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  • Author or Editor: Stephanie J. Valberg x
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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)

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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)

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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

Abstract

Objective—To evaluate effects of fats with odd and even numbers of carbon atoms on muscle metabolism in exercising horses with polysaccharide storage myopathy (PSSM).

Animals—8 horses with PSSM (6 females and 2 males; mean ± SD age, 6.3 ± 3.9 years).

Procedures—Isocaloric diets (grain, triheptanoin, corn oil, and high-fat, low-starch [HFLS] feed) were fed for 3 weeks each; horses performed daily treadmill exercise. Grain was fed to establish an exercise target, and HFLS feed was fed as a negative control diet. Daily plasma samples were obtained. For each diet, a 15-minute exercise test was performed, and gluteus medius muscle specimens and blood samples were obtained before and after exercise.

Results—Feeding triheptanoin, compared with the corn oil diet, resulted in exercise intolerance; higher plasma creatine kinase (CK) activity and concentrations of C3:0- and C7:0-acylcarnitine and insulin; and lower concentrations of nonesterified fatty acids (NEFA) and C16:0-, C18:1-, and C18:2-acylcarnitine, without changes in concentrations of plasma glucose or resting muscle substrates and metabolites. Feeding grain induced higher CK activity and insulin concentrations and lower NEFA concentrations than did corn oil or HFLS feed. Feeding grain induced higher glucose concentrations than did triheptanoin and corn oil. In muscle, feeding grain resulted in lower glucose-6-phosphate, higher citrate, and higher postexercise lactate concentrations than did the other diets.

Conclusions and Clinical Relevance—Triheptanoin had detrimental effects, reflecting decreased availability of NEFA, increased insulin stimulation of glycogen synthesis, and potential inhibition of lipid oxidation. Long-chain fats are the best dietetic for PSSM.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare effects of corn oil or a 7-carbon fat (triheptanoin) on acylcarnitine, lipid, and carbohydrate metabolism in plasma or muscle of exercising horses.

Animals—8 Thoroughbred geldings.

Procedures—Horses received isocaloric diets containing 650 mL of oil (triheptanoin or corn oil)/d for 18 or 25 days in a crossover design with a 26-day washout period. On day 17 or 24 of each feeding period, the respective oil (217 mL) was nasogastrically administered; 120 minutes later, horses performed a 90-minute submaximal exercise test (SET). Blood and muscle samples were obtained before oil administration and immediately before (blood only), during (blood only), immediately after, and 24 hours after SETs.

Results—Compared with values before oil administration, triheptanoin administration increased plasma insulin and C7:0-, C5:0- and C3:0-acylcarnitine concentrations, whereas corn oil administration increased plasma NEFA concentrations. During SETs, plasma C7:0-, C5:0-, and C3:0-acylcarnitine concentrations were higher when triheptanoin, rather than corn oil, was administered to horses. Plasma glucose, NEFA, and C2:0-, C18:1-, and C18:2-acylcarnitine concentrations increased during SETs similarly for both oils. Respiratory quotient and muscle lactate, citrate, malate, glycogen, and ATP concentrations changed similarly from before to after SETs for both oils. Compared with muscle concentrations immediately after SETs, those for glucose-6-phosphate and citrate 24 hours after SETs were lower and for glycogen were similar to values before SETs.

Conclusions and Clinical Relevance—Fatigue was not associated with depletion of citric acid cycle intermediates for either oil. Triheptanoin induced a significantly higher insulin secretion and did not appear to enhance muscle glycogen repletion.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether the basis for recurrent exertional rhabdomyolysis (RER) in Thoroughbreds lies in an alteration in the activation and regulation of the myofibrillar contractile apparatus by ionized calcium.

Animals—4 Thoroughbred mares with RER and 4 clinically normal (control) Thoroughbreds.

Procedure—Single chemically-skinned type-I (slowtwitch) and type-II (fast-twitch) muscle fibers were obtained from punch biopsy specimens, mounted to a force transducer, and the tensions that developed in response to a series of calcium concentrations were measured. In addition, myofibril preparations were isolated from muscle biopsy specimens and the maximal myofibrillar ATPase activity, as well as its sensitivity to ionized calcium, were measured.

Results—Equine type-I muscle fibers were more readily activated by calcium than were type-II muscle fibers. However, there was no difference between the type-II fibers of RER-affected and control horses in terms of calcium sensitivity of force production. There was also no difference between muscle myofibril preparations from RER-affected and control horses in calcium sensitivity of myofibrillar ATPase activity.

