Exertional Rhabdomyolysis (ER), commonly known as tying-up or azoturia, is an exercise-induced condition in horses characterized by the excessive breakdown of muscle tissue. 
This results in muscle spasms, pain and impaired performance following bouts of exercise.  In severe cases, affected horses may exhibit signs of colic or even collapse.
Episodes of tying-up may be influenced by factors such as poor conditioning and abrupt changes in exercise intensity. Some horses inherit a genetic predisposition to ER.
Treatment of this condition includes a combination of stall rest, fluids, dietary adjustment and medication. To prevent tying-up, implement gradual exercise conditioning to build muscle strength, maintain hydration, and ensure a balanced diet with sufficient electrolyte levels.
If you suspect your horse has ER, contact your veterinarian for assessment. Early intervention and treatment improve your horse’s prognosis and reduce the risk of future episodes.
Exertional Rhabdomyolysis in Horses
Exertional Rhabdomyolysis is a muscular disorder affecting horses that is frequently triggered by exertion, stress, hormonal factors or nutritional imbalances. In horses, the condition is characterized by muscle pain, stiffness, and reluctance to move.
This condition is associated with the breakdown of muscle fibers, leading to the release of muscle enzymes and proteins into the bloodstream, some of which can be harmful to the kidneys.
Laboratory tests of affected horses typically show elevated muscle enzyme levels in the blood, such as creatine kinase (CK) and aspartate aminotransferase (AST). In some cases, muscle biopsies may be performed to assess the extent of muscle damage or to identify specific muscular disorders.
Clinical signs of ER often appear following intense exercise or periods of excitation. Episodes of tying-up can vary in intensity, from subclinical symptoms to severe cases where the horse may lie down or even collapse.  The severity of symptoms may even fluctuate in the same horse over time.
- Reluctance to move
- Increased temperature
- Muscle stiffness and pain over the loin and croup
- Tachypnea (rapid breathing)
- Tachycardia (fast heart rate)
- Muscle fasciculation (visible muscle tremors)
- Myoglobinuria (dark urine due to the presence of myoglobin)
- Reduced exercise tolerance
Types of Exertional Rhabdomyolysis
Exertional Rhabdomyolysis in horses can manifest in two primary forms: sporadic and chronic. Understanding the distinctions between these types is crucial for effective management and prevention of the condition.
Sporadic Exertional Rhabdomyolysis
Sporadic ER is an occasional occurrence that typically affects horses subjected to unusual or excessive physical exertion beyond their normal level of training or fitness.
This form is often seen in horses that are otherwise healthy and do not have an underlying predisposition to muscle disorders. In horses affected by sporadic ER, there is no inherent or intrinsic disorder causing abnormal breakdown of the muscle tissue.
Instead, episodes of tying up are caused by external factors, such as intense exercise or environmental stressors, that contribute to muscle cell damage. These episodes may not follow a consistent pattern and may be separated by periods of normal muscle function.
Examples of external factors that can trigger sporadic ER include: 
- Overtraining and muscle strain: ER commonly occurs when horses are exercised beyond their conditioning level, especially after a long period of rest followed by a sudden increase in training intensity. Signs may include muscle stiffness and gait alterations, as well as increased muscle enzyme activity. Overexertion and repetitive muscle use can lead to exercise intolerance. 
- Nutritional deficiencies: Deficiencies in electrolytes or antioxidant nutrients such as selenium and vitamin E can contribute to ER in some horses. Horses may develop electrolyte imbalances during periods of prolonged exercise in hot weather. Dietary imbalances, particularly deficiencies of sodium, potassium and calcium, have also been linked to ER episodes. 
- Exercising while sick: Horses exerting themselves while fighting herpes, the influenza virus or other infections could be at a higher risk for an ER episode. Horses with fever, coughing, nasal discharge or other respiratory symptoms should not be exercised unless under the guidance of a veterinarian.
Chronic Exertional Rhabdomyolysis
Horses with chronic ER experience repeated episodes of muscle breakdown during exercise. Chronic tying-up is often linked to an underlying genetic abnormality affecting muscle cell function, such as such as Polysaccharide Storage Myopathy. 
Type 1 Polysaccharide Storage Myopathy
Type 1 Polysaccharide Storage Myopathy (PSSM1) is a genetic disorder in horses that affects muscle metabolism. It is commonly found in Quarter horses, draft horses and some warmblood breeds.  PSSM1 horses are typically found in halter and pleasure horse disciplines, as they do not perform well at high speeds.
Horses with PSSM1 experience abnormal glycogen storage in muscle tissue. Glycogen is a complex carbohydrate that serves as a primary storage form of energy for muscle cells in horses. It can be broken down into glucose during exercise when the body needs energy to fuel muscle contraction.
PSSM1 is caused by a mutation in the glycogen synthase gene, which leads to continuous glycogen production in the horse’s muscles. This results in difficulty for the horse when switching to burning glycogen for energy during exercise. 
Affected horses may exhibit stiffness, muscle cramping and soreness following light exercise due to impaired energy generation in their muscles. Some horses with this condition show increased insulin sensitivity, which further contributes to glycogen storage in the muscles.
The abnormal glycogen storage in PSSM1 also makes the muscles more susceptible to damage, increasing the risk of ER following exercise.
In severe cases, horses should be tested for Malignant Hyperthermia (MH), another genetic condition. The presence of both MH and PSSM1 can exacerbate ER symptoms, which may be fatal. 
Type 2 Polysaccharide Storage Myopathy
Type 2 Polysaccharide Storage Myopathy (PSSM2) is another muscle disorder in horses that also results in abnormal glycogen storage, potentially contributing to chronic ER.
While PSSM2 shares some similarities with PSSM1, the conditions involve distinct mechanisms.  PSSM2 is characterized by muscle atrophy (muscle loss) and is linked to an as-yet unidentified genetic mutation. 
While PSSM1 can be diagnosed with a DNA test, there is currently no genetic test available for PSSM2. Diagnosis requires a muscle biopsy to identify hallmark cellular abnormalities under examination with a microscope.
PSSM2 leads to weakened muscles, making them more susceptible to damage and breakdown during physical activity, thereby increasing the risk of ER. 
Recurrent Exertional Rhabdomyolysis
Recurrent Exertional Rhabdomyolysis (RER) is a condition characterized by repeated episodes of muscle contractions and pain during and after exercise. Unlike sporadic cases of ER that might occur due to overexertion or dietary imbalances, RER is a chronic condition that can affect horses even under regular training conditions.
In horses with RER, abnormal calcium regulation disrupts these processes, leading to uncontrolled muscle contractions and stiffness. RER episodes are often triggered by stress or intense exercise and require careful management to minimize recurrence.
Risk factors for RER in horses include:
- Breed: Thoroughbred racehorses are particularly susceptible to RER, with 5-10% experiencing the condition during the racing season. Horses that have repeated ER episodes are typically diagnosed with RER. 
- Sex: Female horses have a higher prevalence of RER compared to males, with 67% of affected horses being mares compared to 33% stallions and geldings. 
- Work: Affected horses are typically around 2 years old at the time of diagnosis and actively in race training. 
- Temperament: Horses with a calm demeanor have a lower risk of RER. Nervousness and excitement during training can contribute to muscle damage in horses with RER. 
Understanding How Muscles Work
In order to understand how RER affects horses, it is important to first understand how muscles function normally in the horse’s body.
Skeletal muscle is a type of muscle tissue that is attached to bones by tendons and is responsible for facilitating movement of the body. These muscles are under voluntary control, meaning that their activity is consciously controlled by the horse’s nervous system.
Through repeated bouts of exercise and training, skeletal muscles grow bigger and stronger, adapting to the demands placed on them.  Horses with larger muscles have greater potential power output, meaning their muscles are able to generate more forceful contractions during exercise. This contributes to the horse’s overall performance in activities such as running and jumping.
Movement is facilitated by tendons, which are tough bands of tissue that connect muscles to bone.  When a muscle contracts, it pulls on the tendon, which then transmits the force to the attached bone, causing movement at the joint. 
