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.

Adrenergic Uptake Inhibitors/pharmacology, Adrenergic alpha-Antagonists/pharmacology, Animals, Coronary Vessels/physiology, Desipramine/pharmacology, Dose-Response Relationship, Drug, Electric Stimulation, Epinephrine/*metabolism/pharmacokinetics, Extracellular Space/chemistry/metabolism, Female, Heart/innervation, Hemodynamic Processes/drug effects/physiology, Infusions, Intra-Arterial, Male, Microdialysis, Myocardium/*metabolism, Norepinephrine/analysis/*metabolism, Phentolamine/pharmacology, Research Support, Non-U.S. Gov't, Stellate Ganglion/physiology, Swine, Sympathetic Nervous System/drug effects/*metabolism, Tyramine/pharmacology
Circulation (Baltimore)
Erasmus MC: University Medical Center Rotterdam

Lameris, Th.W, de Zeeuw, P.A, Duncker, D.J.G.M, Tietge, W, Alberts, G, Boomsma, F, … van den Meiracker, A.H. (2002). Epinephrine in the heart: uptake and release, but no facilitation of norepinephrine release. Circulation (Baltimore), 106(7), 860–865. Retrieved from