LSU Equine Veterinary Research: Young and Growing
The Thoroughbred racing and breeding industries in Louisiana were influential in funding and building the veterinary school at Louisiana State University in Baton Rouge, but the school serves all the state's horses and their owners. Although one of the newest schools in terms of number of classes graduated, LSU's School of Veterinary Medicine gets high marks in maintaining progress in research into equine problems during a downturn in the state's and nation's equine industry.
Dean David Huxsoll, DVM, PhD, who formerly was Commander of the U.S. Army's Medical Research Institute of Infectious Diseases, said there are some "interesting opportunities" at the LSU School of Veterinary Medicine.
"We are trying to find areas where we have something special to offer and concentrate on them, but not rule out diversity," said Huxsoll. "Teaching veterinarians is basically the same at all schools, where we see a difference from school to school is in research work."
The five areas of emphasis at the veterinary school are equine, pathobiology, aquaculture, infectious diseases, parasitic diseases, and environmental toxicology. There was a large amount of state funding early in the school's development from the rich racing handle. At one point in the late 1980s, the school received $700,000 a year from the state as a share of the takeout. The state rescinded the funding after three years, and although the school continues to seek state monies, obtaining private and corporate funding for research is a top priority.
"The initial funding left us with some good facilities," said Peter F. Haynes, DVM, MS, Dipl. ACVS, Associate Dean for Research and Advanced Studies. "Now we need the grease to make the wheels spin."
And the wheels are cranking out some interesting, and practical, information for horse owners.
Charles R. Short, DVM, MS, PhD, Diplomate American College of Veterinary Clinical Pharmacology, is head of the Department of Veterinary Physiology, Pharmacology, and Toxicology and Director of the Equine Research Program.
Stress and Immune Response
David Horohov, MS, PhD, a Professor of Veterinary Immunology, has been working on the problem of how stress affects the immune system of horses. While there has been anecdotal stories of stress associated with illness in humans and animals, there had been no scientific research for equines.
Horohov did post-doctoral work in immune response of flu vaccines in humans, and he noted that there was a similarity in the viruses and vaccines used for flu in humans and horses. His question about horses, however, was why was there such a discrepancy in vaccination schedules? Some horses were only vaccinated once a year, and some six times or more a year. He said the vaccine does what it is supposed to do in horses--it encourages the production of antibodies.
What he wanted to demonstrate was that stress could keep immunity levels down and thus interfere with vaccine efficacy and allow diseases to propagate.
To stress horses psychologically and physically, Horohov changed the animals' environment, and he worked them on a treadmill. He monitored heart rate, lactic acid production, respiratory rate, and other stress responses such as cortisol levels (considered the "stress hormone") and the release of other hormones. He took blood samples before, during, and after exercise, and showed that horses under acute stress have changes in their immune systems.
What he discovered when challenging stressed versus non-stressed horses was that their immune response to flu virus decreased during peak exercise or stress periods. Then, after about 20 minutes, the immune system was back to normal.
"There was a transient change in the immune system," said Horohov.
In one study, Horohov took a group of vaccinated ponies and left them in the stable, and took another group of vaccinated ponies and ran them on the treadmill. Blood samples were taken, then after 1 1/2 hours they were challenged with the flu virus. None of the ponies in either group became ill.
Then he switched the groups and the stabled ponies were exercised on the treadmill, then challenged with the flu virus. Four of the ponies in the exercise group became ill.
"The same ponies that were resistant to the same virus a month before then were susceptible," said Horohov. "So, chronic stress probably does have an effect and might contribute to increased incidence of illness."
In lab tests on blood drawn from stressed ponies, it was found that the virus proliferated much faster in those samples than in blood drawn from non-stressed ponies.
Current research focuses on cytokines, which are proteins produced by the body to control the immune system. Horohov said he wonders if the changes in lymphocytes in the immune system were do to cytokines (specifically interleukin 2, or IL2, which is an immune growth factor).
Preliminary data on measuring IL2 in exercised and resting ponies shows that there was decreased responsiveness to the flu vaccine in ponies not producing IL2.
"If we know why ponies fail to respond immunologically, if it is cytokines, then we can provide them with the cytokines," said Horohov. "But in real life, how do you know when peak stress is happening?"
His continuing research focus is on cytokines and their role in regulating immune responses in the normal animal using influenza as a stressor. He will investigate whether IL2 can be added to vaccines to make them work better, or if something can be given at the same time as a vaccination to make the vaccination work better to induce protection in the horse's body.
An area of interest for Ralph E. Beadle, DVM, PhD, Professor of Veterinary Medicine, is obstructive pulmonary disease. When he came to LSU in 1974, he noticed a problem with horses showing signs of heaves, but it was not the typical scenario. He was seeing it in the summer when horses were on pasture rather than with horses kept inside stalls. In fact, since all horses in Louisiana had been vaccinated against VEE (Venezuelan equine encephalomyelitis) in 1971, it was easy for Beadle to get a rough estimate from practitioners in the field of how many horses they saw with this summer pasture associated obstructive pulmonary disease (SPAOPD). The estimate was that between 3-5% of horses showed signs of heaves in the summer.
