Cardiomyocyte Cell-Cycle Activity during Preadolescence

Earlier studies (Soonpaa et al., 1996) revealed a rapid drop-off of ventricular cardiomyocyte cell-cycle activity at birth in mice, followed by a burst of DNA synthesis during the first week of postnatal life which contributed to the formation of multi-nucleated cardiomyocytes by postnatal day 10 (PN10). It has recently been suggested that a second burst of cardiomyocyte cell-cycle activity occurs during preadolescence, between PN14 and PN18, resulting in a 40% increase in cardiomyocyte number (Naqvi et al., 2014). Since there was no overt change in monoversus bi-nuclear cardiomyocyte content and no change in cardiomyocyte nuclear ploidy between PN14 and PN18, a 40% increase in ventricular cardiomyocyte number during preadolescence should result in newly synthesized DNA in 57% of the cardiomyocyte nuclei. To characterize this putative burst of preadolescent cell-cycle activity, MHCnLACmice, expressing a nuclear-localized b-galactosidase reporter in cardiomyocytes and maintained in a DBA/2J background (Soonpaa et al., 1994), were implanted with BrdU-containing osmotic mini-pumps. Cumulative ventricular cardiomyocyte DNA synthesis was quantitated