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Tying Up: Rhabdomyolysis in Horses
by Robert N. Oglesby DVM
Introduction
Tying up syndrome is a preferable name to exertional rhabdomyolysis because not
all horses that tie up have exercised. Tied up horses develop pain and stiffness
in the lower back, gluteals and muscles of the thigh region. The problem can
vary from a transient cramping to a serious problem where muscle destruction
occurs. In cases of muscle destruction the urine turns dark with myoglobin, a
component of muscle cells.
There have been many proposed mechanisms for tying up but frequently
electrolyte concentrations are a factor in horses that tie up during intense
exercise. In the 1990's it is becoming evident that many cases are due to a
defect in carbohydrate metabolism within affected skeletal muscle fibers. This
condition has been dubbed Equine Polysaccharide Storage Myopathy (EPSM), and has
led to some new treatment options that have shown great success. It has been
proposed that this may be an inherited disease with an autosomal recessive
pattern.
Symptoms
Typical signs of tying up are:
1. A stiff walk, that at its worse can immobilize the horse.
2. Hard painful muscles in the rear.
3. If the pain is severe enough sweating may occur.
Horses that tie up usually have a recurring problem, associated with a specific
set of circumstances. When horses worked for a living, a common problem was
"Monday morning's disease." This problem occurred when horses, which
were working all week, did not have their grain cut back while resting over the
weekend. Some horses tie up when they become excited, at a show, breeding, or
traveling. Other horses develop the problem when exercised. Occasionally you run
into the horse that ties up for no reason you can detect.
Moderate to severe cases are not hard to diagnose. The stiffness in the rear
limbs and hard painful muscles are easily seen. But mild cases may present as
decreased performance or a vague lameness originating in the back or hind end.
In cases of possible tying up the diagnosis can be confirmed with blood tests
for increase levels of muscle enzymes.
Possible Causes
There have been several proposed causes for tying up. The different histories,
and varying treatments that horses respond to, strongly suggest that we are
looking at several different diseases. Some proposed causes are:
 | Altered carbohydrate metabolism
Recent work has identified abnormal carbohydrate metabolism as a cause in
many breeds of tying up. The others on the list are at this time unproven
causes of the problem.
| Hypotension and Electrolyte imbalances
Horses which tie up during or following exercise frequently have electrolyte
imbalances. These imbalances cannot be diagnosed with simple blood testing.
| Lactate build up (unproven)
| Too little oxygen getting to the muscles (unproven)
| Vitamin E \ selenium deficiencies (unproven)
| Hypothyroidism (unproven)
| An interesting observation by the University of Calif. is that ear ticks (Otobius
megnini) have been associated with muscle spasms in more than half a dozen
cases. These muscle spasms were very much like tying up. In each case muscle
enzymes were elevated. When the ear ticks were treated the horses got over
the spasms. Other signs identified with theses horses were colic, tremors,
and seizures. (JAVMA, v207, n1) |
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Diagnosis
Diagnosis is generally not complicated except in mild cases which may resemble
founder or generalized stiffness. The muscle enzymes CPK and AST are invariably
elevated during a tying up episode and shortly after. Strenuous exercise can
elevate these enzymes up to 4 fold normal while most tying up episodes result in
a 10 fold rise or greater.
ESPM
Diagnosis of EPSM form of tying up can be made with a muscle biopsy of the
semitendinosus muscle preserved in 10% buffered formalin. The samples are
stained with hematoxylin and eosin, periodic acid-Schiff (PAS) stain and PAS
followed by amylase digestion. Abnormal findings in the Type 2 glycolytic fibers
are:
subsarcolemmal and intra-cytoplasmic pale staining zones,
fiber hypertrophy,
internal nuclei,
excessive glycogen.
Currently this type of pathology is being carried out at Cornell University.
Doctors may contact the Dept of Pathology, College of Veterinary Medicine,
Cornell University, Ithaca, New York 14853, atten: Beth A Valentine, DVM, PhD.
