Chromosomal assignments for the equine AMPK family genes.
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AMP-Activated Protein Kinases↗
Biomedical subjects
S J Valberg
Publications and source records attributed to S J Valberg.
Comparison of histopathologic criteria and skeletal muscle fixation techniques for the diagnosis of polysaccharide storage myopathy in horses.
The purpose of the study reported here was to determine the effect of three methods of fixation of skeletal muscle biopsy specimens on the histopathologic appearance of muscle sections and to determine criteria that were most consistently associated with a diagnosis of polysaccharide storage myopathy (PSSM) in horses. Surgically excised semimembranosus muscle biopsy specimens were obtained from nine horses previously diagnosed with PSSM and from 15 control horses. Portions of each specimen were fixed in formalin, frozen immediately, and chilled for 24 hours prior to freezing. Sections stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and amylase-PAS were scored for histopathologic criteria by three investigators blinded to the sample origin. The presence of amylase-resistant, abnormal polysaccharide was found to be the most sensitive and specific diagnostic indicator for PSSM, and was readily detected regardless of the fixation technique or investigator. Other less-specific features associated with PSSM included atrophy and cytoplasmic and subsarcolemmal vacuoles; however, their histologic scores varied among fixation technique and investigators. Scores for subsarcolemmal and cytoplasmic amylase-sensitive glycogen in horses with PSSM were similar to those for control horses and varied among fixation techniques. In conclusion, PSSM is most accurately diagnosed in muscle biopsy specimens on the basis of appearance of amylase-resistant, abnormal polysaccharide, not amylase-sensitive glycogen, regardless of fixation technique. In general, frozen sections appeared to be better suited for studying myopathies because many histopathologic features of skeletal muscle were obscured by formalin fixation.
Animals↗
Genetic mapping of GBE1 and its association with glycogen storage disease IV in American Quarter horses.
Comparative biochemical and histopathological data suggest that a deficiency in the glycogen branching enzyme (GBE) is responsible for a fatal neonatal disease in Quarter Horse foals that closely resembles human glycogen storage disease type IV (GSD IV). Identification of DNA markers closely linked to the equine GBE1 gene would assist us in determining whether a mutation in this gene leads to the GSD IV-like condition. FISH using BAC clones as probes assigned the equine GBE1 gene to a marker deficient region of ECA26q12-->q13. Four other genes, ROBO2, ROBO1, POU1F1, and HTR1F, that flank GBE1 within a 10-Mb segment of HSA3p12-->p11, were tightly linked to equine GBE1 when analyzed on the Texas A&M University 5000 rad equine radiation hybrid panel, while the GLB1, MITF, RYBP, and PROS1 genes that flank this 10-Mb interval were not linked with markers in the GBE1 group. A polymorphic microsatellite (GBEms1) in a GBE1 BAC clone was then identified and genetically mapped to ECA26 on the Animal Health Trust full-sibling equine reference family. All Quarter Horse foals affected with GSD IV were homozygous for an allele of GBEms1, as well as an allele of the most closely linked microsatellite marker, while a control horse population showed significant allelic variation with these markers. This data provides strong molecular genetic support for the candidacy of the GBE1 locus in equine GSD IV.
1,4-alpha-Glucan Branching Enzyme↗
Molecular characterization and mutational screening of the PRKAG3 gene in the horse.
The PRKAG3 gene encodes a muscle-specific isoform of the regulatory gamma subunit of AMP-activated protein kinase (AMPK). A major part of the coding PRKAG3 sequence was isolated from horse muscle cDNA using reverse-transcriptase (RT)-PCR analysis. Horse-specific primers were used to amplify genomic fragments containing 12 exons. Comparative sequence analysis of horse, pig, mouse, human, Fugu, and zebrafish was performed to establish the exon/intron organization of horse PRKAG3 and to study the homology among different isoforms of AMPK gamma genes in vertebrates. The results showed conclusively that the three different isoforms (gamma1, gamma2, and gamma3) were established already in bony fishes. Seven single nucleotide polymorphisms (SNPs), five causing amino acid substitutions, were identified in a screening across horse breeds with widely different phenotypes as regards muscle development and intended performance. The screening of a major part of the PRKAG3 coding sequence in a small case/control material of horses affected with polysaccharide storage myopathy did not reveal any mutation that was exclusively associated with this muscle storage disease. The breed comparison revealed several potentially interesting SNPs. One of these (Pro258Leu) occurs at a residue that is highly conserved among AMPK gamma genes. In an SNP screening, the variant allele was only found in horse breeds that can be classified as heavy (Belgian) or moderately heavy (North Swedish Trotter, Fjord, and Swedish Warmblood) but not in light horse breeds selected for speed or racing performance (Standardbred, Thoroughbred, and Quarter horse) or in ponies (Icelandic horses and Shetland pony). The results will facilitate future studies of the possible functional significance of PRKAG3 polymorphisms in horses.
