Exertional rhabdomyolysis

Hereditary deficiency of LDH-B was first reported by Kitamura et al. in 1970 (K21). Since then, this enzyme deficiency has been discovered in at least five families in Japan. There were no clinical symptoms in these cases. On the other hand, LDH-A deficiency was associated with an exertional rhabdomyolysis and myoglobinuria after severe exercise (K15). One Japanese and one Italian with LDH-A deficiency showed the typical skin rash. To date, nine LDH-A variants have been analyzed at the molecular level, and four missense mutations, one nonsense mutation, one frameshift mutation due to a single base insertion, and three gene deletions have been elucidated (K16, M5). Missense mutations have also been identified in LDH-B deficiency (M6). 

In 1910, Meyer-Betz reported the first published case of acute renal failure with muscular pain, weakness, and dark urine after intense exercise [5]. In 1960, Howenstine reported that this type of acute renal failure was exercise-related myoglobinuria [6], However, at this time, it was impossible to distinguish hemoglobin from myoglobin, and this type of acute renal failure was considered to be a type of heat stroke. However, in 1970, Jackson [7] reported that this disorder was exercise-related renal failure and muscle damage, and this publication led to a gradual increase in research interest in myoglobinuric acute renal failure. In 1972, Hamilton et al. [8] and Knochel [9], respectively, reported that similar cases were exertional rhabdomyolysis. Matsumoto et al.[10] first reported this disorder in Japan in 1976. 

ALPE is different from exertional rhabdomyolysis (myoglobinuric acute renal failure). 

The treatment of acute episodes of exertional rhabdomyolysis is aimed at alleviating pain and muscle contracture, correcting electrolyte and/or body fluid deficiencies and addressing renal dysfunction, if present. Horses with chronic problems typically benefit more from preventative management strategies, such as the combination of a diet low in carbohydrates (concentrates) with increased daily exercise (compared with stall confinement). Supplementation of horses with fats, in the form of corn oil or rice bran, has shown considerable promise. 

Few drugs have been evaluated scientifically for their efficacy in preventing episodes of rhabdomyolysis in susceptible horses. Similarly, there are no anecdotal reports of a single therapy that prevents exertional rhabdomyolysis in all horses, and many combinations of pharmaceuticals and nutraceuticals have been employed with varying degrees of efficacy. In a recent survey, 59 thoroughbred racehorse trainers used 27 different... 

In Thoroughbred racehorses, dantrolene has been described as having a preventative or limiting role in episodes of exertional rhabdomyolysis, although the ryanodine receptor functions normally in these horses (Klein 1989, Ward et al 2000). It has also been used in draft horse breeds prior to anesthesia to try and reduce the frequency of anesthetic / recumbency-related rhabdomyolysis (Klein 1989). 

To prevent exertional rhabdomyolysis, dantrolene can be administered orally to horses at 2-5 mg/kg, 60-90min prior to exercise (Robinson 1987). Dantrolene has also been used to prevent myositis by giving an oral dose of 10 mg/kg 60-90 min prior to the induction of anesthesia. This is sufficient to produce peak concentrations during surgery that will be sufficient for a 2 h surgical procedure. If additional time is needed, an additional dose can be administered i.v. at 1.9-4mg/kg to provide therapeutic levels for 20min to 2h, respectively (Court et al 1987). 

Phenytoin is not used commonly in horses. It has been used to manage seizures and has been recommended for use in horses with chronic exertional rhabdomyolysis (Beech et al 1998) with... 

Lentz L R, Valberg S J, Balog E M et al 1999 Abnormal regulation of muscle contraction in horses with recurrent exertional rhabdomyolysis. American Journal of Veterinary Reseach 60 992-999... 

MacLeay J M, Valberg S J, Sorum S A et al 1999a Heritability of recurrent exertional rhabdomyolysis in... 

Epidemiologic analysis of factors influencing exertional rhabdomyolysis in thoroughbreds. American Journal of Veterinary Research 60 1562-1566 Miller R D 1995 Skeletal muscle relaxants. In Katzung B G (ed) Basic and clinical pharmacology. Appleton Lange, Norwalk, NJ, pp. 404-418... 

St Louis, MO, pp. 1489-1518 Valberg S J, Geyer C, Sorum S A et al 1996 Familial basis of exertional rhabdomyolysis in quarter horse-related breeds. American Journal of Veterinary Research 57 286-290... 

