Comparison of bronchodilators in alleviating clinical signs in horses with chronic obstructive pulmonary disease

A representative of each of 3 types of bronchodilators was given iv to horses with clinical signs of chronic obstructive pulmonary disease. We used atropine (0.01 mg/kg of body weight) as an anticholinergic, isoproterenol HCl as a beta-adrenergic, and aminophylline, the soluble salt of theophylline, as a methylxanthine. Response to these drugs was evaluated by measuring maximal change in intrathoracic pressures (delta Ppl) and observing clinical signs. Atropine caused a significant (P less than 0.01) reduction in delta Ppl, compared with that caused by aminophylline. Atropine caused the delta Ppl to decrease an average of 83 +/- 15% toward normal. Clinical improvement was noticed in 87% of the cases. Maximal changes in pleural pressures were reduced by an average of 21 +/- 14 mm of Hg, with 27% returning completely to normal. Isoproterenol helped 77% of horses clinically, and caused delta Ppl to decrease an average of 68 +/- 31% toward normal. The average reduction in delta Ppl was 16 +/- 10 mm of Hg. Aminophylline helped alleviate clinical signs of 50% of the horses and caused delta Ppl to decrease an average of 41 +/- 36% toward normal. The average reduction in delta Ppl was 10 +/- 11 mm of Hg.     

Pulmonary gas exchange correlated to clinical signs and lung pathology in horses with chronic bronchiolitis

Eight horses (mean weight 438 kg) with chronic obstructive pulmonary disease (COPD) were studied for clinical signs, ventilation/perfusion relationships (VA/Q) and lung morphology. Four horses were killed and necropsied after the study. In horses with COPD, minute ventilation was almost twice as high as normal, whereas PaO2 was significantly decreased. Cardiac output was normal, but pulmonary artery pressure and pulmonary vascular resistance were significantly increased. The VA/Q distribution was abnormal with an increased scatter of VA/Q ratios. However, shunt (VA/Q = 0) was increased in one horse only. Ventilation of dead space and high VA/Q regions (VA/Q greater than 10) were increased markedly and comprised 74 per cent of minute ventilation. On lung biopsy, all horses showed chronic bronchiolitis with epithelial hyperplasia and metaplasia. Diffuse acinar hyperinflation also was evident at necropsy. There was a significant inverse correlation between the respiratory rate and the fractional ventilation of normal VA/Q regions. Also, there was a significant agreement between the extent of bronchiolar epithelial hyperplasia in necropsy specimens of lungs and the degree of ventilation of high VA/Q regions and dead space. The findings suggest that hyperinflation of the lung due to obstructed airways may be the common denominator of increased ventilation of high VA/Q regions and dead space ventilation and of elevated pulmonary artery pressure in horses with COPD from chronic bronchiolitis.     

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.     

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.     

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.     

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.     

Evaluation of electroacupuncture treatment of horses with signs of chronic thoracolumbar pain

OBJECTIVE: To evaluate use of electroacupuncture for treatment of horses with signs of chronic thoracolumbar pain. DESIGN: Prospective study. ANIMALS: 15 horses with signs of chronic thoracolumbar pain. PROCEDURE: Horses were randomly allocated to 1 of 3 treatment groups. Horses in group 1 received electroacupuncture stimulation (once every 3 days for 5 treatments), those in group 2 received phenylbutazone (2.2 mg/kg [1 mg/lb], PO, q 12 h, for 5 days), and those in group 3 received saline (0.9% NaCl) solution (20 mL, PO, q 12 h, for 5 days). Thoracolumbar pain scores (TPSs) were evaluated before (baseline) and after each treatment. RESULTS: Mean +/- SE TPSs in horses receiving phenylbutazone or saline solution did not change significantly during the study. After the third treatment, mean +/- SE TPS (2.1 +/- 0.6) in horses receiving electroacupuncture stimulation was significantly lower than baseline (6.0 +/- 0.6) TPS. Mean +/- SE TPSs in horses receiving electroacupuncture stimulation were significantly lower than baseline TPSs and TPSs in horses receiving phenylbutazone or saline solution after the third treatment to 14 days after the last treatment. CONCLUSIONS AND CLINICAL RELEVANCE: TPSs are useful for evaluating the efficacy of various analgesic methods used for treatment of thoracolumbar pain in horses. Electroacupuncture was effective for treatment of chronic thoracolumbar pain in horses. Results provided evidence that 3 sessions of electroacupuncture treatment can successfully alleviate signs of thoracolumbar pain in horses. The analgesic effect induced by electroacupuncture can last at least 2 weeks. Phenylbutazone administered PO did not effectively alleviate signs of thoracolumbar pain in horses in this study.     

