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 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 determine effects of dexamethasone
on insulin sensitivity, serum creatine kinase (CK) activity
4 hours after exercise, and muscle glycogen concentration
in Quarter Horses with polysaccharide storage
Animals—4 adult Quarter Horses with PSSM.
Procedure—A 2 × 2 crossover design was used with
dexamethasone (0.08 mg/kg) or saline (0.9% NaCl)
solution administered IV every 48 hours. Horses were
exercised on a treadmill daily for 3 wk/treatment with
a 2-week washout period between treatments. Serum
CK activity was measured daily 4 hours after exercise.
At the end of each treatment period, serum cortisol
concentrations were measured, a hyperinsulinemic
euglycemic clamp (HEC) technique was performed,
and muscle glycogen content was determined.
Results—Mean ± SEM serum cortisol concentration
was significantly lower after 48 hours for the dexamethasone
treatment (0.38 ± 0.08 mg/dL), compared
with the saline treatment (4.15 ± 0.40 mg/dL).
Dexamethasone significantly decreased the rate of glucose
infusion necessary to maintain euglycemia during
the HEC technique, compared with the saline treatment.
Muscle glycogen concentrations and mean CK
activity after exercise were not altered by dexamethasone
treatment, compared with the saline treatment.
Conclusions and Clinical Relevance—Dexamethasone
significantly reduced whole-body insulin-stimulated
glucose uptake in Quarter Horses with PSSM
after a 3-week period but did not diminish serum CK
response to exercise or muscle glycogen concentrations
in these 4 horses. Therefore, a decrease in glucose
uptake for 3 weeks did not appear to alleviate
exertional rhabdomyolysis in these horses. It is possible
that long-term treatment may yield other results.
(Am J Vet Res 2005;66:1718–1723)