Background The scarring of the heart that results from myocardialinfarction has been interpreted as evidence that the heart iscomposed of myocytes that are unable to divide. However, recentobservations have provided evidence of proliferation of myocytesin the adult heart. Therefore, we studied the extent of mitosisamong myocytes after myocardial infarction in humans.
Methods Samples from the border of the infarct and from areasof the myocardium distant from the infarct were obtained from13 patients who had died 4 to 12 days after infarction. Tennormal hearts were used as controls. Myocytes that had enteredthe cell cycle in preparation for cell division were measuredby labeling of the nuclear antigen Ki-67, which is associatedwith cell division. The fraction of myocyte nuclei that wereundergoing mitosis was determined, and the mitotic index (theratio of the number of nuclei undergoing mitosis to the numbernot undergoing mitosis) was calculated. The presence of mitoticspindles, contractile rings, karyokinesis, and cytokinesis wasalso recorded.
Results In the infarcted hearts, Ki-67 expression was detectedin 4 percent of myocyte nuclei in the regions adjacent to theinfarcts and in 1 percent of those in regions distant from theinfarcts. The reentry of myocytes into the cell cycle resultedin mitotic indexes of 0.08 percent and 0.03 percent, respectively,in the zones adjacent to and distant from the infarcts. Eventscharacteristic of cell division — the formation of themitotic spindles, the formation of contractile rings, karyokinesis,and cytokinesis — were identified; these features demonstratedthat there was myocyte proliferation after myocardial infarction.
Conclusions Our results challenge the dogma that the adult heartis a postmitotic organ and raise the possibility that the regenerationof myocytes may contribute to the increase in muscle mass ofthe myocardium.
Source Information
From the Department of Medicine, New York Medical College, Valhalla (A.P.B., K.U., J.K., B.N.-G., A.L., P.A.); the Department of Pathology, University of Udine, Udine, Italy (S.-M.Y., N.F., C.A.B.); and the Department of Pathology, University of Trieste, Trieste, Italy (R.B., F.S.).
Address reprint requests to Dr. Anversa at the Department of Medicine, Vosburgh Pavilion, Rm. 302, New York Medical College, Valhalla, NY 10595, or at piero_anversa{at}nymc.edu.
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