Locked Into Place
- Aug 1, 2002
Much has been learned about exertional rhabdomyolysis (tying-up) in recent years, but unfortunately some of that knowledge has been troubling. For example, at least one newly recognized cause of tying-up in foals has, in identified cases, always been fatal. This syndrome, known as glycogen branching enzyme deficiency (GBED), is an inherited malady for which there is no known cure. For years, researchers and horse owners thought that tying-up in all horses had a common cause. However, research has shown that there are multiple causes and that successful treatment protocols can vary from horse to horse.
There is still much to learn about tying-up. Genetic tests are needed to determine which horses carry the genes that make them susceptible to this affliction. Stephanie J. Valberg, DVM, PhD, of the University of Minnesota, has been a leading researcher on tying-up. Before arriving at the University of Minnesota in 1994, Valberg was involved in studies and research at the Swedish University of Agricultural Sciences in Uppsala, Sweden, where she obtained her PhD, and later at the University of California, Davis.
Perhaps one of the reasons that researchers and horse owners were convinced for years that there was a single cause for tying-up is that no matter what triggers the disorder, the clinical signs are similar. Afflicted horses suffer varying degrees of pain, muscle cramping, and stiffness in the rear quarters. With some horses it might involve stiffness when walking, and in others the pain might be so severe that they writhe on the ground, similar to a horse with colic.
A veterinarian can diagnose tying-up from a blood sample by measuring the activity of three enzymes that are normally found in the muscle. They are creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate transaminase (AST) in serum. The key enzyme is CK because it is specifically released by degenerating muscle cells. CK increases rapidly in a horse that ties up, with peaks reached four to six hours in the wake of muscle damage. The other two enzymes--LDH and AST--aren't specific for muscle damage and can also increase as a result of liver disease. However, LDH and AST are useful markers for chronic problems because they stay elevated for weeks after muscle damage, whereas CK becomes normal in the blood after a few days.
Muscle biopsy is another important diagnostic tool. By studying muscle fibers obtained via biopsy, researchers can pretty much determine the type of tying-up that is afflicting the horse. This information makes it possible to establish a treatment approach that will have both short-term and long-term benefits. Valberg receives about 300 biopsies from horses across North America each year in her laboratory.
The Most Common Causes
There are two syndromes of generalized tying-up from a clinical standpoint, says Valberg--sporadic exertional rhabdomyolysis and chronic exertional rhabdomyolysis.
The sporadic syndrome is less of a long-term concern. Symptoms might appear when a horse which generally performs without problems overexerts himself. This might include a trail horse, normally ridden lightly over level terrain, that one weekend is asked to carry a heavy load up a steep mountainside.
Normally, Valberg says, this horse will recover quickly following a period of rest and recuperation and will likely not have a recurrence, especially if he rounds into better physical condition.
Physical trauma can also be a cause of sporadic tying-up, says Valberg. When a horse is involved in a struggle, such as getting a leg caught in a fence, muscles can be torn in different areas and the result might be stiffness and signs of tying-up for a couple of days after the incident.
The chronic form, on the other hand, includes horses with repeated episodes of tying-up. One form of this syndrome is polysaccharide storage myopathy (PSSM), which generally afflicts calm, well-muscled Quarter Horses, warmbloods, and draft horses, and has recently been proven to affect jumpers and dressage horses (see page 30). Another form is known as recurrent exertional rhabdomyolysis (RER), which generally afflicts Thoroughbred racehorses and possibly Standardbreds and Arabians.
With Valberg's help, we'll look at the latest information concerning tying-up. The discussion will be divided into three parts--polysaccharide storage myopathy, recurrent exertional rhabdomyolysis, and the forms of rhabdomyolysis that afflict foals.
Polysaccharide Storage Myopathy
This syndrome generally afflicts Quarter Horses, draft horses, Paints, Appaloosas, warmbloods, draft crosses, and Thoroughbreds used for pleasure riding. PSSM is a glycogen storage disorder characterized by excessive accumulation of glycogen and abnormal polysaccharide (a carbohydrate) in the muscle, says Valberg.
Each tying-up episode damages muscle cells. In a normal horse, after three weeks the muscle cells heal; in a PSSM horse, abnormal polysaccharide remains in the muscle cell, disrupting energy metabolism.
Often, Valberg says, a tying-up episode in horses with PSSM occurs when a training program is inaugurated after a period of idleness. Such a scenario could be when a horse has been given the winter off and is put back into training in the spring or when a young horse is first put into training.
Exactly how PSSM damages muscle cells is unclear. When PSSM strikes, the muscles have accumulated an abundance of sugar and polysaccharide, which can disrupt the energy metabolism in cells. Simply put, the muscle has an overabundance of fuel, but it might not be utilized by muscle cells properly. As a result, these horses suffer muscle cramps and become stiff.
To correctly diagnose what has occurred, a muscle biopsy is taken. Muscle samples are prepared and frozen in the laboratory, then sectioned and examined under the microscope with stains for abnormal polysaccharide. In addition, glycogen levels in PSSM muscle samples can be 1.5 to four times higher than normal levels.
An exercise test with 15 minutes of trotting on a longe line and measurement of CK in the blood four hours later is a useful way to determine if horses are having repeated mild episodes of tying-up that are only evident by blood tests. A horse at rest, Valberg says, will normally have a CK level less than 380 units per liter (U/L). When the CK level goes above 1,000 U/L after the exercise test, it is a strong indication that tying-up is involved. In severe cases, the CK level can go as high as 80,000 U/L.
When there is a high level of CK activity, she says, it is likely that acute muscle degeneration is taking place. If the CK level remains high, indications are that the horse is suffering from ongoing attacks, which is common with PSSM.
Recurrent Exertional Rhabdomyolysis
While horses with RER might show the same clinical signs as those with PSSM when they are acutely afflicted, that is where the similarity ends. While PSSM normally afflicts quiet, staid stock and draft-type horses with no bias toward gender, RER is most commonly found in high-strung, excitable Thoroughbred fillies in race training. Standardbreds and Arabians are also sometimes afflicted.
While PSSM is a glycogen storage disorder, RER results from a stress-related disorder and muscle calcium regulation. It is a common affliction on the racetrack. In one study of horses at Minnesota's Canterbury Downs (done by Valberg and researchers from the University of Minnesota), 48 (5%) of 984 horses examined had RER. It was reported that 36 (38%) of the 96 trainers at the track had horses in their stables which suffered from bouts of RER. Of the 48 RER horses at the track, eight never made it to the starting gate that year. Seventy-five percent of the afflicted horses had at least four episodes of tying-up, and 25% had more than 10 episodes.
Tying-up in the Canterbury horses occurred most frequently when they were galloped, then jogged or walked. Rarely was it associated with breezing, when the horse travels around the track at racing speed. It was also found that many of these fillies had reached an advanced stage of fitness before the syndrome was manifested.
"Prevention of further episodes of RER in susceptible horses," Valberg says, "should include standardized daily routines and an environment that minimizes stress. Unlike PSSM, grains and sweet feed do not need to be completely eliminated with RER. The diet should be adjusted to include a balanced vitamin and mineral supplement, high-quality hay, and less than five pounds (2.3 kg) per day of concentrates such as grain and sweet feed. Additional dietary fat supplements are necessary for horses in moderate to intense training to maintain weight without providing excessive carbohydrates," says Valberg. "Corn oil, rice bran, or complete pelleted feeds designed for tying-up are beneficial. Daily exercise is essential, whether in the form of turnout, longeing, or riding."
Tying-Up in Foals
Recently recognized as a rhabdomyolysis disorder causing muscle weakness in Quarter Horses and Paint Horses is a syndrome called glycogen branching enzyme deficiency (GBED). This is a separate glycogen storage disorder from PSSM, says Valberg, who with her team of researchers is responsible for much of the known information about the malady.
Afflicted foals are born weak and often all four legs have flexural deformities. Some are born dead--aborted late in the pregnancy. Others are stillborn. Thirteen afflicted foals have been diagnosed by muscle biopsy and studied by Valberg and her team at the University of Minnesota. All 13 died.
It appears, Valberg says, that the syndrome is inherited. Breeding the dam of an affected foal to the same stallion, she says, has a 25% chance of producing another affected foal. A genetic test for the disease is not yet available.
Foals can also be afflicted with PSSM. In one study by Valberg and her colleagues, four foals out of mares with PSSM lineage were followed from birth to three years of age. Three of the foals developed elevations of CK as great as 10,000 U/L as early as one month of age (remember that 380 units is normal and anything above 1,000 is considered highly abnormal) . In a second study, severe tying-up associated with PSSM was identified in three-month-old and six-month-old Quarter Horses.
Management of foals with PSSM, Valberg says, should include minimal box stall confinement, access to as much turnout as possible, and a low-starch diet that features fat supplementation to provide energy.