Fractional Excretion Test
Once a horse has fully recovered from an episode of tying up a fractional
excretion test for electrolyte imbalances should be done. Electrolyte imbalances
are difficult to detect simply and routinely. The estimation of electrolyte
concentrations in the blood cannot be used to detect deficiency or excess with
any accuracy because of the homeostatic mechanisms which maintain normal blood
concentrations. Fractional excretion test is a practical means of assessing
certain alterations in electrolyte status.
Recently a muscle enzyme that tracks the progress of tying up syndrome in
horses has been found. This enzyme, carbonic anhydrase III (CA-III), differs
from other enzyme markers in that it correlates with the severity of the disease
almost instantaneously. Most other enzymes, used to monitor tying up, lag behind
the disease by days or weeks. Another advantage to CA-III is that levels are
markedly elevated in horses with histories of tying up but are not currently
showing signs of the disease. This makes it possible to tag susceptible horses
for preventive care. Currently no labs in the USA are doing this testing
regularly.
Treatment
First aid will depend on severity of signs. When just a little stiffness occurs,
hand walking will help a horse loosen up. Recently it has been suggested that
walking may be harmful but many mild cases have improved by being walked. Bute
should be given for pain. Acepromazine (1 to 2 mg. /1000 lbs.) is helpful to
relax the horse and increase peripheral perfusion. If the stiffness is severe
current recommendations are to not move the horse.
Many severe cases are associated with intense exercise. If dehydration or
electrolyte imbalances are possible, IV fluids should be used to correct these
problems. Corticosteroids make sense for early treatment to help prevent further
cellular damage. Phenylbutazone at the upper end of recommended doses will help
to relieve the pain Acepromazine (given after correcting dehydration) at the
above rates will help increase blood flow to the muscles. If additional sedation
or pain relief is desired narcotics (butorphanol or Valium) would be preferable
over high doses of acepromazine.
Muscle relaxers seem to be rational therapy but questions of efficacy and
potential toxicity do not make them a clear choice. Currently two muscle
relaxers are advocated: dantrolene and methocarbamol. Check with your vet for
the latest on these two.
Prevention
Electrolyte Imbalances
If the results of the fractional excretion (see above) test indicate a
nutritional imbalance these should be corrected first. Routine use of
electrolyte additions to the feed are not neccassarily good. However electrolyte
supplementation during times of maximal stress is recommended.
As a horse sweats more and his electrolyte concentrations deplete his sweat
becomes less salty thereby conserving needed electrolytes. On the other hand,
when the system senses an excess of an electrolyte it cranks up mechanisms to
rid the body of them. IF YOU SUPPLEMENT ELECTROLYTES ON A DAILY BASIS YOU WEAKEN
THE SYSTEM'S ABILITY TO RESPOND TO STRESS. The best time for supplements is just
before and during a time of maximal stress. Electrolytes should be added to the
feed and not the water. An inexpensive but effective electrolyte mixture can be
made using 1 tb. table salt and 1 tb. Salt Substitute (Lite Salt or NoSalt: reg.
TMs) mixed in the feed twice daily.
EPSM
Since the discovery of EPSM and its relation to tying up, dietary management has
been very effective at managing this problem. To clear out the abnormal amount
of glycogen and carbohydrate from the muscle cells requires 3 to 4 months with
improvement noted for up to one year after instituting the diet. So do not
expect rapid results, but with patience they will come with most horses being
normal within a year.
Current recommendations are to remove as much carbohydrate as possible from
the diet and substitute oil and protein as an energy source. Substituted for the
grain portion of the diet is 2 cups (app. 1 lb) of vegetable oil per 1000 lbs
and alfalfa pellets. A basic formula for initial estimation of amounts for a
1000 lb horse would be:
Current daily grain ration (in pounds) - Oil (in cups) = Alfalfa Pellets (in
pounds)
For example take a 1200 lb horse receiving 5 lbs of grain a day: 5 (lbs of
grain a day) - 2.4 (2 cups a day /1000 lbs x 1200 lbs) = 2.6 lbs of alfalfa
pellets a day.
