CARDIAC SYMPATHETIC-NERVE FUNCTION IN CONGESTIVE-HEART-FAILURE

Background Increased availability of norepinephrine (NE) for activatio n of cardiac adrenoceptors (increased cardiac adrenergic drive) and de pletion of myocardial NE stores may contribute to the pathophysiology and progression of congestive heart failure. This study used a compreh ensive neurochemical approach to examine the mechanisms responsible fo r these abnormalities. Methods and Results Subjects with and without c ongestive heart failure received intravenous infusions of [H-3]NE. Car diac spillover, reuptake, vesicular-axoplasmic exchange, and tissue St ores of NE were assessed from arterial and coronary venous plasma conc entrations of endogenous and [H-3]-labeled NE and dihydroxyphenylglyco l. Tyrosine hydroxylase activity was assessed from plasma dopa, and NE turnover was assessed from measurements of NE metabolites. NE release and reuptake were both increased in the failing heart; however, the e fficiency of NE reuptake was reduced such that cardiac spillover of NE was increased disproportionately more than neuronal release of NE. Ca rdiac NE stores were 47% lower and the rate of vesicular leakage of NE was 42% lower in the failing than in the normal heart. Cardiac spillo ver of dopa and NE turnover were increased similarly in congestive hea rt failure. Conclusions Increased neuronal release of NE and decreased efficiency of NE reuptake both contribute to increased cardiac adrene rgic drive hi congestive heart failure. Decreased vesicular leakage of NE, secondary to decreased myocardial stores of NE, limits the increa se in cardiac NE turnover in CHF. Decreased NE store size in the faili ng heart appears to result not from insufficient tyrosine hydroxylatio n but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage.