Hereditary polymyopathy and cardiomyopathy in the syrian hamster. I. Progression of heart and skeletal muscle lesions in the UM‐X7.1 line

Abstract

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.

Diminished Inotropic Response to Amrinone in Ventricular Myocytes from Myopathic Hamsters Is Linked to Depression of High-Gain Ca2+-Induced Ca2+Release

“…Interestingly, reduced synthesis of cAMP also has been shown to underlie reduced sensitivity and maximum effect of PDE-III inhibitors in trabeculae from hearts of patients in end-stage heart failure (Feldman et al, 1987;Bohm et al, 1988). Because CM hamsters eventually develop heart failure (Jasmin and Proschek, 1982;Hunter et al, 1984), our results suggest that a defect in the cAMP-PKA pathway is present before the onset of overt failure and therefore may contribute to development of failure.…”

“…This gene mutation leads to a deficiency in the dystrophin-associated glycoprotein in the sarcolemma of cardiac and skeletal muscles (Roberds et al, 1993) and leads to deleterious changes in contractile function of these muscles (for review, see Howlett et al, 1999). In CM hamster heart, focal necrosis is observed at 40 to 50 days of age and reaches a peak around 90 days of age (Jasmin and Proschek, 1982;Hunter et al, 1984). Necrotic changes are followed by progressive ventricular hypertrophy beginning at about 120 days of age, and heart failure develops between 200 and 300 days of age (Jasmin and Proschek, 1982;Hunter et al, 1984).…”

“…In CM hamster heart, focal necrosis is observed at 40 to 50 days of age and reaches a peak around 90 days of age (Jasmin and Proschek, 1982;Hunter et al, 1984). Necrotic changes are followed by progressive ventricular hypertrophy beginning at about 120 days of age, and heart failure develops between 200 and 300 days of age (Jasmin and Proschek, 1982;Hunter et al, 1984). Thus, the CM hamster exhibits predictable and progressive cardiomyopathy with hypertrophy and terminal heart failure.…”

Autophagic Cardiomyocyte Death in Cardiomyopathic Hamsters and Its Prevention by Granulocyte Colony-Stimulating Factor

“…15,16 Sarcolemmal integrity was assessed by living staining with Evans blue dye. The dye is excluded by cardiomyocytes with normal sarcolemmal permeability but taken up by cardiomyopathic cells with leaky cell membranes.…”

“…15,16 The condition begins at ϳ4 weeks of age and then worsens throughout subsequent weeks. Cardiac hypertrophy is seen by the time the animals are ϳ20 weeks of age and is followed by progressive ventricular remodeling and fibrosis with CHF.…”