In natural movements, such as walking or galloping, the muscle-tendon complex goes through a continuous cycle of stretching (eccentric contraction) and shortening (concentric contraction) to produce coordinated motion.  This cycle is known as the stretch-shortening cycle (SSC) and plays a crucial role in equine locomotion.
Muscle contractions involve a complex interplay between the nervous system and muscle fibers to generate movement: 
- Signal Initiation: Movement begins with a signal from the brain sent via the nervous system to the muscle fibers, instructing them to contract.
- Muscle Contraction: The signal causes calcium ions (Ca2+) to be released within the muscle cells, initiating the sliding filament mechanism. Actin and myosin filaments within the muscle fibers slide past each other, shortening the muscle and generating force.
- Force Transmission: The force generated by the muscle contraction is transmitted through the tendon to the bone.
- Joint Movement: As the tendon pulls on the bone, the bone moves relative to the joint, creating movement such as flexion, extension, abduction, or adduction.
- Muscle Relaxation: When the contraction signal stops, calcium is pumped back into storage, and the muscle fibers relax, allowing the muscle-tendon-bone unit to return to its initial position.
Horses with RER
The exact cause of RER in horses is not fully understood, but it is believed to result from an abnormality in the regulation of calcium levels within muscle cells. This may lead to an excessive release of calcium ions (Ca2+) or impaired reuptake of calcium in the muscle cell following contraction.
This dysregulation could result in prolonged or uncontrolled muscle contractions, contributing to muscle tissue damage and the characteristic symptoms of tying-up observed in ER.
Stress is believed to exacerbate the issues with abnormal calcium regulation, disrupting the normal function of muscle cells and leading to episodes of muscle damage. 
Diagnosing ER in horses involves a combination of veterinary evaluation, assessing patient history and conducting specific diagnostic tests. Your veterinarian will assess your horse for clinical signs including myoglobinuria (dark urine), muscle stiffness and pain after exercise.
They will also perform blood tests to look for moderate to high increases in muscle enzyme levels, including serum CK and AST.
A differential diagnosis involves evaluating potential causes of clinical signs by considering factors such as medical history, physical examination findings, and diagnostic tests to identify the most likely explanation for the observed symptoms.
Horses experiencing an ER episode may have symptoms that mimic the following conditions:
- Colic: Horses with ER may show signs similar to colic, including distress, discomfort, and restlessness. Symptoms including sweating, increased heart rate, and pawing can resemble abdominal discomfort often seen in colic cases. 
- Laminitis: Horses with ER may exhibit signs of lameness or reluctance to move due to muscle soreness and stiffness. These symptoms could be confused with laminitis, which also presents with lameness and changes in gait. 
- Lameness: Horses with ER may display signs of discomfort, stiffness, pain and reluctance to bear weight, which can be signs of lameness. 
- Other Exertional Myopathies: Horses suspected of having ER should also be evaluated for related conditions including, but not limited to, malignant hyperthermia and myofibrillar myopathy. 
- Hyperhidrosis (excessive sweating): In mild cases of ER, horses might display profuse sweating post-exercise, which could be misinterpreted as a normal response to physical activity if other signs are not readily apparent. 
Blood tests can measure specific enzymes present in a horse’s tissues, which serve as indicators of muscle damage and aid in diagnosing ER.
Creatine kinase is an enzyme that plays a role in energy production within the horse’s muscle cells. Found in high concentrations in skeletal, smooth and cardiac muscles, CK facilitates the transformation of creatine phosphate and ADP (adenosine diphosphate) into creatine and ATP (adenosine triphosphate). 
ATP is the primary energy currency of the cell, providing the necessary power for muscle contractions and other cellular activities. 
Strenuous exercise can damage muscle cells, making their cell membrane more permeable. This allows CK to be released into the bloodstream, resulting in elevated plasma CK levels, peaking around 4-6 hours post-exercise.
When a blood sample is taken after an episode of ER, CK serves as a valuable indicator of the extent of muscle damage experienced during the exercise.
Aspartate Transaminase is an enzyme that plays a critical role in amino acid metabolism, which is essential for various cellular processes. AST is found in various tissues in the horse’s body, including skeletal, liver and cardiac muscle. 
