Exercise intolerance in retrievers - Veterinary Medicine
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Exercise intolerance in retrievers
When a dog from one of the popular retriever breeds is brought to you because it collapsed while exercising or seems to tire easily, you need to sift through the many potential underlying causes. It could be anything from an out-of-shape weekend athlete to a dog with an inherited metabolic myopathy. Here are some of the conditions to consider.


Metabolic myopathies

Metabolic myopathies can be broadly characterized as either glycolytic pathway defects or defects of oxidative metabolism.52 Although these disorders are inherited with the metabolic defect present since birth, signs of disease sometimes do not develop until adult life. Clinical findings may include weakness, muscle atrophy, exercise intolerance, and muscle cramping.

Glycogen storage diseases typically cause muscular weakness, fatigability, and hypoglycemia with exercise and may lead to the accumulation of glycogen-like material in hepatocytes and other cells.52 Exercise intolerance and hypoglycemia have been reported in curly coated retrievers with glycogen storage disease type IIIa caused by a mutation of the glycogen debranching enzyme gene.31 Affected dogs have persistently elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and variable increases in CK activity.31 An example of a metabolic disease that results in exercise intolerance is Type VII glycogenosis of English springer spaniels and American cocker spaniels, which is caused by a phosphofructokinase (PFK) deficiency.31,59,60 This disorder directly affects glycolysis, making it impossible for myocytes and erythrocytes to use carbohydrates for energy.60 Affected dogs have a metabolic myopathy characterized by exercise intolerance and mild increases in CK activity.31 Muscle weakness is exacerbated when alkalemia (from panting) results in intravascular hemolysis of PFK-deficient red blood cells.31,60

Pre- and post-exercise serum lactate and pyruvate concentrations should be measured in exercise-intolerant dogs suspected of having a metabolic myopathy (Comparative Neuromuscular Laboratory, School of Medicine, University of California San Diego: http://vetneuromuscular.ucsd.edu/).34,51,61 Dogs with mitochondrial myopathies typically develop very high post-exercise lactate concentrations, and they may also exhibit organic aciduria.34,51,61-67 Dogs with mitochondrial defects affecting the respiratory chain will have an increased lactate-to-pyruvate ratio.51,61-63 Perhaps the best characterized mitochondrial myopathy in dogs is pyruvate dehydrogenase (PDP1) deficiency in the Clumber and Sussex spaniel.64,65 Affected dogs have profound exercise intolerance and markedly elevated resting and post-exercise plasma lactate with a normal lactate-to-pyruvate ratio.64,65

Electrodiagnostic testing and muscle biopsy should be considered in all dogs with muscle weakness and muscle atrophy suggesting a myopathy. Histologic and ultrastructural examination of skeletal muscle biopsy samples can aid in the diagnosis of a metabolic myopathy, but definitive diagnosis requires identification of the actual enzyme deficiency in tissues or detection of the causative mutation in mitochondrial or nuclear DNA.65 Metabolic screening, measurement of urinary organic acids, and DNA testing for inherited metabolic myopathies is available through the Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania (http://research.vet.upenn.edu/penngen/).


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