Equine Exertional Rhabdomyolysis
A Thoroughbred racehorse acts colicky returning to his
stall after a morning workout. An Arabian endurance horse
quits at the 25th mile, trembling at the top of
a hill. A Quarter Horse ranch horse is stymied by progressive
weight loss and decreased performance. A Standardbred trotter
lies sternal in his stall and is reluctant to rise. It’s
equivocal, but a Belgian draft mare seems to be showing a
hind-limb lameness.
What might all these horses have in common?
It’s possible that all five are suffering from Exertional
Rhabdomyolysis, a clinical syndrome denoting muscular pathology,
whose varied etiologies are only beginning to be determined.
“Tying up”, as the condition is commonly described,
has been recognized by horsemen since at least the early part
of the 20th century. Owners of draft teams, especially,
noticed muscular distress in their horses following a full
day of rest on full feed. Their workhorses came out stiff
the “day after” (typically Monday), leading to the
term “Monday Morning Disease”. Curiously, not all
draft horses were similarly affected. More curious still,
not all affected horses were helped by a reduced diet during
the rest day. The conclusion that “tying up” was
associated with both heredity and husbandry governs research
on the syndrome to this day.
Clinical Signs and Diagnosis
In general, exertional rhabdomyolysis elicits a
spectrum of physical signs from mild stiffness and myalgia
to recumbency and death. Diagnosis is based on clinical signs,
with concurrent increases in serum creatinine kinase (CK),
aspartate amino-transferase (AST), myoglobinuria in severe
cases, and distinctive lesions on muscle biopsy. Critical
consideration must be given to ruling out other diagnoses.
From the opening examples, it can be seen that rule-out diagnoses
include colic, fractures, pleuritis, laminitis – anything
that might cause a horse to act painful and reluctant to move.
Serum chemistry can help determine the prognosis as well
as diagnosis. In a small study, one researcher noted that,
while CK, AST, and lactate dehydrogenase (LDH) all increased
immediately after onset of clinical signs, CK had the shortest
half-life. AST and/or LDH, to CK, ratios corresponded with
stage of disease. Ratios were low in acute stages, and high
during recuperation.
Most diagnostic biopsies are taken from the middle gluteal
and semimembranous muscles. These muscles are comprised largely
of Type II (slow twitch or “non-oxidative”) fibers;
specimens are submitted on ice or frozen, not fixed. Histological
signs of rhabdomyolysis (literally, “muscle cell loosening”)
include vacuolization and fragmentation of myocytes, and macrophage
infiltration. Centrally located nuclei (indicating myocyte
regeneration), fibrosis, and fatty infiltration all indicate
chronic damage.
Pathogenesis
Of the many disparate causes for “tying up”,
certain ones are particular to certain breeds. The more heavily
muscled, calmer breeds (e.g. Quarter Horses, warm bloods and
draft breeds) are more likely to be affected by a defect in
muscular metabolism called Polysaccharide Storage Myopathy
(PSSM or EPSM). Thoroughbreds and other hot-blooded breeds,
however, are thought to suffer a defect in intracellular calcium
regulation. Other proposed etiologies tend to be suggested
and unsubstantiated repeatedly, and include Vitamin E deficiency,
electrolyte imbalance, viral infection, and, because of an
increased incidence in mares, normonal influences.
The PSSM subset of rhabdomyolysis is named from an intramyocellular
accumulation of periodic acid-Schiff-positive, abnormal mucopolysaccharide.
Increased intra-cellular glycogen levels
occur also, but are not specific to PSSM. Muscle glycogen
levels may be more than doubled in PSSM positive horses compared
to unaffected counterparts. It was originally thought that
these horses suffered from a decreased ability to use stored
glycogen; however, measurement of muscle glycogen and lactate
during exercise tests have shown that the abnormality lies
in increased synthesis, not decreased usage, of muscle glycogen.
The role of the abnormal polysaccharide is unknown.
Affected thoroughbreds, and other breeds which “tie
up” without histologic evidence of PSSM, have been shown
to have abnormal regulation of myocyte contraction. In
vitro studies compare muscle twitch responses to chemical
stimuli such as caffeine and halothane. Muscle-contracture
thresholds are lower in samples from affected horses, and
the theory is that abnormal calcium regulation is to blame.
Genetic studies of affected horses have revealed different
patterns of inheritance for both the PSSM and calcium related
forms of exertional myopathy. PSSM horses have been shown
to be descendents of one of three stallions, with an autosomal
recessive inheritance pattern. The names of the three stallions
have not been released. In thoroughbred racehorses, pedigree
analysis revealed an autosomal dominant inheritance pattern,
with variable expression. The trait seems to have first appeared
in stallions in the early 20th century.
Treatment and Prevention
Horses acutely affected with rhabdomyoysis should be moved
as little as possible. Mild cases may be walked bak to a
stall, but movement will worsen the pathology in severe cases.
In this regard, treatment should be directed towards reducing
pain and anxiety in these horses to keep them as quiet as
possible. Flunixin meglumine, phenylbutazone, acepromazine,
and butorphanol have all been used with success.
Correcting hydration status is crucial, especially to prevent
kidney damage in cases with myoglobinuria.
Dantrolene, a muscle relaxant which inhibits intracellular
calcium release, and Phenytoin, an anti-convulsant, have been
used for both treatment and prevention. No clinical trials
have demonstrated efficacy, however, and dosing may be expensive
and time consuming. One author suggested use only in horses
known to be affected with abnormal intracellular calcium regulation.
Limited studies have shown a decreased incidence of rhabdomyolysis
following a switch to high-fat, low-carbohydrate diets, based
on the theory that this will decrease muscle glycogen stores.
Regular, daily exercise and turn-out are also suggested; their
success in reducing episodes of rhabdomyolysis is anecdotal.
- by Katherine Ulman, Class 2000
- edited by Janice Lacey, DVM, ADDL Graduate Student
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