MYOCYTE NUCLEAR AND POSSIBLE CELLULAR HYPERPLASIA CONTRIBUTE TO VENTRICULAR REMODELING IN THE HYPERTROPHIC SENESCENT HEART IN HUMANS

Objectives. The present investigation was designed to evaluate the gro wth reserve capacity of the aged and senescent myocardium. Background. Aging affects the ability of the heart to sustain alterations in vent ricular loading, and this phenomenon may be coupled with attenuation o f the hypertrophic reaction of the myocardium. However, because myocyt e cellular hyperplasia has been documented experimentally in the old h eart, a similar adaptation may also occur in humans and play a role in this process. Methods. The changes in number and size of ventricular myocytes were measured quantitatively in pathologic hearts of elderly subjects. Morphometric methodologies were applied to the analysis of 1 3 hypertrophic hearts obtained at autopsy from patients 80 +/- 4 (mean +/- SD) years old. An identical number of nonhypertrophic hearts coll ected from subjects 76 +/- 7 years old were used as control hearts. Re sults. A 71% increase in left ventricular weight was associated with a 33% increase in average myocyte cell volume per nucleus and a 36% aug mentation in the total number of myocyte nuclei in the ventricular myo cardium. However, a 55% increase in right ventricular weight was the r esult of a 59% increase in the aggregate number of myocyte nuclei, wit h no change in myocyte cell volume. These cellular processes were asso ciated with a 95% and 83% enlargement of the myocardial interstitium i n the left and right ventricle, respectively. Conclusions. Myocyte nuc lear and possibly cellular hyperplasia appear to be the prevailing gro wth mechanism of the overloaded aging myocardium. Proliferation of myo cyte nuclei and connective tissue accumulation are the major determina nts of ventricular remodeling in the hypertrophic senescent heart.