Bleeder – Facts, Fiction and Future Direction

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BLEEDER – FACTS, FICTION & FUTURE DIRECTION 

We are now approaching half a century since Bob Cook pioneered the use of the flexible fibreoptic endoscope which allowed examination of the respiratory tract in the conscious horse. One of the important outcomes of this technique was that it opened the door to the study of “bleeding” or Exercise-Induced Pulmonary Haemorrhage. But nearly 50 years on the irony is perhaps that whilst we have become good at describing the prevalence of EIPH and some of the factors that appear to increase the severity of EIPH within individual horses, we still lack a clear understanding of the condition and how to manage it. I use the term manage rather than “treat” or “prevent” as our knowledge of EIPH must show us that EIPH cannot be stopped entirely; it is a consequence of intense exercise. The other irony is that in the past 50 years by far the majority of research into the management of EIPH has focused on the use of the diuretic furosemide. Whilst we have good evidence from controlled studies that furosemide reduces the severity of EIPH on a single occasion, we still lack good evidence to suggest that furosemide is effective when used repeatedly during training and or racing and there is also evidence to the contrary. 

Let’s review some basic facts about EIPH which should not be contentious. 

  • EIPH is the appearance of blood in the airways associated with exercise 
  • EIPH occurs as a result of moderate to intense exercise – in fact EIPH has been found after trotting when deep lung wash (bronchoalveolar lavage or BAL) is done after exercise  
  • EIPH most often involves the smallest blood vessels (capillaries) but can sometimes and less commonly be due to the rupture of larger blood vessels 
  • The smallest blood vessels are extremely thin – around 1/100th the thickness of a human hair. But this extremely thin membrane is also what allows racehorses such as Thoroughbreds, Standardbreds and Arabs to use oxygen at such a high rate and is a major reason for their athleticism  
  • EIPH is a progressive condition – the chance of seeing blood in the trachea after exercise increases with time in racing 
  • EIPH is variable over time, even when horses are scoped after the same type of work 
  • If you ‘scope a horse after three gallops in a row you can expect to see blood in the trachea on at least one occasion 
  • EIPH damage to the lungs starts at the back and top and over time moves forward and down and is approximately symmetrical 
  • Following EIPH the lung becomes fibrotic (as scar tissue), stiffer and does not work as well. The iron from the blood is combined with protein and stored permanently in the lung tissue where it can cause inflammation
  • High blood pressure within the lung is a contributing factor in EIPH. Horses with higher blood pressure appear to suffer worse EIPH 
  • There is also evidence that upper airway resistance and breathing pattern can play a role in EIPH 
  • Airway inflammation and poor air quality may increase the severity of EIPH within individual horses 
  • Increasing severity of EIPH appears to have an increasing negative effect on performance
  • Visible bleeding (epistaxis) has a very clear and marked negative effect on performance 

In order to make progress in the management of EIPH, i.e. to minimise the severity of EIPH in each individual, there are certain steps that trainers can take based on the information we have to date. These include: 

  • Ensuring good air quality in stables 
  • Regular respiratory examination and treatment of airway inflammation
  • Reduced intensity of training during periods of treatment for moderate to severe airway inflammation
  • Extended periods of rest and light work with a slower return to work for horses following viral infection 
  • Addressing anything that increases upper airway resistance e.g. roaring, gurgling
  • Avoiding intense work in cold weather 
  • Avoiding extremes of going
  • Limiting number of training days in race preparation and increasing interval between races

 FUTURE OPPORTUNITIES IN UNDERSTANDING AND MANAGING EIPH 

We have to accept EIPH as a normal consequence of intense exercise in horses. Our aim should be to reduce the severity to a minimum in each individual horse. However, there are areas where we still need a much greater scientific understanding.    

What actually causes the capillaries to leak or rupture? 

If you ask any vet or scientist or informed trainer what is the cause of EIPH they will give the phrase “pulmonary capillary stress-failure”. But this is simply a description of what happens, NOT an explanation of a mechanism. EIPH and pulmonary capillary stress-failure are both descriptions of what’s happening. We know high blood pressure makes the capillaries stiff. But what makes them actually rupture? A balloon filled with water may be distended and under a lot of stress. But a pin prick will actually make it burst. The pin is the cause. 

