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Stephanie J. Valberg - One of the best experts on this subject based on the ideXlab platform.
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A Review of Dietary Fat Supplementation in Horses with Exertional Rhabdomyolysis
2020Co-Authors: Erica C. Mckenzie, Stephanie J. Valberg, Joe D. PaganAbstract:Two forms of Exertional Rhabdomyolysis commonly respond to changes in diet and management. Unfit horses with polysaccharide storage myopathy benefit from daily exercise, removal of high-starch concentrates, and addition of fat to provide a moderate caloric intake. Fit horses with recurrent Exertional Rhabdomyolysis can maintain a high caloric intake if dietary starch is reduced and the ration is heavily supplemented with fat. Authors’ addresses: Department of Clinical and Population Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108 (McKenzie, Valberg); Kentucky Equine Research Inc., 3910 Delaney Ferry Road, Versailles, KY 40383 (Pagan). © 2002 AAEP.
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suspected myofibrillar myopathy in arabian horses with a history of Exertional Rhabdomyolysis
Equine Veterinary Journal, 2016Co-Authors: Stephanie J. Valberg, Erica C. Mckenzie, L. V. Eyrich, Jan Shivers, N. E. Barnes, Carrie J. FinnoAbstract:SummaryReasons for performing study Although Exertional Rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. Objectives To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with Exertional myopathies (retro-ER). Study design Prospective and retrospective histopathological description. Methods Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent Exertional Rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann–Whitney U and Fisher's exact tests. Results Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. Conclusions In a subset of Arabian horses with intermittent episodes of Exertional Rhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder.
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Suspected myofibrillar myopathy in Arabian horses with a history of Exertional Rhabdomyolysis
Equine Veterinary Journal, 2015Co-Authors: Stephanie J. Valberg, Erica C. Mckenzie, L. V. Eyrich, Jan Shivers, N. E. Barnes, Carrie J. FinnoAbstract:SummaryReasons for performing study Although Exertional Rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. Objectives To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with Exertional myopathies (retro-ER). Study design Prospective and retrospective histopathological description. Methods Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent Exertional Rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann–Whitney U and Fisher's exact tests. Results Centrally located myonuclei in mature myofibres were found in significantly more (P
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prevalence of Exertional Rhabdomyolysis in endurance horses in the pacific northwestern united states
Equine Veterinary Journal, 2015Co-Authors: Melissa S Wilberger, Erica C. Mckenzie, Mark E Payton, Johanna D Rigas, Stephanie J. ValbergAbstract:SummaryReasons for performing study Exertional Rhabdomyolysis (ER) is a reported syndrome in competing endurance horses; however, the prevalence and cause of ER in this population have not been defined. Objectives To determine the prevalence of ER in a sample of endurance racing horses and investigate factors, including relevant genetic defects, contributing to the occurrence of Rhabdomyolysis in this group. Study design Prospective clinical study. Methods Riders of 101 horses participating in one of four 50-mile (80.5 km) distance races completed a comprehensive questionnaire regarding the medical history, management and performance of their horse. Serum creatine kinase activity (CK) was measured before and 4 h after completion of exercise. Hair samples were analysed by PCR for the R309H mutation in the glycogen synthase gene (GYS1) responsible for type 1 polysaccharide storage myopathy (PSSM) and the C7360G mutation in the ryanodine receptor 1 (RYR1) gene causing malignant hyperthermia (MH). Results Samples were obtained from 68 Arabians, 20 half-Arabians and 13 horses of other breeds. Serum CK was above the resting reference interval (145–633 u/l) in 38 horses after racing (median 883 u/l, range 658–3739) but was compatible with values previously reported in apparently healthy endurance horses. Pathological ER was suspected to occur in 4 horses with serum CK activities exceeding 10,000 u/l 4 h after racing (median 84,825 u/l; range 10,846–381,790) including 3 Arabians and one half-Arabian horse. GYS1 and RYR1 mutations were not present in hair samples from any horses. Conclusions Exertional Rhabdomyolysis occurred at a prevalence of 4.0% in a sample of horses participating in 50 mile distance events and all affected horses were Arabian or half-Arabian. The cause of ER in the endurance horse population remains unknown; however, ER in competing Arabian endurance horses is unlikely to be due to type 1 PSSM or MH.