Like creatine kinase, AST is released into the bloodstream when muscle cells are stressed or damaged, such as following intense or prolonged exercise. High AST levels in a horse can support a diagnosis of ER.
Lactate dehydrogenase (LDH)
Lactate dehydrogenase, or LDH is another enzyme found in various body tissues, including muscles and the liver. LDH is important for anaerobic energy metabolism, particularly in the conversion of lactate to pyruvate. 
Elevated levels of LDH in blood work indicate muscle damage or injury, as LDH is released into the blood when muscles are damaged.
If your horse is showing signs of tying-up, your veterinarian may order a urinalysis test to examine the urine for markers of muscle damage. This test evaluates the urine for several factors, including color, to assess kidney function and detect any electrolyte imbalances. 
Urinalysis is a valuable diagnostic tool in identifying ER. Muscle damage from ER causes the release of various cellular components into the bloodstream, some of which are filtered by the kidneys and excreted in the urine.
Myoglobinuria in horses refers to the presence of myoglobin, a muscle protein, in the urine. Damaged muscle cells release myoglobin into the bloodstream, leading to its excretion in the urine.  The presence of myoglobin gives urine a dark, reddish-brown color.
Elevated levels of myoglobin in blood can precipitate, or form solid deposits, within renal tubules in the kidneys. Renal tubules play a crucial role in filtering and processing urine.
Horses with severe ER may excrete substantial amounts of myoglobin in the urine, leading to tubular degeneration. This can impair the normal functioning of the kidneys, potentially contributing to kidney dysfunction and, in severe cases, acute renal failure.
A muscle biopsy involves the collection of a small sample of muscle tissue from the affected horse for examination under a microscope. This procedure is typically performed on the gluteal or hamstring muscles under local anesthesia. 
Following collection, the muscle sample undergoes microscopic examination to evaluate the structure of muscle fibers, identify signs of inflammation, degeneration, or necrosis, and detect any abnormal glycogen accumulation.
Muscle biopsies are important for distinguishing between sporadic ER, chronic ER, PSSM and other myositis conditions. A biopsy ensures your veterinarian can tailor treatment and management based on the specific findings observed in the tissue sample. 
Horses experiencing repeated ER episodes may undergo genetic testing for PSSM1. This condition is caused by a mutation in the glycogen synthase-1 gene, resulting in abnormal glycogen storage within muscle cells. 
Horses with PSSM2 can also experience ER episodes, but will not test positive on a genetic test. The exact gene responsible for PSSM2 is currently unknown, requiring more research.
The treatment for ER in horses focuses on managing the acute phase of tying-up episodes and addressing underlying cause.
When a horse shows signs of an ER episode, immediately stop exercise and move the horse to a quiet stall with plenty of fresh water and plain loose salt. Enduring adequate hydration is important to flush myoglobulin and other byproducts of muscle breakdown from the kidneys.
Imbalances in electrolyte minerals, such as potassium, calcium, and phosphate, are common in rhabdomyolysis and need to be corrected. This may require supplements or medications depending on the specific imbalances.
Your veterinarian may recommend administering muscle relaxants, sedatives, analgesics or NSAIDs (non-steroidal anti-inflammatory drugs) to control muscle contractions and alleviate pain.  Consult with your veterinarian before giving any medication to your horse.
Affected horses should be placed on stall rest, with restricted access to turnout or physical activity to aid in their recovery. They may be allowed supervised, regular access to a paddock or be taken for hand-walking sessions.
It is important to monitor muscle enzyme levels in the blood throughout the recovery period. Stall rest should be maintained until these levels have returned to normal.
For chronic cases of ER, veterinarians may prescribe medications to alleviate symptoms and manage the condition.
Dantrolene is a medication primarily used to treat conditions involving muscle spasticity or rigidity. It works by blocking the release of calcium from the muscle cell’s storage sites, a key step in muscle contraction. 
By inhibiting calcium release, dantrolene can help relax muscles and prevent episodes of tying-up. For horses suffering from RER, dantrolene can be administered at a dosage of 4 mg/kg body weight, under the direction of a veterinarian.
