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.
Natural hormones stimulate B2 receptors in the body as well as by synthetic compounds; epinephrine (adrenaline) is the most effective natural catecholamine agonist of B2, while norepinephrine (noradrenaline) is less effective on it, and epinephrine is the hormone responsible for B2 receptor stimulation in the physiological state.
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.
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.
Because >80% of neuronally released NE is taken up by sympathetic nerves of the porcine heart through the U1 mechanism, 13 the U1 inhibitor desipramine was added to the perfusate of one of the microdialysis probes to provide local U1 blockade.
The porcine heart is especially suitable as a model for studying the cardiac sympathetic nervous system, as the distribution of β 1 /β 2 adrenoceptors (80%/20%) 12 and the prevailing parasympathetic control of cardiac function are very much akin to the human heart.
Because tyramine only displaces catecholamines from their storage vesicles in the sympathetic nerve terminals after it has been taken up by the neuronal reuptake (U1) mechanism, 13,14 catecholamines released by tyramine are exclusively from neuronal origin.
U1 inhibition did not affect EPI MIF, LAD at baseline and the lowest EPI infusion rate but caused an increase in EPI MIF, LAD to similar values as EPI CV at the two higher infusion rates. Although the cardiac EPI extraction was 68% to 78%, there was a marked gradient between interstitial and circulatory concentrations.
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, ...