Nishikawa T, Ishiyama S, Nagata M, Sakomura Y, Nakazawa M, Momma K, Hiroe M, Kasajima T
Department of Pathology, Tokyo Women's Medical University, Shinjuku-ku, Japan.
Cardiovasc Pathol. 1999 Jul-Aug;8(4):185-9. doi: 10.1016/s1054-8807(99)00007-1.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of the right ventricular myocardium. Recently, the myocardial loss in ARVC has been suggested to be related to apoptosis. However, it is still unknown whether this phenomenon is already established in the myocardium of pediatric cases with this disease. We examined the histopathologic characteristics of the ventricular myocardium in specimens obtained from 10 patients, including 3 children with ARVC, and investigated the occurrence of apoptosis in the myocardium by terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay and agarose-gel electrophoresis of DNA. Endomyocardial biopsy specimens from the 10 cases and a necropsy sample from one adult case with ARVC were examined. Histopathologic examination of biopsy specimens from the pediatric cases revealed extensive fibrosis. Typical fatty infiltration was demonstrated in one of the 3 pediatric cases. These findings were similar to those in adult cases; the histopathologic index based on the severity of myocardial damage, including myocyte degeneration and fibrosis, was not significantly different from that in adult cases. TUNEL assay revealed positive reactivity of the myocardial cells. The apoptotic index was 1.4 +/- 0.4% in children and 1.6 +/- 0.5% in adults (difference not statistically significant). Agarose-gel electrophoresis of a DNA extract of the myocardial tissue of the autopsy case revealed DNA fragmentation. Cases with idiopathic ventricular tachycardia and control cases with a cardiac transplant (with no rejection) had minimal histopathologic findings and negative reactivity in the TUNEL assay. These results indicate that myocardial damage is already established in cases diagnosed as ARVC in childhood, and suggest that the myocardial damage is closely related to apoptosis in children, as well as in adults, in this disease.
致心律失常性右室心肌病（ARVC）的特征是右室心肌被纤维脂肪组织替代。最近，有人提出ARVC中的心肌损失与细胞凋亡有关。然而，在患有这种疾病的儿科病例的心肌中这种现象是否已经存在仍不清楚。我们检查了从10例患者获取的心室心肌标本的组织病理学特征，其中包括3例患有ARVC的儿童，并通过末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）法和DNA琼脂糖凝胶电泳研究了心肌中细胞凋亡的发生情况。检查了10例患者的心内膜活检标本以及1例成年ARVC患者的尸检样本。儿科病例活检标本的组织病理学检查显示广泛纤维化。3例儿科病例中有1例出现典型的脂肪浸润。这些发现与成年病例相似；基于心肌损伤严重程度（包括心肌细胞变性和纤维化）的组织病理学指数与成年病例相比无显著差异。TUNEL法显示心肌细胞呈阳性反应。儿童的凋亡指数为1.4±0.4%，成人为1.6±0.5%（差异无统计学意义）。尸检病例心肌组织DNA提取物的琼脂糖凝胶电泳显示DNA片段化。特发性室性心动过速病例和心脏移植对照病例（无排斥反应）的组织病理学表现轻微，TUNEL法检测呈阴性反应。这些结果表明，在儿童期被诊断为ARVC的病例中已经存在心肌损伤，提示在这种疾病中，儿童和成人心肌损伤均与细胞凋亡密切相关。
