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CLINICAL STUDIES

Antiadrenergic effect of chronic amiodarone therapy in human heart failure

^a Alfred Baker Medical Unit, Baker Medical Research Institute, Melbourne, Australia

Manuscript received July 2, 1998; revised manuscript received December 1, 1998, accepted January 14, 1999.

Reprint requests and correspondence: Dr. David M. Kaye, Alfred Baker Medical Unit, Baker Medical Research Institute, Commercial Rd, Prahran, Victoria 3181, Australia.
david.kaye{at}baker.edu.au

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 ³H-DHPG, intraneuronal metabolites of NE and ³H-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 ³H-DHPG (51%, p < 0.01) than those patients not treated with amiodarone. Hemodynamic assessment of amiodarone-treated patients revealed higher cardiac output (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 through a sympatholytic process, and this action appears to be relatively cardioselective.

Abbreviations and Acronyms   DHPG = dihydroxyphenylglycol   DOPA = dihydroxyphenylalanine   HF = heart failure

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