Experimental findings suggest a pronounced concentration gradient of norepinephrine (NE) between the intravascular and interstitial compartments of the heart, compatible with an active neuronal reuptake (U1) and/or an endothelial barrier. Using the microdialysis technique in eight anesthetized pigs, we investigated this NE gradient, both under baseline conditions and during increments in either systemic or myocardial interstitial fluid (MIF) NE concentration. At steady state, baseline MIF NE (0.9 +/- 0.1 nmol/l) was higher than arterial NE (0.3 +/- 0.1 nmol/l) but was not different from coronary venous NE (1.5 +/- 0.3 nmol/l). Local U1 inhibition raised MIF NE concentration to 6.5 +/- 0.9 nmol/l. During intravenous NE infusions (0.6 and 1.8 nmol. kg(-1). min(-1)), the fractional removal of NE by the myocardium was 79 +/- 4% to 69 +/- 3%, depending on the infusion rate. Despite this extensive removal, the quotient of changes in MIF and arterial concentration (DeltaMIF/DeltaA ratio) for NE were only 0.10 +/- 0.02 for the lower infusion rate and 0.11 +/- 0.01 for the higher infusion rate, whereas U1 blockade caused the DeltaMIF/DeltaA ratio to rise to 0.21 +/- 0.03 and 0.36 +/- 0.05, respectively. From the differences in DeltaMIF/DeltaA ratios with and without U1 inhibition, we calculated that 67 +/- 5% of MIF NE is removed by U1. Intracoronary infusion of tyramine (154 nmol. kg(-1). min(-1)) caused a 15-fold increase in MIF NE concentration. This pronounced increase was paralleled by a comparable increase of NE in the coronary vein. We conclude that U1 and extraneuronal uptake, and not an endothelial barrier, are the principal mechanisms underlying the concentration gradient of NE between the interstitial and intravascular compartments in the porcine heart.

Animals, Catecholamines/*metabolism, Dose-Response Relationship, Drug, Extracellular Space/metabolism, Female, Hemodynamic Processes/drug effects, Isoproterenol/blood/pharmacokinetics/pharmacology, Male, Microdialysis, Myocardium/*metabolism, Norepinephrine/blood/pharmacokinetics/pharmacology, Swine/*metabolism, Tyramine/blood/pharmacokinetics/pharmacology
hdl.handle.net/1765/9176
American Journal of Physiology (Consolidated)
Erasmus MC: University Medical Center Rotterdam

Lameris, Th.W, van den Meiracker, A.H, Boomsma, F, Alberts, G, de Zeeuw, P.A, Duncker, D.J.G.M, … Man in 't Veld, A.J. (1999). Catecholamine handling in the porcine heart: a microdialysis approach. American Journal of Physiology (Consolidated). Retrieved from http://hdl.handle.net/1765/9176