Valberg S J, Mickelson J R, Gallant E M et al 1999 Exertional rhabdomyolysis in quarter horses and thoroughbreds one syndrome, multiple aetiologies. Equine Veterinary Journal Supplement 30 533-538... 

Valentine B A, Hintz H F, Freels K M et al 1998 Dietary control of exertional rhabdomyolysis in horses. Journal of the American Veterinary Medical Association 212 1588-1593... 

Hildebrand S V, Arpin D, Cardinet G III 1990 Contracture test and histologic and histochemical analyses of muscle biopsy specimens from horses with exertional rhabdomyolysis. Journal of the American Veterinary Medical Association 196 1077-1083 Hubbell J A, Bednarski R M, Muir W W 1989 Xylazine and tiletamine-zolazepam anesthesia in horses. American Journal of Veterinary Research 50 737-742 llkiw J E, Haskins S C, Patz J D 1991 Cardiovascular and respiratory effects of thiopental administration in hypovolemic dogs. American Journal of Veterinary Research 52 576-580... 

In contrast to the typical effects of hypocalcemia, hypokalemia may cause myasthenia and flaccid paralysis of muscle because potassium is a critical activator of intermediary metabolism. Potassium is also critical for vasodilation in muscle during exercise, so hypokalemia may cause exertional rhabdomyolysis. Hypokalemia may be produced by potassium-losing diuretics and secondary to hypomagnesemia (Scola et al. 2007). 

Fibrate monotherapy of hyperlipidemia may predispose to rhabdomyolysis with acute renal insufficiency. Patients using fibrates should be cautioned regarding strenuous exertion, dehydration, and the need for prompt evaluation of myalgia. 

Tenamfetamine ( ecstasy, MDMA methylenedioxymethamphetamine) is structurally related to mescaline as well as to amphetamine. It was originally patented in 1914 as an appetite suppressant and has recently achieved widespread popularity as a dance drug at rave parties (where it is deemed necessary to keep pace with the beat and duration of the music popular names reflect the appearance of the tablets and capsules and include White Dove, White Burger, Red and Black, Denis the Menace). Tenamfetamine stimulates central and peripheral a-and p-adrenoceptors thus the pharmacological effects are compounded by those of physical exertion, dehydration and heat. In susceptible individuals (poor metabolisers who exhibit the CYP450 2D6 polymorphism) a severe and fatal idiosyncratic reaction may occur with fulminant hyperthermia, convulsioirs, disseminated intravascular coagulation, rhabdomyolysis, and acute renal and hepatic failure. Treatment includes activated charcoal, diazepam for convulsions, P-blockade (atenolol) for tachycardia, a-blockade (phentolamine) for hypertension, and dantrolene if the rectal temperature exceeds 39°C. 

The mechanism of muscle damage with opiates is most hkely related to profound and prolonged compression of muscle with compromise of the regional vascular supply [107,109,113,118-120]. The presence of hypovolemia and hypotension may further contribute to the ischemic damage. There is a direct correlation between the duration of altered consciousness and the severity of the rhabdomyolysis. Moreover, there is no evidence for any major direct toxic effect of narcotics on muscle in the vast majority of addicts who present without coma or stupor. Trauma, exertion and seizures may contribute to the muscle damage in some patients. 

Pathological syndromes may result in muscular spasm, as seen in the exertional myopathies, or weakness, as seen in hyperkalemic periodic paralysis (HYPP). Similarly, infectious diseases may result in muscular rigidity (C. tetani infection (tetanus)) or paralysis (C. botulinum intoxication (botulism)). Overt rhabdomyolysis may result from the ingestion of the coccidiostats monensin, rumensin and lasalocid, or one of a number of plant mycotoxins. Dietary deficiencies of selenium or vitamin E have also been described as having severe deleterious effects on skeletal muscle health. 

Shieh, S.D., Lin, Y.F., Lin, S.H. Lu, K.C. 1995. A prospective study of calcium metabolism in exertional heat stroke with rhabdomyolysis and acute renal failure. Nephron, 71, 428-432. 

Prolonged exercise at a high exertion level, which causes muscle damage and leads to a condition called rhabdomyolysis... 

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