The Syrian cardiomyopathic (CM) hamster (BIO 14.6) develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, and eventually, cardiac dilatation and congestive heart failure. Several lines of evidence implicate cellular calcium overload as an important etiologic factor. We previously reported an increased number of receptors for calcium antagonist drugs, which block voltage-dependent calcium channels, in heart, skeletal muscle, and brain tissue of these hamsters in the early necrotic stage of the disease. To better characterize the pathophysiological significance of this abnormality we evaluated calcium antagonist receptor binding and Na+-Ca2+ exchange in CM and control hamsters at different stages of disease as documented by quantitative histopathologic assessment. In CM hamsters as young as 10 days, an age previously thought to be before the onset of disease, we identified cardiac myocyte hypertrophy, a twofold increase in calcium antagonist receptor binding in heart and brain, and a 50% increase in skeletal muscle. Overt histological lesions were present in skeletal muscle at 25 days and in heart between 28-30 days. The size of cardiac lesions increased over time and changed from necrotic foci with cellular infiltration to fibrotic or calcified lesions by 360 days. Myocardial cellular hypertrophy persisted through the late stages of the disease (360 days), but increased calcium antagonist binding was present in heart only to 6 months of age, in skeletal muscle to 90 days, and in brain to 30 days. Na+-Ca2+ exchange in heart was normal until 15 days and then increased by 400% at 30 days suggesting that this augmentation might be a secondary response to the earlier increase in calcium antagonist receptors. At 360 days cardiac Na+-Ca2+ exchange was decreased by 50%, likely reflecting progressive cardiac damage. The increase in calcium antagonist receptors in CM animals as young as 10 days supports the hypothesis that abnormalities in voltage-dependent calcium channels play a role in the pathophysiology of CM hamsters.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine