Objective—To determine whether disruption of adenine
triphosphate (ATP) regeneration and subsequent
adenine nucleotide degradation are potential mechanisms
for rhabdomyolysis in horses with polysaccharide
storage myopathy (PSSM) performing submaximal
Animals—7 horses with PSSM and 4 control horses.
Procedures—Horses with PSSM performed 2-minute
intervals of a walk and trot exercise on a treadmill until
muscle cramping developed. Control horses exercised
similarly for 20 minutes. Serum creatine kinase (CK)
activity was measured 4 hours after exercise. Citrate
synthase (CS), 3-OH-acylCoA dehydrogenase, and lactate
dehydrogenase activities prior to exercise and glucose-
6-phosphate (G-6-P) and lactate concentrations
before and after exercise were measured in gluteal
muscle specimens. Adenine triphosphate, diphosphate
(ADP), monophosphate (AMP), and inosine
monophosphate (IMP) concentrations were measured
before and after exercise in whole muscle, single muscle
fibers, and pooled single muscle fibers.
Results—Serum CK activity ranged from 255 to
22,265 U/L in horses with PSSM and 133 to 278 U/L
in control horses. Muscle CS activity was lower in
horses with PSSM, compared with control horses.
Muscle G-6-P, lactate, ATP, ADP, and AMP concentrations
in whole muscle did not change with exercise in
any horses. Concentration of IMP increased with
exercise in whole muscle, pooled muscle fibers, and
single muscle fibers in horses with PSSM. Large variations
in ATP and IMP concentrations were observed
within single muscle fibers.
Conclusions and Clinical Relevance—Increased IMP
concentration without depletion of ATP in individual
muscle fibers of horses with PSSM during submaximal
exercise indicates an energy imbalance that may contribute
to the development of exercise intolerance and
rhabdomyolysis. (Am J Vet Res 2005;66:839–845)
Objective—To estimate the prevalence of polysaccharide storage myopathy (PSSM) among Quarter Horses in the United States and evaluate possible relationships between muscle glycogen concentration, turnout time, and exercise level.
Animals—164 overtly healthy Quarter Horses > 2 years old from 5 states.
Procedures—Horses with a history of exertional rhabdomyolysis or any other muscular disease were excluded. Muscle biopsy specimens were examined histologically for evidence of PSSM and were submitted for determination of muscle glycogen concentration. A diagnosis of PSSM was made if amylase-resistant inclusions that stained with periodic acid–Schiff stain were detected.
Results—Prevalences of PSSM on the 2 farms with a history of PSSM were 20% (1/5) and 40.7% (11/27); mean prevalence for the other 4 farms was 6.1% (8/132). Sex was not significantly associated with a diagnosis of PSSM, and age was not significantly different between horses with and without PSSM. Total histologic score, serum creatine kinase ac-tivity, and muscle glycogen concentration were significantly higher in horses with PSSM than in horses without.
Conclusions and Clinical Relevance—Results suggested that the prevalence of PSSM among overtly healthy Quarter Horses in the United States is likely to be between 6% and 12%.
Objective—To determine clinical signs, diagnostic findings, tissue tremetone concentrations, and clinical outcome or postmortem findings in horses evaluated for acute severe nonexertional rhabdomyolysis initially attributed to white snakeroot toxicosis.
Design—Retrospective case series.
Procedures—Records of the University of Minnesota Veterinary Medical Center or Diagnostic Laboratory were searched from 1998 to 2005. Inclusion criteria included serum creatine kinase (CK) activity > 45,000 U/L, severe nonexertional myonecrosis of proximal postural muscles at necropsy, or signs of weakness without palpably firm muscles on physical examination. Vitamin E and selenium concentrations were measured in 6 horses; tremetone concentration was measured in 7.
Results—Clinical signs occurred during unfavorable weather conditions. Clinical signs of generalized weakness (n = 11 horses), muscle fasciculations (10), lethargy (6), and prolonged recumbency (4) were common. Serum CK activity ranged from 46,487 to 959,499 U/L (reference range, 82 to 449 U/L), and aspartate transaminase activity was > 1,500 U/L (reference range, 162 to 316 U/L). Two horses survived with aggressive antioxidant and fluid treatment. Postmortem examination revealed acute severe myonecrosis with lipid accumulation primarily in neck, proximal forelimb and hind limb, intercostal, and diaphragm muscles. Histopathologic signs of myocardial necrosis were detected in 7 horses. Vitamin E and selenium concentrations were within reference limits. Tremetone was not detected in liver or urine samples.
Conclusions and Clinical Relevance—Cases of rhabdomyolysis have been attributed to white snakeroot toxicosis; however, tremetone was not detected in any horses. Similarities exist between cases of seasonal pasture myopathy and cases of atypical myopathy in Europe.
Objective—To determine concentrations of proglycogen (PG), macroglycogen (MG), glucose, and glucose-6-phosphate (G-6-P) in skeletal muscle of horses with polysaccharide storage myopathy (PSSM) before and after performing light submaximal exercise.
Animals—6 horses with PSSM and 4 control horses.
Procedures—Horses with PSSM completed repeated intervals of 2 minutes of walking followed by 2 minutes of trotting on a treadmill until muscle cramping developed. Four untrained control horses performed a similar exercise test for up to 20 minutes. Serum creatine kinase (CK) activity was measured before and 4 hours after exercise. Concentrations of total glycogen (Gt), PG, MG, G-6-P, free glucose, and lactate were measured in biopsy specimens of gluteal muscle obtained before and after exercise.
Results—Mean serum CK activity was 26 times higher in PSSM horses than in control horses after exercise. Before exercise, muscle glycogen concentrations were 1.5, 2.2, and 1.7 times higher for PG, MG, and Gt, respectively, in PSSM horses, compared with concentrations in control horses. No significant changes in Gt, PG, MG, G-6-P, and lactate concentrations were detected after exercise. However, free glucose concentrations in skeletal muscle increased significantly in PSSM horses after exercise.
Conclusions and Clinical Relevance—Analysis of the results suggests that glucose uptake in skeletal muscle is augmented in horses with PSSM after light exercise. There is excessive storage of PG and MG in horses with PSSM, and high concentrations of the 2 glycogen fractions may affect functional interactions between glycogenolytic and glycogen synthetic enzymes and glycosomes.
OBJECTIVE To characterize clinical findings for polysaccharide storage myopathy (PSSM) in warmblood horses with type 1 PSSM (PSSM1; caused by mutation of the glycogen synthase 1 gene) and type 2 PSSM (PSSM2; unknown etiology).
SAMPLE Database with 3,615 clinical muscle biopsy submissions.
PROCEDURES Reported clinical signs and serum creatine kinase (CK) and aspartate aminotransferase (AST) activities were retrospectively analyzed for horses with PSSM1 (16 warmblood and 430 nonwarmblood), horses with PSSM2 (188 warmblood and 646 nonwarmblood), and warmblood horses without PSSM (278). Lameness examinations were reviewed for 9 warmblood horses with PSSM2. Muscle glycogen concentrations were evaluated for horses with PSSM1 (14 warmblood and 6 nonwarmblood), warmblood horses with PSSM2 (13), and horses without PSSM (10 warmblood and 6 nonwarmblood).
RESULTS Rhabdomyolysis was more common for horses with PSSM1 (12/16 [75%] warmblood and 223/303 [74%] nonwarmblood) and nonwarmblood horses with PSSM2 (221/436 [51%]) than for warmblood horses with PSSM2 (39/147 [27%]). Gait abnormality was more common in warmblood horses with PSSM2 (97/147 [66%]) than in warmblood horses with PSSM1 (1/16 [7%]), nonwarmblood horses with PSSM2 (176/436 [40%]), and warmblood horses without PSSM (106/200 [53%]). Activities of CK and AST were similar in warmblood horses with and without PSSM2. Muscle glycogen concentrations in warmblood and nonwarmblood horses with PSSM1 were significantly higher than concentrations in warmblood horses with PSSM2.
CONCLUSIONS AND CLINICIAL RELEVANCE Rhabdomyolysis and elevated muscle glycogen concentration were detected in horses with PSSM1 regardless of breed. Most warmblood horses with PSSM2 had stiffness and gait abnormalities with CK and AST activities and muscle glycogen concentrations within reference limits.