In two reported cases of tying-up in foals, one has a happy ending and the other a sad ending. The difference in the outcomes of the two cases point out the necessity of proper management when PSSM is diagnosed in a foal. (The two cases were reported on in the May 2000 issue of the veterinary journal Compendium.)
The case with a sad ending was a 6-month-old Quarter Horse filly referred to the teaching hospital at North Carolina State University in Raleigh, N.C. When brought to the teaching hospital, she was down in the trailer and was unable to rise. She also had an exaggerated heartbeat--60 beats per minute instead of the normal 26-50 beats, reported Samuel L. Jones, DVM, PhD, who examined and treated her.
"The filly could move her limbs and would attempt to rise, but could only dog-sit," he wrote. "The muscles appeared tense and rigid and the horse was sweating." She also had a cough, nasal discharge, and wheezed while breathing.
She was given a varied drug therapy of lactated Ringer's solution, dimethyl sulfoxide (DMSO), erythromycin phosphate, rifampin, flunixin meglumine (Banamine), and cimetidine. The filly showed some improvement and was able to stand. Food consumption was restricted to grass hay and fresh grass.
"Four hours after treatment was initiated," Jones reported, "the filly was able to stand unassisted." However, he added, her gait was stiff and stilted and muscles in the rear quarters were "swollen, firm, and painful on palpation." She was reluctant to walk for the first seven days of hospitalization. After eight days, Jones wrote, the filly appeared to feel much better and was able to be hand walked outside to graze. The symptoms of respiratory disease also disappeared.
Suspecting that PSSM might be involved, Jones took a muscle biopsy and sent it to Valberg's lab. The results confirmed that the filly had PSSM. But that immediately led to the question: Why was this happening in the absence of exercise?
Jones agreed with Valberg's assessment that respiratory stress--indicated by the wheezing, cough, and nasal discharge--set off the episode. "That's what we think," he reported, "but we don't know for certain."
Jones gave this rather grim final account on the filly: "A second muscle biopsy to reevaluate the filly was recommended 30 days after discharge. Because of the evidence that PSSM is heritable, it was also recommended that the dam have a muscle biopsy to determine whether she was affected; however, this was not done. The owner did not follow dietary recommendations. The filly had a second episode of severe rhabdomyolysis as a yearling and was euthanized."
A story with a happier ending was described by Erin Byrne, DVM, who was at Texas A&M University at the time and today is in private practice in California. Involved was a 3-month-old Paint colt, one of the youngest horses to be diagnosed with PSSM.
When admitted, Byrne wrote, the colt was depressed and had a high heart rate--80 beats per minute instead of the normal 26-50 beats--and a high respiration rate of 80 breaths per minute instead of the normal 12-30 breaths. He also walked with a stiff gait and had severe diarrhea.
Immediate treatment involved the intravenous administration of fluids, including lactated Ringer's solution and sodium chloride, metronidazole, ranitidine, bismuth subsalicylate, psyllium, Banamine, and dexamethasone.
The intravenous fluid rate was gradually decreased for four days, and discontinued by Day 4. The colt's diet consisted of free-choice coastal hay and 12% protein pelleted concentrate. The colt was hospitalized for a total of 16 days. After discharge from the hospital, he appeared to be free of PSSM symptoms and no longer had diarrhea.
During hospitalization, a muscle biopsy was taken and sent to Valberg's laboratory. The finding was that the colt was suffering from PSSM. A biopsy was also taken from the colt's dam and sent to the laboratory. The finding was that she, too, had PSSM and apparently had passed it to her foal.
In this case, Byrne reported, there was no respiratory-related problem involved, but she is of the opinion that the severe diarrhea was responsible for creating the stress that caused the PSSM attack.
After being discharged, Byrne wrote, she and Noah Cohen, VMD, PhD, also of Texas A&M University, recommended the following approach for the colt: "Daily pasture turnout and minimal stall rest were recommended for the dam and foal on discharge. A concentrate containing 6% fat and continued feeding of good-quality grass hay were recommended, along with vitamin E and mineral supplementation."
The two clinicians also recommended that a nutritionist be contacted so that the colt's changing nutritional needs could be properly met as he matured and entered training.
Immediate treatment is the same when a horse ties up whether the syndrome is PSSM or RER. Valberg recommends the following steps:
- Stop exercising the horse, and move him to a box stall if possible. However, don't force the horse to walk if he can't. Leave him where he is until a veterinarian arrives or get him a trailer ride.
