Comparison of heart sarcolemmal enzyme activities in normal and cardiomyopathic (UM-X7.1) hamsters.

1. The activities of some membrane-bound enzymes such as adenylate cyclase, Na+ + K+-stimulated adenosine triphosphatase (Na+ + K+-ATPase), Ca2+-stimulated ATPase and Mg2+-stimulated ATPase were examined in heart sarcolemmal fractions from control and cardiomyopathic hamsters at different stages of heart failure. 2. The basal adenylate cyclase activity in sarcolemma from cardiomyopathic animals with early, moderate and late stages of heart failure was not different from the control values whereas the sodium fluoride- and catecholamine-stimulated adenylate cyclase activities were depressed in cardiomyopathic sarcolemma at moderate and late stages. 3. The sarcolemmal Na+ + K+-ATPase activity was decreased and the non-specific phosphatase activity was increased at early, moderate and late stages of heart failure. 4. The sarcolemmal Ca2+-ATPase activity was decreased at moderate and late stages whereas the Mg2+-ATPase activity was decreased at the late stages of heart failure only. 5. A marked decrease was found in calcium binding by heart sarcolemma from cardiomyopathic hamsters at late stages of failure. 6. These results suggest that dramatic sarcolemmal changes are associated with heart failure, and support the view that membrane abnormalities play a crucial role in the development of myocardial dysfunction, cyclase, calcium binding, heart failure, heart membranes, sarcolemmal enzymes.

Membrane alteration in failing hearts of cardiomyopathic hamsters.

Cardiomyopathic hamsters (UM-X7.1) show clinical signs of congestive heart failure and an abnormal EKG pattern. The sarcolemmal fraction obtained from the failing hearts at advanced stages of myopathy exhibited no change in the basal adenylate cyclase activity; however, the activity of this enzyme in the presence of catecholamines or NaF was lower in the failing heart sarcolemma than that in the control. The activities of Ca2+-ATPase, Mg2+-ATPase, and Na+-K+-ATPase in the failing heart sarcolemma were also less than the control values. These results suggest an association of membrane defect with heart failure.

Prevention of myocardial generation in hamsters with hereditary cardiomyopathy.

A number of drugs have been tested for their ability to prevent or change the course of skeletal and heart lesions occurring with a 100% incidence in cardiomyopathic hamsters (UM-X7.1). These drugs were selected because they act either on the metabolism or turnover of Ca or on adrenergic receptors. Verapamil (Isoptin), a potent inhibitor of myocardial transmembrane Ca conductivity, was found to completely prevent the myocardial lesions in myopathic hamsters. The hamsters were 28 to 30 days of age at the beginning of the experiment and were injected subcutaneously twice daily during 30 consecutive days in doses of 0.5 mg during the first week and 0.75 mg during the subsequent weeks. The protection afforded by Verapamil was no longer evident 30 days after interruption of the treatment. The severity of both cardiac and skeletal muscle lesions was found significantly lowered in hamsters receiving Dibenamine. It is assumed that Verapamil acts mainly by preventing excessive calcium influx in cardiomyocytes, whereas Dibenamine improves the microcirculation, which is deficient during the necrotizing phase of the polymyopathy. The latter assumption rests on the fact that, in myopathic hamsters, the reactivity pattern of alkaline phosphatase is altered at the level of the capillaries of cardiac and skeletal muscles.