Muscles

Hypoadrenocorticism
Addison's disease in dogs and cats often results in muscle weakness
presumed to be related to accompanying hyperkalemia. Muscle alterations have not been characterized.

Increased growth hormone exposure

Beagle dogs given exogenous porcine growth hormone had hypertrophy of types 1 and 2 fibers. However, skeletal muscle alterations
have not been described in dogs or cats with acromegaly.

Bibliography
Blot S, Fuhrer L. Myopathies in domestic carnivores. Part 2. Review of conditions.
Eur J CompanAn Pract1996:6:56-69.
Braund KG. Endogenous causes of myopathies in dogs and cats. Vet Med
1997:92:618-628.

Exertionat myopathies

influx of sodium with a decrease in resting membrane potential and

hypopolarization, altered glycogen metabolism in skeletal muscle
fibers, and ischemic injury from hypokalemia-induced vasoconstriction. Treatment with potassium supplementation is generally successful but the syndrome may recur unless supplementation is maintained.

Hypokatemia in cattle
In 1997, a hypokalemic syndrome with muscle weakness and myopathy was reported. Affected cattle were weak, recumbent, and were
unable to elevate their heads off the ground and instead held them
against their flanks.They were post-parturient and had moderate to
severe ketosis with hypokalemia (1.4-2.3 mEq/L).The animals were
treated with isoflupredone, a glucocorticoid with high mineralocorticoid activity.The skeletal muscle damage involved the hindlimbs
and included vacuolar degeneration, necrosis with macrophagic
infiltration, and variably present secondary ischemic injury.

Braund KG, eta[. Subctinica[ myopathy associated with hyperadrenocorticism in

the dog.Vet Patho[ 1980:17:134-148.
Cuddon PA. Feline neuromuscular disease. Feline Pract 1994:22:7-13.
Goedegebuure SA. Spontaneous primary myopathies in domestic mammals: A
review. Vet Quart 1987:9:155-171.
LeCouteur RA, eta[. Metabolic and endocrine myopathies of dogs and cats. Sem
Vet Med Surg (Smat[Anim)1989:4:146-155.
Moton-Nob[et S, eta[. Effect of chronic growth hormone administration in skeletal muscle in dogs.Tox Patho[1998:26:207-212.
Orre[[ RW, eta[. Muscle dysfunction in endocrine disease. In: Lane RJM, ed.
Handbook of Muscle Disease. New York: IVlarce[Dekker, 1996:365-378.
P[att SR. Neuromuscular complications in endocrine and metabolic diseases.Vet
C[in North Am Sma[[Anim Pract 2002:32:125-146.
She[ton GD. Differentia[ diagnosis of muscle diseases in companion animals.
Prog Vet Neuro[ 1991:2:27-33.

MYOPATHIES ASSOCIATEDWITH SERUM

ELECTROLYTE ABNORMALITIES

Hypernatremia in cats
Muscle weakness evident as ventroflexion of the neck has been
observed with hypernatremia and hypodipsia in the cat.

Hypophosphatemia in dogs
Muscle weakness occurs in dogs with hypophosphatemia. Necrosis
of skeletal muscle with myoglobinuria was present in severe acute
phosphorus depletion.

Bibliography
Braund KG. Endogenous causes of myopathies in dogs and cats. Vet Med
1997:92:618-628.
Edwards CM, Be[ford CJ. Hypoka[emic po[ymyopathy in Burmese cats. Aust Vet
Pract 1995:25:58-60.
Leon A, et aL Hypoka[emic episodic po[ymyopathy in cats fed a vegetarian diet.
Aust VetJ 1992:69:249-254.

Hypokatemia in cats

Fettman MJ. Feline katiopenic po[ymyopathy/nephropathy syndrome. Vet C[in

North Am Sma[tAnim Pract1989:19:415-432.

