Tying-Up in Horses: Causes and Management

Perhaps the most frustrating of all problems that affect the athletic horse is the syndrome known as tying-up. Tying-up is a broad term that frequently is used to describe a wide variety of muscle disorders that affect the performance horse. Other names given to this syndrome include exertional rhabdomyolysis, Monday morning disease, and azoturia. Historically, the commonality of the clinical signs associated with an episode of tying-up led to the conclusion that all horses showing evidence of muscle cramping and soreness have the same condition. However, research over the past decade or so has clearly shown that there are a number of specific disorders that fall under the umbrella term tying-up. This research has provided a much better understanding of the causes of tying-up and has led to improved methods for prevention of recurrent episodes. Much of this research has been conducted at the College of Veterinary Medicine, University of Minnesota; a listing of some of the original scientific papers resulting from this research effort can be found on page 90.

In this article, we will discuss some of the specific causes of exertional rhabdomyolysis (ER) or tying-up, with particular attention to methods that can be used to prevent repeat episodes of tying-up in horses predisposed to recurrences.

What Is Tying-Up?

The clinical signs of tying-up are varied, depending on the severity of the episode. In mild cases, affected horses will be somewhat stiff after exercise. At the other end of the spectrum, the intense pain associated with severe and generalized tying-up might incapacitate a horse to the point that it is unable to stand and bear weight. During exercise, affected horses develop a short, stiff stride; these signs can worsen if exercise is continued. Upon stopping, horses often are very reluctant to move and might adopt an unusual stance; males frequently posture as if to urinate. The muscles of the hindquarters usually are the most severely affected. This area will be firm and painful, and cramping is evident when these muscles are palpated. Other signs that the horse is painful include profuse sweating and persistently elevated heart and respiratory rates. The pain persists for several hours after the onset of a tying-up episode.

Tying-up in endurance horses might occur as a single entity or as a component of the "exhausted horse syndrome." In the latter, additional clinical signs include depression, severe dehydration, hyperthermia, and "thumps" (synchronous diaphragmatic flutter). Some endurance horses might develop extensive muscle damage without concurrent signs of muscle cramping.

In severe cases, horses will pass a dark, red-brown colored urine (myoglobinuria). This discoloration is due to the presence of a muscle protein called myoglobin. With extensive damage to muscle fibers, a large amount of myoglobin, together with other muscle proteins, leak into the horse's blood and subsequently are excreted through the kidneys. If horses with myoglobinuria are allowed to become dehydrated, they might develop kidney damage due to the protein accumulation.

Diagnosis of tying-up is confirmed by detection of elevated serum activities of creatine kinase (CK) and aspartate animotransferase (AST). Like myoglobin, these proteins are contained within muscle cells and are released into circulation when cells are damaged. Blood activities of CK, a specific indicator of muscle damage, increase rapidly with peak values occurring four to six hours after an episode of tying-up. Compared to CK, activities of AST increase and decrease more slowly; AST might remain elevated for seven to 10 days after an episode.

Tying-up should be distinguished from muscle soreness and strain. Strain of specific muscle groups is very common in performance horses. The lumbar (back) and gluteal (rump) muscles are most frequently injured in jumpers, dressage competitors, and harness horses, while working Quarter Horses most often strain the semimembranosus and semitendinosus muscles (the "hamstring" area). Although these injuries can cause lameness, necessitating a period of rest and rehabilitation, they usually are localized and the degree of muscle soreness is mild relative to true tying-up. As well, serum activities of CK and AST are only mildly increased, if at all.

Local muscle strain and soreness is common in otherwise sedentary people who over-exert themselves. Similarly, inadequate training for the level of activity undertaken and exercise to absolute fatigue will predispose horses to muscle strain. Other predisposing factors include pre-existing lameness or inadequate warm-up.

What Causes Tying-Up?

Based on our current knowledge, horses which experience episodes of tying-up can be placed in one of two broad categories: 1) Sporadic exertional rhabdomyolysis--this classification applies to horses which, on rare occasion, experience an episode of generalized tying-up; 2) Chronic exertional rhabdomyolysis--when a horse experiences repeated episodes of ER, with the first episode usually occurring at a young age.