AMP-Activated Protein Kinases↗
Calcium sensitivity of force production and myofibrillar ATPase activity in muscles from Thoroughbreds with recurrent exertional rhabdomyolysis.
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. PROCEDURES: Single chemically-skinned type-I (slow-twitch) 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. CONCLUSIONS 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.
Adenosine Triphosphatases↗
Twenty-one new equine dinucleotide repeat microsatellites.
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Alleles↗
Effect of ration and exercise on plasma creatine kinase activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis.
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 (low-grain 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.
Animal Feed↗
Effects of dexamethasone on development of immunoglobulin G subclass responses following vaccination of horses.
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.
Animals↗
Calcium regulation by skeletal muscle membranes of horses with recurrent exertional rhabdomyolysis.
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.
Animals↗
Spinal muscle pathology.
Clinical signs that are easily referred to spinal muscle pathology include atrophy of epaxial muscles, focal swelling and palpable tenderness, as well as enlarged muscles with increased tone. Less easily recognized signs include rigidity of the spine, shortened stride, hindlimb lameness, and indicators of poor performance. Muscle biopsy is one option in evaluating sore backs and is best used when physical examination and imaging procedures do not reveal a likely diagnosis or when conventional treatments are unsuccessful. Rhabdomyolysis of spinal muscles may be due to nutritional myodegeneration (foals), recurrent exertional rhabdomyolysis, and polysaccharide storage myopathy. Atrophy of spinal muscles can be due to severe rhabdomyolysis, immune-related myopathy, or neurogenic atrophy from nerve trauma, EPM, or EMND.
Animals↗
A synteny map of the horse genome comprised of 240 microsatellite and RAPD markers.
To generate a domestic horse genome map we integrated synteny information for markers screened on a somatic cell hybrid (SCH) panel with published information for markers physically assigned to chromosomes. The mouse-horse SCH panel was established by fusing pSV2neo transformed primary horse fibroblasts to either RAG or LMTk mouse cells, followed by G418 antibiotic selection. For each of the 108 cell lines of the panel, we defined the presence or absence of 240 genetic markers by PCR, including 58 random amplified polymorphic DNA (RAPD) markers and 182 microsatellites. Thirty-three syntenic groups were defined, comprised of two to 26 markers with correlation coefficient (r) values ranging from 0.70 to 1.0. Based on significant correlation values with physically mapped microsatellite (type II) or gene (type I) markers, 22 syntenic groups were assigned to horse chromosomes (1, 2, 3, 4, 6, 9, 10, 11, 12, 13, 15, 18, 19, 20, 21, 22, 23, 24, 26, 30, X and Y). The other 11 syntenic groups were provisionally assigned to the remaining chromosomes based on information provided by heterologous species painting probes and work in progress with type I markers.
Animals↗
Skeletal muscle metabolic response to exercise in horses with 'tying-up' due to polysaccharide storage myopathy.
