EIPH: Exercise-Induced Pulmonary Hemorrhage
Perhaps the most widely recognized of all disorders affecting racehorses is "bleeding," or exercise-induced pulmonary hemorrhage (EIPH). We now know that most racehorses bleed at some time during their careers. In fact, many horses might bleed every time they undertake intense exercise, such as breezing and racing. We also know that bleeding can occur in situations other than flat racing. For example, EIPH has been detected in three-day eventers, steeplechasers, and polo ponies, among others. Bleeding has even been observed in draft horses pulling heavy loads. The common denominator is strenuous exercise.
Although EIPH has been recognized for more than 300 years, we still have more questions than answers when it comes to the cause and prevention of this problem. Research in the last 20 or so years has shed some light on why horses bleed during strenuous exercise. But even today, there is no consensus regarding the true cause of EIPH.
How to treat and prevent bleeding is no less contentious, in large part because of controversy concerning the potential performance-enhancing effects of furosemide (Salix, formerly known as Lasix), the drug administered to racehorses with a history of bleeding.
How Common is EIPH?
Just how common is EIPH? To answer this question, we need to define bleeding. Years ago, before the advent of endoscopes, a horse was called a "bleeder" when it shed blood from the nose after a race (epistaxis). However, research studies have shown that epistaxis occurs in only a very small percentage of racehorses. For example, in a Japanese study, epistaxis related to EIPH was recorded in only 369 of 251,609 race starts, or about 0.15% (Takahashi et al. 2001). In other studies, a slightly higher percentage of racehorses--between 1% and 2%--bled from a nostril after racing.
However, if bleeding is defined as the presence of blood in the windpipe or trachea after hard exercise, the percentage of affected horses skyrockets. This type of EIPH has been referred to as "occult" or "internal" bleeding. In this case, the horse bleeds from the lung, but not the nose.
In studies of Thoroughbreds and Standardbreds, where these horses were "scoped" (had their windpipes endoscopically examined) 60-90 minutes after racing, bleeding was detected in 50-60% of horses. In studies where the same horses were examined after three races, almost 90% bled on at least one occasion.
Another indicator of bleeding is the presence of the red blood cell breakdown product hemosiderin in lung macrophages (a type of immune defense cell). These are detected from tracheal wash or bronchoalveolar lavage (BAL), in which a small amount of fluid is placed into the lung and then drawn out for analysis, essentially "washing" part of the lung. Studies have shown that almost all racehorses have these hemosiderin-laden macrophages in lung secretions, indicating that some degree of bleeding has occurred in the recent past.
It is also apparent that racehorses experience some degree of EIPH soon after beginning fast work. In general, the incidence and severity of bleeding increases with age. Consistent with this, the Japanese study mentioned above reported that bleeding from the nose was more prevalent in older horses.
All of this tells us that EIPH occurs in most, if not all, racehorses. The severity of bleeding probably varies greatly between horses, but appears to worsen with increasing age. There have been relatively few studies on bleeding in horses performing other intense exercise (e.g. three-day eventing or polo). In one study of upper-level three-day event horses, about 13% had evidence of bleeding after the cross-country phase of competition.
Why Do Horses Bleed?
No one has the complete answer to this question. The most popular theory for the last 10 years or so is that some lung capillaries rupture under the high-pressure conditions that exist during heavy exercise. Researchers use the term "pulmonary capillary stress failure" to describe this phenomenon. Deep within the lung, thousands of tiny air sacs or alveoli interface with capillaries, forming what is known as the blood-gas barrier (see "Bleeding Airways" above). This incredibly thin barrier readily allows oxygen to move from the lung into the blood (and carbon dioxide to move in the opposite direction).
In most species, the blood-gas barrier is sufficiently strong to withstand high stresses on the capillary wall, such as an increase in blood pressure during exercise. But the horse isn't as strong in this area.
Research studies have shown that blood pressures within the lung increase dramatically during exercise and can be two or three times higher than in other species during equivalent exercise. As well, the harder the exercise, the greater the increase in pulmonary capillary pressure and the probability of blood vessel rupture. Studies conducted by researchers at the University of California, Davis, and the Japan Racing Association have shed some light on why blood pressures in the lung increase so dramatically during exercise.
To understand their findings, we first need a brief review of the flow of blood through the heart and lungs.
The heart has four chambers--the left atrium and ventricle, and the right atrium and ventricle. With each heart beat, the right ventricle pumps blood to the lung so red blood cells can be replenished with oxygen, and the left ventricle pumps freshly oxygenated blood to the rest of the body. Between beats (the relaxation phase), the heart chambers are refilled in readiness for the next beat.
