- Introduction

Exercise induced pulmonary hemorrhage (EIPH), or "bleeding", occurs when blood enters the air passages of a horse’s lung, which may lead to the impairment of lung function.  Evidence of EIPH can be found in almost all horses that engage in short periods of strenuous exercise such as racing (Fig. 1) and barrel racing: thus making it a major welfare and economic concern to both veterinarians, and those involved in the racing and sport horse industries.  EIPH manifests itself in various  ways depending on the severity of the bleeding associated with the condition.  Horses with severe EIPH develop epistaxis (nosebleeds), while horses with less severe cases may not show any signs at all.  There are, and have been, many theories concerning the cause of EIPH, but that is exactly what they are, just theories.  However, in the past fifteen to twenty years, recent advances in technology have enabled deeper investigation into these theories, and learn more about what ultimately causes EIPH.  In addition to the theories concerning the cause of EIPH, there are probably an equal number concerning its treatment.  Currently there is only one treatment that is used to control EIPH in the United States, furosemide (Lasix^® , Hoechst-Roussel).  However, its effectiveness is in question, and its use in racing is illegal in all countries with the exceptions of the U.S. and Canada.

- Causes of EIPH

As previously mentioned, EIPH can be defined as blood entering the small air passages of the lungs. Blood entering these small passages (Figs.2&3) may impair gas exchange, and thus 
decrease lung function.  The question is, how does the blood get there?  There are many hypotheses concerning the cause of EIPH, but before mentioning those a little anatomy and physiology of the horse’s lungs must be understood.

Two circulatory systems provide passage ways for blood to flow within the horse’s lungs, the pulmonary circulation, and the bronchial circulation.  The large volume, low pressure pulmonary circulation is involved in gas exchange and the delivery of oxygen to exercising muscles; while the small volume, high pressure bronchial system supports the lung tissue by providing necessary nutrients.  There is some evidence that most of the bleeding associated with EIPH comes from the pulmonary system.  However, some believe that the bronchial system may contribute to the bleeding as well, even though there is little hard evidence that this occurs.

In the past, the belief was that the distribution of blood flow within the lungs of four-legged animals was determined by gravity.  We now know that this theory is not true, and that blood flow is actually preferentially distributed to the dorsocaudal region of the lung (Fig. 4). As one might expect, upon gross inspection of lungs from EIPH afflicted horses, this region is also where the most hemorrhaging occurs (Fig. 5).
 
 
 
 
 

Among the many hypotheses that try to describe the causes of EIPH in horses, there are two that are currently thought to be viable.  The first theory states that it is the high vascular pressure within the lungs during strenuous exercise that leads to pulmonary hemorrhaging.  The second theory states that the incessant pounding of the horse’s hooves during exercise causes trauma within the lung which leads to bleeding.

During strenuous exercise, the horse must provide an efficient way to deliver oxygen and nutrients to its exercising muscles.  As with all animals the horse relies on red blood cells, the oxygen-carrying portion of the blood, to deliver the oxygen and nutrients needed by these muscles.  The resting horse stores about one-third of its red blood cells within its spleen. During exercise the spleen contracts and infuses these cells into circulation, thus increasing the amount of oxygen that can be carried to the tissues.  However, this increase in the number of red blood cells also raises the volume and the viscosity of blood flowing through the lungs, and the rest of the body.  The increased volume and viscosity of the blood, in combination with an increase in heart rate exceeding 200 beats per minute, not only allows the horse to more efficiently distribute oxygen and nutrients to exercising muscles, but also drastically increases the blood pressure within the pulmonary circulation.  In addition, some investigators believe that because the ventricles of the horse’s heart become distended with the increased volume of blood, they are stiff in comparison to other species. This may also contribute to the large rise in blood pressure.  Due to the additive value of these factors, the pressure in the small blood vessels, or capillaries, within the lungs of a horse can 
increase from approximately 25 mm Hg at rest, up to 85-90 mm Hg during strenuous exercise (Fig. 6).  Most species reach a pressure of about 35 mm Hg during exercise, making a rise in pressure of this magnitude is unique to the horse. This increase in pressure is thought to cause capillaries to rupture and red blood cells to leak into the alveoli, thus leading to EIPH (Fig. 7). Although this theory is widely accepted, many believe that additional mechanisms are necessary to produce the bleeding involved in EIPH.