Polysaccharide storage myopathy (PSSM) is a distinct cause of exertional rhabdomyolysis in Quarter Horses that results in glycogen and abnormal polysaccharide accumulation. The purpose of this study was to determine if excessive glycogen storage in PSSM is due to a glycolytic defect that impairs utilisation of this substrate during exercise. Muscle biopsies, blood lactates and serum CK were obtained 1) at rest from 5 PSSM Quarter Horses, 4 normal Quarter Horses (QH controls) and 6 Thoroughbreds with recurrent exertional rhabdomyolysis (TB RER) and 2) after a maximal treadmill exercise test in PSSM and QH controls. In addition, 3 PSSM horses performed a submaximal exercise test. At rest, muscle glycogen concentrations were 2.4x and 1.9x higher in PSSM vs. QH controls or TB RER, respectively. Muscle lactates at rest were similar between PSSM and QH controls but significantly higher in PSSM vs. TB RER. Muscle glucose-6-phosphate concentrations were also higher in PSSM horses than controls combined. During maximal exercise, mean muscle glycogen concentrations declined 2.7x more and mean lactate increased 2x more in PSSM vs. QH controls; however, differences were not statistically significant. Blood lactate concentrations after maximal exercise did not reflect generally higher muscle lactate in PSSM vs. QH controls. No change in blood lactate concentrations occurred in PSSM horses with submaximal exercise. Serum CK activity increased significantly 4 h after maximal and submaximal exercise and was significantly higher in PSSM vs. QH controls. These results show that during maximal exercise, PSSM horses utilised muscle glycogen and produce lactic acid via a functional glycolytic pathway and that during submaximal exercise oxidative metabolism was unimpaired. The excessive glycogen storage and formation of abnormal polysaccharide in PSSM horses therefore appear to reflect increased glycogen synthesis rather than decreased utilisation. The specific subset of horses with exertional rhabdomyolysis due to PSSM would likely benefit clinically from a diet low in soluble carbohydrates like grain with fat added as well as gradually increasing daily exercise to reduce excessive glycogen accumulation and enhance utilisation.
Adenosine Triphosphate↗
Blood glucose clearance after feeding and exercise in polysaccharide storage myopathy.
Polysaccharide storage myopathy (PSSM) in Quarter Horses (QH) and QH crosses is a glycogen storage disorder in which blood glucose clearance and insulin sensitivity, following an i.v. or oral glucose challenge, are enhanced. Exercise is known also to enhance glucose uptake into skeletal muscle in many animal species. Therefore, the purpose of this study was to compare the effect of exercise on glucose clearance in PSSM and control horses when an oral carbohydrate meal (8 Mcal sweet feed) was fed following either 12 h fasting alone (NEX protocol) or following fasting and a standard exercise protocol (EX protocol). In the NEX protocol, horses fasted 12 h and then were fed 8 megacalories (Mcal) of sweet feed (2.3 kg). In the EX protocol, horses were fed sweet feed 2 h after an exercise test (SET). Blood glucose was analysed for < 480 min after feeding. Muscle biopsies were taken before and after the EX protocol. With the NEX protocol, the mean of all blood glucose and insulin concentrations were significantly lower in fed-PSSM horses than controls (P < 0.013). The EX protocol in control horses caused a less pronounced percentage change in glucose concentration from baseline following feeding compared to the NEX protocol (mean peak EX 26.5% vs. NEX 70.2%, respectively) (P < 0.0003). In PSSM horses, the EX protocol also resulted in a lower percent change in glucose concentration following feeding compared to the NEX protocol (44.7 vs. 67.5%, respectively) (P = 0.021). The magnitude of the difference in percentage change of blood glucose concentration with the EX protocol was less in PSSM than that seen for controls (mean peak PSSM-EX 44.7% vs. 26.5% for controls, respectively) (P < 0.006). No significant differences in the insulin:glucose ratios were found for control horses between NEX and EX. In PSSM horses, the insulin:glucose ratio was significantly increased in the EX vs. NEX. In conclusion, exercise in normal horses results in enhanced glucose clearance following feeding without altering insulin:glucose ratios. At rest, PSSM horses have lower insulin:glucose ratios after feeding than normal horses, however, exercise in PSSM horses significantly increases insulin:glucose ratios. This may explain the beneficial effect of daily exercise for preventing rhabdomyolysis in horses with PSSM.
Animals↗
Effect of diet on thoroughbred horses with recurrent exertional rhabdomyolysis performing a standardised exercise test.
