Epidemiological, pathological and metabolomic characterisation of an acquired myopathy of dogs in New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Manawatū, New Zealand

‘Go Slow’ myopathy (GSM) is an idiopathic myopathy in dogs in New Zealand, characterised by an acute onset of trembling, weakness and collapse, followed by a prolonged period of exercise intolerance. In the first part of this thesis, the epidemiology of the disease was investigated using a telephone survey to obtain information regarding the diet, exercise, and health of affected dogs. Eighty-six confirmed cases were included in this study, and ingestion of wild pig in the week prior to the onset of clinical signs was a consistent finding (76/86 dogs; 88%; 95% confidence interval = 82 – 95%). Cases occurred most commonly in the upper North Island, particularly in Northland. The aim of the second part of this thesis was to characterise the pathology of GSM in the same 86 dogs included in the epidemiological study, using serum biochemistry (78 dogs), histology (20 dogs), and electron microscopy (4 dogs). Acutely, affected dogs had increased serum creatine kinase and aspartate aminotransferase activities, corresponding with the histological finding of skeletal muscle degeneration in the absence of inflammation. Ultrastructural changes in skeletal muscle included mitochondrial hypertrophy, intramitochondrial inclusions and increased sarcoplasmic glycogen. Similar lesions were observed in the skeletal muscle of wild pigs from areas where GSM occurred in dogs. Affected dogs also had increased serum alanine aminotransferase activities due to accumulation of lipid and glycogen in hepatocytes. Overall, the microscopic findings were consistent with a toxic myopathy. To further investigate the pathogenesis of the disease, liver samples were collected from 15 affected dogs and 24 clinically normal dogs for untargeted metabolic profiling using liquid chromatography-mass spectrometry. Comparison of spectra between affected and normal dogs revealed a widespread decrease in phospholipids, and increases in selected dicarboxylic acids and N-acetylated branch chain amino acids in affe