Source: PURDUE UNIVERSITY submitted to
DO ADJUNCT BLEEDER MEDICATIONS MITIGATE EXERCISE-INDUCED PULMONARY HEMORRHAGE IN RACEHORSES?
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0206104
Grant No.
(N/A)
Project No.
IND020767
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Dec 1, 2005
Project End Date
Sep 30, 2010
Grant Year
(N/A)
Project Director
Couetil, L. L.
Recipient Organization
PURDUE UNIVERSITY
(N/A)
WEST LAFAYETTE,IN 47907
Performing Department
VETERINARY CLINICAL SCIENCES
Non Technical Summary
Racehorses commonly bleed into their lungs while racing, a condition called exercise-induced pulmonary hemorrhage (EIPH). The purpose of this study is to evaluate the safety and effects of adjunct bleeder medications and furosemide on EIPH and performance in racehorses.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113810102080%
3113810116020%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3810 - Horses, ponies, and mules;

Field Of Science
1020 - Physiology; 1160 - Pathology;
Goals / Objectives
Racehorses exhibiting moderate to severe exercise-induced pulmonary hemorrhage (EIPH) are likely to perform poorly. To date, only the diuretic furosemide has been shown scientifically to help decrease lung bleeding in racehorses with EIPH. Furosemide is authorized as pre-race medication in the majority of states including Indiana. Anecdotal evidence from trainers and racetrack veterinarians suggest that additional medications may help reduce the severity of EIPH in horses that still experience bleeding despite pre-race administration of furosemide. As a result, a handful of racing jurisdictions have authorized the use of these so-called adjunct bleeder medications in combination with furosemide. However, to date, no scientific studies have examined the safety and efficacy profile of these medications in horses. Therefore, the purpose of this study is to compare the effects of furosemide alone and in combination with an adjunct bleeder medication to a placebo treatment. The primary objective of this study is to quantify the effect of furosemide and adjunct bleeder medications on pulmonary bleeding in exercising Standardbred racehorses using red blood cell count in bronchoalveolar lavage fluid as primary outcome variable. Secondary outcome variables will be arterial blood gases and hemostasis data collected during treadmill tests and total run time during each test. The different adjunct bleeder medications to be tested are carbazochrome, aminocaproic acid, tranexamic acid and conjugated estrogens. Primary hypothesis: The administration of furosemide reduces the severity of EIPH in Standardbred racehorses and the combination of furosemide with an adjunct bleeder medication is more effective than furosemide alone. Secondary hypotheses: The administration of furosemide improves pulmonary gas exchanges, hemostasis, and subsequently, performance in exercising Standardbred racehorses suffering from exercise-induced pulmonary hemorrhage. The combination of furosemide with an adjunct bleeder medication is more effective than furosemide alone.
Project Methods
The study will examine the effects of furosemide and a combination of furosemide and an adjunct bleeder medication (carbazochrome, aminocaproic acid, tranexamic acid or conjugated estrogens) on pulmonary gas exchanges, pulmonary bleeding, hemostasis, and performance during treadmill exercise tests in Standardbred racehorses confirmed bleeders. Horses: Criteria for selection will be prior evidence of EIPH by endoscopy after exercise, no evidence or history of upper airway obstruction, and no evidence of lameness during high-speed work. Eight will participate in each clinical trial. Horses will be acclimatized to the treadmill and trained for eight weeks to establish uniform fitness. Exercise testing: - Experimental design: Each clinical trial will be designed as a 3-way cross-over, placebo-controlled study. Horses will be tested four hours after receiving each one of three intravenous treatments in randomized order: placebo, furosemide (250 mg), or the furosemide (250 mg)-adjunct bleeder medication combination. The dose used for adjunct bleeder medication combination correspond to the amount commonly administered to racehorses by veterinarians practicing in states where adjunct bleeder medications are authorized. - Treadmill test: The exercise testing will consist of incremental speed steps (6, 8, 10,11 and 12 m/s) at 5% incline. The exercise testing will be stopped when the horse exhibits signs of fatigue or after 1 minute at 12 m/s. - Blood sampling and tests: Prior to testing, horses will be fitted with a catheter in the transverse facial artery. Blood samples will be collected during the last 15s of each speed step. - Hemostasis: Activated clotting time, prothrombin time and activated partial thromboplastin time will be measured following the routine coagulation profile used at Purdue University. - Post-exercise evaluation: Horses will be sedated one hour post-treadmill test. A videoendoscope will be passed through the airways to quantify the amount of blood visible in the tracheobronchial tree and then perform a bronchoalveolar lavage (BAL). Red blood cell counts in BAL will be determined using an automated cell counter. Drug safety: Safety of the medications will be assessed during the study by daily physical examination. In addition, blood analyses (hematology and serum biochemistry) will be performed on each horse before the start of the trial (baseline), 24 hours and 7 days after drug administration. Statistical analysis: The effects of treatment and horse on the measured variables (bronchoalveolar lavage fluid red cells, blood gases, hemostasis, run time) and the interaction between treatment and horse will be tested for statistical differences using a mixed-model generalized linear approach. The significance level will be placed at 0.05.