A common cause of sporadic tying-up is exercise that exceeds the horse's underlying state of training, e.g., asking a horse to undertake competition exercise after a lay-off and with only minimal training before the event. Electrolyte imbalances (particularly low sodium) and deficiencies of vitamin E and/or selenium might play a role in some cases. Sporadic tying-up can occur in horses which have concurrent illness, particularly respiratory viral infections.

For owners, trainers, and veterinarians, the most frustrating muscle disorder is chronic exertional rhabdomyolysis. Affected horses are prone to repeated episodes of tying-up, a circumstance that severely hampers preparation of the horse for competition and, in many cases, limits his athletic career. Many different breeds of horses have been reported to have chronic episodes of tying-up, including Thoroughbreds, Arabians, Standardbreds, Quarter Horses, and various breeds of both draft and warmblood horses. Over the years, many different causes of chronic tying-up have been proposed, but few have been proven. These include hormonal imbalances (particularly low thyroid hormone), electrolyte imbalances, lactic acidosis within muscle, and vitamin E and/or selenium deficiency.

Of these, there is evidence that, in some horses, electrolyte imbalances can be an important factor in the development of chronic tying-up. Investigations in England (see article by Harris and Snow) suggested that imbalances of sodium, calcium, and phosphorus contributed to tying-up problems. Many affected horses showed marked improvement after addition of sodium or balancing of the calcium:phosphorus ratio in the diet. Certainly, electrolytes such as sodium, potassium, and chloride are important for muscle function. As well, horses lose a large amount of these electrolytes in sweat. Therefore, endurance horses require electrolyte supplementation before, during, and after competition, and other types of athletic horses require additional salt in their diet (one to two tablespoons daily). Electrolyte imbalances have been identified in North American horses and in other countries, but at least in the United States, dietary electrolyte imbalances are not the main cause of chronic tying-up.

In recent years, research at the University of Minnesota has uncovered two specific causes of chronic tying-up: 1) recurrent exertional rhabdomyolysis (RER), in which there is a defect in the mechanism of muscle contraction; and 2) polysaccharide storage myopathy (PSSM), a disorder that results in storage of excess carbohydrate in muscle.

RER is a common cause of chronic tying-up in Thoroughbred, Standardbred, and Arabian horses. An epidemiological study of racing Thoroughbreds indicated that about 5% of horses develop RER during a season. Highly susceptible horses can experience frequent episodes with persistent elevations of serum AST. Training and racing is severely curtailed, and these horses usually are retired prematurely. This form of chronic tying-up is most common in young fillies with a nervous disposition. Training at a gallop, but restraining the horse from reaching top speed, appears to be an important "trigger" factor. Other trigger factors include prolonged periods of stall rest, high-grain diets, excitement, and the presence of a lameness problem.

Genetic studies, including preliminary breeding trials, suggest that RER is an inherited condition in Thoroughbreds. The underlying problem is a defect in the mechanism for muscle contraction. In essence, the muscle has increased sensitivity to contraction when exposed to certain stimuli. It is possible that excitement triggers this abnormal response in the muscle of horses with RER. A similar abnormality called malignant hyperthermia is common in humans and pigs.

The second common cause of chronic tying-up, polysaccharide storage myopathy, is a condition characterized by accumulation of glycogen (a form of carbohydrate) and an abnormal form of polysaccharide (a complex carbohydrate) in muscle. PSSM has been identified in Quarter Horses and related breeds (Appaloosas, Paints), warmbloods, draft horses, and a few Thoroughbreds. In the Quarter Horses and related breeds, there appears to be a hereditary basis for PSSM. Horses with PSSM have increased ability to clear glucose from the blood, resulting in an increase in the rate of glycogen synthesis in muscle; muscle glycogen concentrations are 1.5 to four times those of normal horses.

Clinical signs of PSSM can develop at a young age, often when the horse enters training. Rest for a few days prior to exercise is a common triggering factor, but unlike RER, horses usually have a quiet demeanor. Sometimes episodes of muscle damage occur when horses acquire an infection, such as pneumonia. As with other forms of chronic tying-up, episodes can range from mild to severe. Some horses can be affected every time they exercise, while others might have only intermittent episodes. However, it also is common for affected horses to have ongoing bouts of muscle damage that are not associated with clinical manifestations of tying-up, but which result in persistent elevations of serum CK.