In 1984, a polymyopathy was identified in cats and in over half of the

affected animals, there was a coexisting hypokalemia. Subsequently,
a distinct syndrome of hypokalemic myopathy was characterized and the disorder was also termed feline katiopenic polymyopathynephropathy syndrome and sporadicfeline hypokalemic polymyopathy.
Clinically, the affected cats had generalized weakness, ventroflexion of the neck, a stiff stilted gait, exercise intolerance, reluctance to
walk, and muscle pain. Serum activity of skeletal muscle origin
enzymes (CK, AST) was elevated and serum potassium levels were
low (<3 rnEq/L). Hypokalemia was attributed to low dietary intake
or excessive renal loss. Low intake occurred in cats fed potassiumdepleted regular diets or high-protein vegetarian diets. Excessive
renal loss of potassium was present in cats with chronic renal disease
and in those fed acidic diets to prevent urolithiasis. Also, the syndrome reported in Burmese kittens 2-6 months of age with intermittent hypokalemia, is presumed to be heritable.
In general, the skeletal muscle lesions have been either mild or absent.
Lesions have been described as a polyphasic myopathy with concurrent
necrosis and regeneration.The skeletal muscle damage was attributed to

Knoche[ JR Skeletal muscle in hypophosphatemia and phosphorus deficiency.

Adv Exp Med Bio[ 1978:103:357-366.
Le Couteur RA, eta[. Metabolic and endocrine myopathies of dogs and cats. Sem
Vet Med Surg (Sma[[Anim)1989:4:146-155.
Sie[man ES, et aL Hypokatemia syndrome in dairy cows: 10 cases (1992-1996).
J Am Vet Med Assoc 1997:210:240-243.

EXERTIONAL MYOPATHIES
The term exertional myopathy is indicative of myofiber damage occurring due to exercise stress. Acute myofiber injury is precipitated by
exercise in a broad group of myopathies, including X-linked muscular dystrophy, nutritional myopathy, metabolic myopathies, malignant hyperthermia, and myopathy due to hypokalemia. In such
cases, the initiation of abnormal excitation-contraction coupling,
inadequate energy metabolism, ionic imbalance, or simply the
mechanical stresses occurring during contraction are thought to
lead to myofiber damage of predisposed muscle.

2 MUSCLEAND TENDON

Historically, the syndrome of passage of myoglobin-pigmented urine

(myoglobinuria) was recognized long before it was determined that
massive skeletal muscle necrosis (rhabdomyolysis) was the cause. Small
wonder that so many names exist for the varying manifestations of
exertional myopathy. In a broad sense, exertional myopathy has included
the group of diseases in which acute musclefiber necrosis is initiated by muscle activity of the major muscle groups but in which the underlying cause is
unknown or poorly understood. Such activity may be intensive or
exhaustive, but in susceptible individuals exertional myopathy may
occur with only minimal exercise. Continued research into causes
of exertional rhabdomyolysis is clearly warranted and, as is true of
equine exertional rhabdomyolysis (see below), may lead to better
understanding of causes and preventive measures.

Exertionat myopathy (rhabdomyotysis) in

the horse
Various manifestations of exertional myopathy have been recognized in horses for many, many years. T h e r e are numerous names
for the disorder, including azoturia (presumably named for nitrogen-containing compounds in the urine, and possibly related to the
resemblance of myoglobin to the red-purple azo dyes), black water,
paralytic myoglobinuria, Monday-morning disease, set fast, and tying up.
Various classifications have distinguished the disorder in heavy
h o r s e breeds that are p r o n e to severe and o f t e n life-threatening
muscle injury, particularly when worked after a day of rest and full
grain ration (hence the term Monday-morning disease), from the
o f t e n less severe disorder in light horse breeds. Muscle injury severe
enough to result in myoglobinuria, profound weakness, and recumbency is common in heavy horse breeds, hence the terms azoturia,
black water, and paralytic myoglobinuria. Exertional myopathy in
light horse breeds is typically less severe, resulting in episodic muscle
pain, sometimes associated with swelling, and reluctance to move,
h e n c e the names set fast and tying up. Given the recent recognition
of a metabolic myopathy leading to exertional rhabdomyolysis in
both heavy and light breeds (see below), it becomes clear that the
same underlying disorder can result in a spectrum of clinical signs.
It has long been suspected that the clinical disorder represents a
syndrome with multiple possible etiologies. It has been proposed
that exertional myopathy in the horse be classified as either sporadic exertional rhabdomyolysis or recurrent exertional rhabdomyolysis, with sporadic exertional rhabdomyolysis possible due to
muscle exhaustion or electrolyte depletion in any horse, and recurrent exertional rhabdomyolysis occurring in horses somehow predisposed to this disorder. Studies of serum activities of CK and AST
following exercise have shown, however, that subclinical exertional
myopathy is common in horses.As exertional myopathy can occur
without obvious clinical signs other than, perhaps, poor performance, it is possible that so-called sporadic cases really represent
recurrent disease, and therefore this classification is difficult to justify based on current knowledge of equine muscle disease.
Previously, etiologies proposed for equine exertional rhabdomyolysis have included muscle lactic acidosis, hypothyroidism, electrolyte imbalance, and vitamin E and/or selenium deficiency. Of
these, only electrolyte imbalance, in particular hypokalemia, is still considered possible. Extensive studies have shown that lactic acid levels in
the muscle of exercising horses prone to exertional rhabdomyolysis
are no different than those of control horses, removal of thyroid

Exertionat myopathies

glands results in poor cardiac output and performance without evidence of muscle damage, and vitamin E and selenium status varies
widely in affected horses. More recently, a metabolic myopathy
thought to involve abnormal starch and sugar metabolism (equine
polysaccharide storage myopathy, see the Metabolic myopathies section) has been shown to be the most common cause of exertional
rhabdomyolysis in many breeds of horses, including Quarter Horse,
Warmblood, draft, Arabian, Standardbred, Tennessee Walker,
Morgan, and Welsh pony-related breeds. It is possible that a similar
metabolic disorder is the cause of recurrent exertional rhabdomyolysis in Thoroughbreds, although this is controversial, with one group
reporting evidence for abnormal calcium handling in muscle fibers
of affected Thoroughbreds. Defective ryanodine receptor function
similar to malignant hyperthermia has not, however, been found in
affected Thoroughbreds.Whether the abnormal muscle contracture
testing reported in in vitro studies of muscle from Thoroughbreds
with recurrent exertional rhabdomyolysis is a primary or secondary
abnormality is still unknown. There is strong evidence that there is an
inherited basisfor the predisposition to exertional rhabdomyolysis in horses.
Both autosomal recessive and autosomal dominant inheritance have
been proposed, depending on the breed studied. Although further
studies are needed, it is now accepted that exertional rhabdomyolysis in
horses is most often due to underlying metabolic abnormalities of muscle
rather than simply due to poor management of diet and exercise.
Although diets high in starches and sugars (grains) are associated
with increased severity of exertional rhabdomyolysis, clinical signs
can still occur in horses fed only forage. Despite differing opinions
regarding cause, almost all horses with recurrent exertional rhabdomyolysis respond positively following a diet change to one that is high in fat, high
in fiber, and low in starches and sugars. Stall rest appears to exacerbate
the signs of equine exertional rhabdomyolysis, however the mechanism by which daily exercise benefits such horses is still unknown.
Weakness and~or pain in the hindlimbs occur suddenly, and the animal soon becomes unable or very reluctant to move. This may be
accompanied by sweating and generalized tremors. The affected
muscles, which are typically those of the gluteal, femoral, and lumbar
groups, may be swollen and board-like in their rigidity. Myoglobinuria
can appear early in the disease, causing dark red-brown discoloration of the urine. Severely affected horses become recumbent, a
sign that is often a prelude to death from myoglobinuric nephrosis
or problems associated with being down and attempting to rise.
Considerable variation occurs between cases as to the nature and
duration of the initiating exercise and severity of clinical signs.
Recovery from mild attacks in quiet animals may occur in a few
hours. Recovery from severe episodes may take days. But, if an animal continues to struggle and is unable to rise, death or euthanasia
is the most likely outcome. Atrophy of the gluteal muscles may be a
feature of recovery in moderate to severe cases. Exertional rhabdomyolysis occurs in both males and females, although females appear
to be predisposed. The activity of the ovarian hormones estrogen and
p r o g e s t e r o n e does not, however, appear to be directly related to
o n s e t of exertional rhabdomyolysis in females, and ovariectomy is
n o t an effective therapy.
The apparent pain and muscle swelling associated with many
cases of equine exertional rhabdomyolysis is curious, as muscle
necrosis per se is neither painful nor does it cause muscle swelling. It
is suspected that increased intramuscular pressure, perhaps exacerbated by
oxidative membrane injury, may causepainful muscle injury in this disorder.

