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A new study on EIPH and Salix

Abstracts have just been released for the upcoming Equine Science Society Symposium to be held in New Mexico at the end of May. Among the abstracts is a very interesting paper on EIPH completed by Dr Joe Pagan and colleagues. The abstract reads:

Furosemide reduces the energetic cost of exercise in Thoroughbreds independent of its effect on EIPH

J.D. Pagan, B.M. Waldridge, C. Whitehouse, L. Dalglish, S. Fuchs, and M. Goff

Kentucky Equine Research, Inc., Versailles, KY 40383

Six fit Thoroughbred geldings (age 6.8, BW 585kg) were used in a 3 by 3 Latin square trial to test the effect of furosemide on energetic efficiency during a standardized exercise test (SET) on an inclined (30) high-speed treadmill. The SET was performed at 1.7 m/s for 5 min, 4 m/s, 6 m/s, and 8 m/s for 2 min per step, and 9 m/s, 10 m/s, 11 m/s, 12 m/s, and 13 m/s for 1 min per step. The horses were not allowed access to water, hay or feed for 4 h before the SET. The treatment groups consisted of an untreated control (C) and two groups (F and FE) which received furosemide (0.5 mg/kg, IV) 4 h before the SET. C and F were fed 60g/d NaCl and (FE) was fed 200 g/d of an electrolyte mix (14 g K+, 37.7 g Na+ and 43.3 g Cl-) for 21 days before the SET along with 5.85 kg hay, 4.0 kg grain and .12 kg of a vitamin/mineral supplement. The horses were weighed 4 h before the SET (before furosemide administration), immediately before and after the SET and 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post exercise. Venous blood samples were taken at -4 h, -3 h and immediately before the SET; at the end of each step throughout the SET and 5 min, 1 h and 4 h post exercise. Blood was analyzed for lactate, glucose, total protein (TP) concentrations, and packed cell volume (PCV). Heart rate (HR), VO2 (l/min), and VCO2 (l/min) were measured during the last 30 s of each step during the SET. An endoscopic tracheobronchial assessment was conducted 1 h post exercise and the degree of EIPH graded.

Weight loss during the 4-h period before the SET was higher in F (avg 12.0 kg) and FE (avg 12.7 kg) compared to C (avg 6.67 kg) (p 0.05). During the SET HR was higher in C compared to F and FE (p 0.05). Absolute VO2 and VCO2 were higher in C compared to F and FE (p 0.05). When expressed on a weight-adjusted basis (ml/kg BW/min) VO2 and VCO2 were not different between treatments. Lactate accumulation was higher in C compared to F (p 0.05). TP was higher in F and FE compared to C (p 0.05) and PCV was higher in FE compared to C (p 0.05). The incidence of EIPH was very low and unrelated to treatment. The energy cost of exercise is the sum of energy generation from aerobic and anaerobic pathways which can be estimated from oxygen consumption and lactic acid accumulation.

Furosemide administration reduced energy generation from both pathways during exercise and this improvement was probably due to a reduction in body weight rather than a reduction in EIPH.

While the study was on a small number of horses (6) it was well constructed (Latin Square trial). The summary of the findings were that Salix (also known as Lasix and Furosemide), essentially acts as a lactate buffer (which is why the TCO2 levels for testing are higher on horses that use lasix than those that don't) and that it also delays oxygen debt. This performance enhancement is independent of alleviation of EIPH (which in this study they found insignificant incidence of).

These are familiar findings to other scientific papers.

Back in 1996, yes that long ago, Dr Ken Hinchcliff (the same that co-authored the widely touted South African Salix study), theorized that furosemide-induced weight reduction would reduce the contribution of anaerobic metabolism to energy expenditure. He co-authored a paper with his findings titled "Furosemide reduces accumulated oxygen deficit in horses during brief intense exertion". You can click on the link and read the abstract but the findings were that the use of Salix delays fatigue in horses. There is of course a lot of papers on Salix use and its performance enhancing characteristics, two of the more interesting ones can be read here, where they found that non-bleeders ran faster with Salix and that Salix did not deter the development of EIPH, or this one here where they found, similar to Pagan's study above, that the improvement of performance with Salix use was due more to the weight-loss related effects of the drug than any apparent alleviation of EIPH.

In the past I have been critical of the "pro-salix" crowd of cherry picking their science, which they have clearly done. They have promoted the South African study and other studies which show that contrary to some studies above, EIPH is reduced with the use of Salix and argued that equine welfare is paramount so we should use Salix to alleviate EIPH as it is the best option available. It would be equally dishonest on my part to not recognize these studies as well constructed and valid studies and that EIPH may in fact be reduced by the use of Salix. It would also be lazy not to recognize the uniqueness of racing in North America where the racing style and surface place unique demands on the physiology of the horse. Blasting out of the gate and running at full speed on a tiring surface is significantly different to the negative splits seen in most other racing jurisdictions.

That all said, the problem the "pro-salix" crowd has to deal with if they are intellectually honest, is that the balance of science shows that Salix confers a performance advantage for the bleeders and non-bleeders alike with delayed oxygen-debt, increased lacate buffering capabilities and weight loss enabling the horses that use it to run faster for longer when compared to horses of similar ability not given Salix. It is a performance disadvantage not to use Salix, but not because it solely reduces EIPH. In an era where anything related to performance enhancement is seen as a negative for a sport, framing a response to the performance enhancing capabilities of Salix is a challenge, especially when weighed with our responsibility to the welfare of the horse and the high heritability of EIPH in the breed.

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