|Medication Committee Corner: Lasix and Bleeders – A Classic American Horsemen’s Story|
The Horsemen's Journal: Archive
The Horsemen's Journal - Winter 2011
By Drs. Thomas Tobin and Kimberly Brewer
The story of Lasix is a classic American horsemen’s story. For many years, American horsemen withheld water prior to racing, believing that horses raced better when water was withdrawn. Then, when furosemide became available in the late 1960s, horsemen found that they could accentuate the water withholding effect by administering Lasix. Among the benefits was a reduced incidence of “bleeders,” technically epistaxis, acute bleeding from the nose during or post-race.
Bleeders have been known for 300 years or more; classically, about one percent of horses bleed from the nose during or post-race. Bleeding is associated with poor performance and, very occasionally, with death of the horse. Based on the perceived efficacy of Lasix in reducing the numbers of bleeders, Lasix was approved for use throughout the United States starting in the early 1970s.
In the 1970s, the flexible fiber-optic endoscope became available, and post-race inspection of the windpipes (tracheas) of racing horses commenced. What was found was that virtually all Thoroughbreds show blood in the trachea post-race. The amounts vary, from barely detectable to very substantial, including amounts associated with bleeding out the nostrils, or epistaxis. Additionally, bronchial wash techniques made clear that all Thoroughbred horses bleed into their lungs during racing; the only variable is the amount of bleeding. The condition also acquired a new and more scientific name, Exercise-Induced Pulmonary Hemorrhage (EIPH).
It also became apparent that pulmonary damage due to EIPH is cumulative, so as horses age, their incidence of bleeding increases. Steeplechase horses, which tend to be older and to have the added stress of heavier jockeys and jumps, show the highest rates of epistaxis. Postmortem studies on horses retired due to EIPH show that the lung lesions are located at the top of the lungs, below the backbone (technically, the dorsocaudal lobes), a highly specific and unusual location. Related work showed that pulmonary blood pressures in racing horses are unusually high, leading to the theory that blood pressure driven stress failure (rupture) of pulmonary capillaries vessels was the cause of EIPH.
In 1995, New York became one of the last American states to approve the use of Lasix. Furthermore, the New York authorities kept records on the incidence of epistaxis in horses racing in New York, both before and after the introduction of Lasix. These data were reported by Bill Heller in his book “Run Baby Run,” published in 2002. These data show that for several years prior to the introduction of Lasix in New York in September of 1995, the rate of epistaxis, or EIPH, was just about five incidents per month. However, as soon as Lasix was introduced, in September of 1995, the number of epistaxis cases dropped to about one per month – an almost 80 percent reduction – and remained at this much lower rate for the following five years. These are extremely compelling data and fully support the claims that American horsemen had been making since the late 1960s (and which one of us (Tom Tobin), had presented before Congress in 1983) concerning the efficacy of furosemide in the prevention of EIPH.
The Jockey Club, however, remained unconvinced, and in or about 2008 commissioned a study supported by the Racing Medication and Testing Consortium (RMTC), the Grayson Jockey Club Research Foundation, and The Jockey Club of Southern Africa. In a very carefully designed and executed study, an international team of veterinary scientists headed by Dr. Ken Hinchcliff conclusively demonstrated that furosemide significantly reduced the incidence of high-score EIPH, very similar to the results observed in New York ten-plus years previously. This Jockey Club-supported study was published in the Journal of the American Veterinary Medical Association in 2009, at which point the efficacy of Lasix in the prevention of EIPH was unequivocally established scientifically.
The next question one might ask is how Lasix acts to reduce the incidence of EIPH. Approaching 20 years ago, the human pulmonary physiologist West and his coworkers proposed that EIPH was associated with pulmonary capillary rupture caused by the unusually high blood pressures observed in the pulmonary systems of racing horses, the “capillary/stress failure” theory of EIPH. More recently, however, Schroeter, a basic scientist by training, has proposed that EIPH is caused by stride-associated shock waves being transmitted up the forelimbs. These shock waves enter the lungs, continue “north” through the lung tissue, and are reflected back into the lung at the upper surface of the lungs, where they act to rupture the delicate alveolar/capillary tissues. This shock wave hypothesis provides an immediate explanation for the unusual location of the EIPH lesions, at the reflection point at the top of the lung, where the shock waves travelling “north” are reflected back into the lung tissue.
Consistent with this shockwave theory, EIPH is not observed in swimming horses, supporting suggestions that EIPH is caused not by exercise, but by strides. Even more interestingly, in treadmill horses that favor a particular lead, evidence of EIPH as assessed by bronchial wash techniques is found only on the lead limb side. Apparently, the lead limb is the limb through which the most substantial stride-related shock waves are transmitted, and as such the hemorrhage occurs predominantly in the lung on that side. In passing, we also respectfully note that these observations suggest that the term Exercise-Induced Pulmonary Hemorrhage may be a misnomer, and that the condition might more correctly be called “stride” induced pulmonary hemorrhage.
