Exertional Rhabdomyolysis

Tying-up is a problem that has troubled horses and their owners for many years, and it has been known by many names. The old-timers who battled the syndrome in their draft horses following a Sunday away from the fields called it Monday morning disease, or azoturia. Others have used the terms "set fast" and paralytic myoglobinuria. The term used most frequently by researchers and the veterinary community today is exertional rhabdomyolysis (ER).

There are classic symptoms of a horse tying-up, and they have remained unchanged through the years. They include sweating, becoming stiff, and a reluctance to move.

"These symptoms," says Stephanie Valberg, DVM, PhD, a leading researcher on the subject at the University of Minnesota, "are all indications of pain resulting from muscle damage to the hind limbs. In fact, tying-up is not really a disease, but a syndrome or description of a horse with muscle damage."

Valberg's research into the causes of exertional rhabdomyolysis has been on-going. She carried out studies on the syndrome while at the University of Uppsala in Sweden; during a tenure at the University of California, Davis; and today continues her research at the University of Minnesota. She was the keynote speaker at the recent annual conference for the Association of Equine Sports Medicine in San Antonio, Texas. In her address and in question and answer sessions, Valberg outlined to her audience both what is known and what is theorized about the tying-up syndrome.

She told the group that researchers have learned a great deal about tying-up in recent years. However, in a manner of speaking, their findings have complicated, rather than simplified, the issue.

First of all, some of the basic assumptions concerning the syndrome that have been treated as truth through the years have not held up under the light of scientific scrutiny. Following on the heels of those revelations has been the conclusion that the syndrome is multi-faceted. There is no single cause and there is no single cure.

"Two horses can look exactly alike clinically," Valberg says, "but are tying-up for totally different reasons."

Thus, what was considered by some early researchers to be a problem that had a basic cause-and-effect has become a broad-scale syndrome that will require continued research on a variety of fronts before every aspect is understood.

Before launching into a discussion on tying-up, it might be well to let Valberg provide information on how muscles are designed to function, along with what sometimes happens when they dysfunction.

"The muscular system of the horse provides the explosive power of the jumper and cutting horse, the speed of the Thoroughbred, the stamina of the endurance horse, and the fine motor control of the advanced dressage horse," Valberg wrote in a report on exercise intolerance published in December of 1996. "It is a remarkable system in terms of both its athletic scope and its capacity to adapt and change according to the demands placed on it.

"Certain fundamental properties apply to optimal muscular performance for all equine athletes. Horses must be able to recruit specific muscle groups in a precisely timed fashion and sustain both the necessary force and speed of muscle contraction to last for the entire time of the performance.

"This ability to maintain muscle contractions is tightly tied to the capacity of other systems to deliver oxygen, glucose, and free fatty acids; to remove and buffer lactate; and to provide the most energy-efficient gait possible. Impairment of any body system's ability to meet the needs of the contracting muscle is eventually expressed as muscular fatigue and decreased power output.

"As such, muscle fatigue may be secondary to a primary dysfunction elsewhere in the body."

These dysfunctions, she explains, might involve a combination of subtle lameness, upper respiratory tract dysfunction, or cardiovascular disease. Whatever the cause or causes, the horse's performance capability will be compromised.

Normally in these circumstances, Valberg points out, clinical indicators exist--such as stridor, heart murmurs, or lameness--that lead to the identification of the primary cause of exercise intolerance that is secondarily expressed as muscle fatigue.

Unfortunately, muscular causes of exercise intolerance in horses are less easily recognized.

"This," reports Valberg, "is because they are not as common as gait and respiratory abnormalities, because they may lack specific clinical signs, and also because the necessary diagnostics, such as exercise testing and muscle biopsy, are only available at specialized laboratories...

"The muscular system in the horse is unique in its extremely high oxidative and anaerobic capacities and in the range of contractile speeds of the three main muscle fibers. In addition, the remarkable ability of muscle to adapt and change with the demands placed on it provides a wide range of athletic versatility. Poor performance of muscular origin in horses is often an intrinsic physiologic limitation. This may be due to an inherent lack of genetic suitability for a performance level or due to insufficient, or, at times, excessive, training adaptations.

"In other cases, poor performance may be a direct result of muscular injury. This damage may be due to ultrastructural changes when an untrained muscle makes a series of contractions, focal tearing of muscle bundles, or specific disorders that manifest during exercise (exertional myopathies).