Progress 12/01/05 to 09/30/10

Outputs
OUTPUTS: Activities: We examined the effects of furosemide and a combination of furosemide and carbazochrome on pulmonary bleeding, hemostasis, pulmonary gas exchanges and performance during a standardized treadmill exercise tests in Standardbred racehorses confirmed bleeders. The clinical trial was designed as a 3-way cross-over, placebo-controlled, Latin square design. Horses were trained on the treadmill for 6 weeks prior to the trial. Then, each horse completed three identical treadmill tests at 1 week intervals. Horses were tested four hours after receiving each one of three intravenous treatments in randomized order: placebo (5 ml of 0.9% sterile saline solution), furosemide (250 mg), or the furosemide (250 mg)-carbazochrome (100 mg) combination. The dose and timing of furosemide administration was based on the protocol authorized by Indiana law. Two MS graduate students worked and were mentored during this project. One student's graduate research was centered on this project and she defended her MS thesis successfully on 4/25/07. Four undergraduate students (Animal Science majors) worked as research assistants on this project. Events: Results from the study were presented in form of a scientific poster at the meeting of the Omicron chapter of Phi Zeta, the honor society for Veterinary Medicine in April 2007 and at the Latino Scholars Forum in September 2007. Both events were hosted at Purdue University. Some of the study results were also delivered as oral and poster presentations during the 25th Symposium of the Veterinary Comparative Respiratory Society in October 2007 in Lafayette, Indiana. The graduate student working on this project presented the public defense for her thesis in April 2007. A seminar that included results from this study was presented to the veterinary research community in form of an oral presentation at the Dorothy R. Havemeyer Foundation Symposium on Exercise-Induced Pulmonary Hemorrhage in November 2008. Products: The project was a collaborative effort between researchers from 2 Departments in the School of Veterinary Medicine (Veterinary Clinical Sciences and Comparative Pathobiology) with expertise in exercise physiology, clinical pathology and epidemiology and biostatistics. PARTICIPANTS: Cecilia Perez-Moreno, DVM worked on this project as a graduate student in the Department of Animal Sciences, School of Agriculture and successfully defended her M.S. thesis in 2007. Suzanne Pratt, DVM was a graduate student in Clinical Pathology in the Department of Veterinary Pathobiology, School of Veterinary Medicine and collaborated with Dr. Perez-Moreno to validate the hemoglobin assay that was used in the study. Rose Raskin, DVM, PhD is a Professor of Clinical Pathology in the Department of Comparative Pathobiology. She supervised graduate student work related to cytological analysis of bronchoalveolar lavage fluid. Dr. Raskin was also a member of Dr. Perez-Moreno's MS advisory committee. Hugo Ochoa-Acuna, DVM, MS, PhD is an Assistant Professor of Environmental Epidemiology in the Department of Comparative Pathobiology. He provided assistance with study design and data analysis. Mark Russell, PhD is a Professor of Animal Sciences, School of Agriculture. He contributed to the study design and was co-Chair of Dr. Perez-Moreno's MS advisory committee. Laurent Couetil, DVM, PhD is a Professor of Large Animal Medicine in the Department of Veterinary Clinical Sciences, School of Veterinary Medicine. He designed the study, supervised all aspect of data collection, analyses and manuscript preparation. Dr. Couetil was also co-Chair of Dr. Perez-Moreno's MS advisory committee and was a member of Dr. Suzanne Pratt's MS advisory committee. TARGET AUDIENCES: The main target audience for this work at this point in time is veterinarians and scientists involved in equine sports medicine. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Racehorses commonly bleed into their lungs while racing and severe bleeding results in poor performance. Some racing jurisdictions authorize bleeder medications such as furosemide (diuretic) and carbazochrome (hemostatic) but scientific proofs of their efficacy are weak (furosemide) or lacking (carbazochrome). Results from this study suggest that measurement of protein and hemoglobin content in lung wash fluid (BALF) collected after exercise is a valuable test for quantification of lung bleeding. Using these methods, we found a mild reduction in lung bleeding in horses exercising strenuously after receiving furosemide - carbazochrome or furosemide. However, the study had insufficient power to reach statistically significant results. Given the variability we observed in our horses; a sample size of more than eight animals would have been needed to achieve the desired power (80%). Unfortunately, we were unsuccessful in our attempts to obtain extramural funding for the completion of a larger clinical trial. Consequently, further studies are warranted but should take into account the shortcomings described in this study in order to determine if horses with EIPH may indeed benefit from carbazochrome therapy.

