Hepatic and gut clearance of catecholamines in the conscious dog

Our aim was to assess hepatic and gut catecholamine clearance under normal and simulated stress conditions. Following a 90-minute saline infusion peri od, epinephrine ([EPI] 180 ng/kg.min) and norepinephrine ([NE] 500 ng/kg.mi n) were infused peripherally for 90 minutes into five 18-hour fasted, consc ious dogs undergoing a pancreatic clamp (somatostatin plus basal insulin an d glucagon), Arterial plasma levels of EPI and NE increased from 44 +/- 9 t o 2,961 +/- 445 and 96 +/- 6 to 6,467 +/- 571 pg/mL, respectively (both P < .05), Portal vein plasma levels of EPI and NE increased from 23 +/- 8 to 1, 311 +/- 173 and 79 +/- 10 to 3,477 +/- 380 pg/mL, respectively (both P <.05 ). Hepatic vein plasma levels of EPI and NE increased from 5 +/- 2 to 117 /- 33 and 48 +/- 10 to 448 +/- 59 pg/mL, respectively (both P <.05), Net he patic and gut EPI uptake increased from 0.5 +/- 0.1 to 30.0 +/- 3.0 and 0.4 +/- 0.1 to 26.3 +/- 4.0 ng/kg.min, respectively (both P <.05). Net hepatic and gut NE uptake increased from 1.5 +/- 0.4 to 74.7 +/- 8.4 and 0.8 +/- 0 .2 to 57.9 +/- 7.6 ng/kg.min, respectively (both P <.05). Neither the net h epatic (0.86 +/- 0.05 to 0.93 +/- 0.02) nor gut (0.45 +/- 0.10 to 0.55 +/- 0.04) fractional extraction of EPI changed significantly during the simulat ed stress condition. Net hepatic and gut spillover of NE increased from 0.8 +/- 0.2 to 3.5 +/- 1.3 and 0.6 +/- 0.2 to 8.8 +/- 2.0 ng/kg.min, respectiv ely, during catecholamine infusion (both P <.05). These results indicate th at (1) approximately 30% of circulating catecholamines are cleared by the s planchnic bed (16% and 14% by the liver and gut, respectively); (2) the liv er and gut remove a large proportion (approximately 86% to 93% and 45% to 5 5%, respectively) of the catecholamines delivered to them on first pass; an d (3) high levels of plasma catecholamines increase NE spillover from both the liver and gut, suggesting that the percentage of NE released from the p resynaptic neuron that escapes the synaptic cleft is increased in the prese nce of high circulating catecholamine levels. Copyright (C) 1999 by W.B. Sa unders Company.