"By definition, muscular fatigue is the inability of muscle to maintain the required or expected power output for a particular contractile event. This definition takes into account that both velocity and force must be maintained to sustain a given work capacity. Because the velocity and force output required by activities ranging from 100-mile endurance rides to one-mile sprints differ so enormously, the fact that many different factors contribute to muscle fatigue is logical.

"The most important of these are the fiber type composition of the contracting muscles; the intensity type and duration of exercise and the level of fitness."

There are a couple ways that muscle fibers are described. One system divides fibers into three types--1, 2A, and 2B. Type-1 fibers have the slowest contraction and relaxation times; type-2A fibers have a rapid rate of contraction; and type-2B fibers are the fastest, contracting with a maximum velocity that is 10 times that of type-1 fibers and three times that of 2A fibers.

Inheritance, sex, and training all influence muscle fiber type composition, says Valberg. In general, Quarter Horses and Thoroughbreds have the highest percentage of fast-twitch muscle fibers--80% to 90%. Standardbreds and Arabians have an intermediate number--75%.

Muscle fiber composition and fiber size appear to be an inherited characteristic. Recent studies of Andalusian horses, says Valberg, suggest that families appear to pass on distinctive fiber type compositions.

"Within and among breeds, however," says Valberg, "a great deal of individual variation exists in fiber composition, such that some Quarter Horses resemble Arabian horses and vice versa. Sex influences also exist, such that stallions and horses treated with anabolic steroids have more type-2A fibers and fewer type-2B fibers than do mares.

"When muscle fiber compositions were first determined in horses, they were hoped to provide predictive information about an individual's suitability for specific types of athletic performance. Endurance horses, for example, would have more type-1 fibers and sprinters more type-2B fibers.

"Although some generalizations in these terms apply, enough other factors affect suitability that muscle fiber composition alone has not been a valuable predictive tool. In addition, longitudinal studies show that fiber composition changes with growth and training.

"In young Standardbred and Thoroughbred horses, the proportion of type-2A fibers increases while the proportion of type-2B fibers decreases concomitant with training at higher speeds."

During exercise, muscle contraction requires electric depolarization of motor nerves supplying a particular number of muscle fibers.

"This orderly recruitment of muscle fibers," says Valberg, "leads to smooth coordinated movement. Each motor nerve supplies a group of muscle fibers of the same type. At slow exercise intensities, type-1 fibers and a small number of type-2A muscle fibers are stimulated. As speed or duration of exercise increases, more muscle fibers are recruited, and this occurs in the order of their contractile speed...Only at near-maximal exercise intensities or after several hours of sub-maximal exercise are type-2B fibers recruited."

One more bit of information, this on the technical side, should be passed on from Valberg before entering the discussion on tying-up:

"Acetylcholine is released at the neuromuscular junction after depolarization of motor nerves. Electric impulses then travel along the sarcolemma and T tubules where charge sensors trigger the release of calcium via the calcium release channel from its storage site in the sarcoplasmic reticulum. Muscle contraction occurs when increased concentrations of intracellular calcium allow the interaction of actin and myosin filaments that then slide over each other.

"The muscle's unique arrangement of contractile proteins aligned in parallel from one end of the cell to the other, bound together by the cytoskeleton, confers the ability to contract. Tension is generated as the shortening filaments tug at both ends of the myofiber toward the middle. The ratchet-like action of actin and myosin interactions that serve to shorten the myofibrils is called cross-bridge cycling. Muscle relaxation occurs between contractions by actively pumping calcium back into the sarcoplasmic reticulum via calcium ATPases."

With that as a base, it is time to take an in-depth look at what happens when these muscles have a problem functioning properly and the tying-up syndrome occurs.


For years, many veterinarians and horsemen thought that draft horses developed "Monday morning disease" because they were given a day of rest after six days of strenuous work. They believed that during the day of rest, there was an excessive accumulation of glycogen (sugar) in the muscles. Then, when the teams were hooked to the plow or another piece of equipment on Monday morning, it was reasoned, this over-supply was rapidly metabolized, creating, in the process, excessive amounts of lactic acid. The lactic acid was believed to cause muscle damage.

Recent research making use of muscle biopsies has revealed that there is not an excessive buildup of lactic acid in the muscles of horses which are tying-up.

