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Abstract

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 exercise.

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)

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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 horse's condition.

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)

Full access
in American Journal of Veterinary Research

Abstract

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) horses.

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)

Full access
in American Journal of Veterinary Research

Abstract

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 with RER.

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 treatment.

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; 65:74–79)

Full access
in American Journal of Veterinary Research

Abstract

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 myopathy (PSSM).

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)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of dexamethasone on development of IgG subclass responses following vaccination of healthy horses.

Animals—11 mature Thoroughbreds.

Procedure—Horses received 2 IM injections at 2- week intervals of a vaccine containing inactivated infectious bovine rhinotracheitis, bovine viral diarrhea, and parainfluenza-3 viral antigens and were then randomly assigned to 2 groups. Six horses received dexamethasone (0.2 mg/kg of body weight, IM) twice weekly for 8 weeks starting the day of the first vaccination. Five control horses received an equivalent volume of saline (0.9% NaCl) solution. Antigen-specific serum IgG subclass titers were determined weekly after vaccination by use of an ELISA.

Results—Vaccination resulted in similar antigen-specific serum IgG(T) titers in dexamethasone-treated and control horses. In contrast, although control horses developed IgGa and IgGb responses after vaccination, corticosteroid administration completely inhibited these responses in treated horses.

Conclusions and Clinical Relevance—Cortico steroids can have profound effects on primary immune responses in horses and can significantly affect IgG responses to inactivated vaccines. Corticosteroid treatment regimens commonly used to treat diseases in horses may result induction of a nonprotective IgG subclass response, leaving treated horses susceptible to disease. Additionally, mechanisms regulating IgGa and IgGb responses appear to differ from those regulating IgG(T) responses. Further defining these mechanisms is a critical step in designing effective vaccines, and corticosteroid-induced immunomodulation may be a valuable tool for studying immune responses in horses. (Am J Vet Res 2000;61:1530–1533)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess changes in muscle glycogen (MG) and triglyceride (MT) concentrations in aerobically conditioned sled dogs during prolonged exercise.

Animals—54 Alaskan sled dogs fed a high-fat diet.

Procedures—48 dogs ran 140-km distances on 4 consecutive days (cumulative distance, up to 560 km); 6 dogs remained as nonexercising control animals. Muscle biopsies were performed immediately after running 140, 420, or 560 km (6 dogs each) and subsequently after feeding and 7 hours of rest. Single muscle biopsies were performed during recovery at 28 hours in 7 dogs that completed 560 km and at 50 and 98 hours in 7 and 6 dogs that completed 510 km, respectively. Tissue samples were analyzed for MG and MT concentrations.

Results—In control dogs, mean ± SD MG and MT concentrations were 375 ± 37 mmol/kg of dry weight (kgDW) and 25.9 ± 10.3 mmol/kgDW, respectively. Compared with control values, MG concentration was lower after dogs completed 140 and 420 km (137 ± 36 mmol/kgDW and 203 ± 30 mmol/kgDW, respectively); MT concentration was lower after dogs completed 140, 420, and 560 km (7.4 ± 5.4 mmol/kgDW; 9.6 ± 6.9 mmol/kgDW, and 6.3 ± 4.9 mmol/kgDW, respectively). Depletion rates during the first run exceeded rates during the final run. Replenishment rates during recovery periods were not different, regardless of distance; only MG concentration at 50 hours was significantly greater than the control value.

Conclusions and Clinical Relevance—Concentration of MG progressively increased in sled dogs undergoing prolonged exercise as a result of attenuated depletion.

Full access
in American Journal of Veterinary Research