Evidence that human cardiac myocytes divide after myocardial infarction

Background The scarring of the heart that results from myocardial infarctio n has been interpreted as evidence that the heart is composed of myocytes t hat are unable to divide. However, recent observations have provided eviden ce of proliferation of myocytes in the adult heart. Therefore, we studied t he extent of mitosis among myocytes after myocardial infarction in humans. Methods Samples from the border of the infarct and from areas of the myocar dium distant from the infarct were obtained from 13 patients who had died 4 to 12 days after infarction. Ten normal hearts were used as controls. Myoc ytes that had entered the cell cycle in preparation for cell division were measured by labeling of the nuclear antigen Ki-67, which is associated with cell division. The fraction of myocyte nuclei that were undergoing mitosis was determined, and the mitotic index (the ratio of the number of nuclei u ndergoing mitosis to the number not undergoing mitosis) was calculated. The presence of mitotic spindles, contractile rings, karyokinesis, and cytokin esis was also recorded. Results In the infarcted hearts, Ki-67 expression was detected in 4 percent of myocyte nuclei in the regions adjacent to the infarcts and in 1 percent of those in regions distant from the infarcts. The reentry of myocytes int o the cell cycle resulted in mitotic indexes of 0.08 percent and 0.33 perce nt, respectively, in the zones adjacent to and distant from the infarcts. E vents characteristic of cell division - the formation of the mitotic spindl es, the formation of contractile rings, karyokinesis, and cytokinesis - wer e identified; these features demonstrated that there was myocyte proliferat ion after myocardial infarction. Conclusions Our results challenge the dogma that the adult heart is a postm itotic organ and raise the possibility that the regeneration of myocytes ma y contribute to the increase in muscle mass of the myocardium. (N Engl J Me d 2001;344:1750-7.) Copyright (C) 2001 Massachusetts Medical Society.