Effects of desipramine on norepinephrine clearance in congestive heart failure

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · American Journal of Physiology; (USA)

OSTI ID:6794746

Clemson, B; Baily, R G; Davis, D; Zelis, R ^[1]

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1. Pennsylvania State Univ., Hershey (USA)

Elevated plasma norepinephrine (NE) in congestive heart failure (CHF) is caused by increased NE spillover and decreased NE clearance. To evaluate the effects of neuronal uptake blockade on NE clearance, we studied NE kinetics during steady-state infusions of (3H)NE, before and after oral desipramine (DMI, 50 mg) in 11 patients with CHF and 8 normal volunteers. Baseline plasma NE was greater in the CHF group (637 +/- 56 vs. 271 +/- 32 pg/ml; P less than 0.001), NE clearance was lower in CHF (1.31 +/- 0.21 vs. 1.94 +/- 0.17 l.min-1.m-2; P = 0.026), and NE spillover was greater in CHF (4.71 +/- 0.78 vs. 3.04 +/- 0.35 nmol.min-1.m-2, P = 0.054). After DMI, plasma NE rose significantly in CHF (778 +/- 67; P = 0.008), and NE clearance decreased further in CHF (0.97 +/- 0.16; P = 0.024), but neither changed in normal subjects. NE spillover did not change in either group. There appears to be an enhanced effect of DMI on NE clearance in CHF patients. Two general mechanisms may be responsible for this finding, an increased concentration of drug, possibly caused by a decreased volume of distribution, and an increased sensitivity of neuronal amine pumps to DMI. Both mechanisms may reflect a more general abnormality of clearance of drugs and hormones related to abnormalities of tissue perfusion in CHF.

• OSTI ID: 6794746
• Journal Information: American Journal of Physiology; (USA), Vol. 259:2 Pt 1; ISSN 0002-9513
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIDEPRESSANTS
BIOLOGICAL EFFECTS
CARDIOVASCULAR DISEASES
PATHOGENESIS
NORADRENALINE
BLOOD-PLASMA CLEARANCE
BLOOD PRESSURE
METABOLISM
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
AUTONOMIC NERVOUS SYSTEM AGENTS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM AGENTS
CLEARANCE
DISEASES
DRUGS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
NEUROREGULATORS
PSYCHOTROPIC DRUGS
SYMPATHOMIMETICS
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