- Call your veterinarian.
- Blanket the horse if the weather is cool.
- Determine if the horse is dehydrated due to excessive sweating. Pinched skin will normally spring back into place quickly, while a dehydrated horse's skin will take longer than one to two seconds. Saliva should be wet, not sticky.
- Provide fluids--give the horse small, frequent sips of water. Electrolytes (potassium, sodium, and chloride) can be added to drinking water if the horse will drink the mixture. Plain water should always be available as an alternative. If the horse is dehydrated, the veterinarian might administer intravenous fluids.
- Relieve anxiety and pain. Drugs such as acepromazine and the anti-inflammatory drug Banamine might be prescribed by the veterinarian.
- Remove grain, and feed only hay until signs subside.
- Utilize small paddock turnout once the horse can walk freely. This normally will be within 12 to 24 hours.
- When blood CK level is normal, slowly recondition the horse to his previous level.
- If the problem recurs, have the horse evaluated for a specific cause of tying-up.
Dietary Concerns for PSSM Horses
It has been found, Valberg says, that diet can play an important role in preventing recurring episodes of PSSM. The dietary approach should involve lowering the intake of starch and increasing the intake of fat. In stock horses, it has been found that PSSM can usually be managed with a diet that includes grass hay or half alfalfa/half grass hay and a fat supplement that is balanced with vitamins and minerals. Starch should be decreased to less than 15% of the diet's digestible energy by eliminating grains, molasses, and corn.
Some controversy exists about how much fat to add to the diet. It has been recommended that 25% of caloric intake be in the form of fat to prevent tying-up. Valberg and her colleagues at the University of Minnesota disagree--they feel that for many easy keepers this might be too much fat. Their approach is to determine the necessary caloric intake to maintain the horse at an appropriate weight and level of conditioning. Once this is done, the researchers say, a diet should be designed with an appropriate amount of starch and fat. Determining the correct diet varies on the age of the horse, the activity he is involved in, and many other factors. Consult your veterinarian.
The fat can come in a number of forms--animal fat, a variety of vegetable oils, rice bran, and soy lecithin. Pelleted and extruded feeds are available and are more palatable than pouring oil on top of a grain mixture. Most of the commercial feeds utilize rice bran as the source of fat.
In addition, Valberg says, daily exercise has been found to be vital in successful dietary control of PSSM. Once a horse has recovered from an episode, a horse might only be able to manage a few minutes of exercise each day, but the exercise should be slowly and gradually increased. Stall confinement should be no more than 12 hours per day, with pasture turnout being the ideal approach to exercise.
Researchers are at something of a frustrating crossroads in seeking to determine what role heredity plays in tying-up. Valberg is convinced that the affliction follows certain bloodlines in both Quarter Horses and Thoroughbreds. Studies of pedigrees plus breeding experiments conducted at the University of Minnesota strongly indicate that these diseases are inherited, but there is no irrefutable scientific proof, since particular bloodlines are not made public.
A genetic test is needed, such as the one that can identify the muscle disorder hyperkalemic periodic paralysis (HYPP) in horses descended from the Quarter Horse stallion Impressive. Valberg and her team, assisted by a grant from the Morris Animal Foundation, are attempting to find an identifying genetic marker for RER.
Owners of mares which have produced foals with GBED need to recognize that there is a 25% chance of a foal being affected if they repeat the same mating and a 50% chance of the foal being a carrier. Valberg does not recommend breeding horses with PSSM because it is such a debilitating disorder. Since RER is a milder and more intermittent disease, owners are often not deterred from breeding affected horses.
We've learned a lot about tying-up in the past decade, but many questions remain. Management can help, but an owner must first know what is causing the tying-up to make management changes. Owners should look out for the classic, and sometimes subtle, signs of tying-up, especially in young horses entering training or those stepping up their training after time off.
You can help horses suffering from the muscle pain of tying-up, but you must recognize the signs and help your horse immediately. Your horse is not being defiant if his muscles hurt too much to move; it's important to recognize the difference.
About the Author
Les Sellnow is a free-lance writer based near Riverton, Wyo. He specializes in articles on equine research, and operates a ranch where he raises horses and livestock. He has authored several fiction and non-fiction books, including Understanding Equine Lameness and Understanding The Young Horse, published by Eclipse Press and available at www.exclusivelyequine.com or by calling 800/582-5604.
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