Muscles

Exertionat myopathies
.........

This may explain the often-reported improvement obtained following vitamin E and selenium supplementation in affected horses.

Muscle fiber membrane injury leads to release of sarcoplasmic proteins,

most notably myoglobin, creatine kinase (CK), and aspartate aminotransferase (A ST). Serum activity of CK peaks at approximately 4-6 hours
post-injury and declines rapidly, with a half-life of approximately 6-10
hours.Therefore, if serum CK activity is not reduced by at least 50%
every 24 hours this is evidence of continued muscle injury. Serum
activity of AST increases more slowly, with a peak at about 48
hours post-injury and a very long half-life that can lead to persistent AST increases for days to weeks. The degree of CK and AST
increase does not, however, correlate with severity of clinical signs.
It is possible that muscle cramping or stiffness in the absence of
overt necrosis may occur in some horses.
Grossly visible changes in muscle may be inapparent. In severe
cases they are most obvious in the gluteal, lumbar, and caudal thigh
regions but lesions often are widespread. Muscles may be moist,

swollen, and dark, and streaks of pallor may be visible in the more extensively involved muscles. If ischemic complications occur, the muscles
also may show blotchy or linear hemorrhage. In animals that have
survived for 2-3 days, muscles may become paler and, although
edema may surround larger muscle divisions, the locally damaged
areas appear dry compared to normal muscle.

Necrosis affects primarily the strongly glycolyticfibers (type 2B glycolytic

and type 2A oxidative-glycolyticfibers; Fig. 2.87), in contrast to the primary involvement of type 1 oxidative fibers in the nutritional
myopathies. The timing and sequence of events are not clear, but

damaged fiber segments generally undergo hypercontraction and hyaline

degeneration (Fig. 2.88)followed by coagulative necrosis.Mineralization is
not typically seen. There is also potential for perpetuation of
myofiber injury due to release of free radicals from damaged membranes and subsequent oxidative membrane injury. This sequence of
events may reduce the capacity of muscle protein to hold water, consequently water is lost to the interstitial compartment where it raises
local pressure and predisposes to ischernia (compartment syndrome),

Figure 2.87 Equine exertional rhabdomyo|ysis with selective necrosis of type 2 (dark staining) fibers (arrow). Frozen section, ATPase, atkatine
preincubation. (Courtesy ofTJ Huttand.)

particularly if moderate muscle movement is continued (see

Circulatory disturbances of muscle). Oxidative injury to muscle capillary endothelium may also contribute to intramuscular edema and
increased pressure. Cardiac involvement is rare.