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Exertional Rhabdomyolysis in quarter horses and thoroughbreds one syndrome multiple aetiologies
Equine Veterinary Journal, 2010Co-Authors: Stephanie J. Valberg, Jennifer M. Macleay, James R Mickelson, Esther M Gallant, Linnea R Lentz, F D De La CorteAbstract:Summary The purpose of this study was to determine if chronic Exertional Rhabdomyolysis (ER) in Quarter Horses and Thoroughbreds represents one or several distinct myopathies. Eighteen Quarter Horses and 18 Thoroughbreds with ER were selected from cases presented to the Veterinary Hospital on the basis of a history of ER, assessment of muscle histopathology, and serum CK activity before and 4 h post exercise. In addition, 2 of 3 of the following parameters were evaluated: muscle glycogen concentrations, thyroid hormones (T3, T4), fractional excretion (FE) of sodium, potassium and chloride. The CK response to training, the metabolic response to a near maximal standardised exercise test (SET), blood glucose concentrations after an i.v. glucose challenge and a skeletal muscle in vitro caffeine contracture test were performed on 5 of the Quarter Horses, selected because of polysaccharide storage myopathy (PSSM), and 5 of the Thoroughbreds. Serum T3 and T4 were all within normal limits. Low FE of sodium and potassium were seen in <20% of Quarter Horses and Thoroughbreds. Four hours post exercise, CK was increased in 77% of Quarter Horses and 72% of Thoroughbreds with ER. Muscle glycogen concentrations in Quarter Horses with ER were significantly higher than in normal Quarter Horses and Thoroughbreds with ER. No Thoroughbreds, but 15/18 Quarter Horses with ER had abnormal polysaccharide accumulation in muscle biopsies consistent with a diagnosis of PSSM. PSSM Quarter Horses had higher CK activity during training than Thoroughbreds and higher glycogen utilisation with the SET. PSSM Quarter Horses also had significantly enhanced glucose clearance compared to normal Quarter Horses and Thoroughbreds with ER. Thoroughbreds with ER had significantly lower thresholds for caffeine-induced contracture than normal horses and PSSM Quarter Horses. It was concluded that there are multiple causes for Exertional Rhabdomyolysis. In Quarter Horses, Rhabdomyolysis is commonly due to a glycogen storage disorder, PSSM, and is readily expressed in untrained horses. In Thoroughbreds, ER is commonly due to an underlying abnormality of muscle contraction. Rhabdomyolysis in Thoroughbreds, however, is only expressed intermittently when key stressors are present.
Priscilla M. Clarkson - One of the best experts on this subject based on the ideXlab platform.
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Perspectives on Exertional Rhabdomyolysis
Sports Medicine, 2017Co-Authors: Eric S. Rawson, Priscilla M. Clarkson, Mark A. TarnopolskyAbstract:Exertional (exercise-induced) Rhabdomyolysis is a potentially life threatening condition that has been the subject of research, intense discussion, and media attention. The causes of Rhabdomyolysis are numerous and can include direct muscle injury, unaccustomed exercise, ischemia, extreme temperatures, electrolyte abnormalities, endocrinologic conditions, genetic disorders, autoimmune disorders, infections, drugs, toxins, and venoms. The objective of this article is to review the literature on Exertional Rhabdomyolysis, identify precipitating factors, and examine the role of the dietary supplement creatine monohydrate. PubMed and SPORTDiscus databases were searched using the terms Rhabdomyolysis, muscle damage, creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Additionally, the references of papers identified through this search were examined for relevant studies. A meta-analysis was not performed. Although the prevalence of Rhabdomyolysis is low, instances still occur where exercise is improperly prescribed or used as punishment, or incomplete medical history is taken, and Exertional Rhabdomyolysis occurs. Creatine monohydrate does not appear to be a precipitating factor for Exertional Rhabdomyolysis. Healthcare professionals should be able to recognize the basic signs of Exertional Rhabdomyolysis so prompt treatment can be administered. For the risk of Rhabdomyolysis to remain low, exercise testing and prescription must be properly conducted based on professional standards.
