Mechanism of norepinephrine depletion in experimental heart failure produced by aortic constriction in the guinea pig

• Increasing evidence indicates that the activity of the sympathetic nervous system is altered in congestive heart failure. The stress of muscular exercise elevates the con-centration of circulating norepinephrine to ab-normally high levels in patients with chronic heart failure,1 and even at rest such patients exhibit evidence of augmented activity of the adrenergic nervous system, as reflected in an increased urinary excretion of norepinephrine.2 Biopsies of atrial tissue obtained from patients with heart failure have shown that the con-centration of norepinephrine may be markedly reduced.3 To determine if depletion of the total cardiac store of norepinephrine is characteris-tic of congestive heart failure in general, it was necessary to study this problem in an experimental model. However, it is appreci-ated that no single experimental preparation can satisfactorily reproduce the various forms of heart failure encountered clinically. Accord-ingly, we have examined this problem in two mammalian species in which heart failure was produced by different interventions. In the dog, primary right heart failure was investi-gated4 while in the guinea pig, primary left heart failure was studied, as described in a preliminary communication.5 The present re-port consists of an analysis of the time course of the changes in cardiac norepinephrine con-centration which occurred in the guinea pig, as well as studies on the mechanisms respon-sible for the alterations of norepinephrine stores