Previous studies have associated recurrent exertional rhabdomyolysis (RER) with a diet high in soluble carbohydrate (CHO). The purpose of this study was to investigate the effect of 3 diets on clinical and metabolic parameters in 5 Thoroughbred horses with RER and 3 healthy Thoroughbreds performing a standardised exercise test (SET). Two diets were formulated to meet energy requirements for the amount of exercise being performed in the form of CHO or fat (21.4 Mcal DE/day). The third diet was formulated to provide 135% of the DE of the other 2 diets in the form of an excessive amount of carbohydrate (28.8 Mcal DE/day). Diets were fed in a crossover design for 3 week blocks and then horses performed a near maximal SET. Changes in heart rate (HR), plasma lactate, plasma glucose, total plasma solids, packed cell volume (PCV), muscle lactate and muscle glycogen concentration were measured immediately prior to, during, and 5 min after exercise. Serum creatine kinase (CK) activity was measured prior to and 4 h post SET. A 2-way ANOVA was used to examine the effect of group and dietary treatment. When dietary treatments were compared, horses fed the high-CHO diet had a mean pre-SET PCV and pre-SET HR that was higher than horses fed the fat diet (P = 0.06 and P = 0.07, respectively). Pre-SET heart rates were highest in RER horses consuming the high-CHO diet compared to RER horses consuming the low-CHO and fat diets (P = 0.02). Horses with RER had 4 h post SET CK activity greater than 400 u/l in 7/14 (50%) measurements compared to control horses which had CK activity greater than 400 u/l in 2/7 (29%) measurements. This study did not demonstrate a significant effect of diet on rhabdomyolysis, indicated by CK activity, or on the metabolic response to exercise. However, diet may have a calming effect on Thoroughbred horses with RER as manifested by decreased pre-exercise heart rates and decreased pre-exercise PCV in horses fed the fat diet.
Animals↗
Exertional rhabdomyolysis in quarter horses and thoroughbreds: one syndrome, multiple aetiologies.
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.
Animals↗
Heritability of recurrent exertional rhabdomyolysis in Thoroughbred racehorses.
OBJECTIVE: To determine the likely mode of inheritance and identify probable foundation horses for recurrent exertional rhabdomyolysis (RER) in Thoroughbred (TB) racehorses. ANIMALS: 4 families of TB racehorses with a high prevalence of RER, consisting of 3 to 53 horses/family, were used to determine mode of inheritance. Sixty-two TB horses with RER and 34 control TB racehorses without RER were used to identify probable foundation horses for the RER trait. PROCEDURE: RER was diagnosed by a veterinarian and verified by detecting high serum creatine kinase activity. Pedigrees dating from 1930 for all horses were entered into a database. Pedigrees of horses in 4 families were visually inspected for a pattern of inheritance and used for calculation of foundation horse contributions and inbreeding coefficients. The Markov chain Monte Carlo technique was used to analyze pedigrees of the 62 affected and 34 control horses for the conditional probability of foundation genotypes. A dominant mode of inheritance with variable expression model was used. RESULTS: Pedigree analysis supported an autosomal dominant mode of inheritance with variable expression. All affected horses from the 4 families shared a common ancestor. This ancestor and 5 other stallions had a conditional probability of 1.00 for being affected. All 6 stallions shared a common male ancestor within 3 to 5 generations. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of this study, the RER trait has been in TB racehorses for more than 70 years and may be inherited as an autosomal dominant trait with variable expression.
Alleles↗
Glucose uptake in horses with polysaccharide storage myopathy.
OBJECTIVE: To determine whether excessive glycogen accumulation in skeletal muscle of Quarter Horses with polysaccharide storage myopathy (PSSM) is a result of enhanced cellular uptake of glucose. ANIMALS: 6 horses with PSSM and 10 healthy (control) horses. PROCEDURE: Intravenous glucose tolerance tests (IVGTT), oral glucose tolerance tests (OGTT), and modified insulin tolerance tests (MITT) were performed. Plasma glucose and insulin concentrations were measured in blood samples collected before and for up to 8 hours after glucose or insulin administration. RESULTS: Peak glucose concentrations during IVGTT were similar for both groups of horses, but rate of glucose clearance was 1.5 times faster in horses with PSSM than in controls. Moreover, circulating concentrations of insulin before and after glucose injection were lower in the PSSM group. Blood glucose concentrations from minute 90 to minute 300 of the OGTT were lower in horses with PSSM than in controls. The MITT resulted in acute decreases in blood glucose concentrations in both groups of horses; however, horses with PSSM sustained low blood glucose concentrations for more than 3 hours after insulin injection, whereas blood glucose concentrations in controls returned to baseline values within 2 hours. CONCLUSIONS: Quarter Horses with PSSM have enhanced cellular uptake of glucose that may be, in part, caused by an increased sensitivity to insulin. CLINICAL RELEVANCE: Horses with PSSM have an increased rate of glucose clearance in response to insulin secretion. Thus, diets low in soluble carbohydrate may be the most effective way to decrease glycogen accumulation in skeletal muscle of these horses.
Animals↗
In vitro contractile responses and contracture testing of skeletal muscle from Quarter Horses with exertional rhabdomyolysis.
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.
Animals↗