Flow dependence of norepinephrine extraction by isolated perfused rat lungs

Disposition of perfused norepinephrine (NE) was studied in isolated rat lungs at several perfusate flows, including that occurring in vivo. Lungs were ventilated with 95% O2-5% CO2 and perfused at 37 degrees C with recirculating medium initially containing 90 nM [14C]NE. In agreement with previous studies the fraction of NE removed in a single pass through the pulmonary vasculature was 0.30 +/- 0.03 by lungs perfused at low flow (10 ml/min; 7.2 ml.min-1.g lung-1). This extraction ratio decreased with increasing flow, so that in lungs perfused at 45 ml/min (31.8 ml.min-1.g lung-1) the extraction ratio was 0.09 +/- 0.01. The concentration of NE metabolites in the perfusate reservoir increased with time of perfusion. The rate of appearance of deaminated and O-methylated metabolites in the recirculating perfusion medium was not markedly influenced by flow. NE that accumulated in lung was metabolized before reentry into the perfusion medium. These results indicate that extraction of NE by rat lung is markedly dependent on flow and suggest that removal of NE by lung is not highly efficient at normal organ perfusion rates.