"In the laboratory," says Valberg, "muscle samples from horses with recurrent tying-up do not produce any more lactic acid when stimulated than muscle samples from normal, healthy horses."

So much for that straightforward, but incorrect theory.

For years it has also been assumed that each case of tying-up emanated from a basic cause that was the same for all horses, no matter what the breed or discipline. Research also has demonstrated that this belief is unfounded.

An excitable 2-year-old Thoroughbred filly, for example, might be tying-up for totally different reasons that a sedate Quarter Horse. That begs another question: Is heredity involved?

Research shows there is a high probability that a recessive gene which has been passed down in a particular family line of Quarter Horses might be responsible for one type of recurrent exertional rhabdomyolysis, and that certain lines of Thoroughbreds seem more susceptible to another form of tying-up. More about that later.

The word "recurrent" is significant here. It, too, reflects the syndrome's complexity. Some horses have only sporadic episodes, and others have recurrent episodes.

While sporadic tying-up is of serious concern, it does not carry the same connotation as does recurrent tying-up. Normally, the horse which has a sporadic episode will recover with rest and be able to return to activity. Depending on the cause and subsequent conditioning and dietary regimen, it might be the animal's only episode.

"Sporadic tying-up," says Valberg, "can occur following several different events. When a horse is asked to exercise more strenuously than what it has been conditioned for, tying-up can occur. This commonly happens in the spring with horses who were rested all winter and then, on the first nice day, are taken on a long trail ride and/or exercised too strenuously. It is also commonly seen in horses whose training programs have been accelerated too quickly.

"Physical trauma can cause sporadic tying-up. When a horse is involved in some type of struggle, for instance--a leg caught in a fence or in a halter, resulting in a struggle to break free--muscles can be torn in different areas. These horses can be very stiff and exhibit signs of tying-up for several days after an injury.

"Horses in surgery which are lying on their sides for several hours are also prone to developing muscle damage from the lack of adequate blood circulation to their tissues.

"Sometimes respiratory infections, such as the flu or strangles, also can cause inflammation in muscles and horses will exhibit symptoms of tying-up. Stiffness during exercise may persist for a month after the horse recovers from the initial respiratory infection. Fever and muscle pain are often key initial findings in these cases.

"Toxic agents can cause tying-up. Some plants, such as cestrum dinurum, an evergreen flowering shrub, can trigger a case of tying-up and, occasionally, drug reactions can cause muscle damage."

As already mentioned, in most of these cases, a period of rest will allow the muscle to recuperate and once that takes place, the horse is ready for activity.

It isn't nearly that simple for horses which have on-going or recurrent problems with tying-up. For some, the problem begins early in life and continues indefinitely. In many cases, only light exercise is required to bring on an episode.

Recurrent exertional rhabdomyolysis has presented researchers with a maze through which they are beginning to find pathways, though the trek is far from over.

Diet, for example, can be a causative factor in some cases of recurrent tying-up.

"Some horses' dietary needs vary, and an imbalance can cause recurrent tying-up," says Valberg. "Key electrolytes include sodium, potassium, and chloride and key minerals include calcium, phosphate, and selenium. In some athletic horses, a normal diet of oats and hay may not provide enough electrolytes and minerals to maintain normal muscle function. By examining the electrolyte content of both blood and urine simultaneously, a deficiency in these factors may be detected. A good dietary mineral and salt supplement which is consumed on a daily basis is strongly recommended in performance horses.

"Horses with recurrent tying-up have been found to store high amounts of glycogen in their muscles and, as a result, these horses should be kept on a low grain diet and exercised regularly. These high levels of glycogen in the muscle could be an indication of a problem with the enzymes involved in breaking down glycogen to lactate. In humans, several defects in enzymes have been identified as causes of tying-up. To date, in over 30 horses studied, no specific enzyme deficiencies in this metabolic pathway have been identified.

"A metabolic defect in muscle energy production has been identified at UC Davis in Arabian horses. These horses would become extremely tired after exercising and show signs of cramping up, but when their muscles and blood were examined, no actual muscle damage could be found. This exercise intolerance was found to be due to a deficiency of an enzyme in the oxygen utilizing pathways of skeletal muscle. Any exercise at all resulted in an excess of lactic acid being produced.

"In addition to abnormalities in metabolic pathways for energy metabolism, some horses may have a defect in the way they regulate calcium in the muscle cells, and this could cause tying-up. Further research needs to be conducted in this area."

