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KHRC Funds Catastrophic Injury Study at UK Gluck Center

By Jenny Evans

 

LEXINGTON, Ky., (Aug. 17, 2018) – The Kentucky Horse Racing Commission recently voted unanimously to fund a project at the University of Kentucky Maxwell H. Gluck Equine Research Center examining inflammatory and anti-inflammatory markers as early indicators for potential catastrophic (life-ending) injury in racehorses.

The occurrence of injuries in horses and jockeys during training and racing is a significant economic and welfare concern for the Thoroughbred industry. While there has been increased interest in the development of techniques to identify individual horses at risk for injury, these approaches have not been widely adopted.

“We have a method to detect inflammation in horses and are proposing to determine its utility in the early detection of an impending catastrophic injury,” said Allen Page, principal investigator and scientist/veterinarian at the Gluck Equine Research Center.

Scientists have made multiple attempts to use biomarkers as indicators of injury, but the data thus far has shown this isn’t reliable. Instead, researchers will rely on measuring mRNA, or the precursors to proteins, from circulating white blood cells.

“Our theory is that these cells pass by areas of bone or soft-tissue damage, which are activated by the damage, and begin producing inflammatory or anti-inflammatory mRNA, which we then measure,” Page explained. “Based on this, our hypothesis for the study is that those Thoroughbred racehorses that experience a catastrophic injury while racing will have evidence of increased inflammation when compared to non-injured horses.”

Researchers in the two-year, $164,488 study, titled “Inflammation in Catastrophically Injured Thoroughbreds,” have been collecting samples since January with the help of multiple state and local racing jurisdictions. Page recently spoke with regulatory racing veterinarians to encourage additional participation in the study, as the ultimate goal is to sample 150 catastrophically injured horses, as well as approximately 1,000 non-injured horses, from across North America.

“By using non-injured horses from the same race, as well as horses in the general racing population, we anticipate identifying patterns of inflammation which may be indicative of a specific injury type,” said David Horohov, co-principal investigator, Gluck Equine Research Center director and Department of Veterinary Science chair. “This may then be of use in the future to help identify horses that need additional examination before a race.”

Page said, while there has been a significant amount of work in the past two decades to take large amounts of data and create models for determining risk factors for racehorse injuries, those models are not being used on a widespread basis yet.

“It’s exciting to think that a single blood sample may be all we need to help identify an individual at-risk horse as we work with the racing industry to further improve the safety and welfare of these incredible athletes,” Page said.

The mission of the Gluck Center, a UK Ag Equine program in the College of Agriculture, Food and Environment, is scientific discovery, education and dissemination of knowledge for the benefit of the health and well-being of horses. The Gluck Center faculty conducts equine research in seven targeted areas: genetics and genomics, immunology, infectious diseases, musculoskeletal science, parasitology, pharmacology/toxicology and reproductive health. Their continuing efforts build upon a tradition of excellence in equine research dating back to 1915. For more information on the Gluck Center, visit http://gluck.ca.uky.edu.

 

Study Narrows Focus on How Furosemide Works

Learning how the medication works could lead to alternative treatments of EIPH.

A recently published study in Comparative Exercise Physiology found a relationship between the administration of the medication furosemide, used to prevent exercise-induced pulmonary hemorrhage, and an enzyme that affects the pressure within the blood vessels in a horse’s lungs.

The relationship potentially points toward new avenues to explore regarding the treatment of EIPH in Thoroughbred racehorses.

The study, conducted at Gávea Racecourse in Rio de Janeiro, Brazil, analyzed post-race blood samples from 73 horses over eight race days. Of the 73 horses, 47 had been treated with 250 mg of furosemide before their race and 26 were not medicated.

These samples were then tested for levels of angiotensin converting enzyme (ACE), a potent vasoconstrictor that when active contributes to higher blood pressure. Several studies have affirmed furosemide’s effectiveness in reducing incidences of EIPH, but how the diuretic drug actually works is still unknown. This study showed ACE activity was significantly reduced in the horses that had been treated with furosemide.

“Multiple regression analysis demonstrated that pre-race furosemide significantly influenced ACE activity post-race, while distance raced, temperature, humidity, and hematocrit did not,” the study concluded. “This is a novel finding which might impact on the search for the exact implications of furosemide use, and its effects on physiology and performance of Thoroughbred racehorses utilizing loop diuretics as treatments for EIPH.”

The horses used in this study were already stabled at Gávea and the treated horses were part of the racetrack’s established protocol on managing EIPH. At Gávea, a horse is entitled to pre-race furosemide if an official racetrack veterinarian has documented a bleeding episode through tracheobronchoscopy exam. A registered bleeder can receive furosemide four hours prior to post time and must continue to receive treatment for every race within 90 days from diagnosis. Horses that are younger than 3 1/2 years old are not allowed to receive pre-race furosemide, and any medicated horse is prohibited from competing in a group 1 or group 2 race.