Publications

  • Book chapters: Couetil LL. Multimodal management of the horse with airway disease. In: Robinson N.E.(Ed.). Current Therapy in Equine Medicine, 6th Edition: Elsevier; 2009:279-283. Couetil L. Diseases of the respiratory system. Chapter 3. In: Abutarbush S. (Ed.). Illustrated Guide to Equine Diseases, Wiley-Blackwell; 2009:175-210. Couetil LL. Detection of respiratory diseases in horses. In: Equine Respiratory Diseases, Lekeux P. (Ed.). International Veterinary Information Service, Ithaca NY (www.ivis.org), Last updated: 19-Sep-2007; B0311.0907.
  • Journal articles: Perez-Moreno CI, Couetil LL, Pratt SM, Ochoa-Acuna HG, Raskin RE, Russell M. Effect of furosemide and furosemide-carbazochrome combination on exercise-induced pulmonary hemorrhage in standardbred racehorses. Can J Vet Res 2009; 50(8):821-827.
  • Abstracts: Couetil L, Perez-Moreno C, Pratt SM, Ochoa-Acuna HG, Raskin RE. Effect of adjunct bleeder medications on pulmonary bleeding in standardbred racehorses. Proceedings of the Dorothy R. Havemeyer Foundation Symposium on EIPH. 2008,30:20. Couetil LL. Inflammatory airway disease and EIPH: is there a link Proceedings of the Dorothy R. Havemeyer Foundation Symposium on EIPH. 2007;20:21-23. Perez-Moreno C, Couetil L, Pratt SM, Ochoa-Acuna HG, Raskin RE. Effect of furosemide and furosemide-carbazochrome combination on pulmonary bleeding in standardbred racehorses. Proceedings of the 25th Symposium of the Veterinary Comparative Respiratory Society. 2007.
  • Other: Perez-Moreno CI. Effect of furosemide and furosemide-carbazochrome combination on exercise-induced pulmonary hemorrhage in standardbred racehorses. M.S. thesis, 2007.


