Rodeheffer R J, Naruse M, Atkinson J B, Naruse K, Burnett J C, Merrill W H, Frist W H, Demura H, Inagami T
Department of Medicine, Mayo Clinic, Rochester, Minn 55905.
Circulation. 1993 Aug;88(2):364-71. doi: 10.1161/01.cir.88.2.364.
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.
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.
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.
心房利钠因子（ANF）由心肌组织产生，已知在充血性心力衰竭（CHF）时血浆ANF浓度会升高。来自动物模型的数据表明，CHF时心肌中ANF浓度会降低，这引发了一种假说，即CHF的特征是储存的ANF耗竭。迄今为止，在正常和衰竭的人类心脏中，ANF的分子形式及其在心房和心室心肌中的浓度仍未得到很好的表征。
我们测量了心脏移植时切除的衰竭人类心脏以及正常心脏无法用于移植的器官供体新鲜组织中的ANF浓度。我们测定了右心耳、左心耳、心房游离壁和心室中的总ANF以及α、β和γ-ANF浓度。在正常心脏中，心耳中的ANF浓度比心房游离壁其余部分和心室中的ANF高40倍。在衰竭心脏中，心耳ANF浓度增加了5至10倍，心房游离壁ANF浓度增加了200倍。对ANF分子形式的分析表明，衰竭心脏左心耳中γ和β形式显著增加。衰竭心脏的右心耳和左心耳游离壁组织中α、β和γ-ANF形式也显著增加。此外，衰竭心脏的特征是前体形式γ-ANF的绝对和相对增加。
来自新鲜组织的数据表明，在人类严重CHF中，心脏ANF储备并未减少；相反，慢性CHF的特征是心房ANF组织浓度显著增加，尤其是β和γ-ANF形式。这些发现与严重慢性人类CHF中前体ANF形式的细胞内积累一致。
