DNA resynthesis and binucleated metamorphosis in cardiac muscle cells after isoproterenol-induced injury: bromodeoxyuridine immunohistochemistry.

In this study, we assessed reactive DNA synthesis in mouse cardiac myocytes after injury in vivo using the Bromodeoxyuridine (BrdU) immunohistochemical method and clarified binucleated metamorphosis of S-phase cardiac myocytes in the myocardial healing process. The animals were injured by isoproterenol i.p., and studied 0, 1, 2, 3, 5 and 10 days after injury. Each animal was killed 3 hr after labeling with BrdU i.p. The BrdU labeling index was calculated 0, 1, 2, 3, 5 and 10 days after injury. Moreover, we observed the morphological difference of S-phase cardiac myocytes between Group A and Group B (A and B group were killed 3 hr and 3 days, respectively, after BrdU i.p.). Most of BrdU positive cells were mesenchymal fibroblastic, and BrdU positive cardiac myocytes were a minor phenomenon during healing process. In cardiac myocytes, the BrdU labeling index is 0.49 +/- 0.02 and 0.05 +/- 0.01 at day 3 and 0 after injury, respectively (P < 0.05). All BrdU positive cardiac myocytes were located around myocardial necrosis. All BrdU positive myocytes in Group A were mononucleated, whereas some were binucleated in Group B. These results indicated that some of the cardiac myocytes could synthesize DNA reactively even after birth, and that in a healing process, myocytic DNA synthesis is probably followed by binucleated metamorphosis.