Progress 10/01/08 to 09/30/09

Outputs
OUTPUTS: Over 80 % of racehorses exhibit some degree of exercise-induced pulmonary hemorrhage (EIPH) or lung bleeding during racing. Horses exhibiting moderate to severe exercise-induced pulmonary hemorrhage (EIPH) are likely to perform poorly. To date, only the diuretic furosemide has been shown scientifically to help decrease lung bleeding in racehorses with EIPH. Pre-race administration of furosemide to racehorses with EIPH is currently an approved therapy in most American racing jurisdictions. Several adjunct bleeder medications such as carbazochrome are permitted in a handful of racing jurisdictions when used in combination with furosemide. However, to date, no scientific studies have examined the safety and efficacy profile of these medications. Therefore, the objective of this study is to quantify the effect of furosemide and adjunct bleeder medication on EIPH in Standardbred horses. We examined the effects of furosemide and a combination of furosemide and carbazochrome on pulmonary bleeding, hemostasis, pulmonary gas exchanges and performance during a standardized treadmill exercise tests in six Standardbred racehorses confirmed bleeders. The clinical trial was designed as a 3-way cross-over, placebo-controlled, Latin square design. Horses were trained on the treadmill for 6 weeks prior to the trial. Then, each horse completed three identical treadmill tests at 1 week intervals. Horses were tested four hours after receiving each one of three intravenous treatments in randomized order: placebo (5 ml of 0.9% sterile saline solution), furosemide (250 mg), or the furosemide (250 mg)-carbazochrome (100 mg) combination. The dose and timing of furosemide administration was based on the protocol authorized by Indiana law. In conclusion, this study found that furosemide - carbazochrome combination had no detectable effect on the severity of exercise-induced pulmonary hemorrhage in Standardbred horses compared to furosemide and placebo treatments. Furthermore, none of the treatments abolished pulmonary hemorrhage following intense exercise in these horses. Yet, horses showed a 25 and 70 percent reduction in hemoglobin concentration in BALF when receiving furosemide - carbazochrome and furosemide when compared to the placebo group, respectively. Consequently, further studies are warranted but should take into account the shortcomings described in this study in order to determine if horses with EIPH may indeed benefit from carbazochrome therapy. Results from this study were presented to the veterinary research community in form of an oral abstract presentation at the Dorothy R. Havemeyer Foundation Symposium on EIPH in November 2008. In addition, a manuscript was published in the Canadian Journal of Veterinary Research in August 2009. A thesis was written by a graduate student (Cecilia Perez-Moreno) based on the work conducted in the study above in partial fulfillment of the requirement for the degree of Master of Science. PARTICIPANTS: Cecilia Perez-Moreno, DVM worked on this project as a graduate student in the Department of Animal Sciences, School of Agriculture and successfully defended her M.S. thesis in 2007. Suzanne Pratt, DVM was a graduate student in Clinical Pathology in the Department of Veterinary Pathobiology, School of Veterinary Medicine and collaborated with Dr. Perez-Moreno to validate the hemoglobin assay that was used in the study. Rose Raskin, DVM, PhD is a Professor of Clinical Pathology in the Department of Comparative Pathobiology. She supervised graduate student work related to cytological analysis of bronchoalveolar lavage fluid. Dr. Raskin was also a member of Dr. Perez-Moreno's MS advisory committee. Hugo Ochoa-Acuna, DVM, MS, PhD is an Assistant Professor of Environmental Epidemiology in the Department of Comparative Pathobiology. He provided assistance with study design and data analysis. Mark Russell, PhD is a Professor of Animal Sciences, School of Agriculture. He contributed to the study design and was co-Chair of Dr. Perez-Moreno's MS advisory committee. Laurent Couetil, DVM, PhD is a Professor of Large Animal Medicine in the Department of Veterinary Clinical Sciences, School of Veterinary Medicine. He designed the study, supervised all aspect of data collection, analyses and manuscript preparation. Dr. Couetil was also co-Chair of Dr. Perez-Moreno's MS advisory committee and was a member of Dr. Suzanne Pratt's MS advisory committee. TARGET AUDIENCES: The main target audience for this work at this point in time is veterinarians and scientists involved in equine sports medicine. Final conclusions from our studies should result in publications for lay audiences concerned with sports and race horses. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Racehorses commonly bleed into their lungs while racing and severe bleeding results in poor performance. Some racing jurisdictions authorize bleeder medications such as furosemide (diuretic) and carbazochrome (hemostatic) but scientific proofs of their efficacy are weak (furosemide) or lacking (carbazochrome). Results from this study suggest that measurement of protein and hemoglobin content in lung wash fluid (BALF) collected after exercise is a valuable test for quantification of lung bleeding. Using these methods, we found a mild reduction in lung bleeding in horses exercising strenuously after receiving furosemide - carbazochrome or furosemide. However, the study had insufficient power to reach statistically significant results. Given the variability we observed in our horses; a sample size of more than eight animals would have been needed to achieve the desired power (80%). Consequently, further studies are warranted but should take into account the shortcomings described in this study in order to determine if horses with EIPH may indeed benefit from carbazochrome therapy.

