THE PATHOGENESIS OF LEFT VENTRICULAR STIFFNESSIN CARDIOMYOPATHIES : ULTRASTRUCTURAL AND IMMUNOHISTOCHEMICAL STUDY.

为了阐明心肌病左心室僵硬的病因，我们进行了以下研究。(1)对14例限制性心肌病（RCM）、21例肥厚型心肌病（HCM）和23例扩张型心肌病（DCM）右心室心肌内膜活检标本进行ⅰ、ⅲ、ⅳ型拼贴蛋白亚型分析，并采用免疫光镜和电镜半定量研究MMP-1和2的表达（分级为0 ~ 3+）。此外，我们将7例KCM和10例DCM患者的MMP-2活性与旁路手术获得的正常对照（n=5）进行比较。免疫组化结果显示，RCM和HCM中ⅲ型胶原明显增多，而DCM中ⅰ型和ⅳ型胶原明显增多。在HCM和DCM中，对MMP-1的免疫反应沿胶原原纤维和部分成纤维细胞呈阳性。随着对I型和III型胶原反应性的增强，MMP-1有增加的趋势。另一方面，MMP-2 - More及其酶活性在DCM中表现突出。(2)为阐明心肌细胞、胶原蛋白和弹性纤维的三维结构，采用扫描电镜对15例尸检心脏（4例RCM、1例梗阻性HCM、3例DCM、2例心肌梗死、OMI和5例无心脏病的正常心脏）和3例手术材料（2例梗阻性HCM和1例OMI）进行研究。在RCM和HCM中，心肌细胞的形状和分支都很奇怪，彼此之间的连接也很不规则。RCM最显著的特征是肌束增厚，其中少于5微米的胶原束形成网状网络，弹性纤维数量增加，与HCM非常相似。另一方面，DCM和OMI组肌内膜和肌周膜均增厚，但弹性纤维较少。此外，在DCM和OMI的肌周中，胶原常被组织成厚束，长约20毫米，沿邻近心肌细胞的纵轴排列。以上结果提示：1)RCM和HCM中网状网络的增加，可能是III型胶原和弹性成分，在左心室僵硬中起重要作用；2)DCM中I型胶原的增加反映了替代纤维化；3)MMP可能参与了心肌病中胶原合成和心脏重塑的级联反应。少

To clarify the etiology of left ventricular stiffness in cardiomyopathies, the following studies were conducted. (1) On the right ventricular endomyocardial biopsy specimens, the subtypes of collage I,III and IV were analyzed ant the expression of MMP-1 and 2 werestudies semiquantitatively (graded from 0 to 3+) in 14 cases of restrictive cardiomyopathy (RCM), 21 of hypetrophic cardiomyopathy (HCM) and 23 of dilated cardiomyopathy (DCM) by immuno-light and electron microscopy. Furthermore, the MMP-2 activity measured by zymography in 7 KCM 10 DCM cases were comparted with the normal control (n=5) obtained at the bypass surgery. Immunohistochemically, type III collagenincreased remarkably in RCM and HCM,whereas type I and IV collagen was prominent in DCM.The immunoreactivity ageinst MMP-1 was positive along collagen fibrils and in some fibroblasts both in HCM and DCM.The MMP-1 tended to increase as the reactivity against type I and III collagen was prominent. On the other hand, the MMP-2 … More and its activity measured by zymography were prominent in DCM.(2) To elucidate the three dimensional architecture of cardiocytes, collagen and elastic fibers, fifteen autopsied hearts (4 RCM,1obstructuve HCM,3 DCM,2 myocardial infarction, OMI and 5 normal hearts without cardiacdisease) and 3 surgical materials (2 obstructive HCM and 1OMI) were studied by scanning electron microscopy. In RCM and HCM,the cardiocytes were bizarrely shaped and branching, and were irregularly connected with one another. The most striking features in RCM was the thickened perimysium in which collagen bundles of less than 5 mum formed reticular networks together with an increased amount of elastic fibers, which were very similar to those in HCM.On the other hand, in DCM and OMI,endomysium and perimysium were both thickened but the elastic fibers was small in amount. Furthermore, in the perimysium of DCM and OMI,collagens were often organized into thick bundles up 20 mum which ran along the longitudinal axis of neighboring cardiocytes. The above findings suggest that 1) increased reticular networks, which were supposed to be type III colllagen, and elastic elements play an important role as the cause of left ventricular stiffness in RCM and HCM,2) the increased collagen type I reflects the replacement fibrosis in DCM,and 3) MMP appeared to be involved in a cascade of collagen synthesis and the remodeling of the heart in cardiomyopathies. Less