Published Online
on August 5, 2002

A more recent version of this article appeared on August 13, 2002

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Submitted on March 26, 2002
Revised on May 14, 2002
Accepted on May 14, 2002

Epinephrine in the Heart. Uptake and Release, but No Facilitation of Norepinephrine Release

Thomas W. Lameris MD, PhD, Sandra de Zeeuw PhD, Dirk J. Duncker MD, PhD, Wouter Tietge MSc, Gooitzen Alberts BSc, Frans Boomsma PhD, Pieter D. Verdouw PhD, and Anton H. van den Meiracker MD, PhD^*

From the Department of Internal Medicine (T.W.L., G.A., F.B., A.H.v.d.M.) and Experimental Cardiology, Thoraxcenter (S.d.Z., D.J.D., W.T., P.D.V.), Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, Rotterdam, the Netherlands.

^* To whom correspondence should be addressed. E-mail: ton.vanden.meiracker{at}12move.nl.

Background—Several studies have suggested that epinephrine augments the release of norepinephrine from sympathetic nerve terminals through stimulation of presynaptic receptors, but evidence pertaining to this mechanism in the heart is scarce and conflicting. Using the microdialysis technique in the porcine heart, we investigated whether epinephrine, taken up by and released from cardiac sympathetic nerves, can increase norepinephrine concentrations in myocardial interstitial fluid (NE_MIF) under basal conditions and during sympathetic activation.

Methods and Results—During intracoronary epinephrine infusion of 10, 50, and 100 ng/kg per minute under basal conditions, large increments in interstitial (from 0.31±0.05 up to 140±30 nmol/L) and coronary venous (from 0.16±0.08 up to 228±39 nmol/L) epinephrine concentrations were found, but NE_MIF did not change. Left stellate ganglion stimulation increased NE_MIF from 3.4±0.5 to 8.2±1.5 nmol/L, but again, this increase was not enhanced by concomitant intracoronary epinephrine infusion. Intracoronary infusion of tyramine resulted in a negligible increase in epinephrine concentration in myocardial interstitial fluid (EPI_MIF), whereas 30 minutes after infusion of epinephrine an increase of 9.5 nmol/L in EPI_MIF was observed, indicating that epinephrine is taken up by and released from cardiac sympathetic neurons. Although 68% to 78% of infused epinephrine was extracted over the heart, the ratio of interstitial to arterial epinephrine concentrations was only 20%, increasing to 29% with neuronal reuptake inhibition.

Conclusions—Our findings demonstrate epinephrine release from cardiac sympathetic neurons, but they do not provide evidence that epinephrine augments cardiac sympathoneural norepinephrine release under basal conditions or during sympathetic activation.

Key words: norepinephrine • receptors • nervous system, sympathetic • heart failure

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