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 approximately 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
