The Syrian hamster polymyopathy is a hereditary disease, transmitted by an autosomal recessive gene, involving the heart and the entire musculature. The chronology of the pathologic events in the myocardium and skeletal muscle has been investigated in UM-X7.1 myopathic hamsters aged 0-250 days. A phasic pattern in the progression of the disease process was evident. Microscopic necrotic changes in the heart were visible prior to or at 50 days of age with increasing severity until 100 days of age and subsidence thereafter. More than 50% of the animals died before 250 days of age with signs of cardiac failure. The intensity and extent of myocardial calcific changes together with scar formation were determinant factors in curtailing the survival of animals. Changes in serum creatine kinase (CK) activity followed a phasic pattern similar to the progression of the myopathic disease. Because of the disparity of disease manifestations between the different myopathic hamster lines, it is essential to consider the time course of the heart and skeletal muscle microscopic changes when evaluating the severity of the hamster polymyopathy.

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.

The heart muscle is very compliant within a wide range of physiologic impulses. The adaptive energy of the myocardium depends, however, upon adequate oxygen supply and the functional state of the plasmalemma. These limitations have been well demonstrated in a number of experimental models with emphasis on the essential role of Ca2+ transmembrane movements for maintenance of heart functions and its viability. This postulate appeared quite important when we found that Ca2+ slow channel blockers could prevent necrotic changes in hamster hereditary cardiomyopathy. However, the effectiveness of beta-adrenoagonists when given in low doses seems more difficult to interpret since these agonists can only promote Ca2+ transmembrane movements. We can only surmise that Ca2+ accumulation in cardiomyopathic hearts does not derive from a primary defect of the plasmalemma but rather from an exhausted hypokinetic state that favours Ca2+ accumulation with progressive deterioration of the structural proteins. It is thus inferred that Ca2+ mediates rather than initiates the degradation process which characterizes this inherited cardiomyopathy.

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