Assessing EIPH 

At present the most common way to assess the severity of EIPH in horses in training and racing is by ‘scoping 30-40 min after exercise and scoring the amount of blood in the trachea. This is a crude method and when we see a horse that has a score of 1 after one gallop and a 3 after the next gallop, we don’t know whether this is due to differences in how quickly the blood has moved from the periphery of the lung into the trachea or due to true difference in the amount of bleeding. We know our ‘scoping scores vary gallop to gallop – we just don’t know why. BAL (deep lung wash) is not the answer either. It will pick up blood when there is none to be seen in the trachea – i.e. it’s a more sensitive technique, but with BAL we are looking at relatively small areas of the lung. What we need is a technique that will allow us to image the whole lung and map the blood that is in the airways and not in the blood vessels so we can assess volume and distribution of haemorrhage. 

Furosemide is not the answer 

A number of well-conducted and well-written scientific studies have shown conclusively that furosemide is effective in reducing the severity of EIPH in individual horses when used ONE time! We lack convincing studies that prove furosemide works as well when used 1-2 times a week for 2-3 months. In fact several studies suggest that furosemide becomes less effective with regular use, such as the return to previous performance of horses after initial racing and improved performance on furosemide. In human medicine, repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) tolerance i.e. if you give the same dose repeatedly, the body becomes tolerant and you get less and less urine production. A study in horses from Michigan State University in 2017 showed horses develop tolerance to furosemide. Why, when we have had nearly 50 years of research into EIPH, with more published studies devoted to furosemide than any other aspect, do we still not know if furosemide is effective when used on a regular basis? 

Is EIPH really blood? 

The assumption has always been that what we see in the airways is blood. That is, it’s the same stuff as we would get if we put a needle in a vein. However, some data from my own studies as yet unpublished and indirect evidence from other studies suggests that initially the high pressures distend the capillaries and open up “holes” that allow protein and some red blood cells to squeeze out into the airways as opposed to obvious tears or ruptures developing in the capillaries. This is consistent with observations that many “holes” close up when the blood pressure returns to normal and that EIPH does not continue once exercise has stopped. If we viewed EIPH as being a protein rich fluid in the airways with some red blood cells as opposed to blood this may have important implications for some lines of research. 

Inflammation cause or effect 

It’s safe to conclude that EIPH and airway inflammation are often associated i.e. observed to occur together, but we still lack clarity on whether one leads to the other. Racehorses experience intense exercise. Racehorses often have airway inflammation. But the two can occur in isolation or together. This does not mean they are related in any way.  

Heritability 

Many trainers believe that there are certain bloodlines that are likely to bleed more severely. As yet there is no good scientific evidence to suggest that EIPH severity is heritable. However, if specific factors which increase the severity of EIPH such as high blood pressure are heritable then it is entirely conceivable that EIPH severity will be found to have some component of heritability.  

Future directions 

EIPH is not a condition solely restricted to racehorses. It has been reported in other horses including polo ponies, showjumpersbarrel-racers, endurance horses and eventers and even in Shetland ponies. It is also not a condition restricted to horses as it has been reported in camels, greyhounds and in human subjects exercising intensely such as swimmers, skiers and military personnel. A primary goal of research into EIPH should be to understand why a proportion of the population bleeds more severely and to attempt to reduce the severity in this population. We also require more sensitive and informative techniques to allow us to research EIPH. ‘Scoping is at best a crude and insensitive and potentially misleading technique which may well be hampering our ability to make significant steps forward in our understanding of EIPH. Within the next decade I also expect to see clear evidence that furosemide is of limited value in the longterm management of EIPH and we will be judged harshly for having relied on it for so long as the mainstay of treatment.  

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About Author

Dr David Marlin is a physiologist and biochemist who has worked in academia, research and professional sport. He has worked in the equestrian and veterinary world and in human sport, healthcare, medicine and exercise science. In 1989 David obtained his PhD from the UK’s leading sports university, Loughborough University following a four-year study on the responses of Thoroughbred racehorses to exercise and training, undertaken at the renowned Animal Health Trust in Newmarket. You can read David's full biography in the Our Website section.