Research studies show the horse's heart does not relax quickly enough between beats during intense exercise, when heart rate can approach 230 beats per minute. When the left side of the heart is insufficiently relaxed, greater pressures within the lung are required to facilitate blood flow from the lung to the heart between beats. This "back-pressure" places strain on the fine-walled pulmonary capillaries and some break, releasing blood into the airways.
Another perplexing aspect of EIPH is why bleeding occurs mainly in the top rear portion of the lungs. A recent theory proposes that pounding of the front legs during running sends shock waves through the shoulder and into the chest, focusing these stresses in the area where bleeding occurs. This idea has been hotly debated, and further studies are required to test this idea. Other studies have shown that blood flow in the top and rear portions of the lung increases to a greater extent than in other areas during exercise. This could be another reason why much of the bleeding takes place in those regions.
Big changes in pressures within the lung's airways also might contribute to the stress on the blood-gas barrier during exercise. During inspiration, a large negative pressure (as in a vacuum) is needed for air to flow into the lung. When combined with the high positive pressure in the capillaries (as in all blood vessels), there is a large tearing force across the thin membranes that separate the air sacs from the capillaries. Some researchers believe that obstruction to the upper airway secondary to laryngeal hemiplegia (roaring) is another contributing factor to EIPH. The impedance to airflow associated with laryngeal hemiplegia could result in even higher inspiratory pressures and greater tearing forces across the blood-gas barrier.
Over time, the damage from repeated episodes of EIPH might set up a vicious cycle that increases the severity of bleeding. Blood itself causes irritation and inflammation in the lung; this process leads to lung scarring and a weakening of the blood vessels. This could explain why bleeding episodes worsen with increasing age.
Does EIPH Alter Athletic Ability?
Many trainers and veterinarians believe there is a marked decrease in racing performance when a horse bleeds. However, this is yet another one of the contentious issues surrounding EIPH. Remember that most horses bleed to some extent during strenuous exercise, making it almost impossible to sort out the effects of bleeding on racing performance. Furosemide (Salix) is administered pre-race in the belief that this drug will prevent bleeding and allow the horse to perform to the best of his ability, thus "evening the playing field" among bleeders and non-bleeders in the race.
Mild bleeding likely has minimal or no effect on performance, but severe bleeding could impair exercise performance by decreasing oxygen uptake in the lung. Blood could flood many of the airways, preventing the normal exchange of oxygen and carbon dioxide. It has been shown that the instillation of 200 mL of blood into the lungs lowers oxygen consumption (compromises the ability to absorb oxygen) in horses during intense treadmill exercise (Roberts and Erickson 1999).
The longer-term effects of repeated bleeding episodes on lung health and function also need to be considered. Some researchers have proposed that EIPH contributes to the development of chronic inflammatory airway disease, a condition that is also associated with a decrease in athletic performance (see "Lower Airway Disease" in the October 2001 issue of The Horse, article #2844).
For now, the jury is still out on the true effect of EIPH on exercise performance. Research is underway to determine how different amounts of blood in the airway alter various measures of exercise performance. Researchers are also interested in developing better methods for measuring how much bleeding occurs during exercise. This also will help determine what level of hemorrhage is significant for performance.
Can We Prevent EIPH?
If we accept that EIPH is a "normal" event during very strenuous exercise, we must also acknowledge that complete prevention of this condition is not a realistic goal. Neither is there a magical "cure" for bleeders. Still, with the knowledge that repeated bleeding episodes can cause cumulative lung damage and the possibility that severe EIPH impairs performance, there is a need for treatments that at least lessen the severity of bleeding.
In the United States and Ontario, Canada, furosemide (Salix) is commonly used to minimize EIPH in horses. In fact, recent studies have shown that on any one day, as many as 70-90% of Thoroughbreds receive furosemide before a race. Surprisingly, a lower percentage of Standardbred horses race on furosemide.
Salix works as a diuretic, increasing urine production and decreasing blood volume (and body weight). During exercise, the drug also lowers blood pressure in the lung, probably because of a decrease in blood volume. This should reduce the amount of stress on the pulmonary capillaries, thereby reducing the severity of bleeding.
Indeed, recent research studies have shown that furosemide does reduce the severity of bleeding episodes. In one study, compared with the control (untreated) condition, furosemide treatment resulted in a 10-fold reduction in the number of red blood cells in BAL samples obtained 30 minutes after treadmill exercise (Kindig et al. 2001). However, furosemide does not stop bleeding completely.
The main controversy surrounding the use of furosemide in racehorses is whether the drug actually enhances a horse's performance ability independent of any effect on the severity of bleeding.
Two large-scale research studies--one in Thoroughbreds and one in Standardbreds--showed that furosemide is associated with superior racing performance (Gross et al. 1999; Soma et al. 2000). There are two schools of thought regarding the results. One interpretation is that furosemide does, indeed, improve racing performance, but the change in performance has nothing to do with lung bleeding.
