Depressed Na-K-ATPase activity in the failing rabbit heart.

Abstract

We studied the changes in the membrane ATPase from hypertrophied rabbit myocardium, and demonstrated a correlation between heart failure and ionic transport mechanism.In 17 animals cardiac hypertrophy was produced by constriction of the ascending aorta. A modification of the method of Tashima was used for preparation of membrane vesicles from the myocardium of the left ventricle. This preparation was carried out 10 days after the operation. Mgand Na-K-ATPases of the membrane ATPases were measured separately by their different responses to ouabain and cations.(1) Ventricular weight and heart weight were significantly greater in the experimental group than in the control group. However, the myocardial water content was almost constant in these groups.(2) The specific activity of Na-K-ATPase in myocardial vesicles was relatively high compared with skeletal muscle and corresponded to about one fourth of its total ATPase activity. This Na-K-ATPase activity was inversely correlated with the left ventricular weight (p<0.02). The difference in Na-K-ATPase activity between heart failure cases and controls was significant at the 5% level. On the other hand, no significant difference in Mg-ATPase activity between the failure and the control group was demonstrated.These results supported the fact that, during the development of heart failure, the myocardium lost potassium. From these findings, it was postulated that the heart in failure would be characterized by a diminished ability to manipulate active ion transport in response to hemodynamic stress due to the decrease in Na-K-ATPase activity.