Management Of Acute Tying-Up

Affected horses which are distressed (sweating profusely, high respiratory rate, anxious appearance), reluctant to move, or have discolored urine require immediate veterinary assistance. Correction of dehydration by administration of oral or intravenous fluids is of critical importance. Myoglobin is toxic to the kidneys, and persistent dehydration in concert with myoglobinuria can result in development of severe renal failure. Your veterinarian also will attempt to relieve anxiety and pain by administration of sedatives and anti-inflammatory drugs.

Physical therapy is an important part of the treatment plan. Beginning approximately 24 hours after an episode, if not sooner, the horse should be provided a large box stall to move about as it desires. A few minutes of hand walking can be performed after 24 hours, but it often is best to allow the horse to move about on its own. At this sensitive time, too much hand walking can precipitate another episode of muscle damage. Small paddock turnout with another quiet horse is beneficial during this recuperative phase. The duration and frequency of walking bouts should be increased gradually by a few minutes over the subsequent week, followed by a gradual return to regular exercise. Massage therapy might aid recovery.

In horses which tie-up two, three, or more times, a detailed diagnostic evaluation to identify an underlying cause of the exertional rhabdomyolysis is warranted. This work-up will include a complete blood count, serum chemistry (particularly for measurement of CK and AST), and collection of a sample of urine to allow assessment of electrolyte balance. Another important test is microscopic evaluation of muscle biopsy samples, particularly if PSSM is suspected or if the clinical signs the horse exhibits appear unusual to the attending veterinarian. Specialized laboratories such as the Neuromuscular Laboratory at the University of Minnesota, St. Paul, are required in order to process the frozen samples and to perform special stains. Veterinarians can obtain information about collecting and shipping samples by contacting one of the laboratories (www.mvdl.umn.edu/muscle1.htm).

Storage of abnormal polysaccharide is the hallmark feature of muscle biopsies from horses with PSSM. Horses with RER do not have abnormal accumulation of polysaccharide in their muscle, but often have other characteristic changes, such as the presence of nuclei in the center rather than the periphery of muscle cells.

Management Of Chronic Tying-Up

1. General Recommendations

Although there is no set "recipe" for the management of horses prone to recurrent episodes of tying-up, some general recommendations can be made. For RER or other situations in which a nervous disposition might be an important trigger factor for tying-up, steps to calm the horse are imperative. All aspects of day-to-day management should be evaluated and, where appropriate, changes made, e.g., moving the horse's location in the barn to be away from main traffic areas or close to compatible horses with quiet dispositions; altering the time of day that the horse is worked; under veterinary supervision, administration of low doses of the tranquilizer acepromazine prior to exercise.

A regular exercise program is important. Affected horses should be exercised daily, either in the form of paddock turnout or more formal exercise, such as riding and longeing. Long periods of complete stall rest (more than two days) should be avoided, particularly in very fit horses. Even when episodes of tying-up occur, rest periods should be kept to a minimum and the horse returned to its normal routine as quickly as possible.

Horses with RER can be returned to exercise when values for serum CK are within normal limits. Horses with PSSM often are very gradually re-introduced to a few minutes of exercise a day regardless of serum CK. PSSM horses should be worked gradually on a lunge line starting with only two to three minutes and adding a few minutes each day. After three weeks, CK can be re-evaluated and riding for 30 minutes can begin. Long recovery periods tend to increase the risk of recurrence when training is resumed, as do long lay-ups of fit horses. For each workout, warm-up should be gradual and thorough.

In Thoroughbreds with RER, keeping a tight hold during warm-up or the early stages of canter/gallop work can be counter-productive by increasing the level of excitement. In Standardbred horses, more than 15 minutes of jogging at a time should be avoided because this form of exercise is most detrimental. Dressage horses should be exercised with intervals of collection and opportunities to stretch in between. As mentioned, overexertion is a risk factor for tying-up; increases in the duration and intensity of training sessions should be gradual, and the horse should not be exercised to fatigue.

Feeding programs must be closely evaluated. In many cases, easily implemented dietary changes have proven effective in the control of chronic tying-up. The most important consideration is a drastic reduction in grain feeding with addition of fat (e.g., corn oil, soya oil, or rice bran) to ensure adequate energy in the diet. This issue is covered in more detail later (also see sidebar on Feeding Fat on page 86).

