MOLECULAR-FORMS OF ATRIAL-NATRIURETIC-FACTOR IN NORMAL AND FAILING HUMAN MYOCARDIUM

Background. Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in co ngestive heart failure (CHF). Data from animal models indicate that my ocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stor ed ANF. To date, the molecular forms of ANF and their concentrations i n 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 no rmal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and le ft atrial appendages, atrial free walls, and ventricles. In normal hea rts, ANF concentration in the atrial appendages was 40-fold higher tha n ANF in the rest of the atrial free wall and in the ventricles. In th e failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. A nalysis of molecular forms of ANF demonstrated significant increases i n the gamma and beta forms in the left atrial appendage of failing hea rts. Alpha, beta, and gamma ANF forms were also significantly increase d in right and left atrial free wall tissue from failing hearts. In ad dition, failing hearts were characterized by absolute and relative inc reases in the precursor form gamma ANF. Conclusions. These data from f resh tissues suggest that cardiac ANF stores are not decreased in seve re CHF in humans; rather, chronic CHF is characterized by marked incre ases in atrial ANF tissue concentrations, particularly the beta and ga mma ANF forms. These findings are consistent with intracellular accumu lation of precursor ANF forms in severe chronic human CHF.