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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.

Lasix Study Backs Four-Hour Administration Time

Pair of Lasix studies of interest outline results.

A study that has some potential to reshape the timing of Salix administration ahead of racing determined that the current four-hour timeframe is more effective than administering 24 hours out in reducing the severity of exercise-induced pulmonary hemorrhage.

The study, led by Dr. Heather Knych, was one of two studies on Salix (furosemide, commonly referred to as Lasix) with results outlined at the American Association of Equine Practitioners convention in late November. The other study, led by Dr. Warwick Bayly, found some potential for a low dosage of Salix 24 hours out combined with controlled access to water in reducing EIPH in racing.

The Paulick Report first posted a story on the results of both studies Jan. 30.

According to the AAEP’s 2017 Convention Proceedings document, the study by Dr. Knych of the Ken L. Maddy Equine Analytical Chemistry Laboratory looked at the efficacy of administering Lasix 24 hours out, instead of the current four hours out called for in racing’s model rules. The study concluded that administering furosemide four hours before a race was more effective in reducing the severity of EIPH than going to 24 hours out.

The Knych study saw 15 Thoroughbreds administered furosemide either four or 24 hours prior to a five-furlong simulated race. Blood samples were collected before and after the simulated race for determination of furosemide, lactate, hemoglobin, and electrolyte concentrations.

One hour after the race, an endoscopic exam and bronchoalveolar lavage (BAL) was performed. Horses were assigned an EIPH score based on previously published criteria. The number of red blood cells in in BAL fluid was also determined.

“There was a statistically significant difference in EIPH scores between the four-hour and 24-hour furosemide administrations,” the study determined. The study noted that none of the treatments prevented EIPH in the horses but that reducted red blood cell counts in bronchoalveolar fluid post-race indicated that administering furesomide four hours before a race was the most effective.

According to its introduction, the study came together following anecdotal reports that suggested furosemide administration 24 hours prior to strenuous exercise could be equally effective at decreasing EIPH.

The United States is one of the few countries that allows the raceday administration of Lasix. A study showing efficacy in preventing EIPH at 24 hours or beyond had potential to reshape current raceday policy of administration four hours before the race.

In the study led by Bayly, it was determined that a 0.5 mg/kg administration of furosemide 24 hours before strenuous exercise combined with controlled access to water shows potential for reducing the severity of EIPH.

The study used six horses who underwent treadmill exercise to fatigue after seven different protocols that adjusted the dosage amount of the Lasix and timing of the administration. The study concluded that, “Furosemide, 0.5 mg/kg, combined with controlled access to water, significantly reduced the severity of EIPH,” adding that, “No ill effects were detected in the horses.”

In its AAEP presentation outline, the study noted that “Although the findings were promising, the number of horses used was small. The effects of furosemide on water and ion excretion were evident for 24 hours but did not adversely affect the horses, likely because of increased absorption of wager and ions from the colon.”

In September 2015, Grayson Jockey Club Foundation announced it had launched funding of the two projects. The AAEP also played a prominent role in funding the projects, along with a number of racetracks.

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