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Exertional Rhabdomyolysis and acute renal failure in marathon runners
Sports Medicine, 2007Co-Authors: Priscilla M. ClarksonAbstract:Strenuous exercise, including marathon running, can result in damage to skeletal muscle cells, a process known as Exertional Rhabdomyolysis. In most cases, this damage is resolved without consequence. However, when the damage is profound, there is a release of muscle proteins into the blood; one of these proteins, myoglobin, in high concentrations and under certain conditions (such as dehydration and heat stress) can precipitate in the kidneys, thereby resulting in acute renal failure. Although the marathon is a gruelling physiological challenge, with races sometimes run in hot and humid weather, acute renal failure is relatively infrequent. From case reports, a high proportion of marathon runners who developed acute renal failure had taken analgesics, had a viral or bacterial infection, or a pre-existing condition. The rare cases of acute renal failure in marathon runners may be a situation of the 'perfect storm' where there are several factors (heat stress, dehydration, latent myopathy, non-steroidal anti-inflammatory or other drug/analgesic use, and viral/bacterial infection) that, in some combination, come together to result in acute renal failure.
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Exertional Rhabdomyolysis does elevated blood creatine kinase foretell renal failure
Current Sports Medicine Reports, 2006Co-Authors: Priscilla M. Clarkson, Randy E EichnerAbstract:Recreational activity frequently produces large increases in circulating CK activity without consequence. Thus, high CK levels alone do not portend renal failure. Most cases of Exertional Rhabdomyolysis can, and probably do, resolve on their own without treatment. When taking a blood sample during a routine check, for example in monitoring patients on statin therapy, a high blood CK activity may indicate that strenuous exercise was performed in the previous 10 days. Patients should be queried as to their exercise history during this time. Snow shoveling, dirt shoveling, lifting and lowering heavy boxes, strenuous resistance training, and excessive calisthenics (such as push-ups and pull-ups) are exercises that may dramatically increase circulating CK activity for several days due to forceful eccentric contractions.
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Exertional Rhabdomyolysis: Does elevated blood creatine kinase foretell renal failure?
Current Sports Medicine Reports, 2006Co-Authors: Priscilla M. Clarkson, E. Randy EichnerAbstract:Recreational activity frequently produces large increases in circulating CK activity without consequence. Thus, high CK levels alone do not portend renal failure. Most cases of Exertional Rhabdomyolysis can, and probably do, resolve on their own without treatment. When taking a blood sample during a routine check, for example in monitoring patients on statin therapy, a high blood CK activity may indicate that strenuous exercise was performed in the previous 10 days. Patients should be queried as to their exercise history during this time. Snow shoveling, dirt shoveling, lifting and lowering heavy boxes, strenuous resistance training, and excessive calisthenics (such as push-ups and pull-ups) are exercises that may dramatically increase circulating CK activity for several days due to forceful eccentric contractions. In addition to elevated CK, factors such as underlying disease, dehydration, environmental heat stress, or genetic predisposition (eg, sickle cell trait) are likely required for Exertional Rhabdomyolysis to result in acute renal failure [8]. Persons who present to the emergency room with painful, swollen muscles about 2 days after a bout of strenuous exercise should be monitored for kidney function (BUN and creatinine), evidence of myoglobinuria and dehydration, and be queried regarding hydration, heat stress during the exercise, and possible trauma. In cases of Exertional Rhabdomyolysis, especially in laboratory situations, CK levels up to 100,000 U/L in the absence of nephrotoxic factors have been found to resolve without consequence when no treatment is provided. However, because few data confirm this in a clinical situation in which there may be comorbidities, it remains conservative and prudent in the emergency room to hydrate intravenously and monitor closely to help avoid hyperkalemia and/or acute renal failure in the face of fulminant Exertional Rhabdomyolysis.
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case report of Exertional Rhabdomyolysis in a 12 year old boy
Medicine and Science in Sports and Exercise, 2006Co-Authors: Priscilla M. ClarksonAbstract:Introduction: Exertional Rhabdomyolysis has been well characterized, and many case reports exist. No cases of Exertional Rhabdomyolysis in young healthy children (preteen) have been published. Case Summary: Reviewed were the medical records of a 12-yr-old boy who participated in an indoor physical education class where excessive (>250) repetitive squat jumps were performed as punishment for talking in class. The boy, who reported intense muscle soreness in the thighs and dark urine 2 d postexercise, was brought to the emergency room by his parent. His serum creatine kinase (CK) was 92,115 U[middle dot]L-1 and urinalysis indicated the presence of blood and protein. He was transferred to another hospital that evening, admitted, and treated for 7 d. His serum CK rose to 244,006 U[middle dot]L-1 at 4 d postexercise. Conclusion: Although Exertional Rhabdomyolysis is rare in young children, it can occur when excessive exercise is spurred on by an adult
R J Piercy - One of the best experts on this subject based on the ideXlab platform.
