MYOCYTE PROLIFERATION IN END-STAGE CARDIAC-FAILURE IN HUMANS

Introduced several decades ago, the dogma persists that cardiac myocyt es are terminally differentiated cells and that division of muscle tel ls is impossible in the adult heart, More recently, nuclear mitotic di visions in myocytes occasionally were seen, but those observations wer e challenged on the assumption that the rate of cell proliferation was inconsequential for actual tissue regeneration. Moreover, mitoses wer e never detected in normal myocardium. However, the analysis of routin e histologic preparations constituted the basis for the belief that my ocytes were unable to reenter the cell cycle and divide, ignoring the limitations of these techniques, We report here by confocal microscopy that 14 myocytes per million were in mitosis in control human hearts, A nearly 10-fold increase in this parameter was measured in end-stage ischemic heart disease (152 myocytes per million) and in idiopathic d ilated cardiomyopathy (131 myocytes per million). Because the left ven tricle contains 5.8 x 10(9) myocytes, these mitotic indices imply that 81.2 x 10(3), 882 x 10(3), and 760 x 10(3) myocytes were in mitosis i n the entire ventricular myocardium of control hearts and hearts affec ted by ischemic and idiopathic dilated cardiomyopathy, respectively, A dditionally, mitosis lasts less than 1 hr, suggesting that large numbe rs of myocytes can be formed in the nonpathologic and pathologic heart with time. Evidence of cytokinesis in myocytes was obtained, providin g unequivocal proof of myocyte proliferation.