Hereditary polymyopathy and cardiomyopathy in the Syrian hamster. II. Development of heart necrotic changes in...

The mitochondrial oxidative phosphorylation, calcium and magnesium contents, and swelling-contraction activity were investigated in relation to the progression of the hereditary hamster cardiomyopathy. The assessment was made in animals between 22 and 232 days of age, which were divided into 7 groups according to stage of disease. In 24-day-old hamsters prior to development of heart necrotic changes, the membrane permeability of isolated mitochondria was altered. In 50-day-old animals, at a stage of disease when myocardial cells undergo degeneration, a defect of oxidative phosphorylation resulting from an increase in mitochondrial calcium was demonstrated. With culmination of the heart necrotic changes, at close to 100 days of age, mitochondrial dysfunction and calcium overload were maximal. There was a transient improvement during the healing stage, but the situation deteriorated with the occurrence of circulatory failure. Since the mitochondrial respiratory pattern and calcium overload parallel the cardiac degeneration, it is inferred that the cell energy depletion is a functional consequence of an abnormal calcium influx.