Publications

  • Perez-Moreno CI. Effect of furosemide and furosemide-carbazochrome combination on exercise-induced pulmonary hemorrhage in standardbred racehorses. M.S. thesis, 2007.
  • Perez-Moreno CI, Couetil LL, Pratt SM, Ochoa-Acuna HG, Raskin RE, Russell M. Effect of furosemide and furosemide-carbazochrome combination on exercise-induced pulmonary hemorrhage in standardbred racehorses. Can. J. Vet. Res. 2009; 50(8):821-827.
  • Couetil L. Adjunct bleeder medications efficacy in racehorses. Proceedings of the Dorothy R. Havemeyer Foundation Symposium on EIPH. Nov. 2008.


Progress 10/01/07 to 09/30/08

Outputs
OUTPUTS: We examined the effects of furosemide and a combination of furosemide and carbazochrome on pulmonary bleeding, hemostasis, pulmonary gas exchanges and performance during a standardized treadmill exercise tests in six Standardbred racehorses confirmed bleeders. The clinical trial was designed as a 3-way cross-over, placebo-controlled, Latin square design. Horses were tested four hours after receiving each one of three intravenous treatments in randomized order: placebo (5 ml of 0.9% sterile saline solution), furosemide (250 mg), or the furosemide (250 mg)-carbazochrome (100 mg) combination. We examined the effect of strenuous exercise on the composition of bronchoalveolar lavage fluid (BALF) and found that both hemoglobin and protein concentrations increased in BALF collected 1 hour after a standardized treadmill test. Cell differential counts in BALF were not significantly affected by exercise. Then, we used BALF hemoglobin and protein measurements to quantify lung bleeding. We observed that treatment of Standardbred racehorses suffering from EIPH with furosemide or furosemide/carbazochrome combination did not result in statistically significant reduction in pulmonary hemorrhage when compared to placebo treatment. However, standard deviations were large and may have masked small treatment effects. In fact, a reduction of 25 and 70 % in hemoglobin concentration was observed in the furosemide and furosemide - carbazochrome treatments, respectively, when compared to the placebo group. Poor statistical power may also be an important consideration when endeavoring to explain the lack of significance in our results. Due to the difficulty in recruiting the desired number of eight horses, the sample size originally sought, the statistical power of the analyses performed on hemoglobin concentration with six horses was 0.60, less than the desired value of 0.80 when the alpha error was set at 0.05. A sample size of more than eight animals would have been needed to achieve a power of 80%. In conclusion, this study found that furosemide - carbazochrome combination had no detectable effect on the severity of exercise-induced pulmonary hemorrhage in Standardbred horses compared to furosemide and placebo treatments. Furthermore, none of the treatments abolished pulmonary hemorrhage following intense exercise in these horses. Yet, horses showed a 25 and 70 percent reduction in hemoglobin concentration in BALF when receiving furosemide - carbazochrome and furosemide when compared to the placebo group, respectively. Consequently, further studies are warranted but should take into account the shortcomings described in this study in order to determine if horses with EIPH may indeed benefit from carbazochrome therapy. Results from this study were presented to the veterinary research community in form of an oral abstract and poster presentation during the Veterinary Comparative Respiratory Society meeting that was held at Purdue University in October 2007. In addition, a manuscript was submitted to the Canadian Journal of Veterinary Research and accepted for publication in July 2007. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Equine veternarians PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Racehorses commonly bleed into their lungs while racing and severe bleeding results in poor performance. Some racing jurisdictions authorize bleeder medications such as furosemide (diuretic) and carbazochrome (hemostatic) but scientific proofs of their efficacy are weak (furosemide) or lacking (carbazochrome). Results from this study suggest that measurement of protein and hemoglobin content in lung wash fluid (BALF) collected after exercise is a valuable test for quantification of lung bleeding. Using these methods, we found a mild reduction in lung bleeding in horses exercising strenuously after receiving furosemide - carbazochrome or furosemide. However, the study had insufficient power to reach statistically significant results. Given the variability we observed in our horses; a sample size of more than eight animals would have been needed to achieve the desired power ( 80%). Consequently, further studies are warranted but should take into account the shortcomings described in this study in order to determine if horses with EIPH may indeed benefit from carbazochrome therapy.

