Regression of cardiac hypertrophy after closing an aortocaval fistula in rats.

To determine whether the series addition of sarcomeres observed during eccentric hypertrophic growth is reversible upon removal of the initiating stimulus, an aortocaval fistula was created and myocyte geometry evaluated at 2 and 12 wk after shunt occlusion. A 76% cardiac enlargement was produced in rats with an aortocaval fistula. This enlargement was reduced to 22 and 18% at 2 and 12 wk of fistula reversal, respectively. Hemodynamic performance was altered as a result of fistula induction as evidenced by a 28% increase in peak rate of pressure rise. This pressure increase remained elevated by 30% 2 wk after fistula reversal but was not different from sham-operated control animals at 12 wk of reversal. Significant increases in overall myocyte length were detected as a result of the creation of the fistula [left ventricle (LV), 20%; right ventricle (RV), 29%; septum, 23% greater than shams]. Although these increases diminished only slightly 2 wk after closure of the fistula (LV, 12%; RV, 17%; septum, 12% greater than shams), linear measurements of myocyte length in two of three regions had reverted to values that were not significantly different from those of age-matched, sham-operated controls at 12 wk after fistula closure (LV, 8%; RV, 10%; septum, 7%). Myocyte cross-sectional area and cell volume followed a similar pattern. Thus myocytes possess the necessary machinery to remove recently added series sarcomeres, returning altered pump function and dilated ventricular chamber geometry toward control values. In addition, it appears that cardiac hypertrophic growth with this experimental model of volume overload is largely, but not completely, reversible.