Nutritional Articles

All tied up: metabolic factors and nutritional management of equine exertional rhabdomyolysis by Meghan Waller and Amanda Waller

Published: 2008-06-25

Introduction
Commonly clumped together under the broad term of ‘tying-up’, equine metabolic muscle disorders are one of the most misunderstood afflictions within the horse world. In the broad sense, tying-up refers to overall muscle stiffness or weakness in the horse, often paired with excessive sweating, increased heart rate or dark urine. Generally thought to be caused by the single factor of lactic acid buildup, ‘tying-up’ can have many causes and instigators, with various levels of severity. Few other diseases within the horse community have generated so many theories on its causes and the success of various treatments only deepens the confusion.

It is now known there are various forms of muscle disorders broadly termed under exertional rhabdomyolysis (ER). Although the factors of the disease are still being investigated, certain specific forms of metabolic muscle disorders have been defined. Across all forms of this disease, nutrition plays a crucial role in the treatment and prevent of muscle disorders

Symptoms
Rhabdomyolysis is defined as the destruction or degeneration of muscle tissue (Macleay et al., 1999). Within the horse, clinical signs of exertional rhabdomyolysis relate to muscle pain and stiffness, generally occurring at the beginning of exercise or a few hours after a strenuous workout. The most common site of muscle stiffness and pain is the lumbar and sacral regions, including the gluteals (McKenzie, 2003). This can be accompanied by excessive sweating, shallow breathing or rapid heartbeat. In severe cases, horses may refuse to move and excrete darkened urine due to excess myoglobin being released from the damaged tissue. These symptoms can vary from minimal, acute stiffness to extreme muscle necrosis and myoglobinuria due to renal failure (McKenzie, 2003). To confirm ER, a blood sample is taken to test the serum levels of creatine kinase (CK) and aspartate transaminase (AST). If muscle cells are damaged, within hours AST and CK are released into the bloodstream, elevating serum levels.

Pathophysiology of exertional rhabdomyolysis
There are two main types of ER, affecting different breeds and types of horses, however both disorders result in similar symptoms and treatments. Polysaccharide storage myopathy (PSSM) is most common in heavily muscled, colder blooded breeds, such as Draft and Quarter Horses, or descendants of these breeds, such as Warmbloods, Paints and Appaloosas (Valberg et al., 1993). PSSM is a glycogen storage disorder, caused by the intramyocellular accumulation of abnormal mucopolysaccharide. Muscle glycogen concentrations can increase two to four-fold in affected horses and intra-cellular glycogen levels may also increase (de la Corte, F. et al, 1999) PSSM has been defined as an autosomal recessive disease, traced back to three specific Quarter Horse stallions, however many environmental factors play a role in onset and treatment. Symptoms of PSSM include sweating, stretching out as if trying to urinate, involuntary muscle contractions or twitching and repeated pawing or rolling after exercise (Valberg and McKenzie, 2005).

The other type of ER is recurrent exertional rhabdomyolysis (RER), most commonly affecting hot blooded breeds such as Thoroughbreds, Standardbreds and Arabians. RER is usually stress induced and most cases are found in horses described as having nervous temperaments. Unlike PSSM, RER appears to be a disruption in the muscle contraction due to excitation or exercise in susceptible horses. Similar to malignant hyperthermia in humans, the threshold for contracture is much lower in RER horses than normal. When calcium is released from the muscle storage sites it is immediately taken back up again, altering the contraction and relaxation of the muscle. The immediate reuptake of calcium allows for extremely small concentrations of intramuscular calcium to have a profound affect on contracture, resulting in muscle spasms, stiffness, weakness and elevated levels of serum CK and AST (Valberg et al., 2000).

The role of fat and carbohydrates
Although both types of exertional rhabdomyolysis have varying etiologies, nutrition remains a key piece of the puzzle in both the treatment and prevention of these muscle disorders. Primarily, episodes of rhabdomyolysis can be significantly minimized by decreasing the amount of soluble carbohydrate in the feed, such as the removal of sweet feed or molasses from the diet. Further evidence is now indicating that diets not only low in starch, but also high in fat can maximize beneficial results in the management of both conditions.