That last sentence concerning the need for more research can be repeated for virtually every facet of the syndrome. Every door opened by researchers provides some assistance in understanding the syndrome, but, at the same time, the hallway of new and unanswered questions seems to broaden.

One thing is certain, the syndrome affects a large of number of horses in a variety of disciplines.

Tying-Up In Thoroughbreds

One of Valberg's colleagues at the University of Minnesota, Sandy Sorum, DVM, told the AESM group in San Antonio that, "Exertional rhabdomyolysis (ER) is one of the most common soft tissue injuries reported at Thoroughbred tracks."

During her talk at the conference, Sorum gave a report on a study conducted at Canterbury Downs in Minnesota. The purpose of the study was to determine the incidence, age distribution, sex distribution, and racing performance of horses with ER and to identify other contributing factors during one racing season. The study was supported by the Grayson-Jockey Club Research Foundation.

Involved were horses treated by a track veterinarian who had a large racetrack practice. During the year, some 984 horses were studied, with exertional rhabdomyolysis being diagnosed on the basis of clinical signs and high serum kinase.

Of the 984 horses studied, 48 (5%) had ER. Thirty-six of the 96 trainers at the track had horses with ER.

Some other interesting facts emerged. Females were much more susceptible than males. It could be broken down even further. Among the females suffering from ER, most of them were young, excitable fillies.

It was also found that the syndrome could severely limit a horse's ability to perform. Of the 48 ER horses at the track, eight never raced.

Interestingly, tying-up occurred most frequently when horses were galloped, followed by jogging or walking. Rarely was it associated with breezing.

It was also found in many of these fillies that they had reached an advanced stage of fitness before the syndrome was manifested.

The matter of genetics also rears its head in Thoroughbred circles. In a report to Grayson-Jockey Club, Valberg had this to say:

"We believe that a specific form of tying-up exists in certain families of Thoroughbred horses and that this is due to abnormal regulation of calcium by membrane systems in the skeletal muscle.

"Muscle contractions are initiated by propagation of electrical impulses along the outer cell membrane and along membranous connections extending into the cell which then stimulate the release of calcium from intracellular membrous storage sites. Muscle relaxation requires energy-dependent pumping of calcium back into storage sites. We are currently studying tying-up Thoroughbreds to determine if the pattern of muscle contractions are abnormal in these horses because of abnormal regulation of calcium inside the muscle cells.

"The narrow genetic origin of Thoroughbreds and the common lineage of the pedigrees of horses with tying-up would support the possibility of a common recessive trait. More statistical analyses of these pedigrees need to be performed.

"Four Thoroughbred fillies with recurrent tying-up have been bred to a stallion that has sired affected horses in order to determine if tying-up will be inherited by their offspring."

In another study aimed at determining whether the syndrome is inherited, nine mares were bred to a stallion which had many offspring (80%) which tied up. The resultant foals in the study also manifested the classic symptoms of the syndrome.

The same mares then were bred to a stallion whose offspring had not exhibited symptoms of tying-up. Those foals did not tie up.

What To Do

The next logical question is this: How does one handle or treat horses in the above category--young, excitable fillies which are tying-up?

Here are Valberg's recommendations:

"Prevention of further episodes of ER in susceptible horses should include standardized daily routines and an environment that minimizes stress. The diet should be adjusted to include a balanced vitamin and mineral supplement, high-quality hay, and a minimum of carbohydrates, such as grain and sweet feed.

"Dietary fat supplements may help to maintain weight in nervous fillies without providing excessive carbohydrates.

"The use of low doses of acepromazine before exercise in excitable horses is believed to help some horses.

"Daily exercise is essential, either in the form of turn-out, longing, or riding. In the past, horses have been box stall rested for several weeks after an episode of ER. The author's (Valberg) opinion is that this is counter-productive and increases the likelihood that the horse will develop ER when put back into training.

"The initial muscle pain usually subsides within 24 hours of acute ER and daily turn-out in a small paddock can be provided at this time. Subsequently, a gradual return to performance once serum CK (creatinine kinase, an enzyme) is within normal range.

"Dantrolene (2 milligrams per kilogram orally) given one hour before exercise is believed effective in preventing ER in some horses. Dantrolene is used to prevent malignant hyperthermia in humans and swine by decreasing the release of calcium from the calcium release channel.