Objective—To characterize onset and clinical signs of
polysaccharide storage myopathy (PSSM) in a welldefined
population of affected Quarter Horses, identify
risk factors for PSSM, determine compliance of
owners to dietary and exercise recommendations,
and evaluate the efficacy of dietary and exercise recommendations.
Animals—40 Quarter Horses with PSSM and 37
unaffected control horses.
Procedures—Owners of horses with PSSM completed
a retrospective questionnaire concerning their
Results—Between horses with PSSM and control
horses, no significant differences were found in sex
distribution (21 vs 15 females and 16 vs 22 males,
respectively), temperament, muscle build, diet, or
amount of turnout. In horses with PSSM, signs of
muscle stiffness, muscle fasciculations, sweating,
exercise intolerance, weakness, muscle wasting,
reluctance to move, colic, abnormal gait, recumbency,
lameness, and swollen muscles began between the
age of 1 day and 14 years (mean age, 4.9 ± 3.5 years).
Five horses with PSSM developed acute muscle atrophy.
Sixty-three percent (25/40) of owners fed the recommended
diet, 55% (22/40) provided regular exercise,
and 40% (16/40) followed both dietary and exercise
recommendations. Owners of affected horses
for which a decrease in severity or frequency of
PSSM was not found did not follow the exercise,
dietary, or both recommendations. All horses for
which both dietary and exercise recommendations
were followed had improvement in signs of PSSM.
Conclusions and Clinical Relevance—In addition to
exertional rhabdomyolysis, signs of PSSM include
acute muscle atrophy and gait abnormalities. It
appears that PSSM can be managed by following
dietary recommendations combined with gradual
increases in daily exercise. (Am J Vet Res 2003; 64:1319–1327)
Objective—To determine prevalences of polysaccharide
storage myopathy (PSSM) and shivers in Belgian
Draft Horses (BDHs) and determine whether there
was an association between these 2 conditions.
Design—Prospective cohort study.
Animals—103 BDHs > 1 year old.
Procedure—Owners were questioned regarding clinical
signs of PSSM, shivers, and hindquarter weakness,
defined as poor hindquarter muscling and lack
of propulsion. Blood samples were collected for
determination of serum creatine kinase and aspartate
transferase activities and serum selenium and vitamin
E concentrations. A biopsy sample from the gluteus
medius muscle was submitted for histologic, histochemical,
and biochemical analysis. A diagnosis of
PSSM was made if abnormal amylase-resistant polysaccharide
inclusions were seen histologically.
Results—37 (36%) horses had PSSM and 19 (18%)
had shivers, but only 6 (6%) had both PSSM and shivers,
whereas 31 (30%) had PSSM alone, 13 (13%)
had shivers alone, and 53 (51%) had neither, and a
significant association between PSSM and shivers
was not detected. Hindquarter weakness was found
in 30 horses. Only 13 of 37 (35%) horses with PSSM
and 11 of 19 (58%) horses with shivers had hindquarter
weakness. Serum creatine kinase and aspartate
transferase activities and serum selenium and vitamin
E concentrations were not significantly different
between horses with and without PSSM or between
horses with and without shivers.
Conclusions and Clinical Relevance—Results suggest
that PSSM and shivers are common but unrelated
disorders in BDHs. (J Am Vet Med Assoc 2005;227:1958–1964)
OBJECTIVE To compare effects of training on conventional and underwater treadmills on fiber properties and metabolic responses of the superficial digital flexor (SDF) and gluteal muscles to high-speed exercise in horses.
SAMPLE 6 unconditioned Quarter Horse–type horses.
PROCEDURES 6 horses were walked on underwater and conventional treadmills for 5 d/wk (maximum, 40 min/d) for 8 weeks in a randomized crossover design (60-day detraining period). Horses underwent a standardized exercise test (SET) at high speed before and after training. Analyte concentrations and fiber characteristics were measured in muscle biopsy specimens obtained from horses before and after each SET.
