The amino acid composition of actin and myosin and Ca2+ activated myosin adenosine triphosphatase in chronic canine congestive heart failure

Abstract

The Ca2+ activated myosin ATPase and the amino acid compositions of actin and myosin were determined for preparations from chronically failing dog hearts. Hypertrophy and congestive heart failure were produced by combined tricuspid valve insufficiency and pulmonary artery stenosis. Control, sham operated, and noncardiac circulatory failure (inferior vena cava constriction) dogs also were studied. All hearts were divided into right ventricle, septum, and left ventricle and each sample was individually analyzed. Calcium activated ATPase decreased in the failing hearts and showed a distinct gradient of depression from right to left ventricles. There were no changes in ATPase activity among the other groups. The amino acid composition of actin was the same regardless of origin. The amino acid composition of myosin was unaltered except that cystine/2 residues were markedly decreased in failing heart myosin. The same gradient of depression was present as was found for Ca2+ activated myosin ATPase. This study suggests that protein metabolism is abnormal and that altered proteins are produced in hypertrophy and congestive heart failure. It appears that these changes do not affect all proteins, since actin was normal by the parameters studied. It is clear that the stressed ventricle is the most severely involved, but the entire heart is altered to some degree. Thus, it is concluded that altered protein metabolism may be an important primary factor in the genesis of heart failure.