Quarter horses and other breeds affected by PSSM have increased insulin sensitivity, as indicated by the ability to rapidly metabolize blood glucose after the feeding of grain or the injection of intravenous glucose (de la Corte, F. et al, 1999). Affected horses also had lower resting insulin concentrations after intravenous or oral administration of glucose. This enhanced sensitivity is a contributing factor to the excessive muscle glycogen storage. Diets high in starches or sugars promote the expression of the disease, by supplying a substrate for glycogen synthesis. It is essential to the dietary management of PSSM to restrict hydrolysable carbohydrate, however there is also increasing evidence that the increase of fat in the diet also has a positive effect (Geor, 2005). Horses recovering from PSSM are most successful when fed the minimum amount of dietary energy to meet their requirements (Valberg and McKenzie, 2005). A change in diet alone is not sufficient as the horse must also be provided with adequate exercise and muscle rehabilitation.

The role of diet on the pathogenesis of RER is less definitive, although specific dietary changes produce beneficial results. Reduced starch intake and increased fat supplementation is shown to be advantageous in managing RER, however multiple studies have indicated the change in dietary ratio is only beneficial when overall caloric intake is high, about 28 – 30 Mcal DE per day for a 500 kg horse (Macleay, et al., 1999). When energy intake is low to moderate (20-22 Mcal DE/day/ 500 kg), diet composition has little effect on exercise-induced CK levels. These studies indicate that the effects of increased fat in RER horses’ diets may be due an indirect consequence of the exclusions of dietary starch when replaced by a higher fat intake, rather that a specific effect of fat (Valentine et al., 2001). It has been suggested that horses fed a higher calorie diet with increased starch are more excitable and susceptible to stress, increasing CK levels. This association is further demonstrated by lower resting heart rates and more subdued temperaments when the same horses are fed a lower starch, higher fat diet (Macleay, et al., 1999). Other speculations as to how a high fat diet benefits RER horses includes the modification of muscle membrane fatty acid composition, which results in a beneficial increase in inflammatory mediator production (de la Corte, F. et al, 1999). Rice bran has been shown to be an excellent choice for supplementation in cases of RER, mainly due to its high oil content of up to 22%. It also contains an excellent spectrum of fatty acids, comprised of almost 40% oleic acid as well as a good balance of linoleic and a-linolenic acids (Macleay et al., 1999). The ingestion of polyunsaturated fatty acids has been associated with the modification of muscle membrane fatty acid composition, which may cause increased production of inflammatory mediators (Geor, 2005). It is noted that rice bran may have an inverted calcium: phosphorus ratio. Phytates present in rice bran may lower calcium digestibility (Van Doorn et al., 2004). This should be considered when incorporating rice bran in the horse diet.

Other nutritional factors
In addition to changes in fat and carbohydrate composition of the diet as well as the overall decrease in dietary energy, there are other possible nutritional factors that may influence rhabdomyolysis. Increased oxygen utilized during extended bouts of exercise can lead to an increase in free radical production, which is believed to contribute to post-exercise stiffness and fatigue (Ji and Leitchtweis, 1997). Caused by the peroxidation of lipid membranes, cell damage is minimized by a cascade of free radical scavengers and antioxidants which include the selenium-dependent enzyme glutathione peroxidase and vitamin E.