RESULTS Lactate concentration increased 2- to 3-fold in SDF and gluteal muscle after SETs. No training effect was identified on muscle fiber type composition, type II fiber diameter, muscle analyte concentrations, blood lactate concentration, or heart rate responses. Maximum diameters of type I fibers decreased significantly in gluteal muscle with conventional treadmill training and decreased in SDF muscle with both types of training, with maximum diameters greater for horses after underwater versus conventional treadmill training. No change was identified in minimum fiber diameters.
CONCLUSIONS AND CLINICAL RELEVANCE SETs involving near-maximal exertion resulted in an anaerobic response in SDF and gluteal muscles of horses. Eight weeks of conventional or underwater treadmill training resulted in minor changes in type I muscle fiber sizes, with no effect on muscle metabolic or heart rate responses to SETs. After rehabilitation involving underwater treadmills, training at progressing speeds is recommended for horses to develop the required fitness for speed work.
Objective—To determine whether an alteration in calcium
regulation by skeletal muscle sarcoplasmic reticulum,
similar to known defects that cause malignant
hyperthermia (MH), could be identified in membrane
vesicles isolated from the muscles of Thoroughbreds
with recurrent exertional rhabdomyolysis (RER).
Sample Population—Muscle biopsy specimens
from 6 Thoroughbreds with RER and 6 healthy (control)
Procedures—RER was diagnosed on the basis of a history
of > 3 episodes of exertional rhabdomyolysis confirmed
by increases in serum creatine kinase (CK) activity.
Skeletal muscle membrane vesicles, prepared by
differential centrifugation of muscle tissue
homogenates obtained from the horses, were characterized
for sarcoplasmic reticulum (SR) activities, including
the Ca2+ release rate for the ryanodine receptor-Ca2+
release channel, [3H]ryanodine binding activities, and
rate of SR Ca2+-ATPase activity and its activation by Ca2+.
Results—Time course of SR Ca2+-induced Ca2+
release and [3H]ryanodine binding to the ryanodine
receptor after incubation with varying concentrations
of ryanodine, caffeine, and ionized calcium did not differ
between muscle membranes obtained from control
and RER horses. Furthermore, the maximal rate
of SR Ca2+-ATPase activity and its affinity for Ca2+ did
not differ between muscle membranes from control
horses and horses with RER.
Conclusions and Clinical Relevance—Despite clinical
and physiologic similarities between RER and MH,
we concluded that RER in Thoroughbreds does not
resemble the SR ryanodine receptor defect responsible
for MH and may represent a novel defect in muscle
excitation-contraction coupling, calcium regulation,
or contractility. (Am J Vet Res 2000;61:242–247)
Objective—To determine the effect of oral administration
of dantrolene sodium on serum creatine
kinase (CK) activity after exercise in horses with
recurrent exertional rhabdomyolysis (RER).
Animals—2 healthy horses and 5 Thoroughbreds
Procedure—3 horses received 2 doses of dantrolene
(4, 6, or 8 mg/kg, PO, with and without withdrawal of
food) 2 days apart; 90 minutes after dosing, plasma
dantrolene concentration was measured spectrofluorometrically.
On the basis of these results, 5
Thoroughbreds with RER from which food was withheld
received dantrolene (4 mg/kg) or an inert treatment
(water [20 mL]) orally 90 minutes before treadmill
exercise (30 minutes, 5 d/wk) during two 3-week
periods. Serum CK activity was determined 4 hours
after exercise. Plasma dantrolene concentration was
measured before and 90 minutes after dosing on the
first and last days of dantrolene treatment and before
dosing on the first day of the inert treatment period.
Results—90 minutes after dosing, mean ± SEM plasma
dantrolene concentration was 0.62 ± 0.13 and 0
µg/mL in the dantrolene and inert treatment groups,
respectively. Serum CK activity was lower in dantrolene-
treated horses (264 ± 13 U/L), compared with
activity in water-treated horses (1,088 ± 264 U/L). Two
horses displayed marked muscle stiffness on the inert
Conclusions and Clinical Relevance—In 5 horses
with RER from which food had been withheld, 4 mg
of dantrolene/kg administered orally provided measurable,
though variable, plasma concentrations and
significantly decreased serum CK activity after exercise
in 4 of those horses. ( Am J Vet Res 2004;