The second, and more recent, theory of what causes EIPH states that as a horse exercises, pressure waves travel through the lungs, causing trauma.   As a horse engages in moderate to heavy exercise, pressure waves are produced with each footfall of the forelimbs.  This wave is transmitted from the shoulder blade (scapula), and moves along the dorsal region of the lungs in a caudal direction (Fig. 8).  As the waves move in this dorsocaudal direction, the shape of the lungs begins to narrow, causing the waves to become focused and damage to be most severe in the dorsocaudal region.   It is this trauma which may lead to the bleeding associated with EIPH.  As previously mentioned, the dorsocaudal region of the lung is the area where the most hemorrhaging occurs in EIPH.  Again, this theory is very recent and research concerning the mechanisms involved is in its infancy.  Both of these theories are viable, and it is very possible that both are involved in producing EIPH. 

Another factor related to the cause of EIPH is that unhealthy lungs are likely to be more susceptible to hemorrhaging than those that are healthy.  This is due to the fact that in unhealthy lungs, such as in a horse afflicted with infectious or allergic bronchitis, there is inflammation within the airways.  Inflammation is the body's attempt to destroy what is causing the damage, and to repair what tissue damage has occured.  The repair process requires an increase in blood supply to the affected area.  During the inflammatory response, the region that is inflamed has an increase in blood flow from the bronchial circulation, and new capillaries form.  These new capillaries are weaker than those that are already established in the area, and are more likely to rupture during the increased blood pressure associated with strenuous exercise.  The lung in figure 9 was removed from a horse after strenuous exercise, and shows increased hemorrhaging in the areas where inflammation was present.  In addition to infections and allergies, the blood that enters the airways during EIPH also elicits an inflammatory response.  Most of the hemorrhaged blood is cleared out of the lungs by mucocilliary clearance (mucous is continually transported out of the lungs and up the trachea by means of cilia in the airways).  However, some of the blood is engulfed by macrophages, which leads to further inflammation of the airways, and prolongs the effects of EIPH.  This is a slow process and blood can remain in the lung as long as two to three weeks after the hemorrhaging has occurred.

Obstruction of the air passages may also be a factor that affects the severity of EIPH. When a horse has an obstruction such as laryngeal hemiplegia (roaring) or bronchitis, it needs to work harder to breathe. This extra work can increase the tendency to bleed by putting additional stress on the capillaries.

- Diagnosis

 Horses with severe EIPH may slow down or stop during a race and bleed from the nose. Signs of less severe EIPH can include coughing during cool down, and blood trickling from the nose during this period (Fig. 10).    Horse owners may bring an EIPH horse to a veterinarian complaining that the horse is showing poor performance for no reason.  Many times however, horses will show no signs of the disease, and it will go undiagnosed.  Since it is believed that almost all racehorses experience EIPH, it is the severity of the disease that determines what signs, if any, a horse will show.

Diagnosis of EIPH can be achieved by endoscopy, tracheal washing, and/or a bronchoalveolar lavage (BAL). Endoscopy involves passing a small camera through the nostril and into the  windpipe (trachea) of the horse.  This procedure is performed 60 – 90 minutes after exercise; the evidence of blood in the trachea is indicative of EIPH (Fig. 11).  However, in many horses, endoscopy alone is not enough to definitively diagnose the disease, and a tracheal wash is often needed. 
 
 
 
 

A tracheal wash collects cells from the trachea, the tube through which air passes from the mouth to the lungs.   The presence of white blood cells containing pigment from engulfed red blood cells (Fig. 12), indicates that recent hemorrhaging has occurred.  This technique is particularly useful if endoscopy cannot be performed within 60 – 90 minutes after exercise.  However, as with endoscopy, tracheal washing has its shortcomings as a diagnostic tool for two reasons.  First, the results of a tracheal wash do not give the veterinarian an idea of the time course of the hemorrhage.  Secondly, because the trachea is much higher in the respiratory system than where the hemorrhaging occurs within the lung, the cell population obtained in the results of a tracheal wash can be vastly different than that deeper within the lung.  Therefore yet another diagnostic tool is needed to evaluate EIPH in the horse.

The final diagnostic tool at the veterinarian’s disposal is the brochoalveolar lavage (BAL).  This technique involves passing a tube through the horse's nostril, down the trachea, and into the smaller air passages deep within the lung to obtain a sample of cells.  By knowing the number and types of cells located deep within the lungs, a veterinarian can better diagnose the disease and detect any underlying inflammation.  A BAL can also be used to determine the degree of hemorrhaging in the lungs by looking at the number of red blood cells obtained in a sample.

All three of these diagnostic tools, endoscopy, tracheal washing, and BALs, can be utilized to diagnose EIPH.  Because the degree of hemorrhaging varies between horses, it is useful to use a combination of these techniques to accurately diagnose EIPH, and to determine the amount of bleeding within the lungs.  To study EIPH more deeply, investigators may run the horse on a large treadmill to induce bleeding (Fig.13).  When diagnosing EIPH it is important to rule out two other diseases that present similar signs; guttural pouch mycosis (the deterioration of the internal carotid artery), and ethmoid hematoma (a hemorrhagic mass attached to the ethmoid bone which causes nosebleeds). 
 
 
 

- Treatment

Unfortunately there is no proven, effective treatment for horses with EIPH.  Currently there is only one legal treatment for horses racing in the United States, furosemide,  more commonly known as Lasix.  This treatment is illegal in most other countries. 

Lasix is a diuretic, a drug used to induce urination, commonly used in human medicine to treat high blood pressure (hypertension).  Essentially it plays the same role in the treatment of EIPH, because it is the high blood pressure within the circulation of the lungs which is believed to be a major cause of EIPH.  Lasix is administered intravenously about four hours before exercise, and acts rapidly on the kidneys, resulting in an increase in urine production.  When given Lasix, horses can lose up to 2.4% of their body weight in urine excretion.  By filtering this large amount of water and electrolytes from the blood, the kidneys reduce the blood plasma volume and blood volume by approximately 8.4% and 11% respectively.  By reducing the volume of blood flowing through the vascular system, while retaining the same number of red blood cells necessary for oxygen transport, the blood pressure within the lungs has been shown to drop approximately 7-10 mm Hg without compromising 
oxygen transport to the muscles (Fig. 14).  Thus, by reducing the pressure in the pulmonary circulation during strenuous exercise there should be a decrease in the amount of hemorrhaging seen in EIPH horses.  Using Lasix does not completely stop the bleeding associated with EIPH, but it may reduce its severity. The reduction in bleeding due to Lasix is difficult to measure, but one study noted less blood in the trachea after exercising on the drug. The results of research involving the effectiveness of this drug vary to say the least; from horses responding well to treament, to those that don’t respond at all.  The effectiveness of Lasix is only part of the controversy surrounding this drug.

There is a concern that horses treated with Lasix show an increase in race performance compared to those horses that are untreated.  There is evidence that this does occur, but why?  Some may argue that if the drug decreases the amount of hemorrhaging in the lungs, there should be an increase in performance.  However, the lack of evidence supporting the efficacy of Lasix, does not allow these assumptions to be made.  A horse treated with Lasix loses a large amount of weight by urinating, and it stands to reason that a lighter horse is a faster horse. A light weight horse expends less energy, and requires less oxygen to get around the track.  These factors contribute to the decrease in racing times turned in by horses treated with Lasix.  With all of the controversy surrounding this drug new treatments for EIPH are being explored.

Other treatments currently being investigated, such as nitric oxide (NO), take another approach to treating EIPH.  These drugs work as vasodilators (giving the vessels a larger circumference) and vascular smooth muscle relaxants allowing the blood vessels within the lungs to accommodate the large increases in blood volume that occur during strenuous exercise.  If this occurs, the pressure within the vessels will decrease, and the hemorrhaging associated with EIPH should be decreased.  However, these hypotheses are still under investigation, and only time will tell how effective these treatments will be in the battle against EIPH. 

*Photo by Anne M. Eberhardt, courtesy of the Horse

Click here for the Referenced articles containing additional information on EIPH.

If your computer has Powerpoint you can view the figures in a slideshow by clicking here. If not, click here.

This article was prepared by Todd D. East under the direction of the faculty and staff of the Equine Pulmonary Laboratory.