This interested Beadle, and he wondered what caused this, how to provide relief for the horses, and what was the best treatment.
"I realized we needed a more sensitive pulmonary testing device to pick up on the horses that were not showing signs clinically and to study pulmonary function," said Beadle, "so we worked with creating a pulmonary function testing device."
The device, the only one like it in the world, is called a whole-body plethysmograph. Fabrication of the device was undertaken as a joint project between the Departments of Veterinary Physiology, Pharmacology, and Toxicology in the School of Veterinary Medicine and the Department of Chemical Engineering in the College of Engineering at Louisiana State University. The device allows measurement of airway resistance, thoracic gas volume, and alveolar pressure that previously could not be measured by any other means. Values for other variables such as tidal volume, respiratory frequency, minute volume, flow-volume loops, and pulmonary capillary blood volume can also be measured using this device. The whole-body plethysmograph allows study of therapies that might be helpful in treating horses with pulmonary disease and discovering the duration of a treatment's effect.
Bronchodilators have been evaluated using this device. The system also is useful in evaluating changes in horses when they are moved to different environments or undergo management changes, i.e., stabling vs. pasture or feeding different rations.
"We understand now that it is best for horses to be taken off pasture and put in barns, but what are the alternatives?" questioned Beadle. "One way is to leave them on pasture and give them a pelleted ration so they are not grazing so much."
Although the researchers don't know the cause of the summer pasture heaves, Beadle theorized it might be mold spores, since the mold counts rise in the summer in Louisiana. "But it could be pollens or something else," he admitted.
Barns that are best for these horses are open and well-ventilated, with no source of dust. Also, rubber flooring and pelleted feed will reduce the signs of heaves in these horses.
"The barns aren't that far removed from the pastures, but at least they aren't sticking their nose in the grass," he said.
Beadle has maintained a herd of SPAOPD horses for a number of years, and they have been monitored daily.
"Some of these horses develop infection in the airways as well as heaves," he noted. "We treat the infection, then get the airway inflammation under control. But we've found that if you give them something like poor-quality hay, you can throw them back into heaves. It stimulates a response in the airways."
Part of his research now focuses on inflammatory mediators that are released in the airways, such as prostaglandins, platelet activating factor, and leucotrienes.
Help From Above
As part of Beadle's study on summer heaves, researchers want to know what common elements in the environment might stimulate these horses to have an acute episode of pulmonary distress. In order to help map these similarities, Jill J. McClure, DVM, MS, Dipl. ACVIM, Dipl. ABVP, a Professor of Veterinary Medicine, has gone where no equine researcher has gone before.
McClure wrote a computer program that allows environmental or other data obtained from a satellite to be layered on a map of the state and studied for equine use. This will allow her to look at the environment for SPAOPD horses.
The herd of heaves horses that has been maintained at the university for the past several years has had daily data and observations recorded by researchers. Utilizing that and environmental data obtained from the satellite, factors can be mapped to see where changes preceded heaves. Researchers also can map locations that practitioners in the field report heaves horses to look at other factors that might predispose the horses to the problem.
While computers and epidemiology are occupying quite a bit of McClure's time at present, her other research interests have focused on immunogenetics. That interest lead her and her colleagues to discover a previously unknown blood factor in mules known as "donkey factor." She said this occurs in all mules and causes anemia. While neonatal isoerythrolysis (NI) occasionally occurs in horses, she discovered that this "donkey factor" occurs in all mules and can cause foals to become anemic and platelets to be destroyed.
Potential Damage From Joint Distention
George S. Martin, DVM, MS, MBA, Dipl. ACVS, is Associate Professor of Veterinary Surgery and Section Chief, Equine Services, Veterinary Teaching Hospital and Clinics. Martin's research interests involve the musculoskeletal system, particularly the fetlock joint.
Ongoing studies have focused on the role of intra-articular synovial fluid pressure as the initial cause of fetlock joint injury in young racehorses. The domino theory goes like this:
"Development of fetlock injury appears to occur first as soft tissue injury due to hyperextention of the joint, which occurs during training or racing," Martin noted. "Synovial fluid is trapped in the dorsal compartment of the joint and compressed during hyperextension. Compression results in increased intra-articular synovial fluid pressure during hyperextension. The increased pressure results in tearing of the fibrous joint capsule. The tearing of the joint capsule results in inflammation, pain, heat, and increased production of synovial fluid, the condition know as synovitis and capsulitis."
Martin and his colleagues are looking at statistical modeling of Thoroughbreds to take a horse's performance before and after injury and compare pre- and post-treatment parameters.
One thing he noted from his research: "We found that the pressures decreased after therapy and rest. The results so far have made us more aware of the potential damage caused simply by joint distention. This has made us more aggressive in treating with intra-articular medication, whereas previously, we would not have treated the joint unless it was clearly the cause of lameness."
Official Testing Laboratory
The LSU School of Veterinary Medicine became the official drug testing laboratory for the state racing commission in 1987. Testing is operated through the Department of Veterinary Physiology, Pharmacology, and Toxicology under the direction of Steven A. Barker, MS, PhD. Barker also serves as Chief Chemist for the state racing commission. Steven G. Kamerling, PhD, Professor of Pharmacology and a registered pharmacist, serves as a consultant to the commission in equine pharmacology.