The early irreversiblefiber change as monitored by electron microscopy consists of myofibrillar waving and architectural loss, irregular mitochondrial
swelling, and inte~fibrillar edema. After 12h, more marked sarcomere
destruction occurs along with streaming of Z-bands. Histologically,
the lesions are characterized by scattered single or small groups of
necrotic fiber segments admixed with intact fibers. In the more severe,
acute tying-up cases, 1-5% of muscle fibers in a biopsy sample may be
affected. In the less severe cases, the amount of fiber damage involves
less than 0.2% of fibers in irreversible change but many more fibers
can undergo hypercontraction that is potentially reversible. If muscle
is examined days after injury, fiber regeneration will be apparent.
Lesions are often monophasic and multifocal, but can be polyphasic in
horses with repeated bouts of necrosis or on-going injury (Fig. 2.89).
In horses with polysaccharide storage myopathy, abnormal inclusions
of pale blue-gray complex polysaccharide may be seen within scattered myofibers on H&E stain (see Fig. 2.60). Inclusions may be
numerous or very rare, and have been shown to occur only within
type 2A and type 2B fibers. Inclusions stain intensely with periodic acidSchiff (PAS) for glycogen and resist amylase digestion. In severe chronic
cases, interstitial aggregates of complex polysaccharide-laden macrophages may be seen, indicative of previous necrosis of polysaccharideladen segments, and marked fatty infiltration is possible (see Fig. 2.60).
Subsarcolemmal aggregates of amylase-sensitive glycogen are also a
feature of this disorder, and may occur in the absence of complex
polysaccharide in some affected horses (see Fig. 2.62). Chronic myopathic changes, including excessive fiber size variation due to fiber
hypertrophy and atrophy and increased numbers of internal nuclei are
common. Given the high incidence of underlying equine polysaccharide storage myopathy in horses with histories of exertional rhabdomyolysis or postanesthetic myopathy (see below), PAS staining and

careful evaluation of musclefrom all such casesfor evidence of chronic myopathy and abnormal glycogen and complex polysaccharide storage is warranted.

Figure 2.88 Segmentat hypercontraction and acute necrosis in myofibers

in a horse with exertional rhabdomyolysis. (Courtesy ofTJ Huttand.)

2 MUSCLE AND TENDON

Exertionat myopathies

In racing Greyhounds, the disorder primarily affects longissimus,

quadriceps, and biceps femoris muscles. Affected dogs may display
distress and generalized muscle pain associated with a stiff gait.
Myoglobinuria can lead to death due to renal failure. In less severe
cases, myoglobinuria is not evident, and muscle pain may only be
mild to moderate. Similar to exertional rhabdomyolysis in horses,
affected muscles may be swollen as well as painful, indicative of
mechanisms besides simple muscle necrosis as a cause of pain and
swelling. Predisposing factors proposed include an excitable nature,

lack of physical fitness, hot and humid conditions, and overexertion of physically fit dogs. Gross lesions are not often seen in affected muscles,

Figure 2.89 Concurrent myofiber necrosis and regeneration in a horse

with recurrent exertionat rhabdomyotysis with episodes 12 days apart.
(Courtesy ofTJ Huttand.)

Other equine degenerative myopathies

In addition to nutritional myopathy and exertional rhabdomyolysis, degenerative myopathy can occur in horses recoveringfrom general anesthesia. This syndrome of postanesthetic myopathy has been
recognized most often in hea W horse breeds. Although experimental induction of hypotension during general anesthesia will cause
postanesthetic myopathy in any horse (see Circulatory disturbances
of muscle), recent studies of clinical cases indicate that many occur due
to underlying polysaccharide storage myopathy. Persistently high CK serum
levels can occur in horses with postanesthetic myopathy due to
polysaccharide storage myopathy, indicative of on-going muscle
injury occurring even after the horse has stood up. A form of
malignant hyperthermia has also been proposed as a cause of
anesthetic-related myopathy in horses. This may be appropriate for
those cases in which hyperthermia occurs during inhalant anesthesia, but most affected horses develop myopathy during recovery
rather than during anesthesia. Although such horses may develop
dangerously high body temperatures during recovery, this condition is best considered to be a hypermetabolic state rather than
malignant hyperthermia. Underlying myopathy of any type may be
a predisposing factor in horses that develop life-threatening hyperthermia either during or following general anesthesia.
Nutritional myopathy in horses causes a degenerative myopathy
(see Nutritional myopathy), as do various plant toxins and ionophores
(see Toxic myopathies).A myoglobinuric disease of pastured horses
has also been described in Britain, in which extensive myolysis is
triggered by an as yet unknown factor.

