Antiadrenergic effect of chronic amiodarone therapy in human heart failure

作者:Kaye DM*; Dart AM; Jennings GL; Esler MD
来源:Journal of the American College of Cardiology, 1999, 33(6): 1553-1559.
DOI:10.1016/S0735-1097(99)00042-X

摘要

OBJECTIVES
The aim of the present study was to evaluate the influence of amiodarone on neurochemical parameters of sympathetic nervous activity in patients with congestive heart failure.
BACKGROUND
Unlike most antiarrhythmic agents, amiodarone has been shown to exert a beneficial effect on survival in some studies of patients with congestive heart failure. The pharmacology of this agent is complex, and as such, the mode of its action is unclear in humans. Some experimental studies suggest that amiodarone exerts a sympatholytic effect.
METHODS
To evaluate the effect of amiodarone on sympathetic nervous activity, we measured the total systemic and cardiac norepinephrine (NE) spillover rate by isotope dilution in 58 patients with severe heart failure (left ventricular ejection fraction 20 +/- 1%), 22 of whom were receiving chronic amiodarone treatment Release rates for dihydroxyphenylalanine (DOPA, a precursor of NE), and endogenous and radiolabeled dihydroxyphenylglycol (DHPG and H-3-DHPG, intraneuronal metabolites of NE and H-3-NE, respectively) were also determined to assess sympathetic neuronal integrity.
RESULTS
Amiodarone-treated patients had significantly lower cardiac spillover rates for NE (42%, p = 0.001), DOPA (74%, p < 0.001), DHPG (44%, p < 0.01) and H-3 DHPG (51%, p < 0.01) than those patients not treated with amiodarone Hemodynamic assessment of amiodarone-treated patients revealed higher cardiac out-put (4.4 +/- 0.2 vs. 3.7 +/- 0.2 liters/min, p < 0.01), and slightly lower pulmonary capillary wedge pressure (18 +/- 2 vs. 22 +/- 1, p = NS) than in untreated patients. After correction for the potential confounding effect of hemodynamic differences, amiodarone-treated patients continued to demonstrate significantly lower spillover rates of NE, DOPA and DHPG from the heart.
CONCLUSIONS
These data indicate that amiodarone may exert beneficial effects on the failing human heart and this action appears to be relatively cardioselective a through a sympatholytic process, and this action appears to be relatively cardiovascular.

  • 出版日期1999-5