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Related Experiment Videos

Endothelin in human congestive heart failure

C M Wei1, A Lerman, R J Rodeheffer

  • 1Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905.

Circulation
|April 1, 1994
PubMed
Summary

In severe congestive heart failure (CHF), elevated plasma endothelin (ET) is mainly the precursor big-ET, not the active ET-1. Cardiac ET remains ET-1 and unchanged, with plasma ET correlating to CHF severity.

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Area of Science:

  • Cardiovascular Research
  • Biochemistry
  • Molecular Biology

Background:

  • Plasma endothelin (ET) elevation in congestive heart failure (CHF) is reported, but its molecular form (ET-1 vs. big-ET) and myocardial involvement are unclear.
  • It is unknown if ET levels increase in early CHF stages (asymptomatic left ventricular dysfunction) and correlate with ventricular dysfunction severity.

Purpose of the Study:

  • To investigate plasma and cardiac tissue endothelin (ET) concentrations and molecular forms in healthy individuals and CHF patients across New York Heart Association (NYHA) classes I-IV.
  • To determine the relationship between circulating ET levels and the severity of cardiac dysfunction and functional class in CHF.

Main Methods:

  • Utilized cardiac radionuclide angiogram, myocardial biopsy, radioimmunoassay, gel permeation chromatography (GPC), and immunohistochemical staining (IHCS).

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  • Analyzed plasma and cardiac tissue samples from healthy subjects and CHF patients (NYHA class I-IV).
  • Main Results:

    • Plasma ET increased significantly in moderate (NYHA III) and severe (NYHA IV) CHF, correlating negatively with left ventricular ejection fraction and positively with functional class.
    • In severe CHF, plasma ET comprised both mature ET-1 and its precursor big-ET, with big-ET being predominant; cardiac ET remained ET-1 and was present in both healthy and failing hearts.
    • Circulating ET elevation was specific to severe CHF and correlated with hemodynamic alterations and functional class.

    Conclusions:

    • Elevated plasma ET in severe CHF is primarily due to the precursor big-ET, not mature ET-1.
    • Cardiac endothelin (ET) is present in both healthy and failing hearts as ET-1 and its activity is unchanged in CHF.
    • Increased plasma ET is characteristic of severe CHF and correlates with disease severity and hemodynamic impairment.