If electrolyte imbalances are suspected, salt (one to three tablespoons per day) should be added to the ration. The actual amount of salt required will depend on the season and the level of training (see April Sports Medicine article). The diet might require additional vitamin E and/or selenium.

The diet must contain adequate fiber (forage). As an absolute minimum, each day horses should consume 1% of their body weight in forage. An 1,100-pound horse would need 11 pounds of hay. Ideally, the level of hay feeding should approach 1.5% of body weight (about 15 pounds of hay in this example). Finally, strict attention to overall energy balance is critical--provide enough energy to meet the demands of exercise training and to maintain body condition.

2. Fat-Supplemented Diets

It long has been recognized that reducing the level of grain feeding reduces the risk of tying-up. A study in the 1930s demonstrated that working draft horses were more likely to tie-up if fed a diet high in non-structural carbohydrates, such as that provided by grains and molasses. Addition of fat to the diet of horses prone to tying-up is beneficial for two main reasons. First, in some horses, diets high in non-structural carbohydrates can cause excitement; a reduction in grain/sugar feeding with addition of fat to the diet tends to calm these horses. Second, recall that for horses with PSSM, the underlying problem is one of excess carbohydrate storage in muscle. In this respect, grain and sugar feeding simply "fuel the fire" by providing sugar for glycogen synthesis. It therefore is important to completely eliminate grain, sweet feed, and other simple sugars from the diet and to provide fat as an alternative source of energy.

There are various options for fat supplementation. These include vegetable oils such as corn and soya, rice bran (a 20% fat product), and purified animal fats. All of these fat sources are highly palatable and the choice will vary depending on individual circumstances. At present, there is no consensus as to the level of fat feeding required for beneficial effects. In addition, there is much confusion over how the amount of fat in the diet is expressed (see the sidebar on page 86). The following are general guidelines; we recommend consultation with an equine nutritionist when developing a diet for horses with RER or PSSM.

For Thoroughbred and Standardbred racehorses, the diet should consist of good quality hay (grass or a grass/alfalfa mix), a vitamin-mineral mix, a small amount of grain (maximum five pounds), fat (in the form of rice bran and/or oil), and added salt. Beet pulp or soya hulls, both highly digestible fiber sources, provide an alternative means for provision of energy and might allow for complete elimination of grain from the diet. In a recent study funded by the Southern California Equine Foundation, feeding Thoroughbred horses a diet of grass hay and a pelleted supplement containing highly fermentable fiber and fat resulted in a significant reduction in post-exercise muscle damage. This supplement, developed by Kentucky Equine Research, soon will be commercially available.

A combination of good-quality grass hay, one to two pounds of rice bran, and a vitamin-mineral mix works well for horses with PSSM when combined with daily exercise and turnout. Corn oil (one to two cups per day) mixed with hay cubes or alfalfa pellets is an alternative (soak the pellets or cubes with oil, then add the water).

One final point deserves emphasis--there is no cure for horses with chronic forms of tying-up, such as RER and PSSM.

Rather, the goal of preventative measures is to reduce or eliminate clinical "expression" of the disease. Through a combination of regular exercise, daily turnout, changes in environment, and diet, it has been possible for many affected horses to return to competition.

By Ray J. Geor, BVSc, PhD, Dipl. ACVIM, and Stephanie J. Valberg, DVM, PhD, Dipl. ACVIM

Feeding Fat

Just how much fat should be added to the diets of horses with chronic exertional rhabdomyolysis?There is mounting evidence that low-grain, fat-supplemented

diets are beneficial in the management of horses prone to repeated episodes of tying-up. However, there are some questions yet to be answered. For example, at present, there is no consensus as to which form of fat works best. As well, the level of fat feeding required for beneficial effects has not been established.

Some researchers have recommended that the diet of horses with chronic tying-up problems should contain 20%-25% fat. However, it often is not specified whether this 20%-25% value applies to the total diet or just the "concentrate" portion of the diet. This distinction is very important, as the following example illustrates.