Conclusion and Clinical Relevance—An alteration in myofibrillar calcium sensitivity is not a basis for pathologic contracture development in muscles from RER-affected horses. Recurrent exertional rhabdomyolysis in Thoroughbreds may represent a novel heritable defect in the regulation of muscle excitation-contraction coupling or myoplasmic calcium concentration. (Am J Vet Res 2001;62:1647–1652)

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in American Journal of Veterinary Research

Abstract

Objective—To determine whether alterations in myoplasmic calcium regulation can be identified in muscle cell cultures (myotubes) and intact muscle fiber bundles derived from Thoroughbreds affected with recurrent exertional rhabdomyolysis (RER).

Animals—6 related Thoroughbreds with RER and 8 clinically normal (control) Thoroughbred or crossbred horses.

Procedures—Myotube cell cultures were grown from satellite cells obtained from muscle biopsy specimens of RER-affected and control horses. Fura-2 fluorescence was used to measure resting myoplasmic calcium concentration as well as caffeine- and 4-chloro-m-cresol (4-CMC)-induced increases in myoplasmic calcium. In addition, intact intercostal muscle fiber bundles were prepared from both types of horses, and their sensitivities to caffeine- and 4-CMC-induced contractures were determined.

Results—Myotubes of RER-affected and control horses had identical resting myoplasmic calcium concentrations. Myotubes from RER-affected horses had significantly higher myoplasmic calcium concentrations than myotubes from control horses following the addition of ≥ 2mM caffeine; however, there was no difference in their response to 4-CMC (≥ 1mM). Caffeine contracture thresholds for RER and control intact muscle cell bundles (2 vs 10mM, respectively) were significantly different, but 4-CMC contracture thresholds of muscle bundles from RER-affected and control horses (500µM) did not differ.

Conclusions and Clinical Relevance—An increase in caffeine sensitivity of muscle cells derived from a family of related RER-affected horses was detected in vitro by use of cell culture with calcium imaging and by use of fiber bundle contractility techniques. An alteration in muscle cell calcium regulation is a primary factor in the cause of this heritable myopathy. (Am J Vet Res 2002;63:1724–1731)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of 3 rations (low grain, fat, high grain) on plasma creatine kinase (CK) activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis (RER).

Animals—5 Thoroughbreds with RER and 3 healthy Thoroughbreds (control horses).

Procedures—Rations were formulated to meet (lowgrain and fat rations) or exceed (high-grain ration) daily energy requirements. Each ration was fed to horses in a crossover design for 3 weeks. Horses were exercised on a treadmill Monday through Friday; maximum speed on Monday and Friday was 11 m/s (6% slope), on Tuesday and Thursday was 9 m/s, and on Wednesday was 4.5 m/s. Plasma CK activity and lactate concentration were determined before and after exercise.

Results—Horses with RER fed the high-grain ration had significantly greater CK activity and change in CK activity 4 hours after exercise, compared with those fed the low-grain ration. Horses with RER exercised at the trot or canter had significantly greater increases in CK activity, compared with those exercised at the gallop. Plasma lactate concentrations after exercise were similar in control and affected horses. Lactate concentration and CK activity were not correlated in horses with RER.

Conclusions and Clinical Relevance—Rations high in grain and formulated to exceed daily energy requirements may increase episodes of rhabdomyolysis in Thoroughbred horses susceptible to RER. (Am J Vet Res 2000;61:1390–1395)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine insulin sensitivity, proportions of muscle fiber types, and activities of glycogenolytic and glycolytic enzymes in Belgians with and without polysaccharide storage myopathy (PSSM).

Animals—10 Quarter Horses (QHs) and 103 Belgians in which PSSM status had been determined.

Procedures—To determine insulin sensitivity, a hyperinsulinemic euglycemic clamp (HEC) technique was used in 5 Belgians with PSSM and 5 Belgians without PSSM. Insulin was infused IV at 3 mU/min/kg for 3 hours, and concentrations of blood glucose and plasma insulin were determined throughout. An IV infusion of glucose was administered to maintain blood glucose concentration at 100 mg/dL. Activities of glycogenolytic and glycolytic enzymes were assessed in snap-frozen biopsy specimens of gluteus medius muscle obtained from 4 Belgians with PSSM and 5 Belgians without PSSM. Percentages of type 1, 2a, and 2b muscle fibers were determined via evaluation of ≥ 250 muscle fibers in biopsy specimens obtained from each Belgian used in the aforementioned studies and from 10 QHs (5 with PSSM and 5 without PSSM).

Results—Belgians with and without PSSM were not significantly different with respect to whole-body insulin sensitivity, muscle activities of glycogenolytic and glycolytic enzymes, or proportions of muscle fiber types. However, Belgians had an increased proportion of type 2a and decreased proportion of type 2b muscle fibers, compared with proportions in QHs, regardless of PSSM status.

Conclusions and Clinical Relevance—PSSM in Belgians may be attributable to excessive glycogen synthesis rather than decreased glycogen utilization or enhanced glucose uptake into muscle cells.

Full access
in American Journal of Veterinary Research