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Related Experiment Videos

Abnormalities in systemic norepinephrine kinetics in human congestive heart failure.

D Davis1, R Baily, R Zelis

  • 1Division of Cardiology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.

The American Journal of Physiology
|June 1, 1988
PubMed
Summary

High norepinephrine (NE) levels in congestive heart failure (CHF) are linked to poor outcomes. This study found that both decreased NE clearance and increased NE spillover contribute to elevated NE levels in CHF patients.

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Area of Science:

  • Cardiology
  • Pharmacokinetics
  • Physiology

Background:

  • Elevated venous plasma norepinephrine (NE) levels are a known predictor of poor prognosis in patients with congestive heart failure (CHF).
  • The underlying mechanisms contributing to these elevated NE levels in CHF remain incompletely understood.

Purpose of the Study:

  • To investigate the kinetic mechanisms responsible for high plasma NE levels in patients with CHF.
  • To compare NE kinetics in CHF patients versus normal subjects.

Main Methods:

  • A steady-state intravenous infusion of tracer [3H]NE was administered over 90 minutes to 19 CHF patients and 18 normal subjects.
  • Norepinephrine (NE) clearance and NE spillover were calculated using established kinetic equations based on tracer infusion rates and plasma concentrations.

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Main Results:

  • Venous plasma NE levels were significantly higher in CHF patients (634 pg/ml) compared to normal subjects (247 pg/ml).
  • NE clearance was significantly decreased in CHF patients (0.99 l.min-1.m-2) compared to normal subjects (1.48 l.min-1.m-2).
  • NE spillover was significantly increased in CHF patients (3.60 nmol.min-1.m-2) compared to normal subjects (2.08 nmol.min-1.m-2).

Conclusions:

  • Both reduced NE clearance and increased NE spillover contribute nearly equally to the elevated plasma NE levels observed in CHF.
  • These findings suggest that abnormalities in NE clearance mechanisms in CHF may be linked to factors associated with early mortality.