Exertionat myopathy in dogs

Exertional rhabdomyolysis is recognized as a syndrome affecting racing Greyhounds and racing sled dogs. Given the vast difference in type
of exercise (i.e., sprint vs endurance racing) in these two breeds of
dog, there are likely to be differing underlying etiologies.

although histopathologic evidence of acute degenerative changes is

found in susceptible muscles.
Racing sled dogs may undergo massive rhabdomyolysis during racing that can lead to sudden death.There is often selective involvement
of certain muscle groups; in one case studied there were moderate
to severe polyfocal and monophasic necrotizing lesions involving
quadriceps, psoas, deep digital flexor, and gastrocnernius muscles,
with sparing of triceps brachii, epaxial, and cranial tibial muscles.
Gross lesions are not typically seen, and sampling of multiple muscle
groups may be necessary to determine the extent of injury. It has
been suggested that prolonged endurance-type exercise leads to
increased lipid peroxidation and reduced plasma antioxidant concentrations, however vitamin E supplementation does not appear to
ameliorate exercise-induced muscle injury in racing sled dogs, and
pre-race plasma vitamin E levels do not appear to correlate with risk
of exertional rhabdomyolysis. As in horses, dietary management is
likely to play a role in canine exertional rhabdomyolysis, as a highfat and low-carbohydrate diet has been reported to reduce exerciseinduced muscle injury in these dogs.

Exertionat myopathy in other species

("capture myopathy")
Massive muscle injury associated with exertion reported in other
domestic animals such as sheep and cattle can occur due to overexertion. Underlying nutritional myopathy (see the section on Nutritional
myopathy) or metabolic myopathy (see the section on Metabolic
myopathies) is also possible. Of spedal interest is exertional myopathy occur-

ring in wild animals following capture and~or immobilization, an entity

known as"capture myopathy."First described in wild ungulates, this
disorder has been seen in multiple species, including wild ruminants,
captured otters, cetaceans, mustelids, canids, marsupials, and wild birds.
Clinically affected animals can exhibit dyspnea, weakness, muscle tremors
or muscle rigidity, hyperthermia, collapse, and, often, death. Thigh muscle
rupture may occur.Those that do not die acutely show myoglobinuria
and increased levels of muscle enzymes in the blood and may subsequently die of renal failure.When the animal is down, ischemic complications may be secondary (see Circulatory disturbances of muscle).
The muscle lesions are capable of more or less complete repair over a
few weeks unless infarction has intervened.
Capture myopathy is associated with stress to the affected animal, and increased circulating catecholamines may play a role, particularly
in the cardiac damage that can be seen. Hyperthermia and metabolic acidosis have also been associated with capture myopathy.
Extreme overexertion likely also contributes. In some cases, marginal selenium status or electrolyte abnormality such as hypokalemia
or hyperkalemia may be predisposing factors.

Musctes

Exertiona[ myopathies

(Fig. 2.90), and hemorrhagicstreaking is not uncommon. Degenerative

lesions in skeletal muscle are typically monophasicand polffocal. In most
cases, death occurs during the degenerative phase and therefore acute
myodegeneration, often with macrophage invasion of affected segments, is seen affecting various muscles (Fig. 2.91). Cardiac lesions,
when present, are most often acute, although animals that survive capture myopathy may die acutely at a later date due to myocardial fibrosis. Myoglobinuric nephrosis may be seen.

BibUography
Bartsch RC, et at. A review of exertionaL rhabdomyo[ysis in wild and domestic
animals and man. Vet Patho[ 1977;14:314-324.
Beech J. Equine muscle disorders 1: Chronic intermittent rhabdomyo[ysis. Equine
Vet Educ 2000;12:163-167.
BLoom BA, et aL Postanaesthetic recumbency in a Belgian filly with po[ysaccharide storage myopathy. Vet Rec 1999;144:73-75.
Btythe LL, et aL. MetaboLic disorders of racing greyhounds. In: AbiLene KS, ed. Care

Figure 2.90 Marked pallor of affected muscle (arrow)in bovine transport myopathy. (Courtesy ofTJ HuLLand.)

ofthe Racing Greyhound. Portland:American Greyhound Council 1994:267-274.

Frauenfe[der HC, et aL Changes in serum muscle enzyme LeveLsassociated with
training schedules and stage of the oestrous cycle in Thoroughbred racehorses. Equine VetJ 1986;18:371-374.
Freestone JE CaroLson GP. MuscLe disorders in the horse: a retrospective study
Equine VetJ 1991;23:86-90.
Gericke MD, HofmeyrJM. AetioLogy and treatment of capture stress and myopathy in springbok, Antidorcas rnarsupialis. S Afr J Sci 1976;72:28.
Harris R CoLles C. The use of creatinine dearance ratios in the prevention of
equine rhabdomyoLysis: a report of four cases. Equine VetJ 1988;20:459-463.
Harthoorn AM, Young E. A relationship between acid-base balance and capture
myopathy in zebra, Equus burchelli and an apparent therapy Vet Rec
1974;95:337-342.
Hartup BK, et aL. Exertionat myopathy in translocated river otters from New York.
J WiLdLife Dis 1999;35:542-547.
Hildebrand SV, et aL Contracture test and histo[ogic and histochemica[ analyses
of muscle biopsy specimens from horses with exertiona[ rhabdomyo[ysis.
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Hinchdiff KW, et at. Oxidant stress in sLed dogs subjected to repetitive endurance
exercise. Am J Vet Res 2000;61:512-517.
Kock MD, et aL Effects of capture on biobgica[ parameters in free-ranging bighorn
sheep (Ovis canadensis): evaluation of normaL, stressed and mortality outcomes
and documentation of postcapture survivat.J WiLd[ Dis 1987;23:652-662.
Lentz LR, eta[. Abnormal regulation of muscle contraction in horses with recurrent exertionaL rhabdomyoLysis. Am J Vet Res 1999;60:992-999.
Lewis RJ, et aL Capture myopathy in elk in ALberta, Canada: a report of three
cases. J Am Vet Med Assoc 1977;171:927-932.
LindhoLm A, et at. Acute rhabdomyoLysis ("tying-up") in Standardbred horses.
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Lindsay WA, et aL. Induction of equine postanesthetic myositis after haLothaneinduced hypotension. Am J Vet Res 1989;50:404-410.
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Figure 2.91 Extensive myofiber necrosis in a bighorn sheep with capture

myopathy. (Courtesy ofT Spraker.)

Thoroughbred racehorses. Am J Vet Res 1999;60:250-256.

Martin BB, et aL Causes of poor performance of horses during training, racing, or
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Gross and histologic lesions are often similar to those occurring

due to other causes of severe exertional myopathy. They may also

resemble those ofhyperthermia in pigs, with prominent muscle edema
in animals dying acutely. Muscles may contain indistinct pale streaks

McEwen SA, Hul[and TJ. Histochemica[ and morphometric evaluation of skeletal

muscle from horses with exertiona[ rhabdomyoLysis (tying-up). Vet PathoL
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Munday BL. Myonecrosis in free-living and recently-captured macropods.
J WitdL Dis 1972;8:191-192.

2 MUSCLE AND TENDON

Immune-mediated conditions

Peet RL, et aL. ExertionaL rhabdomyoLysis in sheep. Aust VetJ 1980:56:155-156.

Piercy RJ, et aL.Vitamin E and exertionaL rhabdomyoLysis during endurance sled
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creatine kinase and myogLobin changes with exercise in horses with recurrent exertionaL rhabdomyoLysis. Equine VetJ 1993;25:11-16.
VaLberg SJ, et at. FamiLiaLbasis of exertiona[ rhabdomyoLysis in Ouarter Horserelated breeds. Am J Vet Res 1996;57:286-290.
VaLberg SJ, et aL SkeLetaL muscLe metabolic response to exercise in horses
with "tying up" due to poLysaccharide storage myopathy Equine Vet J 1999:
31:43-47.

