Continuous infusion of tracer norepinephrine may miscalculate unidirectional nerve uptake of norepinephrine in humans.
In order to evaluate uptake kinetics of norepinephrine (NE) in different tissues, a catheterization study was performed in control subjects (n = 6) and patients with enhanced sympathetic nervous activity (cirrhosis, n = 12) during constant intravenous infusion of L[3H]norepinephrine ([3H]NE) for 75 minutes. In spite of a higher NE spillover from kidneys in patients compared with controls (82 vs. 49 ng/min, p less than 0.01), renal extraction ratios of [3H]NE were similar in the two groups (0.33 vs. 0.32, NS), and no significant change was observed during the time of infusion. In contrast, liver-intestine extraction ratios of [3H]NE decreased significantly and equally with infusion time in patients (from 0.57 to 0.44, p less than 0.01) and controls (from 0.59 to 0.46, p less than 0.01). This was observed despite the fact that spillover of NE from this vascular bed was observed only in patients with cirrhosis and not in controls (41 vs. -5 ng/min, p less than 0.02). In the lower limb, net release of NE was similar in patients and controls, and extraction ratios of [3H]NE decreased almost equally with infusion time (from 0.35 to 0.30, p less than 0.01 and from 0.40 to 0.24, p less than 0.1, respectively). Whole-body clearance of [3H]NE decreased over time in patients (-6%, p less than 0.01) and controls (-20%, p less than 0.01), but significant difference was not observed between the groups. We conclude that failure to attain a steady state with respect to [3H]NE removal was demonstrated in areas of large tissue volume relative to blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Henriksen
J H
JH
Department of Clinical Physiology, Hvidovre Hospital, Denmark.
Christensen
N J
NJ
Ring-Larsen
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D008103:Liver Cirrhosis / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000378:metabolism*; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000378:metabolism* / Q000503:physiopathology; D014018:Tissue Distribution; D014316:Tritium
D014316:Tritium; D009638:Norepinephrine