Cardiac myocyte nuclear size and ploidy status decrease after mechanical support

Two patients with end-stage dilated cardiomyopathy of ischemic and idiopathic origin were treated with a left ventricular assist device (LVAD) as a bridge for heart transplantation. Myocardial tissue was collected during LVAD insertion and from the left ventricular apex of the explanted hearts. The myocyte diameter, nuclear area and DNA content of myocyte nuclei were measured by static cytomorphometry in tissue sections and in isolated myocytes with a digital analysis system. The presence of apoptotic nuclei was investigated by the TdT mediated X-dUTP nick end labeling technique (TUNEL). The prolonged use of a LVAD was associated with a reduction in myocyte diameter, indicating that the LVAD may induce a reversion of myocyte hypertrophy, a process described as "reverse remodeling." In addition, unloading of the heart induced a reduction in the size and DNA content of myocyte nuclei. These results suggest that the cardiomyocyte nuclei are in a dynamic state and, as it occurs with cell hypertrophy, nuclear hypertrophy and polyploidization may be a reversible phenomenon.