Incidence and risk factors for exertional rhabdomyolysis in thoroughbred racehorses in the United Kingdom

Telephone surveys of 34 racing yards with 1276 horses in training were made to establish the overall incidence of exertional rhabdomyolysis in the previous year. A case-control study was used to investigate the risk factors for the syndrome in 12 yards selected on the basis of the routine confirmation of diagnoses by the evaluation of the serum activities of creatine kinase and aspartate aminotransferase. The overall incidence of the syndrome was 6.7 per cent and 80 per cent of the trainers had at least one affected horse. In 74 per cent of the affected horses it frequently recurred, with an average of six lost training days per episode. Risk factors identified for the syndrome included being female, having a nervous, excitable temperament, and being two years old.     

Prevalence and demographic characteristics of exertional rhabdomyolysis in horses in Australia

The proportion of the horses, of both sexes and of different ages, breeds and levels of activity, owned by a stratified random sample of Australian owners, which had suffered one or more episodes of exertional rhabdomyolysis during the previous 12 months was determined. The proportion in the general population was 1.9 per cent, and horses which exercised were significantly more likely to have experienced the condition than horses which did not. There were significant differences between the sexes and between certain breeds and activity groups in the proportions of horses affected.     

Myoplasmic calcium regulation in myotubes from horses with recurrent exertional rhabdomyolysis

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 > or = 2mM caffeine; however, there was no difference in their response to 4-CMC (> or = 1 mM). 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 (500 microM) 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.     

Abnormal regulation of muscle contraction in horses with recurrent exertional rhabdomyolysis.

OBJECTIVE: To determine whether abnormal regulation of muscle contraction similar to that associated with malignant hyperthermia (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.     

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.     

Acute kidney injury mediated by oxidative stress in Egyptian horses with exertional rhabdomyolysis

The present study was carried out to evaluate the role of oxidative stress in the pathophysiologic process of acute renal failure associated with exertional rhabdomyolysis (ER) in Egyptian horses. ER was tentatively diagnosed in 31 Baladi horses based on case history, physical examination findings and confirmed by elevation of plasma creatine kinase (CK) and urine myoglobin concentrations. According to severity of the condition, the diseased horses were categorized into two main groups; the first group included 18 horses with minimal clinical signs and plasma CK <60 000 IU/L; whereas, the second group included 13 horses with overt clinical signs and plasma CK >100 000 IU/L). It was found that plasma creatol (CTL) was positively correlated (p < 0.01) with plasma malondialdehyde (MDA) (r = 0.775), nitric oxide (NO) (r = 0.768), methyguanididne (MG) (r = 0.995), CK (r = 0.768), urine glucose (r = 0.778), urine protein (r = 0.767), renal failure index (RFI) (r = 0.814) and urine sodium (r = 0.799) and negatively correlated (p < 0.01) with total antioxidant capacity (TAC) (r = −0.795), superoxide dismutase (SOD) (r = −0.815), glutathione peroxidase (GSH-Px) (r = −0.675), Vitamin C (r = −0.830), urine creatinine (r = −0.800), urine/plasma creatinine ratio (r = −0.827) and urine/plasma urea ratio (r = −0.807). The correlation between these biochemical variables might suggest a possible role of oxidative stress in renal injury associated with severe rhabdomyolysis in horses. It is suggested that exaggeration of oxidative stress associated with increased muscle membrane leakage plays a key role in acute kidney injury in Baladi horses with severe rhabdomyolysis.     

Keratomycosis in six horses in the United Kingdom

Six horses with keratomycosis were examined and three different clinical expressions of the disease were recognised. The diagnostic work-up and response to treatment is described.     

Contracture test and histologic and histochemical analyses of muscle biopsy specimens from horses with exertional rhabdomyolysis

Biopsy specimens of the cutaneous omobrachialis muscle were obtained from 10 horses with a problem of myositis from mild exercise. One horse had been evaluated previously and malignant hyperthermia-like contractures developed in its muscle biopsy specimen during the contracture test. In this study, the halothane-caffeine contracture test and histologic and histochemical evaluations were performed on muscle biopsy specimens. In the contracture test, no muscle biopsy specimen developed contracture in the presence of 2 or 4% halothane alone. The mean (+/- SEM) caffeine-specific concentration in the presence of halothane was 5.23 +/- 0.5 mM for 2% halothane, and 4.46 +/- 0.6 mM for 4% halothane. The caffeine-specific concentration values were not significantly different. Contracture response for any muscle specimen did not resemble contracture associated with malignant hyperthermia. The cutaneous omobrachialis muscle was composed of type-II fibers, with type-I fibers seldom seen. For 9 of the 10 horses, overall fiber morphology was normal; 1 horse had necrotic fibers. Of the 10 muscle specimens, 9 had fibers that had positive reaction for alkaline phosphatase activity; 3 muscle specimens contained ringed myofibers. Three horses of this study were administered general anesthesia; 2 were research horses, anesthetized with halothane and succinylcholine, and 1 was a clinical case given halothane anesthesia plus a non-depolarizing muscle relaxant. One research horse developed a malignant hyperthermia-like reaction to anesthesia, with severe rhabdomyolysis evident after anesthesia, and an episode of muscle cramping in its stall 2 days after anesthesia. The other 2 horses had unremarkable postanesthetic periods.     

