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Fit to be Tied: Part OneBy Drs. Peter Huntington and Stephanie Valberg · March 2, 2011

Tying-up is a generic term commonly used to describe muscle disease in performance horses.  Other terms often used interchangeably with tying-up include exertional rhabdomyolysis, azoturia, and Monday morning sickness. Classically, tying-up occurs after 15 to 30 minutes of aerobic exercise. Horses lose impulsion, develop a stiff, stilted gait, and may pause and stretch out as if to urinate or paw the ground. If pushed to continue exercise, horses sweat excessively, develop a high respiratory rate, and then upon standing become locked in place, unable to walk forward due to painful muscle contractures largely involving the back and hindquarters.In addition to clinical signs, horses that tie-up will have moderate to marked elevations in blood serum levels of muscle proteins and enzymes including myoglobin, creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) activities. Such elevations indicate muscle cell damage and are considered a diagnostic tool to detect tying-up.


 For years, horses that tied-up following exercise were thought to suffer from the same disease. However, treatment and prevention protocols that worked on some horses did not help other horses. As a result, confusion and controversy developed regarding the cause and treatment of tying-up.


One of the most important developments into understanding tying-up in horses has been the recognition that while acute signs of muscle pain and cramping are similar among horses, the causes of tying-up are varied. For decades, progress in understanding tying-up was hampered by searching for one specific cause of muscle pain and by the false assumption that tying-up pain was due to a lactic acidosis. In fact, there is no scientific validation that lactic acid accumulates in the muscle of horses with tying-up, and many studies show that lactic acid is not present in high levels in horses with tying-up.


The incorporation of the muscle biopsy technique into clinical practice over the last 20 years has served to enhance the accuracy of diagnosis of muscle disease in individual horses and also to provide a valuable tool for further research into muscle diseases in horses.  As equine genome mapping techniques progress, DNA-based tests are increasingly becoming a part of the diagnostic approach to muscle disease in horses. There are currently four DNA-based tests for muscle disorders in horses, and research is underway to identify more. DNA testing for hyperkalemic periodic paralysis (HYPP), glycogen branching enzyme deficiency (GBED), malignant hyperthermia (MH), and type 1 polysaccharide storage myopathy (PSSM1) are all available. Tests derived from hair roots or blood samples provide a less invasive and more accurate diagnosis than a muscle biopsy. Studies have now defined the breeds affected with these disorders and in many cases the prevalence of the disorders within breeds.


Initial classification of tying-up is now based on frequency of the disease symptoms following exercise.  Horses that tie-up only a few times in their lifetime are classified as “sporadic,” while those horses that tie-up on a repeated basis are termed “chronic.” The following is a brief discussion of both sporadic and chronic tying-up and steps that can be implemented to help prevent the disease. Much of the research involving tying-up and treatment/prevention protocols has been conducted by the College of Veterinary Medicine at the University of Minnesota (Stephanie Valberg, D.V.M., Ph.D.), and Kentucky Equine Research has collaborated in a number of these studies.


Sporadic Tying-Up

Many horses experience some muscle soreness and strain associated with exercise. These horses often are mistakenly thought to be suffering from a specific muscle disease. Inadequate warm-up, preexisting lameness, exercise to the point of fatigue, and insufficient training can result in muscle soreness and injury. A similar human scenario might be overexertion from strenuous physical activity in a person conditioned to sit behind a desk. In horses that actually tie-up, muscle soreness is much more severe and is typically accompanied with elevated blood serum muscle proteins and myoglobinuria (coffee-colored urine). This darkening of the urine is a result of the kidneys filtering myoglobin (a muscle protein) from blood, an indication of severe muscle damage. The most frequent causes of sporadic tying-up are exercise that exceeds a horse's level of training, electrolyte imbalances, hyperthermia, and strenuous exercise while suffering from a viral respiratory disease.


Sporadic tying-up should be considered a veterinary emergency if horses are sweating profusely, reluctant to move or have dark urine. Veterinarians may administer medicine to relieve anxiety and muscle pain. In addition, corrections in hydration are made to account for fluid losses and myoglobinuria that may impair kidney function. Further treatment strategies include stall rest followed by hand walking and turnout once initial muscle stiffness has resolved. Prolonged stall rest is not recommended. Grain intake is drastically reduced or eliminated because these horses are likely to be on a reduced exercise program. The amount of time the horse must remain out of training has not been firmly established. However, any training regime following an episode of tying-up should be resumed gradually and consistently to prevent further muscle damage.


Horses consuming a high-grain diet appear to be more likely to develop tying-up than horses fed a low-grain or fat-supplemented diet. The grain itself may not be responsible for rhabdomyolysis; however, high starch intake may trigger rhabdomyolysis in horses with particular myopathies such as RER and PSSM.  Electrolyte depletion in horses can occur due to dietary deficiency and losses in sweat with strenuous exercise. Sodium, potassium, magnesium, and calcium play key roles in muscle fiber contractility.


Another proposed cause of sporadic tying-up is the increased generation of free radicals from oxidative metabolism associated with exercise. Selenium, acting via the enzyme glutathione peroxidase, and vitamin E, acting within the lipid component of cell membranes, scavenge free radicals and prevent lipid peroxidation of cell membranes. Primary selenium deficiency is common in young animals living in areas with selenium-deficient soil; however, it has rarely been demonstrated as a cause of exertional rhabdomyolysis. In fact, many racehorses with chronic tying-up have higher concentrations of selenium and vitamin E due to zealous dietary supplementation by the trainer. It is not known whether horses that experience repeated episodes of tying-up may generate more free radicals than normal horses. Low vitamin E intake is becoming a more common occurrence in many horses with restricted pasture access. Horses with low serum vitamin E may present with muscle soreness, muscle tremors, muscle weakness, and loss of muscle mass. In early stages this may be due to a reversible muscular process. After years of deficiency, oxidative damage to motor nerves can result in permanent damage typical of equine motor neuron disease.


Sound management practices and training may help prevent tying-up. Learning not to overexert unfit horses and remembering to fortify the diet with salt on a daily basis as well as electrolytes prior to heavy sweat loss are logical strategies. Adjusting the amount of grain fed to satisfy the energy needs of the horse is also tremendously important. In other words, one does not want to overfeed carbohydrate (grain) to horses as this may be potentiate tying-up in some horses. Feeding grain concentrates fortified with fat and necessary antioxidant vitamins and minerals will provide energy while supplying the building blocks to protect muscle tissue. The combination of these strategies will often prevent healthy horses from having another bout of tying-up. In areas where the soil is deficient in selenium, a selenium and vitamin E supplement may improve muscle health.


Chronic Tying-Up

When horses have repeated episodes of tying-up, the disease is considered chronic. Members of many different breeds of horses have been reported to have chronic bouts of tying-up, including Quarter Horses, Thoroughbreds, Standardbreds, Paints, Morgans, Arabians, and various breeds of draft and warmblood horses. The proposed causes of chronic tying-up have included electrolyte imbalances, hormonal imbalances, hypothyroidism, muscle ischemia with lactic acidosis, and vitamin E and/or selenium deficiency. However recent research has found new causes and discredited some old theories.


While chronic episodes of tying-up are frustrating and painful for both the horses and their owners, it is the study of these chronic cases that has advanced our knowledge of the causes, treatment and prevention of the disease. There are now four specific causes of chronic tying-up that have been recognized, though there are likely many more underlying causes yet to be recognized. These include recurrent exertional rhabdomyolysis, polysaccharide storage myopathy type 1 and type 2, and malignant hyperthermia.

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