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epidemiology of Exertional Rhabdomyolysis susceptibility in standardbred horses reveals associated risk factors and underlying enhanced performance
PLOS ONE, 2010Co-Authors: C M Isgren, M M Upjohn, M Fernandezfuente, Claire Massey, G E Pollott, K L P Verheyen, R J PiercyAbstract:Background Exertional Rhabdomyolysis syndrome is recognised in many athletic horse breeds and in recent years specific forms of the syndrome have been identified. However, although Standardbred horses are used worldwide for racing, there is a paucity of information about the epidemiological and performance-related aspects of the syndrome in this breed. The objectives of this study therefore were to determine the incidence, risk factors and performance effects of Exertional Rhabdomyolysis syndrome in Standardbred trotters and to compare the epidemiology and genetics of the syndrome with that in other breeds. Methodology/Principal Findings A questionnaire-based case-control study (with analysis of online race records) was conducted following identification of horses that were determined susceptible to Exertional Rhabdomyolysis (based on serum biochemistry) from a total of 683 horses in 22 yards. Thirty six Exertional Rhabdomyolysis-susceptible horses were subsequently genotyped for the skeletal muscle glycogen synthase (GYS1) mutation responsible for type 1 polysaccharide storage myopathy. A total of 44 susceptible horses was reported, resulting in an annual incidence of 6.4 (95% CI 4.6–8.2%) per 100 horses. Female horses were at significantly greater risk than males (odds ratio 7.1; 95% CI 2.1–23.4; p = 0.001) and nervous horses were at a greater risk than horses with calm or average temperaments (odds ratio 7.9; 95% CI 2.3–27.0; p = 0.001). Rhabdomyolysis-susceptible cases performed better from standstill starts (p = 0.04) than controls and had a higher percentage of wins (p = 0.006). All Exertional Rhabdomyolysis-susceptible horses tested were negative for the R309H GYS1 mutation. Conclusions/Significance Exertional Rhabdomyolysis syndrome in Standardbred horses has a similar incidence and risk factors to the syndrome in Thoroughbred horses. If the disorder has a genetic basis in Standardbreds, improved performance in susceptible animals may be responsible for maintenance of the disorder in the population.
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a glycogen synthase 1 mutation associated with equine polysaccharide storage myopathy and Exertional Rhabdomyolysis occurs in a variety of uk breeds
Equine Veterinary Journal, 2009Co-Authors: R L Stanley, Stephanie J. Valberg, Molly E Mccue, James R Mickelson, I G Mayhew, C M Mcgowan, Caroline Hahn, J C Pattersonkane, R J PiercyAbstract:REASONS FOR PERFORMING STUDY A glycogen synthase (GYS1) mutation has been described in horses with histopathological evidence of polysaccharide storage myopathy (PSSM) in the USA. It is unknown whether the same mutation is present in horses from the UK. OBJECTIVES To determine whether the GYS1 mutation occurs in UK horses with histopathological evidence of PSSM and Exertional Rhabdomyolysis. HYPOTHESIS The R309H GYS1 mutation is present in a variety of UK horse breeds and that the mutation is commonly associated with Exertional Rhabdomyolysis. METHODS DNA was extracted from 47 muscle or blood samples from UK horses with histories of Exertional Rhabdomyolysis in which muscle biopsy diagnosis had been pursued. The proportions of GYS1 mutation positive cases were compared among histopathologically defined groups. In addition, breeds that carried the GYS1 mutation were identified from a total of 37 grade 2 (amylase-resistant) PSSM cases. RESULTS Of 47 horses with Exertional Rhabdomyolysis in which a muscle biopsy diagnosis was pursued, 10 (21%) carried the GYS1 mutation. The mutation was only found in horses with grade 2 PSSM (i.e. not in horses with normal, idiopathic myopathy or grade 1 PSSM biopsy samples). In total, the GYS1 mutation was found in 24/37 (65%) of grade 2 PSSM cases. A variety of breeds, including Quarter Horse, Appaloosa, Warmblood, Connemara-cross, Cob, Polo Pony and Thoroughbred cross carried the mutation. CONCLUSIONS The GYS1 mutation is an important cause of Exertional Rhabdomyolysis of UK horse breeds but does not account for all forms of PSSM. POTENTIAL RELEVANCE Genotyping is recommended in cases of Exertional Rhabdomyolysis, prior to or in combination with, muscle biopsy. However a significant proportion of horses with histopathological evidence of PSSM and/or Exertional Rhabdomyolysis have different diseases.
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vitamin e and Exertional Rhabdomyolysis during endurance sled dog racing
Neuromuscular Disorders, 2001Co-Authors: R J Piercy, K W Hinchcliff, Paul S Morley, Robert A Disilvestro, Gregory A Reinhart, Stuart L Nelson, Karin E Schmidt, Morrie A CraigAbstract:Exertional Rhabdomyolysis (ER) is common in sled dogs, animals with high energy expenditures that consume high fat (60% of ingested calories) diets. Associations between pre-race plasma [vitamin E] and total antioxidant status (TAS) and risk of developing ER were examined in dogs competing in the 1998 Iditarod race. Pre-race blood samples were collected from 750 dogs and a second sample was collected from 158 dogs withdrawn from the race at various times. Plasma creatine kinase activity was used to identify withdrawn dogs with ER. There was no association between pre-race plasma [vitamin E] and risk of development of ER. Dogs that developed ER started the race with higher TAS, but when withdrawn, had lower TAS than unaffected dogs and had similar pre-race [vitamin E] but higher [vitamin E] at time of withdrawal. Hence, the risk of ER in sled dogs is not affected by plasma [vitamin E] before the race.
J B Robinson - One of the best experts on this subject based on the ideXlab platform.
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acute Exertional Rhabdomyolysis and its relationship to sickle cell trait
Journal of Athletic Training, 1995Co-Authors: G L Harrelson, A L Fincher, J B RobinsonAbstract:Abstract Exertional Rhabdomyolysis, a syndrome characterized by skeletal muscle degeneration and muscle enzyme leakage, has been shown to occur in normal, healthy individuals following strenuous exercise. In severe cases, this syndrome can result in renal failure and sudden death. Although anyone who performs strenuous exercise may be at risk for developing Exertional Rhabdomyolysis, some individuals may be more susceptible than others. A number of case reports of Exertional Rhabdomyolysis involve persons with sickle-cell trait, leading to the theory that these individuals might be at greater risk for developing the syndrome than those without this trait. This article discusses the etiology of Exertional Rhabdomyolysis, the associated risk factors for persons with sickle-cell trait, and the recommended preventive measures. Additionally, several case studies of Exertional Rhabdomyolysis are reviewed.
James R Mickelson - One of the best experts on this subject based on the ideXlab platform.
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Exertional Rhabdomyolysis in quarter horses and thoroughbreds one syndrome multiple aetiologies
Equine Veterinary Journal, 2010Co-Authors: Stephanie J. Valberg, Jennifer M. Macleay, James R Mickelson, Esther M Gallant, Linnea R Lentz, F D De La CorteAbstract:Summary The purpose of this study was to determine if chronic Exertional Rhabdomyolysis (ER) in Quarter Horses and Thoroughbreds represents one or several distinct myopathies. Eighteen Quarter Horses and 18 Thoroughbreds with ER were selected from cases presented to the Veterinary Hospital on the basis of a history of ER, assessment of muscle histopathology, and serum CK activity before and 4 h post exercise. In addition, 2 of 3 of the following parameters were evaluated: muscle glycogen concentrations, thyroid hormones (T3, T4), fractional excretion (FE) of sodium, potassium and chloride. The CK response to training, the metabolic response to a near maximal standardised exercise test (SET), blood glucose concentrations after an i.v. glucose challenge and a skeletal muscle in vitro caffeine contracture test were performed on 5 of the Quarter Horses, selected because of polysaccharide storage myopathy (PSSM), and 5 of the Thoroughbreds. Serum T3 and T4 were all within normal limits. Low FE of sodium and potassium were seen in <20% of Quarter Horses and Thoroughbreds. Four hours post exercise, CK was increased in 77% of Quarter Horses and 72% of Thoroughbreds with ER. Muscle glycogen concentrations in Quarter Horses with ER were significantly higher than in normal Quarter Horses and Thoroughbreds with ER. No Thoroughbreds, but 15/18 Quarter Horses with ER had abnormal polysaccharide accumulation in muscle biopsies consistent with a diagnosis of PSSM. PSSM Quarter Horses had higher CK activity during training than Thoroughbreds and higher glycogen utilisation with the SET. PSSM Quarter Horses also had significantly enhanced glucose clearance compared to normal Quarter Horses and Thoroughbreds with ER. Thoroughbreds with ER had significantly lower thresholds for caffeine-induced contracture than normal horses and PSSM Quarter Horses. It was concluded that there are multiple causes for Exertional Rhabdomyolysis. In Quarter Horses, Rhabdomyolysis is commonly due to a glycogen storage disorder, PSSM, and is readily expressed in untrained horses. In Thoroughbreds, ER is commonly due to an underlying abnormality of muscle contraction. Rhabdomyolysis in Thoroughbreds, however, is only expressed intermittently when key stressors are present.