Inheritance of recurrent exertional rhabdomyolysis in thoroughbreds

OBJECTIVE: To develop a diagnostic test for recurrent exertional rhabdomyolysis (RER) in Thoroughbreds that relied on in vitro contracture of muscle biopsy specimens and determine whether the inheritance pattern of RER diagnosed on the basis of this contracture test was consistent with an autosomal dominant trait. DESIGN: Clinical trial. ANIMALS: 8 adult horses with RER and 16 control adult horses for development of the contracture test; 23 foals for inheritance of RER. PROCEDURE: External intercostal muscle biopsy specimens from the 24 adult horses were tested for contracture in response to halothane and caffeine, and criteria for a positive test result were determined. These criteria were then applied to results for the 23 foals to determine whether they had RER. Simple segregation analysis was performed to determine whether results were consistent with a dominant pattern of inheritance. RESULTS: Results of the contracture test were positive for 5 of the 12 colts and 4 of the 11 fillies. Results of segregation analysis were consistent with an auto-. somal dominant pattern of inheritance. Two sires with RER produced colts with RER, supporting the hypothesis that RER had an autosomal, rather than an X-linked, inheritance pattern. In addition, in 1 instance, an unaffected colt was produced by 2 affected parents, which was not consistent with a recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: Although the expression of the RER trait is influenced by sex, temperament, and diet, among other factors, results from the in vitro muscle contracture test and this breeding trial suggest that RER in Thoroughbreds can be modeled as a genetic trait with an autosomal dominant pattern of inheritance.     

Incidence and risk factors associated with exertional rhabdomyolysis syndrome in National Hunt racehorses in Great Britain

A telephone survey of 51 National Hunt racing yards with 1140 horses in training was made in April and May 2003 to establish the incidence of exertional rhabdomyolysis syndrome during the previous year. A case-control study was used to investigate the risk factors for the syndrome in eight yards selected on the basis that cases had been confirmed by the analysis of serum muscle enzymes. The overall incidence of syndrome was 6.1 cases per 100 horses per year, and 55 per cent of the yards reported at least one case. The risk factors identified were sex, the average length of the training gallop, and the type of horse (steeplechaser, bumper/unraced or hurdler). There were no significant associations with the horses' temperament, age or Timeform rating.     

Factors associated with mortality of geriatric horses in the United Kingdom

Geriatric horses (aged≥15 years) now represent a substantial proportion of the equine population, yet mortality rates for aged horses in the UK have not previously been described. Although post-mortem studies have provided some data regarding specific causes of death, "old age" is a common owner-reported reason for euthanasia of adult horses, indicating further elucidation of reasons for death or euthanasia is required for the geriatric equine population. The objective of this cohort study was to describe mortality rates, causes of death or euthanasia and factors associated with mortality in geriatric horses and ponies. Veterinary registered horses randomly selected for a cross-sectional questionnaire survey on geriatric health were enrolled in the cohort study (n=908). Follow-up information was obtained over an 18-month period via telephone questionnaires and mortality questionnaires, providing data regarding reasons for death or euthanasia, were completed for 118 cases of mortality. Overall and stratified mortality rates were calculated and Cox proportional hazards models were used to investigate risk factors associated with mortality. The majority (94%) of mortalities were euthanised, most frequently due to lameness (24%) and colic (21%). Veterinary advice was important in owner decision making regarding euthanasia of cases of colic or other acute illnesses, while poor quality of life was considered an important factor where euthanasia was due to chronic diseases or lameness. Overall mortality rate was 11.1 (95% C.I. 9.2-13.2) per 100 horse-years at risk, with the mortality rate of animals >30 years of age over five times the rate in horses aged 15-19 years. On multivariable analysis, increasing age was associated with increasing mortality and Cob/Cob crossbreeds and Thoroughbred/Thoroughbred crossbreeds had an increased risk of mortality. Horses considered to be underweight had a greater risk of mortality than those in good condition. Increasing number of owner-reported clinical signs and the degree to which pain was reported to limit normal daily activities were associated with increased risk of mortality. The results of this study provide useful information about rates and factors associated with mortality in geriatric horses in the UK, which should be relevant to veterinary surgeons involved in the treatment of aged horses.     

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.     

Exercised-induced pulmonary hemorrhage in polo and racing horses

Philippine polo and racing horses were examined for exercise-induced pulmonary hemorrhage after their competitive exercise. Exercise-induced pulmonary hemorrhage occurred in 11.1% of the polo horses and 64% of the racing horses. None of the horses had blood at the nostrils.     

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.