Longitudinal study describing the clinical signs observed in horses naturally infected with equine influenza

We describe the clinical signs and disease course during an outbreak of equine influenza (EI) in na?ve horses in a police stables in Sydney, New South Wales, Australia.     

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.     

Prevalences and clinical signs of polysaccharide storage myopathy and shivers in Belgian draft horses

OBJECTIVE: To determine prevalences of polysaccharide storage myopathy (PSSM) and shivers in Belgian Draft Horses (BDHs) and determine whether there was an association between these 2 conditions. DESIGN: Prospective cohort study. ANIMALS: 103 BDHs > 1 year old. PROCEDURE: Owners were questioned regarding clinical signs of PSSM, shivers, and hindquarter weakness, defined as poor hindquarter muscling and lack of propulsion. Blood samples were collected for determination of serum creatine kinase and aspartate transferase activities and serum selenium and vitamin E concentrations. A biopsy sample from the gluteus medius muscle was submitted for histologic, histochemical, and biochemical analysis. A diagnosis of PSSM was made if abnormal amylase-resistant polysaccharide inclusions were seen histologically. RESULTS: 37 (36%) horses had PSSM and 19 (18%) had shivers, but only 6 (6%) had both PSSM and shivers, whereas 31 (30%) had PSSM alone, 13 (13%) had shivers alone, and 53 (51%) had neither, and a significant association between PSSM and shivers was not detected. Hindquarter weakness was found in 30 horses. Only 13 of 37 (35%) horses with PSSM and 11 of 19 (58%) horses with shivers had hindquarter weakness. Serum creatine kinase and aspartate transferase activities and serum selenium and vitamin E concentrations were not significantly different between horses with and without PSSM or between horses with and without shivers. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PSSM and shivers are common but unrelated disorders in BDHs.     

Effect of growth and training on muscle adaptation in Thoroughbred horses

OBJECTIVE: To determine the effect of growth and training on metabolic properties in muscle fibers of the gluteus medius muscle in adolescent Thoroughbred horses. ANIMALS: Twenty 2-year-old Thoroughbreds. PROCEDURE: Horses were randomly assigned to 2 groups. Horses in the training group were trained for 16 weeks, and control horses were kept on pasture without training. Samples were obtained by use of a needle-biopsy technique from the middle gluteus muscle of each horse before and after the training period. Composition and oxidative enzyme (succinic dehydrogenase [SDHI) activity of each fiber type were determined by use of quantitative histochemical staining procedures. Whole-muscle activity of SDH and glycolytic enzyme (phosphofructokinase) as well as myosin heavy-chain isoforms were analyzed biochemically and electrophoretically, respectively. RESULTS: The SDH activity of type-I and -IIA fibers increased during growth, whereas whole-muscle activity was unchanged. Percentage of type-IIX/B muscle fibers decreased during training, whereas that of myosin heavy-chain IIa increased. The SDH activity of each fiber type as well as whole-muscle SDH activity increased during training. An especially noticeable increase in SDH activity was found in type-IIX/B fibers. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in muscle fibers of adolescent Thoroughbreds are caused by training and not by growth.The most noticeable change was for the SDH activity of type-IIX/B fibers. These changes in the gluteus medius muscle of adolescent Thoroughbreds were considered to be appropriate adaptations to running middle distances at high speeds.     

Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis

OBJECTIVE: To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). ANIMALS: 2 healthy horses and 5 Thoroughbreds with RER. PROCEDURE: 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, RESULTS: 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.     

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.     

Artifactually increased serum bicarbonate values in two horses and a calf with severe rhabdomyolysis

Extremely high bicarbonate (HCO3-) and anion gap values were measured in two horses and a calf using the Hitachi 911 automated serum biochemistry analyzer. All three animals had severe muscle disease as evidenced by markedly increased aspartate aminotransferase and creatine kinase activities. Laboratory error was suspected as the source of the increased HCO3- because values calculated from blood gas analysis were normal. It was hypothesized that increased serum lactate dehydrogenase (LDH) activity and pyruvate concentration overwhelmed the oxamate LDH inhibitor in the enzymatic HCO3- assay, resulting in consumption of NADH and falsely elevated spectrophotometric reading. Serum LDH activity was markedly increased in all three patients. In an attempt to reproduce this interference in vitro, LDH and pyruvate were added to normal bovine serum. Bicarbonate concentration was artifactually increased in a linear, dose-response relationship proportional to the amount of LDH activity in the sample; addition of pyruvate augmented this increase. It was concluded that increased serum LDH activity and pyruvate concentration secondary to severe muscle disease can result in artifactual increases in serum HCO3- values obtained by routine enzymatic assay.