Another possible conclusion from this work is that because EIPH impairs athletic performance, treatment with furosemide is simply correcting the performance decrease associated with bleeding. Also, because most horses bleed, it can be argued that most should receive furosemide as a pre-race treatment.
Perhaps the truth lies somewhere in between. What we do know is that bettors consider the "first time on Salix (furosemide)" a critical factor in handicapping. Experienced horsemen will tell you a horse performs better that first time on furosemide. Also, information from research studies provides a plausible explanation as to why furosemide enhances performance (Hinchcliff 1999). Horses lose weight when they receive a shot of furosemide, perhaps as much as 15-20 pounds if feed and water intake is restricted until after the race. Just as adding lead weights to the saddle can slow a horse, removing weight could provide a real boost coming down the stretch.
Research studies spearheaded by Kenneth Hinchcliff, BVSc, MS, PhD, of The Ohio State University, demonstrated that adding back the weight lost after furosemide administration completely offsets the drug's performance edge. It has even been suggested that horses treated with furosemide be required to carry an extra 10 pounds or so to level the playing field with non-treated horses.
The real solution to this dilemma is to come up with a treatment that effectively lessens the severity of bleeding without altering performance. A newer approach is the use of the Flair equine nasal strip (see "Opening the Airways" in the August 2001 issue of The Horse, article #938). This simple device is designed to support the nasal passages and optimize air flow. Much of the resistance to air flow occurs as air travels through the horse's nasal passages. This resistance probably contributes to the overall stress on the blood-gas barrier during strenuous exercise. Therefore, lowering the resistance to airflow could help reduce bleeding.
The initial research findings have been very promising (Kindig et al. 2001). Lung bleeding associated with fast treadmill exercise is reduced by 40-45% when horses are equipped with the Flair nasal strip. Given the controversies surrounding the use of any kind of medication in performance horses, the nasal strip is a useful addition to the list of treatments targeted for the management of EIPH.
Overall respiratory health management is also important. Because the low-grade lung inflammation associated with repeated bleeding episodes can worsen EIPH over time, it is very important to minimize further insults to the respiratory system. Horses should be kept in well-ventilated barns, bedded on low-dust materials, and fed high-quality feedstuffs. Many trainers use complete feeds (that include roughage) to minimize the risk of inhaling dusts and molds from hay, which can worsen airway inflammation. Giving the horse as much turnout time as possible also improves "lung hygiene."
Finally, a word on the many nutritional supplements marketed for use in "bleeder" horses. These supplements generally contain substances (such as vitamin C or bioflavonoids) that are supposed to strengthen lung capillaries, thereby reducing their tendency to rupture during strenuous exercise. Sounds good in theory, but there is no published research on the effects of these supplements on EIPH and, in my opinion, there is no value in using them.
Many horses do not work at a high enough energy intensity to bleed, but those that do and bleed from it require special management. While the jury is still out on some of the available treatments, minimizing your horse's exposure to dust and maximizing his level of fitness for his job will ensure that every breath he takes is as healthy as possible.
Gross, D.K.; Morley, P.S.; Hinchcliff, K.W.; Wittum, T.E. Effect of furosemide on performance of Thoroughbreds racing in the United States and Canada. Journal of the American Veterinary Medical Association, 215, 670-675, 1999.
Hinchcliff, K.W. Effects of furosemide on athletic performance and exercise-induced pulmonary hemorrhage in horses. Journal of the American Veterinary Medical Association, 215, 630-635, 1999.
Kindig, C.A.; McDonough, P.; Fenton, G.; Poole, D.C.; Erickson, H.H. Efficacy of the nasal strip and furosemide in mitigating EIPH in Thoroughbred horses. Journal of Applied Physiology, 91, 1396-1400, 2001.
Roberts, C.A.; Erickson, H.H. Exercise-induced pulmonary hemorrhage workshop. Equine Veterinary Journal, Supplement 30, 642-644. 1999.
Soma, L.R.; Birks, E.K.; Uboh, C.E.; May, L.; Teleis, D.; Martini, J. The effects of furosemide on racing times of Standardbred pacers. Equine Veterinary Journal, 32, 334-340, 2000.
Takahashi, T.; Hiraga, A.; Ohmura, H.; Kai, M.; Jones, J.H. Frequency and risk factors for epistaxis associated with exercise-induced pulmonary hemorrhage in horses: 251,609 race starts (1992-1997). Journal of the American Veterinary Medical Association, 218, 1462-1464, 2001.
About the Author
Ray Geor, BVSc, PhD, Dipl. ACVIM, is professor and chairperson of Large Animal Clinical Sciences at the College of Veterinary Medicine at Michigan State University
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