Norepinephrine spillover to plasma during steady-state supine bicycle exercise. Comparison of patients with congestive heart failure and normal subjects.

This study was performed to determine the relative contributions of plasma norepinephrine clearance and norepinephrine release to the increase in plasma norepinephrine concentration that occurs during exercise and to determine whether the high rates of cardiac norepinephrine release from the heart and kidney in patients with heart failure are associated with diminished reserve for regional sympathetic nervous stimulation. During supine steady-state bicycle exercise at 50% of maximum voluntary exercise capacity, the plasma norepinephrine concentration of six patients with congestive heart failure rose from 385 +/- 88 to 2,200 +/- 497 pg/ml, whereas that of nine normal subjects rose from 208 +/- 21 to 882 +/- 257 pg/ml. The change in plasma concentration in both groups was due to an increase in norepinephrine spillover to plasma without a change in plasma norepinephrine clearance. In patients with heart failure, cardiac spillover increased from 80 +/- 26 to 528 +/- 265 ng/min during exercise, and renal spillover rose from 146 +/- 71 to 418 +/- 69 ng/min. In the normal subjects, cardiac spillover rose from 5 +/- 2 to 73 +/- 23 ng/min, and renal spillover increased from 76 +/- 27 to 275 +/- 106 ng/min. There is no evidence of a reduced reserve for overall or regional sympathetic stimulation in patients with heart failure. Reduced reflex responses in these patients are more likely due to end-organ refractoriness than to inadequate stimulation.