Of course this is best fed divided twice daily and changes should be made
slowly. A problem in this diet is that high fat diets are may not be palatable
to some horses and you may have to reduce the oil portion slightly to get the
horse to eat it, particularly if the pellet portion is small. Some adjustments
may need to be made. The horses weight should be watched and adjusted using the
pellet portion of the diet. Of course during this time grass and hay should be
available as usual. If you love in a selenium deficient area of the country you
should consider having vitamin E (normal = 2.5 -4.0 ug/ml) and selenium (normal
= 180 - 240 ng/ml) values run on the blood.
Other Possibilities
With some of the causes of tying up being unknown, and probably multifactorial,
other preventive measures are trial and error. Identifying predisposing factors
may allow prevention. For instance, if nervousness in certain situations results
in tying up, mild tranquillizers where practical, might help. If intensive
exercise brings on the problem consider better conditioning regimens and
electrolyte supplementation. Drugs reported to help in some cases are:
1.Vitamin E \ Selenium (1 to 5 micrograms / lb. of horse / day) as a feed
supplement. Selenium is potentially toxic so review any supplement plans with
your veterinarian.
2.Bicarbonate (180 mg. / lb. of horses / day or app. 1/3 lb. per 900 lb. horse
per day) as a feed supplement
3.Electrolyte supplementation (1 tsp. of table salt and 1/2 tsp. of Lite salt in
the feed daily is an inexpensive sodium and potassium supplement)
4.Oral phenytoin has been very useful in some cases. Start at 5 mg.\ lb. twice
daily for three days then reduce by half every three days. The dosage is reduced
to the lowest effective dosage.
More On EPSM:
Equine Polysaccharide Storage Myopathy
Equine polysaccharide storage myopathy (EPSM) is a sub-type of
exertional rhabdomyolysis characterized by a defect in glycogen storage
in skeletal muscle. This disease is seen in many different breeds
including Quarter horses, draft horses and crosses of these breeds.
There is evidence that the disease is heritable in Quarter horses; this
question has not been answered for other breeds. Skeletal muscles
in affected horses have higher amounts of stored glycogen than in normal
horses. Affected horses also have higher levels of a complex
polysaccharide which is resistant to amylase digestion, aiding
identification of the disease by histopathology as described below.
Clinical signs of EPSM are similar to those of all forms of
rhabdomyolysis: stiff gait, pain, muscle cramping, and reluctance
to move after exercise. However, in some subclinically affected
horses, EPSM is not discovered until unusual events (such as anesthesia
and subsequent postanesthetic recumbency) occur. A diagnosis of
rhabdomyolysis can be made from clinical signs and serum chemistry
values. Muscle enzymes such as creatine kinase (CK), lactate
dehydrogenase (LDH) and aspartate transminase (AST) will be high after
episodes of rhabdomyolysis. Furthermore, diagnosis of
rhabdomyolysis does not specify the underlying metabolic problem.
In humans and other species there are numerous metabolic disturbances in
glycogenolysis or glycolysis that cause rhabdomyolysis. To date,
however, the specific etiology of EPSM has not been elucidated.
Studies have shown that EPSM is not a defect in glycogenolysis or
glycolysis. Instead, it is believed to be due to increased glucose
uptake, possibly due to up-regulation of insulin receptors because
affected horses have an exaggerated response to insulin.
EPSM must be differentiated from equine motor
neuron disease (EMND), colic, equine protozoal myeloencephalitis (EPM),
musculoskeletal injury, hyperkalemic periodic paralysis (HYPP) and even
Lyme disease. EMND is an idiopathic degenerative disease of
somatic nerves originating in the ventral horn of the spinal cord.
