EIPH

The Innerworkings of EIPH

Drs. Bayly and Poole have spent years of their highly notable careers in pursuit of answers surrounding EIPH. Their pedigrees certainly lend themselves to the assumption that, if answers will be found, it’s these two men who will likely play a role in bringing them forward to the world. Dr. Bayly — a native of Melbourne, Australia — is a 30-year veteran and former Dean of Washington State University’s celebrated College of Veterinary Medicine, as well as a former president of the World Equine Veterinary Association. His areas of expertise include equine exercise science and exercise-associated diseases of the respiratory system specifically. The man is an exceptional compilation of knowledge, experience and an adventuresome spirit who has led his research to areas of veterinary medicine left previously unanswered and largely untouched. Dr. Bayly’s work is internationally recognized, considering he has authored and published 170-plus peer-reviewed papers and several book chapters that help educate the next generation of physicians, specialized therapists and veterinarians.

Where Dr. Bayly has been fascinated by the horse since the outset of his career, Dr. Poole’s road to EIPH research was considerably more unexpected. A native of Great Britain and a University Distinguished Professor in Kansas State University’s Departments of Kinesiology and Anatomy and Physiology, Dr. Poole has long been captivated by the athlete — both human and equine alike. He’s the Director of the institution’s National Institutes of Health–funded Cardiorespiratory Research Lab, where his research focus has centered on cardiorespiratory diseases, respiration and microcirculation to better understand the oxygen transport pathway from lungs to muscles in health and disease. Dr. Poole is the author of nearly 400 research publications and three books and has been cited over 22,000 times. His colleague, Professor Howard H. Erickson, introduced him to the problem of EIPH, and together they performed a series of investigative studies running horses on K-State’s high-speed treadmill.

One aspect of EIPH that both Drs. Bayly and Poole are quick to establish from the outset is that we’re talking about a condition; an important fact in discussing EIPH. Dr. Bayly points out that, through years of research, veterinarians now know that EIPH is, in fact, not a disease state at all, but rather a direct result of the physiology of the horse. In a 2016 paper titled, “Exercise-Induced Pulmonary Hemorrhage: Where are We Now?,” Dr. Poole explained that racehorses, for instance, are running up to about 45 mph with their heart beating four times per second; they may pump over 100 gallons of oxygenated blood from their lungs to their muscles each minute. This blood flows in capillaries past a blood gas barrier that is just 1/50,000 of an inch thick. The numbers are mind blowing and make a clear case as to just why and how bleeding occurs in speed athletes. “Envision a capillary in the lung, which is about 10 microns across with walls 1/200 of the thickness of a human hair,” says Dr. Poole, beginning to paint a picture of the internal workings of EIPH. “Red blood cells make their way through, sometimes in single file and sometimes two or three at a time,” he continues. “They’re very, very small vessels. That’s where oxygen exchange and CO2 exchange occur in the lung. The equine lung has a prodigious surface area; it’s probably 2,800 square meters or so. It’s massive.” Couple this exceptionally large surface area with hundreds of millions — perhaps even billions — of thin-walled capillaries, and the stage is set for EIPH to occur when a horse exerts itself during intense exercise at speed. “We’ve bred horses for at least six millenia for speed, which has resulted in these enormous hearts,” says Dr. Poole of the horse’s anatomy. “Secretariat was unlike any other horse; his heart was around 22 pounds. That’s like a basketball.” While horses evolved to have an incredibly large heart, their chests didn’t grow proportionally, leaving a large heart, relatively small chest cavity and lungs that are undersized in comparison to the heart. “Now we have a horse that has a huge heart, a massive cardiac output, and it has to pump all that blood through those modest lungs,” explains Dr. Poole. “This raises the pressure in those pulmonary capillaries.” According to the measurements made by Drs. Poole and Erickson, “A horse and human athlete have very similar resting pulmonary artery pressure, which at about 25 over 10 millimeters of mercury are far lower than systemic values in the rest of the body. But, during exercise, when human pulmonary artery pressures only increase a little, the horse’s may increase several-fold to 120 over 80,” says Dr. Poole. It’s the perfect storm, really, and this combination of increased pressure inside the thin-walled capillary together with a negative alveolar pressure on the other side of the capillary wall creates a huge pressure difference across the capillary wall, causing rupture and EIPH. “The horse will suck in maybe 15 or 20 liters — three or four gallons — per breath, and that’s 120 times per minute. This generates a massive negative pressure in the alveoli of the lungs,” Dr. Poole says of the anatomical and physiological factors precipitating EIPH within the horse. “It used to be thought that the airways were the source of bleeding, but some beautiful studies with colored microspheres, by Dr. Jim Jones and others at the University of California at Davis, have shown that it’s certainly the blood gas barrier rupturing. And we now have wonderful electron microscopy of red blood cells in the alveolar space itself,” Dr. Poole explains of advancements that have allowed for a better understanding of EIPH. “If we look at epistaxis, which is blood streaming down from the nostrils, only 1 to 3 percent of racehorses will show that visible epistaxis. That doesn’t mean they aren’t bleeding.” It’s an important point and one that both Drs. Poole and Bayly emphasize — even in the absence of epistaxis, there is still a high likelihood of EIPH in high-performance speed athletes.

One way that racetrack veterinarians can and do measure the occurrence rate of EIPH is through post-race bronchoscopy often just called “scoping.” Dr. Poole says of the diagnostic method, “They’re looking for the presence of blood in the trachea and grading it on a zero to four scale.” While scoping is certainly a popular and relied-upon diagnostic tool, bronchial alveolar lavage (BAL) is the gold standard. “With BAL, we can flush fluid down, suck that fluid back out and actually count the red blood cells and assess the severity of the EIPH based on the color of the fluid we’re seeing.”

While EIPH is beginning to show itself as the consequence of a physiologic event within the horse, there are many unique indicators of the condition that veterinarians are just now — with the help of advancing science — being able to pinpoint, then clarify. A commonly asked question in relation to EIPH is why some breeds and disciplines are so much more susceptible while others see an almost non-existent occurrence of EIPH. “EIPH most often becomes a factor in events that are relatively short in duration and require supreme effort,” explains Dr. Bayly. “I think is inevitable, given the anatomic and physiologic adaptations bred into horses for millennia to allow them to run faster,” Dr. Bayly says plainly. “In addition to the relatively small lungs in relation to the tremendous pumping capacity of the large heart, horses have developed the ability to store red blood cells in their spleens. When they get excited, this release of adrenaline during stress can cause the spleen to contract and express red blood cells into circulation.” When the spleen fully contracts, it has the capacity to increase circulating blood volume in the horse by upwards of 30 to 40 percent. Dr. Bayly often likes to illustrate the occurrence by encouraging students to picture the lungs as a balloon. “If you start putting fluid into the lungs like a balloon, they’ll expand; those closed capillaries will expand to accommodate the added volume. As you continue to put in more and more blood, you eventually reach the point beyond which you cannot expand any further. Then pressure starts to increase as you try to force more fluid or blood into a space that is already maximally expanded. You essentially have a volume overload situation.” Dr. Bayly’s picture makes perfect sense. With the heart, lungs and spleen all playing a significant role in EIPH, there’s a clear connection and pathway that allows the condition to develop. “With the heart beating nearly four times per second — just try to imagine that — the large chamber, called the left ventricle, that is responsible for pumping the blood out into the body is not able to fill with as much blood as it needs to, and it also might not have enough time to fully empty itself when it does contract. As a consequence, there is an increase in the back pressure upstream from the left heart and the pressure in the veins and capillaries of the lungs rises in what can be a fairly quick timeframe. When the pressure in these capillaries exceeds a certain level or threshold, the walls of the capillaries are disrupted and blood escapes into the airways and surrounding tissues, and you have EIPH. The amount of blood lost and the severity of the EIPH is probably dependent on the magnitude of this back pressure and the number and size of the blood vessels that are subject to these disruptions,” Dr. Bayly says, matter-of-factly.

While EIPH is, in fact, a condition rather than an acquired disease state, Dr. Poole points out that the condition can have a progressive nature. “Horses only bleed out of the nostrils a small percentage of time, but those red blood cells, once they’re in the lung, they can cause inflammation. They’re broken down by alveolar macrophages and the free radicals they produce, and they form something called a hemosiderophage, which is a ghastly, nasty looking cell. This process damages the lung after repeated bouts of EIPH.” Dr. Poole and his team have found evidence that after a horse experiences repeated bouts of EIPH, a portion of their lung becomes stiffer and more rigid than normal, healthy lung tissue. At the point where healthy lung tissue meets the stiffer portion of the lung, there appears to be high shearing forces that can contribute to more damage. This phenomenon creates a high probability that horses who have bled in the past and sustained this lung damage will have a higher likelihood of bleeding again and potentially heavier the next time. The general idea — taking racehorses, for example — is that the more race starts a horse has, the higher the chance that EIPH will come into play.

Clinical Signs and Diagnostics

With EIPH significantly more prominent than once thought, identifying clinical signs can give riders and practitioners an early indication that the condition may be present. “Probably the two most commonly reported clinical signs would be coughing and an increased amount of swallowing soon after exercise,” details Dr. Bayly. When a horse is identified as a potential EIPH case, the veterinarian will likely turn to the imaging method of choice, endoscopy. Tracheal or bronchial endoscopy allows the practitioner to evaluate the upper airway by passing an endoscope — a flexible fiberoptic device with a light — up the nose and down into the trachea. In certain cases, if the endoscope is long enough, there’s the potential to see the bottom of the trachea, otherwise known as the windpipe. “It’s basically impossible to get a false positive with endoscopy,” points out Dr. Bayly. “If you see blood, you see blood. Plain as that.”

While false positives are almost never an issue, false negatives can occur in up to one-third of cases where endoscopy is used as a diagnostic method. “The two main reasons are either that there isn’t enough blood that’s been lost or that the horse hasn’t moved blood up the airway to the point where it is visible at the time the horse is scoped. Timing is everything. “The most convenient time to scope a racehorse is probably as soon as it gets back to its stall, which is often about 20 to 30 minutes after a race,” explains Dr. Bayly. “There’s even more variability possible when we’re talking barrel horses.” In some cases, this quick timeframe means that veterinarians could be scoping horses before blood has had the opportunity to appear, creating a false negative with an endoscope. “If a horse was swallowing a lot or the horse has not performed well and no blood is observed about 30 minutes after competing, it might be advisable to scope the horse again an hour or 75 minutes after the exercise is completed,” advises Dr. Bayly of the not always convenient but perhaps more accurate time window. “This does not necessarily mean, however, that if the horse did not meet expectations performance-wise, it bled. It should not be automatically assumed that when performance isn’t meeting expectations it’s due to EIPH,” insists Dr. Bayly.

Dr. Poole adds yet another factor that veterinarians should consider when performing an endoscopy on a suspected case of EIPH. “If that horse has been allowed to put his head down to nibble or drink, that actually helps the blood be cleared or leak from the alveoli down into the trachea.” This can result in the appearance of a heavier bleed for horses that have had their head down versus a horse that has been haltered and tied without eating or drinking. “If you can take a bit more time, you may in fact, increase the likelihood that you will get a positive and more accurate finding based on endoscopy,” encourages Dr. Bayly in agreement.

Due to these subtleties affecting the results of endoscopy, the most sensitive diagnostic method is unequivocally bronchoalveolar lavage. “With BAL you’re at nearly a 100 percent accuracy,” says Dr. Bayly concretely. Here, a veterinarian gently passes a tube into the lungs to the point where it won’t proceed any farther. Fluid is infused down the tube, then suctioned out. Essentially, you’re washing or lavaging the lungs to then evaluate the extracted fluid for color and count the red blood cells. “This is the single most sensitive diagnostic test for EIPH,” Dr. Bayly reaffirms.

Whatever diagnostic method is chosen, it’s important to take an individualized approach to both diagnostics and management. “If a horse bled last weekend, it’s not necessarily predictive of how severely the horse might bleed in two week’s time,” Dr. Bayly insists. “These horses are individuals, and EIPH isn’t cut and dried. There are certainly a lot of management considerations.”

Management Strategies — Furosemide to Nasal Strips

While the goal of equine veterinarians is always prevention over treatment, unfortunately, with EIPH there isn’t a viable preventive approach. At least not yet. “You have to set the goal of mitigating or reducing the severity of EIPH. It’s not feasible to say, ‘I’m going to prevent it,’ ” says Dr. Bayly. The primary techniques used for managing the condition are seen in the use of both furosemide, also known as Lasix® or Salix®, and also nasal strips. “Furosemide has been shown to reduce the pressure in the lung capillaries from which the blood emanates. If you can lower the pressure in the capillaries, you can, in many cases, reduce the amount of EIPH,” explains Dr. Bayly of the mechanism of furosemide. “This is the only scientifically demonstrated pharmacologic agent that’s been shown to reduce the severity of EIPH.” Exactly how furosemide accomplishes this mitigating effect isn’t entirely clear. Though the drug is a diuretic agent that can assist horses in excreting up to 20 to 30 pounds in urine on race day and may have some impact on total circulating blood volume, it likely has an effect on the ability of vessels within the lungs to relax and accommodate greater volume expansion as well. In 2020, and following much controversy over many years in the Thoroughbred racing industry, furosemide was banned on race day at many, but not all, American tracks, leaving veterinarians and trainers to establish a plan that will allow for horses to race safely in the absence of furosemide. “A lot of people think that it’s wrong to use furosemide,” says Dr. Bayly of the controversy surrounding the popular drug. “Some believe that it’s forcefully dehydrating a horse, and that can’t be good for the animal. Certainly, in the first two hours after its administration the horse’s circulating blood volume and body water diminishes rapidly. Anybody who’s seen furosemide at work or has used it themselves knows that it induces urination pretty quickly. But in our hands, in some of the work we have done, when we’ve looked at the circulating blood volume four hours after administration, it’s nearly back to what it was before the furosemide was administered.” Dr. Bayly concludes, “When that horse comes to race, it is not usually dehydrated, per se. That’s one of the biggest concerns from a welfare aspect concerning the administration of furosemide. The net effect of giving furosemide is that the horse loses some weight, but most of that is reflected as a loss of water from the colon, secondary to movement of fluid from the colon into the circulation and cells to replace the fluid lost initially due to the diuretic action of the furosemide.”