Electrolyte supplementation has also been implicated in the treatment of both forms of ER. Some studies have indicated a low electrolyte clearance ratio in both potassium and chloride levels, although electrolyte dietary metabolism in ER horses does not appear to vary from normal horses (McKenzie et al., 2002). Lower muscle potassium concentrations can cause rhabdomyolysis in other species and compared to normally functioning animals, the dry muscle weight potassium concentrations were lower in ER susceptible horses (Beech et al., 1993). In other electrolyte studies, Thoroughbreds were administered furosemide and sodium bicarbonate to develop lowered plasma calcium, magnesium, chloride and potassium concentrations. The subsequent serum CK activity matched that of a typical RER case, indicating electrolyte imbalances are a possible instigator of ER (Beech et al., 1993). A balanced electrolyte supplementation has also shown marked improvements in ER horses of varying breeds, suggesting that an electrolyte supplement mimicking the horse’s natural ratio of calcium, magnesium, chloride and potassium would be beneficial in the treatment and prevention of rhabdomyolysis. Occasionally, sodium bicarbonate is prescribed to help prevent exercise related rhabdomyolysis, however numerous studies indicate that dietary supplementation with sodium bicarbonate appears to have no beneficial effect on RER specifically and could possibly cause further damage due to altered acid-base balance or electrolyte ratios. The only instance in which sodium bicarbonate should be used to treat muscle disorders is when the urine remains acidic despite fluid therapy, as the excess myoglobin in the urine is significantly more nephrotoxic to the animal when present in acidic urine (McKenzie et al., 2003) .

Conclusion
Exertional rhabdomyolysis is a complicated and often misunderstood variety of muscle disorders with genetic and environmental factors. There is no one solution to the prevention or maintenance of these diseases, however the proper understanding of the nutritional and metabolic factors involved allows for the successful management and overall health and performance of the affected horse.

About the authors
Meghan is a veterinary assistant for McKee-Pownall Equine Services, which has several sport horse veterinary clinics throughout Ontario Canada. Amanda is a PhD candidate in equine exercise physiology at the University of Guelph (Guelph, ON, Canada).

References
- Beech, J., Lindborg, S. and Braund, K. (1993). Potassium concentrations in muscle, plasma and erythrocytes and urinary fractional excretion in normal horses and those with chronic intermittent exercise-associated rhabdomyolysis. Res. Vet. Sci. 55: 43-51

- de la Corte, F., Valberg, S and Macleay, J. (1999). Glucose uptake in horses with polysaccharide storage myopathy. Am. J. Vet. Res. 60: 1390-1395

- Geor, R. (2005) Role of dietary energy source in the expression of chronic exertional myopathies in horses. J. Anim. Sci. 83(E. Suppl.): E32–E36

- Ji, L. and Letchtweis, S. (1997). Exercise ans oxidative strees: sources of free radicals and their impact on anti-oxidant systems. Age. 20: 91-106

- Macleay, J., Valberg, S., Pagan, J. and Gustavsson, B. (1999) Effectof diet on Thoroughbred horses with recurrent excertional rhabdomyolysis. Equine Vet. J. 30: 458-462

- McKenzie, E., Valberg, S. and Godden, S. (2002) Plasma and urine electrolyte and mineral concentrations in Thoroughbred horses with recurrent exertional rhabdomyolysis after consumption of diets varying in cation-anion balance. AJVR. 63 (7)

- McKenzie, E., Valberg, S. and Godden, S. (2003) Effect of Dietary Starch, Fat, and Bicarbonate Content on Exercise Responses and Serum Creatine Kinase Activity in Equine Recurrent Exertional Rhabdomyolysis. J. Vet. Intern. Med.17:693–701

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- Valberg, S. and McKenzie, E. (2005) Nutritional management of exertional rhabdomyolysis: feeding fat to manage muscle disorders. In: E. Robinson (Ed.) Current Therapy in Equine Medicine 5: 169-179

- Valentine, B., Van Saun, R., and Thompson, K. (2001). Role of dietary carbohydrate and fat in horses with equine polysaccharide storage myopathy. J. Am. Vet. Med. Assn. 219:1537-1544

- Van Doorn, D.A., Everts, H, Wouterse, H and Beynen, A.C.(2004). The apparent digestibility of phytate phosphorus and the influence of supplemental phytase in horses. J. Anim. Sci. 82: 1756-1763.