"Phenytoin (1.4 to 2.7 milligrams per kilogram) twice daily also has been advocated as a treatment for horses with recurrent ER. Therapeutic levels vary so oral doses are adjusted by monitoring serum levels... Phenytoin acts on a number of ion channels within muscle and nerves, including sodium and calcium channels.

"Unfortunately, long-term treatment with dantrolene or phenytoin is expensive."

Tying-Up In Pleasure Horses

Now for a look at tying-up in horses that in no way resemble their excitable young female counterparts. These horses often have a calm and sedate demeanor. In many cases, they might be suffering from what has been termed polysaccharide storage myopathy. Their muscles accumulate an abundance of non-bioavilable polysaccharide. Simply put, glycogen (sugar) accumulates in the muscle because the muscle cannot use it normally. Thus, the muscle has an abundance of fuel, but can't burn it. Without the energy the glycogen is designed to supply, these horses cramp and become stiff. Because the glycogen was not utilized, the lactic acid level in these horses when they tied up was very low.

To date, reports Valberg, the syndrome has been noted in Quarter Horses, Paints, Appaloosas, draft horses, draft crossbreds, warmbloods, and even a few Thoroughbreds.

"Treatment of horses with polysaccharide storage myopathy," says Valberg, "involves supplying them with an alternative source of energy. Fats are calorically dense and enter the metabolic pathways of muscle at a different site than glycogen. This makes a diet using fats as the primary source of energy an alternative to high-carbohydrate diets.

"Initial data supports the use of high fat supplements such as processed rice bran (20% fat) in the diet of these horses. Grain and sweet feed are replaced by rice bran products and a balanced alfalfa/grass hay.

"Horses with mild to moderate clinical signs may be able to return to full athletic performance with careful dietary and management changes, which include regular daily exercise without extended periods of inactivity. Stall rest or irregular exercise may cause another episode of tying-up."

Here again, heredity raises its head. In a joint study, researchers at the University of Minnesota and the University of California, Davis, identified 23 horses with polysaccharide storage myopathy. Of that number, 13 were Quarter Horses, four were American Paint Horses, three were Appaloosas, and three were Quarter Horse crossbreds. Pedigrees were available for 18 of the horses.

Three stallions, identified by the researchers as A, B, and C, were featured prominently in the pedigrees.

Valberg had this to say in a paper that resulted from the study:

"Horses with polysaccharide storage myopathy appeared to have common bloodlines. Two stallions featured prominently in the pedigrees of all horses with polysaccharide storage myopathy. The sire and dam of four horses were descendants of stallion A, the sire and dam of one horse were descendants of stallion B, and the sire and dam of 11 horses were descendants of a combination of stallions A and B. Further analysis of pedigrees indicated that stallions A and B were descendants of a common sire. The pattern of inheritance in the degrees evaluated resembled an autosomal recessive disorder.

"Computer analyses identified a third stallion C as a likely contributing founder. Stallion C was present on the sire's and dam's sides of two affected horses and on the sire's or dam's side of three horses."

Again, researchers insist that more research is needed in this area.

Even as research continues, episodes of tying-up continue to occur, and horsemen and veterinarians are forced to cope with them. Following are Valberg's suggestions for handling the horse which ties up:

1. Stop exercising the horse and move it to a box stall. Do not force the horse to walk.

2. Call your veterinarian.

3. Blanket the horse if weather is cool.

4. Determine if the horse is dehydrated due to excessive sweating. When skin is pinched, it normally will spring back, and the horse's saliva should be wet, not tacky.

5. Provide fluids--small frequent sips of water. Electrolytes (potassium, sodium, and chloride) may be added to drinking water, if palatable to the horse. Plain water should always be available as an alternative. If the horse is dehydrated, your veterinarian might give intravenous fluids. Once cool, the horse can have free access to water.

6. Relieve anxiety and pain. Drugs may be prescribed by your veterinarian.

7. Remove grain and feed; provide only hay until signs subside.

8. Hand walking or small paddock turnout is good once the horse walks freely, usually in 12-24 hours.

9. When blood creatine kinase is normal, slowly recondition the horse to the previous work level.

10. If the problem reoccurs, have the horse evaluated for a specific cause of recurrent exertional rhabdomyolysis.

11. Consider changing the diet--feed less grain and more fat, and make sure mineral intake is balanced.

About the Author

Les Sellnow

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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