REGIONAL EPINEPHRINE KINETICS IN HUMAN HEART-FAILURE - EVIDENCE FOR EXTRAADRENAL, NONNEURAL RELEASE

A number of neurohumoral processes are activated in heart failure, inc luding an increase in the plasma concentration of epinephrine. Radiotr acer methods were applied in 42 patients with severe heart failure and 31 healthy volunteers to ascertain the rate at which epinephrine is r eleased to plasma and to evaluate the contribution of extra-adrenal so urces. The increase in arterial plasma epinephrine observed in the hea rt failure patients was explained principally by a 34% (P < 0.001) red uction in the whole body clearance rate of epinephrine from plasma. Re gional venous sampling from the heart, lungs, and hepatomesenteric bed s was performed in a subgroup of the study population, revealing a sig nificant increase in the release rate of epinephrine to plasma from th ese organs in heart failure which accounted for 26% of the whole body plasma epinephrine appearance rate. To establish whether the cardiac e pinephrine release was of neuronal origin, a physical (cycling) or men tal (difficult mental arithmetic) stressor was applied as a sympathoex citatory stimulus, given that a proportional release of norepinephrine and epinephrine could be expected if sympathetic nerves were the sour ce. These interventions caused significant increases in the regional s pillover of norepinephrine to plasma but not that of epinephrine. Thes e findings suggest that nonadrenal tissues contribute significantly to the whole body epinephrine release rate in heart failure and that thi s may arise from a site other than sympathetic neurons.