TY - JOUR T1 - F. SYMPATHETIC ACTIVITY AND NEUROTRANSMITTER DEPLETION IN CONGESTIVE HEART FAILURE JF - Pharmacological Reviews JO - Pharmacol Rev SP - 685 LP - 700 VL - 18 IS - 1 AU - Charles A. Chidsey AU - Eugene Braunwald Y1 - 1966/03/01 UR - http://pharmrev.aspetjournals.org/content/18/1/685.abstract N2 - The physiology and pharmacology of the sympathetic nervous system has been studied in congestive heart failure, both in man and in experimental animals. Increased plasma NE during muscular exercise and increased urinary excretion of NE at rest in patients with heart failure have provided evidence of augmented activity in the sympathetic nervous system; no evidence of an accompanying augmentation of adrenal medullary function has been obtained. Associated with the overall increase of sympathetic activity in the body, a depletion of NE stores in the failing human heart was observed. Marked reduction of NE concentration was found both in the atrium and ventricle; in the latter the reduction of NE was related directly to the contractile state of the myocardium, although it has been emphasized that this relationship cannot be considered to be causal. Frequently, the diminution of ventricular NE was sufficient to have abolished the response to tyramine. These findings in man have led to investigations in chronic heart failure preparations in the dog and the guinea pig, in which similar changes in cardiac NE concentration were observed. The depression in cardiac NE concentration was found to reflect a reduction of the total amount in the ventricles. In the guinea pig, left ventricular failure was associated with both diminished cardiac NE formation and diminished binding capacity in the heart. Evidence is presented, however, that in the failing heart there is no alteration of those binding mechanisms which remain intact. These findings are consonant with the hypothesis that the absolute number of nerve endings in the heart is diminished. Some of the possible effects of the altered cardiac sympathetic nerve function which were described on the contractile state of the failing heart were discussed. ER -