Publications

  • Perez-Moreno C, Couetil L, Pratt SM, Ochoa-Acuna HG, Raskin RE. Effect of furosemide and furosemide-carbazochrome combination on pulmonary bleeding in standardbred racehorses. Proceedings of the 25th Symposium of the Veterinary Comparative Respiratory Society. 2007.


Progress 10/01/06 to 09/30/07

Outputs
OUTPUTS: Results from the study were presented in form of a scientific poster at the meeting of the Omicron chapter of Phi Zeta, the honor society for Veterinary Medicine in April 2007 and at the Latino Scholars Forum in September 2007. Both events were hosted at Purdue University. Study results were also delivered as oral and poster presentations during the 25th Symposium of the Veterinary Comparative Respiratory Society in October 2007 in Lafayette, Indiana. The graduate student working on this project defended her MS thesis successfully on 4/25/07. PARTICIPANTS: Laurent L Couetil: PI, supervised project and training of graduate student including participation in data analyses, writing of research abstracts and manuscript and co-chaired MS thesis defense committee meeting for Dr. Perez-Moreno. Cecilia I Perez-Moreno: Graduate student (DVM) working on this project. She defended her MS thesis successfully on 4/25/07. Suzanne M Pratt: Graduate student (DVM) in Clinical Pathology at Purdue University who interpreted bronchoalveolar lavage samples cytology. Hugo G Ochoa-Acuna: Epidemiologist who conducted statistical analyses of the data. Rose E Raskin: Professor of Clinical Pathology who supervised Dr. Pratt during interpretation of bronchoalveolar lavage samples and participated in the training of Dr. Perez-Moreno as member her MS committee. Mark A Russell: co-chaired MS thesis defense committee meeting for Dr. Perez-Moreno. TARGET AUDIENCES: Veterinarians, equine extension specialists, equine industry

