Download EIPH panel report here

Exercise-Induced Pulmonary Hemorrhage: A Veterinary Medical
Conundrum
Exercise-induced pulmonary hemorrhage (EIPH) refers to the presence of blood in the airways
of a horse’s lung during exercise. EIPH is commonly reported in racehorses but also occurs in
eventers, jumpers, endurance horses, draft horses, polo ponies and in western speed events such
as reining, cutting and barrel racing. It can occur in any horse during strenuous exercise. EIPH
also occurs in human athletes, racing camels and racing greyhounds.
Horses that experience EIPH are referred to as “bleeders” because in a small proportion of
exercising horses, there is enough hemorrhage to cause bleeding from the nose. In the majority
of cases, EIPH is not apparent unless an endoscopic examination of the airways is performed
following exercise. In fact, up to 60% of Thoroughbred racehorses have evidence of blood in
their trachea, with 20% having moderate to severe EIPH (grades 2-4) after any given race
(Morely et al. 2015). Horses with a grade 2 score or higher have significantly decreased
performance.
Research has shown that bleeding is the result of increased pressure in pulmonary veins as the
heart attempts to pump 450-500 liters of blood per minute during maximal exertion. Pulmonary
venous pressure can reach as high as 90-100 mm of mercury, which is more than the thin-walled
capillaries in the lung can tolerate. At the same time the negative pressure created by airflow of
60-70 liters/second through each nostril creates negative airway pressures of minus 40-60 cm of
water. The pressure difference between the vasculature and airways causes capillary stress
failure with rupture and extravasation of blood into the airway, predominately in the dorsal
caudal lung lobes.
With repeated EIPH episodes, the lung responds with increased thickness of the pulmonary veins
and fibrous tissue formation in the lung parenchyma, particularly evident in the dorsal caudal
lung lobes where blood flow is the highest. Potentially this leads to higher pulmonary vein
pressures, creating the environment for more capillary failure and bleeding. This pathological
change is silent with no external signs indicating the damage to the lung. Lung damage is most
likely permanent; thus far, however, there is no evidence these lesions affect the horse’s ability
to participate in future activities requiring physical exertion.
Epidemiologic studies have not identified risk factors linked to EIPH. Sex, age, track
characteristics, pollution and lung inflammation have all been incriminated, but none has proven
to be related. Anything that increases upper airway resistance can increase negative pressure in
the airways, thereby making EIPH more likely.
Recently, the American College of Veterinary Internal Medicine published a consensus
statement which summarized what is known about EIPH and its prevention (Hinchliff KW, et al.,
2015). Only furosemide (Salix™) has been shown to decrease EIPH, most likely by decreasing
pulmonary artery and left atrial pressure, thus decreasing the likelihood of capillary stress. Other
drugs tested, including aminocaproic acid, clenbuterol, corticosteroids, and non-steroidal antiinflammatory drugs did not demonstrate efficacy for EIPH. Similarly, there is little evidence
from single drug studies that carbazochrome, equine serum concentrate, conjugated estrogens,
endothelin 1-A antagonist, nedocromil, nitric oxide and snilednafil prevent or decrease EIPH.
Existing research, however, on nasal strips indicates some benefit but more research is needed to
quantify the benefit.
More than 90% of racehorses in North America receive a furosemide treatment on race day
(Hinchcliff et al. 2009). The AAEP supports the use of furosemide to control the negative effects
of EIPH in racehorses. However, race-day administration of any medication is seen by many as
problematic for the sport. Because furosemide helps prevent EIPH in the horse, veterinarians are
caught in a conundrum of wanting to do what is in the best interest of horse health versus public
and industry sentiment regarding race-day medication.
In an effort to address this issue, the AAEP hosted a research panel in November 2015 to
investigate alternative EIPH management strategies which would not require race-day
medication administration. The panel*, which included experts in the fields of equine EIPH,
pulmonary and cardiac physiology, lung pathology and human sports medicine, focused on a
review of current scientific knowledge and identification of future research. Funding for the
meeting was provided by the AAEP Foundation.
Topics discussed included epidemiology, vascular physiology, pathology, venous remodeling,
role of the heart, pathophysiology of blood flow, efficacy of furosemide and regenerative
medicine in the lung.
The panel was unanimous in its opinion that EIPH is a consequence of the horse being a superb
equine athlete selectively bred over centuries for maximal performance. All agreed hemorrhage
results from ruptured pulmonary capillaries due to a very high capillary transmural pressure
resulting from some combination of increased pressure in pulmonary arteries and veins, and
decreased airway pressure in the alveoli during maximal inspiration. Furthermore, all recognized
the physiological challenges of completely eliminating the occurrence of EIPH but that results
from further research could decrease bleeding and reduce the severity of lung pathology.
The following list of research topics were considered by the panel as important to the goal of
understanding EIPH:
 Experimentally validate the contributions of pulmonary arterial and venous pressures and
decreased alveolar pressures to EIPH and to subsequent lung lesions.
 Characterize the venous remodeling and fibrosis found in chronic bleeders.
 Define the long-term progression of lung lesions from the early days of training
throughout the racing career.
 Determine the acute and chronic effects of EIPH on horse health.
 Determine the incidence of EIPH during training, including galloping.
 Understand how Lasix decreases EIPH, including possible effects on the vasculature.
 Define the benefit of nasal strips through further testing.
 Investigate phenotypic traits that represent genetic susceptibility to EIPH.
The panel went on to outline specific research projects or areas that are the logical next steps to
help understand the mechanism and to provide evidence of efficacy of drugs or treatments.
Further understanding of the pathophysiology is required before steps to mitigate EIPH are
possible. Major initiatives to look at the cardiopulmonary alterations during racing or training are
needed. This will require collaborative work and significant funding to move the research
forward. There was no consensus when the group was asked to prioritize these areas of research;
it was concluded that each area had significant relevance to the problem.
The panel recommended initiating a consortium of researchers who frequently communicate and
establish goals for each area of research. By organizing the research into specific projects, the
consortium can decrease duplication and save valuable research dollars and the time required to
find a science-based solution.
The AAEP is dedicated to finding solutions for EIPH to benefit the horse, the racing industry and
all horses involved in athletic competition. This will require significant resources and investment
in technology and manpower. Short-term projects already underway include testing the effect of
furosemide administration 24 hours prior to racing, which received funding from the GraysonJockey Club Research Foundation with AAEP assistance.
Next steps include prioritizing the needed research and meeting with industry stakeholders to
discuss the amount of funding needed to pursue these projects. Investment in research to
understand cardiopulmonary physiology and response to exercise and disease will benefit all
horses, particularly horses in performance competition.
*EIPH research panelists:
Nat White, Virginia Tech, Panel Chair
Warwick Bayly, Washington State University
Jeff Blea, Racetrack practitioner, Sierra Madre, CA, AAEP past president
Dale Brown, University of Colorado
Kent Carter, Texas A&M University, AAEP immediate past president
Gordon Cohen, University of California, San Francisco
Paul Morley, Colorado State University
David Poole, Kansas State University
Ed Robinson, Michigan State University
Corrine Sweeney, University of Pennsylvania
Dan Weiss, University of Vermont
Kurt Williams, Michigan State University
References
Hinchcliff KW, Morley PS, Guthrie AJ, Efficacy of furosemide for prevention of exercise-induced
pulmonary hemorrhage in Thoroughbred racehorses. J Am Vet Med Assoc 2009; 235:76-82.
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; 29:743-758.
Morley PS, Bromberek JL, Saulez MN, Hinchcliff KW, Guthrie AJ, Exercise-induced pulmonary
haemorrhage impairs racing performance in Thoroughbred racehorses. Equine Vet J 2015;
47:358-365.