Davison G, Whittaker P, Wickline S A
Division of Cardiology of Barnes-Jewish Hospital at Washington University School of Medicine, St. Louis, Missouri USA.
Heart Institute, Good Samaritan Hospital and Department of Medicine, Section of Cardiology, University of Southern California, Los Angeles, California USA.
Cardiovasc Pathol. 1997 Nov-Dec;6(6):307-13. doi: 10.1016/S1054-8807(97)00003-3.
Previous studies of the effect of angiotensin-converting enzyme (ACE) inhibitors on the process of cardiac remodeling have devoted little attention to potentially beneficial alterations in collagen fiber morphology and microscopic organization. The present work is part of a continuing effort to define mechanisms responsible for changes in microscopic material properties of cardiac tissue that are induced by such pharmacologic therapy. Morphologic evaluation of 11 cardiomyopathic (CM) and 5 control hamsters was performed. Six CM hamsters received captopril for 3 months in their drinking water (2 gm/l), and five other CM hamsters and five normal control hamsters received no treatment. Myocyte and collagen content, organization, and fiber size were defined with the use of circular statistics in fixed sections that were stained with picrosirius red and viewed with polarized light. The scar regions from both treated and untreated CM hearts manifested similar collagen fiber thicknesses, organization (angular deviation 21.1 ± 0.7 degrees vs. 19.2 ± 2.2 degrees, untreated vs. treated, p = NS), and content (65.0% ± 2.2% vs. 65.7% ± 3.7%, untreated vs. treated, p = NS). However, significant muscle fiber disarray was observed in myocytes in the non-necrotic zones near scars for both treated and untreated CM heart, and a strong trend toward normalization of myocyte alignment was observed after captopril therapy. In the present study, captopril exerted no significant effect on collagen content, two-dimensional fiber organization, or fiber thickness in either scar or nonscar regions. Thus, the beneficial effects of captopril on cardiac material properties in ventricular remodeling associated with heritable cardiomyopathy does not appear to be related to alterations in collagen fiber morphology or organization. However, the trend toward normalization of myocyte alignment induced by captopril in non-necrotic zones suggests a possible mechanism for the known beneficial effects of captopril on favorable ventricular remodeling.
先前关于血管紧张素转换酶（ACE）抑制剂对心脏重塑过程影响的研究，很少关注胶原纤维形态和微观组织结构中潜在的有益改变。目前的工作是持续努力的一部分，旨在确定由这种药物治疗引起的心脏组织微观材料特性变化的机制。对11只心肌病（CM）仓鼠和5只对照仓鼠进行了形态学评估。6只CM仓鼠在饮用水中接受卡托普利治疗3个月（2克/升），另外5只CM仓鼠和5只正常对照仓鼠未接受治疗。使用圆周统计学方法，在经苦味酸天狼星红染色并用偏光显微镜观察的固定切片中，确定心肌细胞和胶原含量、组织结构及纤维大小。治疗和未治疗的CM心脏的瘢痕区域表现出相似的胶原纤维厚度、组织结构（角偏差分别为21.1±0.7度和19.2±2.2度，未治疗组与治疗组，p=无显著性差异）和含量（分别为65.0%±2.2%和65.7%±3.7%，未治疗组与治疗组，p=无显著性差异）。然而，在治疗和未治疗的CM心脏瘢痕附近的非坏死区心肌细胞中均观察到明显的肌纤维紊乱，卡托普利治疗后观察到心肌细胞排列有强烈的正常化趋势。在本研究中，卡托普利对瘢痕或非瘢痕区域的胶原含量、二维纤维组织结构或纤维厚度均无显著影响。因此，卡托普利对遗传性心肌病相关心室重塑中心脏材料特性的有益作用似乎与胶原纤维形态或组织结构的改变无关。然而，卡托普利在非坏死区诱导的心肌细胞排列正常化趋势，提示了卡托普利对有利的心室重塑已知有益作用的一种可能机制。