While furosemide has proven to be the most effective method of reducing EIPH, the medication still does not entirely prevent its occurrence. In the Gávea study, 36.2% of the non-medicated horses showed some degree of post-race bleeding compared with 76.9% of the treated horses.

“This study confirms that, although furosemide might reduce EIPH severity after a single bout of exercise, it does not abolish or reduce its occurrence,” wrote the study’s authors. “This conclusion does not argue against the use of furosemide as a treatment for control of EIPH, but indicates the continuing need for better alternatives to limit the progressive and deleterious effects of repeated episodes of EIPH on the lungs of horses, and that further research into the possible role of renin-angiotensin aldosterone system components (like ACE) in developing new treatments is needed.”

The study was published by Dr. Maria Fernanda de Mello Costa, Dr. Fernanda Aparecida Ronchi, Dr. Yoonsuh Jung, Dr. A. Ivanow, Dr. Juliana Braga, Dr. M.T. Ramos, Dr. Dulce Elena Casarini; and Dr. Ronald F. Slocombe.

Equine Biological Passports: Years Away, But Receiving Industry Support

by

04.12.2018

 

The Kentucky Equine Drug Research Council (KEDRC) unanimously voted this week to allocate $15,000 to funding ongoing research into biological passport. Although the technology is at least a couple of years from implementation, Dr. Scott Stanley of the University of California-Davis said the passports could solve several problems in drug testing.

Regulators face particular challenges testing for long-acting prohibited substances like erythropoietin (EPO) and drugs creating steroid-like effects in the body. EPO in particular withdraws from the blood very quickly, but its impact (increasing the concentration of oxygen-carrying red blood cells in the body) lingers considerably longer. Both steroids and blood doping agents also tend to be used repeatedly but often weeks in advance of a race. Out-of-competition testing can act as a deterrent for these substances, but regulators still have a short window to actually find a positive level of the drugs in the horse’s system.

Biological passports track the responses of proteins and biomarkers to the administration of drugs like these even after the drugs themselves are gone. Stanley said the technology also gets around a common concern on the part of horsemen: what if a given horse, through no manipulation, is a natural outlier in the range of ‘normal’ for a hormone or protein? Sampling for passports would be taken repeatedly over an extended period of time, allowing regulators to compare a given reading not just with the normal range of the whole population, but also to the horse’s own previous readings.

Before the technology is ready for use at the racetrack though, Stanley and other researchers have to look at a range of markers in the equine body to decide which are the truest indicators of drug administration. Hormones and blood levels fluctuate naturally in response to the time of day, the season, and maybe a horse’s location.

Initial tests on a research horse looking at P27425 (an iron binding protein) produced exactly the results scientists expected. They plan to collect data from 50 to 100 horses in California in over one or more years to see how biomarkers behave in horses and which are the most consistent. When passport testing begins, Stanley anticipates a cross-section of horses will need to be sampled on a monthly basis in addition to post-race readings. As a greater cache of data is collected and stored, the monthly testing will become unnecessary.

The California Horse Racing Board and Grayson-Jockey Club Foundation have already provided funding to the project.

Dr. Andy Roberts, member of the KEDRC, questioned whether different (completely legal) training or feed routines could also cause a noticeable change in a horse’s passport levels. Stanley said it’s possible they could, so changes in passport readings would need to be taken as just a piece of the greater puzzle in what’s going on with a horse.

“Right now we would definitely see it as [a tool to initiate] an investigation: ‘This horse has been flagged for further follow-up’ and we’d get additional sequential samples from that to see if that horse is naturally outside the normal boundary,” said Stanley. “In the future, I think we could have enough additional data to say, ‘The upstream and downstream changes are not consistent with anything other than an administration.’ We just don’t have that data definitively yet to say what those changes should be.”

Unfortunately for equine researchers, the work that has been done on human biological passports with regard to blood-doping agents doesn’t seem as though it will be applicable to horses. The equine spleen is considerably different from that of humans, and its ability to suddenly contract with exertion causes changes in blood levels that would not be typical in a human.

The good thing about biological passports for racing regulators is that the technology won’t care what type of drug a trainer may have used to influence red blood cells or muscle tone, since they measure the body’s reaction instead of the size of drug molecules.

Like drug testing however, Stanley cautioned biological passports will be a constantly-evolving scientific process – but one that could have major impacts on integrity down the road.

“It isn’t a short-term project. It is years-long to get enough data,” he said. “The whole project is underfunded and it would take a long time even if it was fully-funded. I suspect we’ll be looking at more data in a couple years rather than a couple weeks.”

“The long-term intent is to provide deterrence. I truly believe that drug testing is about deterrence. We want to convince people we can test for everything and anything at any concentration that is prohibited. Just as we’re doing in Quarter Horse racing with a lot of hair testing right now, we would like to prevent [violators] from racing rather than penalize them after the race as an unfair competition.”

 

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