What Louisiana wanted was fair drug testing that was based on pharmacology and what happens to a drug in the horse, said Barker. Louisiana became the first state to adopt an organized category of drugs and a penalty scale. These are policies that regulate testing so that trace levels of therapeutic agents are not called as a "positive" drug find.
"We don't call positives on drug traces when we know they could have no effect on the horse in a race," explained Barker. "We work with the horsemen and veterinarians to see their concerns and why horses come up positive for therapeutic agents."
During peak racing years in the late 1980s and 1990, the laboratory handled about 15,000 blood and urine samples a year. Now, said Barker, they are down to about 5,600 of each tested every year.
The testing had a direct effect on what happened to the racing industry in the state, said Barker. "Our positive rates came down significantly, and the positives we find are less-serious drugs, such as therapeutic agents. But every now and then someone tries to slip one by," he concluded with a grin.
Short's research interests center around inflammation by looking at mediators of inflammation and studying what anti-inflammatories do to these mediators. For these studies, Short and his colleagues developed subcutaneous tissue chambers that could be surgically implanted on the neck of a horse and which could be made on campus. The body of the chambers was constructed of a thermoplastic (Delrin) with the open face covered with a silastic membrane that lay directly under the skin after insertion. This facilitated sampling of interstitial fluid via percutaneous needle puncture.
Recent studies have looked at the effect of ketoprofen (commercial name Ketofen), a registered anti-inflammatory agent for use in horses. Studying the pharmacologic effects and changes of this drug in horses has proven insightful because the drug can convert to a different form (metabolite changes) in the horse's body. Ongoing research will focus on new assays to study mediators of inflammation by polymerase chain reaction (PCR) testing.
Kamerling was working in Kentucky on human drug addiction and abuse when he met Tom Tobin, MVB, of the Gluck Equine Research Center. Tobin's research into drugs and testing for equines became Kamerling's interest for two years. He conducted research on pain perception and pain threshold measurements in horses. Then, a position opened at LSU investigating drugs in horses because of the school's drug testing laboratory.
Kamerling's research centers around the effects, and side effects, drugs have on horses, and how to better evaluate medications in the equine. He also is investigating the action of non-steroidal anti-inflammatory drugs on acute and chronic inflammation and pain. His research has led to several developments of scientific, objective determination of pain and medication effects, which will be covered in an upcoming article in The Horse.
Parasites And Control
Dennis French, DVM, Dipl. ABVP, Professor at the Veterinary Teaching Hospital and Clinics, and Thomas R. Klei, PhD, Professor of Parasitology in the Department of Veterinary Microbiology and Parasitology, have been active in the search for better ways to help equines fight parasites. (See What's On The Horizon For Parasite Control in The Horse of April 1996, page 43.) Developing, researching, and field testing anthelmintics has been just part of their ongoing work into parasites and control at the university.
An important part of fighting parasites is to understand the "bug" and know its life cycle and how it relates to the horse and the environment. Also, the researchers want to know how the horse naturally fights off parasites and how to better utilize that "natural" parasite control.
Bruce E. Eilts, DVM, MS, Diplomate American College of Theriogenology (ACT), Associate Professor of Theriogenology, and Dale Paccamonti, DVM, MS, Diplomate ACT, Associate Professor of Theriogenology. share the therio-genology responsibilities for large and small animals at LSU's veterinary school. Eilts, who has been at LSU since December of 1984, said about 40% of the caseload is equine.
The effect of endometrial cysts on fertility is recent research conducted by Eilts and his colleagues. Before ultrasound came into general practice, endoscopic examination of problem mares showed many of them had endometrial cysts, which were blamed for the fertility problems.
After the advent of ultrasound in general practice, mares which didn't have fertility problems were found with endometrial cysts. This lead the researchers to wonder just what effect the cysts had on fertility.
Their research, based on records from private practitioners, revealed that there was not a higher risk of fetal loss in mares with endometrial cysts compared to mares without cysts, nor was there a greater problem of getting the mares in foal which had endometrial cysts.
Researchers at Louisiana State University also looked at endometrial cup formation in Mares. They wanted to see if using a laser to get rid of the endometrial cups in mares which aborted after 60 days of pregnancy would allow those mares to come back into heat. This would allow them to be bred again that season. The data is still being compiled on that research.
Other research focused on the problem of urine in the semen of stallions, antisperm antibodies, predicting how a stallion's book directly affected his fertility and conception rate, freezing of semen collected and shipped from another part of the state or country, and follicular development and growth.
"We generally try to do practical research," said Eilts. "The things we see that are problems clinically we want to try and solve."
That idea of looking into the practical and working toward solutions seems to be the overriding theme at LSU, and horsemen are the beneficiaries of that focus.
About the Author
Kimberly S. Brown was the Publisher/Editor of The Horse: Your Guide To Equine Health Care from June 2008 to March 2010, and she served in various positions at Blood-Horse Publications since 1980.