Assume you have an 1,100 pound (500 kg) Thoroughbred racing filly with a chronic tying-up problem. The main components of the current diet are seven pounds (3.2 kg) of sweet feed and 12 pounds (5.4 kg) of a grass/alfalfa hay mix. For this diet to be 20%-25% fat (by weight), 3.8 to 4.4 pounds (1.75-2.0 kg) of fat must be added. On the other hand, if the "20%-25% fat" applies only to the grain portion of the diet, the amount of fat to be added is 1.4 to 1.75 pounds (0.6-0.8 kg) of fat. In this scenario, fat would represent 8%-10% of the total diet.

Even this level of fat supplementation is not practical; because oil is less dense than water, 0.6 kg of oil is actually 860 ml, or nearly 31⁄2 cups. For the average-sized horse in athletic training, 600 ml of oil (21⁄2 cups) would represent the upper limit of daily fat supplementation.

Also remember that when fat is fed, less grain is required to provide the same amount of energy—of course, this is the very reason for adding fat to the diet. In the above example, if 600 ml (0.42 kg) of corn oil is added to the diet, the amount of grain required is decreased to 4.8 pounds (2.2 kg). In some horses, it might be necessary to further reduce the amount of grain in the diet. This can be achieved by adding rice bran (20% fat) to the ration. For example, feeding about two pounds of rice bran removes a further 1 kg of sweet feed from the diet, and the total diet is about 7% fat.

So, the bottom line is that a high-fat diet in horses feasibly will be between 7% and 10% fat. To meet the high-energy requirements of racehorses in training, some level of grain feeding is required in addition to fat supplementation. For Thoroughbred and Standardbred racehorses with chronic tying-up, diets with some grain (not more than five pounds per day) and supplemental fat (such that fat represents, by weight, 6% to 7% of the diet) are beneficial for prevention of the problem.

The situation is much different for horses with polysaccharide storage myopathy—here, grain is an absolute "no-no." (This restriction also applies to other simple sugars, such as molasses. Do not feed beet pulp that has added molasses.) Fortunately, these horses often are "easy-keepers" and will thrive on a diet of hay, pasture, a small amount of a fat supplement (such as one to two pounds of rice bran), and a vitamin-mineral supplement.

Further Reading

Harris, P.A.; Snow, D.H. Role of electrolyte imbalances in the pathophysiology of the equine rhabdomyolysis syndrome. In: Persson SGB, Lindholm A, Jeffcott L.B., eds. Equine Exercise Physiology 3. Davis, California: ICEEP Publications, 1991; 435-442.

Lentz, L.R.; Valberg, S.J.; Balog, E.M.; Mickelson, J.R.; Gallant, E.M. Abnormal regulation of muscle contraction in horses with recurrent exertional rhabdomyolysis. American Journal of Veterinary Research 1999; 60: 992-999.

MacLeay, J.M.; Valberg, S.J.; Geyer, G.J.; Sorum, S.A.; Sorum, M.D. Heritable basis for recurrent exertional rhabdomyolysis in Thoroughbred racehorses. American Journal of Veterinary Research 1999; 60: 250-256.

MacLeay, J.M.; Sorum, S.A.; Valberg, S.J.; Marsh, W.E.; Sorum, M.D. Epidemiologic analysis of factors influencing exertional rhabdomyolysis in Thoroughbreds. American Journal of Veterinary Research 1999; 60: 1562-1566.

Valberg, S.J. Muscular causes of exercise intolerance in horses. Veterinary Clinics of North America: Equine Practice 1996; 12: 459-517.

Valberg, S.J.; Geyer, C.; Sorum, S.A.; Cardinet III, G.H. Familial basis for exertional rhabdomyolysis in Quarter Horse-related breeds. American Journal of Veterinary Research 1996; 57: 286-290.

Valberg, S.J.; MacLeay, J.M.; Mickelsen, J.R. Polysaccharide storage myopathy associated with exertional rhabdomyolysis in horses. Compendium for Continuing Education of the Practicing Veterinarian 1997; 19: 1077-1086.

Valberg, S.J.; Mickelsen, J.R.; Gallant, E.M.; MacLeay, J.M.; De La Corte, F. Recurrent exertional rhabdomyolysis in Quarter Horses and Throughbreds: one syndrome, multiple aetiologies. Equine Veterinary Journal 1999; Supplement 30: 533-538.

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