Takemura G, Fujiwara H, Horike K, Mukoyama M, Saito Y, Nakao K, Matsuda M, Kawamura A, Ishida M, Kida M
Third Division, Faculty of Medicine, Kyoto University, Japan.
Circulation. 1989 Nov;80(5):1137-47. doi: 10.1161/01.cir.80.5.1137.
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 alpha-human 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%). 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.
为研究人心室中利钠肽（ANP）的表达机制，我们对49例因扩张型心肌病（21例）、心肌炎后（18例）或容量负荷过重（5例）导致心脏扩张的患者以及作为对照的无心脏扩张的受试者（5例）的双心室心内膜活检标本进行了ANP的免疫组织化学研究。使用抗α-人ANP单克隆抗体作为一抗，通过间接免疫过氧化物酶法对4微米厚的切片进行染色。计算每个标本中存在ANP的心肌细胞频率，并与临床、超声心动图、血流动力学、血管造影和组织学参数进行比较。在21例扩张型心肌病患者中均发现了存在ANP的心肌细胞，18例心肌炎后患者中有11例，5例容量负荷过重患者中有4例，而5例对照者中均未发现。左侧标本中存在ANP的心肌细胞的平均百分比（35±37%）显著高于右侧标本（2±4%）。左侧标本中存在ANP的心肌细胞百分比与收缩期峰值或舒张末期壁应力（r = 0.67和0.58）、左心室收缩末期或舒张末期容积指数（r = 0.75和0.69）或左心室舒张末期压力（r = 0.42）显著相关，与射血分数（r = -0.73）、左心室收缩期壁厚度（r = -0.58）或心脏指数（r = -0.30）呈负相关。在壁应力正常、射血分数正常、容积正常或心肌细胞大小正常的病例中很少见到ANP的表达。然而，即使在左心室舒张末期压力和心脏指数正常（代偿性心脏）的心脏中也经常见到。两侧存在ANP的心肌细胞百分比与心肌细胞大小（右侧r = 0.48，左侧r = 0.57）或纤维化程度（右侧r = 0.45，左侧r = 0.48）显著相关。这些结果表明，无论扩张的原因如何，扩张心室中ANP的表达都会增加，并且这种增加是一种代偿机制，可防止因心脏扩张和心肌肥大同时出现的收缩力降低、壁应力过大或两者兼而有之而导致的失代偿。
