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  • Author or Editor: Linnea R. Lentz x
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Abstract

Objective

To determine whether increased sensitivity to pharmacologic agents was a general property of equine exertional myopathies, including polysaccharide storage myopathy (PSSM) in Quarter Horses.

Animals

5 adult Quarter Horses with exertional rhabdomyolysis and abnormal polysaccharide accumulation in skeletal muscle and 4 clinically normal adult Quarter or Quarter-type horses.

Procedures

Twitch time course measurements and contracture responses to various concentrations of caffeine and halothane for small bundles of intact external intercostal muscle fibers were measured in all horses.

Results

Caffeine contracture threshold of muscles from Quarter Horses with PSSM was not different from that of clinically normal horses (5 mM in both groups). Muscles from horses with PSSM and from clinically normal horses did not have contracture in response to up to 2% halothane.

Conclusions and Clinical Relevance

Results were in contrast to the increased sensitivity to caffeine and halothane for muscles from Thoroughbreds with recurrent exertional rhabdomyolysis (RER). Although clinical signs of muscular stiffness after exercise are similar between Quarter Horses with PSSM and Thoroughbreds with RER, these breeds appear to have 2 distinct myopathies with different pathophysiologic bases. Unlike RER in Thoroughbreds, PSSM in Quarter Horses does not appear to be accompanied by a defect in regulation of muscle contraction. (Am J Vet Res 1999;60:684–688)

Free access
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 whether abnormal regulation of muscle contraction similar to that associated with malignant hyperthemia (MH) was evident in intact external intercostal muscle cells from Thoroughbreds with recurrent exertional rhabdomyolysis (RER).

Animals

5 adult Thoroughbred horses with RER and 7 clinically normal adult Thoroughbred or mixed-breed horses.

Procedures

Twitch time course variables and contracture responses to various concentrations of potassium, caffeine, and halothane were measured in small bundles of intact external intercostal muscle cells from clinically normal horses and horses with RER.

Results

Threshold for significant contracture induced by potassium depolarization was lower for RER-affected muscles, compared with normal muscles, although the relationship between potassium concentration and membrane potential were not different. Thresholds for contracture induced by caffeine and halothane were also lower for RER-affected muscles, compared with normal muscles. Lower thresholds for caffeine- and halothane-induced contractures, as well as depolarization-elicited contractures, in RER-affected muscles suggest a defect in myoplasmic calcium regulation.

Conclusions and Clinical Relevance

Regulation of muscle contraction is abnormal in Thoroughbreds with RER. The specific defect may be attributable to abnormal intracellular calcium regulation. Knowledge of the specific defect involved in RER may lead to improved prevention and treatment of RER-affected horses. (Am J Vet Res 1999;60:992-999)

Free access
in American Journal of Veterinary Research