Reduced Cardiac Myosin Adenosinetriphosphatase Activity in Dogs with Spontaneously Occurring Heart Failure

Abstract

Cardiac myosin was isolated from the hearts of seven dogs with naturally occurring heart failure. Six of the seven dogs had heart failure secondary to acquired mitral valvular insufficiency; the seventh was believed to have a primary myocardiopathy. The characteristics of this myosin were compared to cardiac myosin from a group of normal dogs studied concurrently. Cardiac myosin was extracted from heart muscle with a phosphate salt solution and purified by repeated fractionation with ammonium sulfate in the presence of 2M lithium chloride. Myosin from dogs with heart failure had a significantly reduced adenosinetriphosphatase activity compared to myosin from the control group. Sulfhydryl group content, shown to influence myosin enzyme activity, was unchanged in myosin from dogs with heart failure. Molecular weight of myosin was similar in both groups. Sedimentation velocity of myosin from dogs with heart failure was suggestive of a configurational change in the molecule, but this was not confirmed by measurement of the intrinsic viscosity and helical content of the protein. These studies suggested that the reduced contractile performance of the myocardium in congestive heart failure complicating a disease process is, in part at least, the result of depressed myosin adenosinetriphosphatase activity.