CHRONIC ISCHEMIC VIABLE MYOCARDIUM IN MAN - ASPECTS OF DEDIFFERENTIATION

Histologic analysis of biopsies derived from patients with chronic dys functional but viable (hibernating) myocardium showed characteristic c ell alterations. These changes consisted of a partial to complete loss of sarcomeres, accumulation of glycogen, and disorganization and loss of sarcoplasmic reticulum. Most of the adaptive changes that these af fected cells undergo are suggestive of dedifferentiation. In the prese nt study the expression and organizational pattern of contractile and cytoskeletal proteins such as titin, cardiotin, and alpha-smooth muscl e actin were assessed in hibernating and normal myocardium because the expression and organization of these constituents have been related t o certain stages of cardiomyocyte differentiation. In normal cells tit in shows a cross-striated staining pattern, whereas cardiotin displays a fibrillar array, parallel to the sacromeres. Alpha-Smooth muscle ac tin is not expressed in adult cardiomyocytes. The expression of titin in a punctuated pattern and the marked decrease to virtual absence of cardiotin in hibernating cardiomyocytes speak in favor of an embryonic phenotype of these cells. The re-expression of alpha-smooth muscle ac tin in hibernating cells strongly supports this hypothesis. The observ ations on three different structural proteins of heart muscle suggest that hibernating myocardium acquired aspects of muscle cell dedifferen tiation.