Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis.

A previous report suggests a substantial incidence of exertional rhabdomyolysis (ER) in Arabian horses performing endurance racing. This study compared formalin histopathology and clinical and metabolic responses to a standardised field exercise test (SET) between Arabians with and without ER. Arabian horses with (n = 10; age 15.4 ± 5.6 years) and without (n = 9; 12.9 ± 6.1 years) prior ER were stall-rested for 24-48 h, after which paired ER and control horses were fitted with a telemetric ECG and performed a 47 min submaximal SET. Plasma glucose, lactate, electrolyte and total protein concentrations and packed cell volume were measured before and immediately after exercise. Blood and percutaneous gluteal muscle samples were also obtained before and 3 h after exercise for measurement of plasma creatine kinase (CK) activity and muscle glycogen concentration, respectively. Histopathologic analysis of formalin-fixed pre-exercise muscle sections was performed. Data were analyzed by ANOVA and non-parametric tests (P <0.05). No horses displayed clinical signs of ER during exercise, and plasma CK increased similarly in ER and control Arabians. Muscle glycogen, heart rate, and remaining plasma variables did not differ between horses with ER and control horses. Horses with ER had more internalised nuclei in mature myofibers, more aggregates of cytoplasmic glycogen and desmin, and higher myopathic scores than control horses. Although many horses with ER had histopathologic evidence of chronic myopathy, muscle glycogen concentrations and metabolic exercise responses were normal. Results did not support a consistent metabolic myopathy or a glycogen storage disorder in Arabians with ER.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis.

REASONS 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 αß-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of ß-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.

Prevalence of exertional rhabdomyolysis in endurance horses in the Pacific Northwestern United States.

REASONS 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.

Vertebral fractures in two alpaca crias with rickets syndrome.

CASE REPORT: Two dark-coloured alpaca crias aged 5 and 5.5 months, respectively, born in September in the Pacific Northwest, USA, were presented for evaluation of acute recumbency. Both crias had cervical spine fractures and one had additional fractures in other locations within the spine. Both crias had valgus deformities of the forelimbs and one had similar deformities of the hindlimbs. Both crias showed characteristic radiological signs of rickets syndrome, including wide, irregular physes, cupping of the metaphyses, bowing of long bones, pathological fractures and enlarged costochondral junctions. One cria responded clinically to treatment with parenteral administration of vitamin D. The other cria was euthanased because of the multiple spinal fractures and postmortem examination supported the diagnosis of rickets syndrome. CONCLUSIONS: Hypovitaminosis D is associated with abnormal bone formation in young growing animals. The clinical and laboratory findings of rickets syndrome in camelids in the Pacific Northwest, and other regions with low annual sunlight exposure, have been described, although there are only few reports of the radiological signs associated with this condition in camelids and other animals. Additionally, vertebral fractures have not been previously reported in animals with rickets syndrome. Because vertebral fractures were identified in both crias in this report, it suggests that this is a common and clinically important manifestation of the disease in alpaca crias. Hence, in geographic regions with low sunlight exposure, rickets syndrome should be considered as a differential diagnosis in crias presenting with clinical signs consistent with vertebral fracture.

Effect of feed restriction on plasma dantrolene concentrations in horses.

REASONS FOR PERFORMING STUDY: Dantrolene sodium is used to prevent exertional rhabdomyolysis in predisposed horses. Food intake might negatively impact dantrolene bioavailability in horses; however, prolonged feed restriction might be detrimental to performance. OBJECTIVE: To determine a minimum duration of feed restriction that would optimise plasma dantrolene concentrations in horses after nasogastric administration. It was hypothesised that feed restriction for 4, 8 or 12 h before dantrolene administration would result in higher plasma dantrolene concentrations than achieved with no feed restriction before treatment. METHODS: Five healthy horses were randomly rotated through 4 feed restriction periods of 0, 4, 8 and 12 h duration prior to nasogastric administration of dantrolene sodium (6 mg/kg bwt). Plasma dantrolene concentration was measured by spectrofluorometry at 60, 90, 120, 150, 180 and 210 min after administration. Data were analysed via repeated measures ANOVA. RESULTS: Peak plasma dantrolene concentration was highest when horses had 0 and 4 h of feed restriction (0.65 ± 0.10 µg/ml at 120 min; 0.66 ± 0.17 at 180 min, respectively) and was lower when horses were restricted from feed for 8 h (0.45 ± 0.15 at 150 min) and 12 h (0.21 ± 0.09 at 180 min). Mean plasma dantrolene concentration did not differ between 0 and 4 h feed restriction at any sample time, but feed restriction for 8 h resulted in significantly lower plasma dantrolene concentration at 60 and 180 min after treatment than when horses were restricted 0 and 4 h, respectively. Plasma dantrolene concentration was significantly lower at all sample times when horses were restricted from feed 12 h compared to 0 or 4 h. CONCLUSIONS: Absorption of nasogastrically administered dantrolene is inhibited by feed restriction before administration. To achieve optimal plasma dantrolene concentrations, feed restriction before oral administration should not exceed 4 h.

Cold air-induced late-phase bronchoconstriction in horses.

REASON FOR PERFORMING STUDY: Inspired air is warmed to body temperature and fully humidified by the upper airway mucosa under normal resting conditions. This conditioning process may not be completed by the upper airways during conditions of increased minute ventilation or when the inspired air is unusually cold, resulting in cooling and desiccation of lower respiratory surfaces. Excess heat and water loss from intrapulmonary airways is believed to be the provocative stimulus for exercise-induced bronchoconstriction (occurring immediately after exercise) and associated late phase airway obstruction (occurring a few hours after exercise). HYPOTHESIS: Exercise while breathing cold air results in airway obstruction in horses. METHODS: Eight healthy horses performed a 15 min submaximal exercise challenge in a random crossover design. Independent variable was inspired air temperature during the challenge (25 or -5 degrees C). The dependent variables were total respiratory impedance, resistance, and reactance at 5, 24 and 48 h post exercise challenge, expressed as a percentage of the prechallenge baseline. RESULTS: No significant effect of inspired air temperature was found on any respiratory mechanical parameter 5 h after exercise challenge. However, cold inspired air was associated with higher respiratory impedance and resistance 48 h after the exercise challenges. CONCLUSIONS: These findings support the hypothesis that submaximal exercise while breathing subfreezing air can adversely affect respiratory mechanical properties in normal horses. However, the timecourse for development of abnormal respiratory mechanical properties is longer than that reported in other mammals. CLINICAL RELEVANCE: Exercise in cold weather may be a common cause of lower airway disease in horses.

Gastric squamous cell carcinoma in three horses.

Gastric squamous cell carcinoma was diagnosed in three horses. Clinical signs observed in all cases were weight loss, anorexia and lethargy. Respiratory signs were prominent in one case. All three horses had depressed albumin and elevated globulin and fibrinogen concentrations. Two horses were mildly anaemic. Inflammatory exudates were present in peritoneal cavities in all cases, and cytological evaluation provided a positive diagnosis of squamous cell carcinoma in two cases. Pleural fluid samples taken from two cases were also classified as inflammatory exudates, but no neoplastic cells were detected on initial examination. In all cases the neoplasms had arisen from the oesophageal region of the stomach, and had metastised throughout the abdomen. Two cases had metastatic lesions within the pleural cavity.