Impacts
The aim of this study was to quantify the effect of furosemide and carbazochrome on pulmonary bleeding in exercising Standardbred racehorses using red blood cell count, hemoglobin and protein concentrations in bronchoalveolar lavage fluid as primary outcome variable. Secondary outcome variables measured were arterial blood gases and hemostasis data collected during each treadmill test. We hypothesized that a combination of furosemide and carbazochrome would help decrease the severity of EIPH and improve pulmonary gas exchanges in exercising racehorses. Data collection from the clinical trial was successfully completed in May 2006. Statistical analysis was completed in December 2006. The graduate student working on this project defended her MS thesis successfully on 4/25/07. A manuscript was written and submitted for publication to a scientific journal in August 2007. We did not detect a statistically significant effect of the drugs used (furosemide and carbazochrome) on the severity of lung hemorrhage in racehorse Standardbred exercising on a high-speed treadmill. However, the low statistical power of the study (0.6) and the fact that horses treated with the drugs experienced less severe bleeding suggest that additional studies including a larger number of horses are needed. Nevertheless, findings from this study showed that selection of horses for future studies should be performed using specific criteria based a minimum number of red blood cells in bronchoalveolar lavage fluid collected 1 hour after a standardized test run on the high-speed treadmill and not based only on the fact that horses had blood detected in the trachea during post-race endoscopy and were placed on the bleeders' list.

Publications

  • No publications reported this period


Progress 10/01/05 to 09/30/06

Outputs
Racehorses exhibiting moderate to severe exercise-induced pulmonary hemorrhage (EIPH) are likely to perform poorly. To date, only the diuretic furosemide has been shown scientifically to help decrease lung bleeding in racehorses with EIPH. Furosemide is authorized as pre-race medication in the majority of states including Indiana. Anecdotal evidence from trainers and racetrack veterinarians suggest that additional medications may help reduce the severity of EIPH in horses that still experience bleeding despite pre-race administration of furosemide. As a result, a handful of racing jurisdictions have authorized the use of these so-called adjunct bleeder medications in combination with furosemide. However, to date, no scientific studies have examined the safety and efficacy profile of these medications in horses. Therefore, the purpose of this study is to compare the effects of furosemide alone and in combination with an adjunct bleeder medication to a placebo treatment. This past year's study examined the effects of furosemide and a combination of furosemide and an adjunct bleeder medication called carbazochrome on pulmonary gas exchanges, pulmonary bleeding, hemostasis, and performance during a standardized treadmill exercise tests in six Standardbred racehorses confirmed bleeders. The clinical trial was designed as a 3-way cross-over, placebo-controlled, Latin square design. Horses were trained on the treadmill for 6 weeks prior to the trial. Then, each horse completed three identical treadmill tests at 1 week intervals. Horses were tested four hours after receiving each one of three intravenous treatments in randomized order: placebo (5 ml of 0.9% sterile saline solution), furosemide (250 mg), or the furosemide (250 mg)-carbazochrome (100 mg) combination. The dose and timing of furosemide administration was based on the protocol authorized by Indiana law. In the first phase of the study, we examined the effect of strenuous exercise on the composition of bronchoalveolar lavage fluid (BALF) and found that both hemoglobin and protein concentrations increased in BALF collected 1 hour after a standardized treadmill test. Cell differential counts in BALF were not significantly affected by exercise. In the second phase of the study, we used BALF hemoglobin and protein measurements to quantify lung bleeding. We observed that treatment of Standardbred racehorses suffering from EIPH with furosemide or furosemide/carbazochrome combination did not result in significantly less pulmonary hemorrhage when compared to placebo treatment. Additional variables concerning hemostasis, pulmonary gas exchanges and performance are currently being analyzed.

Impacts
Some racing jurisdictions authorize bleeder medications such as furosemide (diuretic) and carbazochrome (hemostatic) but scientific proofs of their efficacy are weak (furosemide) or lacking (carbazochrome). Preliminary results from this study suggest that measurement of protein and hemoglobin content in lung wash fluid collected after exercise is a valuable test for mild lung bleeding. Using these methods, we found that treatment of standardbred racehorses with furosemide or furosemide-carbazochrome combination does not decrease lung bleeding during exercise.

Publications

  • No publications reported this period