One argument presented by those wishing to eliminate Lasix is that its use “weakens the breed.” There is little scientific literature to support this theory and much to refute it. First, horses have bled as far back as the days of Eclipse, who bled so severely at times that he collapsed. Because the genes of Eclipse are prevalent in the lineages of most modern Thoroughbreds, if one wished to breed from “bleeding-free” pedigrees, there are very few pedigrees from which to choose. Furthermore, bleeding is not determined by genetics or heritability, but is simply a result of applied physics. Bleeding occurs due to stride-related shock waves acting on lung tissues, as demonstrated by the fact that all horses bleed. Furthermore, bleeding is related to shock waves in the lead leg, and physical factors such as racing surface, speed and distance traveled, weight carried, number of performances, hydration status, shoe type and so forth, all likely come into play in exerting shock wave stress on the horse’s lungs. Exercise Induced Pulmonary Hemorrhage, therefore, is a stride driven phenomenon and not something that can be prevented purely through genetic manipulation.
With regard to the mechanism of action of furosemide, the shock wave theory of EIPH suggests that Lasix (or water deprivation) may act in part by reducing the water content of the delicate lung alveolar/capillary tissue, thereby reducing its susceptibility to shock wave damage. This possibility is particularly intriguing in view of the fact that the original approach to epistaxis was to withhold water, suggesting that American horsemen were correct all along when they withheld water prior to post and also when, more recently, they began administering furosemide to racing horses.
This mechanism action of Lasix may also help answer the question of why furosemide is effective in the prevention of EIPH four hours after administration, after the drug has largely been eliminated from the horse. The answer is now obvious. While the furosemide is, as a practical matter, gone from the body of the horse by race time, the critically important change in the fluid balance of the horse persists fully until after the race, when the horses is again allowed free access to water.
As well as reducing the susceptibility of the lung to shockwave damage, we must also consider the likelihood that what I will call a “dry,” or water-withheld, lung is a more efficient lung. In this regard, it is well established that if you put too much fluid into a horse, the ability of the lung to oxygenate the blood is reduced, most likely because the extra lung water increases the distance that inspired oxygen has to travel from the alveolus to the pulmonary capillary red blood cells. This is important because the horse, as a practical matter, is unable to fully oxygenate its blood at maximal exercise. As such, any factor which improves the oxygenation of blood has the potential to optimize the delivery of oxygen to the musculoskeletal system of the horse, and thus its athletic performance.
The above leads to an unexpected possible outcome with regard to the banning of furosemide in racing horses. This is because a prohibition on Lasix may make it easier to run horses “hot” and “cold,” as follows. In this procedure, a “cold” horse would be a horse from which water has not been withdrawn, or a horse to which additional fluid has been provided to reduce its pulmonary efficiency and the oxygenation capacity of the lung. Conversely, the “hot” horse would be a horse from which water has been withdrawn to the maximum amount, which horse would race as close to racing on furosemide as would be possible in the absence of furosemide administration. With virtually all horses currently running on furosemide, and furosemide use being very carefully regulated, the betting public is in a much better position to assess the pulmonary and performance capacity of the Lasix horse than a horse in the absence of Lasix, where the hydration status of the horse can be manipulated at will, and for which manipulation no test is available.
Finally, manipulation of the betting outcome is improper, but in the last analysis involves only money. There is, however, another clear-cut outcome to the banning of furosemide that involves human and equine lives. When Kentucky instituted its first routine necropsy program for racing horses, one of the early necropsy candidates was a horse that had “crashed” on the racetrack about one-quarter of a mile out of the starting gate. On necropsy, the horse was found to have two fractured vertebrate, but full necropsy established the proximate cause of death as massive pulmonary hemorrhage. This horse was a classic EIPH-related sudden death, in which a horse bleeds sufficiently heavily into its lungs to die acutely on the racetrack or soon post-race. Based on this experience, we noted that the definition of EIPH should be extended to include an incidence of sudden death on the racetrack, and these EIPH-related sudden death events place at risk the lives of both horses and jockeys.
These EIPH acute sudden deaths have been reported in Pennsylvania, Kentucky, Caracas, Arizona, New Mexico, and elsewhere. Based on data reported by our colleagues in Pennsylvania, the estimated incidence of EIPH-related acute sudden death on the racetrack is about one episode in every 1,500 races. Because pretreatment with Lasix is close to 80 percent effective in reducing the incidence of high score EIPH and epistaxis, there is no reason not to think that pretreatment with Lasix does not equivalently reduce the incidence of acute deaths associated with EIPH in racing horses. As such, the administration of furosemide serves to protect the lives of both horses and their riders/jockeys, which creates a compelling ethical circumstances for veterinarians and others associated with the protecting the health and welfare of racing horses and their riders.
In summary, American horsemen had long observed that withholding water prior to post improved the performance of racing horses and reduced the incidence of epistaxis. When injectable Lasix became available 40 or so years ago, American horsemen rapidly and correctly identified its ability to prevent EIPH. They lobbied for its approval in American racing, and its use spread throughout the entire Americas. Science now fully supports their long-held belief that Lasix prevents EIPH and allows horses to run more consistently and truer to form. Additionally, the presence of Lasix makes it more difficult to alter the performance of horses by manipulating their hydration status prior to post. More importantly, EIPH/epistaxis is associated with a small incidence of sudden death in racing horses, with an attendant risk to life and limb for horses and jockeys. Withdrawal of approval for Lasix in North American racing will, therefore, increase the risk to life and limb for horses and their jockeys, and also increases the potential for manipulation of the hydration status of horses prior to post, for which manipulation no testing procedures are currently available.