PROLIFERATING CELL KINETICS IN HEALING FOLLOWING ISOPROTERENOL-INDUCED MYOCARDIAL INJURY

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The kinetics of the proliferating cells in rat myocardial injury induced by isoproterenol was immunohistochemically observed using monoclonal antibodies against bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA). The number of PCNA-positive cells began to increase in necrotic areas of myocardium and its adjacent areas at as early as 12 hours after isoproterenol injection, reaching a maximum value on day 5. On the other hand, an increase in number of BrdU labelling cells was seen in similar areas at 24 hours and reached a peak on day 3. Thereafter, immunoreactive cells for both PCNA and BrdU gradually decreased along with scar tissue formation. The number of PCNA-positive cells was consistently greater than that of BrdU labelling cells. On day 3 when granulation tissues began to be formed, BrdU-positive cells dominated at the edge of the lesion, whereas PCNA-positive cells were found within the injured areas and in surrounding myocardium. These findings suggested that granulation tissue-constituting cells might be derived from interstitial connective tissue cells adjacent to myocardial lesions.