Phenytoin is an anticonvulsant medication originally used to treat seizures and epilepsy in humans. It helps regulate electrical activity in the brain to control seizure symptoms. 
In horses, Phenytoin has been explored as a potential treatment for ER due to its ability to modulate the activity of sodium and calcium channels in muscle and nerve tissues. These channels are crucial for the transmission of electrical signals and the regulation of cellular functions, including muscle contraction.
Phenytoin should only be used under a veterinarian’s guidance to ensure the correct dosage, administration and monitoring based on the horse’s condition and medical history.
Proper nutrition is important for recovery from ER episodes and the ongoing management of the condition.  Ensure that your horse’s diet is well-balanced and has no deficiencies in essential vitamins, minerals and amino acids.
These nutrients are important for muscle repair, metabolic function, electrolyte status, kidney function, tissue healing and the immune system.  Deficiencies in vitamins and minerals could slow down the recovery from bouts of ER and prolong the time it takes to return to performance.
Following an ER episode, horses should be provided with a forage-based diet fortified with a complete vitamin and mineral supplement. Eliminate grains from the diet to reduce sugar and starch intake, and feed a fat supplement if additional energy is required.
It is recommended to work with your veterinarian and an equine nutritionist to ensure your horse’s diet is properly balanced. While on stall rest, your horse will need to reduce their calorie intake to prevent weight gain.
Horses may benefit from additional antioxidant supplementation to protect muscle cells from damage caused by oxidative stress. Increasing selenium and vitamin E in the diet can support muscle health in affected horses.
Prevention & Management
The long-term management of horses with chronic ER involves careful attention to exercise routines, appropriate feeding programs, and regular veterinary check-ups to monitor the condition. Following these steps can help to prevent episodes of tying-up and maintain optimal health and performance over time.
Intense bouts of exercise without proper conditioning or warm-up can trigger episodes of tying-up. Work with your veterinarian and trainer to implement an appropriate training regimen for your horse. 
- Fitness level: Gradually increasing a horse’s fitness can prevent overexertion, reducing the risk of muscle strain and recurrent ER episodes. Proper conditioning supports muscle function and minimizes stress-related damage. 
- Warm-up: Warming up a horse prior to exercise helps improve readiness of muscles, tendons and ligaments. A proper warm-up increases blood flow to the muscles, making them more flexible and responsive, reducing the likelihood of muscle damage.
- Cool-down: A thorough cool-down routine after exercise helps the horse’s body temperature and heart rate return to normal, reducing muscle damage and heat intolerance. A cool-down period also aids in relaxation and supports the clearance of metabolic byproducts from the muscles, reducing soreness, stiffness, and lowering the likelihood of ER.
Your trainer may recommend using a hot walker before and after exercise.  A hot walker is a mechanical device used to exercise horses by walking them in a circular pattern.
Hot walkers are commonly used in training facilities, boarding barns, and rehabilitation centers to provide horses with structured exercise sessions without the need for a rider. They are especially useful for warming up or cooling down horses before or after training sessions, as well as for conditioning and maintaining fitness levels.
Avoid Days Off Exercise
Historically, tying-up was referred to as “Monday Morning Disease“. This name originated from the early 20th century when draft horses, used extensively for heavy work throughout the week, often experienced episodes of muscle stiffness and pain when returning to work after a period of rest.
These episodes typically occurred on Mondays, reflecting the abrupt transition from rest to strenuous activity after a period of inactivity over the weekend.
Horses with chronic ER should be turned out daily in large paddocks to keep them active. Consistent exercise helps maintain muscle tone and conditioning, improving resistant to physical stress.
Consistent exercise also helps regulate blood sugar levels and improves metabolic function, reducing the risk of imbalances that can contribute to ER. 
Research shows that stress and “hot” behavior in horses can increase the risk of ER episodes.  To combat this, ensure your horse is in a low-stress environment and implement management practices that closely mimic the natural lifestyle of horses, allowing for species-appropriate behaviors.
You can reduce your horse’s stress level by providing ample turnout time in an appropriate social grouping, maintaining consistent routines, and minimizing exposure to stressors such as loud noises or unfamiliar surroundings.
