Myocyte DNA synthesis with aging: correlation with ventricular loading in rats.

To determine whether the detrimental mechanical and anatomical changes that occur biventricularly with aging are associated with activation of DNA synthesis, flow cytometric analysis was performed on myocyte nuclei prepared from the left and right ventricles of rats at 4, 12, 20, and 29 months of age. Heart weight increased significantly with age, and this growth adaptation was associated with the development of left ventricular failure and right ventricular dysfunction. These phenomena were coupled with marked elevations in diastolic wall stress and increases in the percentage of myocyte nuclei in S+G2M in both ventricles. Linear regression analyses revealed a direct correlation between the fraction of myocytes that entered the cell cycle and diastolic pressure and wall stress. An inverse relation was found between the percentage of myocyte nuclei in S+G2M and +dP/dt and systolic wall stress. Thus the depression of hemodynamic performance coupled with alterations in the loading conditions contributes, at least in part, to increased DNA synthesis in cardiac myocytes with age.