Exercise-Induced Pulmonary Hemorrhage: A Veterinary Medical Conundrum
Exercise-induced pulmonary hemorrhage (EIPH) refers to the presence of blood in the airways of ahorse’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. EIPHalso 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 significantlydecreased performance.
Research has shown thatbleeding 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 pressurecreatedby 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 airwayscauses 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. Lungdamage is most likely permanent; thus far, however, there is no evidence these lesions affectthe 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 increasenegative 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 anti-inflammatory drugsdid 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 snilednafilpreventor decreaseEIPH. 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 Americareceive 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 regardingrace-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*, whichincluded 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 andidentification offutureresearch. 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 bredover 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 thatresults from further research could decrease bleeding and reduce the severity of lung pathology.
The following list of research topics were considered by the panel asimportant 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 dollarsand 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 Grayson-Jockey Club Research Foundation with AAEP assistance.
Next steps include prioritizing the needed research and meeting with industry stakeholders to discussthe 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.