Catecholamine handling in the porcine heart: a microdialysis approach

Experimental findings suggest a pronounced concentration gradient of norepi nephrine (NE) between the intravascular and interstitial compartments of th e heart, compatible with an active neuronal reuptake (U1) and/or an endothe lial 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 co ncentration. At steady state, baseline MIF NE (0.9 +/- 0.1 nmol/l) was high er than arterial NE (0.3 +/- 0.1 nmol/l) but was not different from coronar y venous NE (1.5 +/- 0.3 nmol/l). Local U1 inhibition raised MIF NE concent ration 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 extensiv e removal, the quotient of changes in MIF and arterial concentration (Delta MIF/Delta A ratio) for NE were only 0.10 +/- 0.02 for the lower infusion r ate and 0.11 +/- 0.01 for the higher infusion rate, whereas U1 blockade cau sed the Delta MIF/Delta A ratio to rise to 0.21 +/- 0.03 and 0.36 +/- 0.05, respectively. From the differences in Delta MIF/Delta A ratios with and wi thout U1 inhibition, we calculated that 67 +/- 5% of MIF NE is removed by U 1. Intracoronary infusion of tyramine (154 nmol . kg(-1).min(-1)) caused a 15-fold increase in MIF NE concentration. This pronounced increase was para lleled by a comparable increase of NE in the coronary vein. We conclude tha t U1 and extraneuronal uptake, and not an endothelial barrier, are the prin cipal mechanisms underlying the concentration gradient of NE between the in terstitial and intravascular compartments in the porcine heart.