While furosemide has been long used to combat the effects of EIPH, diligent management of the barn environment is critical as well. Trainers who have seen success in managing the occurrence and severity of EIPH in their horses have paid close attention to dust mitigation by using various tactics — proper ventilation, choosing appropriate bedding, eliminating dust-causing factors like ground fans and blowers as much as possible and more carefully storing hay to minimize dust and mold. “We’re talking especially about the small particulates — the ones that you can only really see in the sunshine,” points out Dr. Poole. “They can go really deep down into the lungs. We’ve thought for many years, ‘it’s a stable. It’s dirty. We can’t get around it.’ They certainly don’t have to be. You can have millions of dollars of horses in there. A high standard of dust control can mean less lower airway disease.”

In addition to furosemide and particulate control, nasal strips are a more recent advancement that may seem simple but can have a profound impact on horses with EIPH or a high risk of the condition. Dr. Poole has done significant work in the area of nasal strip and illustrates their effectiveness by painting a picture of how they go to work in the horse. “Keep your mouth closed,” he instructs. “Inhale as rapidly as you can just through your nose. You can feel your nostrils getting sucked in, and since the horse is an obligate nasal breather, they don’t breathe through their mouths. There’s 15 to 22 liters of air coming through each nostril per second.” Dr. Poole and his team showed that they could decrease EIPH close to 50 percent using nasal strips. “What was particularly interesting is that studies by Susan Holcombe, VMD, MD, PhD, DACVS, DACVECC, and Ed Robinson, BVetMed, PhD, of Michigan State University showed that nasal strips reduced the resistance to inhalation,” says Dr. Poole “With roughly 70 percent of resistance to breathing or inhalation in the horse being in the upper airway. This is significant. “It’s a really big deal,” reiterates Dr. Poole.

Racing On

Thanks to curious and qualified minds such as those of Drs. Bayly and Poole, much progress is being made in the study of EIPH, its origins and potential interventions from pharmacologic tools to environmental factors. “There’s much about the etiology of EIPH that we still don’t know,” says Dr. Poole. “It’s a very complex thing, but that doesn’t mean it can’t be understood. What it does mean is that we can’t necessarily predict it.” Both Drs. Bayly and Poole are insistent that EIPH cannot be painted with a broad brushstroke; it’s a condition that often expresses itself differently from one horse to the next and even from one occurrence to the next in the same horse. “Fundamentally, if you ask, ‘why does a horse bleed for the first time?’ it’s not a disease problem. Those lungs are working just fine in 99 percent of cases. There is no disease,” says Dr. Bayly emphatically. “There’s evidence that horses start to bleed when they’re first put into training as early 2-year-olds. They don’t have lung disease, but it is recognized that with repeated bouts of EIPH over time, there can be inflammatory changes that may ultimately lead to permanent changes in the architecture of the lungs, particularly around the veins.” While this development constitutes a pathologic condition, researchers are convinced that at its outset, EIPH is not a primary pathologic problem.

For Drs. Bayly and Poole, there is still much work to be done, and they’re certainly up for the challenge. EIPH affects a tremendous number of horses and is significantly more prevalent than once thought. With a changing landscape surrounding administration of furosemide and more being learned all the time regarding management, training alternatives and the availability of nasal strips, there seems to be substantial hope on the horizon for horses with EIPH and the veterinarians trying to best manage their cases with long-term health as a paramount priority.

Contributing Researchers