Ventricular expression of atrial natriuretic polypeptide and its relations with hemodynamics and histology in dilated human hearts. Immunohistochemical study of the endomyocardial biopsy specimens.

Abstract

To investigate the mechanism of expression of atrial natriuretic polypeptide (ANP) in human ventricles, we conducted an immunohistochemical study of ANP in biventricular endomyocardial biopsy specimens obtained from a total of 49 patients with cardiac dilatation due to dilated cardiomyopathy (21 patients), postmyocarditis (18 patients), or volume overload (five patients) and subjects with no dilatation as controls (five patients). Four-micron thick sections were stained by an indirect immunoperoxidase method using monoclonal antibody to ahuman ANP as the primary antibody. The frequency of ANP-present myocytes was calculated in each specimen and compared with clinical, echocardiographic, hemodynamic, angiographic, and histologic parameters. ANP-present myocytes were noted in all of the 21 patients with dilated cardiomyopathy, in 11 of the 18 patients with postmyocarditis, in four of the five patients with volume overload, and in zero of the five controls. The mean percentage of ANP-present myocytes was significantly greater in the left-side specimens (35±37%) than in the right-side ones (2±4%o). The percentage of ANP-present myocytes in the left-side specimens significantly correlated with peak systolic or end-diastolic wall stress (r=0.67 and 0.58), left ventricular end-systolic or end-diastolic volume index (r=0.75 and 0.69), or left ventricular end-diastolic pressure (r=0.42) and inversely correlated with ejection fraction (r=-0.73), systolic left ventricular wall thickness (r= -0.58), or cardiac index (r= -0.30). Expression of ANP was rarely seen in the cases with normal wall stresses, normal ejection fraction, normal volume, or normal myocyte size. However, it was seen frequently even in hearts with normal levels of left ventricular end-diastolic pressure and cardiac index (compensated hearts). The percent of ANP-present myocytes in both sides significantly correlated with size of myocytes (r=0.48 at right and r=0.57 at left side) or degree of fibrosis (r=0.45 at right and r=0.48 at left side). These results suggest that ANP expression is augmented in the dilated ventricles regardless of the causes of dilatation and that the augmentation is a compensatory mechanism as prevention against decompensation responding to reduced contractility, excess of wall stresses, or both, concomitantly occurring with cardiac dilatation and myocardial hypertrophy. (Circulation

Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction.

“…There was a significant correlation between both methods (r = 0.69, P < 0.05) (Fig. 5 A) (44)(45)(46). Conversely, the very low expression of ANF in our nonfailing tissues support the notion that the samples of these 'donors' were indeed normal.…”

The pathogenesis of so-called cardiac rhabdomyoma in swine: a histological, immunohistochemical and ultrastructural study

“…It develops as multiple intracavitary or intramural nodules found mostly in the ventricles, undergoes spontaneous regression, and is frequently associated with tuberous sclerosis and other congenital malformations and neoplasms [2,11,16,27]. For these reasons with the histological and ultrastructural findings, most investigators have proposed that CR is a hamartoma of fetal cardiac myocyte (synonymous with developmental abnormality, congenital malformation, or arrested cardiac myocyte maturation) [17,34,35]. Other speculations have included a neoplasm of cardiac myocyte or Purkinje cell (Purkinjeoma), glycogen storage disease, cellular gigantism, and dysplasia [2,5,13].…”

Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium

“…Bloch et al (1986) have suggested that neonatal ventricular cells utilize a constitutive pathway for ANP release because they lack secretory granules characteristic of atrial cardiocytes, which store the peptide before secretion. However, the presence of ANP granules in hypertrophied ventricular tissue (Ding et al, 1987;Tsuchimochi et al., 1988;Edwards et al, 1988;Gu et al, 1989;Mercadier et al, 1989;Takemura et al, 1989) suggests that a segretagogue could enhance ANP release from ventricular cells by a regulatory pathway analogous to that in atria.…”