Whenever possible, avoid long periods of stall confinement and give your horse enough exercise to prevent boredom and excess energy.
Horses with chronic ER thrive on diets consisting of mid-maturity grass hay, with minimal or no grains. Avoid high-sugar and high-starch commercial feeds, which can cause a rapid increase in blood glucose levels, leading to heightened excitability and nervousness in many horses. 
Forage should make up the bulk of the diet to support proper digestion and provide adequate fiber. A typical mature horse is expected to consume 2% of their bodyweight in hay per day.
To prevent episodes of tying up, intake of hydrolysable carbohydrates (HC) should be restricted to less than 12% of the total diet.  Consuming a diet with higher levels of HC increases the risk of ER episodes in susceptible horses. 
To meet energy requirements, up to 20% of the horse’s calories can be supplied by fat sources. Fat provides cool calories and sustained energy release, while also reducing the risk of muscle dysfunction due to grain-based diets. Fat supplements such as rice bran, flax oil, or Mad Barn’s W-3 Oil are ideal for exercising horses.
Work with an equine nutritionist to ensure your horse’s diet is balanced and appropriate for their needs.
Selenium and vitamin E are especially important for maintaining the integrity of muscle cell membranes in exercising horses. Deficiencies in these nutrients can lead to muscle damage and serious diseases in horses.
Work with an equine nutritionist to determine if your horse could benefit from antioxidant supplementation to help manage ER.
Research shows that deficiencies in electrolytes are linked to ER episodes in horses.  Electrolytes are minerals that carry an electrical charge and are essential for various physiological processes in the body. They include sodium, potassium, chloride, calcium, magnesium, and phosphate.
Electrolytes help regulate fluid balance, maintain proper pH levels, support nerve function, and facilitate muscle contractions. During periods of intense exercise, horses lose electrolytes through sweat, making it crucial to replenish them to prevent dehydration, exercise intolerance, muscle cramping, and electrolyte imbalances. 
Supplementation with electrolytes is often necessary, especially in hot and humid conditions or during prolonged exercise, to support optimal performance and maintain overall health. Horses also need free-choice access to fresh water and loose salt to maintain adequate hydration.
Mad Barn’s Performance XL: Electrolyte is scientifically balanced to replenish the electrolyte minerals that horses lose through their sweat. Performance XL also provides antioxidants, such as vitamin E and vitamin C to support post-exercise care and muscle function. This supplement should be administered at a rate of 30 grams for every hour of exercise.
The prognosis for ER in horses varies depending on the severity of the condition, the underlying causes, and how well it is managed. In mild cases, where prompt treatment is initiated, horses can often recover fully and resume normal activities with appropriate management strategies in place.
In horses that experience a single episode of acute ER, muscles typically heal within 3-4 weeks, without significant lasting signs of damage. 
In severe cases, episodes of tying-up can cause muscle atrophy, requiring a longer recovery period of 2-4 months with proper care.
Once the acute episode resolves, horses can usually resume normal activity with adjustments to exercise, diet, and management to prevent future occurrences.
PSSM horses require additional dietary management to control clinical signs and prevent episodes of tying-up. Approximately 90% of PSSM1 horses maintained on a strict exercise schedule and diet experience very few or no ER episodes, indicating the effectiveness of managing this condition. 
- Exertional Rhabdomyolysis (ER), often referred to as “tying-up,” is a condition in horses caused by excessive muscle tissue breakdown after exercise, leading to muscle spasms, pain, and sometimes severe symptoms like colic or collapse.
- ER can be triggered by factors such as abrupt changes in exercise intensity, poor conditioning, and in some cases, a genetic predisposition.
- Diagnosing ER involves evaluating clinical signs, especially after intense exercise, and conducting laboratory tests to check elevated muscle enzyme levels such as creatine kinase and aspartate aminotransferase.
- Managing ER involves a combination of stall rest, hydration, dietary adjustments, and gradual exercise conditioning. For chronic cases, specific treatments based on the underlying cause may be necessary.
- Consult a veterinarian if you suspect your horse is affected by ER. Your veterinarian can provide an accurate diagnosis, determine a treatment plan, and help you minimize the risk of recurrence.
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