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a glycogen synthase 1 mutation associated with equine polysaccharide storage myopathy and Exertional Rhabdomyolysis occurs in a variety of uk breeds
Equine Veterinary Journal, 2009Co-Authors: R L Stanley, Stephanie J. Valberg, Molly E Mccue, James R Mickelson, I G Mayhew, C M Mcgowan, Caroline Hahn, J C Pattersonkane, R J PiercyAbstract:REASONS FOR PERFORMING STUDY A glycogen synthase (GYS1) mutation has been described in horses with histopathological evidence of polysaccharide storage myopathy (PSSM) in the USA. It is unknown whether the same mutation is present in horses from the UK. OBJECTIVES To determine whether the GYS1 mutation occurs in UK horses with histopathological evidence of PSSM and Exertional Rhabdomyolysis. HYPOTHESIS The R309H GYS1 mutation is present in a variety of UK horse breeds and that the mutation is commonly associated with Exertional Rhabdomyolysis. METHODS DNA was extracted from 47 muscle or blood samples from UK horses with histories of Exertional Rhabdomyolysis in which muscle biopsy diagnosis had been pursued. The proportions of GYS1 mutation positive cases were compared among histopathologically defined groups. In addition, breeds that carried the GYS1 mutation were identified from a total of 37 grade 2 (amylase-resistant) PSSM cases. RESULTS Of 47 horses with Exertional Rhabdomyolysis in which a muscle biopsy diagnosis was pursued, 10 (21%) carried the GYS1 mutation. The mutation was only found in horses with grade 2 PSSM (i.e. not in horses with normal, idiopathic myopathy or grade 1 PSSM biopsy samples). In total, the GYS1 mutation was found in 24/37 (65%) of grade 2 PSSM cases. A variety of breeds, including Quarter Horse, Appaloosa, Warmblood, Connemara-cross, Cob, Polo Pony and Thoroughbred cross carried the mutation. CONCLUSIONS The GYS1 mutation is an important cause of Exertional Rhabdomyolysis of UK horse breeds but does not account for all forms of PSSM. POTENTIAL RELEVANCE Genotyping is recommended in cases of Exertional Rhabdomyolysis, prior to or in combination with, muscle biopsy. However a significant proportion of horses with histopathological evidence of PSSM and/or Exertional Rhabdomyolysis have different diseases.
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myoplasmic calcium regulation in myotubes from horses with recurrent Exertional Rhabdomyolysis
American Journal of Veterinary Research, 2002Co-Authors: Linnea R Lentz, Stephanie J. Valberg, James R Mickelson, Gary Onan, Lee V Herold, Esther M GallantAbstract: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 myoplas...
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calcium regulation by skeletal muscle membranes of horses with recurrent Exertional Rhabdomyolysis
American Journal of Veterinary Research, 2000Co-Authors: Tara L Ward, Stephanie J. Valberg, Esther M Gallant, James R MickelsonAbstract: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.
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in vitro contractile responses and contracture testing of skeletal muscle from quarter horses with Exertional Rhabdomyolysis
American Journal of Veterinary Research, 1999Co-Authors: Linnea R Lentz, Stephanie J. Valberg, James R Mickelson, Esther M GallantAbstract: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.