasing Ppa and hence, causing EIPH during intense exercise.
- Therefore, they believe that using an ET-1A antagonist would not be practical or effective in preventing this health issue in horses.
Cite This Article
APA
Padilla DJ, Epp TS, McDonough P, Marlin DJ, Erickson HH, Poole DC.
(2007).
Effects of a specific endothelin-1A antagonist on exercise-induced pulmonary haemorrhage (EIPH) in thoroughbred horses.
Equine Vet J Suppl(36), 198-203.
https://doi.org/10.1111/j.2042-3306.2006.tb05539.x Publication
Researcher Affiliations
- Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506, USA.
MeSH Terms
- Animals
- Blood Chemical Analysis / veterinary
- Blood Gas Analysis / veterinary
- Cross-Over Studies
- Endothelin-1 / antagonists & inhibitors
- Endothelin-1 / blood
- Hemorrhage / blood
- Hemorrhage / prevention & control
- Hemorrhage / veterinary
- Horse Diseases / blood
- Horse Diseases / prevention & control
- Horses
- Isoxazoles / therapeutic use
- Lung Diseases / blood
- Lung Diseases / prevention & control
- Lung Diseases / veterinary
- Oxygen Consumption / physiology
- Physical Conditioning, Animal / adverse effects
- Physical Conditioning, Animal / physiology
- Pulmonary Wedge Pressure / drug effects
- Pulmonary Wedge Pressure / physiology
- Sulfonamides / therapeutic use
Grant Funding
- HL-69739 / NHLBI NIH HHS
Citations
This article has been cited 3 times.- Hinchcliff KW, Couetil LL, Knight PK, Morley PS, Robinson NE, Sweeney CR, van Erck E. Exercise induced pulmonary hemorrhage in horses: American College of Veterinary Internal Medicine consensus statement. J Vet Intern Med 2015 May-Jun;29(3):743-58.
- Gauff FC, Patan-Zugaj B, Licka TF. Effect of short-term hyperinsulinemia on the localization and expression of endothelin receptors A and B in lamellar tissue of the forelimbs of horses. Am J Vet Res 2014 Apr;75(4):367-74.
- Ruest LB, Clouthier DE. Elucidating timing and function of endothelin-A receptor signaling during craniofacial development using neural crest cell-specific gene deletion and receptor antagonism. Dev Biol 2009 Apr 1;328(1):94-108.
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