These horses will show weakness and trembling due to neurogenic atrophy
of type 1, versus type 2 in EPSM, muscle fibers which make up the
postural muscles. EPSM can mimic colic because affected horses
show signs of discomfort; however, a thorough examination of the
gastrointestinal tract will rule out colic. Horses with EPM will
often have asymmetrical atrophy. The stiff gait of horses with
EPSM may mimic the proprioceptive deficits associated with EPM, but a
thorough neurological exam will reveal that horses with EPSM do not
cross their pelvic limbs on tight turns. EPSM can look like
musculoskeletal injury, as a crouched gait can be a sign of back injury.
Stiff gate with decreased flexion is common in both disorders. A
thorough physical examination, radiographs, and nuclear scintigraphy
should determine if the horse actually has a musculoskeletal disorder.
As there is a familial basis in Quarter horses for both EPSM and HYPP,
the two must be differentiated. HYPP DNA testing can be done by
submitting a blood sample to Veterinary Genetics Laboratory (phone
916.752.7416 for instructions.)
Finally, Lyme disease can manifest as shifting leg
lameness, stiffness and discomfort. Polymerase chain reaction of
synovial fluid of affected horses will reveal infection with Borrelia
burgdorferi if the horse is infected with Lyme disease. If the
above diseases and syndromes cannot be differentiated, a muscle biopsy
can be done.
EPSM and EMND are best differentiated by muscle biopsy.
The epaxial muscles, specifically the sacrocaudalis dorsalis medialis,
are made of type 1 fibers and are good samples for EMND diagnosis.
For diagnosis of EPSM, a biopsy of the semitendinosus muscle is a
good choice as this is a type 2 muscle, therefore locomotory, and is
affected in EPSM. To obtain the best biopsy sample, the horse
should be sedated and administered local anesthesia with either a caudal
epidural or line block over the incision site, without actually
injecting into the muscle to be sampled. Make a 5 cm longitudinal
skin incision parallel to the muscle fibers. Repeat through the
fascia. Obtain a strip of muscle approximately 5 cm in length by 1
cm in diameter. Be sure to undermine the muscle first so it does
not retract when one end is cut. Place the tissue sample in 10%
formalin and submit for histopathologic examination. Punch
biopsies do not provide enough tissue for evaluation of EPSM or EMND.
The best tissue stain to identify EMND is Masson’s trichrome.
EPSM is identified best by staining with both PAS and PAS with amylase
digestion. In both EMND and EPSM, there will be excessive
variation in muscle fiber size, internal nuclei, and hypertrophy.
If the horse has EMND, the muscle cells will have fibrosis and fat
infiltration, scattered necrotic and regenerative areas, and
intramuscular nerves will be atrophied. In the case of EPSM, the
muscle cells will have vacuoles, small rounded fibers, normal
intramuscular nerves and glycogen/polysaccharide granules which will not
be digested by amylase.
Treatment for EPSM, once diagnosis is made, is primarily
dietary therapy. In the past, standard therapy for horses with
rhabdomyolysis has been to remove excess carbohydrate, often in the form
of grain, from the diet. In the case of EPSM, this is not enough
as the horse still makes too much abnormal polysaccharide.
Replacement of carbohydrates with a diet high in fat (up to 25%) and
protein has worked well to control signs of EPSM by forcing the horse to
metabolize fat and protein for energy. Within six months, many
horses treated with this diet resumed training to previous levels,
without signs of EPSM and without elevated CK, LDH or AST.
Furthermore, horses benefited most from as little rest as possible and
recovered sooner than horses treated only with diet modification.
Horses with EPSM often have abnormal thyroid hormone levels
despite normally functioning thyroid glands (“euthyroid sick
syndrome”); therefore thyroid supplements do not help.
Interestingly, horses on the high fat diet resolved their thyroid and
vitamin E/ selenium imbalances. This is likely due to better
muscle function with fat as an energy source. Once diagnosed, EPSM
is treatable; the animal has a reasonable prognosis for return to work.
However, because EPSM may be inherited, the veterinarian should advise
clients against breeding affected horses.
- by Catherine Alinovi, Class of 2001
- edited by Karen Tucker-Gillum, DVM,
ADDL Graduate Student
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