Related Experiment Videos
Molecular forms of atrial natriuretic factor in normal and failing human myocardium
R J Rodeheffer1, M Naruse, J B Atkinson
1Department of Medicine, Mayo Clinic, Rochester, Minn 55905.
Insights
Congestive heart failure (CHF) in humans does not deplete cardiac atrial natriuretic factor (ANF) stores. Instead, failing hearts show increased atrial ANF concentrations, particularly precursor forms, suggesting intracellular accumulation.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Atrial natriuretic factor (ANF) is produced by the heart and elevated in congestive heart failure (CHF).
- Animal models suggest ANF depletion in CHF, but human data on cardiac ANF forms and concentrations are limited.
- Understanding ANF's role in human CHF requires characterizing its molecular forms in failing and normal hearts.
Purpose of the Study:
- To characterize the molecular forms and concentrations of ANF in human atrial and ventricular myocardium.
- To investigate whether ANF stores are depleted in the failing human heart.
- To compare ANF levels and forms in normal versus CHF human hearts.
Main Methods:
- Measured total ANF and alpha, beta, and gamma ANF concentrations in fresh myocardial tissues from transplanted failing hearts and organ donors.
- Analyzed ANF in right and left atrial appendages, atrial free walls, and ventricles.
- Compared ANF concentrations and molecular forms between normal and failing human hearts.
Main Results:
- Normal hearts had 40-fold higher ANF in appendages than free walls/ventricles.
- Failing hearts showed 5-10 fold increases in atrial appendage ANF and 200-fold increases in atrial free wall ANF.
- Failing hearts exhibited increased beta and gamma ANF forms, with a notable rise in precursor gamma ANF in atrial tissues.
Conclusions:
- Severe CHF in humans is not characterized by depleted cardiac ANF stores.
- Failing human hearts show significantly increased atrial ANF tissue concentrations, especially beta and gamma forms.
- Findings suggest intracellular accumulation of precursor ANF forms in chronic human CHF.
Background:
Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart.
Methods And Results:
We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF.
Conclusions:
These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.