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VaLentine BA, et aL Severe poLysaccharide storage myopathy in BeLgian and

Percheron draught horses. Equine VetJ 1997;29:220-225.
VaLentine BA, et aL. MuscLebiopsy diagnosis of equine motor neuron disease and
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VaLentine BA, et aL. Dietary control of exertionaL rhabdomyoLysis in horses. J Am
Vet IViedAssoc 1998;212:1588-1593.
VaLentine BA, et aL PoLysaccharide storage myopathy in Morgan, Arabian, and
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2000;37:193-196.
Van den Hoven R, Breukink HJ. Normal resting values of plasma free carnitine
and acytcarnitine in horses predisposed to exertionaL rhabdomyoLysis.
Equine VetJ 1989;21:307-308.

Figure 2.92 Interstitial and perivascuLar infiltration of mononudear inflammatory cells characteristic of immune-mediated myositis in the temporat muscle of a dog.

Ward TL et aL CaLcium regulation by skeLetaLmuscle membranes of horses with

recurrent exertionat rhabdomyoLysis.Am J Vet Res 2000;61:242-247.
WhitweLL KE, Harris P, Farrington PG.AtypicaLmyogLobinuria: an acute myopathy
in grazing horses. Equine VetJ 1988;20:357-363.
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Locke LN, Hoff GL, eds. Noninfectious Diseases of WiLdLife. Ames, IA: The
Iowa State Press, 1996:181-193.

IMMUNE-MEDIATED CONDITIONS
Immune-mediated disorders are those in which abnormal activation
of the immune system results in tissue damage. Immune-mediated
muscle damage can involve circulating antibodies directed against muscle cell
components, cytotoxic T lymphocytes that infiltrate and attack muscle cells,
or immune-complex deposition that subsequently exposes muscles to
inflammatory mediators and ischemia.
It is important to distinguish primary immune-mediated myositis
from florid degenerative myopathy in which cellular infiltrates, primarily composed of macrophages, can mimic those of true inflammatory disease. It may be necessary to employ special
procedures to
identify the type of infiltrating cells or to detect specific antibody
binding to muscle components. Immune-mediated disease of muscle is
characterized by interstitial and perivascular infiltration of lymphocytes and~or
plasma cells (Fig. 2.92). These cells may be mixed with macrophages
and with eosinophils and neutrophils, particularly in cases accompanied by severe myofiber necrosis. The diagnosis is dependent on
determining that cellular infiltrates actually cause the myofiber necrosis and
are not secondary to the muscle damage. The finding of mononuclear
leukocytic invasion of otherwise intact myofibers is the hallmark of
primary myositis. Infiltrating cells may be seen surrounding intact
myofibers, or may be seen centrally, causing a characteristic "coring

Figure 2.93 Mononudear inflammatory celt infiltrate at the periphery and

"coring out" the interior of an otherwise intact myofiber characteristic of
immune-mediated myositis in a dogl Frozen section, modified Gomori's
trichrome.

out" of myofibers with otherwise intact peripheral myofibrils (Fig.

2.93). Lymphocytic myositis must be distinguished from infiltration
of skeletal muscle by malignant lymphoma.

Masticatory myositis of dogs

An immune-mediated myositis localized to the masticatory muscles occurs
in dogs. The masseter, temporal, and pterygoid muscles are selectively affected.
Although previously designated as two separate d i s o r d e r s eosinophilic myositis and atrophic myositis- these are now recognized to be
two ends of the spectrum of a single disease known as masticatory
myositis. Given the thick fascia of the masticatory muscles in dogs,
the swelling that can occur in masticatory myositis may be due, at
least in part, to ischemic damage due to compartment syndrome
initiated by increased pressure within inflamed muscle. Atrophic myositis is the result of prominent atrophy of temporal and masseter muscles.The
masticatory muscles of dogs have a unique myosin isoform, known
as type 2M myosin.This unique myosin isoform results in an inability