Differences in Antiapoptotic, Proliferative Activities and Morphometry in Dilated and Ischemic Cardiomyopathy: Study of Hearts Explanted From Transplant Recipients

Abstract: Background: Antiapoptotic as well as replacement and proliferative mechanisms take place in the myocardium in dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). We sought to estimate antiapoptotic, proliferative and replacement activities in cardiomyopathies. Materials: The study groups included seven hearts with DCM and eight with IHD, which had been explanted at the time of transplantation. The comparator group consisted of cases of myocardial hypertrophy and the control group, donor fragments. Methods: Antiapoptotic and proliferative responses were determined immunohistochemically as Bcl-2 and Ki67 expression by semiquantitative assessment of the intensity of staining. We also measured and statistically analyzed the integrative morphometric measurements of the fraction of fibrosis area, the nucleosarcoplasmic ratio, and cardiocyte diameter. Results: No Bcl-2 expression was observed in the controls. The strongest reaction was seen in the DCM group, then in the IHD, and in the comparator group of myocardial hypertrophy. Proliferative activity was seen only in endocardial and interstitial fibroblasts in DCM and IHD cases. The cardiocyte diameter showed no statistical association between myocardial hypertrophy and IHD, or IHD and DCM, whereas the nucleosarcoplasmic ratios were significantly different from control groups for all comparisons. Myocardial fibrosis showed the highest values in DCM and IHD. Discriminant analysis showed the value of interstitial fibrosis and cardiocyte diameter to categorize the analyzed groups. Conclusions: Antiapoptotic Bcl-2 activity seemed to play an important role in cardiocyte preservation, while proliferative activity was resticted to interstitial connective tissue cells as a replacement process. Myocardial Bcl-2 expression, the extent of myocardial fibrosis, and cardiocyte diameter may serve as additional diagnostic tools to differentiate cardiomyopathies. [Copyright &y& Elsevier]